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# Overview
More than one in four migraineurs are indicated for porphylactic therapy, and a substantial proportion of those who might benefit from prevention do not receive it.
Following treatment of an acute migraine, it is important to consider preventive measures. Petasites are one of the preventive measures as well as medications such as NSAIDs, amitryptilline, devalproex, valproic acid, propranolol, timolol and topiramate among others. If the preventive measure is not effective after two to three months, the dose of the medication should be adjusted. If no improvement is noted, another first line therapy or a combination of two first line therapies should be initiated.
# Indications for Pharmacologic Prophylaxis of Migraine
According to the guideline from American Academy of Neurology (AAN), prophylaxis may be more appropriately guided by one or more of the following:
- Recurring migraines that, in the patients' opinion, significantly interfere with their daily routines, despite acute treatment
- Frequent headaches
- Contraindication to, failure of, or overuse of acute therapies
- Adverse events with acute therapies
- The cost of both acute and preventive therapies
- Patient preference
- The presence of uncommon migraine conditions, including hemiplegic migraine, basilar migraine, migraine with prolonged aura, or migrainous infarction.
European Federation of Neurological Societies (EFNS) proposed that prophylactic treatment should be considered and discussed with the patient when:
- The quality of life, business duties, or school attendance are severely impaired
- Frequency of attacks per month is two or higher
- Migraine attacks do not respond to acute drug treatment
- Frequent, very long, or uncomfortable auras occur
United States guidelines recommend to initiate preventive therapy when attacks regularly exceed two times per week, whereas European guidelines suggest migraine prophylaxis for two or more attacks per month.
# Principles of Prophylaxis
The main goal of preventive therapy is to reduce the frequency, severity, and durations of migraines, and to increase the effectiveness of abortive therapy. Another reason is to avoid medication overuse headache (MOH), otherwise known as rebound headache, which is an extremely common problem among migraneurs. This occurs in part due to overuse of pain medications. MOH results in the development of chronic daily headache due to "transformed" migraine. Preventive medication has to be taken on a daily basis, usually for a few weeks, before the effectiveness can be determined. Supervision by a neurologist is advisable. A large number of medications with varying modes of action can be used. Selection of a suitable medication for any particular patient is a matter of trial and error, since the effectiveness of individual medications varies widely from one patient to the next. Often preventive medications do not have to be taken indefinitely. Sometimes as little as six months of preventive therapy is enough to "break the headache cycle" and then they can be discontinued. The most effective prescription medications include several drug classes:
- Beta blockers such as propranolol and atenolol. A meta-analysis by the Cochrane Collaboration of nine randomized controlled trials or crossover studies, which together included 668 patients, found that propranolol had an "overall relative risk of response to treatment (here called the 'responder ratio')" was 1.94.
- Anticonvulsants such as valproic acid and topiramate. A meta-analysis by the Cochrane Collaboration of ten randomized controlled trials or crossover studies, which together included 1341 patients, found anticonvulsants had an "2.4 times more likely to experience a 50% or greater reduction in frequency with anticonvulsants than with placebo" and a number needed to treat of 3.8. However, concerns have been raised about the marketing of gabapentin.
- Antidepressants include tricyclic antidepressants (TCAs) such as amitriptyline and the newer selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine. A meta-analysis by the Cochrane Collaboration found selective serotonin reuptake inhibitors are no more effective than placebo. Another meta-analysis found benefit from SSRIs among patients with migraine or tension headache; however, the effect of SSRIs on only migraines was not separately reported. A randomized controlled trial found that amitriptyline was better than placebo and similar to propranolol.
Other drugs:
- Sansert was withdrawn from the US market by Novartis, but is available in Canadian pharmacies. Although highly effective, it has rare but serious side effects, including retroperitoneal fibrosis.
- Namenda, memantine HCI tablets, which is used in the treatment of Alzheimer's Disease, is beginning to be used off label for the treatment of migraines. It has not yet been approved by the FDA for the treatment of migraines.
- ASA or Asprin can be taken daily in low doses such as 80 to 81 mg, the blood thinners in ASA has been shown to help some migrainures, especially those who have an aura.
## NSAIDs and Complementary Drugs
Shown below is an image depicting the classification of NSAIDs and complementary drugs for migraine prevention according to the American Academy of Neurology and the American Headache Society.
## Migraine Specific Therapies
Shown below is an image depicting the classification of migraine specific therapies according to the American Academy of Neurology and the American Headache Society.
## Menstruation Associated Migraine Specific Therapies
Shown below is an image depicting the classification of migraine specific therapies recommended for short-term prevention of menstruation associated migraine according to the American Academy of Neurology and the American Headache Society.
## Side Effects
# Non Pharmacological Prevention
## Physical Therapy
Many physicians believe that exercise for 15-20 minutes per day is helpful for reducing the frequency of migraines.Massage therapy and physical therapy are often very effective forms of treatment to reduce the frequency and intensity of migraines. However, it is important to be treated by a well-trained therapist who understands the pathophysiology of migraines. Deep massage can 'trigger' a migraine attack in a person who is not used to such treatments. It is advisable to start sessions as short in duration and then work up to longer treatments.Frequent migraines can leave the sufferer with a stiff neck which can cause stress headaches that can then exacerbate the migraines. Claims have been made that Myofascial Release can relieve this tension and in doing so reduce or eliminate the stress headache element.
## Prism Eyeglasses
At least two British studies have shown a relationship between the use of eyeglasses containing prisms and a reduction in migraine headaches. Turville, A. E. (1934) "Refraction and migraine". Br. J. Physiol. Opt. 8, 62–89, contains a good review of the literature and theories existing in 1934, and includes the vascular theory of migraine, which is popular today. In that study, Turville suggests that many patients were provided with complete relief from migraine symptoms with proper eyeglass prescriptions, which included prescribed prism. Wilmut, E. B. (1956) "Migraine". Br. J. Physiol. Opt. 13, 93–97, replicated Turville's work. Both studies are subject to criticism because of sample bias, sample size, and the lack of a control group. Neither study is available online, but another study that found that precision tinted lenses may be an effective migraine treatment and which references the Turville and Wilmut studies can be found at . Turville's and Wilmut's conclusions have largely been ignored since 1956 and it is widely believed that vision problems are not migraine triggers. Most optometrists avoid prescribing prism because, when incorrectly prescribed, it can cause headaches.
## Herbal and Nutritional Supplements
50 mg or 75 mg/day of butterbur (Petasites hybridus) rhizome extract was shown in a controlled trial to provide 50% or more reduction in the number of migraines to 68% of participants in the 75 mg dose group, 56% in the 50 mg dose group and 49% in the placebo group after four months. Native butterbur contains some carcinogenic compounds, but a purified version, Petadolex®, does not. Cannabis was a standard treatment for migraines from the mid-19th century until it was outlawed in the early 20th century in the USA. It has been reported to help people through an attack by relieving the nausea and dulling the head pain, as well as possibly preventing the headache completely when used as soon as possible after the onset of pre-migraine symptoms, such as aura. There is some indication that semi-regular use may reduce the frequency of attacks. Further studies are being conducted. Some migraine sufferers report that cannabis increases throbbing and pain, especially if smoked. A pharmaceutical company is currently conducting trials of a whole cannabis extract spray for migraine. Supplementation of coenzyme Q10 has been found to have a beneficial effect on the condition of some sufferers of migraines. In an open-label trial, Young and Silberstein found that 61.3% of patients treated with 100 mg/day had a greater than 50% reduction in number of days with migraine, making it more effective than most prescription prophylactics. Fewer than 1% reported any side effects. A double-blind placebo-controlled trial has also found positive results.The plant feverfew (Tanacetum parthenium) is a traditional herbal remedy believed to reduce the frequency of migraine attacks. Clinical trials have been carried out (example), and appear to confirm that the effect is genuine (though it does not completely prevent attacks). Kudzu root (Pueraria lobata) has been demonstrated to help with menstrual migraine headaches and cluster headaches. While the studies on menstrual migraine assumed that kudzu acted by imitating estrogen, it has since been shown that kudzu has significant effects on the serotonin receptors. Kudzu Monograph at Med-Owl. Magnesium citrate has reduced the frequency of migraine in an experiment in which the magnesium citrate group received 600 mg per day oral of trimagnesium dicitrate. In weeks 9-12, the frequency of attacks was reduced by 41.6% in the magnesium citrate group and by 15.8% in the placebo group. The supplement Riboflavin or Vitamin B2 has also been used, often with magnesium citrate, to reduce the number of migraines. Its effectiveness is less well documented.
## Non-Drug Medical Treatments
Botox is being used by many headache specialists for patients with frequent or chronic migraines with encouraging results.Spinal cord stimulators are an implanted medical device sometimes used for those who suffer severe migraines several days each month.Transcranial Magnetic Stimulation (TMS): At the 49th Annual meeting of the American Headache Society in June 2006, scientists from Ohio State University Medical Center presented medical research on 47 candidates that demonstrated that TMS — a medically non-invasive technology for treating depression, obsessive compulsive disorder and tinnitus, among other ailments — helped to prevent and even reduce the severity of migraines among its patients. This treatment essentially disrupts the aura phase of migraines before patients develop full-blown migraines. In about 74% of the migraine headaches, TMS was found to eliminate or reduce nausea and sensitivity to noise and light. Their research suggests that there is a strong neurological component to migraines. A larger study will be conducted soon to better assess TMS's complete effectiveness.
## Alternatives
Because the conventional approaches to migraine prevention are not 100% effective and can have unpleasant side effects, many seek alternative treatments.Some migraine sufferers find relief through acupuncture, which is usually used to help prevent headaches from developing. Sometimes acupuncture is used to relieve the pain of an active migraine headache. In one controlled trial of acupuncture with a sham control in migraine, the acupuncture was not more effective than the sham acupuncture but was more effective than delayed acupuncture.Additionally acupressure is used by some for relief. For instance pressure between the thumbs and index finger to help subside headaches if the headache or migraine isn't too severe.Incense and scents are shown to help. The smell and incense of peppermint and lavender have been proven to help with migraines and headaches more so than most other scents. Mauskop A, Fox B, What Your Doctor May Not Tell You About Migraines. Warner Books, New York, 2001
Biofeedback has been used successfully by some to control migraine symptoms through training and practice. Mauskop A, Fox B, What Your Doctor May Not Tell You About Migraines. Warner Books, New York, 2001There is evidence that magnesium supplements can reduce the frequency of migraine headaches. Riboflavin (vitamin B2), co-enzyme Q10 and butterbur extract has been also subjected to double-blind studies suggesting their efficacy in preventing migraine headaches. Mauskop A: "Alternative therapies in headache: Is there a role?" In: Medical Clinics of North America 85 (4): 1077-1084, 2001. Sleep is often a good solution if a migraine is not so severe as to prevent it, as when a person awakes the symptoms will have most likely subsided.Diet, visualization, and self-hypnosis are also alternative treatments and prevention approaches.Bruxism, clenching or grinding of teeth, especially at night, is a trigger for many migraineurs. A device called a nociceptive trigeminal inhibitor (NTI) takes advantage of a reflex limiting the force of clenching. It can be fitted by dentists and clips over the front teeth at night, preventing contact between the back teeth. It has a success rate similar to butterbur and co-enzyme Q10, although it has not been subjected to the same rigorous testing as the supplements. Massage therapy of the jaw area can also reduce such pain.Sexual activity has been reported by a proportion of male and female migraine sufferers to relieve migraine pain significantly in some cases. In many cases where a migraine follows a particular cycle, attempting to interrupt the cycle may prolong the symptoms. Letting a headache "run its course" by not using painkillers can sometimes decrease the length of an episode. This is especially true of cases where vomiting is common, as often the headache will subside immediately after vomiting. Curbing the pain may delay vomiting, and prolong the headache. | Sandbox/m01
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
More than one in four migraineurs are indicated for porphylactic therapy, and a substantial proportion of those who might benefit from prevention do not receive it.[1]
Following treatment of an acute migraine, it is important to consider preventive measures. Petasites are one of the preventive measures as well as medications such as NSAIDs, amitryptilline, devalproex, valproic acid, propranolol, timolol and topiramate among others. If the preventive measure is not effective after two to three months, the dose of the medication should be adjusted. If no improvement is noted, another first line therapy or a combination of two first line therapies should be initiated.[2][3]
# Indications for Pharmacologic Prophylaxis of Migraine
According to the guideline from American Academy of Neurology (AAN), prophylaxis may be more appropriately guided by one or more of the following:[4]
- Recurring migraines that, in the patients' opinion, significantly interfere with their daily routines, despite acute treatment
- Frequent headaches
- Contraindication to, failure of, or overuse of acute therapies
- Adverse events with acute therapies
- The cost of both acute and preventive therapies
- Patient preference
- The presence of uncommon migraine conditions, including hemiplegic migraine, basilar migraine, migraine with prolonged aura, or migrainous infarction.
European Federation of Neurological Societies (EFNS) proposed that prophylactic treatment should be considered and discussed with the patient when:[5]
- The quality of life, business duties, or school attendance are severely impaired
- Frequency of attacks per month is two or higher
- Migraine attacks do not respond to acute drug treatment
- Frequent, very long, or uncomfortable auras occur
United States guidelines recommend to initiate preventive therapy when attacks regularly exceed two times per week, whereas European guidelines suggest migraine prophylaxis for two or more attacks per month.[5][6]
# Principles of Prophylaxis
The main goal of preventive therapy is to reduce the frequency, severity, and durations of migraines, and to increase the effectiveness of abortive therapy. Another reason is to avoid medication overuse headache (MOH), otherwise known as rebound headache, which is an extremely common problem among migraneurs. This occurs in part due to overuse of pain medications. MOH results in the development of chronic daily headache due to "transformed" migraine. Preventive medication has to be taken on a daily basis, usually for a few weeks, before the effectiveness can be determined. Supervision by a neurologist is advisable. A large number of medications with varying modes of action can be used. Selection of a suitable medication for any particular patient is a matter of trial and error, since the effectiveness of individual medications varies widely from one patient to the next. Often preventive medications do not have to be taken indefinitely. Sometimes as little as six months of preventive therapy is enough to "break the headache cycle" and then they can be discontinued. The most effective prescription medications include several drug classes:
- Beta blockers such as propranolol and atenolol. A meta-analysis by the Cochrane Collaboration of nine randomized controlled trials or crossover studies, which together included 668 patients, found that propranolol had an "overall relative risk of response to treatment (here called the 'responder ratio')" was 1.94.[7]
- Anticonvulsants such as valproic acid and topiramate. A meta-analysis by the Cochrane Collaboration of ten randomized controlled trials or crossover studies, which together included 1341 patients, found anticonvulsants had an "2.4 times more likely to experience a 50% or greater reduction in frequency with anticonvulsants than with placebo" and a number needed to treat of 3.8.[8] However, concerns have been raised about the marketing of gabapentin.[9]
- Antidepressants include tricyclic antidepressants (TCAs) such as amitriptyline and the newer selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine. A meta-analysis by the Cochrane Collaboration found selective serotonin reuptake inhibitors are no more effective than placebo.[10] Another meta-analysis found benefit from SSRIs among patients with migraine or tension headache; however, the effect of SSRIs on only migraines was not separately reported.[11] A randomized controlled trial found that amitriptyline was better than placebo and similar to propranolol.[12]
Other drugs:
- Sansert was withdrawn from the US market by Novartis, but is available in Canadian pharmacies. Although highly effective, it has rare but serious side effects, including retroperitoneal fibrosis.
- Namenda, memantine HCI tablets, which is used in the treatment of Alzheimer's Disease, is beginning to be used off label for the treatment of migraines. It has not yet been approved by the FDA for the treatment of migraines.
- ASA or Asprin can be taken daily in low doses such as 80 to 81 mg, the blood thinners in ASA has been shown to help some migrainures, especially those who have an aura.
## NSAIDs and Complementary Drugs
Shown below is an image depicting the classification of NSAIDs and complementary drugs for migraine prevention according to the American Academy of Neurology and the American Headache Society.[2][3]
## Migraine Specific Therapies
Shown below is an image depicting the classification of migraine specific therapies according to the American Academy of Neurology and the American Headache Society.[2][3]
## Menstruation Associated Migraine Specific Therapies
Shown below is an image depicting the classification of migraine specific therapies recommended for short-term prevention of menstruation associated migraine according to the American Academy of Neurology and the American Headache Society.[2][3]
## Side Effects
# Non Pharmacological Prevention
## Physical Therapy
Many physicians believe that exercise for 15-20 minutes per day is helpful for reducing the frequency of migraines.[13]Massage therapy and physical therapy are often very effective forms of treatment to reduce the frequency and intensity of migraines. However, it is important to be treated by a well-trained therapist who understands the pathophysiology of migraines. Deep massage can 'trigger' a migraine attack in a person who is not used to such treatments. It is advisable to start sessions as short in duration and then work up to longer treatments.Frequent migraines can leave the sufferer with a stiff neck which can cause stress headaches that can then exacerbate the migraines. Claims have been made that Myofascial Release can relieve this tension and in doing so reduce or eliminate the stress headache element.
## Prism Eyeglasses
At least two British studies have shown a relationship between the use of eyeglasses containing prisms and a reduction in migraine headaches. Turville, A. E. (1934) "Refraction and migraine". Br. J. Physiol. Opt. 8, 62–89, contains a good review of the literature and theories existing in 1934, and includes the vascular theory of migraine, which is popular today. In that study, Turville suggests that many patients were provided with complete relief from migraine symptoms with proper eyeglass prescriptions, which included prescribed prism. Wilmut, E. B. (1956) "Migraine". Br. J. Physiol. Opt. 13, 93–97, replicated Turville's work. Both studies are subject to criticism because of sample bias, sample size, and the lack of a control group. Neither study is available online, but another study that found that precision tinted lenses may be an effective migraine treatment and which references the Turville and Wilmut studies can be found at [14] . Turville's and Wilmut's conclusions have largely been ignored since 1956 and it is widely believed that vision problems are not migraine triggers. Most optometrists avoid prescribing prism because, when incorrectly prescribed, it can cause headaches.
## Herbal and Nutritional Supplements
50 mg or 75 mg/day of butterbur (Petasites hybridus) rhizome extract was shown in a controlled trial to provide 50% or more reduction in the number of migraines to 68% of participants in the 75 mg dose group, 56% in the 50 mg dose group and 49% in the placebo group after four months. Native butterbur contains some carcinogenic compounds, but a purified version, Petadolex®, does not. Cannabis was a standard treatment for migraines from the mid-19th century until it was outlawed in the early 20th century in the USA. It has been reported to help people through an attack by relieving the nausea and dulling the head pain, as well as possibly preventing the headache completely when used as soon as possible after the onset of pre-migraine symptoms, such as aura. There is some indication that semi-regular use may reduce the frequency of attacks. Further studies are being conducted. Some migraine sufferers report that cannabis increases throbbing and pain, especially if smoked. A pharmaceutical company is currently conducting trials of a whole cannabis extract spray for migraine. Supplementation of coenzyme Q10 has been found to have a beneficial effect on the condition of some sufferers of migraines. In an open-label trial,[15] Young and Silberstein found that 61.3% of patients treated with 100 mg/day had a greater than 50% reduction in number of days with migraine, making it more effective than most prescription prophylactics. Fewer than 1% reported any side effects. A double-blind placebo-controlled trial has also found positive results.[16]The plant feverfew (Tanacetum parthenium) is a traditional herbal remedy believed to reduce the frequency of migraine attacks. Clinical trials have been carried out (example[17]), and appear to confirm that the effect is genuine (though it does not completely prevent attacks). Kudzu root (Pueraria lobata) has been demonstrated to help with menstrual migraine headaches and cluster headaches. While the studies on menstrual migraine assumed that kudzu acted by imitating estrogen, it has since been shown that kudzu has significant effects on the serotonin receptors. Kudzu Monograph at Med-Owl[18]. Magnesium citrate has reduced the frequency of migraine in an experiment in which the magnesium citrate group received 600 mg per day oral of trimagnesium dicitrate. In weeks 9-12, the frequency of attacks was reduced by 41.6% in the magnesium citrate group and by 15.8% in the placebo group.[19] The supplement Riboflavin or Vitamin B2 has also been used, often with magnesium citrate, to reduce the number of migraines. Its effectiveness is less well documented.
## Non-Drug Medical Treatments
Botox is being used by many headache specialists for patients with frequent or chronic migraines with encouraging results.[20]Spinal cord stimulators are an implanted medical device sometimes used for those who suffer severe migraines several days each month.[21]Transcranial Magnetic Stimulation (TMS): At the 49th Annual meeting of the American Headache Society in June 2006, scientists from Ohio State University Medical Center[22] presented medical research on 47 candidates that demonstrated that TMS — a medically non-invasive technology for treating depression, obsessive compulsive disorder and tinnitus, among other ailments — helped to prevent and even reduce the severity of migraines among its patients. This treatment essentially disrupts the aura phase of migraines before patients develop full-blown migraines.[23] In about 74% of the migraine headaches, TMS was found to eliminate or reduce nausea and sensitivity to noise and light. Their research suggests that there is a strong neurological component to migraines. A larger study will be conducted soon to better assess TMS's complete effectiveness.[24]
## Alternatives
Because the conventional approaches to migraine prevention are not 100% effective and can have unpleasant side effects, many seek alternative treatments.Some migraine sufferers find relief through acupuncture, which is usually used to help prevent headaches from developing. Sometimes acupuncture is used to relieve the pain of an active migraine headache. In one controlled trial of acupuncture with a sham control in migraine, the acupuncture was not more effective than the sham acupuncture but was more effective than delayed acupuncture.Additionally acupressure is used by some for relief. For instance pressure between the thumbs and index finger to help subside headaches if the headache or migraine isn't too severe.Incense and scents are shown to help. The smell and incense of peppermint and lavender have been proven to help with migraines and headaches more so than most other scents. Mauskop A, Fox B, What Your Doctor May Not Tell You About Migraines. Warner Books, New York, 2001
Biofeedback has been used successfully by some to control migraine symptoms through training and practice. Mauskop A, Fox B, What Your Doctor May Not Tell You About Migraines. Warner Books, New York, 2001There is evidence that magnesium supplements can reduce the frequency of migraine headaches. Riboflavin (vitamin B2), co-enzyme Q10 and butterbur extract has been also subjected to double-blind studies suggesting their efficacy in preventing migraine headaches. Mauskop A: "Alternative therapies in headache: Is there a role?" In: Medical Clinics of North America 85 (4): 1077-1084, 2001. Sleep is often a good solution if a migraine is not so severe as to prevent it, as when a person awakes the symptoms will have most likely subsided.Diet, visualization, and self-hypnosis are also alternative treatments and prevention approaches.Bruxism, clenching or grinding of teeth, especially at night, is a trigger for many migraineurs. A device called a nociceptive trigeminal inhibitor (NTI) takes advantage of a reflex limiting the force of clenching. It can be fitted by dentists and clips over the front teeth at night, preventing contact between the back teeth. It has a success rate similar to butterbur and co-enzyme Q10, although it has not been subjected to the same rigorous testing as the supplements. Massage therapy of the jaw area can also reduce such pain.Sexual activity has been reported by a proportion of male and female migraine sufferers to relieve migraine pain significantly in some cases. In many cases where a migraine follows a particular cycle, attempting to interrupt the cycle may prolong the symptoms. Letting a headache "run its course" by not using painkillers can sometimes decrease the length of an episode. This is especially true of cases where vomiting is common, as often the headache will subside immediately after vomiting. Curbing the pain may delay vomiting, and prolong the headache. | https://www.wikidoc.org/index.php/Sandbox/m01 | |
c924fcbe6c0c784b06dd35360b8ebcd191e9a053 | wikidoc | Sandbox/mdr | Sandbox/mdr
# Treatment of Drug-Resistant Tuberculosis
WHO has recommended the following for the susceptibility and response monitoring of MDR-TB Treatment:
- Rapid drug susceptibility testing (DST) of isoniazid and rifampicin or of rifampicin alone is recommended over conventional testing or no testing at the time of diagnosis of TB(subject to available resources
- The use of sputum smear microscopy and culture rather than sputum smear microscopy alone is recommended for the monitoring of patients with MDR-TB during treatment
### General principles for Designing MDR-TB Treatment Regimens
### Drugs Groups for Treatment of MDR-TB
- Anti-TB drugs are grouped according to efficacy, experience of use and drug class.
- All the first-line anti-TB drugs are in (Group 1), except streptomycin, which is classified with the other injectable agents in (Group 2).
- All the drugs in Groups 2–5 (except streptomycin) are second-line, or reserve, drugs.
- The features of the cross-resistance means that resistance mutations (in M. tuberculosis bacteria) to one anti-TB drug may confer resistance to some or all of the members of the drug family of the same group and less commonly to other members of different drug groups (1).
### Drugs Groups for Treatment of MDR-TB
- Anti-TB drugs are grouped according to efficacy, experience of use and drug class.
- All the first-line anti-TB drugs are in (Group 1), except streptomycin, which is classified with the other injectable agents in (Group 2).
- All the drugs in Groups 2–5 (except streptomycin) are second-line, or reserve, drugs.
- The features of the cross-resistance means that resistance mutations (in M. tuberculosis bacteria) to one anti-TB drug may confer resistance to some or all of the members of the drug family of the same group and less commonly to other members of different drug groups (1).
# WHO Guidelines for second-line Anti-TB Regimens for MDR
- In the treatment of patients with MDR-TB, a Fluoroquinolone should be used (strong recommendation,very low quality evidence).
- In the treatment of patients with MDR-TB, a Ethionamide (or prothionamide) should be used (strong recommendation, very low quality evidence).
- In the treatment of patients with MDR-TB, a later-generation fluoroquinolone rather than an earlier-generation fluoroquinolone should be used (conditional recommendation,very low quality evidence).
- In the treatment of patients with MDR-TB, four second-line antituberculosis drugs likely to be effective (including a parenteral agent), as well as pyrazinamide, should be included in the intensive phase3 (conditional recommendation,very low quality evidence).
- In the treatment of patients with MDR-TB, regimens should include at least pyrazinamide, a fluoroquinolone, a parenteral agent, ethionamide (or prothionamide), and either cycloserine or PAS (p-aminosalicylic acid) if cycloserine cannot be used (conditional recommendation,very low quality evidence).
Major changes in recommendation for second-line Anti-TB Regimens for MDR:
- Include at least four second-line Anti-TB drugs likely to be effective as well as pyrazinamide during the intensive phase of treatment.
- No evidence found to support the use of more than four second-line anti-tuberculosis drugs in patients with extensive disease. Increasing the number of second-line drugs in a regimen is permissible if the effectiveness of some of the drugs is uncertain.
- Ethambutol may be used but is not included among the drugs making up the standard regimen.
- Group 5 drugs may be used but are not included among the drugs making up the standard regimen.
## Treatment in Special Situations
## Culture-Negative Pulmonary Tuberculosis and Radiographic Evidence of Prior Pulmonary Tuberculosis
Failure to isolate M. tuberculosis from persons suspected of having pulmonary tuberculosis on the basis of clinical features and chest radiographic examination does not exclude a diagnosis of active tuberculosis. Alternative diagnoses should be considered carefully and further appropriate diagnostic studies undertaken in persons with apparent culture-negative tuberculosis. The general approach to management is shown in Figure 2. A diagnosis of tuberculosis can be strongly inferred by the clinical and radiographic response to antituberculosis treatment. Careful reevaluation should be performed after 2 months of therapy to determine whether there has been a response attributable to antituberculosis treatment. If either clinical or radiographic improvement is noted and no other etiology is identified, treatment should be continued for active tuberculosis. Treatment regimens in this circumstance include one of the standard 6-month chemotherapy regimens or INH, RIF, PZA, and EMB for 2 months followed by INH and RIF for an additional 2 months (4 months total). However, HIV-infected patients with culture-negative pulmonary tuberculosis should be treated for a minimum of 6 months.
Persons with a positive tuberculin skin test who have radiographic evidence of prior tuberculosis (e.g., upper lobe fibronodular infiltrations) but who have not received adequate therapy are at increased risk for the subsequent development of tuberculosis. Unless previous radiographs are available showing that the abnormality is stable, it is recommended that sputum examination (using sputum induction if necessary) be performed to assess the possibility of active tuberculosis being present. Also, if the patient has symptoms of tuberculosis related to an extrapulmonary site, an appropriate evaluation should be undertaken. Once active tuberculosis has been excluded (i.e., by negative cultures and a stable chest radiograph), the treatment regimens are those used for latent tuberculosis infection: INH for 9 months, RIF (with or without INH) for 4 months, or RIF and PZA for 2 months (for patients who are unlikely to complete a longer course and who can be monitored closely).
### Pregnancy and Breastfeeding
Because of the risk of tuberculosis to the fetus, treatment of tuberculosis in pregnant women should be initiated whenever the probability of maternal disease is moderate to high. The initial treatment regimen should consist of INH, RIF, and EMB. Although all of these drugs cross the placenta, they do not appear to have teratogenic effects. Streptomycin is the only antituberculosis drug documented to have harmful effects on the human fetus (congenital deafness) and should not be used. Although detailed teratogenicity data are not available, PZA can probably be used safely during pregnancy and is recommended by the World Health Organization (WHO) and the International Union against Tuberculosis and Lung Disease (IUATLD). If PZA is not included in the initial treatment regimen, the minimum duration of therapy is 9 months.
Breastfeeding should not be discouraged for women being treated with the first-line antituberculosis agents because the small concentrations of these drugs in breast milk do not produce toxicity in the nursing newborn. Conversely, drugs in breast milk should not be considered to serve as effective treatment for tuberculosis or for latent tuberculosis infection in a nursing infant. Pyridoxine supplementation (25 mg/day) is recommended for all women taking INH who are either pregnant or breastfeeding. The amount of pyridoxine in multivitamins is variable but generally less than the needed amount.
## Treatment of Tuberculosis in Low-Income Countries: Recommendations of the WHO and Guidelines from the IUATLD
The rise in HIV infections and the neglect of TB control programs have enabled a resurgence of tuberculosis. The emergence of drug-resistant strains has also contributed to this new epidemic with, from 2000 to 2004, 20% of TB cases being resistant to standard treatments and 2% resistant to second-line drugs. TB incidence varies widely, even in neighboring countries, apparently because of differences in health care systems. The World Health Organization declared TB a global health emergency in 1993, and the Stop TB Partnership developed a Global Plan to Stop Tuberculosis aiming to save 14 million lives between 2006 and 2015.
To place the current guidelines in an international context it is necessary to have an understanding of the approaches to treatment of tuberculosis in high-incidence, low-income countries. It is important to recognize that the American Thoracic Society/CDC/Infectious Diseases Society of America (ATS/CDC/IDSA) recommendations cannot be assumed to be applicable under all epidemiologic and economic circumstances. The incidence of tuberculosis and the resources with which to confront the disease to an important extent determine the approaches used. Given the increasing proportion of patients in low-incidence countries who were born in high-incidence countries, it is also important for persons managing these cases to be familiar with the approaches used in the countries of origin.
The major international recommendations and guidelines for treating tuberculosis are those of the WHO and of the IUATLD. The WHO document was developed by an expert committee whereas the IUATLD document is a distillation of IUATLD practice, validated in the field.
The WHO and IUATLD documents target, in general, countries in which mycobacterial culture, drug susceptibility testing, radiographic facilities, and second-line drugs are not widely available as a routine. A number of differences exist between these new ATS/CDC/IDSA recommendations, and the current tuberculosis treatment recommendations of the WHO and guidelines of the IUATLD. Both international sets of recommendations are built around a national case management strategy called "DOTS", the acronym for "Directly Observed Therapy, Short course", in which direct observation of therapy (DOT) is only one of five key elements. The five components of DOTS are 1) government commitment to sustained tuberculosis control activities, 2) case detection by sputum smear microscopy among symptomatic patients self-reporting to health services, 3) a standardized treatment regimen of 6-8 months for at least all confirmed sputum smear-positive cases, with DOT for at least the initial 2 months, 4) a regular, uninterrupted supply of all essential antituberculosis drugs, and 5) a standardized recording and reporting system that enables assessment of treatment results for each patient and of the tuberculosis control program overall.
### A Number of Other Differences Exist as Well
The WHO and the IUATLD recommend diagnosis and classification of tuberculosis cases and assessment of response based on sputum AFB smears. Culture and susceptibility testing for new patients is not recommended because of cost, limited applicability, and lack of facilities.
Chest radiography is recommended by both the WHO and IUATLD only for patients with negative sputum smears and is not recommended at all for follow-up.
Both 6- and 8-month treatment regimens are recommended by the WHO. The IUATLD recommends an 8-month regimen with thioacetazone in the continuation phase for HIV-negative patients. For patients suspected of having or known to have HIV infection, ethambutol is substituted for thioacetazone
The WHO and the IUATLD recommend a standardized 8-month regimen for patients who have relapsed, had interrupted treatment, or have failed treatment. Patients who have failed supervised retreatment are considered "chronic" cases and are highly likely to have tuberculosis caused by MDR organisms. Susceptibility testing and a tailored regimen using second-line drugs based on the test results are recommended by the WHO, if testing and second-line drugs are available. The IUATLD recommendations do not address the issue.
Neither baseline nor follow-up biochemical testing is recommended by the WHO and the IUATLD. It is recommended that patients be taught to recognize the symptoms associated with drug toxicity and to report them promptly.
## New Advances in Pharmacotherapy
A new drug, called Bedalaquine, was recently approved by the FDA in December 2012, to treat multi-drug resistant tuberculosis. About 12 million people worldwide had tuberculosis in 2011, and about 630,000 had multidrug-resistant forms of tuberculosis. Bedaquiline affects theproton pump for ATP synthase, which is unlike the quinolones, whose target is DNA gyrase . It was formally approved for use by the U.S. Food and Drug Administration (FDA) for use intuberculosis (TB) treatment- but it is to be used normally only in cases of multi-drug-resistant tuberculosis, and in an even more resistant category, extensively drug resistant tuberculosis. Multi-drug resistant tuberculosis is defined as tuberculosis cases that do not respond to at least two of the four primary (first-line) antibiotics, developed mostly in the 1950s and 1960s, that are used to treat tuberculosis. The drug has been given a black-box warning for arrhythmias which may cause cardiac arrest .
In addition, a novel, 3-drug, anti-TB regimen (PaMZ) consisting of the chemical entity, nitroimidazooxazine, PA-824 (Pa), the fluoroquinolone, moxifloxacin (M), and the first-line TB drug, pyrazinamide (Z), has shown recent promise in the treatment of tuberculosis. The results of a recent phase II clinical trial published in the Lancet, showed that the three drug regimen killed more than 99% of TB bacteria within 2 weeks of treatment.
## A Research Agenda for Tuberculosis Treatment
New antituberculosis drugs are needed for three main reasons: 1) to shorten or otherwise simplify treatment of tuberculosis caused by drug-susceptible organisms, 2) to improve treatment of drug-resistant tuberculosis, and 3) to provide more efficient and effective treatment of latent tuberculosis infection. No truly novel compounds that are likely to have a significant impact on tuberculosis treatment are close to clinical trials. However, further work to optimize the effectiveness of once-a-week rifapentine regimens using higher doses of the drug and using rifapentine in combination with moxifloxacin is warranted, on the basis of experimental data.
New categories of drugs that have shown promise for use in treating tuberculosis include the nitroimidazopyrans and the oxazolidinones. Experimental data also suggest that a drug to inhibit an enzyme, isocitrate lyase, thought to be necessary for maintaining the latent state, might be useful for treatment of latent tuberculosis infection.
A number of other interventions that might lead to improved treatment outcome have been suggested, although none has undergone rigorous clinical testing. These include various drug delivery systems, cytokine inhibitors, administration of protective cytokines such as interferon-g and interleukin-2, and nutritional supplements, especially vitamin A and zinc.
Research is also needed to identify factors that are predictive of a greater or lesser risk of relapse to determine optimal length of treatment. Identification of such factors would enable more efficient targeting of resources to supervise treatment. In addition, identification of behavioral factors that identify patients at greater or lesser likelihood of being adherent to therapy would also enable more efficient use of DOT.
### Drugs Groups for Treatment of MDR-TB
- Anti-TB drugs are grouped according to efficacy, experience of use and drug class.
- All the first-line anti-TB drugs are in (Group 1), except streptomycin, which is classified with the other injectable agents in (Group 2).
- All the drugs in Groups 2–5 (except streptomycin) are second-line, or reserve, drugs.
- The features of the cross-resistance means that resistance mutations (in M. tuberculosis bacteria) to one anti-TB drug may confer resistance to some or all of the members of the drug family of the same group and less commonly to other members of different drug groups (1).
# WHO Guidelines for second-line Anti-TB Regimens for MDR
- In the treatment of patients with MDR-TB, a Fluoroquinolone should be used (strong recommendation,very low quality evidence).
- In the treatment of patients with MDR-TB, a Ethionamide (or prothionamide) should be used (strong recommendation, very low quality evidence).
- In the treatment of patients with MDR-TB, a later-generation fluoroquinolone rather than an earlier-generation fluoroquinolone should be used (conditional recommendation,very low quality evidence).
- In the treatment of patients with MDR-TB, four second-line antituberculosis drugs likely to be effective (including a parenteral agent), as well as pyrazinamide, should be included in the intensive phase3 (conditional recommendation,very low quality evidence).
- In the treatment of patients with MDR-TB, regimens should include at least pyrazinamide, a fluoroquinolone, a parenteral agent, ethionamide (or prothionamide), and either cycloserine or PAS (p-aminosalicylic acid) if cycloserine cannot be used (conditional recommendation,very low quality evidence).
Major changes in recommendation for second-line Anti-TB Regimens for MDR:
- Include at least four second-line Anti-TB drugs likely to be effective as well as pyrazinamide during the intensive phase of treatment.
- No evidence found to support the use of more than four second-line anti-tuberculosis drugs in patients with extensive disease. Increasing the number of second-line drugs in a regimen is permissible if the effectiveness of some of the drugs is uncertain.
- Ethambutol may be used but is not included among the drugs making up the standard regimen.
- Group 5 drugs may be used but are not included among the drugs making up the standard regimen.
## Treatment in Special Situations
## Culture-Negative Pulmonary Tuberculosis and Radiographic Evidence of Prior Pulmonary Tuberculosis
Failure to isolate M. tuberculosis from persons suspected of having pulmonary tuberculosis on the basis of clinical features and chest radiographic examination does not exclude a diagnosis of active tuberculosis. Alternative diagnoses should be considered carefully and further appropriate diagnostic studies undertaken in persons with apparent culture-negative tuberculosis. The general approach to management is shown in Figure 2. A diagnosis of tuberculosis can be strongly inferred by the clinical and radiographic response to antituberculosis treatment. Careful reevaluation should be performed after 2 months of therapy to determine whether there has been a response attributable to antituberculosis treatment. If either clinical or radiographic improvement is noted and no other etiology is identified, treatment should be continued for active tuberculosis. Treatment regimens in this circumstance include one of the standard 6-month chemotherapy regimens or INH, RIF, PZA, and EMB for 2 months followed by INH and RIF for an additional 2 months (4 months total). However, HIV-infected patients with culture-negative pulmonary tuberculosis should be treated for a minimum of 6 months.
Persons with a positive tuberculin skin test who have radiographic evidence of prior tuberculosis (e.g., upper lobe fibronodular infiltrations) but who have not received adequate therapy are at increased risk for the subsequent development of tuberculosis. Unless previous radiographs are available showing that the abnormality is stable, it is recommended that sputum examination (using sputum induction if necessary) be performed to assess the possibility of active tuberculosis being present. Also, if the patient has symptoms of tuberculosis related to an extrapulmonary site, an appropriate evaluation should be undertaken. Once active tuberculosis has been excluded (i.e., by negative cultures and a stable chest radiograph), the treatment regimens are those used for latent tuberculosis infection: INH for 9 months, RIF (with or without INH) for 4 months, or RIF and PZA for 2 months (for patients who are unlikely to complete a longer course and who can be monitored closely).
### Pregnancy and Breastfeeding
Because of the risk of tuberculosis to the fetus, treatment of tuberculosis in pregnant women should be initiated whenever the probability of maternal disease is moderate to high. The initial treatment regimen should consist of INH, RIF, and EMB. Although all of these drugs cross the placenta, they do not appear to have teratogenic effects. Streptomycin is the only antituberculosis drug documented to have harmful effects on the human fetus (congenital deafness) and should not be used. Although detailed teratogenicity data are not available, PZA can probably be used safely during pregnancy and is recommended by the World Health Organization (WHO) and the International Union against Tuberculosis and Lung Disease (IUATLD). If PZA is not included in the initial treatment regimen, the minimum duration of therapy is 9 months.
Breastfeeding should not be discouraged for women being treated with the first-line antituberculosis agents because the small concentrations of these drugs in breast milk do not produce toxicity in the nursing newborn. Conversely, drugs in breast milk should not be considered to serve as effective treatment for tuberculosis or for latent tuberculosis infection in a nursing infant. Pyridoxine supplementation (25 mg/day) is recommended for all women taking INH who are either pregnant or breastfeeding. The amount of pyridoxine in multivitamins is variable but generally less than the needed amount.
## Treatment of Tuberculosis in Low-Income Countries: Recommendations of the WHO and Guidelines from the IUATLD
The rise in HIV infections and the neglect of TB control programs have enabled a resurgence of tuberculosis. The emergence of drug-resistant strains has also contributed to this new epidemic with, from 2000 to 2004, 20% of TB cases being resistant to standard treatments and 2% resistant to second-line drugs. TB incidence varies widely, even in neighboring countries, apparently because of differences in health care systems. The World Health Organization declared TB a global health emergency in 1993, and the Stop TB Partnership developed a Global Plan to Stop Tuberculosis aiming to save 14 million lives between 2006 and 2015.
To place the current guidelines in an international context it is necessary to have an understanding of the approaches to treatment of tuberculosis in high-incidence, low-income countries. It is important to recognize that the American Thoracic Society/CDC/Infectious Diseases Society of America (ATS/CDC/IDSA) recommendations cannot be assumed to be applicable under all epidemiologic and economic circumstances. The incidence of tuberculosis and the resources with which to confront the disease to an important extent determine the approaches used. Given the increasing proportion of patients in low-incidence countries who were born in high-incidence countries, it is also important for persons managing these cases to be familiar with the approaches used in the countries of origin.
The major international recommendations and guidelines for treating tuberculosis are those of the WHO and of the IUATLD. The WHO document was developed by an expert committee whereas the IUATLD document is a distillation of IUATLD practice, validated in the field.
The WHO and IUATLD documents target, in general, countries in which mycobacterial culture, drug susceptibility testing, radiographic facilities, and second-line drugs are not widely available as a routine. A number of differences exist between these new ATS/CDC/IDSA recommendations, and the current tuberculosis treatment recommendations of the WHO and guidelines of the IUATLD. Both international sets of recommendations are built around a national case management strategy called "DOTS", the acronym for "Directly Observed Therapy, Short course", in which direct observation of therapy (DOT) is only one of five key elements. The five components of DOTS are 1) government commitment to sustained tuberculosis control activities, 2) case detection by sputum smear microscopy among symptomatic patients self-reporting to health services, 3) a standardized treatment regimen of 6-8 months for at least all confirmed sputum smear-positive cases, with DOT for at least the initial 2 months, 4) a regular, uninterrupted supply of all essential antituberculosis drugs, and 5) a standardized recording and reporting system that enables assessment of treatment results for each patient and of the tuberculosis control program overall.
### A Number of Other Differences Exist as Well
The WHO and the IUATLD recommend diagnosis and classification of tuberculosis cases and assessment of response based on sputum AFB smears. Culture and susceptibility testing for new patients is not recommended because of cost, limited applicability, and lack of facilities.
Chest radiography is recommended by both the WHO and IUATLD only for patients with negative sputum smears and is not recommended at all for follow-up.
Both 6- and 8-month treatment regimens are recommended by the WHO. The IUATLD recommends an 8-month regimen with thioacetazone in the continuation phase for HIV-negative patients. For patients suspected of having or known to have HIV infection, ethambutol is substituted for thioacetazone
The WHO and the IUATLD recommend a standardized 8-month regimen for patients who have relapsed, had interrupted treatment, or have failed treatment. Patients who have failed supervised retreatment are considered "chronic" cases and are highly likely to have tuberculosis caused by MDR organisms. Susceptibility testing and a tailored regimen using second-line drugs based on the test results are recommended by the WHO, if testing and second-line drugs are available. The IUATLD recommendations do not address the issue.
Neither baseline nor follow-up biochemical testing is recommended by the WHO and the IUATLD. It is recommended that patients be taught to recognize the symptoms associated with drug toxicity and to report them promptly.
## New Advances in Pharmacotherapy
A new drug, called Bedalaquine, was recently approved by the FDA in December 2012, to treat multi-drug resistant tuberculosis. About 12 million people worldwide had tuberculosis in 2011, and about 630,000 had multidrug-resistant forms of tuberculosis. Bedaquiline affects theproton pump for ATP synthase, which is unlike the quinolones, whose target is DNA gyrase . It was formally approved for use by the U.S. Food and Drug Administration (FDA) for use intuberculosis (TB) treatment- but it is to be used normally only in cases of multi-drug-resistant tuberculosis, and in an even more resistant category, extensively drug resistant tuberculosis. Multi-drug resistant tuberculosis is defined as tuberculosis cases that do not respond to at least two of the four primary (first-line) antibiotics, developed mostly in the 1950s and 1960s, that are used to treat tuberculosis. The drug has been given a black-box warning for arrhythmias which may cause cardiac arrest .
In addition, a novel, 3-drug, anti-TB regimen (PaMZ) consisting of the chemical entity, nitroimidazooxazine, PA-824 (Pa), the fluoroquinolone, moxifloxacin (M), and the first-line TB drug, pyrazinamide (Z), has shown recent promise in the treatment of tuberculosis. The results of a recent phase II clinical trial published in the Lancet, showed that the three drug regimen killed more than 99% of TB bacteria within 2 weeks of treatment.
## A Research Agenda for Tuberculosis Treatment
New antituberculosis drugs are needed for three main reasons: 1) to shorten or otherwise simplify treatment of tuberculosis caused by drug-susceptible organisms, 2) to improve treatment of drug-resistant tuberculosis, and 3) to provide more efficient and effective treatment of latent tuberculosis infection. No truly novel compounds that are likely to have a significant impact on tuberculosis treatment are close to clinical trials. However, further work to optimize the effectiveness of once-a-week rifapentine regimens using higher doses of the drug and using rifapentine in combination with moxifloxacin is warranted, on the basis of experimental data.
New categories of drugs that have shown promise for use in treating tuberculosis include the nitroimidazopyrans and the oxazolidinones. Experimental data also suggest that a drug to inhibit an enzyme, isocitrate lyase, thought to be necessary for maintaining the latent state, might be useful for treatment of latent tuberculosis infection.
A number of other interventions that might lead to improved treatment outcome have been suggested, although none has undergone rigorous clinical testing. These include various drug delivery systems, cytokine inhibitors, administration of protective cytokines such as interferon-g and interleukin-2, and nutritional supplements, especially vitamin A and zinc.
Research is also needed to identify factors that are predictive of a greater or lesser risk of relapse to determine optimal length of treatment. Identification of such factors would enable more efficient targeting of resources to supervise treatment. In addition, identification of behavioral factors that identify patients at greater or lesser likelihood of being adherent to therapy would also enable more efficient use of DOT.
- ↑ Iademarco MF, Castro KG (2003). "Epidemiology of tuberculosis". Seminars in respiratory infections. 18 (4): 225–40. PMID 14679472..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Jump up to: 2.0 2.1 "Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs—worldwide, 2000–2004". MMWR Morb Mortal Wkly Rep. 55 (11): 301–5. 2006. PMID 16557213.
- ↑ Jump up to: 3.0 3.1 Sobero R, Peabody J (2006). "Tuberculosis control in Bolivia, Chile, Colombia and Peru: why does incidence vary so much between neighbors?". Int J Tuberc Lung Dis. 10 (11): 1292–5. PMID 17131791.
- ↑ World Health Organization (WHO). Stop TB Partnership. Retrieved on 3 October 2006.
- ↑ Matteelli A, Carvalho AC, Dooley KE, Kritski A (2010). "TMC207: the first compound of a new class of potent anti-tuberculosis drugs". Future Microbiol. 5 (6): 849–58. doi:10.2217/fmb.10.50. PMC 2921705. PMID 20521931. Unknown parameter |month= ignored (help)CS1 maint: Multiple names: authors list (link)
- ↑ Jump up to: 6.0 6.1 Kotz J (2005). "Targeting tuberculosis". Nature Chemical Biology. doi:10.1038/nchembio002. Unknown parameter |month= ignored (help)
- ↑ Iademarco MF, Castro KG (2003). "Epidemiology of tuberculosis". Seminars in respiratory infections. 18 (4): 225–40. PMID 14679472.
- ↑ World Health Organization (WHO). Stop TB Partnership. Retrieved on 3 October 2006.
- ↑ Matteelli A, Carvalho AC, Dooley KE, Kritski A (2010). "TMC207: the first compound of a new class of potent anti-tuberculosis drugs". Future Microbiol. 5 (6): 849–58. doi:10.2217/fmb.10.50. PMC 2921705. PMID 20521931. Unknown parameter |month= ignored (help)CS1 maint: Multiple names: authors list (link) | Sandbox/mdr
# Treatment of Drug-Resistant Tuberculosis
WHO has recommended the following for the susceptibility and response monitoring of MDR-TB Treatment:
- Rapid drug susceptibility testing (DST) of isoniazid and rifampicin or of rifampicin alone is recommended over conventional testing or no testing at the time of diagnosis of TB(subject to available resources
- The use of sputum smear microscopy and culture rather than sputum smear microscopy alone is recommended for the monitoring of patients with MDR-TB during treatment
### General principles for Designing MDR-TB Treatment Regimens
### Drugs Groups for Treatment of MDR-TB
- Anti-TB drugs are grouped according to efficacy, experience of use and drug class.
- All the first-line anti-TB drugs are in (Group 1), except streptomycin, which is classified with the other injectable agents in (Group 2).
- All the drugs in Groups 2–5 (except streptomycin) are second-line, or reserve, drugs.
- The features of the cross-resistance means that resistance mutations (in M. tuberculosis bacteria) to one anti-TB drug may confer resistance to some or all of the members of the drug family of the same group and less commonly to other members of different drug groups (1).
### Drugs Groups for Treatment of MDR-TB
- Anti-TB drugs are grouped according to efficacy, experience of use and drug class.
- All the first-line anti-TB drugs are in (Group 1), except streptomycin, which is classified with the other injectable agents in (Group 2).
- All the drugs in Groups 2–5 (except streptomycin) are second-line, or reserve, drugs.
- The features of the cross-resistance means that resistance mutations (in M. tuberculosis bacteria) to one anti-TB drug may confer resistance to some or all of the members of the drug family of the same group and less commonly to other members of different drug groups (1).
# WHO Guidelines for second-line Anti-TB Regimens for MDR
- In the treatment of patients with MDR-TB, a Fluoroquinolone should be used (strong recommendation,very low quality evidence).
- In the treatment of patients with MDR-TB, a Ethionamide (or prothionamide) should be used (strong recommendation, very low quality evidence).
- In the treatment of patients with MDR-TB, a later-generation fluoroquinolone rather than an earlier-generation fluoroquinolone should be used (conditional recommendation,very low quality evidence).
- In the treatment of patients with MDR-TB, four second-line antituberculosis drugs likely to be effective (including a parenteral agent), as well as pyrazinamide, should be included in the intensive phase3 (conditional recommendation,very low quality evidence).
- In the treatment of patients with MDR-TB, regimens should include at least pyrazinamide, a fluoroquinolone, a parenteral agent, ethionamide (or prothionamide), and either cycloserine or PAS (p-aminosalicylic acid) if cycloserine cannot be used (conditional recommendation,very low quality evidence).
Major changes in recommendation for second-line Anti-TB Regimens for MDR:
- Include at least four second-line Anti-TB drugs likely to be effective as well as pyrazinamide during the intensive phase of treatment.
- No evidence found to support the use of more than four second-line anti-tuberculosis drugs in patients with extensive disease. Increasing the number of second-line drugs in a regimen is permissible if the effectiveness of some of the drugs is uncertain.
- Ethambutol may be used but is not included among the drugs making up the standard regimen.
- Group 5 drugs may be used but are not included among the drugs making up the standard regimen.
## Treatment in Special Situations
## Culture-Negative Pulmonary Tuberculosis and Radiographic Evidence of Prior Pulmonary Tuberculosis
Failure to isolate M. tuberculosis from persons suspected of having pulmonary tuberculosis on the basis of clinical features and chest radiographic examination does not exclude a diagnosis of active tuberculosis. Alternative diagnoses should be considered carefully and further appropriate diagnostic studies undertaken in persons with apparent culture-negative tuberculosis. The general approach to management is shown in Figure 2. A diagnosis of tuberculosis can be strongly inferred by the clinical and radiographic response to antituberculosis treatment. Careful reevaluation should be performed after 2 months of therapy to determine whether there has been a response attributable to antituberculosis treatment. If either clinical or radiographic improvement is noted and no other etiology is identified, treatment should be continued for active tuberculosis. Treatment regimens in this circumstance include one of the standard 6-month chemotherapy regimens or INH, RIF, PZA, and EMB for 2 months followed by INH and RIF for an additional 2 months (4 months total). However, HIV-infected patients with culture-negative pulmonary tuberculosis should be treated for a minimum of 6 months.
Persons with a positive tuberculin skin test who have radiographic evidence of prior tuberculosis (e.g., upper lobe fibronodular infiltrations) but who have not received adequate therapy are at increased risk for the subsequent development of tuberculosis. Unless previous radiographs are available showing that the abnormality is stable, it is recommended that sputum examination (using sputum induction if necessary) be performed to assess the possibility of active tuberculosis being present. Also, if the patient has symptoms of tuberculosis related to an extrapulmonary site, an appropriate evaluation should be undertaken. Once active tuberculosis has been excluded (i.e., by negative cultures and a stable chest radiograph), the treatment regimens are those used for latent tuberculosis infection: INH for 9 months, RIF (with or without INH) for 4 months, or RIF and PZA for 2 months (for patients who are unlikely to complete a longer course and who can be monitored closely).
### Pregnancy and Breastfeeding
Because of the risk of tuberculosis to the fetus, treatment of tuberculosis in pregnant women should be initiated whenever the probability of maternal disease is moderate to high. The initial treatment regimen should consist of INH, RIF, and EMB. Although all of these drugs cross the placenta, they do not appear to have teratogenic effects. Streptomycin is the only antituberculosis drug documented to have harmful effects on the human fetus (congenital deafness) and should not be used. Although detailed teratogenicity data are not available, PZA can probably be used safely during pregnancy and is recommended by the World Health Organization (WHO) and the International Union against Tuberculosis and Lung Disease (IUATLD). If PZA is not included in the initial treatment regimen, the minimum duration of therapy is 9 months.
Breastfeeding should not be discouraged for women being treated with the first-line antituberculosis agents because the small concentrations of these drugs in breast milk do not produce toxicity in the nursing newborn. Conversely, drugs in breast milk should not be considered to serve as effective treatment for tuberculosis or for latent tuberculosis infection in a nursing infant. Pyridoxine supplementation (25 mg/day) is recommended for all women taking INH who are either pregnant or breastfeeding. The amount of pyridoxine in multivitamins is variable but generally less than the needed amount.
## Treatment of Tuberculosis in Low-Income Countries: Recommendations of the WHO and Guidelines from the IUATLD
The rise in HIV infections and the neglect of TB control programs have enabled a resurgence of tuberculosis.[1] The emergence of drug-resistant strains has also contributed to this new epidemic with, from 2000 to 2004, 20% of TB cases being resistant to standard treatments and 2% resistant to second-line drugs.[2] TB incidence varies widely, even in neighboring countries, apparently because of differences in health care systems.[3] The World Health Organization declared TB a global health emergency in 1993, and the Stop TB Partnership developed a Global Plan to Stop Tuberculosis aiming to save 14 million lives between 2006 and 2015.[4]
To place the current guidelines in an international context it is necessary to have an understanding of the approaches to treatment of tuberculosis in high-incidence, low-income countries. It is important to recognize that the American Thoracic Society/CDC/Infectious Diseases Society of America (ATS/CDC/IDSA) recommendations cannot be assumed to be applicable under all epidemiologic and economic circumstances. The incidence of tuberculosis and the resources with which to confront the disease to an important extent determine the approaches used. Given the increasing proportion of patients in low-incidence countries who were born in high-incidence countries, it is also important for persons managing these cases to be familiar with the approaches used in the countries of origin.
The major international recommendations and guidelines for treating tuberculosis are those of the WHO and of the IUATLD. The WHO document was developed by an expert committee whereas the IUATLD document is a distillation of IUATLD practice, validated in the field.
The WHO and IUATLD documents target, in general, countries in which mycobacterial culture, drug susceptibility testing, radiographic facilities, and second-line drugs are not widely available as a routine. A number of differences exist between these new ATS/CDC/IDSA recommendations, and the current tuberculosis treatment recommendations of the WHO and guidelines of the IUATLD. Both international sets of recommendations are built around a national case management strategy called "DOTS", the acronym for "Directly Observed Therapy, Short course", in which direct observation of therapy (DOT) is only one of five key elements. The five components of DOTS are 1) government commitment to sustained tuberculosis control activities, 2) case detection by sputum smear microscopy among symptomatic patients self-reporting to health services, 3) a standardized treatment regimen of 6-8 months for at least all confirmed sputum smear-positive cases, with DOT for at least the initial 2 months, 4) a regular, uninterrupted supply of all essential antituberculosis drugs, and 5) a standardized recording and reporting system that enables assessment of treatment results for each patient and of the tuberculosis control program overall.
### A Number of Other Differences Exist as Well
The WHO and the IUATLD recommend diagnosis and classification of tuberculosis cases and assessment of response based on sputum AFB smears. Culture and susceptibility testing for new patients is not recommended because of cost, limited applicability, and lack of facilities.
Chest radiography is recommended by both the WHO and IUATLD only for patients with negative sputum smears and is not recommended at all for follow-up.
Both 6- and 8-month treatment regimens are recommended by the WHO. The IUATLD recommends an 8-month regimen with thioacetazone in the continuation phase for HIV-negative patients. For patients suspected of having or known to have HIV infection, ethambutol is substituted for thioacetazone
The WHO and the IUATLD recommend a standardized 8-month regimen for patients who have relapsed, had interrupted treatment, or have failed treatment. Patients who have failed supervised retreatment are considered "chronic" cases and are highly likely to have tuberculosis caused by MDR organisms. Susceptibility testing and a tailored regimen using second-line drugs based on the test results are recommended by the WHO, if testing and second-line drugs are available. The IUATLD recommendations do not address the issue.
Neither baseline nor follow-up biochemical testing is recommended by the WHO and the IUATLD. It is recommended that patients be taught to recognize the symptoms associated with drug toxicity and to report them promptly.
## New Advances in Pharmacotherapy
A new drug, called Bedalaquine, was recently approved by the FDA in December 2012, to treat multi-drug resistant tuberculosis[5]. About 12 million people worldwide had tuberculosis in 2011, and about 630,000 had multidrug-resistant forms of tuberculosis. Bedaquiline affects theproton pump for ATP synthase, which is unlike the quinolones, whose target is DNA gyrase [6]. It was formally approved for use by the U.S. Food and Drug Administration (FDA) for use intuberculosis (TB) treatment- but it is to be used normally only in cases of multi-drug-resistant tuberculosis, and in an even more resistant category, extensively drug resistant tuberculosis. Multi-drug resistant tuberculosis is defined as tuberculosis cases that do not respond to at least two of the four primary (first-line) antibiotics, developed mostly in the 1950s and 1960s, that are used to treat tuberculosis. The drug has been given a black-box warning for arrhythmias which may cause cardiac arrest [7].
In addition, a novel, 3-drug, anti-TB regimen (PaMZ) consisting of the chemical entity, nitroimidazooxazine, PA-824 (Pa), the fluoroquinolone, moxifloxacin (M), and the first-line TB drug, pyrazinamide (Z), has shown recent promise in the treatment of tuberculosis. The results of a recent phase II clinical trial published in the Lancet, showed that the three drug regimen killed more than 99% of TB bacteria within 2 weeks of treatment.
## A Research Agenda for Tuberculosis Treatment
New antituberculosis drugs are needed for three main reasons: 1) to shorten or otherwise simplify treatment of tuberculosis caused by drug-susceptible organisms, 2) to improve treatment of drug-resistant tuberculosis, and 3) to provide more efficient and effective treatment of latent tuberculosis infection. No truly novel compounds that are likely to have a significant impact on tuberculosis treatment are close to clinical trials. However, further work to optimize the effectiveness of once-a-week rifapentine regimens using higher doses of the drug and using rifapentine in combination with moxifloxacin is warranted, on the basis of experimental data.
New categories of drugs that have shown promise for use in treating tuberculosis include the nitroimidazopyrans and the oxazolidinones. Experimental data also suggest that a drug to inhibit an enzyme, isocitrate lyase, thought to be necessary for maintaining the latent state, might be useful for treatment of latent tuberculosis infection.
A number of other interventions that might lead to improved treatment outcome have been suggested, although none has undergone rigorous clinical testing. These include various drug delivery systems, cytokine inhibitors, administration of protective cytokines such as interferon-g and interleukin-2, and nutritional supplements, especially vitamin A and zinc.
Research is also needed to identify factors that are predictive of a greater or lesser risk of relapse to determine optimal length of treatment. Identification of such factors would enable more efficient targeting of resources to supervise treatment. In addition, identification of behavioral factors that identify patients at greater or lesser likelihood of being adherent to therapy would also enable more efficient use of DOT.
### Drugs Groups for Treatment of MDR-TB
- Anti-TB drugs are grouped according to efficacy, experience of use and drug class.
- All the first-line anti-TB drugs are in (Group 1), except streptomycin, which is classified with the other injectable agents in (Group 2).
- All the drugs in Groups 2–5 (except streptomycin) are second-line, or reserve, drugs.
- The features of the cross-resistance means that resistance mutations (in M. tuberculosis bacteria) to one anti-TB drug may confer resistance to some or all of the members of the drug family of the same group and less commonly to other members of different drug groups (1).
# WHO Guidelines for second-line Anti-TB Regimens for MDR
- In the treatment of patients with MDR-TB, a Fluoroquinolone should be used (strong recommendation,very low quality evidence).
- In the treatment of patients with MDR-TB, a Ethionamide (or prothionamide) should be used (strong recommendation, very low quality evidence).
- In the treatment of patients with MDR-TB, a later-generation fluoroquinolone rather than an earlier-generation fluoroquinolone should be used (conditional recommendation,very low quality evidence).
- In the treatment of patients with MDR-TB, four second-line antituberculosis drugs likely to be effective (including a parenteral agent), as well as pyrazinamide, should be included in the intensive phase3 (conditional recommendation,very low quality evidence).
- In the treatment of patients with MDR-TB, regimens should include at least pyrazinamide, a fluoroquinolone, a parenteral agent, ethionamide (or prothionamide), and either cycloserine or PAS (p-aminosalicylic acid) if cycloserine cannot be used (conditional recommendation,very low quality evidence).
Major changes in recommendation for second-line Anti-TB Regimens for MDR:
- Include at least four second-line Anti-TB drugs likely to be effective as well as pyrazinamide during the intensive phase of treatment.
- No evidence found to support the use of more than four second-line anti-tuberculosis drugs in patients with extensive disease. Increasing the number of second-line drugs in a regimen is permissible if the effectiveness of some of the drugs is uncertain.
- Ethambutol may be used but is not included among the drugs making up the standard regimen.
- Group 5 drugs may be used but are not included among the drugs making up the standard regimen.
## Treatment in Special Situations
## Culture-Negative Pulmonary Tuberculosis and Radiographic Evidence of Prior Pulmonary Tuberculosis
Failure to isolate M. tuberculosis from persons suspected of having pulmonary tuberculosis on the basis of clinical features and chest radiographic examination does not exclude a diagnosis of active tuberculosis. Alternative diagnoses should be considered carefully and further appropriate diagnostic studies undertaken in persons with apparent culture-negative tuberculosis. The general approach to management is shown in Figure 2. A diagnosis of tuberculosis can be strongly inferred by the clinical and radiographic response to antituberculosis treatment. Careful reevaluation should be performed after 2 months of therapy to determine whether there has been a response attributable to antituberculosis treatment. If either clinical or radiographic improvement is noted and no other etiology is identified, treatment should be continued for active tuberculosis. Treatment regimens in this circumstance include one of the standard 6-month chemotherapy regimens or INH, RIF, PZA, and EMB for 2 months followed by INH and RIF for an additional 2 months (4 months total). However, HIV-infected patients with culture-negative pulmonary tuberculosis should be treated for a minimum of 6 months.
Persons with a positive tuberculin skin test who have radiographic evidence of prior tuberculosis (e.g., upper lobe fibronodular infiltrations) but who have not received adequate therapy are at increased risk for the subsequent development of tuberculosis. Unless previous radiographs are available showing that the abnormality is stable, it is recommended that sputum examination (using sputum induction if necessary) be performed to assess the possibility of active tuberculosis being present. Also, if the patient has symptoms of tuberculosis related to an extrapulmonary site, an appropriate evaluation should be undertaken. Once active tuberculosis has been excluded (i.e., by negative cultures and a stable chest radiograph), the treatment regimens are those used for latent tuberculosis infection: INH for 9 months, RIF (with or without INH) for 4 months, or RIF and PZA for 2 months (for patients who are unlikely to complete a longer course and who can be monitored closely).
### Pregnancy and Breastfeeding
Because of the risk of tuberculosis to the fetus, treatment of tuberculosis in pregnant women should be initiated whenever the probability of maternal disease is moderate to high. The initial treatment regimen should consist of INH, RIF, and EMB. Although all of these drugs cross the placenta, they do not appear to have teratogenic effects. Streptomycin is the only antituberculosis drug documented to have harmful effects on the human fetus (congenital deafness) and should not be used. Although detailed teratogenicity data are not available, PZA can probably be used safely during pregnancy and is recommended by the World Health Organization (WHO) and the International Union against Tuberculosis and Lung Disease (IUATLD). If PZA is not included in the initial treatment regimen, the minimum duration of therapy is 9 months.
Breastfeeding should not be discouraged for women being treated with the first-line antituberculosis agents because the small concentrations of these drugs in breast milk do not produce toxicity in the nursing newborn. Conversely, drugs in breast milk should not be considered to serve as effective treatment for tuberculosis or for latent tuberculosis infection in a nursing infant. Pyridoxine supplementation (25 mg/day) is recommended for all women taking INH who are either pregnant or breastfeeding. The amount of pyridoxine in multivitamins is variable but generally less than the needed amount.
## Treatment of Tuberculosis in Low-Income Countries: Recommendations of the WHO and Guidelines from the IUATLD
The rise in HIV infections and the neglect of TB control programs have enabled a resurgence of tuberculosis.[8] The emergence of drug-resistant strains has also contributed to this new epidemic with, from 2000 to 2004, 20% of TB cases being resistant to standard treatments and 2% resistant to second-line drugs.[2] TB incidence varies widely, even in neighboring countries, apparently because of differences in health care systems.[3] The World Health Organization declared TB a global health emergency in 1993, and the Stop TB Partnership developed a Global Plan to Stop Tuberculosis aiming to save 14 million lives between 2006 and 2015.[9]
To place the current guidelines in an international context it is necessary to have an understanding of the approaches to treatment of tuberculosis in high-incidence, low-income countries. It is important to recognize that the American Thoracic Society/CDC/Infectious Diseases Society of America (ATS/CDC/IDSA) recommendations cannot be assumed to be applicable under all epidemiologic and economic circumstances. The incidence of tuberculosis and the resources with which to confront the disease to an important extent determine the approaches used. Given the increasing proportion of patients in low-incidence countries who were born in high-incidence countries, it is also important for persons managing these cases to be familiar with the approaches used in the countries of origin.
The major international recommendations and guidelines for treating tuberculosis are those of the WHO and of the IUATLD. The WHO document was developed by an expert committee whereas the IUATLD document is a distillation of IUATLD practice, validated in the field.
The WHO and IUATLD documents target, in general, countries in which mycobacterial culture, drug susceptibility testing, radiographic facilities, and second-line drugs are not widely available as a routine. A number of differences exist between these new ATS/CDC/IDSA recommendations, and the current tuberculosis treatment recommendations of the WHO and guidelines of the IUATLD. Both international sets of recommendations are built around a national case management strategy called "DOTS", the acronym for "Directly Observed Therapy, Short course", in which direct observation of therapy (DOT) is only one of five key elements. The five components of DOTS are 1) government commitment to sustained tuberculosis control activities, 2) case detection by sputum smear microscopy among symptomatic patients self-reporting to health services, 3) a standardized treatment regimen of 6-8 months for at least all confirmed sputum smear-positive cases, with DOT for at least the initial 2 months, 4) a regular, uninterrupted supply of all essential antituberculosis drugs, and 5) a standardized recording and reporting system that enables assessment of treatment results for each patient and of the tuberculosis control program overall.
### A Number of Other Differences Exist as Well
The WHO and the IUATLD recommend diagnosis and classification of tuberculosis cases and assessment of response based on sputum AFB smears. Culture and susceptibility testing for new patients is not recommended because of cost, limited applicability, and lack of facilities.
Chest radiography is recommended by both the WHO and IUATLD only for patients with negative sputum smears and is not recommended at all for follow-up.
Both 6- and 8-month treatment regimens are recommended by the WHO. The IUATLD recommends an 8-month regimen with thioacetazone in the continuation phase for HIV-negative patients. For patients suspected of having or known to have HIV infection, ethambutol is substituted for thioacetazone
The WHO and the IUATLD recommend a standardized 8-month regimen for patients who have relapsed, had interrupted treatment, or have failed treatment. Patients who have failed supervised retreatment are considered "chronic" cases and are highly likely to have tuberculosis caused by MDR organisms. Susceptibility testing and a tailored regimen using second-line drugs based on the test results are recommended by the WHO, if testing and second-line drugs are available. The IUATLD recommendations do not address the issue.
Neither baseline nor follow-up biochemical testing is recommended by the WHO and the IUATLD. It is recommended that patients be taught to recognize the symptoms associated with drug toxicity and to report them promptly.
## New Advances in Pharmacotherapy
A new drug, called Bedalaquine, was recently approved by the FDA in December 2012, to treat multi-drug resistant tuberculosis[10]. About 12 million people worldwide had tuberculosis in 2011, and about 630,000 had multidrug-resistant forms of tuberculosis. Bedaquiline affects theproton pump for ATP synthase, which is unlike the quinolones, whose target is DNA gyrase [6]. It was formally approved for use by the U.S. Food and Drug Administration (FDA) for use intuberculosis (TB) treatment- but it is to be used normally only in cases of multi-drug-resistant tuberculosis, and in an even more resistant category, extensively drug resistant tuberculosis. Multi-drug resistant tuberculosis is defined as tuberculosis cases that do not respond to at least two of the four primary (first-line) antibiotics, developed mostly in the 1950s and 1960s, that are used to treat tuberculosis. The drug has been given a black-box warning for arrhythmias which may cause cardiac arrest [11].
In addition, a novel, 3-drug, anti-TB regimen (PaMZ) consisting of the chemical entity, nitroimidazooxazine, PA-824 (Pa), the fluoroquinolone, moxifloxacin (M), and the first-line TB drug, pyrazinamide (Z), has shown recent promise in the treatment of tuberculosis. The results of a recent phase II clinical trial published in the Lancet, showed that the three drug regimen killed more than 99% of TB bacteria within 2 weeks of treatment.
## A Research Agenda for Tuberculosis Treatment
New antituberculosis drugs are needed for three main reasons: 1) to shorten or otherwise simplify treatment of tuberculosis caused by drug-susceptible organisms, 2) to improve treatment of drug-resistant tuberculosis, and 3) to provide more efficient and effective treatment of latent tuberculosis infection. No truly novel compounds that are likely to have a significant impact on tuberculosis treatment are close to clinical trials. However, further work to optimize the effectiveness of once-a-week rifapentine regimens using higher doses of the drug and using rifapentine in combination with moxifloxacin is warranted, on the basis of experimental data.
New categories of drugs that have shown promise for use in treating tuberculosis include the nitroimidazopyrans and the oxazolidinones. Experimental data also suggest that a drug to inhibit an enzyme, isocitrate lyase, thought to be necessary for maintaining the latent state, might be useful for treatment of latent tuberculosis infection.
A number of other interventions that might lead to improved treatment outcome have been suggested, although none has undergone rigorous clinical testing. These include various drug delivery systems, cytokine inhibitors, administration of protective cytokines such as interferon-g and interleukin-2, and nutritional supplements, especially vitamin A and zinc.
Research is also needed to identify factors that are predictive of a greater or lesser risk of relapse to determine optimal length of treatment. Identification of such factors would enable more efficient targeting of resources to supervise treatment. In addition, identification of behavioral factors that identify patients at greater or lesser likelihood of being adherent to therapy would also enable more efficient use of DOT.
- ↑ Iademarco MF, Castro KG (2003). "Epidemiology of tuberculosis". Seminars in respiratory infections. 18 (4): 225–40. PMID 14679472..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Jump up to: 2.0 2.1 "Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs—worldwide, 2000–2004". MMWR Morb Mortal Wkly Rep. 55 (11): 301–5. 2006. PMID 16557213.
- ↑ Jump up to: 3.0 3.1 Sobero R, Peabody J (2006). "Tuberculosis control in Bolivia, Chile, Colombia and Peru: why does incidence vary so much between neighbors?". Int J Tuberc Lung Dis. 10 (11): 1292–5. PMID 17131791.
- ↑ World Health Organization (WHO). Stop TB Partnership. Retrieved on 3 October 2006.
- ↑ Matteelli A, Carvalho AC, Dooley KE, Kritski A (2010). "TMC207: the first compound of a new class of potent anti-tuberculosis drugs". Future Microbiol. 5 (6): 849–58. doi:10.2217/fmb.10.50. PMC 2921705. PMID 20521931. Unknown parameter |month= ignored (help)CS1 maint: Multiple names: authors list (link)
- ↑ Jump up to: 6.0 6.1 Kotz J (2005). "Targeting tuberculosis". Nature Chemical Biology. doi:10.1038/nchembio002. Unknown parameter |month= ignored (help)
- ↑ http://news.msn.com/science-technology/fda-approves-1st-new-tuberculosis-drug-in-40-years-1?
- ↑ Iademarco MF, Castro KG (2003). "Epidemiology of tuberculosis". Seminars in respiratory infections. 18 (4): 225–40. PMID 14679472.
- ↑ World Health Organization (WHO). Stop TB Partnership. Retrieved on 3 October 2006.
- ↑ Matteelli A, Carvalho AC, Dooley KE, Kritski A (2010). "TMC207: the first compound of a new class of potent anti-tuberculosis drugs". Future Microbiol. 5 (6): 849–58. doi:10.2217/fmb.10.50. PMC 2921705. PMID 20521931. Unknown parameter |month= ignored (help)CS1 maint: Multiple names: authors list (link)
- ↑ http://news.msn.com/science-technology/fda-approves-1st-new-tuberculosis-drug-in-40-years-1? | https://www.wikidoc.org/index.php/Sandbox/mdr | |
0df37aafb80050dc7d97108024748433f7bf78e1 | wikidoc | Sandbox/v13 | Sandbox/v13
# Goal
WikiDoc is dedicated to a transparent and objective process of evaluating your performance as a WikiDoc Scholar. You can use this checklist for self-assessment as well.
# Evaluation Throughout The Year
Throughout the year we will ask that you print out this document and circle those metrics that best characterize your contributions to WikiDoc. You and you alone will determine the trajectory ("D" below average, "C" average, "B" good, or "A" excellent) that you would like to set for yourself.
# Your Trajectory
The quality and quantity of your academic performance will define your career trajectory. In circling the quality metric at the top of each category, you are indicating the career track you would like to purse:
Quality Poor (Cannot Follow, Far Below Average): You will likely not match into a U.S. residency program.
Quality Needs Improvement (Has A Hard Time Following, Below Average): You will likely not match into a U.S. residency program.
Quality Meets Requirements (Follows, Average, a "C"): Matching in a US community hospital residency program will be a stretch goal. You may match if you are in a very very high percentile on your USMLE tests.
Quality Exceeds Requirements (Independent, Good, a "B"):
Quality Outstanding (Leads, Excellent, an "A"):
# Process
- Contact Meghan Ford at [email protected] to request a letter of recommendation.
- Provide an updated CV
- Provide a list of topics which best represent your work
# Objective Metrics
Depending upon your career path at WikiDoc, the following objective metrics may be included in your letter of recommendation:
- Dr. ________________ has made _________ edits to WikiDoc.org.
- Dr. ________________ participated in the WikiDoc Scholars program for _________ months.
- Dr. ________________ completed topics within the differential project.
- Dr. ________________ completed chapters in the Resident Survival Guide.
- Dr. ________________ completed ________ Board Review Questions.
- Dr. ________________ became a certified angiographer.
- Dr. ________________ read _________ films.
# Work Product - The quality and quantity of work produced by you
Quality Poor (Cannot Follow, Far Below Average):
- He / she makes numerous typographical and formatting errors.
- He / she does not consistently capitalize words, proper nouns are not capitalized, a space is not present after a comma, and there are not two spaces between sentences.
- Unfortunately, when or he / she writes to me, they act as though they are communicating with one of their “besties” via text message. The first words of sentences are not capitalized and periods are missing.
- He / she has made frequent errors in collecting or recording data that are harmful to the integrity of our research.
- I have received numerous complaints about the quality of his / her work.
- The quality of his / her work is unacceptable.
- He / she was unable to follow the template for adding content to WikiDoc necessitating extensive revisions by myself and others within our organization. He / she was more of a liability than an asset.
- He / she and does not complete the required work, and moves on to another project before the first project is completed. He / she is not a “closer”.
Quality Needs Improvement (Has A Hard Time Following, Below Average):
- He / she is not as careful in checking work product for errors as he / she could be.
- He / she tends to miss small errors in work product.
- His / her work is completed late or is only partially completed.
Quality Meets Requirements (Follows, Average, a "C"):
- He / she does not require constant supervision.
- His / her error rate is acceptable, and all work is completed in a timely fashion.
- His / her work is completed on time with minimal errors.
Quality Exceeds Requirements (Independent, Good, a "B"):
- The director and co-workers have commented on the consistently high quality of his / her work product.
- He / she takes pride in work and strives to improve their work performance.
- All his / her changes to WikiDoc, slides, letters, reports, and correspondence are completed on time with few errors.
Quality Outstanding (Leads, Excellent, an "A"):
- He / she has less than a 1% error rate when adding content to WikiDoc or when preparing correspondence.
- The accuracy of his / her work is excellent.
Quantity Poor (Cannot Follow, Far Below Average):
- His / her work ethic is poor.
- He / she was often not present in the workplace.
- When at work, he / she has poor time management skills. This individual will not be able to manage multiple competing priorities as an intern or resident and compromise patient care.
- He / she is often on social media sites when I walk by their workstation.
- He / she is often watching videos when I walk by their workstation.
- He / she is often gaming in the workplace.
- He / she talks excessively to his peers and impedes not only his own progress, but that of others around him.
Quantity Needs Improvement (Has A Hard Time Following, Below Average):
- His / her work ethic needs improvement.
- He / she was sometimes not present in the workplace.
- When he / she does come to work, at least the first one hour is spent drinking coffee and conversing about social issues with co-workers.
- This individual may not be able to manage multiple competing priorities as an intern or resident and this may compromise patient care.
Quantity Meets Requirements (Follows, Average, a "C"):
- His / her work ethic is satisfactory and meets but does not exceed requirements for the job.
- He / she was consistently present in the workplace daily five days a week.
- He / she refrains from participating in social media, watching videos, and gaming in the workplace.
- Conversations with his / her peers are of appropriate nature and duration.
- This individual will be challenged to manage multiple competing priorities as an intern or resident.
Quantity Exceeds Requirements (Independent, Good, a "B"):
- His / her work ethic exceeds requirements, and this individual is an emerging professional who is striving to make a career in medicine. He / she consistently works 6 days a week and many evenings.
Quantity Outstanding (Leads, Excellent, an "A"):
- His / her work ethic is outstanding.
- He / she often works 7 days a week and many evenings. When I am editing WikiDoc late at night, I’m always heartened to see him / her editing alongside me. When I am here at 7 PM or on a weekend, he / she is often / always here. I strongly believe that internship and residency is a test of one’s work ethic and character. In selecting a resident, what we all want to know is "would he / she get up at 3:00 AM to see a patient who the nurse thought didn’t look right?” He / she has the commitment, character and work ethic to do just that. As a result of his / her commitment and strong work ethic, I invited him / her on clinical rounds with me. I could tell from his / her interactions with patients that he / she will be a warm, caring, conscientious physician. Given his / her commitment and work ethic, I would be happy to have him / her be my physician. I would like to recruit him / her to return to work with our group.
# Dependability - Being where he / she should be doing what he / she is supposed to do
Poor (Cannot Follow, Far Below Average)
- He / she is often absent from work without prior approval, resulting in excessive unscheduled absences. Obviously this will be disastrous as an intern or resident and could result in adverse patient outcomes.
- He / she leaves the work area unattended to run personal errands. Obviously this will be disastrous as an intern or resident and could result in adverse patient outcomes.
- He / she is frequently late to work and often misses our 8:30 AM team meeting. I worry that this individual will not come to morning report as required by your training program.
- He / she frequently leaves work early. I’m concerned that his /her teammates will have to take up the slack in caring for patients and that this individual will engender enormous amounts of resentment from his / her teammates (as he / she has here). Obviously this may lead to adverse patient outcomes.
Needs Improvement: (Has A Hard Time Following, Below Average):
- He / she is occasionally absent from work without prior approval, resulting in unscheduled absences. Obviously this will be disastrous as an intern or resident and could result in adverse patient outcomes.
- He / she occasionally arrives late to work and occasionally misses our 8:30 AM team meeting. I hope this individual will come to morning report as required by your training program.
- He / she sometimes does not make sure all agreed upon work is completed before leaving for the day. Obviously this will be disastrous as an intern or resident and could result in adverse patient outcomes.
- He / she occasionally leaves work early.
Meets Requirements (Follows, Average, a "C"):
- He / she consistently arrives to work on time.
- He / she makes sure his / her responsibilities are covered at all times.
- He / she has had no unscheduled absences, except for documented personal or family emergencies.
Exceeds Requirements (Independent, Good, a "B"):
- He / she has an excellent attendance record.
Outstanding (Leads, Excellent, an "A"):
- He / she is always at work and on time, if not early.
- He / she never misses work without prior approval and appropriate notification.
- He / she has had no unscheduled absences during the rating period.
- He / she can always be counted on to step up to the plate and work overtime when necessary without complaint.
- I would like to say “if you want something done give it to a busy person”. Despite being very busy I know I can always count on him / her to accomplish our mutual goals.
# Cooperativeness - Working with people
Poor (Cannot Follow, Far Below Average)
- He / she projects an attitude of superiority that turns off other employees.
- At the hospital, we have a fairly small workspace, and he / she is nosy and is always looking over others shoulders at their computer screen or is listening in to others’ conversations inappropriately.
- He / she is not cooperative and frequently criticizes others.
- He / she displays excessive negativity when working with others.
- He / she takes credit for others’ ideas.
- He / she lacks empathy and does not have insight into the emotions of their peers.
- He / she is not sensitive to cultural differences and nuances.
- He / she has made statements that demean others based on gender or race.
- He / she is not a team player.
- He / she cleverly unloads their own work on to others.
- He / she will do anything to get ahead: he / she engages in a two-pronged approach of promoting their own work while demeaning the work of others.
- While he / she was here as a visiting scholar, they were repeatedly disrespectful to the full-time staff.
- He / she is divisive.
- He / she never offers to assist others in the office.
Needs Improvement (Has A Hard Time Following, Below Average):
- He / she displays occasional negativity when working with others.
- He / she rarely offers to assist others in the office.
- He / she makes negative comments that affect working relationships with others.
Meets Requirements (Follows, Average, a "C"):
- He / she is friendly and works with clinical sites, peers and sponsors in a courteous and respectful fashion.
Exceeds Requirements (Independent, Good, a "B"):
- He / she is a “team player” but has become a “team leader” as well.
- He / she is direct, straightforward, honest and polite.
Outstanding (Leads, Excellent, an "A"):
- He / she is the consummate “team player”.
- He / she is well-liked by both those below and above them on the organizational chart.
- He / she is well-liked by clinical sites and sponsors as well as other collaborators.
- He / she is a natural born leader.
- He / she always cordial and willing to help both those above them and below them on the organizational chart as well as collaborators.
- His / her enthusiasm is contagious and lifts the whole group up.
# Adaptability - Adjusting to change
Poor (Cannot Follow, Far Below Average):
- He / she requires repetitive direct supervision, even for mundane and everyday tasks.
- He / she is not able to think independently or to deal with unexpected occurrences.
- Unfortunately the lack of this person’s adaptability will be an impediment to their residency training and may adversely affect patient outcomes.
Needs Improvement (Has A Hard Time Following, Below Average):
- He / she gets flustered in unusual situations.
- He / she does not always make the best decisions to fit the situation.
- Unfortunately the lack of this person’s adaptability will be an impediment to their residency training and may adversely affect patient outcomes.
Meets Requirements (Follows, Average, a "C"):
- He / she usually adjusts as expected to changes in the work place.
- Even during stressful situations, he / she maintains his / her composure.
Exceeds Requirements (Independent, Good, a "B"):
- He / she independently proposes solutions to current problems and develops ways to improve processes to improve our odds of success in the future.
- He / she independently adjusts priorities as needed when unexpected situations arise.
Outstanding (Leads, Excellent, an "A"):
- He / she adapts to new systems and processes well and seeks out training to enhance knowledge, skills and abilities.
- He / she knows when they are in over their head and when to get help. This will be critical to their success as a resident.
- I can tell that they will know when to appropriately contact the supervising resident fellow or attending.
- He / she is proactive rather than reactive.
# Communication - Giving and receiving information
Poor (Cannot Follow, Far Below Average)
- Reports, forms, memos and correspondence are often completed late or not at all by him / her.
- He / she uses a condescending or disdainful tone when talking to others in the office.
- He / she does not take phone messages.
- He / she does not answer the phone.
- He / she does not answer the door.
- He / she does not deliver phone messages to the recipient in a timely fashion.
- His / her phone etiquette is poor.
- He / she does not answer the phone by saying “PERFUSE Study Group, this is ________________ speaking, how may I help you?”
- He / she does not record the call back number for phone messages.
- He / she does not record the date of phone messages.
Needs Improvement (Has A Hard Time Following, Below Average):
- I have received several complaints from sites and sponsors about contradictory or bad information being provided by him / her.
- His / her phone messages are often unclear or incomplete.
Meets Requirements (Follows, Average, a "C"):
- He / she takes messages, writes correspondence, deals with sites and sponsors as well as peers in a polite and courteous fashion.
- His / her reports are accurate, clear and well written using proper grammar and punctuation.
Exceeds Requirements (Independent, Good, a "B"):
- He / she has read and adopted the suggested writing style of the organization.
- The documents he / she prepares are excellent and require little if any editing by me.
- He / she is able to independently respond to the questions of sites, peers and sponsors in a mature and intelligent fashion.
Outstanding (Leads, Excellent, an "A"):
- He / she exhibits an emotionally intelligent, non-confrontational, empathic way of communicating with both those above and below him / her on the organizational chart.
- He / she demonstrates excellent oral and written communication skills.
- He / she is at ease speaking in front of large groups of people.
- He / she is a natural orator and speaks in a way that is compelling.
# Daily Decision Making / Problem Solving - Thinking on the job
Poor (Cannot Follow, Far Below Average)
- He / she frequently comes to the wrong conclusions based on faulty information gathering and poor processing of that information.
- As a supervisor, he / she did not assure that all his / her subordinates were productive at all times, which is a daily requirement of this job.
- I found him / her always in a reactive mode: he / she is always putting out fires, and never planning ahead.
- He / she has poor executive functioning / planning skills.
- He / she cannot triage issues.
- He / she has problems with time management.
Needs Improvement (Has A Hard Time Following, Below Average):
- He / she needs to develop acumen necessary to weigh options and choose the best way to deal with situations.
- He / she spends too much time focusing on less important aspects of daily job.
Meets Requirements (Follows, Average, a "C"):
- He / she often offers workable solutions to problems.
- He / she uses good judgment in solving problems and working with others.
- He / she is objective and uses an objective performance review process to make decisions related to new hires, promotions and merit increases.
Exceeds Requirements (Independent, Good, a "B"):
- He / she can zero in on the cause of problems and offer creative solutions.
- He / she displays strong analytical skills.
Outstanding (Leads, Excellent, an "A"):
- He / she always offers creative ideas to solve problems based on unbiased, high quality information and sound judgment.
- He / she gathers good quality data upon which to make good decisions. He / she listens to both sides the story.
- He / she works to proactively prevent problems rather than functioning in a reactive mode.
- He / she has excellent “court sense” and instinctively knows all that is going on around him / her in the workplace.
- As Wayne Gretzky would say “He / she skates to where the puck is going to be”. He / she anticipates and prevents problems in the workplace before they occur.
- He / she is a “survivor”.
# Service to Clinical Sites / Sponsors / Collaborators
Poor (Cannot Follow, Far Below Average):
- He / she is frequently rude and impolite.
- He / she is lacking in emotional intelligence.
- I’m sad to say I am not comfortable being in a room with this person, and I’ve heard the same for the rest of my staff.
- He / she demonstrates poor relationship skills with sites, sponsors, and other collaborators.
- I don’t trust him / her in dealing with our collaborators as I’m worried they may embarrass our group as they have in the past.
- He / she fails to realize that we are in a service industry, and he / she puts their personal interests and needs at all moments in time above that of our collaborators and their teammates.
Needs Improvement (Has A Hard Time Following, Below Average):
- He / she gets annoyed with collaborators who ask too many questions.
- He / she frequently forgets to follow through on collaborator requests.
Meets Requirements (Follows, Average, a "C"):
- He / she usually maintains a competent and professional demeanor in dealing with clinical sites, sponsors, and collaborators.
- He / she courteous and knowledgeable.
- He / she tries to be helpful to our clinical sites, sponsors and collaborators.
- He / she forwards any complaints or problems to me immediately so that I’m not surprised by any emails or phone calls from our collaborators.
Exceeds Requirements (Independent, Good, a "B"):
- He / she answers all questions courteously, promptly and accurately.
Outstanding (Leads, Excellent, an "A"):
- He / she is a “promise keeper”: he / she always follows through and finds the answers to any questions and reports back to the clinical site, sponsor or collaborator promptly.
- I have received numerous emails and letters praising his / her superb attention to details.
# Use of Equipment and Materials
Poor (Cannot Follow, Far Below Average):
- He / she has damaged equipment through misuse.
- He / she wastes toner, paper and other valuable supplies.
- He / she has deleted software and/or data in error.
- He / she does not provide appropriate care for the equipment at their workstation.
- He / she has unfortunately lost equipment or data.
- He / she has opened others emails during off hours.
- He / she has left the door ajar to the entire office which posed an enormous security risk.
- He / she does not install antivirus software.
- He / she shares their password with others.
Needs Improvement (Has A Hard Time Following, Below Average):
- He / she sometimes forgets to turn equipment off at the end of the day.
- He / she does not always get equipment serviced as recommended by the manufacturer.
- He / she does not renew antivirus software and data has been lost as a result.
- He / she does not retain the warranties of equipment that is purchased.
Meets Requirements (Follows, Average, a "C"):
- He / she takes good care of equipment and uses supplies efficiently.
- He / she turns off and secures all equipment at the end of their shift.
Exceeds Requirements (Independent, Good, a "B"):
- He / she makes recommendations as to new hardware / software that should be acquired to improve our organization.
- He / she quickly masters new software programs.
- He / she can independently troubleshoot IT and equipment problems.
Outstanding (Leads, Excellent, an "A"):
- He / she independently develops code, software or databases to solve problems for our organization.
- He / she is able to independently troubleshoot and solve all work related hardware / software problems quickly and efficiently.
# Project Management
Poor (Cannot Follow, Far Below Average):
- He / she is not a “closer”. Work projects have suffered from lack of follow-through.
- He / she has lost or destroyed important documentation for projects.
- He / she does not have the executive functioning skills to plan ahead to meet project deadlines.
- He / she does not file documents in Google drive.
Needs Improvement (Has A Hard Time Following, Below Average):
- He / she did not keep his / her supervisors of potential problems as they arose.
- Project plans are poorly designed.
- Project plans are not carried out as assigned or on time.
Meets Requirements (Follows, Average, a "C"):
- Prepares project plans on time and in sufficient detail.
- Maintains and monitors progress of project plan in order to stay on target.
Exceeds Requirements (Independent, Good, a "B"):
- He / she independently develops and deploys databases to track trial / project progress.
- He / she acts pro-actively to identify and overcome barriers to enrollment.
- He / she provides meaningful comments regarding the scientific merit and feasibility of clinical trial protocols.
- He / she contributes as a co-author of manuscripts.
Outstanding (Leads, Excellent, an "A"):
- He / she functions in a leadership capacity now in managing trials and core laboratory activities.
- He / she independently prepares CEC and DSMB charters that meet the needs of individual trials.
- He / she independently prepares manuscripts for publication.
# Leadership Skills
Poor (Cannot Follow, Far Below Average):
- He / she dictates to others rather than involving them in the decision making process.
- He / she has reduced subordinates to tears.
- He / she yells and screams at subordinates.
- He / she does not have the capacity to lead a residency team.
Needs Improvement (Has A Hard Time Following, Below Average):
- He / she assumes others should know what to do and how to do it with little or no training.
- He / she frequently becomes impatient when things aren’t going their way.
- He / she may not have the capacity to lead a residency team.
Meets Requirements (Follows, Average, a "C"):
- He / she draws upon the knowledge and skills of others.
- He / she is available when needed to lead the team and has an open door policy for subordinates.
- He / she assigns work fairly and resolves disputes and grievances of subordinates fairly.
- He / she can lead a residency team.
Exceeds Requirements (Independent, Good, a "B"):
- He / she has the confidence and skills to independently lead a team of individuals to complete a simple projects with minimal oversight.
Outstanding (Leads, Excellent, an "A"):
- He / she leads by example.
- He / she seeks consensus, but takes final responsibility for decisions and failures.
- He / she does not ask others to engage in a task that they have not / would not undertake themselves.
- He / she has performed many of the tasks of the organization in the past and has insight into the struggles of employees.
- He / she has exceptional emotional intelligence and is empathic.
- He / she inspires others to improve their performance.
- He / she is charismatic.
- He / she is a visionary.
- He / she sets goals and drives a team to attain those goals.
- He / she is courageous and leads from the “front lines”.
- He / she is self-actualized.
- He / she is “in it to win it”. He / she plays to win and not to avoid losing.
- He / she offers appropriate rewards and praises in recognition of others accomplishments.
- He / she is motivated by the success of the team rather than their individual success.
# What Summary Statement Would You Like Dr. Gibson to Write About You:
- Dr. ________________ attended our WikiDoc scholars program. His / her performance was typical for his peer group. He / she is a nice person.
- Dr. ________________ has successfully met all of the requirements of the Wiki Doc scholars program, and I think he / she will do the same at your residency program.
- On a daily basis, Dr. ________________ has exceeded all of the requirements of the Wiki Doc scholars program, and I am confident that he / she will be an amazing addition to your residency program. In fact I’m so confident of his / her future record of achievement, I hope that he / she will return and undertake cardiovascular training or further research training here in our Harvard program.
- I would like to recruit him / her back to our Harvard program in the future.
- Dr. ________________ will be an excellent addition to any of the most competitive Residency Programs.
- Dr. ________________ has all of the qualities necessary to achieve great success in his / her career.
- Of the hundreds of people that I have supervised in my research laboratory (many of whom have been physicians) over the past 25 years, I would say that Dr. ________________ is at the top 60th 50th 40th 30th 25th 20th 10th 5th 1st _________ percentile.
- Of the hundreds of people that I have mentored over the past 25 years, I would say that Dr. ________________ is among the top 5.
- Of the hundreds of people that I have mentored over the past 25 years, I would say that Dr. ________________ is the top person.
- Dr. ________________ is more likely than any other Brigham resident in the past 10 years to become a Chief of Cardiology. | Sandbox/v13
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Goal
WikiDoc is dedicated to a transparent and objective process of evaluating your performance as a WikiDoc Scholar. You can use this checklist for self-assessment as well.
# Evaluation Throughout The Year
Throughout the year we will ask that you print out this document and circle those metrics that best characterize your contributions to WikiDoc. You and you alone will determine the trajectory ("D" below average, "C" average, "B" good, or "A" excellent) that you would like to set for yourself.
# Your Trajectory
The quality and quantity of your academic performance will define your career trajectory. In circling the quality metric at the top of each category, you are indicating the career track you would like to purse:
Quality Poor (Cannot Follow, Far Below Average): You will likely not match into a U.S. residency program.
Quality Needs Improvement (Has A Hard Time Following, Below Average): You will likely not match into a U.S. residency program.
Quality Meets Requirements (Follows, Average, a "C"): Matching in a US community hospital residency program will be a stretch goal. You may match if you are in a very very high percentile on your USMLE tests.
Quality Exceeds Requirements (Independent, Good, a "B"):
Quality Outstanding (Leads, Excellent, an "A"):
# Process
- Contact Meghan Ford at [email protected] to request a letter of recommendation.
- Provide an updated CV
- Provide a list of topics which best represent your work
# Objective Metrics
Depending upon your career path at WikiDoc, the following objective metrics may be included in your letter of recommendation:
- Dr. ________________ has made _________ edits to WikiDoc.org.
- Dr. ________________ participated in the WikiDoc Scholars program for _________ months.
- Dr. ________________ completed topics within the differential project.
- Dr. ________________ completed chapters in the Resident Survival Guide.
- Dr. ________________ completed ________ Board Review Questions.
- Dr. ________________ became a certified angiographer.
- Dr. ________________ read _________ films.
# Work Product - The quality and quantity of work produced by you
Quality Poor (Cannot Follow, Far Below Average):
- He / she makes numerous typographical and formatting errors.
- He / she does not consistently capitalize words, proper nouns are not capitalized, a space is not present after a comma, and there are not two spaces between sentences.
- Unfortunately, when or he / she writes to me, they act as though they are communicating with one of their “besties” via text message. The first words of sentences are not capitalized and periods are missing.
- He / she has made frequent errors in collecting or recording data that are harmful to the integrity of our research.
- I have received numerous complaints about the quality of his / her work.
- The quality of his / her work is unacceptable.
- He / she was unable to follow the template for adding content to WikiDoc necessitating extensive revisions by myself and others within our organization. He / she was more of a liability than an asset.
- He / she and does not complete the required work, and moves on to another project before the first project is completed. He / she is not a “closer”.
Quality Needs Improvement (Has A Hard Time Following, Below Average):
- He / she is not as careful in checking work product for errors as he / she could be.
- He / she tends to miss small errors in work product.
- His / her work is completed late or is only partially completed.
Quality Meets Requirements (Follows, Average, a "C"):
- He / she does not require constant supervision.
- His / her error rate is acceptable, and all work is completed in a timely fashion.
- His / her work is completed on time with minimal errors.
Quality Exceeds Requirements (Independent, Good, a "B"):
- The director and co-workers have commented on the consistently high quality of his / her work product.
- He / she takes pride in work and strives to improve their work performance.
- All his / her changes to WikiDoc, slides, letters, reports, and correspondence are completed on time with few errors.
Quality Outstanding (Leads, Excellent, an "A"):
- He / she has less than a 1% error rate when adding content to WikiDoc or when preparing correspondence.
- The accuracy of his / her work is excellent.
Quantity Poor (Cannot Follow, Far Below Average):
- His / her work ethic is poor.
- He / she was often not present in the workplace.
- When at work, he / she has poor time management skills. This individual will not be able to manage multiple competing priorities as an intern or resident and compromise patient care.
- He / she is often on social media sites when I walk by their workstation.
- He / she is often watching videos when I walk by their workstation.
- He / she is often gaming in the workplace.
- He / she talks excessively to his peers and impedes not only his own progress, but that of others around him.
Quantity Needs Improvement (Has A Hard Time Following, Below Average):
- His / her work ethic needs improvement.
- He / she was sometimes not present in the workplace.
- When he / she does come to work, at least the first one hour is spent drinking coffee and conversing about social issues with co-workers.
- This individual may not be able to manage multiple competing priorities as an intern or resident and this may compromise patient care.
Quantity Meets Requirements (Follows, Average, a "C"):
- His / her work ethic is satisfactory and meets but does not exceed requirements for the job.
- He / she was consistently present in the workplace daily five days a week.
- He / she refrains from participating in social media, watching videos, and gaming in the workplace.
- Conversations with his / her peers are of appropriate nature and duration.
- This individual will be challenged to manage multiple competing priorities as an intern or resident.
Quantity Exceeds Requirements (Independent, Good, a "B"):
- His / her work ethic exceeds requirements, and this individual is an emerging professional who is striving to make a career in medicine. He / she consistently works 6 days a week and many evenings.
Quantity Outstanding (Leads, Excellent, an "A"):
- His / her work ethic is outstanding.
- He / she often works 7 days a week and many evenings. When I am editing WikiDoc late at night, I’m always heartened to see him / her editing alongside me. When I am here at 7 PM or on a weekend, he / she is often / always here. I strongly believe that internship and residency is a test of one’s work ethic and character. In selecting a resident, what we all want to know is "would he / she get up at 3:00 AM to see a patient who the nurse thought didn’t look right?” He / she has the commitment, character and work ethic to do just that. As a result of his / her commitment and strong work ethic, I invited him / her on clinical rounds with me. I could tell from his / her interactions with patients that he / she will be a warm, caring, conscientious physician. Given his / her commitment and work ethic, I would be happy to have him / her be my physician. I would like to recruit him / her to return to work with our group.
# Dependability - Being where he / she should be doing what he / she is supposed to do
Poor (Cannot Follow, Far Below Average)
- He / she is often absent from work without prior approval, resulting in excessive unscheduled absences. Obviously this will be disastrous as an intern or resident and could result in adverse patient outcomes.
- He / she leaves the work area unattended to run personal errands. Obviously this will be disastrous as an intern or resident and could result in adverse patient outcomes.
- He / she is frequently late to work and often misses our 8:30 AM team meeting. I worry that this individual will not come to morning report as required by your training program.
- He / she frequently leaves work early. I’m concerned that his /her teammates will have to take up the slack in caring for patients and that this individual will engender enormous amounts of resentment from his / her teammates (as he / she has here). Obviously this may lead to adverse patient outcomes.
Needs Improvement: (Has A Hard Time Following, Below Average):
- He / she is occasionally absent from work without prior approval, resulting in unscheduled absences. Obviously this will be disastrous as an intern or resident and could result in adverse patient outcomes.
- He / she occasionally arrives late to work and occasionally misses our 8:30 AM team meeting. I hope this individual will come to morning report as required by your training program.
- He / she sometimes does not make sure all agreed upon work is completed before leaving for the day. Obviously this will be disastrous as an intern or resident and could result in adverse patient outcomes.
- He / she occasionally leaves work early.
Meets Requirements (Follows, Average, a "C"):
- He / she consistently arrives to work on time.
- He / she makes sure his / her responsibilities are covered at all times.
- He / she has had no unscheduled absences, except for documented personal or family emergencies.
Exceeds Requirements (Independent, Good, a "B"):
- He / she has an excellent attendance record.
Outstanding (Leads, Excellent, an "A"):
- He / she is always at work and on time, if not early.
- He / she never misses work without prior approval and appropriate notification.
- He / she has had no unscheduled absences during the rating period.
- He / she can always be counted on to step up to the plate and work overtime when necessary without complaint.
- I would like to say “if you want something done give it to a busy person”. Despite being very busy I know I can always count on him / her to accomplish our mutual goals.
# Cooperativeness - Working with people
Poor (Cannot Follow, Far Below Average)
- He / she projects an attitude of superiority that turns off other employees.
- At the hospital, we have a fairly small workspace, and he / she is nosy and is always looking over others shoulders at their computer screen or is listening in to others’ conversations inappropriately.
- He / she is not cooperative and frequently criticizes others.
- He / she displays excessive negativity when working with others.
- He / she takes credit for others’ ideas.
- He / she lacks empathy and does not have insight into the emotions of their peers.
- He / she is not sensitive to cultural differences and nuances.
- He / she has made statements that demean others based on gender or race.
- He / she is not a team player.
- He / she cleverly unloads their own work on to others.
- He / she will do anything to get ahead: he / she engages in a two-pronged approach of promoting their own work while demeaning the work of others.
- While he / she was here as a visiting scholar, they were repeatedly disrespectful to the full-time staff.
- He / she is divisive.
- He / she never offers to assist others in the office.
Needs Improvement (Has A Hard Time Following, Below Average):
- He / she displays occasional negativity when working with others.
- He / she rarely offers to assist others in the office.
- He / she makes negative comments that affect working relationships with others.
Meets Requirements (Follows, Average, a "C"):
- He / she is friendly and works with clinical sites, peers and sponsors in a courteous and respectful fashion.
Exceeds Requirements (Independent, Good, a "B"):
- He / she is a “team player” but has become a “team leader” as well.
- He / she is direct, straightforward, honest and polite.
Outstanding (Leads, Excellent, an "A"):
- He / she is the consummate “team player”.
- He / she is well-liked by both those below and above them on the organizational chart.
- He / she is well-liked by clinical sites and sponsors as well as other collaborators.
- He / she is a natural born leader.
- He / she always cordial and willing to help both those above them and below them on the organizational chart as well as collaborators.
- His / her enthusiasm is contagious and lifts the whole group up.
# Adaptability - Adjusting to change
Poor (Cannot Follow, Far Below Average):
- He / she requires repetitive direct supervision, even for mundane and everyday tasks.
- He / she is not able to think independently or to deal with unexpected occurrences.
- Unfortunately the lack of this person’s adaptability will be an impediment to their residency training and may adversely affect patient outcomes.
Needs Improvement (Has A Hard Time Following, Below Average):
- He / she gets flustered in unusual situations.
- He / she does not always make the best decisions to fit the situation.
- Unfortunately the lack of this person’s adaptability will be an impediment to their residency training and may adversely affect patient outcomes.
Meets Requirements (Follows, Average, a "C"):
- He / she usually adjusts as expected to changes in the work place.
- Even during stressful situations, he / she maintains his / her composure.
Exceeds Requirements (Independent, Good, a "B"):
- He / she independently proposes solutions to current problems and develops ways to improve processes to improve our odds of success in the future.
- He / she independently adjusts priorities as needed when unexpected situations arise.
Outstanding (Leads, Excellent, an "A"):
- He / she adapts to new systems and processes well and seeks out training to enhance knowledge, skills and abilities.
- He / she knows when they are in over their head and when to get help. This will be critical to their success as a resident.
- I can tell that they will know when to appropriately contact the supervising resident fellow or attending.
- He / she is proactive rather than reactive.
# Communication - Giving and receiving information
Poor (Cannot Follow, Far Below Average)
- Reports, forms, memos and correspondence are often completed late or not at all by him / her.
- He / she uses a condescending or disdainful tone when talking to others in the office.
- He / she does not take phone messages.
- He / she does not answer the phone.
- He / she does not answer the door.
- He / she does not deliver phone messages to the recipient in a timely fashion.
- His / her phone etiquette is poor.
- He / she does not answer the phone by saying “PERFUSE Study Group, this is ________________ speaking, how may I help you?”
- He / she does not record the call back number for phone messages.
- He / she does not record the date of phone messages.
Needs Improvement (Has A Hard Time Following, Below Average):
- I have received several complaints from sites and sponsors about contradictory or bad information being provided by him / her.
- His / her phone messages are often unclear or incomplete.
Meets Requirements (Follows, Average, a "C"):
- He / she takes messages, writes correspondence, deals with sites and sponsors as well as peers in a polite and courteous fashion.
- His / her reports are accurate, clear and well written using proper grammar and punctuation.
Exceeds Requirements (Independent, Good, a "B"):
- He / she has read and adopted the suggested writing style of the organization.
- The documents he / she prepares are excellent and require little if any editing by me.
- He / she is able to independently respond to the questions of sites, peers and sponsors in a mature and intelligent fashion.
Outstanding (Leads, Excellent, an "A"):
- He / she exhibits an emotionally intelligent, non-confrontational, empathic way of communicating with both those above and below him / her on the organizational chart.
- He / she demonstrates excellent oral and written communication skills.
- He / she is at ease speaking in front of large groups of people.
- He / she is a natural orator and speaks in a way that is compelling.
# Daily Decision Making / Problem Solving - Thinking on the job
Poor (Cannot Follow, Far Below Average)
- He / she frequently comes to the wrong conclusions based on faulty information gathering and poor processing of that information.
- As a supervisor, he / she did not assure that all his / her subordinates were productive at all times, which is a daily requirement of this job.
- I found him / her always in a reactive mode: he / she is always putting out fires, and never planning ahead.
- He / she has poor executive functioning / planning skills.
- He / she cannot triage issues.
- He / she has problems with time management.
Needs Improvement (Has A Hard Time Following, Below Average):
- He / she needs to develop acumen necessary to weigh options and choose the best way to deal with situations.
- He / she spends too much time focusing on less important aspects of daily job.
Meets Requirements (Follows, Average, a "C"):
- He / she often offers workable solutions to problems.
- He / she uses good judgment in solving problems and working with others.
- He / she is objective and uses an objective performance review process to make decisions related to new hires, promotions and merit increases.
Exceeds Requirements (Independent, Good, a "B"):
- He / she can zero in on the cause of problems and offer creative solutions.
- He / she displays strong analytical skills.
Outstanding (Leads, Excellent, an "A"):
- He / she always offers creative ideas to solve problems based on unbiased, high quality information and sound judgment.
- He / she gathers good quality data upon which to make good decisions. He / she listens to both sides the story.
- He / she works to proactively prevent problems rather than functioning in a reactive mode.
- He / she has excellent “court sense” and instinctively knows all that is going on around him / her in the workplace.
- As Wayne Gretzky would say “He / she skates to where the puck is going to be”. He / she anticipates and prevents problems in the workplace before they occur.
- He / she is a “survivor”.
# Service to Clinical Sites / Sponsors / Collaborators
Poor (Cannot Follow, Far Below Average):
- He / she is frequently rude and impolite.
- He / she is lacking in emotional intelligence.
- I’m sad to say I am not comfortable being in a room with this person, and I’ve heard the same for the rest of my staff.
- He / she demonstrates poor relationship skills with sites, sponsors, and other collaborators.
- I don’t trust him / her in dealing with our collaborators as I’m worried they may embarrass our group as they have in the past.
- He / she fails to realize that we are in a service industry, and he / she puts their personal interests and needs at all moments in time above that of our collaborators and their teammates.
Needs Improvement (Has A Hard Time Following, Below Average):
- He / she gets annoyed with collaborators who ask too many questions.
- He / she frequently forgets to follow through on collaborator requests.
Meets Requirements (Follows, Average, a "C"):
- He / she usually maintains a competent and professional demeanor in dealing with clinical sites, sponsors, and collaborators.
- He / she courteous and knowledgeable.
- He / she tries to be helpful to our clinical sites, sponsors and collaborators.
- He / she forwards any complaints or problems to me immediately so that I’m not surprised by any emails or phone calls from our collaborators.
Exceeds Requirements (Independent, Good, a "B"):
- He / she answers all questions courteously, promptly and accurately.
Outstanding (Leads, Excellent, an "A"):
- He / she is a “promise keeper”: he / she always follows through and finds the answers to any questions and reports back to the clinical site, sponsor or collaborator promptly.
- I have received numerous emails and letters praising his / her superb attention to details.
# Use of Equipment and Materials
Poor (Cannot Follow, Far Below Average):
- He / she has damaged equipment through misuse.
- He / she wastes toner, paper and other valuable supplies.
- He / she has deleted software and/or data in error.
- He / she does not provide appropriate care for the equipment at their workstation.
- He / she has unfortunately lost equipment or data.
- He / she has opened others emails during off hours.
- He / she has left the door ajar to the entire office which posed an enormous security risk.
- He / she does not install antivirus software.
- He / she shares their password with others.
Needs Improvement (Has A Hard Time Following, Below Average):
- He / she sometimes forgets to turn equipment off at the end of the day.
- He / she does not always get equipment serviced as recommended by the manufacturer.
- He / she does not renew antivirus software and data has been lost as a result.
- He / she does not retain the warranties of equipment that is purchased.
Meets Requirements (Follows, Average, a "C"):
- He / she takes good care of equipment and uses supplies efficiently.
- He / she turns off and secures all equipment at the end of their shift.
Exceeds Requirements (Independent, Good, a "B"):
- He / she makes recommendations as to new hardware / software that should be acquired to improve our organization.
- He / she quickly masters new software programs.
- He / she can independently troubleshoot IT and equipment problems.
Outstanding (Leads, Excellent, an "A"):
- He / she independently develops code, software or databases to solve problems for our organization.
- He / she is able to independently troubleshoot and solve all work related hardware / software problems quickly and efficiently.
# Project Management
Poor (Cannot Follow, Far Below Average):
- He / she is not a “closer”. Work projects have suffered from lack of follow-through.
- He / she has lost or destroyed important documentation for projects.
- He / she does not have the executive functioning skills to plan ahead to meet project deadlines.
- He / she does not file documents in Google drive.
Needs Improvement (Has A Hard Time Following, Below Average):
- He / she did not keep his / her supervisors of potential problems as they arose.
- Project plans are poorly designed.
- Project plans are not carried out as assigned or on time.
Meets Requirements (Follows, Average, a "C"):
- Prepares project plans on time and in sufficient detail.
- Maintains and monitors progress of project plan in order to stay on target.
Exceeds Requirements (Independent, Good, a "B"):
- He / she independently develops and deploys databases to track trial / project progress.
- He / she acts pro-actively to identify and overcome barriers to enrollment.
- He / she provides meaningful comments regarding the scientific merit and feasibility of clinical trial protocols.
- He / she contributes as a co-author of manuscripts.
Outstanding (Leads, Excellent, an "A"):
- He / she functions in a leadership capacity now in managing trials and core laboratory activities.
- He / she independently prepares CEC and DSMB charters that meet the needs of individual trials.
- He / she independently prepares manuscripts for publication.
# Leadership Skills
Poor (Cannot Follow, Far Below Average):
- He / she dictates to others rather than involving them in the decision making process.
- He / she has reduced subordinates to tears.
- He / she yells and screams at subordinates.
- He / she does not have the capacity to lead a residency team.
Needs Improvement (Has A Hard Time Following, Below Average):
- He / she assumes others should know what to do and how to do it with little or no training.
- He / she frequently becomes impatient when things aren’t going their way.
- He / she may not have the capacity to lead a residency team.
Meets Requirements (Follows, Average, a "C"):
- He / she draws upon the knowledge and skills of others.
- He / she is available when needed to lead the team and has an open door policy for subordinates.
- He / she assigns work fairly and resolves disputes and grievances of subordinates fairly.
- He / she can lead a residency team.
Exceeds Requirements (Independent, Good, a "B"):
- He / she has the confidence and skills to independently lead a team of individuals to complete a simple projects with minimal oversight.
Outstanding (Leads, Excellent, an "A"):
- He / she leads by example.
- He / she seeks consensus, but takes final responsibility for decisions and failures.
- He / she does not ask others to engage in a task that they have not / would not undertake themselves.
- He / she has performed many of the tasks of the organization in the past and has insight into the struggles of employees.
- He / she has exceptional emotional intelligence and is empathic.
- He / she inspires others to improve their performance.
- He / she is charismatic.
- He / she is a visionary.
- He / she sets goals and drives a team to attain those goals.
- He / she is courageous and leads from the “front lines”.
- He / she is self-actualized.
- He / she is “in it to win it”. He / she plays to win and not to avoid losing.
- He / she offers appropriate rewards and praises in recognition of others accomplishments.
- He / she is motivated by the success of the team rather than their individual success.
# What Summary Statement Would You Like Dr. Gibson to Write About You:
- Dr. ________________ attended our WikiDoc scholars program. His / her performance was typical for his peer group. He / she is a nice person.
- Dr. ________________ has successfully met all of the requirements of the Wiki Doc scholars program, and I think he / she will do the same at your residency program.
- On a daily basis, Dr. ________________ has exceeded all of the requirements of the Wiki Doc scholars program, and I am confident that he / she will be an amazing addition to your residency program. In fact I’m so confident of his / her future record of achievement, I hope that he / she will return and undertake cardiovascular training or further research training here in our Harvard program.
- I would like to recruit him / her back to our Harvard program in the future.
- Dr. ________________ will be an excellent addition to any of the most competitive Residency Programs.
- Dr. ________________ has all of the qualities necessary to achieve great success in his / her career.
- Of the hundreds of people that I have supervised in my research laboratory (many of whom have been physicians) over the past 25 years, I would say that Dr. ________________ is at the top 60th 50th 40th 30th 25th 20th 10th 5th 1st _________ percentile.
- Of the hundreds of people that I have mentored over the past 25 years, I would say that Dr. ________________ is among the top 5.
- Of the hundreds of people that I have mentored over the past 25 years, I would say that Dr. ________________ is the top person.
- Dr. ________________ is more likely than any other Brigham resident in the past 10 years to become a Chief of Cardiology. | https://www.wikidoc.org/index.php/Sandbox/v13 | |
7ced0909bc3d8e9b7911e47c70b9f90d427f9463 | wikidoc | Sandbox/v22 | Sandbox/v22
# The WikInfect Project — Mission Statement
▸ Thank you for your interest in the WikInfect Project!
▸ The WikInfect Project covers informations of anti-infective agents from FDA package insert as well as treatment recommendations for organ- and pathogen-based infections developed on the basis of guidelines, consensus statements, review articles, and expert opinions by the Infection Mission Force (IMF) team.
▸ The content provided herein is not intended to supplant but supplement clinical judgment. Given the variable nature of epidemiologic scenarios, mandatory adjustments in treatment and infectious disease consultations should always be considered to optimize patient care.
▸ Please let us know if there is specific or more detailed information you would like to see included. Team IMF welcomes your comments to email. | Sandbox/v22
# The WikInfect Project — Mission Statement
▸ Thank you for your interest in the WikInfect Project!
▸ The WikInfect Project covers informations of anti-infective agents from FDA package insert as well as treatment recommendations for organ- and pathogen-based infections developed on the basis of guidelines, consensus statements, review articles, and expert opinions by the Infection Mission Force (IMF) team.
▸ The content provided herein is not intended to supplant but supplement clinical judgment. Given the variable nature of epidemiologic scenarios, mandatory adjustments in treatment and infectious disease consultations should always be considered to optimize patient care.
▸ Please let us know if there is specific or more detailed information you would like to see included. Team IMF welcomes your comments to email. | https://www.wikidoc.org/index.php/Sandbox/v22 | |
3133d306115ab8af7f8653a0a73c4115b3bfad57 | wikidoc | Sandbox/v24 | Sandbox/v24
# Current WikiDoc User Pages
- Once you create a username, you have a User Page.
- On this page you can tell everyone about yourself and your medical qualifications.
- We recommend that post a brief biography including your medical training, degree, specialty, research, or anything else you would like our users to know about you. Do not post your DEA number, medical license number or any other sensitive information
- Learn how to insert your picture here.
- This is also a page that your patients or co-workers can view if they perform a Google search on you.
# WikiDoc Physician Space Page
- Simply click here to see an example of a WikiDoc.
- You can click on your user name at the very top of the page and edit it as desired.
# Discussion Page
- Every registered user has a discussion page (also known as a talk page). To view it, click on the red discussion tab at the top of the page.
- You can leave messages to other users on their discussion page.
- Occasionally, check your own discussion page (by clicking on the my talk link next to your user name at the top of the screen). This is where other members of the community may sometimes leave messages for you. | Sandbox/v24
## Current WikiDoc User Pages
- Once you create a username, you have a User Page.
- On this page you can tell everyone about yourself and your medical qualifications.
- We recommend that post a brief biography including your medical training, degree, specialty, research, or anything else you would like our users to know about you. Do not post your DEA number, medical license number or any other sensitive information
- Learn how to insert your picture here.
- This is also a page that your patients or co-workers can view if they perform a Google search on you.
## WikiDoc Physician Space Page
- Simply click here to see an example of a WikiDoc.
- You can click on your user name at the very top of the page and edit it as desired.
## Discussion Page
- Every registered user has a discussion page (also known as a talk page). To view it, click on the red discussion tab at the top of the page.
- You can leave messages to other users on their discussion page.
- Occasionally, check your own discussion page (by clicking on the my talk link next to your user name at the top of the screen). This is where other members of the community may sometimes leave messages for you. | https://www.wikidoc.org/index.php/Sandbox/v24 | |
a6c9e6327108255702fa452cef5925657fc425ac | wikidoc | Sandbox/v25 | Sandbox/v25
# How to Get Started
- If you would like to watch a video on how to get started click the Getting Started Video
- Experiment with editing in the Sandbox
# Visit the Help Page
- The Help Menu has everything you need to know to get started
- Learn how to Search articles
- Learn more about Creating pages
- Link to other WikiDoc articles and other Web sites
# Write a new article...
- To create an article for WikiDoc, simply enter the title of the article in the search box on the left hand side of the page and click search. | Sandbox/v25
## How to Get Started
- If you would like to watch a video on how to get started click the Getting Started Video
- Experiment with editing in the Sandbox
## Visit the Help Page
- The Help Menu has everything you need to know to get started
- Learn how to Search articles
- Learn more about Creating pages
- Link to other WikiDoc articles and other Web sites
## Write a new article...
- To create an article for WikiDoc, simply enter the title of the article in the search box on the left hand side of the page and click search. | https://www.wikidoc.org/index.php/Sandbox/v25 | |
6595a2b4958dad94458c2813fe3a12b48df68302 | wikidoc | Sandbox/v30 | Sandbox/v30
# Thymic Tumor, Resectable Adapted from NCCN Guidelines: Thymomas and Thymic Carcinomas
† CT scan every 6 months for 2 years, then annually every 5 years for thymic carcinoma and every 10 years for thymoma.
### Chemotherapy Regimens
Return to top
### Radiation Dose
Return to top
- A dose of 60-70 Gy should be given to patients with unresectable disease.
- For adjuvant treatment, the radiation dose consists of 45-50 Gy for clear/close margins and 54 Gy for microscopically positive resection margins. A total dose of 60 Gy and above should be given to patients with gross residual disease (similar to patients with unresectable disease), when conventional fractionation (1.8 to 2.0 Gy per daily fraction) is applied.
- ↑ "" (PDF). External link in |title= (help).mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | Sandbox/v30
# Thymic Tumor, Resectable Adapted from NCCN Guidelines: Thymomas and Thymic Carcinomas[1]
† CT scan every 6 months for 2 years, then annually every 5 years for thymic carcinoma and every 10 years for thymoma.
### Chemotherapy Regimens
Return to top
### Radiation Dose
Return to top
- A dose of 60-70 Gy should be given to patients with unresectable disease.
- For adjuvant treatment, the radiation dose consists of 45-50 Gy for clear/close margins and 54 Gy for microscopically positive resection margins. A total dose of 60 Gy and above should be given to patients with gross residual disease (similar to patients with unresectable disease), when conventional fractionation (1.8 to 2.0 Gy per daily fraction) is applied.
- ↑ "https://www.nccn.org/store/login/login.aspx?ReturnURL=http://www.nccn.org/professionals/physician_gls/pdf/thymic.pdf" (PDF). External link in |title= (help).mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | https://www.wikidoc.org/index.php/Sandbox/v30 | |
bfe23db20e904c7a392adc3214744a9c481a35aa | wikidoc | Sandbox/v46 | Sandbox/v46
# Overview
Acute bacterial meningitis is a medical emergency; commence empiric treatment after obtaining blood and/or cerebrospinal fluid (CSF) cultures if the possibility of bacterial meningitis becomes evident. Once a bacterial etiology has been identified on a CSF Gram stain, treatment regimen should be optimized accordingly. Further modifications may be required after the culture and/or in vitro susceptibility results are available. Neuroimaging (such as CT scan and MRI) or lumbar puncture must not delay antimicrobial therapy.
# Principles of Therapy for Bacterial Meningitis
### Factors Determining Antimicrobial Activity
- Factors determine the acitivity of antimicrobial agents include pharmacodynamics, pharmacokinetics, penetration into the CSF, and bactericidal activity within the CSF.
- Beta-lactams, aminoglycosides, glycopeptides, linezolid, and daptomycin are considered to have poor penetration into the CSF, while fluoroquinolones, chloramphenicol, aztreonam, and tigecycline generally achieve minimum inhibitory concentration (MIC) in the CSF at standard dosage.
- Aminoglycosides and fluoroquinolones express a concentration-dependent manner of bactericidal activity; beta-lactams typically follow a a time-dependent antimicrobial pattern (i.e., the activity is dependent on the time that CSF concentration exceeds MIC as a proportion of the dosing interval).
- Penetration into the CSF is less prominent for drugs with a high molecular weight, high protein-binding ability, low lipid solubility, and drugs that are subject to active transport in the choroid plexus such as penicillins and cephalosporins. Toxicity due to dose escalation may limit the usage the aminoglycosides, glycopeptides, and polymyxins, thus intrathecal or intraventricular administration might be occasionally required (see table below).
### Duration of Antimicrobial Therapy
- The duration of therapy in patients with bacterial meningitis has not been well-supported by evidence-based data.
- The IDSA Practice Guideline provides recommendations on the duration of antimicrobial agents based on microorganisms (see table below). However, the duration of antimicrobial therapy should be individualized in accordance with patient's clinical response.
- Maximum parenteral dosage should be maintained throughout the recommended duration of therapy to ensure adequate bactericidal concentrations are attained since antimicrobial entry attenuates as meningeal inflammation subsides, especially when dexamethasone is co-administered.
### Adjunctive Dexamethasone Therapy
- Evidences for beneficial effects of dexamethasone are variable. In some studies, adjunctive use of dexamethasone for bacterial meningitis in selected groups are associated with an improved survival or prognosis. However, other studies fail to demonstrate a substantial reduction of death or neurological disability. The occurrence of delayed cerebral thrombosis with dexamethasone therapy has been reported.
- In infants and children with Haemophilus influenzae type b meningitis, the IDSA Practice Guideline supports the use of adjunctive Dexamethasone at 0.15 mg/kg q6h for 2—4 days with the first dose administered 10—20 minutes prior to, or at least concomitant with, the first antimicrobial dose.
- In adults with suspected or proven Streptococcus pneumoniae meningitis, the IDSA also recommends Dexamethasone at 0.15 mg/kg q6h for 2—4 days with the first dose administered 10—20 minutes prior to, or at least concomitant with, the first antimicrobial dose. Dexamethasone should only be continued if the CSF Gram stain reveals Gram-positive diplococci, or if blood or CSF cultures are positive for S. pneumoniae. In this scenario, certain authorities advocate the addition of rifampin to the empirical combination of vancomycin plus a third-generation cephalosporin pending culture results and in vitro susceptibility testing.
- Dexamethasone should not be given to patients who have already received animicrobial therapy because it is unlikely to improve clinical outcome.
# Empiric Therapy Adapted from Lancet. 2012;380(9854):1693-702. and N Engl J Med. 2010;362(2):146-54.
# CSF Gram Stain-Based Therapy Adapted from Lancet. 2012;380(9854):1693-702. and Clin Infect Dis. 2004;39(9):1267-84.
# Pathogen-Based Therapy Adapted from Lancet. 2012;380(9854):1693-702. and Clin Infect Dis. 2004;39(9):1267-84. | Sandbox/v46
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [3], Sheng Shi, M.D. [4]
# Overview
Acute bacterial meningitis is a medical emergency; commence empiric treatment after obtaining blood and/or cerebrospinal fluid (CSF) cultures if the possibility of bacterial meningitis becomes evident. Once a bacterial etiology has been identified on a CSF Gram stain, treatment regimen should be optimized accordingly. Further modifications may be required after the culture and/or in vitro susceptibility results are available. Neuroimaging (such as CT scan and MRI) or lumbar puncture must not delay antimicrobial therapy.
# Principles of Therapy for Bacterial Meningitis
### Factors Determining Antimicrobial Activity
- Factors determine the acitivity of antimicrobial agents include pharmacodynamics, pharmacokinetics, penetration into the CSF, and bactericidal activity within the CSF.[1]
- Beta-lactams, aminoglycosides, glycopeptides, linezolid, and daptomycin are considered to have poor penetration into the CSF, while fluoroquinolones, chloramphenicol, aztreonam, and tigecycline generally achieve minimum inhibitory concentration (MIC) in the CSF at standard dosage.[2]
- Aminoglycosides and fluoroquinolones express a concentration-dependent manner of bactericidal activity; beta-lactams typically follow a a time-dependent antimicrobial pattern (i.e., the activity is dependent on the time that CSF concentration exceeds MIC as a proportion of the dosing interval).
- Penetration into the CSF is less prominent for drugs with a high molecular weight, high protein-binding ability, low lipid solubility, and drugs that are subject to active transport in the choroid plexus such as penicillins and cephalosporins. Toxicity due to dose escalation may limit the usage the aminoglycosides, glycopeptides, and polymyxins, thus intrathecal or intraventricular administration might be occasionally required (see table below).
### Duration of Antimicrobial Therapy
- The duration of therapy in patients with bacterial meningitis has not been well-supported by evidence-based data.
- The IDSA Practice Guideline provides recommendations on the duration of antimicrobial agents based on microorganisms (see table below). However, the duration of antimicrobial therapy should be individualized in accordance with patient's clinical response.
- Maximum parenteral dosage should be maintained throughout the recommended duration of therapy to ensure adequate bactericidal concentrations are attained since antimicrobial entry attenuates as meningeal inflammation subsides, especially when dexamethasone is co-administered.
### Adjunctive Dexamethasone Therapy
- Evidences for beneficial effects of dexamethasone are variable. In some studies, adjunctive use of dexamethasone for bacterial meningitis in selected groups are associated with an improved survival or prognosis.[7][8][9][10][11][12] However, other studies fail to demonstrate a substantial reduction of death or neurological disability.[3][13][14][15] The occurrence of delayed cerebral thrombosis with dexamethasone therapy has been reported.[16]
- In infants and children with Haemophilus influenzae type b meningitis, the IDSA Practice Guideline supports the use of adjunctive Dexamethasone at 0.15 mg/kg q6h for 2—4 days with the first dose administered 10—20 minutes prior to, or at least concomitant with, the first antimicrobial dose.[6]
- In adults with suspected or proven Streptococcus pneumoniae meningitis, the IDSA also recommends Dexamethasone at 0.15 mg/kg q6h for 2—4 days with the first dose administered 10—20 minutes prior to, or at least concomitant with, the first antimicrobial dose. Dexamethasone should only be continued if the CSF Gram stain reveals Gram-positive diplococci, or if blood or CSF cultures are positive for S. pneumoniae. In this scenario, certain authorities advocate the addition of rifampin to the empirical combination of vancomycin plus a third-generation cephalosporin pending culture results and in vitro susceptibility testing.[6][17]
- Dexamethasone should not be given to patients who have already received animicrobial therapy because it is unlikely to improve clinical outcome.[6]
# Empiric Therapy Adapted from Lancet. 2012;380(9854):1693-702.[18] and N Engl J Med. 2010;362(2):146-54.[3]
# CSF Gram Stain-Based Therapy Adapted from Lancet. 2012;380(9854):1693-702.[18] and Clin Infect Dis. 2004;39(9):1267-84.[6]
# Pathogen-Based Therapy Adapted from Lancet. 2012;380(9854):1693-702.[18] and Clin Infect Dis. 2004;39(9):1267-84.[6] | https://www.wikidoc.org/index.php/Sandbox/v46 | |
14c3cf69a3802a6edfa8c437c319252c91249770 | wikidoc | Sandbox:ABC | Sandbox:ABC
Synonyms and keywords: Broad beta disease; broad beta hyperlipoproteinemia; broad-beta hyperlipoproteinemia; dysbetalipoproteinemia; familial dysbetalipoproteinemia; familial hypercholesterolemia with hyperlipemia; type III hyperlipoproteinemia
# Overview
Familial dysbetalipoproteinemia is a disorder passed down through families in which there are high amounts of cholesterol and triglycerides in the blood. This form is due to high chylomicrons and IDL (intermediate density lipoprotein). Also known as broad beta disease or dysbetalipoproteinemia, the most common cause for this form is the presence of ApoE E2/E2 genotype. It is due to cholesterol-rich VLDL (β-VLDL). Prevalence is 0.02% of the population.
Hyperlipoproteinemia type III, also known as dysbetalipoproteinemia or broad beta disease, is a rare genetic disorder characterized by improper breakdown (metabolism) of certain fatty materials known as lipids, specifically cholesterol and triglycerides. This results in the abnormal accumulation of lipids in the body (hyperlipidemia). Affected individuals may develop multiple yellowish, lipid-filled bumps (papules) or plaques on the skin (xanthomas). Affected individuals may also develop the buildup of fatty materials in the blood vessels (artherosclerosis) potentially obstructing blood flow and resulting in coronary heart disease or peripheral vascular disease. Most cases of hyperlipoproteinemia type III are inherited as an autosomal recessive trait.
# Causes
A genetic defect causes this condition. The defect results in the build up of large lipoprotein particles that contain both cholesterol and triglycerides, a type of fat. The disease is linked to defects in the gene for apolipoprotein E in many cases.
Hypothyroidism, obesity, or diabetes can make the condition worse. Risk factors for familial dysbetalipoproteinemia include a family history of the disorder or coronary artery disease.
Most cases of hyperlipoproteinemia type III are inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.
Symptoms of hyperlipoproteinemia type III develop due to the improper function or imbalance of special proteins in the blood (protein-lipid molecules known as apo E) that transport cholesterol and other fats from one area of the body to another and help clear fats from the blood.
The gene that is responsible for the production of apo E is located on the long arm of chromosome 19 (19q13). The gene occurs in many forms (alleles), the three most common of which are known as e2, e3 and e4. Every person had two apo E genes in some combination of these various forms. Physicians consider apo e3 the “normal” form of the gene; others are considered mutations of the apo E gene.
Most cases of recessively inherited hyperlipoproteinemia type III result from inheritance of two genes that code for apo e2. Apo e2 clears dietary fats from the body at a slower rate than apo e3. However, the presence of two apo e2-coding genes by itself usually does not result in the development of symptoms of hyperlipoproteinemia type III. In fact, fewer than 10 percent of individuals with two genes coding for apo e2 ever develop outward symptoms of hyperlipoproteinemia type III. Researchers believe that additional genetic, environmental, or hormonal factors play a role in the development of the disorder. These factors may include the presence of other disorders (e.g., hypothyroidism, diabetes), obesity, or age. In women, low estrogen levels may contribute to the development of symptoms, which is why the disorder occurs in women after menopause.
There are approximately 25 additional, extremely rare variants of apo E, some of which also cause hyperlipoproteinemia type III. These rare variants of the apo E gene are inherited as autosomal dominant traits.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
Individuals with the dominant forms of hyperlipoproteinemia type III may experience symptoms from birth. Additional genetic, environmental and hormonal factors may determine the severity of the disorder.
# Differential Diagnosis
Symptoms of the following disorders can be similar to those of hyperlipoproteinemia type III. Comparisons may be useful for a differential diagnosis:
Hyperlipoproteinemias are a group of inherited lipid storage and transport diseases that are characterized by excessive levels of certain fats (lipoproteins) in the blood. In addition to hyperlipoproteinemia type III, this group of disorders includes hyperlipoproteinemia type I (familial hyperchylomicronemia); hyperlipoproteinemia type II (familial hyperbetalipoproteinemia); familial hyperlipoproteinemia type IV (carbohydrate induced hyperlipemia); and hyperlipoproteinemia type V (fat and carbohydrate hyperlipemia). Symptoms of all of these forms of hyperlipoproteinemia include the abnormal accumulation of fatty material in the walls that line medium and large arteries and the presence of multiple yellow fatty deposits (xanthomas) on certain areas of the skin. (For more information on these disorders, choose “Hyperlipoproteinemia” as your search term in the Rare Disease Database.)
Hyperlipoproteinemia type IV is an inborn error of metabolism characterized by an abnormal increase in the blood level of certain fats called triglycerides. The body’s ability to use sugar (glucose tolerance) may also be impaired. Symptoms include fatty nodules or plaques (xanthomas) on the arms, legs, and/or buttocks. Hyperlipoproteinemia type IV usually leads to the degeneration of blood vessels and heart disease. The liver and spleen may also be enlarged (hepatosplenomegaly). Hyperlipoproteinemia type IV is inherited as an autosomal dominant trait. (For more information on this disorder, choose “Hyperlipoproteinemia Type IV” as your search term in the Rare Disease Database.)
Hyperlipoproteinemia type I (familial hyperchylomicronemia) is a rare inherited disorder that prevents children born with it from transporting dietary cholesterol and/or triglycerides properly. (Chylomicrons are another lipoprotein-complex essential to the transport of fat from the stomach to various organs of the body.) In this case, the presence of extremely high levels of triglycerides does not commonly lead to hardening of the arteries (atherosclerosis) but potentially serious inflammation of the pancreas (pancreatitis) may accompany the symptoms of this disorder. Severe abdominal pain is experienced after eating fatty foods. Fatty growths on the skin (eruptive xanthomas) are not uncommon. People with this form must minimize the eating of dietary fats of any kind.
### Related Disorders
Symptoms of the following disorders can be similar to those of hyperlipoproteinemia type III. Comparisons may be useful for a differential diagnosis:
Hyperlipoproteinemias are a group of inherited lipid storage and transport diseases that are characterized by excessive levels of certain fats (lipoproteins) in the blood. In addition to hyperlipoproteinemia type III, this group of disorders includes hyperlipoproteinemia type I (familial hyperchylomicronemia); hyperlipoproteinemia type II (familial hyperbetalipoproteinemia); familial hyperlipoproteinemia type IV (carbohydrate induced hyperlipemia); and hyperlipoproteinemia type V (fat and carbohydrate hyperlipemia). Symptoms of all of these forms of hyperlipoproteinemia include the abnormal accumulation of fatty material in the walls that line medium and large arteries and the presence of multiple yellow fatty deposits (xanthomas) on certain areas of the skin. (For more information on these disorders, choose “Hyperlipoproteinemia” as your search term in the Rare Disease Database.)
Hyperlipoproteinemia type IV is an inborn error of metabolism characterized by an abnormal increase in the blood level of certain fats called triglycerides. The body’s ability to use sugar (glucose tolerance) may also be impaired. Symptoms include fatty nodules or plaques (xanthomas) on the arms, legs, and/or buttocks. Hyperlipoproteinemia type IV usually leads to the degeneration of blood vessels and heart disease. The liver and spleen may also be enlarged (hepatosplenomegaly). Hyperlipoproteinemia type IV is inherited as an autosomal dominant trait. (For more information on this disorder, choose “Hyperlipoproteinemia Type IV” as your search term in the Rare Disease Database.)
Hyperlipoproteinemia type I (familial hyperchylomicronemia) is a rare inherited disorder that prevents children born with it from transporting dietary cholesterol and/or triglycerides properly. (Chylomicrons are another lipoprotein-complex essential to the transport of fat from the stomach to various organs of the body.) In this case, the presence of extremely high levels of triglycerides does not commonly lead to hardening of the arteries (atherosclerosis) but potentially serious inflammation of the pancreas (pancreatitis) may accompany the symptoms of this disorder. Severe abdominal pain is experienced after eating fatty foods. Fatty growths on the skin (eruptive xanthomas) are not uncommon. People with this form must minimize the eating of dietary fats of any kind.
### Diagnosis
There is no specific diagnostic test for hyperlipoproteinemia type III. A diagnosis is made based upon a thorough clinical evaluation, a detailed patient history, and identification of characteristic findings such as xanthoma striata palmaris. Tests may be performed that demonstrate elevated levels of cholesterol and triglycerides (hyperlipidemia), which occurs after fasting; reveal the presence of very low density lipoproteins (VLDLs), a type of lipoprotein that is elevated in individuals with hyperlipoproteinemia type III; and demonstrate an increased ratio between VLDLs to plasma triglycerides. A test known as electrophoresis may be used to demonstrate abnormal lipoproteins. Electrophoresis is a laboratory test that measures protein levels in the blood or urine by using an electric current to separate proteins by molecular size.
Genotyping is a test that determines what form (allele) of gene is present. A simple blood test can determine whether an individual has two apo e2 genes. When these genes are found a person with characteristic symptoms, it is diagnostic of hyperlipoproteinemia type III.
### Standard Therapies
Treatment
Most individuals with hyperlipoproteinemia type III respond to dietary therapy that consists of a diet that is low in cholesterol and saturated fat. The reduction of the intake of dietary cholesterol and other fats generally prevents xanthomas and high lipid levels in the blood (hyperlipidemia). Exercise in addition to dietary therapy may help lower lipid levels.
In individuals in whom dietary modification does not lower lipid levels, certain drugs may be used. These drugs include niacin, gemfibrozil, clofibrate, and/or lovastatin. Other drugs, such as cholestyramine and colestipol are not effective for the treatment of Broad Beta Disease; they may actually raise blood levels of beta-lipoproteins.
Xanthomas can sometimes be removed surgically. Treatment of cardiovascular disease is symptomatic. Because estrogen improves the clearance of specific lipids associated with hyperlipoproteinemia type III, estrogen therapy may help some postmenopausal women with this disorder.
Genetic counseling may be of benefit for people with hyperlipoproteinemia type III and their families. Other treatment is symptomatic and supportive.
### Investigational Therapies
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
### Affected Populations
Hyperlipoproteinemia type III affects males more often than females. The majority of cases occur during early adulthood, although cases have been reported in children and the elderly. Women are rarely affected until after menopause.
The incidence of hyperlipoproteinemia is unknown. It is estimated to affect approximately 1 in 5,000-10,000 people in the general population.
# Symptoms
Symptoms may not be seen until age 20 or older.
Yellow deposits of fatty material in the skin called xanthomas may appear on the eyelids, palms of the hands, soles of the feet, or on the tendons of the knees and elbows.
Atherosclerosis develops. There may be early chest pain (angina) or decreased blood flow to specific parts of the body, causing transient ischemic attacks of the brain or peripheral artery disease.
# Exams and Tests
Tests that may be done to diagnose this condition include:
- Angiogram
- Genetic testing for apolipoprotein E (apoE)
- Heart stress test
- Total cholesterol
- Triglyceride level
- Very low density lipoprotein (VLDL) test
# Treatment
The goal of treatment is to control underlying conditions such as obesity, hypothyroidism, and diabetes.
Reducing calories, saturated fats, and cholesterol may significantly reduce cholesterol levels.
If high cholesterol and triglyceride levels continue despite diet changes, your doctor may recommend medicine to lower your cholesterol. Medicine to lower cholesterol levels include:
- Bile acid-sequestering resins
- Fibrates
- Nicotinic acid
- Statins
Treatment
Most individuals with hyperlipoproteinemia type III respond to dietary therapy that consists of a diet that is low in cholesterol and saturated fat. The reduction of the intake of dietary cholesterol and other fats generally prevents xanthomas and high lipid levels in the blood (hyperlipidemia). Exercise in addition to dietary therapy may help lower lipid levels.
In individuals in whom dietary modification does not lower lipid levels, certain drugs may be used. These drugs include niacin, gemfibrozil, clofibrate, and/or lovastatin. Other drugs, such as cholestyramine and colestipol are not effective for the treatment of Broad Beta Disease; they may actually raise blood levels of beta-lipoproteins.
Xanthomas can sometimes be removed surgically. Treatment of cardiovascular disease is symptomatic. Because estrogen improves the clearance of specific lipids associated with hyperlipoproteinemia type III, estrogen therapy may help some postmenopausal women with this disorder.
Genetic counseling may be of benefit for people with hyperlipoproteinemia type III and their families. Other treatment is symptomatic and supportive.
# Prognosis
Persons with this condition have an increased risk for coronary artery disease and peripheral vascular disease.
With treatment, most people show a significant reduction in lipid levels.
# Possible Complications
- Heart attack
- Stroke
- Peripheral vascular disease
- Intermittent claudication
- Gangrene of the lower extremities
# Prevention
Screening the family members of those with familial dysbetalipoproteinemia may lead to early detection and treatment.
Early treatment and avoiding other risk factors for vascular disease (such as smoking) are crucial to preventing early heart attacks, strokes, and blocked blood vessels. | Sandbox:ABC
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Broad beta disease; broad beta hyperlipoproteinemia; broad-beta hyperlipoproteinemia; dysbetalipoproteinemia; familial dysbetalipoproteinemia; familial hypercholesterolemia with hyperlipemia; type III hyperlipoproteinemia
# Overview
Familial dysbetalipoproteinemia is a disorder passed down through families in which there are high amounts of cholesterol and triglycerides in the blood. This form is due to high chylomicrons and IDL (intermediate density lipoprotein). Also known as broad beta disease or dysbetalipoproteinemia, the most common cause for this form is the presence of ApoE E2/E2 genotype. It is due to cholesterol-rich VLDL (β-VLDL). Prevalence is 0.02% of the population.
Hyperlipoproteinemia type III, also known as dysbetalipoproteinemia or broad beta disease, is a rare genetic disorder characterized by improper breakdown (metabolism) of certain fatty materials known as lipids, specifically cholesterol and triglycerides. This results in the abnormal accumulation of lipids in the body (hyperlipidemia). Affected individuals may develop multiple yellowish, lipid-filled bumps (papules) or plaques on the skin (xanthomas). Affected individuals may also develop the buildup of fatty materials in the blood vessels (artherosclerosis) potentially obstructing blood flow and resulting in coronary heart disease or peripheral vascular disease. Most cases of hyperlipoproteinemia type III are inherited as an autosomal recessive trait.
# Causes
A genetic defect causes this condition. The defect results in the build up of large lipoprotein particles that contain both cholesterol and triglycerides, a type of fat. The disease is linked to defects in the gene for apolipoprotein E in many cases.
Hypothyroidism, obesity, or diabetes can make the condition worse. Risk factors for familial dysbetalipoproteinemia include a family history of the disorder or coronary artery disease.
Most cases of hyperlipoproteinemia type III are inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.
Symptoms of hyperlipoproteinemia type III develop due to the improper function or imbalance of special proteins in the blood (protein-lipid molecules known as apo E) that transport cholesterol and other fats from one area of the body to another and help clear fats from the blood.
The gene that is responsible for the production of apo E is located on the long arm of chromosome 19 (19q13). The gene occurs in many forms (alleles), the three most common of which are known as e2, e3 and e4. Every person had two apo E genes in some combination of these various forms. Physicians consider apo e3 the “normal” form of the gene; others are considered mutations of the apo E gene.
Most cases of recessively inherited hyperlipoproteinemia type III result from inheritance of two genes that code for apo e2. Apo e2 clears dietary fats from the body at a slower rate than apo e3. However, the presence of two apo e2-coding genes by itself usually does not result in the development of symptoms of hyperlipoproteinemia type III. In fact, fewer than 10 percent of individuals with two genes coding for apo e2 ever develop outward symptoms of hyperlipoproteinemia type III. Researchers believe that additional genetic, environmental, or hormonal factors play a role in the development of the disorder. These factors may include the presence of other disorders (e.g., hypothyroidism, diabetes), obesity, or age. In women, low estrogen levels may contribute to the development of symptoms, which is why the disorder occurs in women after menopause.
There are approximately 25 additional, extremely rare variants of apo E, some of which also cause hyperlipoproteinemia type III. These rare variants of the apo E gene are inherited as autosomal dominant traits.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
Individuals with the dominant forms of hyperlipoproteinemia type III may experience symptoms from birth. Additional genetic, environmental and hormonal factors may determine the severity of the disorder.
# Differential Diagnosis
Symptoms of the following disorders can be similar to those of hyperlipoproteinemia type III. Comparisons may be useful for a differential diagnosis:
Hyperlipoproteinemias are a group of inherited lipid storage and transport diseases that are characterized by excessive levels of certain fats (lipoproteins) in the blood. In addition to hyperlipoproteinemia type III, this group of disorders includes hyperlipoproteinemia type I (familial hyperchylomicronemia); hyperlipoproteinemia type II (familial hyperbetalipoproteinemia); familial hyperlipoproteinemia type IV (carbohydrate induced hyperlipemia); and hyperlipoproteinemia type V (fat and carbohydrate hyperlipemia). Symptoms of all of these forms of hyperlipoproteinemia include the abnormal accumulation of fatty material in the walls that line medium and large arteries and the presence of multiple yellow fatty deposits (xanthomas) on certain areas of the skin. (For more information on these disorders, choose “Hyperlipoproteinemia” as your search term in the Rare Disease Database.)
Hyperlipoproteinemia type IV is an inborn error of metabolism characterized by an abnormal increase in the blood level of certain fats called triglycerides. The body’s ability to use sugar (glucose tolerance) may also be impaired. Symptoms include fatty nodules or plaques (xanthomas) on the arms, legs, and/or buttocks. Hyperlipoproteinemia type IV usually leads to the degeneration of blood vessels and heart disease. The liver and spleen may also be enlarged (hepatosplenomegaly). Hyperlipoproteinemia type IV is inherited as an autosomal dominant trait. (For more information on this disorder, choose “Hyperlipoproteinemia Type IV” as your search term in the Rare Disease Database.)
Hyperlipoproteinemia type I (familial hyperchylomicronemia) is a rare inherited disorder that prevents children born with it from transporting dietary cholesterol and/or triglycerides properly. (Chylomicrons are another lipoprotein-complex essential to the transport of fat from the stomach to various organs of the body.) In this case, the presence of extremely high levels of triglycerides does not commonly lead to hardening of the arteries (atherosclerosis) but potentially serious inflammation of the pancreas (pancreatitis) may accompany the symptoms of this disorder. Severe abdominal pain is experienced after eating fatty foods. Fatty growths on the skin (eruptive xanthomas) are not uncommon. People with this form must minimize the eating of dietary fats of any kind.
### Related Disorders
Symptoms of the following disorders can be similar to those of hyperlipoproteinemia type III. Comparisons may be useful for a differential diagnosis:
Hyperlipoproteinemias are a group of inherited lipid storage and transport diseases that are characterized by excessive levels of certain fats (lipoproteins) in the blood. In addition to hyperlipoproteinemia type III, this group of disorders includes hyperlipoproteinemia type I (familial hyperchylomicronemia); hyperlipoproteinemia type II (familial hyperbetalipoproteinemia); familial hyperlipoproteinemia type IV (carbohydrate induced hyperlipemia); and hyperlipoproteinemia type V (fat and carbohydrate hyperlipemia). Symptoms of all of these forms of hyperlipoproteinemia include the abnormal accumulation of fatty material in the walls that line medium and large arteries and the presence of multiple yellow fatty deposits (xanthomas) on certain areas of the skin. (For more information on these disorders, choose “Hyperlipoproteinemia” as your search term in the Rare Disease Database.)
Hyperlipoproteinemia type IV is an inborn error of metabolism characterized by an abnormal increase in the blood level of certain fats called triglycerides. The body’s ability to use sugar (glucose tolerance) may also be impaired. Symptoms include fatty nodules or plaques (xanthomas) on the arms, legs, and/or buttocks. Hyperlipoproteinemia type IV usually leads to the degeneration of blood vessels and heart disease. The liver and spleen may also be enlarged (hepatosplenomegaly). Hyperlipoproteinemia type IV is inherited as an autosomal dominant trait. (For more information on this disorder, choose “Hyperlipoproteinemia Type IV” as your search term in the Rare Disease Database.)
Hyperlipoproteinemia type I (familial hyperchylomicronemia) is a rare inherited disorder that prevents children born with it from transporting dietary cholesterol and/or triglycerides properly. (Chylomicrons are another lipoprotein-complex essential to the transport of fat from the stomach to various organs of the body.) In this case, the presence of extremely high levels of triglycerides does not commonly lead to hardening of the arteries (atherosclerosis) but potentially serious inflammation of the pancreas (pancreatitis) may accompany the symptoms of this disorder. Severe abdominal pain is experienced after eating fatty foods. Fatty growths on the skin (eruptive xanthomas) are not uncommon. People with this form must minimize the eating of dietary fats of any kind.
### Diagnosis
There is no specific diagnostic test for hyperlipoproteinemia type III. A diagnosis is made based upon a thorough clinical evaluation, a detailed patient history, and identification of characteristic findings such as xanthoma striata palmaris. Tests may be performed that demonstrate elevated levels of cholesterol and triglycerides (hyperlipidemia), which occurs after fasting; reveal the presence of very low density lipoproteins (VLDLs), a type of lipoprotein that is elevated in individuals with hyperlipoproteinemia type III; and demonstrate an increased ratio between VLDLs to plasma triglycerides. A test known as electrophoresis may be used to demonstrate abnormal lipoproteins. Electrophoresis is a laboratory test that measures protein levels in the blood or urine by using an electric current to separate proteins by molecular size.
Genotyping is a test that determines what form (allele) of gene is present. A simple blood test can determine whether an individual has two apo e2 genes. When these genes are found a person with characteristic symptoms, it is diagnostic of hyperlipoproteinemia type III.
### Standard Therapies
Treatment
Most individuals with hyperlipoproteinemia type III respond to dietary therapy that consists of a diet that is low in cholesterol and saturated fat. The reduction of the intake of dietary cholesterol and other fats generally prevents xanthomas and high lipid levels in the blood (hyperlipidemia). Exercise in addition to dietary therapy may help lower lipid levels.
In individuals in whom dietary modification does not lower lipid levels, certain drugs may be used. These drugs include niacin, gemfibrozil, clofibrate, and/or lovastatin. Other drugs, such as cholestyramine and colestipol are not effective for the treatment of Broad Beta Disease; they may actually raise blood levels of beta-lipoproteins.
Xanthomas can sometimes be removed surgically. Treatment of cardiovascular disease is symptomatic. Because estrogen improves the clearance of specific lipids associated with hyperlipoproteinemia type III, estrogen therapy may help some postmenopausal women with this disorder.
Genetic counseling may be of benefit for people with hyperlipoproteinemia type III and their families. Other treatment is symptomatic and supportive.
### Investigational Therapies
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
### Affected Populations
Hyperlipoproteinemia type III affects males more often than females. The majority of cases occur during early adulthood, although cases have been reported in children and the elderly. Women are rarely affected until after menopause.
The incidence of hyperlipoproteinemia is unknown. It is estimated to affect approximately 1 in 5,000-10,000 people in the general population.
# Symptoms
Symptoms may not be seen until age 20 or older.
Yellow deposits of fatty material in the skin called xanthomas may appear on the eyelids, palms of the hands, soles of the feet, or on the tendons of the knees and elbows.
Atherosclerosis develops. There may be early chest pain (angina) or decreased blood flow to specific parts of the body, causing transient ischemic attacks of the brain or peripheral artery disease.
# Exams and Tests
Tests that may be done to diagnose this condition include:
- Angiogram
- Genetic testing for apolipoprotein E (apoE)
- Heart stress test
- Total cholesterol
- Triglyceride level
- Very low density lipoprotein (VLDL) test
# Treatment
The goal of treatment is to control underlying conditions such as obesity, hypothyroidism, and diabetes.
Reducing calories, saturated fats, and cholesterol may significantly reduce cholesterol levels.
If high cholesterol and triglyceride levels continue despite diet changes, your doctor may recommend medicine to lower your cholesterol. Medicine to lower cholesterol levels include:
- Bile acid-sequestering resins
- Fibrates
- Nicotinic acid
- Statins
Treatment
Most individuals with hyperlipoproteinemia type III respond to dietary therapy that consists of a diet that is low in cholesterol and saturated fat. The reduction of the intake of dietary cholesterol and other fats generally prevents xanthomas and high lipid levels in the blood (hyperlipidemia). Exercise in addition to dietary therapy may help lower lipid levels.
In individuals in whom dietary modification does not lower lipid levels, certain drugs may be used. These drugs include niacin, gemfibrozil, clofibrate, and/or lovastatin. Other drugs, such as cholestyramine and colestipol are not effective for the treatment of Broad Beta Disease; they may actually raise blood levels of beta-lipoproteins.
Xanthomas can sometimes be removed surgically. Treatment of cardiovascular disease is symptomatic. Because estrogen improves the clearance of specific lipids associated with hyperlipoproteinemia type III, estrogen therapy may help some postmenopausal women with this disorder.
Genetic counseling may be of benefit for people with hyperlipoproteinemia type III and their families. Other treatment is symptomatic and supportive.
# Prognosis
Persons with this condition have an increased risk for coronary artery disease and peripheral vascular disease.
With treatment, most people show a significant reduction in lipid levels.
# Possible Complications
- Heart attack
- Stroke
- Peripheral vascular disease
- Intermittent claudication
- Gangrene of the lower extremities
# Prevention
Screening the family members of those with familial dysbetalipoproteinemia may lead to early detection and treatment.
Early treatment and avoiding other risk factors for vascular disease (such as smoking) are crucial to preventing early heart attacks, strokes, and blocked blood vessels. | https://www.wikidoc.org/index.php/Sandbox:ABC | |
627c1fd26649047327593970b7389a64bf807f4c | wikidoc | Sandbox:M.B | Sandbox:M.B
Synonyms and keywords:
# Special consideration when adding information from observational studies
# Overview
Systemic lupus erythematous (SLE) is an autoimmune disease (when immune system attacks your own body tissues)
# Historical Perspective
Systematic Lupus Erythematous (SLE) was first discovered by Rogerius, an Italian physician, in 12th century to describe the facial lesions of lupus .
The association between sunlight and Lupus was made 19th century.
In 1907, Rasce was the first to discover the association between sunlight and the development of Lupus.
In 1984, genetic predisposition was first implicated in the pathogenesis of lupus.
In 1982, eleven criteria were developed by American College of Rheumatology (ACR) to diagnose SLE.
# Classification
SLE has been classified based on different criteria, such as dermatologic symptoms , renal involvement, and clinical characteristics.
Dermatologic classification
Acute cutaneous lupus erythematosus (ACLE)
Subacute cutaneous lupus erythematosus (SCLE)
Chronic cutaneous lupus erythematosus (CCLE)
Intermittent cutaneous lupus erythematosus (ICLE)
classification based on disease characteristics
Systemic lupus erythematosus (SLE)
Cutaneous lupus erythematosus (CLE)
Drug-induced lupus
Neonatal lupus
classification based on renal microscopic features
International society of nephrology classified lupus nephritis into six classes based on microscopic findings:
I: Minimal mesangial lupus nephritis
II: Mesangial proliferative lupus nephritis
III: Focal lupus nephritis
IV: Diffuse lupus nephritis
V: Lupus membranous nephropathy
VI: Advanced sclerosing lupus nephritis
# Pathophysiology
SLE is a chronic inflammatory disease which is classified as a type III hypersensitivity reaction. In SLE body produces antibodies against itself proteins, particularly cell nucleus proteins. SLE can be triggered by environmental factors.
The exact pathogenesis of is not fully understood.
SLE patients have severe polyclonal B-cell activation, with considerable immature B cells. Memory B cells with increased CD27+/IgD—are less susceptible to immunosuppression. CD27-/IgD- memory B cells are associated with increased disease activity and renal lupus. T cells, which regulate B-cell responses and infiltrate target tissues, have defects in signaling, adhesion, co-stimulation, gene transcription, and alternative splicing. The cytokines B-lymphocyte stimulator (BAFF), interleukins (6, 17, 18), type I interferons, and tumor necrosis factor α (TNFα) are involved in the inflammatory process. In addition, low level of C3 is associated with this disease.
# Causes
Patients with SLE usually have a genetic susceptibility which is triggered by environmental factors. However, no single gene is identified to cause SLE and multiple genes have been found to be associated with this disease. Vitamin D deficiency has been shown to be one of the triggers, such as SLE classes I, II, III. Genes which have been found to date, are IRF5, PTPN22, STAT4,BANK1, ITGAM, BLK, TNFSF4 and CDKN1A. Therefore, SLE is considered an oligogenic trait.
Drug-induced lupus and cutaneous lupus (Discoid lupus erythematous) are the other two forms of lupus. Near 40 medications can induce lupus, among which procainamide, isoniazid, hydralazine, quinidine, and phenytoin are the most famous ones.
# Differentiating ((Page name)) from other Diseases
Since SLE involves several organs, it has a long list of differential diagnosis, such as adult onset still disease, sarcoidosis, Behcet disease, psoriatic arthritis, endocarditis, rheumatoid arthritis, chronic fatigue syndrome, fibromyalgia, HIV infection, mixed connective tissue disease, lyme disease, and reactive arthritis.
# Epidemiology and Demographics
The incidence/prevalence of is approximately per 100,000 individuals worldwide.
OR
In , the incidence/prevalence of was estimated to be cases per 100,000 individuals worldwide.
OR
In , the incidence of is approximately per 100,000 individuals with a case-fatality rate of %.
Patients of all age groups may develop .
OR
The incidence of increases with age; the median age at diagnosis is years.
OR
commonly affects individuals younger than/older than years of age.
OR
is usually first diagnosed among .
OR
commonly affects .
There is no racial predilection to .
OR
usually affects individuals of the race. individuals are less likely to develop .
affects men and women equally.
OR
are more commonly affected by than . The to ratio is approximately to 1.
The majority of cases are reported in .
OR
is a common/rare disease that tends to affect and .
# Risk Factors
There are no established risk factors for .
OR
The most potent risk factor in the development of is . Other risk factors include , , and .
OR
Common risk factors in the development of include , , , and .
OR
Common risk factors in the development of may be occupational, environmental, genetic, and viral.
# Screening
There is insufficient evidence to recommend routine screening for .
OR
According to the , screening for is not recommended.
OR
According to the , screening for by is recommended every among patients with , , and .
# Natural History, Complications, and Prognosis
If left untreated, % of patients with may progress to develop , , and .
OR
Common complications of include , , and .
OR
Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with is approximately %.
# Diagnosis
## Diagnostic Study of Choice
The diagnosis of is made when at least of the following diagnostic criteria are met: , , , and .
OR
The diagnosis of is based on the criteria, which include , , and .
OR
The diagnosis of is based on the definition, which includes , , and .
OR
There are no established criteria for the diagnosis of .
## History and Symptoms
The majority of patients with are asymptomatic.
OR
The hallmark of is . A positive history of and is suggestive of . The most common symptoms of include , , and . Common symptoms of include , , and . Less common symptoms of include , , and .
## Physical Examination
Patients with usually appear . Physical examination of patients with is usually remarkable for , , and .
OR
Common physical examination findings of include , , and .
OR
The presence of on physical examination is diagnostic of .
OR
The presence of on physical examination is highly suggestive of .
## Laboratory Findings
An elevated/reduced concentration of serum/blood/urinary/CSF/other is diagnostic of .
OR
Laboratory findings consistent with the diagnosis of include , , and .
OR
is usually normal among patients with .
OR
Some patients with may have elevated/reduced concentration of , which is usually suggestive of .
OR
There are no diagnostic laboratory findings associated with .
## Electrocardiogram
There are no ECG findings associated with .
OR
An ECG may be helpful in the diagnosis of . Findings on an ECG suggestive of/diagnostic of include , , and .
## X-ray
There are no x-ray findings associated with .
OR
An x-ray may be helpful in the diagnosis of . Findings on an x-ray suggestive of/diagnostic of include , , and .
OR
There are no x-ray findings associated with . However, an x-ray may be helpful in the diagnosis of complications of , which include , , and .
## Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with .
OR
Echocardiography/ultrasound may be helpful in the diagnosis of . Findings on an echocardiography/ultrasound suggestive of/diagnostic of include , , and .
OR
There are no echocardiography/ultrasound findings associated with . However, an echocardiography/ultrasound may be helpful in the diagnosis of complications of , which include , , and .
## CT scan
There are no CT scan findings associated with .
OR
CT scan may be helpful in the diagnosis of . Findings on CT scan suggestive of/diagnostic of include , , and .
OR
There are no CT scan findings associated with . However, a CT scan may be helpful in the diagnosis of complications of , which include , , and .
## MRI
There are no MRI findings associated with .
OR
MRI may be helpful in the diagnosis of . Findings on MRI suggestive of/diagnostic of include , , and .
OR
There are no MRI findings associated with . However, a MRI may be helpful in the diagnosis of complications of , which include , , and .
## Other Imaging Findings
There are no other imaging findings associated with .
OR
may be helpful in the diagnosis of . Findings on an suggestive of/diagnostic of include , , and .
## Other Diagnostic Studies
There are no other diagnostic studies associated with .
OR
may be helpful in the diagnosis of . Findings suggestive of/diagnostic of include , , and .
OR
Other diagnostic studies for include , which demonstrates , , and , and , which demonstrates , , and .
# Treatment
## Medical Therapy
There is no treatment for ; the mainstay of therapy is supportive care.
OR
Supportive therapy for includes , , and .
OR
The majority of cases of are self-limited and require only supportive care.
OR
is a medical emergency and requires prompt treatment.
OR
The mainstay of treatment for is .
OR
The optimal therapy for depends on the stage at diagnosis.
OR
is recommended among all patients who develop .
OR
Pharmacologic medical therapy is recommended among patients with , , and .
OR
Pharmacologic medical therapies for include (either) , , and/or .
OR
Empiric therapy for depends on and .
OR
Patients with are treated with , whereas patients with are treated with .
## Surgery
Surgical intervention is not recommended for the management of .
OR
Surgery is not the first-line treatment option for patients with . Surgery is usually reserved for patients with either , , and
OR
The mainstay of treatment for is medical therapy. Surgery is usually reserved for patients with either , , and/or .
OR
The feasibility of surgery depends on the stage of at diagnosis.
OR
Surgery is the mainstay of treatment for .
## Primary Prevention
There are no established measures for the primary prevention of .
OR
There are no available vaccines against .
OR
Effective measures for the primary prevention of include , , and .
OR
vaccine is recommended for to prevent . Other primary prevention strategies include , , and .
## Secondary Prevention
There are no established measures for the secondary prevention of .
OR
Effective measures for the secondary prevention of include , , and . | Sandbox:M.B
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Synonyms and keywords:
# Special consideration when adding information from observational studies
# Overview
Systemic lupus erythematous (SLE) is an autoimmune disease (when immune system attacks your own body tissues)
# Historical Perspective
Systematic Lupus Erythematous (SLE) was first discovered by Rogerius, an Italian physician, in 12th century to describe the facial lesions of lupus .
The association between sunlight and Lupus was made 19th century.
In 1907, Rasce was the first to discover the association between sunlight and the development of Lupus.
In 1984, genetic predisposition was first implicated in the pathogenesis of lupus.
In 1982, eleven criteria were developed by American College of Rheumatology (ACR) to diagnose SLE.
# Classification
SLE has been classified based on different criteria, such as dermatologic symptoms , renal involvement, and clinical characteristics.
Dermatologic classification
Acute cutaneous lupus erythematosus (ACLE)
Subacute cutaneous lupus erythematosus (SCLE)
Chronic cutaneous lupus erythematosus (CCLE)
Intermittent cutaneous lupus erythematosus (ICLE)
classification based on disease characteristics
Systemic lupus erythematosus (SLE)
Cutaneous lupus erythematosus (CLE)
Drug-induced lupus
Neonatal lupus
classification based on renal microscopic features
International society of nephrology classified lupus nephritis into six classes based on microscopic findings:
I: Minimal mesangial lupus nephritis
II: Mesangial proliferative lupus nephritis
III: Focal lupus nephritis
IV: Diffuse lupus nephritis
V: Lupus membranous nephropathy
VI: Advanced sclerosing lupus nephritis
# Pathophysiology
SLE is a chronic inflammatory disease which is classified as a type III hypersensitivity reaction. In SLE body produces antibodies against itself proteins, particularly cell nucleus proteins. SLE can be triggered by environmental factors.
The exact pathogenesis of [disease name] is not fully understood.
SLE patients have severe polyclonal B-cell activation, with considerable immature B cells. Memory B cells with increased CD27+/IgD—are less susceptible to immunosuppression. CD27-/IgD- memory B cells are associated with increased disease activity and renal lupus. T cells, which regulate B-cell responses and infiltrate target tissues, have defects in signaling, adhesion, co-stimulation, gene transcription, and alternative splicing. The cytokines B-lymphocyte stimulator (BAFF), interleukins (6, 17, 18), type I interferons, and tumor necrosis factor α (TNFα) are involved in the inflammatory process. In addition, low level of C3 is associated with this disease.
# Causes
Patients with SLE usually have a genetic susceptibility which is triggered by environmental factors. However, no single gene is identified to cause SLE and multiple genes have been found to be associated with this disease. Vitamin D deficiency has been shown to be one of the triggers, such as SLE classes I, II, III. Genes which have been found to date, are IRF5, PTPN22, STAT4,BANK1, ITGAM, BLK, TNFSF4 and CDKN1A. Therefore, SLE is considered an oligogenic trait.
Drug-induced lupus and cutaneous lupus (Discoid lupus erythematous) are the other two forms of lupus. Near 40 medications can induce lupus, among which procainamide, isoniazid, hydralazine, quinidine, and phenytoin are the most famous ones.
# Differentiating ((Page name)) from other Diseases
Since SLE involves several organs, it has a long list of differential diagnosis, such as adult onset still disease, sarcoidosis, Behcet disease, psoriatic arthritis, endocarditis, rheumatoid arthritis, chronic fatigue syndrome, fibromyalgia, HIV infection, mixed connective tissue disease, lyme disease, and reactive arthritis.
# Epidemiology and Demographics
The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
OR
In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
OR
In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate of [number range]%.
Patients of all age groups may develop [disease name].
OR
The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.
OR
[Disease name] commonly affects individuals younger than/older than [number of years] years of age.
OR
[Chronic disease name] is usually first diagnosed among [age group].
OR
[Acute disease name] commonly affects [age group].
There is no racial predilection to [disease name].
OR
[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].
[Disease name] affects men and women equally.
OR
[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.
The majority of [disease name] cases are reported in [geographical region].
OR
[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].
# Risk Factors
There are no established risk factors for [disease name].
OR
The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].
OR
Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
OR
Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.
# Screening
There is insufficient evidence to recommend routine screening for [disease/malignancy].
OR
According to the [guideline name], screening for [disease name] is not recommended.
OR
According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].
# Natural History, Complications, and Prognosis
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
OR
Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
OR
Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
# Diagnosis
## Diagnostic Study of Choice
The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
OR
The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].
OR
The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].
OR
There are no established criteria for the diagnosis of [disease name].
## History and Symptoms
The majority of patients with [disease name] are asymptomatic.
OR
The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].
## Physical Examination
Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].
OR
Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
The presence of [finding(s)] on physical examination is diagnostic of [disease name].
OR
The presence of [finding(s)] on physical examination is highly suggestive of [disease name].
## Laboratory Findings
An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
OR
Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
OR
[Test] is usually normal among patients with [disease name].
OR
Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].
OR
There are no diagnostic laboratory findings associated with [disease name].
## Electrocardiogram
There are no ECG findings associated with [disease name].
OR
An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
## X-ray
There are no x-ray findings associated with [disease name].
OR
An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
## Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with [disease name].
OR
Echocardiography/ultrasound may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no echocardiography/ultrasound findings associated with [disease name]. However, an echocardiography/ultrasound may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
## CT scan
There are no CT scan findings associated with [disease name].
OR
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
## MRI
There are no MRI findings associated with [disease name].
OR
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
## Other Imaging Findings
There are no other imaging findings associated with [disease name].
OR
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
## Other Diagnostic Studies
There are no other diagnostic studies associated with [disease name].
OR
[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].
# Treatment
## Medical Therapy
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
OR
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
OR
The majority of cases of [disease name] are self-limited and require only supportive care.
OR
[Disease name] is a medical emergency and requires prompt treatment.
OR
The mainstay of treatment for [disease name] is [therapy].
OR
The optimal therapy for [malignancy name] depends on the stage at diagnosis.
OR
[Therapy] is recommended among all patients who develop [disease name].
OR
Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
OR
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
OR
Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
OR
Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
## Surgery
Surgical intervention is not recommended for the management of [disease name].
OR
Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
OR
The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
OR
The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
OR
Surgery is the mainstay of treatment for [disease or malignancy].
## Primary Prevention
There are no established measures for the primary prevention of [disease name].
OR
There are no available vaccines against [disease name].
OR
Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
OR
[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].
## Secondary Prevention
There are no established measures for the secondary prevention of [disease name].
OR
Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3]. | https://www.wikidoc.org/index.php/Sandbox:M.B | |
687a9ae9adeeb8f8eb5f5cc7f705fb8844e41b74 | wikidoc | Sandbox:MAD | Sandbox:MAD
# Overview
If left untreated, patients with lymphatic filariasis may progress to develop chronic lymphedema, hydrocele, skin pigmentation, and chyluria. Prognosis is generally good in early cases, but in chronic cases the disease can leave an individual severely disabled with genital damage.
# Natural history
Lymphatic filariasis can be asymptomatic or symptomatic. Symptoms may include acute adenolymphangitis, filarial fever, and tropical pulmonary eosinophilia. If left untreated, disease can progress to lymphatic dilatation, abnormalities in lymphatic drainage, and microscopic hematuria and proteinuria.
# Complications
Complications that may develop as a result of lymphatic filariasis include:
- Lymphedema: It refers to non-pitting edema in limbs due to chronic inflammation and obstruction of lymphatic vessels. Lymphedema commonly occurs in upper limbs and may involve breasts. Lower limb is a common place for lymphedema that commonly spares genitalia except W.bancrofti endemic areas.
- Hydrocele: it was also reported up to 30 cm in diameter due to lymphedema in the genitalia that may lead to bacterial infection. Some cases of filariasis of the ovary and mesosalpinx were also reported.
- Renal involvement: Increased intestinal lymph drainage in renal vessels causes loss of lymph fluid in urine giving it milky appearance.
# Prognosis
Early or mild filariasis, including acute inflammatory episodes, typically responds well to treatment. It can be reduced and prevented with simple measures of hygiene, skin care, exercise, and elevation of affected limbs, chronic infection does not. Filariasis does not commonly lead to mortality, however, disease can leave an individual severely disabled with genital damage or elephantiasis. Lymphatic filariasis is the second leading cause of disability worldwide with 40 million persons suffering from complications that limit occupational activities, educational and employment opportunities, and mobility. | Sandbox:MAD
Template:Fialriasis
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]
# Overview
If left untreated, patients with lymphatic filariasis may progress to develop chronic lymphedema, hydrocele, skin pigmentation, and chyluria. Prognosis is generally good in early cases, but in chronic cases the disease can leave an individual severely disabled with genital damage.
# Natural history
Lymphatic filariasis can be asymptomatic or symptomatic. Symptoms may include acute adenolymphangitis, filarial fever, and tropical pulmonary eosinophilia. If left untreated, disease can progress to lymphatic dilatation, abnormalities in lymphatic drainage, and microscopic hematuria and proteinuria.
# Complications
Complications that may develop as a result of lymphatic filariasis include:
- Lymphedema: It refers to non-pitting edema in limbs due to chronic inflammation and obstruction of lymphatic vessels. Lymphedema commonly occurs in upper limbs and may involve breasts. Lower limb is a common place for lymphedema that commonly spares genitalia except W.bancrofti endemic areas.[1]
- Hydrocele: it was also reported up to 30 cm in diameter due to lymphedema in the genitalia that may lead to bacterial infection. Some cases of filariasis of the ovary and mesosalpinx were also reported.[2]
- Renal involvement: Increased intestinal lymph drainage in renal vessels causes loss of lymph fluid in urine giving it milky appearance.[3]
# Prognosis
Early or mild filariasis, including acute inflammatory episodes, typically responds well to treatment. It can be reduced and prevented with simple measures of hygiene, skin care, exercise, and elevation of affected limbs, chronic infection does not. Filariasis does not commonly lead to mortality, however, disease can leave an individual severely disabled with genital damage or elephantiasis. Lymphatic filariasis is the second leading cause of disability worldwide with 40 million persons suffering from complications that limit occupational activities, educational and employment opportunities, and mobility.[4] | https://www.wikidoc.org/index.php/Sandbox:MAD | |
bc66d7a2fdd07532ef15d66f36fdf36c9df30818 | wikidoc | Sandbox:MGS | Sandbox:MGS
# Discovery
- The oldest evidence of cancer is discovered in the Egyptian literature and dates back to about 3000 BC. The textbook is called the 'Edwin Smith Papyrus' and describes 8 cases of tumors of the breast that were removed by cauterization with a tool called the fire drill. The writing says about the disease, “There is no treatment.”
# Landmark Events in the Development of Treatment Strategies
- In 1761, Giovanni Morgagni of Padua became the first to perform an autopsy to relate the illness to the pathology.
- The Scottish surgeon John Hunter (1728-1793) suggested that cancer could be removed if tumor had not invaded nearby tissue and was 'moveable'.
- In 1700s, John Hunter, the Scottish surgeon suggested that tumors grow from lymph constantly thrown out by the blood.
- In 19th century, Rudolf Virchow became the first to correlate the illness to microscopic pathology.
- Zacutus Lusitani (1575-1642) and Nicholas Tulp (1593-1674), 2 doctors in Holland, publicized their work in 1649 and 1652 respectively that concluded that breast cancer was contagious based on their observation of the tumor in the members of the same household.
- In the 1990s, BRCA1 and BRCA2 genes were associated with development of breast cancer for first time.
- In 1713, Bernardino Ramazzini, an Italian doctor, reported the relatively high incidence of breast cancer in nuns. This observation made it a clear association between breast cancer and role of hormones.
- In late 1960s, modern mammography methods were developed.
- In 1976, mammography became officially recommended by the American cancer society.
- In the last decade of the 19th century, William Stewart Halsted, professor of surgery at Johns Hopkins University, came up with the radical mastectomy procedure.
- In 1719, Lorenz Heister, a German surgeon wrote about his ideas for mastectomy and lumpectomy in his book, Chirurgie.
- In 1896, Thomas Beatson, a graduate from the University of Edinburgh, described the relationship between oophorectomy and breast cancer. This study laid down the foundation of the hormonal therapy of the breast cancer.
- In the 1970s, modern clinical trials demonstrated that less extensive surgery is equally effective for most women with breast cancer.
- During the final decades of the 20th century, technices were developed to minimizing the amount of normal tissue removed along with the tumor.
- In late 1990s, first therapeutic monoclonal antibodies, trastuzumab (Herceptin) was approved for breast cancer.
- ↑ "The History of Cancer". American Cancer Society. 2002-03-25. Retrieved 2006-10-09..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | Sandbox:MGS
## Discovery
- The oldest evidence of cancer is discovered in the Egyptian literature and dates back to about 3000 BC. The textbook is called the 'Edwin Smith Papyrus' and describes 8 cases of tumors of the breast that were removed by cauterization with a tool called the fire drill. The writing says about the disease, “There is no treatment.”[1]
## Landmark Events in the Development of Treatment Strategies
- In 1761, Giovanni Morgagni of Padua became the first to perform an autopsy to relate the illness to the pathology.
- The Scottish surgeon John Hunter (1728-1793) suggested that cancer could be removed if tumor had not invaded nearby tissue and was 'moveable'.
- In 1700s, John Hunter, the Scottish surgeon suggested that tumors grow from lymph constantly thrown out by the blood.
- In 19th century, Rudolf Virchow became the first to correlate the illness to microscopic pathology.
- Zacutus Lusitani (1575-1642) and Nicholas Tulp (1593-1674), 2 doctors in Holland, publicized their work in 1649 and 1652 respectively that concluded that breast cancer was contagious based on their observation of the tumor in the members of the same household.
- In the 1990s, BRCA1 and BRCA2 genes were associated with development of breast cancer for first time.
- In 1713, Bernardino Ramazzini, an Italian doctor, reported the relatively high incidence of breast cancer in nuns. This observation made it a clear association between breast cancer and role of hormones.
- In late 1960s, modern mammography methods were developed.
- In 1976, mammography became officially recommended by the American cancer society.
- In the last decade of the 19th century, William Stewart Halsted, professor of surgery at Johns Hopkins University, came up with the radical mastectomy procedure.
- In 1719, Lorenz Heister, a German surgeon wrote about his ideas for mastectomy and lumpectomy in his book, Chirurgie.
- In 1896, Thomas Beatson, a graduate from the University of Edinburgh, described the relationship between oophorectomy and breast cancer. This study laid down the foundation of the hormonal therapy of the breast cancer.
- In the 1970s, modern clinical trials demonstrated that less extensive surgery is equally effective for most women with breast cancer.
- During the final decades of the 20th century, technices were developed to minimizing the amount of normal tissue removed along with the tumor.
- In late 1990s, first therapeutic monoclonal antibodies, trastuzumab (Herceptin) was approved for breast cancer.
- ↑ "The History of Cancer". American Cancer Society. 2002-03-25. Retrieved 2006-10-09..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | https://www.wikidoc.org/index.php/Sandbox:MGS | |
274b9a18925a4afad18f23c827c3b38d5b1d349f | wikidoc | Sandbox:MRI | Sandbox:MRI
# Overview
- There are no MRI findings associated with .
OR
- MRI may be helpful in the diagnosis of . Findings on MRI suggestive of/diagnostic of include , , and .
OR
- There are no MRI findings associated with . However, a MRI may be helpful in the diagnosis of complications of , which include , , and .
# MRI
- There are no MRI findings associated with .
OR
- MRI may be helpful in the diagnosis of . Findings on MRI suggestive of/diagnostic of include:
OR
- There are no MRI findings associated with . However, a MRI may be helpful in the diagnosis of complications of , which include: | Sandbox:MRI
Template:Page name
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
# Overview
- There are no MRI findings associated with [disease name].
OR
- [Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
- There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
# MRI
- There are no MRI findings associated with [disease name].
OR
- [Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include:
[finding 1]
[finding 2]
[finding 3]
- [finding 1]
- [finding 2]
- [finding 3]
OR
- There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include:
[complication 1]
[complication 2]
[complication 3]
- [complication 1]
- [complication 2]
- [complication 3] | https://www.wikidoc.org/index.php/Sandbox:MRI | |
bdd8bbd77e6f2af4c60e097305c072b3ef052282 | wikidoc | Sandbox:P.L | Sandbox:P.L
- Median interval of transplantation - 4 years. (range .25-30.1) Fatality rate: 17.4% (4/23).
- Renal transplant patients of all ages groups are at a higher risk of COVID-19 due to immunosuppression may develop COVID-19.
- The youngest renal transplant patient who died of COVID-19 according to analysis of 14 studies was 71 years old.
- ↑ Wells, Samuel A.; Pacini, Furio; Robinson, Bruce G.; Santoro, Massimo (2013). "Multiple Endocrine Neoplasia Type 2 and Familial Medullary Thyroid Carcinoma: An Update". The Journal of Clinical Endocrinology & Metabolism. 98 (8): 3149–3164. doi:10.1210/jc.2013-1204. ISSN 0021-972X..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | Sandbox:P.L
-
- Median interval of transplantation - 4 years. (range .25-30.1) Fatality rate: 17.4% (4/23).
- Renal transplant patients of all ages groups are at a higher risk of COVID-19 due to immunosuppression may develop COVID-19.
- The youngest renal transplant patient who died of COVID-19 according to analysis of 14 studies was 71 years old.[1]
- ↑ Wells, Samuel A.; Pacini, Furio; Robinson, Bruce G.; Santoro, Massimo (2013). "Multiple Endocrine Neoplasia Type 2 and Familial Medullary Thyroid Carcinoma: An Update". The Journal of Clinical Endocrinology & Metabolism. 98 (8): 3149–3164. doi:10.1210/jc.2013-1204. ISSN 0021-972X..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | https://www.wikidoc.org/index.php/Sandbox:P.L | |
5997345b9032915eb0556b4aeb2cf990862fe0a6 | wikidoc | Sandbox:PNH | Sandbox:PNH
# Overview
# Historical Perspective
## Discovery
Although some question the diagnostic importance of nocturnal haemoglobinuria , it was this symptom that defined PNH as a distinct clinical entity and ignited the curiosity of early investigators (Table I). Further, the nocturnal aspect of the paroxysms suggested to Strübing (1882) a mechanism for the haemoglobinuria. He hypothesized that this symptom was a consequence of the abnormal sensitivity of PNH erythrocytes to systemic acidosis resulting from accumulation of CO2 during sleep. Although the validity is still debated, systematic investigation of this hypothesis by Strübing (1882), Hijmans van den Berg (1911) and Ham (1937) lead directly to the development of a specific diagnostic test for PNH (the acidified serum lysis test of Ham) and to the discovery by Ham of the fundamental role of complement in the lysis of PNH erythrocytes (Ham, 1939; Ham & Dingle, 1939).
In a 1953 review, Crosby reported the high incidence of thrombosis‐related deaths in PNH, and subsequent clinical studies have confirmed that thromboembolic events are a major cause of morbidity and mortality (Crosby, 1953a). Thus, in addition to being classified as a haemolytic anaemia, PNH is included on the list of thrombophilic conditions. The fundamental basis of the thrombophilia of PNH is undefined and represents one of two major unsolved mysteries of PNH (Table I) (Dacie, 1963).
PNH is also included among the bone marrow failure syndromes because, at some point during the course of their illness, almost all patients have (in addition to anaemia) thrombocytopenia, leucopenia or both. Further, there is a clear, albeit incompletely understood, connection between PNH and acquired aplastic anaemia. PNH is also a stem cell disorder because platelets and leucocytes share, with erythrocytes, the deficiency of GPI‐anchored proteins (the exact stage of differentiation in which the genetic mutation occurs is undefined, but it must be effected in a very primitive stem cell because mutant PIG‐A is found in erythroid, myeloid and lymphoid elements from the same patient).
PNH is remarkable because it is a clonal disease but not a malignant disease, and the bone marrow and peripheral blood are mosaics of normal and abnormal cells. Further, individual patients often have multiple abnormal clones that are phenotypically and genotypically discrete. The abnormal stem cells are a consequence of somatic mutation and the mutant gene is located on the X‐chromosome. Thus, inactivation of only one gene in somatic tissues is necessary for manifestation of the phenotype, explaining why all cases of PNH are due to mutant PIG‐A (this hypothesis assumes that all other genes that could cause the phenotype are autosomal). Genetically, females and males are equally susceptible because only one X‐chromosome is active in the somatic tissue of females.
The mutant gene, PIG‐A, is an essential component of the pathway required for synthesis of the GPI moiety that serves as an anchor for a functionally diverse group of membrane proteins. Of the 20 or so proteins that are deficient on the haematopoietic cells of PNH, only DAF (CD55) and MIRL (CD59) share an obvious functional relationship (they are both complement regulatory proteins). Absence of these two proteins accounts for the marked susceptibility of PNH erythrocytes to complement‐mediated lysis. The PIG‐A mutation is necessary for the development of PNH, but it appears insufficient to result in clonal expansion in the absence of some other selective pressure. Defining the nature of the selective process that results in the expansion and clonal dominance of the PIG‐A mutant stem cells is currently the most active area of investigation and represents Dacie's ultimate problem –‘the aetiology of the disease and its relationship to marrow hypoplasia’ (Dacie, 1963). Whatever the solution to this problem, it must somehow depend on the absence of one or more GPI‐anchored proteins.
After reviewing Table I, I hope it is apparent why this elegant, complex disease is a source of continuing fascination for haematologists. This history of PNH is intended to chronicle the landmark events that defined the disease over the past century. | Sandbox:PNH
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
# Overview
# Historical Perspective
## Discovery
Although some question the diagnostic importance of nocturnal haemoglobinuria [Dacie and Lewis (1972) reported it to be the presenting symptom in only 26% of patients], it was this symptom that defined PNH as a distinct clinical entity and ignited the curiosity of early investigators (Table I). Further, the nocturnal aspect of the paroxysms suggested to Strübing (1882) a mechanism for the haemoglobinuria. He hypothesized that this symptom was a consequence of the abnormal sensitivity of PNH erythrocytes to systemic acidosis resulting from accumulation of CO2 during sleep. Although the validity is still debated, systematic investigation of this hypothesis by Strübing (1882), Hijmans van den Berg (1911) and Ham (1937) lead directly to the development of a specific diagnostic test for PNH (the acidified serum lysis test of Ham) and to the discovery by Ham of the fundamental role of complement in the lysis of PNH erythrocytes (Ham, 1939; Ham & Dingle, 1939).
In a 1953 review, Crosby reported the high incidence of thrombosis‐related deaths in PNH, and subsequent clinical studies have confirmed that thromboembolic events are a major cause of morbidity and mortality (Crosby, 1953a). Thus, in addition to being classified as a haemolytic anaemia, PNH is included on the list of thrombophilic conditions. The fundamental basis of the thrombophilia of PNH is undefined and represents one of two major unsolved mysteries of PNH (Table I) (Dacie, 1963).
PNH is also included among the bone marrow failure syndromes because, at some point during the course of their illness, almost all patients have (in addition to anaemia) thrombocytopenia, leucopenia or both. Further, there is a clear, albeit incompletely understood, connection between PNH and acquired aplastic anaemia. PNH is also a stem cell disorder because platelets and leucocytes share, with erythrocytes, the deficiency of GPI‐anchored proteins (the exact stage of differentiation in which the genetic mutation occurs is undefined, but it must be effected in a very primitive stem cell because mutant PIG‐A is found in erythroid, myeloid and lymphoid elements from the same patient).
PNH is remarkable because it is a clonal disease but not a malignant disease, and the bone marrow and peripheral blood are mosaics of normal and abnormal cells. Further, individual patients often have multiple abnormal clones that are phenotypically and genotypically discrete. The abnormal stem cells are a consequence of somatic mutation and the mutant gene is located on the X‐chromosome. Thus, inactivation of only one gene in somatic tissues is necessary for manifestation of the phenotype, explaining why all cases of PNH are due to mutant PIG‐A (this hypothesis assumes that all other genes that could cause the phenotype are autosomal). Genetically, females and males are equally susceptible because only one X‐chromosome is active in the somatic tissue of females.
The mutant gene, PIG‐A, is an essential component of the pathway required for synthesis of the GPI moiety that serves as an anchor for a functionally diverse group of membrane proteins. Of the 20 or so proteins that are deficient on the haematopoietic cells of PNH, only DAF (CD55) and MIRL (CD59) share an obvious functional relationship (they are both complement regulatory proteins). Absence of these two proteins accounts for the marked susceptibility of PNH erythrocytes to complement‐mediated lysis. The PIG‐A mutation is necessary for the development of PNH, but it appears insufficient to result in clonal expansion in the absence of some other selective pressure. Defining the nature of the selective process that results in the expansion and clonal dominance of the PIG‐A mutant stem cells is currently the most active area of investigation and represents Dacie's ultimate problem –‘the aetiology of the disease and its relationship to marrow hypoplasia’ (Dacie, 1963). Whatever the solution to this problem, it must somehow depend on the absence of one or more GPI‐anchored proteins.
After reviewing Table I, I hope it is apparent why this elegant, complex disease is a source of continuing fascination for haematologists. This history of PNH is intended to chronicle the landmark events that defined the disease over the past century. | https://www.wikidoc.org/index.php/Sandbox:PNH | |
3cb278f9e263c9afdd68aac878cd771d9bf0f503 | wikidoc | Sandbox: DD | Sandbox: DD
must be differentiated from other diseases causing oral lesions such as leukoplakia and herpes simplex virus infection.
- ↑ Ann M. Gillenwater, Nadarajah Vigneswaran, Hanadi Fatani, Pierre Saintigny & Adel K. El-Naggar (2013). "Proliferative verrucous leukoplakia (PVL): a review of an elusive pathologic entity!". Advances in anatomic pathology. 20 (6): 416–423. doi:10.1097/PAP.0b013e3182a92df1. PMID 24113312. Unknown parameter |month= ignored (help)CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Andrès E, Zimmer J, Affenberger S, Federici L, Alt M, Maloisel F. (2006). "Idiosyncratic drug-induced agranulocytosis: Update of an old disorder". Eur J Intern Med. 17 (8): 529–35. Text "pmid 17142169" ignored (help)CS1 maint: Multiple names: authors list (link)
- ↑ title="By Internet Archive Book Images , via Wikimedia Commons" href=":A_manual_of_syphilis_and_the_venereal_diseases%2C_(1900)_(14595882378).jpg"
- ↑ Feikin DR, Lezotte DC, Hamman RF, Salmon DA, Chen RT, Hoffman RE (2000). "Individual and community risks of measles and pertussis associated with personal exemptions to immunization". JAMA. 284 (24): 3145–50. PMID 11135778.CS1 maint: Multiple names: authors list (link)
- ↑ Ratnam S, West R, Gadag V, Williams B, Oates E (1996). "Immunity against measles in school-aged children: implications for measles revaccination strategies". Can J Public Health. 87 (6): 407–10. PMID 9009400.CS1 maint: Multiple names: authors list (link) | Sandbox: DD
must be differentiated from other diseases causing oral lesions such as leukoplakia and herpes simplex virus infection.
- ↑ Ann M. Gillenwater, Nadarajah Vigneswaran, Hanadi Fatani, Pierre Saintigny & Adel K. El-Naggar (2013). "Proliferative verrucous leukoplakia (PVL): a review of an elusive pathologic entity!". Advances in anatomic pathology. 20 (6): 416–423. doi:10.1097/PAP.0b013e3182a92df1. PMID 24113312. Unknown parameter |month= ignored (help)CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Andrès E, Zimmer J, Affenberger S, Federici L, Alt M, Maloisel F. (2006). "Idiosyncratic drug-induced agranulocytosis: Update of an old disorder". Eur J Intern Med. 17 (8): 529–35. Text "pmid 17142169" ignored (help)CS1 maint: Multiple names: authors list (link)
- ↑ title="By Internet Archive Book Images [No restrictions], via Wikimedia Commons" href="https://commons.wikimedia.org/wiki/File:A_manual_of_syphilis_and_the_venereal_diseases%2C_(1900)_(14595882378).jpg"
- ↑ Feikin DR, Lezotte DC, Hamman RF, Salmon DA, Chen RT, Hoffman RE (2000). "Individual and community risks of measles and pertussis associated with personal exemptions to immunization". JAMA. 284 (24): 3145–50. PMID 11135778.CS1 maint: Multiple names: authors list (link)
- ↑ Ratnam S, West R, Gadag V, Williams B, Oates E (1996). "Immunity against measles in school-aged children: implications for measles revaccination strategies". Can J Public Health. 87 (6): 407–10. PMID 9009400.CS1 maint: Multiple names: authors list (link) | https://www.wikidoc.org/index.php/Sandbox:_DD | |
12f5444b71974ebf5c399a0927ed6aa30f82d12a | wikidoc | Sandbox: LG | Sandbox: LG
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# English Language WikiDoc
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Santosh Patel M.D., FRCA Consultant Anesthetist, Rochdale Infirmary / Pennine Acute Hospitals NHS Trust, UK
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For a listing of prior WikiDoc Scholars, click here
# English Language WikiDoc
## Deputy Editors-In-Chief
Will Gibson, M.D., Ph.D. Harvard Medical School
Rim Halaby, M.D. Research Fellow, Harvard Medical School
Gerald Chi, M.D. Research Fellow, Harvard Medical School
Serge Korjian, M.D. Research Fellow, Harvard Medical School
## Anesthesia
John Bramhall, M.D. Ph.D. Associate Medical Director, University of Washington, Harborview Medical Center
Santosh Patel M.D., FRCA Consultant Anesthetist, Rochdale Infirmary / Pennine Acute Hospitals NHS Trust, UK
## Cardiology
John Alexander, M.D. Duke Clinical Research Institute
Dominick Angiolillo, M.D. University of Florida
Richard C. Becker, M.D. Duke Clinical Research Institute
Nic Chronos, M.D. Atlanta
Paul Gurbel, M.D. Sinia, Baltimore
Robert Harrington, M.D. Chairman of Medicine, Stanford Medical School
Mark Josephson, M.D. Chief of Cardiology, Beth Israel Deaconess Medical Center, Harvard
Harlan Krumholz, M.D. Yale University
Kenneth Mehaffey, M.D. Stanford Medical School
Kristin Newby, M.D. Duke Clinical Research Institute
Thach Nguyen, M.D. Indiana, USA
Alan Niederman, M.D. Florida, USA
Christopher O'Connor, M.D. Duke Clinical Research Institute
Duane Pinto, M.D. Direct Cardiology Fellowship Program, Beth Israel Deaconess Medical Center, Harvard
Jeffrey J. Popma, M.D. Harvard
Mathew Roe, M.D. Duke Clinical Research Institute
Marv Slepian, M.D. University of Arizona
Robert Superko, M.D Saint Joseph Hospital, Atlanta
Alan Yeung, M.D. Chief of Cardiology, Stanford
Peter Zimmetbaum, M.D. Chief, Clinical Cardiology, Beth Israel Deaconess Medical Center, Harvard
Cafer Zorkun, M.D. Istanbul, Turkey
## Chiropractic
Stephen J. Press, D.C., PhD, CCSP, FACSM, FICC Englewood, NJ, - Exec. Tech Dir., OurMed.org
## Emergency Medicine
James Hoekstra, M.D. Wake Forest University
Liudvikas Jagminas, M.D., FACEP Yale University
W. Frank Peacock, M.D. Cleveland Clinic Foundation
Ivan Rokos, M.D. UCLA - Olive View
## Gastroenterology
Bulent Ender, M.D. Wake Gastroenterology, Raleigh, North Carolina
Timothy Koch, M.D. Professor of Medicine, Georgetown University School of Medicine
## Genetics
Charis Eng, M.D., PhD, FACP Sondra J. & Stephen R. Hardis Endowed Chair of Cancer Genomic Medicine, Chair and Director, Genomic Medicine Institute, Director, Center for Personalized Genetic Healthcare, Cleveland Clinic Lerner Research Institute
## Hematology
David T. Teachey, M.D. Assistant Professor of Pediatrics, Divisions of Hematology and Oncology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine
Robert Killeen, M.D.
## Infectious Disease
Mark Poznansky MBChB, Ph.D. Harvard
## Nephrology
Mark L. Zeidel, M.D. Chairman of Medicine, Beth Israel Deaconess Medical Center, Harvard
## Nutritional and Metabolic Disorders
Timothy Koch, M.D. Professor of Medicine, Georgetown University School of Medicine
## Ophthalmology
Kenneth J. Hoffer, M.D. Clinical Professor of Ophthalmology, UCLA, St. Mary's Eye Center, Santa Monica, CA
## Orthopedic Surgery & Sports Medicine
Nicholas A. DiNubile, M.D. Havertown PA
## Otolaryngology
Robert M. Kellman, M.D. Professor and Chair, Department of Otolaryngology & Communication Sciences, SUNY -- Upstate Medical University
## Pain Management
Steven D. Feinberg, M.D. Adjunct Clinical Professor, Stanford University School of Medicine
## Pediatrics
Grover Robinson, M.D. Clinical Professor of Pediatrics at the Medical College of Virginia, Virginia Commonwealth University School of Medicine
## Plastic and Reconstructive Surgery
Martin I. Newman, M.D., F.A.C.S. Associate Program Director and Educational Director, Plastic Surgery Residency Program, Cleveland Clinic Florida Department of Plastic Surgery.
Michel C. Samson, M.D., FRCSC, FACS Program Director, Cleveland Clinic Florida ACGME
Residency Training Program in Plastic Surgery, Cleveland Clinical Foundation, Florida
Paul C. Zwiebel, M.D., D.M.D. Littleton, Colorado
Jay Pensler, M.D. Associate Professor of Clinical Plastic Surgery, Northwestern University Feinberg School of Medicine
## Psychiatry
Mark J. Warren, M.D., M.P.H., Founder and Medical Director, Cleveland Center for Eating Disorder, Assistant Clinical Professor of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, OH
## Pulmonary / Critical Care
Ben deBoisblanc, M.D. Fred Allison, Jr., M.D. Professor of Medicine & Physiology Section of Pulmonary/Critical Care Medicine, LSU Health Sciences Center
Philip Marcus, M.D., M.P.H. Chief, Division of Pulmonary Medicine, St. Francis Hospital-The Heart Center, Roslyn, NY
## Rehabilitation Medicine
Robert G. Schwartz, M.D. Piedmont Physical Medicine and Rehabilitation, P.A., Greenville, SC
Jeff Cohen, M.D. Clinical Professor of Rehabilitation Medicine, New York University School of Medicine
## Transplant Medicine
Vijay S. Gorantla, M.D., PH.D. Assistant Professor of Surgery, Administrative Director of Pittsburgh CTA Program, Division of Plastic Surgery, University of Pittsburgh Medical Center
## Urology
Steven C. Campbell, M.D., Ph.D. Professor of Surgery, Residency Program Director, Section of Urologic Oncology, Glickman Urological and Kidney Institute, Cleveland Clinic
Joel Gelman, M.D. Department of Urology, University of California, Irvine Medical Center
## Vascular Medicine and Peripheral Arterial Intervention
Christopher J. White, M.D., FACC, FSCAI, FAHA, FESC Chairman, Department of Cardiovascular Diseases, Ochsner Clinic Foundation
# French Language WikiDoc
Managing Editor:
Maryse Levacher Paris Descartes University [1]
# Japanese Language WikiDoc
Editors-In-Chief:
Hisao Ogawa, M.D. Kumamoto University, Japan
# Korean Language WikiDoc
Editors-In-Chief:
Sueng Uk Lee, M.D. [2] Gwangju Christian Hospital Heart Center
# WikiDoc Lebanon
Editor-In-Chief:
Rim Halaby, M.D. Lebanese American University LAU (2009- 2013)
# Portugese (Brazil) Language WikiDoc
Editors-In-Chief:
Marcelo Zacarkim, M.D.
Vanessa Cherniauskas, M.D.
# Spanish Language WikiDoc
Editor-In-Chief:
Gonzalo Romero, M.D.
# Turkish Language WikiDoc
Editors-In-Chief:
Cafer Zorkun, M.D., Ph.D. [3]
# Vietnamese Language WikiDoc
Editors-In-Chief:
Le Dinh Phuong, M.D.
Thach Nguyen, M.D.
Kim-Son Nguyen, M.D., Beth Israel Deaconess Medical Center, Harvard
# 2014 Mathew Southard Scholars in Medicine
- Christopher Popma
- Rim Halaby, M.D.
- Gerald Chi, M.D. | https://www.wikidoc.org/index.php/Sandbox:_LG | |
e1857a62ec29f6ba8ab2e2c48a81d93375ea2e93 | wikidoc | Sandbox: PE | Sandbox: PE
# Overview
Examination reveals signs of acute abdomen and in advanced cases, shows signs of shock and septicemia.
# Physical Examination
## Appearance of the patient
- Patients with peritonitis are usually ill-appearing.
- Initially they appear alerted, restless and irritable.
- They may later become apathetic and delirious.
- They are often noticed lying quietly supine, on the bed with the knees flexed and with frequent limited intercostal respirations because any motion intensifies the abdominal pain.
## Vital Signs
### Temperature
- Hyperthermia (temperatures as high as 42° C) is a sign of infection and hypothermia (temperatures as low as 35° C) indicates septic shock.
- Hypothermia is a grave sign,seen late in the course of the disease in patients with on-going intra-abdominal sepsis or septic shock.
### Blood Pressure
- Hypertension can be seen if associated with any heart condition or renal disease.
- The blood pressure is maintained within normal limits early in the disease process but as peritonitis progresses, the blood pressure decreases due to volume loss diarrhea or severe ascites.
### Pulse
- Tachycardia with weak, thready peripheral pulses represents decreased effective circulating blood volume, indicating a stage of shock later in the disease.
- May be normal or increased in rate due to infection.
- It may be low in volume due to dehydration.
### Respiration
- Tachypnea due to infection and increased demand.
## Skin
- Skin over abdomen is tense due to ascites.
- Skin changes such as spider nevus, palmar erythema, large abdominal wall collateral veins are suggestive of parenchymal liver disease and portal hypertension
## Eyes
- Jaundice may be seen in cases of liver cirrhosis.
- Periorbital puffiness may be noticed in cases of renal failure.
## Neck
- Jugular venous distension may be seen in cases of heart failure causing ascites.
## Heart
- Signs of heart failure may be seen like S3.
## Lungs
- Signs of any infection, or signs of volume overload in lungs due to heart failure.
## Neurologic
Following may be noticed when spontaneous bacterial peritonitis complicates or due to underlying liver or renal failure.
- Stupor
- Confusion
- Seizures
## Abdomen
- Usually tense and distended due to ascites
- Marked abdominal tenderness to palpation is present.
- Shifting dullness on percussion is noted in patients with ascites, but may be painful due to infection.
- Bowel sounds vary along the course of peritonitis, are initially hypoactive, and may disappear later.
- Absence of bowel sounds may be the only manifestation of peritonitis in some patients, and a high index of suspicion is necessary
- The absence of any of these findings does not exclude peritonitis.
## Extremities
- When present, peripheral edema in patients with liver disease is usually found in the lower extremities and occasionally may involve the abdominal wall. Patients with nephrotic syndrome or cardiac failure may have total body edema (anasarca). | Sandbox: PE
# Overview
Examination reveals signs of acute abdomen and in advanced cases, shows signs of shock and septicemia.
# Physical Examination
## Appearance of the patient
- Patients with peritonitis are usually ill-appearing.
- Initially they appear alerted, restless and irritable.
- They may later become apathetic and delirious.
- They are often noticed lying quietly supine, on the bed with the knees flexed and with frequent limited intercostal respirations because any motion intensifies the abdominal pain.
## Vital Signs
### Temperature
- Hyperthermia (temperatures as high as 42° C) is a sign of infection and hypothermia (temperatures as low as 35° C) indicates septic shock.
- Hypothermia is a grave sign,seen late in the course of the disease in patients with on-going intra-abdominal sepsis or septic shock.
### Blood Pressure
- Hypertension can be seen if associated with any heart condition or renal disease.
- The blood pressure is maintained within normal limits early in the disease process but as peritonitis progresses, the blood pressure decreases due to volume loss diarrhea or severe ascites.
### Pulse
- Tachycardia with weak, thready peripheral pulses represents decreased effective circulating blood volume, indicating a stage of shock later in the disease.
- May be normal or increased in rate due to infection.
- It may be low in volume due to dehydration.
### Respiration
- Tachypnea due to infection and increased demand.
## Skin
- Skin over abdomen is tense due to ascites.
- Skin changes such as spider nevus, palmar erythema, large abdominal wall collateral veins are suggestive of parenchymal liver disease and portal hypertension
## Eyes
- Jaundice may be seen in cases of liver cirrhosis.
- Periorbital puffiness may be noticed in cases of renal failure.
## Neck
- Jugular venous distension may be seen in cases of heart failure causing ascites.
## Heart
- Signs of heart failure may be seen like S3.
## Lungs
- Signs of any infection, or signs of volume overload in lungs due to heart failure.
## Neurologic
Following may be noticed when spontaneous bacterial peritonitis complicates or due to underlying liver or renal failure.
- Stupor
- Confusion
- Seizures
## Abdomen
- Usually tense and distended due to ascites
- Marked abdominal tenderness to palpation is present.
- Shifting dullness on percussion is noted in patients with ascites, but may be painful due to infection.
- Bowel sounds vary along the course of peritonitis, are initially hypoactive, and may disappear later.
- Absence of bowel sounds may be the only manifestation of peritonitis in some patients, and a high index of suspicion is necessary
- The absence of any of these findings does not exclude peritonitis.
## Extremities
- When present, peripheral edema in patients with liver disease is usually found in the lower extremities and occasionally may involve the abdominal wall. Patients with nephrotic syndrome or cardiac failure may have total body edema (anasarca). | https://www.wikidoc.org/index.php/Sandbox:_PE | |
3a40748c6c7b91697a44820ff36efc769e45651f | wikidoc | Sandbox: ay | Sandbox: ay
# Historical prespective
B. Lagenbeck in 1839 in Germany was the first to demonstrate that a yeast-like fungus existed in the human oral infection "thrush." He also found that a fungus was able to cause thrush.
The genera Candida, species albicans was described by botanist Christine Marie Berkhout. She described the fungus in her doctoral thesis, at the University of Utrecht in 1923. Over the years the classification of the genera and species has evolved. Obsolete names for this genus include Mycotorula and Torulopsis. The species has also been known in the past as Monilia albicans and Oidium albicans. The current classification is nomen conservandum, which means the name is authorized for use by the International Botanical Congress (IBC).
The full current taxonomic classification is available at Candida albicans.
The genus Candida includes about 150 different species. However, only a few of those are known to cause human infections. C. albicans is the most significant pathogenic (=disease-causing) species. Other Candida species causing diseases in humans include C. tropicalis, C. glabrata, C. krusei, C. parapsilosis, C. dubliniensis, and C. lusitaniae.
# Classification:
Candidiasis can be classified according to the site of infection into:
## Localoized mucocutaneous:
- Oropharyngeal candidiasis
- Esophageal candidiasis
- Candida vulvovaginitis
- Chronic mucocutaneous candidiasis.
### Invasive Candidiasis:
More serious and usually presenting in an immunocompromised host.
- Candidaemia
- Candida endophthalmitis
- Candida endocarditis
- Candida osteoarticular disease
# Pathophysiology:
Candida is a normal commensal of skin and mucous membranes. A competent immune system and an intact regenerating healthy skin prevent the virulence of Candida.
The main virulence factors that mediate the infection: (2)
- Secreting molecules that mediate adherence into host cells
- Production of hydrolases which has a lytic effect on tissues and facilitate the invasion by the bacteria.
- Polymorphism: Candida has the ability to grow either as pseudohyphae (elongated elipsoid form) or in a yeast form (rounded to oval budding form. While the role of #polymorphism is not clearly understood in the virulence of Candida, it’s noted that species capable of producing the most severe form of the disease has this ability.
- Biofilm production: which means the ability to form a thick layer of the organism on the mucosal surfaces or even on catheters and dentures.
Patients was candida vulvovaginitis were found to have decreased levels of mannose binding lectins (MBL) . Further investigations revealed that 2 genetic mutations in genes responsible for MBL and IL4 production increase the host susceotibility of getting recurrent candidal vulvovaginitis.(3)
# Risk factors:
Any condition that compromises cell mediated immunity, worsens the general status of the patient or provide a favorable medium for candida to form biofilms put the patient at increased risk for having candidiasis.(4)
## Conditions that compromises cell mediated immunity:
- T cell deficiencies as in DiGeorge syndrome, Wiscot-Aldrich syndrome and ataxia-telengictasia.
- Bone marrow transplant
- Leukaemias
- Corticosteroids use or immunosuppresive drugs.
## Conditions that worsens the general condition:
- Malignancies
- Recent chemotherapy
- Trauma
- Recent surgery
- Prolonged hospitalization
- Broad spectrum antibiotics
- Renal failure
- Haemodialysis (especially if prolonged)
## Dentures that provide a favorable media for forming biofilms:
- Prolonged central venous catheters insertion
- Prolonged foley’s catheter insertion
- Prolonged mechanical ventilation
# Clinical manifaestations:
Oropharyngeal candidiasis:(5), (6)
Many cases are asymptomatic (mild disease or poor general condition)
Dysphagia or odynphagia
Difficulty tasting food
feeling of mouth fullness and discomfort
Candida esophagitis:(7)
Candida esophagitis usually comes late in the course of AIDS (or any immunodeficiency) (8), so patient has the symptoms and signs of the underlying disease.
Odynophagia
Weight loss due to decreased food intake.
Candida vulvovaginitis:
Symptoms of vulvovaginitis caused by Candida species are indistinguishable and include the following:
- Pruritus is the most significant symptom
- Change in the amount and the color of vaginal discharge: It is characterized by a thick, white "cottage cheese-like" vaginal discharge
- Pain on urination (dysuria)
- Pain on sexual intercourse (dyspareunia)
- Vulvovaginal soreness
- Symptoms aggravate a week before the menses.
Chronic mucocutaneous candidiasis (CMCC): (9)
CMCC is a syndrome characterized by chronic or recurrent superficial candida infection in the skin and mucous membranes in association with endocrinal and autoimmune deficiencies. (10)
Characterized by inability of T cells to react to candidal antigens.
Presents with:
Recurrent or chronic candidal infections.
Infection is usually superficial though invasive candidiasis is encountered especially in new born.(11)
Enocrinopathies as hypoparathyroidism and adrenal insufficiency may accompany chronic candidiasis.
Invasive candidiasis:
Candidaemia: (12)
mimics the presentation of sepsis:
- Fever: in patient who is known immunodeficient, fevers are usually high and spiking.
- A capillary leak syndrome can develop with severe swelling, edema, and third spacing of fluids.
- General symptoms can include flu like symptoms as well as shaking chills or rigors.(13)
- If the respiratory system is the primary source for sepsis then sore throat, productive cough, and pleuritic chest pain may be present.
Candida osteoarticular disease:
invasion of bones usually presents after weks to months after candidaemia.
Fever is not present in all patients
Loss of function, pain and tenderness are the main presenting symptoms.
Candida endophthalmitis:
Candida endophthalmitis presents in severly immunocompromised patients but most common risk factor is IV drug abuse.
Fever: is not present consistently in all patients except associated candiaemia is present.
Red eye.
Floaters and decreased visual acuity: but markedly decreased vision is not present till very late in the course of the disease.
Eye pain | Sandbox: ay
# Historical prespective
B. Lagenbeck in 1839 in Germany was the first to demonstrate that a yeast-like fungus existed in the human oral infection "thrush." He also found that a fungus was able to cause thrush.[1]
The genera Candida, species albicans was described by botanist Christine Marie Berkhout. She described the fungus in her doctoral thesis, at the University of Utrecht in 1923. Over the years the classification of the genera and species has evolved. Obsolete names for this genus include Mycotorula and Torulopsis. The species has also been known in the past as Monilia albicans and Oidium albicans. The current classification is nomen conservandum, which means the name is authorized for use by the International Botanical Congress (IBC).
The full current taxonomic classification is available at Candida albicans.
The genus Candida includes about 150 different species. However, only a few of those are known to cause human infections. C. albicans is the most significant pathogenic (=disease-causing) species. Other Candida species causing diseases in humans include C. tropicalis, C. glabrata, C. krusei, C. parapsilosis, C. dubliniensis, and C. lusitaniae.
# Classification:[2]
Candidiasis can be classified according to the site of infection into:
## Localoized mucocutaneous:
- Oropharyngeal candidiasis
- Esophageal candidiasis
- Candida vulvovaginitis
- Chronic mucocutaneous candidiasis.
### Invasive Candidiasis:
More serious and usually presenting in an immunocompromised host.
- Candidaemia
- Candida endophthalmitis
- Candida endocarditis
- Candida osteoarticular disease
# Pathophysiology:
Candida is a normal commensal of skin and mucous membranes. A competent immune system and an intact regenerating healthy skin prevent the virulence of Candida.
The main virulence factors that mediate the infection: (2)
- Secreting molecules that mediate adherence into host cells
- Production of hydrolases which has a lytic effect on tissues and facilitate the invasion by the bacteria.
- Polymorphism: Candida has the ability to grow either as pseudohyphae (elongated elipsoid form) or in a yeast form (rounded to oval budding form. While the role of #polymorphism is not clearly understood in the virulence of Candida, it’s noted that species capable of producing the most severe form of the disease has this ability.
- Biofilm production: which means the ability to form a thick layer of the organism on the mucosal surfaces or even on catheters and dentures.
Patients was candida vulvovaginitis were found to have decreased levels of mannose binding lectins (MBL) . Further investigations revealed that 2 genetic mutations in genes responsible for MBL and IL4 production increase the host susceotibility of getting recurrent candidal vulvovaginitis.(3)
# Risk factors:
Any condition that compromises cell mediated immunity, worsens the general status of the patient or provide a favorable medium for candida to form biofilms put the patient at increased risk for having candidiasis.(4)
## Conditions that compromises cell mediated immunity:
- T cell deficiencies as in DiGeorge syndrome, Wiscot-Aldrich syndrome and ataxia-telengictasia.
- Bone marrow transplant
- Leukaemias
- Corticosteroids use or immunosuppresive drugs.
## Conditions that worsens the general condition:
- Malignancies
- Recent chemotherapy
- Trauma
- Recent surgery
- Prolonged hospitalization
- Broad spectrum antibiotics
- Renal failure
- Haemodialysis (especially if prolonged)
## Dentures that provide a favorable media for forming biofilms:
- Prolonged central venous catheters insertion
- Prolonged foley’s catheter insertion
- Prolonged mechanical ventilation
# Clinical manifaestations:
Oropharyngeal candidiasis:(5), (6)
Many cases are asymptomatic (mild disease or poor general condition)
Dysphagia or odynphagia
Difficulty tasting food
feeling of mouth fullness and discomfort
Candida esophagitis:(7)
Candida esophagitis usually comes late in the course of AIDS (or any immunodeficiency) (8), so patient has the symptoms and signs of the underlying disease.
Odynophagia
Weight loss due to decreased food intake.
Candida vulvovaginitis:
Symptoms of vulvovaginitis caused by Candida species are indistinguishable and include the following:[3][4][5]
- Pruritus is the most significant symptom
- Change in the amount and the color of vaginal discharge: It is characterized by a thick, white "cottage cheese-like" vaginal discharge
- Pain on urination (dysuria)
- Pain on sexual intercourse (dyspareunia)
- Vulvovaginal soreness
- Symptoms aggravate a week before the menses.
Chronic mucocutaneous candidiasis (CMCC): (9)
CMCC is a syndrome characterized by chronic or recurrent superficial candida infection in the skin and mucous membranes in association with endocrinal and autoimmune deficiencies. (10)
Characterized by inability of T cells to react to candidal antigens.
Presents with:
Recurrent or chronic candidal infections.
Infection is usually superficial though invasive candidiasis is encountered especially in new born.(11)
Enocrinopathies as hypoparathyroidism and adrenal insufficiency may accompany chronic candidiasis.
Invasive candidiasis:
Candidaemia: (12)
mimics the presentation of sepsis:
- Fever: in patient who is known immunodeficient, fevers are usually high and spiking.
- A capillary leak syndrome can develop with severe swelling, edema, and third spacing of fluids.
- General symptoms can include flu like symptoms as well as shaking chills or rigors.(13)
- If the respiratory system is the primary source for sepsis then sore throat, productive cough, and pleuritic chest pain may be present.
Candida osteoarticular disease:
invasion of bones usually presents after weks to months after candidaemia.
Fever is not present in all patients
Loss of function, pain and tenderness are the main presenting symptoms.
Candida endophthalmitis:
Candida endophthalmitis presents in severly immunocompromised patients but most common risk factor is IV drug abuse.
Fever: is not present consistently in all patients except associated candiaemia is present.
Red eye.
Floaters and decreased visual acuity: but markedly decreased vision is not present till very late in the course of the disease.
Eye pain | https://www.wikidoc.org/index.php/Sandbox:_ay | |
292d97b14991803da497d9de8616db12c4c99ff4 | wikidoc | Sandbox Epi | Sandbox Epi
# Prevalence
- In the United States, the age-adjusted prevalence of (insert disease name here) is _____ % in 2011.
# Incidence
- The delay-adjusted incidence of (insert disease name here) in 2011 was estimated to be _____ per 100,000 persons in the United States.
- In 2011, the age-adjusted incidence of (insert disease name here) was _____ per 100,000 persons in the United States.
# Age
- While the overall age-adjusted incidence of (insert disease name here) in the United States between 2007 and 2011 is _____ per 100,000, the age-adjusted incidence of (insert disease name here) by age category is:
Under 65 years: _____ per 100,000
65 and over: _____ per 100,000
- Under 65 years: _____ per 100,000
- 65 and over: _____ per 100,000
# Gender
- In the United States, the age-adjusted prevalence of (insert disease name here) by gender in 2011 is:
In males: _____ %
In females: _____ %
- In males: _____ %
- In females: _____ %
- In the United States, the delay-adjusted incidence of (insert disease name here) by gender in 2011 is:
In males: _____ per 100,000 persons
In females: _____ per 100,000 persons
- In males: _____ per 100,000 persons
- In females: _____ per 100,000 persons
- In the United States, the age-adjusted incidence of (insert disease name here) by gender on 2011 is:
In males: _____ per 100,000 persons
In females: _____ per 100,000 persons
- In males: _____ per 100,000 persons
- In females: _____ per 100,000 persons
- Shown below is an image depicting the delay-adjusted incidence and observed incidence of (insert disease name here) by gender and race in the United States between 1975 and 2011. These graphs are adapted from SEER: The Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.
# Race
- Shown below is a table depicting the age-adjusted prevalence of (insert disease name here) by race in 2011 in the United States.
- Shown below is an image depicting the incidence of (insert disease name here) by race in the United States between 1975 and 2011.
API: Asian/Pacific Islander; AI/AN: American Indian/ Alaska Native
# Percent Distribution of (insert disease name here) by Histology
- Among patients with histologically confirmed cases of (insert disease name here), the percent distribution of the types of the disease between 2007 and 2011 in the United States are:
Type X: _____ %
Type Y: _____ %
Type Z: _____ %
- Type X: _____ %
- Type Y: _____ %
- Type Z: _____ %
# 5-Year Survival
- Between 2004 and 2010, the 5-year relative survival of patients with (insert disease name here) was _____ %.
- When stratified by age, the 5-year relative survival of patients with (insert disease name here) was ____ % and ____ % for patients <65 and ≥ 65 years of age respectively.
- The survival of patients with (insert disease name here) varies with the stage of the disease. Shown below is a table depicting the 5-year relative survival by the stage of (insert disease name here):
- Shown below is an image depicting the 5-year conditional relative survival (probability of surviving in the next 5-years given the cohort has already survived 0, 1, 3 years) between 1998 and 2010 of (insert disease name here) by stage at diagnosis according to SEER. These graphs are adapted from SEER: The Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.
- ↑ Jump up to: 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, /, based on November 2013 SEER data submission, posted to the SEER web site, April 2014. | Sandbox Epi
## Prevalence
- In the United States, the age-adjusted prevalence of (insert disease name here) is _____ % in 2011.[1]
## Incidence
- The delay-adjusted incidence of (insert disease name here) in 2011 was estimated to be _____ per 100,000 persons in the United States.[1]
- In 2011, the age-adjusted incidence of (insert disease name here) was _____ per 100,000 persons in the United States.[1]
## Age
- While the overall age-adjusted incidence of (insert disease name here) in the United States between 2007 and 2011 is _____ per 100,000, the age-adjusted incidence of (insert disease name here) by age category is:[1]
Under 65 years: _____ per 100,000
65 and over: _____ per 100,000
- Under 65 years: _____ per 100,000
- 65 and over: _____ per 100,000
## Gender
- In the United States, the age-adjusted prevalence of (insert disease name here) by gender in 2011 is:[1]
In males: _____ %
In females: _____ %
- In males: _____ %
- In females: _____ %
- In the United States, the delay-adjusted incidence of (insert disease name here) by gender in 2011 is:[1]
In males: _____ per 100,000 persons
In females: _____ per 100,000 persons
- In males: _____ per 100,000 persons
- In females: _____ per 100,000 persons
- In the United States, the age-adjusted incidence of (insert disease name here) by gender on 2011 is:[1]
In males: _____ per 100,000 persons
In females: _____ per 100,000 persons
- In males: _____ per 100,000 persons
- In females: _____ per 100,000 persons
- Shown below is an image depicting the delay-adjusted incidence and observed incidence of (insert disease name here) by gender and race in the United States between 1975 and 2011. These graphs are adapted from SEER: The Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.[1]
[Insert figure x.1 from the report]
## Race
- Shown below is a table depicting the age-adjusted prevalence of (insert disease name here) by race in 2011 in the United States.[1]
- Shown below is an image depicting the incidence of (insert disease name here) by race in the United States between 1975 and 2011.[1]
[Insert figure x.2 from the report]
API: Asian/Pacific Islander; AI/AN: American Indian/ Alaska Native
## Percent Distribution of (insert disease name here) by Histology
- Among patients with histologically confirmed cases of (insert disease name here), the percent distribution of the types of the disease between 2007 and 2011 in the United States are:[1]
Type X: _____ %
Type Y: _____ %
Type Z: _____ %
- Type X: _____ %
- Type Y: _____ %
- Type Z: _____ %
## 5-Year Survival
- Between 2004 and 2010, the 5-year relative survival of patients with (insert disease name here) was _____ %.[1]
- When stratified by age, the 5-year relative survival of patients with (insert disease name here) was ____ % and ____ % for patients <65 and ≥ 65 years of age respectively.[1]
- The survival of patients with (insert disease name here) varies with the stage of the disease. Shown below is a table depicting the 5-year relative survival by the stage of (insert disease name here):[1]
- Shown below is an image depicting the 5-year conditional relative survival (probability of surviving in the next 5-years given the cohort has already survived 0, 1, 3 years) between 1998 and 2010 of (insert disease name here) by stage at diagnosis according to SEER. These graphs are adapted from SEER: The Surveillance, Epidemiology, and End Results Program of the National Cancer Institute.[1]
[Insert figure x.5 here]
- ↑ Jump up to: 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2011/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014. | https://www.wikidoc.org/index.php/Sandbox_Epi | |
d6c373f1fcb80a4345ac1a11e4793a16c0c85374 | wikidoc | Sandbox ID2 | Sandbox ID2
# Bacteria – Gram-Positive Cocci
- Enterococci
- Enterococcus faecalis
- Bacteremia
- Ampicillin or Penicillin susceptible : Ampicillin 2 g IV q4-6h OR (Ampicillin AND Gentamicin 1 mg/kg q8h).
- Ampicillin resistant and vancomycin susceptible or Penicillin allergy : (Vancomycin 15 mg/kg IV q12h AND Gentamicin 1 mg/kg q8h) OR Linezolid 600 mg q12h OR Daptomycin 6 mg/kg per day.
- Ampicillin and Vancomycin resistant : Linezolid 600 mg q12h OR Daptomycin 6 mg/kg IV per day
- Endocarditis in Adults
- Strains Susceptible to Penicillin, Gentamicin, and Vancomycin
- Preferred regimen : (Ampicillin 12 g/day IV for 4–6weeks OR Aqueous crystalline penicillin G sodium 18–30 MU/day IV for 4–6weeks) AND Gentamicin sulfate 3 mg/kg/day IV/IM for 4–6 weeks
- Note : In case of native valve endocarditis, 4-wk therapy recommended for patients with symptoms of illness ≤3 months and 6-wk therapy recommended for patients with symptoms >3 months and prosthetic valve or other prosthetic cardiac material a minimum of 6 wk of therapy recommended
- Alternate regimen : Vancomycin hydrochloride 30 mg/kg/day IV for 6 weeks AND Gentamicin sulfate 3 mg/kg/day IV/IM for 6weeks
- Strains Susceptible to Penicillin, Streptomycin, and Vancomycin and Resistant to Gentamicin
- Preferred regimen : (Ampicillin 12 g/day IV for 4–6 weeks OR Aqueous crystalline penicillin G sodium 24 MU/day IV for 4–6weeks)AND Streptomycin sulfate 15 mg/kg/day IV/IM for 4–6weeks
- Alternate regimen: Vancomycin hydrochloride 30 mg/kg/day IV 6weeks AND Streptomycin sulfate 15 mg/kg per 24 h IV/IM for 6weeks
- Strains Resistant to Penicillin and Susceptible to Aminoglycoside and Vancomycin
- β Lactamase–producing strain
- Preferred regimen : Ampicillin-sulbactam 12 g/day IV for 6weeks AND Gentamicin sulfate 3 mg/kg/day IV/IM 6weeks
- Alternate regimen : Vancomycin hydrochloride 30 mg/kg/day IV for 6weeks AND Gentamicin sulfate 3 mg/kg/day IV/IM for 6weeks
- Intrinsic penicillin resistance : Vancomycin hydrochloride 30 mg/kg/day IV for 6weeks AND Gentamicin sulfate 3 mg/kg/day IV/IM for 6weeks
- Strains Resistant to Penicillin, Aminoglycoside, and Vancomycin
- Preferred regimen : (Imipenem OR Cilastatin 2 g/day IV for ≥ 8weeks AND Ampicillin 12 g/day IV for ≥ 8weeks) OR (Ceftriaxone sodium 4 g/day IV/IM for ≥ 8weeks AND Ampicillin 12 g/day IV for ≥ 8weeks)
- Endocarditis in Pediatrics
- Strains Susceptible to Penicillin, Gentamicin, and Vancomycin
- Preferred regimen : (Ampicillin 300 mg/kg/day IV for 4–6 weeks OR Penicillin 300,000U/kg/day IV for 4–6 weeks) AND Gentamicin 3 mg/kg per 24 h IV/IM 4–6 weeks
- Note : In case of native valve endocarditis, 4-wk therapy recommended for patients with symptoms of illness ≤3 months and 6-wk therapy recommended for patients with symptoms >3 months and prosthetic valve or other prosthetic cardiac material a minimum of 6 wk of therapy recommended
- Alternate regimen : Vancomycin 40 mg/kg/day IV for 6weeks AND Gentamicin 3 mg/kg/day IV/IM for 6weeks
- Strains Susceptible to Penicillin, Streptomycin, and Vancomycin and Resistant to Gentamicin
- Preferred regimen : (Ampicillin 300 mg/kg/day IV for 4–6 weeks OR Penicillin 300,000 U/kg/day IV for 4–6 weeks) AND Streptomycin 20–30 mg/kg/day IV/IM for 4–6 weeks
- Alternate regimen: Vancomycin hydrochloride 40 mg/kg/day IV for 6weeks AND Streptomycin sulfate 15 mg/kg/day IV/IM for 6weeks
- Strains Resistant to Penicillin and Susceptible to Aminoglycoside and Vancomycin
- β Lactamase–producing strain
- Preferred regimen : Ampicillin-sulbactam 300 mg/kg/day IV for 6weeks AND Gentamicin 3 mg/kg/day IV/IM for 6weeks
- Alternate regimen : Vancomycin 40 mg/kg/day IV for 6weeks AND Gentamicin 3 mg/kg/day IV/IM for 6weeks
- Intrinsic penicillin resistance : Vancomycin 40 mg/kg/day IV AND Gentamicin 3 mg/kg/day IV/IM for 6weeks
- Strains Resistant to Penicillin, Aminoglycoside, and Vancomycin
- Preferred regimen : Imipenem/cilastatin 60–100 mg/kg/day IV for ≥ 8weeks AND Ampicillin 300 mg/kg/day IVfor ≥ 8weeks
- Alternate regimen : Ceftriaxone 100 mg/kg/day IV/IM AND Ampicillin 300 mg/kg/day IV for ≥ 8weeks
- Meningitis
- Ampicillin susceptible
- Preferred regimen: Ampicillin 12 g/day IV q4h AND Gentamicin 5 mg/kg/day IV q8h
- Ampicillin resistant
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Gentamicin 5 mg/kg/day IV q8h
- Ampicillin and vancomycin resistant
- Preferred regimen: Linezolid 600 mg IV q12h
- Urinary tract infections
- Preferred regimen : Nitrofurantoin 100 mg PO q6h for 5 days OR Fosfomycin 3 g PO single dose OR Amoxicillin 875 mg-1 g PO q12h for 5 days
- Intra abdominal or Wound infections
- Penicillin or Ampicillin are preferred agents, Vancomycin in setting of penicillin allergy or high-level penicillin resistance.
- For complicated skin-skin structure and intra-abdominal infection : Tigecycline 100 mg IV single dose and 50 mg IV q12h
- Enterococcus faecium
- Bacteremia
- Ampicillin or Penicillin susceptible : Ampicillin 2 g IV q4-6h OR (Ampicillin AND Gentamicin 1 mg/kg q8h).
- Ampicillin resistant and vancomycin susceptible or Penicillin allergy : (Vancomycin 15 mg/kg IV q12h AND Gentamicin 1 mg/kg q8h) OR Linezolid 600 mg q12h OR Daptomycin 6 mg/kg per day.
- Ampicillin and Vancomycin resistant : Linezolid 600 mg q12h OR Daptomycin 6 mg/kg IV per day
- Endocarditis in Adults
- Strains Susceptible to Penicillin, Gentamicin, and Vancomycin
- Preferred regimen : (Ampicillin 12 g/day IV for 4–6weeks OR Aqueous crystalline penicillin G sodium 18–30 MU/day IV for 4–6weeks) AND Gentamicin sulfate 3 mg/kg/day IV/IM for 4–6 weeks
- Note : In case of native valve endocarditis, 4-wk therapy recommended for patients with symptoms of illness ≤3 months and 6-wk therapy recommended for patients with symptoms >3 months and prosthetic valve or other prosthetic cardiac material a minimum of 6 wk of therapy recommended
- Alternate regimen : Vancomycin hydrochloride 30 mg/kg/day IV for 6 weeks AND Gentamicin sulfate 3 mg/kg/day IV/IM for 6weeks
- Strains Susceptible to Penicillin, Streptomycin, and Vancomycin and Resistant to Gentamicin
- Preferred regimen : (Ampicillin 12 g/day IV for 4–6 weeks OR Aqueous crystalline penicillin G sodium 24 MU/day IV for 4–6weeks)AND Streptomycin sulfate 15 mg/kg/day IV/IM for 4–6weeks
- Alternate regimen: Vancomycin hydrochloride 30 mg/kg/day IV 6weeks AND Streptomycin sulfate 15 mg/kg per 24 h IV/IM for 6weeks
- Strains Resistant to Penicillin and Susceptible to Aminoglycoside and Vancomycin
- β Lactamase–producing strain
- Preferred regimen : Ampicillin-sulbactam 12 g/day IV for 6weeks AND Gentamicin sulfate 3 mg/kg/day IV/IM 6weeks
- Alternate regimen : Vancomycin hydrochloride 30 mg/kg/day IV for 6weeks AND Gentamicin sulfate 3 mg/kg/day IV/IM for 6weeks
- Intrinsic penicillin resistance : Vancomycin hydrochloride 30 mg/kg/day IV for 6weeks AND Gentamicin sulfate 3 mg/kg/day IV/IM for 6weeks
- Strains Resistant to Penicillin, Aminoglycoside, and Vancomycin
- Preferred regimen : Linezolid 1200 mg/day IV/PO ≥8weeks OR Quinupristin-Dalfopristin22.5 mg/kg/day IV ≥8weeks
- Endocarditis in Pediatrics
- Strains Susceptible to Penicillin, Gentamicin, and Vancomycin
- Preferred regimen : (Ampicillin 300 mg/kg/day IV for 4–6 weeks OR Penicillin 300,000U/kg/day IV for 4–6 weeks) AND Gentamicin 3 mg/kg per 24 h IV/IM 4–6 weeks
- Note : In case of native valve endocarditis, 4-wk therapy recommended for patients with symptoms of illness ≤3 months and 6-wk therapy recommended for patients with symptoms >3 months and prosthetic valve or other prosthetic cardiac material a minimum of 6 wk of therapy recommended
- Alternate regimen : Vancomycin 40 mg/kg/day IV for 6weeks AND Gentamicin 3 mg/kg/day IV/IM for 6weeks
- Strains Susceptible to Penicillin, Streptomycin, and Vancomycin and Resistant to Gentamicin
- Preferred regimen : (Ampicillin 300 mg/kg/day IV for 4–6 weeks OR Penicillin 300,000 U/kg/day IV for 4–6 weeks) AND Streptomycin 20–30 mg/kg/day IV/IM for 4–6 weeks
- Alternate regimen: Vancomycin hydrochloride 40 mg/kg/day IV for 6weeks AND Streptomycin sulfate 15 mg/kg/day IV/IM for 6weeks
- Strains Resistant to Penicillin and Susceptible to Aminoglycoside and Vancomycin
- β Lactamase–producing strain
- Preferred regimen : Ampicillin-sulbactam 300 mg/kg/day IV for 6weeks AND Gentamicin 3 mg/kg/day IV/IM for 6weeks
- Alternate regimen : Vancomycin 40 mg/kg/day IV for 6weeks AND Gentamicin 3 mg/kg/day IV/IM for 6weeks
- Intrinsic penicillin resistance : Vancomycin 40 mg/kg/day IV AND Gentamicin 3 mg/kg/day IV/IM for 6weeks
- Strains Resistant to Penicillin, Aminoglycoside, and Vancomycin
- Preferred regimen : Linezolid 30 mg/kg/day IV/PO ≥ 8weeks OR Quinupristin-Dalfopristin22.5 mg/kg/day IV ≥ 8weeks
- Meningitis
- Ampicillin susceptible
- Preferred regimen: Ampicillin 12 g/day IV q4h AND Gentamicin 5 mg/kg/day IV q8h
- Ampicillin resistant
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Gentamicin 5 mg/kg/day IV q8h
- Ampicillin and vancomycin resistant
- Preferred regimen: Linezolid 600 mg IV q12h
- Urinary tract infections
- Preferred regimen : Nitrofurantoin 100 mg PO q6h for 5 days OR Fosfomycin 3 g PO single dose OR Amoxicillin 875 mg-1 g PO q12h for 5 days
- Intra abdominal or Wound infections
- Penicillin or Ampicillin are preferred agents, Vancomycin in setting of penicillin allergy or high-level penicillin resistance.
- For complicated skin-skin structure and intra-abdominal infection : Tigecycline 100 mg IV single dose and 50 mg IV q12h
- Staphylococci
- Staphylococcus aureus
- (1)Infectious endocarditis
- In adults
- Preferred regimen: Vancomycin, 15-20 mg/kg IV q8-12h OR Daptomycin 6mg/kg/dose IV qd
- (2) Intravascular catheter-related infections
- Methicillin susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Nafcillin 2 g IV q6h OR Oxacillin, 2 g IV q6h.
- Alternative regimen: Cefazolin, 2 g IV q8h OR Vancomycin, 15 mg/kg IV q12h.
- Pediatric dose:
- Nafcillin
- Neonates
- 0–4 weeks of age and 1200 g- 50 mg/kg/day q12h.
- ≤7 days and 1200–2000 g- 50 mg/kg/day q12h.
- >7 days of age and <2000g- 75 mg/kg/day q8h.
- >7 days of age and >1200 g - 100 mg/kg/day q6h.
- Oxacillin
- Neonates
- 0–4 weeks of age and 1200 g - 50 mg/kg/day q12h.
- Postnatal age <7 days and 1200–2000 g- 50–100 mg/kg/day q12h.
- Postnatal age 2000 g, 75–150 mg/kg/day q8h.
- Postnatal age ≥7 days and 1200–2000 g- 75–150 mg/kg/day q8h.
- Postnatal age ≥7 days and >2000 g, 100–200 mg/kg/day q6h.
- Infants and children Nafcillin 100–200 mg/kg/day q4–6h.
- Cefazolin
- Neonates
- Postnatal age ≤7 days: 40 mg/kg/day q12h.
- Postnatal age >7 days and 2000 g: 40 mg/kg/day q12h.
- Postnatal age >7 days and 12000 g: 60 mg/kg/day q8h.
- Infants and children: 50 mg/kg/day q8h.
- Vancomycin
- Neonates
- Postnatal age ≤7 days and <1200 g, 15 mg/kg/day q24h.
- Postnatal age ≤7 days and 1200–2000 g, 10–15 mg/kg q12–18h.
- Postnatal age ≤7 days and >2000 g, 10–15 mg/kg q8–12h.
- Postnatal age >7 days and <1200 g, 15 mg/kg/day q24h.
- Postnatal age >7 days and 1200–2000 g, 10–15 mg/kg q8–12h.
- Postnatal age >7 days and >2000 g, 15–20 mg/kg q8h.
- Infants and children: 40 mg/kg/day q6–8h.
- Methicillin resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin, 15 mg/kg IV q12h OR Daptomycin, 6–8 mg/kg per day IV, or Linezolid 10 mg/kg q 12 hr IV or PO ; OR Vancomycin 15 mg/kg IV q12h AND (Rifampicin IV or Gentamycin IV); or Trimethoprim-Sulfamethoxazole 6–12 mg TMP/kg/day in divided doses q12h alone (if susceptible).
- Pediatric dose
- Linezolid 10 mg/kg IV or PO q12h
- Neonates
- 0–4 weeks of age and birthweight <1200 g: 10 mg/kg q8–12h (note: q12h in patients <34 weeks gestation and <1 week of age).
- 1200 g, 10 mg/kg q8–12h (note: q12h in patients <34 weeks gestation and <1 week of age).
- 7 days and birthweight >1200 g, 10 mg/kg q8h.
- Infants and children <12 years of age: 10 mg/kg q8h Children 12 years of age and adolescents: 10 mg/kg q12h.
- Gentamycin
- Neonates
- Premature neonates and <1000 g, 3.5 mg/kg q24h; 0–4 weeks and <1200 g, 2.5 mg/kg q18-24h.
- Postnatal age 7 days: 2.5 mg/kg q12h.
- Postnatal age 17 days and 1200–2000 g, 2.5 mg/kg q8-12h.
- Postnatal age 17 days and 12000 g, 2.5 mg/kg q8h.
- Once daily dosing for premature neonates with normal renal function, 3.5–4 mg/kg q24h.
- Once daily dosing for term neonates with normal renal function, 3.5–5 mg/kg q24h.
- Infants and children <5 years of age: 2.5 mg/kg q8h; qd dosing in patients with normal renal function, 5–7.5 mg/kg q24h.
- Children >5 years of age: 2–2.5 mg/kg q8h; qd s with normal renal function, 5–7.5 mg/kg every 24 h.
- Trimethoprim-Sulfamethoxazole
- Infants 12 months of age and children: mild-to-moderate infections, 6–12 mg TMP/kg/day q12h; serious infection, 15–20 mg TMP/kg/day q6-8h.
- (3) Purulent cellulitis (defined as cellulitis associated with purulent drainage or exudate in the absence of a drainable abscess)
- In adults
- Preferred regimen: Clindamycin 300–450 mg PO TID OR Trimethoprim-Sulfamethoxazole 1–2 DS tab PO BID OR Doxycycline 100 mg PO BID OR Minocycline 200 mg as a single dose, then 100 mg PO BID OR Linezolid 600 mg PO BID
- In childern
- Preferred regimen: Clindamycin 10–13 mg/kg/dose PO q6–8 h, not to exceed 40 mg/kg/day OR Trimethoprim 4–6 mg/kg, Sulfamethoxazole 20–30 mg/kg PO q12h OR Doxycycline If patient body weight <45kg: 2 mg/kg/dose PO q12 h.
- Nonpurulent cellulitis (defined as cellulitis with no purulent drainage or exudate and no associated abscess)
- In adults
- Preferred regimen: Beta-lactam (eg, Cephalexin and Dicloxacillin) 500 mg PO QID OR Clindamycin 300–450 mg PO TID OR Amoxicillin 500 PO mg TID OR Linezolid 600 mg PO BID
- In childern
- Preferred regimen: Clindamycin 10–13 mg/kg PO q6–8 h, not to exceed 40 mg/kg/day OR Trimethoprim 4–6 mg/kg, Sulfamethoxazole 20–30 mg/kg PO q12h OR Linezolid 10 mg/kg PO q8h, not to exceed 600 mg
- (4) Brain abscess
- Methicillin-resistant Staphylococcus aureus (MRSA)
- In adults
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 4–6 weeks
- Alternative regimen: Linezolid 600 mg PO/IV q12h for 4–6 weeks OR Trimethoprim-Sulfamethoxazole 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks
- In childern
- Preferred regimen: Vancomycin15 mg/kg/dose IV q6h OR Linezolid 10 mg/kg/dose PO/IV q8h
- Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Nafcillin 2 g IV q4h OR Oxacillin 2 g IV q4h
- Alternative regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
- (5) Cerebrospinal fluid shunt infection
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND/OR Rifampin 600 mg IV or PO q24h
- Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: (Nafcillin 2 g IV q4h OR Oxacillin 2 g IV q4h) AND/OR Rifampin 600 mg IV/PO q24h
- (6) Spinal epidural abscess
- Penicillin-susceptible Staphylococcus aureus or Streptococcus
- Preferred regimen: Penicillin G 4 MU IV q4h for 2–4 weeks, then PO to complete 6–8 weeks
- Methicillin-susceptible Staphylococcus aureus or Streptococcus
- Preferred regimen: Cefazolin 2 g IV q8h for 2–4 weeks, then PO to complete 6–8 weeks OR Nafcillin 2 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks OR Oxacillin 2 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks
- Alternative regimen: Clindamycin 600 mg IV q6h for 2–4 weeks, then PO to complete 6–8 weeks
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin loading dose 25–30 mg/kg IV followed by 15–20 mg/kg IV q8–12h for 2–4 weeks, then PO to complete 6–8 weeks
- Alternative regimen: Linezolid 600 mg PO or IV q12h for 4–6 weeks OR TMP-SMX 5 mg/kg PO or IV q8–12h for 4–6 weeks
- Pediatric dose: Vancomycin 15 mg/kg IV q6h OR Linezolid 10 mg/kg PO or IV q8h
- (7) Bacterial meningitis
- Methicillin susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Nafcillin 9–12 g/day IV q4h OR Oxacillin 9–12 g/day IV q4h
- Alternative regimen: Vancomycin 30–45 mg/kg/day IV q8–12h OR Meropenem 6 g/day IV q8h
- Methicillin resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
- Alternative regimen: Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h OR Linezolid 600 mg IV q12h
- (8) Septic thrombosis of cavernous or dural venous sinus
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h for 4–6 weeks
- Alternative regimen: Linezolid 600 mg PO IV q12h for 4–6 weeks OR TMP-SMX 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks
- Pediatric dose: Vancomycin 15 mg/kg IV q6h OR Linezolid 10 mg/kg PO or IV q8h
- (9) Subdural empyema
- Methicillin-resistant Staphylococcus aureus (MRSA)
- In adults
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 4–6 weeks
- Alternative regimen: Linezolid 600 mg PO or IV q12h for 4–6 weeks OR TMP-SMX 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks
- In childern
- Preferred regimen: Vancomycin 15 mg/kg/dose IV q6h OR Linezolid 10 mg/kg/dose PO/IV q8h
- (10) Acute conjunctivitis
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin ointment 1% qid
- (11) Appendicitis
- (12) Diverticulitis
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h.
- (13) Peritonitis secondary to bowel perforation, peritonitis secondary to ruptured appendix, peritonitis secondary to ruptured appendix, typhlitis
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h
- (14) Cystic fibrosis
- Preferred Regimen (Adult)
- If methicillin sensitive staphylococcus aureus: Nafcillin 2 gm IV q4hs OR Oxacillin 2 gm IV q4hs
- If methicillin resistant staphylococcus aureus: Vancomycin 15-20 mg/kg IV q8-12h OR Linezolid 600 mg po/IV q12h
- Preferred regimen (Pediatric)
- If methicillin sensitive staphylococcus aureus: Nafcillin 5 mg/kg q6h (Age >28 days) OR Oxacillin 75 mg/kg q6h (Age >28 days)]]
- If methicillin resistant staphylococcus aureus: Vancomycin 40 mg/kg q6-8h (Age >28 days) OR Linezolid 10 mg/kg po or IV q8h (up to age 12)
- (15) Bronchiectasis
- (a) Preferred Regimen in adults
- Recommended first-line treatment and length of treatment
- Recommended second-line treatment and length of treatment
- (b) Preferred Regimen in children
- Recommended first-line treatment and length of treatment
- Recommended second-line treatment and length of treatment
- (B)Long-term oral antibiotic treatment
- (a) Preferred Regimen in adults
- Recommended first-line treatment and length of treatment
- Recommended second-line treatment and length of treatment
- (16) Empyema
- Preferred regimen: Nafcillin 2 gm IV q4h OR oxacillin 2 gm IV q4h if MSSA
- Alternate regimen: Vancomycin 1 gm IV q12h OR Linezolid 600 mg po bid if MRSA
- (17) Community-acquired pneumonia
- Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred Regimen : Nafcillin 1000-2000 mg q4h OR Oxacillin 2 g IV q4h OR Flucloxacillin 250 mg IM/IV q6h
- Alternative Regimen : Cefazolin 500 mg IV q12h OR Clindamycin 150-450 mg PO q6-8h
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred Regimen : Vancomycin 45-60 mg/kg/day divided q8-12h (max: 2000 mg/dose) for 7-21 days OR Linezolid 600 mg PO/IV q12h for 10-14 days
- Alternative Regimen: Trimethoprim-Sulfamethoxazole 1-2 double-strength tablets (800/160 mg) q12-24h
- (18) Olecranon bursitis or prepatellar bursitis
- Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Nafcillin 2 g IV q4h OR Oxacillin 2 g IV q4h OR Dicloxacillin 500 mg PO qid
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 1 g IV q12h OR Linezolid 600 mg PO qd
- (19) Septic arthritis
- In adults
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regime: Vancomycin 15–20 mg/kg IV q8–12h
- Alternative regimen (1): Daptomycin 6 mg/kg IV q24h in adults
- Alternative regimen (2): Linezolid 600 mg PO/IV q12h
- Alternative regimen (3): Clindamycin 600 mg PO/IV q8h
- Alternative regimen (4): TMP-SMX 3.5–4.0 mg/kg PO/IV q8–12h
- In childern
- Preferred regimen: Vancomycin 15 mg/kg IV q6h OR Daptomycin 6–10 mg/kg IV q24h OR Linezolid 10 mg/kg PO/IV q8h OR Clindamycin 10–13 mg/kg/dose PO/IV q6–8h
- Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regime: Nafcillin 2 g IV q6h OR Clindamycin 900 mg IV q8h
- Alternative regime: Cefazolin 0.25–1 g IV/IM q6–8h OR Vancomycin 500 mg IV q6h or 1 g IV q12h
- (20) Septic arthritis, prosthetic joint infection (device-related osteoarticular infections)
- Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Nafcillin 2 g IV q4–6h OR Oxacillin 2 g IV q4–6h
- Alternative regimen: Cefazolin 1–2 g IV q8h OR Ceftriaxone 2 g IV q24h
- Alternative regimen (if allergic to penicillins): Clindamycin 900 mg IV q8h OR Vancomycin 15–20 mg/kg IV q8–12 hours, not to exceed 2 g per dose
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Early-onset (< 2 months after surgery) or acute hematogenous prosthetic joint infections involving a stable implant with short duration (< 3 weeks) of symptoms and debridement (but device retention)
- Preferred regimen: Vancomycin AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks
- Alternative regimen: (Daptomycin 6 mg/kg IV q24h OR Linezolid 600 IV q8h) AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks
- (21) Hematogenous osteomyelitis
- Adult (>21 yrs)
- Methicillin-resistant Staphylococcus aureus (MRSA) possible
- Preferred regimen: Vancomycin 1 gm IV q12h (if over 100 kg, 1.5 gm IV q12h)
- Methicillin-resistant Staphylococcus aureus (MRSA) unlikely
- Preferred regimen: Nafcillin OR Oxacillin 2 gm IV q4h
- Children (>4 mos.)-Adult
- Methicillin-resistant Staphylococcus aureus (MRSA) possible
- Preferred regimen: Vancomycin 40 div q6–8h
- Methicillin-resistant Staphylococcus aureus (MRSA) unlikely
- Preferred regimen: Nafcillin OR Oxacillin 37 q6h (to max. 8–12 gm per day)
- Newborn (<4 mos.)
- Methicillin-resistant Staphylococcus aureus (MRSA) possible
- Preferred regimen: Vancomycin AND (Ceftazidime 2 gm IV q8h or Cefepime 2 gm IV q12h)
- Methicillin-resistant Staphylococcus aureus (MRSA) unlikely
- Preferred regimen: (Nafcillin OR Oxacillin) AND (Ceftazidime OR Cefepime)
- Specific therapy
- Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Nafcillin OR Oxacillin 2 gm IV q4h OR Cefazolin 2 gm IV q8h
- Alternative regimen: Vancomycin 1 gm IV q12h (if over 100 kg, 1.5 gm IV q12h)
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 1 gm IV q12h
- Alternative regimen: Linezolid 600 mg q12h IV/po ± Rifampin 300 mg po/IV bid
- (22) Diabetic foot osteomyelitis
- High Risk for MRSA
- Preferred regimen: Linezolid 600 mg IV/PO q12h OR Daptomycin 4 mg/kg IV q24h OR Vancomycin 15–20 mg/kg IV q8–12h (trough: 10–20 mg/L)
- (23) Necrotizing fasciitis
- In adult
- Preferred regimen (1): Nafcillin 1–2 g IV q4h (Severe Pencillin allergy: Vancomycin, linezolid, quinupristin/dalfopristin, daptomycin)
- Preferred regimen (2): Oxacillin 1–2 g IV q4h
- Preferred regimen (3): Cefazolin 1 g IV q8h
- Preferred regimen (4): Vancomycin 15 mg/kg IV bid
- Preferred regimen (5): Clindamycin 600–900 mg IV q8h
- In childern
- Preferred regimen (1): Nafcillin 50 mg/kg/dose IV q6h (Severe Pencillin allergy: Vancomycin, linezolid, quinupristin/dalfopristin, daptomycin)
- Preferred regimen (2): Oxacillin 50 mg/kg/dose IV q6h
- Preferred regimen (3): Cefazolin 33 mg/kg/dose IV q8h
- Preferred regimen (4): Vancomycin 15 mg/kg/dose IV q6h
- Preferred regimen (5): Clindamycin 10–13 mg/kg/dose IV q8h (Bacteriostatic; potential cross-resistance and emergence of resistance in erythromycin-resistant strains; inducible resistance in methicillin resistent staphylococcus aureus)
- (24) Staphylococcal toxic shock syndrome
- Methicillin sensitive Staphylococcus aureus
- Preferred regimen: Cloxacillin 250-500 mg PO q6h (max dose: 4 g/24 hr) OR Nafcillin 4-12 g/24 hr divided IV q4-6hr (max dose: 12 g/24 hr) OR Cefazolin 0.5-2g IV or IM q8h (max dose: 12 g/24 hr), AND Clindamycin 150-600 mg IV, IM, or PO q6-8h (max dose: 5 g/24 hr IV or IM or 2 g/24 hr PO)
- Alternative regimen (1):Clarithromycin 250-500 mg PO q12h (max dose: 1 g/24 hr) AND Clindamycin 150-600 mg IV, IM, or PO q6-8h (max dose: 5 g/24 hr IV or IM or 2 g/24 hr PO)
- Alternative regimen (1):Rifampicin, AND Linezolid 600 mg IV or PO q12h OR Daptomycin OR Tigecycline 100 mg loading dose followed by 50 mg IV q12h
- Methicillin resistant Staphylococcus aureus
- Preferred regimen: Clindamycin 150-600 mg IV, IM, or PO q6-8h (max dose: 5 g/24 hr IV or IM or 2 g/24 hr PO) OR Linezolid 600 mg IV or PO q12h AND Vancomycin 15 to 20 mg/kg IV q8-12h, not to exceed 2 g per dose or Teicoplanin
- Alternative regimen (1):Rifampicin, AND Linezolid 600 mg q12h IV or PO OR Daptomycin OR Tigecycline 100 mg loading dose followed by 50 mg q12h IV
- Glycopeptide resistant or intermediate Staphylococcus aureus
- Preferred regimen: Linezolid 600 mg IV or PO q12h AND Clindamycin 150-600 mg IV, IM, or PO q6-8h (max dose: 5 g/24 hr IV or IM or 2 g/24 hr PO) (if sensitive)
- Alternative regimen (1):Daptomycin OR Tigecycline 100 mg loading dose followed by 50 mg IV q12h
- Prophylaxis for coronary artery bypass graft-associated acute mediastinitis
- Methicillin susceptible staphylococcus aureus (MSSA)
- Preferred regimen: A first- or second-generation Cephalosporin is recommended for prophylaxis in patients without methicillin-resistant Staphylococcus aureus colonization.
- Methicillin resistant staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin alone or in combination with other antibiotics to achieve broader coverage is recommended for prophylaxis in patients with proven or suspected methicillin-resistant S. aureus colonization
- Staphylococcus, coagulase-negative species (CoNS)
- Staphylococcus epidermidis group (Staphylococcus epidermidis, Staphylococcus haemolyticus)
- 1. Bacteremia: most often due to IV lines, vascular grafts, cardiac valves (30-40% of all coagulase-negative staphylococcus infections)
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h AND Vancomycin AND Rifampin 300 mg q8h IV/PO for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg q8h IV/PO.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- 2. CSF shunt: meningitis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h added to Vancomycin AND Rifampin 300 mg IV/PO q8h for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg IV/PO q8h.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- 3. Peritoneal dialysis catheter: peritonitis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h added to Vancomycin AND Rifampin 300 mg q8h IV/PO for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg q8h IV/PO.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- 4. Prosthetic joint: septic arthritis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h added to Vancomycin AND Rifampin 300 mg q8h IV/PO for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg q8h IV/PO.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- 5. Prosthetic or natural cardiac valve: endocarditis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h added to Vancomycin AND Rifampin 300 mg q8h IV/PO for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg q8h IV/PO.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- 6. Post-sternotomy: osteomyelitis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h added to Vancomycin AND Rifampin 300 mg q8h IV/PO for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg q8h IV/PO.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- 7. Implants (breast, penile, pacemaker) and other prosthetic devices: local infection
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h added to Vancomycin AND Rifampin 300 mg q8h IV/PO for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg q8h IV/PO.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- 8. Post-ocular surgery: endophthalmitis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h added to Vancomycin AND Rifampin 300 mg q8h IV/PO for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg q8h IV/PO.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- 9. Surgical site infections
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h added to Vancomycin AND Rifampin 300 mg q8h IV/PO for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg q8h IV/PO.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- Staphylococcus lugdunensis
- 1. Postpartum mastitis with or without abscess
- Preferred regimen: In outpatient is Dicloxacillin 500 mg po qid OR Cephalexin 500 mg po qid and in inpatient is Oxacillin OR Nafcillin 2 gm IV q4h
- Alternative regimen: In outpatient is Trimethoprim-Sulfamethoxazole-DS tabs 1-2 po bid or, if susceptible, Clindamycin 300 mg po qid and in inpatient is Vancomycin 1 gm IV q12h; if over 100 kg, 1.5 gm IV q12h.
- 2. Non-puerperal mastitis with abscess
- Preferred regimen: In outpatient is Dicloxacillin 500 mg po qid OR Cephalexin 500 mg po qid and in inpatient is Oxacillin OR Nafcillin 2 gm IV q4h
- Alternative regimen: In outpatient is Trimethoprim-Sulfamethoxazole-DS tabs 1-2 po bid or, if susceptible, Clindamycin 300 mg po qid and in inpatient is Vancomycin 1 gm IV q12h; if over 100 kg, 1.5 gm IV q12h.
- Staphylococcus saprophyticus
- 1. Urinary tract infection
- 1.1 Acute uncomplicated urinary tract infection (cystitis-urethritis) in females
- Preferred regimen : Cephalosporin PO OR Amoxicillin-Clavulanate 625 mg PO OR Trimethoprim-Sulfamethoxazole-DS bid for 3 days; if sulfa allergy, Nitrofurantoin 100 mg po bid for 5 days OR Fosfomycin 3 gm po as a single dose AND Pyridium.
- Alternative regimen (in sulfa allergy): then 3 days of Ciprofloxacin 250 mg bid OR Ciprofloxacin-Erythromycin 500 mg q24h OR Levofloxacin 250 mg q24h OR Moxifloxacin 400 mg q24h OR Nitrofurantoin 100 mg bid OR Fosfomycin single 3 gm dose AND Phenazopyridine Pyridium 200 mg po tid times 2 days.
- 1.2 Recurrent urinary tract infection in postmenopausal women
- Preferred regimen : Trimethoprim-Sulfamethoxazole-DS bid for 3 days; if sulfa allergy, Nitrofurantoin 100 mg po bid for 5 days OR Fosfomycin 3 gm po as a single dose AND Pyridium.
- Alternative regimen (in sulfa allergy): then 3 days of Ciprofloxacin 250 mg bid OR Ciprofloxacin-Erythromycin 500 mg q24h OR Levofloxacin 250 mg q24h OR Moxifloxacin 400 mg q24h OR Nitrofurantoin 100 mg bid OR Fosfomycin single 3 gm dose AND Phenazopyridine Pyridium 200 mg po tid times 2 days.
- Streptococci
- Streptobacillus moniliformis
- Streptococcus moniliformis treatment
- 1. Migratory arthropathy and arthritis
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 2. Diarrhea, (especially kids) liver or spleen abscess
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 3. Undifferentiated fever
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 4. Endocarditis, myocarditis, pericarditis (cardiac)
- Preferred regimen: Penicillin 20 MU/day IV divided q4h. Optimal duration recommendation for infective endocarditis is 4 weeks.
- Alternative regimen: Cephalosporins-Ceftriaxone OR Clindamycin OR Erythromycin OR Chloramphenicol AND Streptomycin.
- 5. Meningitis, brain abscess
- Preferred regimen: Penicillin 20 MU/day IV divided q4h.
- Alternative regimen: Cephalosporins-Ceftriaxone OR Clindamycin OR Erythromycin OR Chloramphenicol AND Streptomycin.
- 6. Anemia
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 7. Pneumonia
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 8. Amnionitis (pregnancy)
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 9. Renal abscess
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- Streptococcus anginosus
Group comprises 3-15% of streptococcal isolates of endocarditis. See Diagnosis section for Endocarditis module for management, follow viridans Streptococci recommendations.
Dental abscesses, sinusitis, fasciitis of head and neck: can be life threatening and require aggressive surgical management. See appropriate HEENT module for specific management.
Bacteremia often associated with deep-seated abscess. Investigate for abscess—most often intraabdominal. Drainage is usually recommended.
Brain abscesses often polymicrobial, but S. intermedius found in 50-80%. See Brain abscess module for management.
Implicated in aspiration pneumonia, lung abscess and empyema.
- Preferred regimen: Penicillin G 2-4 MU IV q4h .
- Alternative regimen: Ceftriaxone 2 g IV qd; Clindamycin 600-900 mg IV q8h or 300-450 mg PO qid OR Vancomycin 15 mg/kg IV q12h ([[Penicillin-allergic).
- Streptococcus pneumoniae
- Streptococcus pneumonia treatment
- 1. Lung (pneumonia)
- Community-acquired pneumonia
- Penicillin sensitive (minimum inhibitory concentration ≤ 2)
- Preferred regimen: Penicillin G 1-2 MU q6h IV OR Ceftriaxone 2 g IV q24h OR Cefotaxime 1-2 g IV q6-8h.
- Penicillin-resistant (Penicillin minimum inhibitory concentration >8)
- Preferred regimen:: Levofloxacin (Levaquin) 750 mg OR Moxifloxacin (Avelox) 400 mg IV/PO q24h, Telithromycin (Ketek) 800 mg PO qd, Ceftriaxone IV, Cefotaxime IV, Vancomycin 15 mg/kg IV q12h OR Linezolid 600 mg IV/PO q12h.
- 2. Sinuses (sinusitis)
- Sinusitis (empiric therapy)
- Preferred regimen: amoxicillin 500-1000 mg PO tid OR Amoxicillin/Clavulanate 875/125 mg PO bd.
- 3. Middle ear (otitis media)
- (4)Bronchi (acute exacerbation of chronic bronchitis)
- Preferred regimen: amoxicillin 2-3 PO g/day OR Doxycycline 100 mg PO bd.
- (5)CNS (meningitis)
- Empiric therapy
- In age group of 1 months– 50 years
Adult dosage: (Cefotaxime 2 gm IV q4–6h OR Ceftriaxone 2 gm IV q12h) AND Dexamethasone AND Vancomycin 15 mg/kg/day IV q12h
- Preferred regimen: Vancomycin 15 mg/kg/day IV q12h AND Ceftriaxone 2 g IV q12h OR Cefotaxime 2 g IV q4h or 3 g q6h.
- Penicillin sensitive (minimum inhibitory concentration ≤ 0.06)
- Preferred regimen: Ceftriaxone 2 g IV q12h, OR Cefotaxime 2 g IV q4h or 3 g IV q6h.
- Penicillin resistant (minimum inhibitory concentration ≥ 0.12) or beta-lactam hypersensitivity
- Preferred regimen: Vancomycin 30-45 mg/kg/day IV.
- (6)Peritoneum (spontaneous bacterial peritonitis)
- (7)Pericardium (purulent pericarditis)
- (8)Skin (cellulitis)
- (9)Eye (conjunctivitis)
- Streptococcus pyogenes
- (1) Pharyngitis
- Preferred regimen: Penicillin-benzathine]] Penicillin 1.2 mU IM once OR Penicillin VK 500 mg PO bd or tid for 10 days.
- Alternative regimen (1): Amoxicillin 750 PO bd or tid for 10 days.
- Alternative regimen (Penicillin allergy): Erythromycin 500 mg PO bd or tid for 10 days OR (Azithromycin 500 mg, then 250 mg for 5 days, Clarithromycin (Biaxin) 1 g XR/day or 500 mg bd for 10 days. Note: 5-10% isolates are macrolide resistant) OR Cefpodoxime proxetil (Vantin) 200 mg bd for 5 days OR Cefdinir 300 mg bd PO for 5 days OR Cefadroxil 500 mg bd PO for 5 days OR Loracarbef 200 mg PO bd for 5 days.
- (2) Skin: erysipelas, lymphangitis, cellulitis
- Preferred regimen: Clindamycin 600 mg IV q8h AND Penicillin G G 4 mU IV q4h. (clindamycin to stop toxin production).
- Alternative regimen: Penicillin G 2-4 mU IV q4h OR Clindamycin 600 mg IV q8h OR Cefazolin 1-2 g IV q6-8h OR Cefotaxime 2-3 g IV q6-8h OR Ceftriaxone 2 g/day IV OR Vancomycin 15 mg/kg IV q12h.
- (3) Soft tissue
- Necrotizing fasciitis: surgical consultation for emergent fasciotomy and debridement; repeat debridements usually necessary.
- (4) Muscle
- Myositis: debirdement
- (5) Endometrium
- (6) Puerperal sepsis
- (7) Lung
- pneumonia with or without early bloody effusion Bacteremia
- (8) Cardiac are endocarditis (very rare in antibiotic era)
- (9) Toxin mediated
- Scarlet fever
- Toxic shock syndrome
- Preferred regimen: Immunoglobulin-G 2 or more doses IV , massive IV fluids (10-20 L/day), Albumin if <2 g/dL, debridement of necrotic tissue.
- (10)Non-suppurative complications are rheumatic fever and glomerulonephritis
- Prophylaxis
- Acute rheumatic fever prophylaxis
- Preferred regimen: Benzathine Penicillin 1.2 mu IM q mo, Penicillin V 250 mg PO bd, Erythromycin 250 mg PO bd until >5 yrs post-acute rheumatic fever and age in 20years.
- Recurrent cellulitis, chronic lymphedema prophylaxis
- Preferred regimen: Clindamycin 150 mg PO qd OR Trimethoprim-Sulfamethoxaole 1 DS PO qd OR “stand-by therapy” immediate treatment with Penicillin V OR Amoxicillin 500-750 mg PO bd at onset of symptoms.
- Streptococcus agalactiae
# Bacteria – Gram-Positive Bacilli
- Actinomyces israelii
- Arcanobacterium haemolyticum
- Bacillus
- Bacillus anthracis, treatment
- (A) Treatment for cutaneous anthrax, without systemic involvement
- Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown): Ciprofloxacin 500 mg PO q12h OR Doxycycline 100 mg PO q12h OR Levofloxacin 750 mg PO q24h OR Moxifloxacin 400 mg PO q24h
- Alternative regimen: Clindamycin 600 mg PO q8h OR Amoxicillin 1 g PO q8h (for penicillin-susceptible strains) OR Penicillin VK 500 mg PO q6h (for penicillin-susceptible strains)
- (B) Treatment for systemic anthrax including anthrax meningitis, inhalational anthrax, injectional anthrax, and gastrointestinal anthrax; and cutaneous anthrax with systemic involvement, extensive edema, or lesions of the head or neck
- (B-1) Systemic anthrax with possible/confirmed meningitis
- (1) Bactericidal agent (fluoroquinolone): Ciprofloxacin 400 mg IV q8h (OR Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h) AND
- (2) Bactericidal agent (β-lactam) for all strains, regardless of penicillin susceptibility or if susceptibility is unknown: Meropenem 2 g IV q8h OR Imipenem 1 g IV q6h OR Doripenem 500 mg IV q8h OR Penicillin G 4 MU IV q4h (for penicillin-susceptible strains) OR Ampicillin 3 g IV q6h (for penicillin-susceptible strains) AND
- (3) Protein synthesis inhibitor: Linezolid 600 mg IV q12h OR Clindamycin 900 mg IV q8h OR Rifampin 600 mg IV q12h OR Chloramphenicol 1 g IV q6-8h
- (B-2) Systemic anthrax when meningitis has been excluded
- (1) Bactericidal agent: Ciprofloxacin 400 mg IV q8h OR Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg q24h OR Meropenem 2 g IV q8h OR Imipenem 1 g IV q6h OR Doripenem 500 mg IV q8h OR Vancomycin 20 mg/kg IV q8h (maintain serum trough concentrations of 15-20 µg/mL) OR Penicillin G 4 MU IV q4h (penicillin-susceptible strains) OR Ampicillin 3 g IV q6h (penicillin-susceptible strains) AND
- (2) Protein synthesis inhibitor: Clindamycin 900 mg IV q8h OR Linezolid 600 mg IV q12h OR Doxycycline 200 mg IV initially, then 100 mg IV q12h OR Rifampin 600 mg IV q12h
- Specific considerations
- Treatment of anthrax for pregnant Women
- (A) Intravenous antimicrobial treatment for systemic anthrax with possible/confirmed meningitis
- (1) A Bactericidal Agent (Fluoroquinolone): Ciprofloxacin 400 mg IV q8h is preferred, OR Levofloxacin 750 mg IV q24h, OR
- (2). A Bactericidal Agent (β-lactam)
- (a). For all strains, regardless of penicillin susceptibility or if susceptibility is unknown : Meropenem 2 g q8h,OR
- (b). Alternatives for penicillin-susceptible strains: Ampicillin 3 g IV q6h,OR Penicillin G 4 million units IV q4h, OR
- (3). A Protein Synthesis Inhibitor: Clindamycin 900 IV mg q8h,OR Rifampin 600 IV mg q12h
- (B) Intravenous antimicrobial treatment for systemic anthrax when meningitis has been excluded
- (1). A Bactericidal Antimicrobial: Ciprofloxacin 400 mg IV q8h is preferred, OR Levofloxacin 750 mg IV q24h, OR
- (2). A Bactericidal Agent (β-lactam)
- (a). For all strains, regardless of penicillin susceptibility or if susceptibility is unknown : Meropenem 2 g q8h,OR
- (b). Alternatives for penicillin-susceptible strains:Ampicillin 3 g IV q6h,OR Penicillin G 4 million units IV q4h, OR
- (3). A Protein Synthesis Inhibitor:Clindamycin 900 IV mg q8h,OR Rifampin 600 IV mg q12h
- (C) Oral antimicrobial treatment for cutaneous anthrax without systemic involvement
- (a).For all strains, regardless of penicillin susceptibility or if susceptibility is unknown: Ciprofloxacin 400 mg IV q8h is preferred.
- Treatment for anthrax in children
- (1). Treatment of cutaneous anthrax without systemic involvement (for children 1 month of age and older)
- (A). For all strains, regardless of penicillin susceptibility or if susceptibility is unknown : Ciprofloxacin, 30 mg/kg/day, by mouth (PO), divided q12h (not to exceed 500 mg/dose) OR Doxycycline, 50 kg: 500 mg, PO, given q24h OR
- (B). Alternatives for penicillin-susceptible strains: Amoxicillin, 75 mg/kg/day, PO, divided q8h (not to exceed 1 g/dose) OR Penicillin VK, 50-75 mg/kg/day, PO, divided q6h to q8h
- (2). Combination therapy for systemic anthrax when meningitis can be ruled out (for children 1 month of age and older)
- (A). A bactericidal antimicrobial
- (a). For all strains, regardless of penicillin susceptibility or if susceptibility is unknown: Ciprofloxacin, 30 mg/kg/day, intravenously (IV), divided q8h (not to exceed 400 mg/dose) OR Meropenem, 60 mg/kg/day, IV, divided q8h (not to exceed 2 g/dose) OR Levofloxacin 50 kg: 500 mg, IV, q24h OR Imipenem/Cilastatin,a 100 mg/kg/day, IV, divided q6h (not to exceed 1 g/dose) OR Vancomycin, 60 mg/kg/day, IV, divided q8h (follow serum concentrations)
- (b). Alternatives for penicillin-susceptible strains: Penicillin G, 400 000 U/kg/day, IV, divided q4h (not to exceed 4 MU/dose) OR Ampicillin, 200 mg/kg/day, IV, divided q6h (not to exceed 3 g/dose) AND
- (B). A Protein Synthesis Inhibitor: Clindamycin, 40 mg/kg/day, IV, divided q8h (not to exceed 900 mg/dose) OR Linezolid (non-CNS infection dose): <12 y old: 30 mg/kg/day, IV, divided q8h ≥12 y old: 30 mg/kg/day, IV, divided q12h (not to exceed 600 mg/dose) OR Doxycycline <45 kg: 4.4 mg/kg/day, IV, loading dose (not to exceed 200 mg); ≥45 kg: 200 mg, IV, loading dose then <45 kg: 4.4 mg/kg/day, IV, divided q12h (not to exceed 100 mg/dose); ≥45 kg: 100 mg, IV, given q12h OR Rifampin,d 20 mg/kg/day, IV, divided q12h (not to exceed 300 mg/dose)
- (3).Triple therapy for systemic anthrax (anthrax meningitis or disseminated infection and meningitis cannot be ruled out) for Children 1 Month of Age and Older
- (A). A bactericidal antimicrobial (fluoroquinolone): Ciprofloxacin, 30 mg/kg/day, intravenously (IV), divided q8h (not to exceed 400 mg/dose)OR Levofloxacin 50 kg: 500 mg, IV, q24h OR Moxifloxacin 3 months to <2 years: 12 mg/kg/day, IV, divided q12h (not to exceed 200 mg/dose)
- (B). A bactericidal antimicrobial (β-lactam or glycopeptide)
- (a). For all strains, regardless of penicillin susceptibility testing or if susceptibility is unknown : Meropenem, 120 mg/kg/day, IV, divided q8h (not to exceed 2 g/dose) OR Imipenem/Cilastatin, 100 mg/kg/day, IV, divided q6h (not to exceed 1 g/dose) OR Doripenem, 120 mg/kg/day, IV, divided q8h (not to exceed 1 g/dose) OR Vancomycin, 60 mg/kg/day, IV, divided q8h
- (b). Alternatives for penicillin-susceptible strains: Penicillin G, 400 000 U/kg/day, IV, divided q4h (not to exceed 4 MU/dose) OR Ampicillin, 400 mg/kg/day, IV, divided q6h (not to exceed 3 g/dose) AND
- (C). A Protein Synthesis Inhibitor: Linezolid <12 y old: 30 mg/kg/day, IV, divided every 8 h≥12 y old: 30 mg/kg/day, IV, divided q12h (not to exceed 600 mg/dose) OR Clindamycin, 40 mg/kg/day, IV, divided q8h (not to exceed 900 mg/dose) OR Rifampin, 20 mg/kg/day, IV, divided q12h (not to exceed 300 mg/dose) OR Chloramphenicol, 100 mg/kg/day, IV, divided q6h
- (4).Oral follow-up combination therapy for severe anthrax (for Children 1 Month of Age and Older)
- (A). A bactericidal antimicrobial
- (B). A protein synthesis inhibitor: Clindamycin 30 mg/kg/day, PO, divided q8h (not to exceed 600 mg/dose) OR Doxycycline <45 kg: 4.4 mg/kg/day, PO, divided q12h (not exceed 100 mg/dose) ≥45 kg: 100 mg, PO, given q12h OR Linezolid (non-CNS infection dose):
- (5). Dosing in preterm and term neonates 32 to 44 Weeks postmenstrual Age (Gestational Age Plus Chronologic Age)
- (A). Triple therapy for severe anthrax(anthrax meningitis or disseminated infection and meningitis cannot be ruled out)
- (1). Bactericidal antimicrobial (fluoroquinolone) therapy
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (2). A bactericidal antimicrobial (β-lactam)
- a. For all strains, regardless of penicillin susceptibility or if susceptibility is unknown :
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- b. Alternatives for penicillin-susceptible strains
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (3).A protein synthesis inhibitor
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (B). Therapy for severe anthrax when meningitis can be ruled out
- (1).A bactericidal antimicrobial
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (2).A protein synthesis inhibitor
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (C). Oral follow-up combination therapy for severe anthrax
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (D).Treatment of cutaneous anthrax without systemic involvement
- (1).For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (2).Alternatives for penicillin-susceptible strains
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- Bacillus anthracis, postexposure prophylaxis
- For adults
- (1) For all strains, regardless of penicillin susceptibility or if susceptibility is unknown: Ciprofloxacin, 500 mg q12h OR Doxycycline, 100 mg q12h OR Levofloxacin, 750 mg q24h OR Moxifloxacin, 400 mg q24h OR Clindamycin, 600 mg q8h OR
- (2) Alternatives for penicillin-susceptible strain Amoxicillin, 1 g q8h OR Penicillin VK, 500 mg q6h
- For children ≥ 1 month
- (1) For penicillin-resistant strains or prior to susceptibility testing: Ciprofloxacin, 30 mg/kg/day, by mouth (PO), divided q12h (not to exceed 500 mg/dose) OR Doxycycline, 45 kg: 100 mg/dose, PO, given q12h OR Clindamycin, 30 mg/kg/day, PO, divided q8h (not to exceed 900 mg/dose) OR Levofloxacin, 50 kg: 500 mg, PO, given q24h OR
- (2) For penicillin-susceptible strains: Amoxicillin, 75 mg/kg/day, PO, divided every q8h (not to exceed 1 g/dose) OR Penicillin VK, 50-75 mg/kg/day, PO, divided q6h to q8h
- For children < 1 month
- (1) For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (2) Alternatives for penicillin-susceptible strains
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- Bacillus cereus
- Bacillus cereus
- (1) Food poisoning
- Preferred treatment: Food poisoning is self-limited, no antibiotics necessary. Treatment is Supportive therapy, hydration, and anti-emetics. Prevention is by fried/boiled rice should be maintained >60° C or rapidly cooled <8 ° C to avoid room temperature germination of spores and toxin.
- (2) Bacteremia
- Preferred regimen: Vancomycin 15 mg/kg IV q12h.
- Alternative regimen: Clindamycin 600 mg IV q8h
- (3) Meningitis, brain abscess
- Preferred regimen: Vancomycin 15 mg/kg IV q12h.
- Alternative regimen: Clindamycin 600 mg IV q8h.
- (4) Endophthalmitis
- Preferred regimen: Clindamycin 450 mcg intravitreal AND Gentamicin 400 mcg intravitreal OR Dexamethasone intravitreal AND Vancomycin 15 mg/kg IV q12h.
- Alternative regimen: Clindamycin 600 mg IV q8h
- (5) Endocarditis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h OR Clindamycin 600 mg IV q8h.
- (6) Soft tissue
- Preferred regimen: Vancomycin 15 mg/kg IV q12h.
- Alternative regimen: Clindamycin 600 mg IV q8h.
- (7) Pneumonia
- Preferred regimen: Vancomycin 15 mg/kg IV q12h.
- Alternative regimen: Clindamycin 600 mg IV q8h.
- Bacillus subtilis
- 1. Food poisoning
- Preferred regimen: supportive treatment
- 2. Other infections
- Preferred regimen: Vancomycin OR Clindamycin
- Alternative regimen: Ciprofloxacin OR Imipenem
- Clostridium
- Clostridium botulinum
- Clostridium difficile
- Clostridium perfringens
- Clostridium tetani
- Corynebacterium
- Corynebacterium diphtheriae
- Diphtheria treatment
- Antitoxin
- Preferred regimen: 20,000-40,000 U pharyngeal disease 72 hrs; Adiminister IV (severe disease) or IM
- Antibiotics:
- Preferred regimen: Procaine Penicillin G (20 lbs: 600,000 U) IM q12h until patient can swallow then Penicillin VK 125-250 mg PO QID OR Erythromycin 125-500 mg PO QID for 14 days total.
- Alternative regimen (1): Erythromycin 20-25mg/kg IV q6h (max 4g/day; β-lactam allergic patients)
- Alternative regimen (2): Clindamycin 600 mg IV q8h
- C. diphtheriae carrier
- Preferred regimen: Erythromycin 250-500 mg PO QID
- Alternative regimen: Benzathine Penicillin G 600,000-1,200,000 units IM single dose
- Endocarditis treatment
- Preferred regimen: Penicillin G OR Ampicillin IV for 4-6 weeks ± Aminoglycoside
- Corynebacterium jeikeium
- Corynebacterium urealyticum
- Coxiella burnetii
- Adults:
- Preferred Regimen: DoxycyclinePO 100 mg bid for 14 days
- Children
- Children with age ≥8 years:
- Preferred regimen:Doxycycline PO 2.2 mg/kg per dose bid for 14 days (maximum 100 mg per dose)
- children with age <8 years with high risk criteria
- Preferred regimen:Doxycycline PO 2.2 mg/kg per dose bid for 14 days (maximum: 100 mg per dose)
- children with age < 8 years with mild or uncomplicated illness:
- Preferred regimen:Doxycycline PO 2.2 mg/kg per dose bid for 5 days (maximum 100 mg per dose). If patient remains febrile past 5 days of treatment: Trimethoprim/Sulfamethoxazole 4-20 mg/kg bid for 14 days (maximum: 800 mg per dose)
- Pregnant women
- Preferred regimen: Trimethoprim/sulfamethoxazole PO 160 mg/800 mg bid a day throughout pregnancy
- Endocarditis or vascular infection
- Preferred regimen:Doxycycline PO 100 mg bid and hydroxychloroquine PO 200 mg tid for ≥18 months
- Note: childern and pregnant women- consultation Recommended
- Noncardiac organ disease
- Preferred regimen: Doxycycline PO 100 mg bid and hydroxychloroquine PO 200 mg tid
- Note: childern and pregnant women- consultation Recommended
- Postpartumwith serologic profile for chronic Q fever
- Preferred regimen:Doxycycline PO 100 mg bid and hydroxychloroquine PO 200 mg tid for 12 months
- Note: Women should only be treated postpartum if serologic titers remain elevated >12 months after delivery (immunoglobulin G phase I titer ≥1:1024). Women treated during pregnancy for acute Q fever should be monitored similarly to other patients who are at high risk for progression to chronic disease (e.g., serologic monitoring at 3, 6, 12, 18, and 24 months after delivery)
- Note:Post-Q fever fatigue syndrome- no current recommendation
- Ehrlichia
- Human Monocytic Ehrlichiosis or Human Granulocytic Anaplasmosis (adult)
- Preferred regimen: Doxycycline 100 mg PO/IV q12h for 7-14 days
- NOTE: Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement
- Alternative regimen: Chloramphenicol 500mg QID OR Rifampin 600 mg PO/IV daily for 7-10 days
- Human Monocytic Ehrlichiosis or Human Granulocytic Anaplasmosis (pediatric)
- ≥8 years old
- Preferred regimen: Doxycycline 2 mg/kg IV/PO q12h (max 200 mg/day) for 10 days
- <8 years old without Lyme disease
- Preferred regimen: Doxycycline 2 mg/kg IV/PO q12h (max 200 mg/day) for 4-5 days (or 3 days after resolution of fever)
- co-infected with Lyme disease
- Preferred regimen: At the conclusion of Doxycycline then give Amoxicillin 50 mg/kg in 3 divided doses (max 500 mg/dose) OR Cefuroxime 30 mg/kg in 2 divided doses (max 500 mg/dose) for 14 days
- Erysipelothrix rhusiopathiae
- Erysipeloid of Rosenbach (localized cutaneous infection)
- Preferred regimen (1): Penicillin G benzathine 1.2 MU IV as a single dose
- Preferred regimen (2): Penicillin VK 250 mg PO qid for 5-7 days
- Preferred regimen (3): Procaine penicillin 0.6-1.2 MU IM qd for 5-7 days
- Alternative regimen (1): Erythromycin 250 mg PO qid for 5-7 days
- Alternative regimen (2): Doxycycline 100 mg PO bid for 5-7 days
- Diffuse cutaneous infection
- Preferred regimen: As for localized infection
- Bacteremia or endocarditis
- Preferred regimen: Penicillin G benzathine 2-4 MU IV q4h for 4-6 weeks
- Alternative regimen (1): Ceftriaxone 2 g IV q24h for 4-6 weeks
- Alternative regimen (2): Imipenem 500 mg IV q6h for 4-6 weeks
- Alternative regimen (3): Ciprofloxacin 400 mg IV q12h for 4-6 weeks
- Alternative regimen (4): Daptomycin 6 mg/kg IV q24h for 4-6 weeks
- Listeria monocytogenes
- Meningitis
- Preferred regimen: Ampicillin 2g IV q4-6h ± Gentamicin 1.7 mg/kg IV q8h for more than 3 weeks
- Alternative regimen: TMP-SMX 3-5 mg/kg (trimethoprim) q6h IV for more than 3 weeks
- Bacteremia
- Preferred regimen: Ampicillin 2g IV q4-6h ± Gentamicin 1.7 mg/kg IV q8h for 2 weeks
- Alternative regimen: TMP-SMX 3-5 mg/kg (trimethoprim) q6h IV for 2 weeks
- Brain abscess or rhomboencephalitis
- Preferred regimen: Ampicillin 2g IV q4-6h ± Gentamicin 1.7 mg/kg IV q8h for 4-6 weeks
- Alternative regimen: TMP-SMX 3-5 mg/kg (trimethoprim) q6h IV for 4-6 weeks
- Gastroenteritis
- Preferred regimen: Amoxicillin OR TMP-SMX for 7 days
- Lactobacillus
- Endovascular Infection
- Preferred regiemn (1): Penicillin G 20 Million units/day for 6 weeks
- Preferred regiemn (2): Gentamicin 1.3 mg/kg IV q8h (trough <1.5 mg/L) AND Polychlorinated naphthalene
- Odontogenic Infection
- Preferred regiemn: Clindamycin 450 mg PO q6h
- Intrabdominal Abscess
- Preferred regiemn: Clindamycin 450 mg PO q6h
- Leuconostoc
- Preferred regimen: Penicillin G OR Ampicillin
- Alternative regimen: Clindamycin OR Erythromycin OR Minocycline
- Nocardia
- Sulfonamide-based therapies
- Pulmonary
- Preferred regimen: TMP-SMX 10 mg/kg/day (TMP) in 2-4 doses IV for 3-6 weeks, then PO (2 DS BID) for >5 months
- Pulmonary alternatives
- Preferred regimen: Sulfisoxazole OR Sulfadiazine OR Trisulfapyrimidine 3-6 g/day PO 2- 4 doses OR TMP-SMX 2 DS twice daily up to 2 DS TID
- CNS (AIDS, severe or disseminated disease)
- Preferred regimen: TMP-SMX 15 mg/kg/day (TMP) IV for 3-6 weeks, then PO (3 DS BID) for 6-12 months
- CNS alternatives
- Preferred regimen: Imipenem 1000 mg IV q8h OR Ceftriaxone 2 g IV q12h OR Cefotaxime 2-3 g IV q6h AND Amikacin
- Severe disease, compromised host, multiple sites
- Preferred regimen: TMP-SMX IV (above doses) AND Amikacin 7.5 mg/kg q12h (adjust per levels) OR Sulfonamide PO 6-12 m/day
- Sporotrichoid (cutaneous)
- Preferred regimen: TMP-SMX 1 DS BID for 4-6 months
- NOTE(1): Immunocompetent medicine use for 6 months; Immunosuppressed medicine for 12 months
- NOTE(2): Treat based on host, site of disease and in vitro activity; Sulfonamide usually preferred, must treat for 6-12 months; Preferred drugs for resistant strains are Amikacin and/or Imipenem
- NOTE(3): Seriously ill usually treated with IV Imipenem or Sulfonamide or Cefotaxime all potentially combined with Amikacin; less seriously ill treated with oral agents— especially TMP-SMX or Minocycline
- Sulfonamide alternatives
- Severe
- Preferred regimen(1): (AIDS) (Imipenem 1000mg IV q8h OR Meropenem (CNS) 2g q8h) AND Amikacin 7.5 mg/kg q12h IV
- Preferred regimen(2): Cefotaxime 2-3g q6-8h OR Ceftriaxone 2 g/day IV ± Amikacin
- Mild
- Preferred regimen: Minocycline 100 mg BID for > 6 months (initial treatment of local disease or maintenance)
- Alternative regimen: Amoxicillin/Clavulanate 875/125 mg BID OR Doxycycline OR Erythromycin OR Clarithromycin OR Linezolid OR Fluoroquinolone OR combinations for >6 months
- Propionibacterium acnes
- Systemic infection
- Preferred regimen: Penicillin G 2 MU IV q4h for 2-4 weeks
- Alternative regimen: Clindamycin 600 mg IV q8h for 2-4 weeks OR Vancomycin 15 mg/kg IV q12h for 2-4 weeks
- Shoulder prosthesis infection
- Preferred regimen: Amoxicillin AND Rifampin for 3-6 months
- Acne vulgaris
- Topical antibiotics: Erythromycin OR Clindamycin
- Systemic antibiotics: Minocycline OR Doxycycline OR Trimethoprim-Sulfamethoxazole
- Rhodococcus equi
- Rhodococcus equi
- Preferred regimen:
- First line: vancomycin 1 g IV q12h (15 mg/kg q12 for >70 kg) OR Imipenem 500 mg IV q6h AND Rifampin 600 mg PO once daily OR Ciprofloxacin 750 mg PO twice daily OR Erythromycin 500 mg PO four times a day for at least 4 weeks or until infiltrate disappears (at least 8 weeks in immunocompromised patients)
- Oral/maintenance therapy (after infiltrate clears): Ciprofloxacin 750 mg PO twice daily OR Erythromycin 500 mg PO four times a day
- Alternative regimen: Azithromycin OR TMP-SMX OR Chloramphenicol OR Clindamycin
- NOTE: Avoid Penicillins/Cephalosporins due to development of resistance; Linezolid effective in vitro, but no clinical reports of use
- Rickettsia
- Rickettsia rickettsii
- Preferred regimen: Doxycycline 200 mg load (severe disease) and then 100 mg PO/IV BID for 3-7 days after defervescence
- Alternative regimen: Chloramphenicol 500 mg PO QID for 3-7 days after defervescence
- Pediatric regimen: Doxycycline 2-4 mg/kg/day (up to 200 mg/day) q12h OR Tetracycline 25-50 mg/kg/day PO in 4 divided doses OR Chloramphenicol 50-75 mg/kg/day PO in 4 divided doses
# Bacteria – Gram-Negative Cocci and Coccobacilli
- Aggregatibacter aphrophilus
- Bordetella pertussis
- Brucella
- Eikenella corrodens
- Haemophilus ducreyi
- Chancroid Treatment
- Preferred Regimen: Azithromycin 1 g PO in a single dose OR Ceftriaxone 250 mg IM in a single dose OR Ciprofloxacin 500 mg PO bid for 3 days OR Erythromycin base 500 mg PO three tid for 7 days
- Note(1): Regardless of whether symptoms of the disease are present, sex partners of patients who have chancroid should be examined and treated if they had sexual contact with the patient during the 10 days preceding the patient’s onset of symptoms.
- Note(2):Persons with HIV infection might require repeated or longer courses of therapy, and treatment failures can occur with any regimen.
- Haemophilus influenzae
- Neisseria gonorrhoeae
- Neisseria gonorrhoeae, treatment
- 1. Gonococcal infections in adolescents and adults
- 1.1 Uncomplicated gonococcal infections of the cervix, urethra, and rectum
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- Alternative regimen: Cefixime 400 mg PO in a single dose AND Azithromycin 1 g PO in a single dose (if ceftriaxone is not available)
- 1.2 Uncomplicated gonococcal infections of the pharynx
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.2.1 Management of sex partners
- Expedited partner therapy: Cefixime 400 mg PO in a single dose AND Azithromycin 1 g PO in a single dose
- 1.2.2 Allergy, intolerance, and adverse reactions
- Preferred regimen (1): Gemifloxacin 320 mg PO in a single dose AND Azithromycin 2 g PO in a single dose
- Preferred regimen (2): Gentamicin 240 mg IM in a single dose AND Azithromycin 2 g PO in a single dose
- 1.2.3 Pregnancy
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.2.4 Suspected cephalosporin treatment failure
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Gemifloxacin 320 mg PO single dose AND Azithromycin 2 g PO single dose (when isolates have elevated cephalosporin MICs)
- Alternative regimen (2): Gentamicin 240 mg IM single dose AND Azithromycin 2 g PO single dose (when isolates have elevated cephalosporin MICs)
- Alternative regimen (3): Ceftriaxone 250 mg IM as a single dose AND Azithromycin 2 g PO as a single dose (failure after treatment with cefixime and azithromycin)
- 1.3 Gonococcal conjunctivitis
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.3.1 Management of sex partners
- Patients should be instructed to refer their sex partners for evaluation and treatment.
- 1.4 Disseminated gonococcal infection
- 1.4.1 Arthritis and arthritis-dermatitis syndrome
- Preferred regimen: Ceftriaxone 1 g IM/IV q24h for 7 days AND Azithromycin 1 g PO in a single dose
- Alternative regimen: Cefotaxime 1 g IV q8h for 7 days OR Ceftizoxime 1 g IV q 8 h for 7 days AND Azithromycin 1 g PO in a single dose
- 1.4.2 Gonococcal meningitis and endocarditis
- Preferred regimen : Ceftriaxone 1-2 g IV q 12-24 h for 10-14 days AND Azithromycin 1 g PO in a single dose
- 2. Gonococcal infections among neonates
- 2.1 Ophthalmia neonatorum caused by N. gonorrhoeae
- Preferred regimen: Ceftriaxone 25-50 mg/kg IV or IM in a single dose, not to exceed 125 mg
- 2.1.1 Management of mothers and their sex partners
- Mothers of infants with ophthalmia neonatorum caused by N. gonorrhoeae should be evaluated, tested, and presumptively treated for gonorrhea, along with their sex partner(s).
- 2.2 Disseminated gonococcal infection and gonococcal scalp abscesses in neonates
- Preferred regimen: Ceftriaxone 25-50 mg/kg/day IM/IV qd for 7 days OR Cefotaxime 25 mg/kg IV /IM q12h for 7 days.
- 2.2.1 Management of mothers and their sex partners
- Mothers of infants who have DGI or scalp abscesses caused by N. gonorrhoeae should be evaluated, tested, and presumptively treated for gonorrhea, along with their sex partner(s).
- 2.3 Neonates born to mothers who have gonococcal infection
- Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg
- 2.3.1 Management of mothers and their sex partners
- Mothers who have gonorrhea and their sex partners should be evaluated, tested, and presumptively treated for gonorrhea.
- 3. Gonococcal infections among infants and children
- 3.1 Infants and children who weigh ≤ 45 kg and who have uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis
- Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg
- 3.2 Children who weigh > 45 kg and who have uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1g PO in a single dose
- Alternative regimen: Cefixime 400 mg PO single dose AND Azithromycin 1 g PO single dose.(If ceftriaxone is not available)
- 3.3 Children who weigh ≤ 45 kg and who have bacteremia or arthritis
- Preferred regimen: Ceftriaxone 50 mg/kg (maximum dose: 1 g) IM/IV q24h for 7 days
- 3.4 Children who weigh > 45 kg and who have bacteremia or arthritis
- Preferred regimen: Ceftriaxone 1 g IM/IV q24h for 7 days
- Neisseria gonorrhoeae, prophylaxis
- 1. Ophthalmia neonatorum
- Preferred regimen: Erythromycin 0.5% ophthalmic ointment in each eye in a single application at birth
- Alternative regimen: Ceftriaxone 25–50 mg/kg IV/IM in a single dose, not to exceed 125 mg (if erythromycin ointment is not available)
- Neisseria meningitidis
- Meningococcal Meningitis or Bacteremia
- Antimicrobials:
- Preferred regimen : Ceftriaxone 2 g IV q24h OR Cefotaxime 2 g IV q4-6h for 7-10 days.
- Alternatives regimen (1): Chloramphenicol 4-6 g/day for 7-10 days
- Alternatives regimen (2): Penicillin 18-24 MU/day IV
- Alternatives regimen (3): Ampicillin 12 g/day IV
- Alternatives regimen (4): Aztreonam 6-8 g/day IV OR moxifloxacin 400 mg/day IV.
- Steroids: Dexamethasone 10 mg IV q6h for 2-4 days starting before or with first dose.
- Moraxella catarrhalis
- Pasteurella multocida
# Bacteria – Spirochetes
- Borrelia
- Borrelia burgdorferi
- Lyme disease
- Early Lyme Disease
- Erythema migrans
- Preferred regimen: Doxycycline 100 mg twice per day for 10-21 days OR Amoxicillin 500 mg 3 times per day for 14-21 days OR Cefuroxime axetil 500 mg twice per day for 14-21 days
- Alternatie regimen: : Azithromycin 500 mg PO per day for 7–10 days OR Clarithromycin 500 mg PO twice per day for 14–21 days (if the patient is not pregnant) OR Erythromycin 500 mg PO 4 times per day for 14–21 days
- Pediatric regimen (1): (children <8 years of age) Amoxicillin 50 mg/kg per day in 3 divided doses OR Cefuroxime axetil 30 mg/kg per day in 2 divided doses （maximum of 500 mg per dose)
- Pediatric regimen (2):（children ≥8 years of age）Doxycycline 4 mg/kg per day in 2 divided doses（maximum of 100 mg per dose）
- Pediatric regimen (3): Azithromycin 10 mg/kg per day (maximum of 500 mg per day) OR Clarithromycin 7.5 mg/kg twice per day (maximum of 500 mg per dose) OR Erythromycin 12.5 mg/kg 4 times per day (maximum of 500 mg per dose)
- When erythema migrans cannot be reliably distinguished from community-acquired bacterial cellulitis
- Preferred regimen: Amoxicillin–clavulanic acid 500 mg 3 times per day;
- Pediatric regimen；Amoxicillin–clavulanic acid 50 mg/kg per day in 3 divided doses (maximum of 500 mg per dose)
- Lyme meningitis and other manifestations of early neurologic Lyme disease
- Preferred regimen: Ceftriaxone 2g once per day IV for 10–28 days
- Alternative regimen (1): Cefotaxime 2 g IV q8h OR Penicillin G 18–24 million U q4h per day for patients with normal renal function
- Alternative regimen (2): Doxycycline 200–400 mg per day in 2 divided doses PO for 10–28 days
- Pediatric regimen (1): Ceftriaxone 50–75 mg/kg per day in a single daily intravenous dose (maximum, 2g)
- Pediatric regimen (2): Cefotaxime 150–200 mg/kg per day divided into 3 or 4 intravenous doses per day (maximum, 6 g per day)
- Pediatric regimen (3): Penicillin G 200,000–400,000 units/kg per day (maximum, 18–24 million U per day) divided into doses given intravenously q4h for those with normal renal function
- Pediatric regimen (4): (≥8 years old) Doxycycline 4–8 mg/kg PO per day in 2 divided doses (maximum, 100–200 mg per dose)
- Lyme carditis
- Preferred regimen: Ceftriaxone 2g once per day IV for 10–28 days
- NOTE: patients with advanced heart block, a temporary pacemaker may be required; expert consultation with a cardiologist is recommended; Use of the pacemaker may be discontinued when the advanced heart block has resolved; An oral antibiotic treatment regimen should be used for completion of therapy and for outpatients, as is used for patients with erythema migrans without carditis (see above)
- Borrelial lymphocytoma
- Preferred regimen: The same regimens used to treat patients with erythema migrans (see above)
- Late Lyme Disease
- Lyme arthritis
- Preferred regimen: Doxycycline 100 mg twice per day OR Amoxicillin 500 mg 3 times per day
- Alternative regimen: Cefuroxime axetil 500 mg twice per day for 28 days
- Pediatric regimen: Amoxicillin 50 mg/kg per day in 3 divided doses (maximum of 500 mg per dose) OR Cefuroxime axetil 30 mg/kg per day in 2 divided doses (maximum of 500 mg per dose) OR (≥8 years of age) Doxycycline 4 mg/ kg per day in 2 divided doses (maximum of 100 mg per dose)
- NOTE: For patients who have persistent or recurrent joint swelling after a recommended course of oral antibiotic therapy, we recommend re-treatment with another 4-week course of oral antibiotics or with a 2–4-week course of Ceftriaxone IV
- patients with arthritis and objective evidence of neurologic disease
- Preferred regimen: Ceftriaxone IV for 2–4 weeks
- Alternative regimen: Cefotaxime OR Penicillin G IV
- Pediatric regime: Ceftriaxone OR Cefotaxime OR Penicillin G IV
- Late neurologic Lyme disease
- Preferred regimen: Ceftriaxone IV for 2 to 4 weeks
- Alternative regimen: Cefotaxime OR Penicillin G IV
- Pediatric regimen: Ceftriaxone OR Cefotaxime OR Penicillin G
- Acrodermatitis chronica atrophicans
- Preferred regimen: Doxycycline 100 mg twice per day OR Amoxicillin 500 mg 3 times per day OR Cefuroxime axetil 500 mg twice per day for 21 days
- Post–Lyme Disease Syndromes
- Preferred regimen: Further antibiotic therapy for Lyme disease should not be given unless there are objective findings of active disease (including physical findings, abnormalities on cerebrospinal or synovial fluid analysis, or changes on formal neuropsychologic testing)
- Borrelia recurrentis
- Tick-Borne Relapsing Fever
- Preferred regimen: Doxycycline 100 mg PO twice daily for 5-10 days
- Alternative regimen: Erythromycin 500 mg PO four times a day for 5-10 days
- NOTE: If meningitis/encephalitis present, use Ceftriaxone 2 g IV q12h for 14 days
- Louse-Borne Relapsing Fever
- Preferred regimen: single dose Tetracycline 500 mg PO
- Alternative regimen: single dose Erythromycin 500 mg PO
- Leptospira
- Treatment
- Severe
- Preferred regimen: Penicillin 1.5 million units IV q6hr for 5-7 days
- Less severe
- Preferred regimen: Amoxycillin OR Ampicillin OR Doxycycline 100 mg BID IV or PO for 5-7 days OR Erythromycin OR Ceftriaxone 1g IV per day for 5-7 days OR Cefotaxime OR Quinolone PO
- Prophylaxis
- Leptospira interrogans
- Preferred regimen: Doxycycline 200 mg PO once per week
- Treponema pallidum
- Syphilis Among non-HIV-Infected Persons
- Primary and Secondary Syphilis
- Preferred regimen (adult): Benzathine penicillin G 2.4 million units IM in a single dose
- Preferred regimen (pediatric): Benzathine penicillin G 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose
- Latent Syphilis
- Early Latent Syphilis
- Preferred regimen: Benzathine penicillin G 2.4 million units IM in a single dose
- Pediatric regimen: Benzathine penicillin G 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose
- Late Latent Syphilis or Latent Syphilis of Unknown Duration
- Preferred regimen: Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervalspediatric
- Pediatric regimen: Benzathine penicillin G 50,000 units/kg IM, up to the adult dose of 2.4 million units, administered as 3 doses at 1-week intervals (total 150,000 units/kg up to the adult total dose of 7.2 million units)
- Tertiary Syphilis
- Preferred regimen: Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals
- Neurosyphilis and ocular syphilis
- Preferred regimen: Aqueous crystalline penicillin G 18--24 million units per day, administered as 3--4 million units IV every 4 hours or continuous infusion, for 10--14 days
- Alternative regimen: Procaine penicillin 2.4 million units IM once daily AND Probenecid 500 mg orally four times a day, both for 10--14 days
- Syphilis Among HIV-Infected Persons
- Primary and Secondary Syphilis Among HIV-Infected Persons
- Preferred regimen: Benzathine penicillin G 2.4 million units IM in a single dose.
- Latent Syphilis Among HIV-Infected Persons
- early latent
- Preferred regimen: Benzathine penicillin G 2.4 million units IM in a single dose.
- late latent
- Preferred regimen: Benzathine penicillin G at weekly doses of 2.4 million units for 3 weeks.
- Neurosyphilis Among HIV-Infected Persons
- Preferred regimen: Aqueous crystalline penicillin G 18--24 million units per day, administered as 3--4 million units IV every 4 hours or continuous infusion, for 10--14 days
- Alternative regimen: Procaine penicillin 2.4 million units IM once daily AND Probenecid 500 mg orally four times a day, both for 10--14 days
- Syphilis During Pregnancy
- Preferred regimen: Pregnant women should be treated with the penicillin regimen appropriate for their stage of infection
- Congenital Syphilis in neonates
- condition 1 : Infants with proven or highly probable disease and (1)an abnormal physical examination that is consistent with congenital syphilis;（2）a serum quantitative nontreponemal serologic titer that is fourfold higher than the mother's titer;¶ or（3）a positive darkfield test of body fluid(s).
- Preferred regimen: Aqueous crystalline penicillin G 100,000--150,000 units/kg/day, administered as 50,000 units/kg/dose IV every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days OR Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days
- NOTE: If more than 1 day of therapy is missed, the entire course should be restarted. Data are insufficient regarding the use of other antimicrobial agents (e.g., ampicillin). When possible, a full 10-day course of penicillin is preferred, even if ampicillin was initially provided for possible sepsis. The use of agents other than penicillin requires close serologic follow-up to assess adequacy of therapy. In all other situations, the maternal history of infection with T. pallidum and treatment for syphilis must be considered when evaluating and treating the infant.
- condition 2: Infants who have a normal physical examination and a serum quantitive nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1)mother was not treated, inadequately treated, or has no documentation of having received treatment; (2)mother was treated with erythromycin or another nonpenicillin regimen;†† or (3)mother received treatment < 4 weeks before delivery.
- Preferred regimen: Aqueous crystalline penicillin G 100,000--150,000 units/kg/day, administered as 50,000 units/kg/dose IV every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days OR Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days OR Benzathine penicillin G 50,000 units/kg/dose IM in a single dose
- NOTE:If the mother has untreated early syphilis at delivery, 10 days of parenteral therapy can be considered.
- condition 3:Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1)mother was treated during pregnancy, treatment was appropriate for the stage of infection, and treatment was administered >4 weeks before delivery and (2)mother has no evidence of reinfection or relapse.
- Preferred regimen: Benzathine penicillin G 50,000 units/kg/dose IM in a single dose
- condition 4: Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1)mother's treatment was adequate before pregnancy and (2)mother's nontreponemal serologic titer remained low and stable before and during pregnancy and at delivery (VDRL <1:2; RPR <1:4).
- Preferred regimen: No treatment is required; however, benzathine penicillin G 50,000 units/kg as a single IM injection might be considered, particularly if follow-up is uncertain.
- Congenital Syphilis in infants and children
- Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg q4–6h for 10 days
# Bacteria – Gram-Negative Bacilli
- Enteric flora
- Aeromonas hydrophila
- Preferred regimen: (consider if not self-limiting, or if severe), Ciprofloxacin 500 mg PO BID.
- Alternate regimen: TMP-SMX single dose PO BID
- Preferred regimen (mild infection) : Ciprofloxacin 500 mg PO BID OR Levofloxacin 500 mg OD.
- Preferred regimen (severe infection) or sepsis: Ciprofloxacin 400 mg IV q8h OR Levofloxacin 750 mg IV q24
- Citrobacter koseri
- Preferred regimen: Ceftriaxone 1-2 g IV q12-24 OR Cefotaxime 1-2 g IV q6h OR Cefepime 1-2 IV q8h.
- Alternate regimen: Ciprofloxacin 400 mg IV q12h (or 500 mg PO q12h for UTI)OR Imipenem 1 g IV q6h OR Doripenem 500 mg IV q8h OR Meropenem 1-2 g IV q8h OR Aztreonam 1-2 g IV q6hOR TMP-SMX 5 mg/kg q6h IV (or DS PO twice daily for UTI).
- Citrobacter freundii
- Preferred regimen: Meropenem 1-2 g IV q8h OR Imipenem 1 g IV q6h OR Doripenem 500 mg IVq8hOR Cefepime 1-2 g IV q8h, Ciprofloxacin 400 mg IV q12h(or 500 mg PO twice daily for UTI) OR Gentamicin 5 mg/kg/day.
- Alternate regimen: Piperacillin/tazobactam 3.375 mg q6h IV OR Aztreonam 1-2 g IV q6h OR TMP-SMX 5 mg/kg q6h IV (or DS PO twice daily for UTI).
- Enterobacter cloacae
- UTI
- Preferred regimen: Ciprofloxacin 250 mg PO bid
- Enterobacter aerogenes
- UTI
- Preferred regimen: Ciprofloxacin 250 mg PO bid
- Escherichia coli
- 1.Meningitits
- 1.1.Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- 1.2.Alternative regimen: Aztreonam 6–8 g/day IV q6–8h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h OR Meropenem 6 g/day IV q8h OR Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h OR Ampicillin 12 g/day IV q4h
- 2.Uncomplicated urinary tract infection
- 2.1.Preferred agents (IDSA/AUA Guidelines): TMP-SMX DS PO bid for 3-day
- 2.2.Alternative regimen(1): Ciprofloxacin 250 mg PO bid OR Ciprofloxacin 500 mg XR once daily for 3 days OR Levofloxacin 250 mg PO OD for 3 days.
- 2.3.Alternative regimen(2): Nitrofurantoin 100 mg PO q6h OR Nitrofurantoin macrocrystals (Macrobid) 100 mg PO bid for 7 days.
- 2.4.Alternative regimen(3): Fosfomycin 3 g sachet PO single dose.
- 3.Pyelonephritis
- 3.1.1.Acute uncomplicated pyelonephritis
- Preferred regimen: Ciprofloxacin 500 mg bid PO for 5-7 days OR Ciprofloxacin-Erythromycin 1000 mg q24h OR Levofloxacin 750 mg q24h OR Ofloxacin 400 mg bid, Moxifloxacin 400 mg q24h
- Alternative regimen: Amoxicillin-Clavulanic acid875/125 mg PO q12h or 500/125 mg PO tid or 1000 /125 mg PO bid OR Oral Cephalosporins OR TMP-SMX 2 mg/kg IV q6h PO for 14 days
- 3.1.2.Acute pyelonephritis (Hospitalized)
- Preferred regimen: Ciprofloxacin 400 mg IV q12h OR (Ampicillin Gentami-cin) OR Piperacillin-Tazobactam 3.375 gm IV q4-6h for 14 days.
- Alternative regimen: Ticarcillin-Clavulanate3.1 gm IV q6h or Ampicillin-Salbactam 3 gm IV q6h or Piperacillin-Tazobactam 3.375 gm IV q4-6h OR Ertapenem 1 gm IV q24h or Doripenem 500 mg q8h for 14 days.
- 4.Traveler’s diarrhea
- Preferred regimen : Ciprofloxacin 750 mg PO OD for 1-3 days or other Fluoroquinolones
- Pediatrics & pregnancy: Azithromycin 10 mg/kg/day single dose OR Ceftriaxone 50 mg/kg/day IV OD for 3 days.
- 5.Malacoplakia
- Bethanechol chloride AND (Ciprofloxacin 400 mg IV q12h OR TMP-SMX 2 mg/kg (TMP component) IV q6h)
- 6.Bacteremia/Pneumonia
- Preferred regimen : Ceftriaxone 1-2g IV q24h OR other third or fourth generation cephalosporin OR Ciprofloxacin 400mg IV q12h or 500mg PO q12h OR Levofloxacin 500mg PO/IV q24h OR Moxifloxacin 400mg IV/PO q24h OR Ampicillin(if sensitive) 2g IV q6h OR TMP-SMX(if sensitive) 5-10mg/kg/day for q6-8hIV
- Alternative regimen : Imipenem, Meropenem, Ertapenem, Doripenem, Ceftazidime, Cefepime, Cefazolin or Cefuroxime(ifsensitive), Aztreonam, Ticarcillin, Piperacillin, Piperacillin-Tazobactam, Aminoglycosides, Tigecycline(intra-abdorskin/softtissue).
- Alternative regimen : Ampicillin-sulbactam 3g IV q6h ANDGentamicin 1.5mg/kg/q8h or 5-7mg/kg/dayIV OR Gentamicin 5mg/kg/day OR Tobramycin 5mg/kg/dayIV for 7-14days
- Klebsiella pneumoniae
- Aspiration Pneumonia
- Preferred regimen : Piperacillin-Tazobactam 3.375 gm IV q6h or 4-hr infusion of 3.375 gm q8h
- Alternate regimen : (Ceftriaxone 1 gm IV q24h AND Metronidazole 500 mg IV q6h or 1 gm IV q12h) OR Moxifloxacin 400 mg IV/po q24h
- Klebsiella rhinoscleromatis
- Morganella morganii
- Proteus vulgaris
- Providencia
- Salmonella
- Serratia marcescens
- Shigella
- Non-fermenters
- Acinetobacter baumannii
- Achromobacter xylosoxidans
- Bordetella pertussis
- Burkholderia cepacia
- Burkholderia pseudomallei
- Stenotrophomonas maltophilia
- Elizabethkingia meningoseptica
- Moraxella catarrhalis
- Bartonella
- Campylobacter
- Campylobacter fetus
- Campylobacter jejuni
- Capnocytophaga
- Francisella tularensis
- Helicobacter pylori
- Legionella
- Plesiomonas shigelloides
- Pseudomonas aeruginosa
- Vibrio
- Vibrio cholerae
- Vibrio parahaemolyticus
- Vibrio vulnificus
# Bacteria – Atypical Organisms
- Chlamydophila pneumoniae
- 1. Pneumonia
- 1.1 Adult
- Preferred regimen (1): Doxycycline 100 mg PO bid for 14-21 days
- Preferred regimen (2): Tetracycline 250 mg PO qid for 14-21 days
- Preferred regimen (3): Azithromycin 500 mg PO as a single dose, followed by 250 mg PO qd for 4 days
- Preferred regimen (4): Clarithromycin 500 mg PO bid for 10 days
- Preferred regimen (5): Levofloxacin 500 mg IV or PO qd for 7 to 14 days
- Preferred regimen (6): Moxifloxacin 400 mg PO qd for 10 days.
- 1.2 Pediatric
- Preferred regimen (1):Erythromycin suspension,PO 50 mg/kg/day for 10 to 14 days
- Preferred regimen (2):Clarithromycin suspension, 15 mg/kg/day for 10 days
- Preferred regimen (3): Azithromycin suspension, PO 10 mg/kg once on the first day, followed by 5 mg/kg qd daily for 4 days
- 2.Upper respiratory tract infection
- Bronchitis
- Antibiotic therapy for C. pneumoniae is not required.
- Pharyngitis
- Antibiotic therapy for C. pneumoniae is not required.
- Sinusitis
- Antibiotic therapy is advisable if symptoms remain beyond 7-10 days.
- Chlamydia trachomatis
- Chlaymydial infections
- 1. Chlamydial Infections in Adolescents and Adults
- Preferred regimen : Doxycycline 100 mg PO bid for 7 days OR Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days OR Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (2): Levofloxacin 500 mg PO qd for 7 days OR Ofloxacin 300 mg PO bid for 7 days.
- Note: Patients should be instructed to refer their sex partners for evaluation, testing, and treatment if they had sexual contact with the patient during the 60 days preceding onset of the patient's symptoms or chlamydia diagnosis.
- 1.1 Chlamydial Infections in patients with HIV Infection
- Preferred regimen : Doxycycline 100 mg PO bid for 7 days OR Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days OR Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (2): Levofloxacin 500 mg PO qd for 7 days OR Ofloxacin 300 mg PO bid for 7 days.
- 1.2Pregancy
- Preferred regimen :Azithromycin 1 g PO in a single dose
- Alternative regimen (1):Amoxicillin 500 mg PO tid for 7 days
- Alternative regimen (2):Erythromycin base 500 mg PO qid for 7 days OR Erythromycinbase 250 mg PO qid for 14 days
- Alternative regimen (3):Erythromycin ethylsuccinate 800 mg PO qid for 7 days OR Erythromycin ethylsuccinate 400 mg PO four qid for 14days
- Note:Doxycycline, Ofloxacin, and Levofloxacin are contraindicated in pregnant women.
- 2 Chlamydial infection among neonates
- 2.1 Ophthalmia Neonatorumcaused by C. trachomatis
- Preferred regimen :Erythromycin base or ethylsuccinate ,PO 50 mg/kg/ day divided into 4 doses daily for 14 days
- Alternative regimen : Azithromycin suspension, PO 20 mg/kg /day qd for 3 days
- Note: The mothers of infants who have chlamydial infection and the sex partners of these women should be evaluated and treated.
- 2.2Infant Pneumonia
- Preferred regimen :Erythromycin base or ethylsuccinate PO 50 mg/kg/ day divided into 4 doses daily for 14 days
- Alternative regimen : Azithromycin suspension, PO 20 mg/kg /day qd for 3 days
- 3.Chlamydial infection among infants and childern
- 3.1 Infants and childern who weigh < 45 kg
- Preferred regimen :Erythromycin base or ethylsuccinate PO 50 mg/kg/ day divided into 4 doses daily for 14 days
- 3.2 Infants and childern who weigh ≥45 kg but who are aged <8 years
- Preferred regimen :Azithromycin 1 g PO in a single dose
- 3.3 Infants and childern aged ≥8 years
- Preferred regimen :Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
- Lymphogranuloma venereum (LGV)
- Lymphogranuloma venereum (LGV) is caused by C. trachomatis serovars L1, L2, or L3
- Preferred regimen : Doxycycline 100 mg PO bid for 21 days
- Alternative regimen: Erythromycin base 500 mg PO qid for 21 days
- Note (1): azithromycin 1 g orally once weekly for 3 weeks is probably effective based on its chlamydial antimicrobial activity. Fluoroquinolone-based treatments might also be effective, but extended treatment intervals are likely required.
- Note (2): Patients should be followed clinically until signs and symptoms have resolved.
- Note (2): Pregnant and lactating women should be treated with erythromycin. Azithromycin might prove useful for treatment of LGV in pregnancy, but no published data are available regarding its safety and efficacy. Doxycycline is contraindicated in pregnant women.
- Note (3): Persons with both LGV and HIV infection should receive the same regimens as those who are HIV negative. Prolonged therapy might be required, and delay in resolution of symptoms might occur.
- Note(4): Persons who have had sexual contact with a patient who has LGV within the 60 days before onset of the patient’s symptoms should be examined and tested for urethral, cervical, or rectal chlamydial infection depending on anatomic site of exposure. They should be presumptively treated with a chlamydia regimen ( Azithromycin 1 g PO single dose OR Doxycycline 100 mg PO bid for 7 days).
- Chlamydophila psittaci
- 1. Pneumonia
- 1.1 Adult
- Preferred regimen : Doxycycline 100 mg PO bid daily OR Tetracycline 500 mg PO qid for 10-21 days
- Alternative regimen :Minocycline
- 1.2 Pediatric
- Preferred regimen: Azithromycin
- Alternative regimen: fluoroquinolones
- 1.3 Pregnant Patients
- Preferred regimen : Azithromycin
- Alternative regimen: fluoroquinolones
- 2.Endocarditis in valve replacement patients
- Preferred regimen : Doxycycline
- Alternative regimen : fluoroquinolones.
- Coxiella burnetii
- Q fever
- 1.Acute Q fever
- 1.1 Adults:
- Preferred Regimen: DoxycyclinePO 100 mg bid for 14 days
- 1.2 Children
- 1.2.1Children with age ≥8 years:
- Preferred regimen:Doxycycline PO 2.2 mg/kg per dose bid for 14 days (maximum 100 mg per dose)
- 1.2.2 children with age <8 years with high risk criteria
- Preferred regimen:Doxycycline PO 2.2 mg/kg per dose bid for 14 days (maximum: 100 mg per dose)
- 1.2.3 children with age <8 years with mild or uncomplicated illness:
- Preferred regimen:Doxycycline PO 2.2 mg/kg per dose bid for 5 days (maximum 100 mg per dose). If patient remains febrile past 5 days of treatment: Trimethoprim/Sulfamethoxazole 4-20 mg/kg bid for 14 days (maximum: 800 mg per dose)
- 1.3 Pregnant women
- Preferred regimen: Trimethoprim/Sulfamethoxazole PO 160 mg/800 mg bid a day throughout pregnancy
- 2. Chronic Q fever
- 2.1 Endocarditis or vascular infection
- Preferred regimen:Doxycycline PO 100 mg bid and Hydroxychloroquine PO 200 mg tid for ≥18 months
- Note: childern and pregnant women- consultation Recommended
- 2.2 Noncardiac organ disease
- Preferred regimen: Doxycycline PO 100 mg bid and Hydroxychloroquine PO 200 mg tid
- Note: childern and pregnant women- consultation Recommended
- 2.3 Postpartumwith serologic profile for chronic Q fever
- Preferred regimen:Doxycycline PO 100 mg bid and Hydroxychloroquine PO 200 mg tid for 12 months
- Note: Women should only be treated postpartum if serologic titers remain elevated >12 months after delivery (immunoglobulin G phase I titer ≥1:1024). Women treated during pregnancy for acute Q fever should be monitored similarly to other patients who are at high risk for progression to chronic disease (e.g., serologic monitoring at 3, 6, 12, 18, and 24 months after delivery)
- Note:Post-Q fever fatigue syndrome- no current recommendation
- Legionella
- Legionella pneumonia (atypical bacterial pneumonia)
- Preferred Regimen: Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h OR Azithromycin 500 mg PO on day 1 followed by 250 mg q24h
- Alternate Regimen: Doxycycline 100 mg PO/IV q12h
- Mycoplasma pneumoniae
- Atypical pneumonia caused by Mycoplasma pneumoniae
- Preferred regimen (1): Azithromycin 500 mg PO day 1 and 250 mg day 2 to 5
- Preferred regimen (2): Doxycycline 100 mg PO bid for 14 days
- Preferred regimen (3): Moxifloxacin 400 mg PO qd for 14 days
- Mycoplasma genitalium
- 1.Urethritis and cervicitis caused due to Mycoplasma Genitalium
- Preferred regimen: Azithromycin 1 g PO single dose
- Note(1): Resistant strains -Azithromycin PO in 500 mg single dose followed by 250 mg qd for 4 days
- Note(2): previous treatment failures- Moxifloxacin PO 400 mg qd for 7, 10 or 14 days) has been successfully used to treat both men and women
- 2. PID caused due to Mycoplasma Genitalium
- Preferred regimen: Moxifloxacin PO 400 mg/day for 14 days
# Bacteria – Miscellaneous
- Gardnerella vaginalis
- Eikenella corrodens
- Human bite/soft tissue infections
- Severe
- Preferred regimen: Ampicillin/Sulbactam 1.5-3 g IV q6h
- Alternative regimen: Doxycycline 100 mg IV BID OR Moxifloxacin 400 mg IV OD OR Levofloxacin 500 mg IV OD
- Mild
- Preferred regimen: Amoxicillin/Clavulanate 250-500 mg TID or 875/125 mg PO BID
- Alternative regimen: Doxycycline 100 mg PO BID OR Moxifloxacin 400 mg PO OD OR Levofloxacin 500 mg PO OD
- Head and neck infections
- Severe
- Preferred regimen: Ampicillin/Sulbactam 1.5-3 g IV q6h
- Alternative regimen: Doxycycline 100 mg IV BID OR Moxifloxacin 400 mg IV OD OR Levofloxacin 500 mg IV OD
- Mild
- Preferred regimen: Amoxicillin/Clavulanate 250-500 mg TID or 875/125 mg PO BID
- Alternative regimen: Doxycycline 100 mg PO BID OR Moxifloxacin 400 mg PO OD OR Levofloxacin 500 mg PO OD
- Endocarditis
- Preferred regimen: Ceftriaxone 1g IV q12h OR Cefotaxime 1-2 g IV q8h OR Cefepime 1-2g IV q8h
- Bordetella pertussis
- Bartonella
- Stenotrophomonas maltophilia
- Acinetobacter baumannii
- Preferred regimen: Imipenem (Primaxin) 0.5-1 g IV q6h OR Ampicillin/sulbactam (Unasyn) 3g q4h OR Cefepime (Maxipime) 1-2 g IV q8h OR Colistin 2.5 mg/kg IV q12h OR Tigecycline (Tygacil) 100 mg IV, then 50 mg IV q12h OR Amikacin 7.5 mg/kg q12h IV or 15 mg/kg/day IV
- Alternative regimen: Ceftriaxone 1-2g IV every day OR Cefotaxime 2-3g IV q6-8h OR Ciprofloxacin (Cipro) 400 mg IV q8-12h or 750 mg PO BID OR TMP-SMX 15-20 mg (TMP)/kg/day IV divided 3 or 4 doses/day or 2 DS PO BID
# Bacteria – Anaerobic Gram-Negative Bacilli
- Bacteroides fragilis
- Monotherapy
- Preferred regimen: Imipenem (Primaxin) OR Ertapenem OR Meropenem OR Doripenem 0.5-1.0 g IV q6h OR Piperacillin-tazobactam (Zosyn) 3.375 g IV q6h OR Ampicillin-sulbactam (Unasyn) 1-2 g IV q6h OR Tigecycline (Tygacil) 100 mg IV, then 50 mg IV q12h
- Combination therapy
- Preferred regimen: Metronidazole 0.75-1.0 g IV q12h AND Cefotaxime 1.5-2 g IV q6h OR Aztreonam 1-2 g IV q8h OR Ceftriaxone 1 g IV q12h
- Fusobacterium necrophorum
# Fungi
- Aspergillosis
- Blastomycosis
- 1.Mild to moderate pulmonary blastomycosis
- Preferred regimen: Itraconazole 200 mg PO once or twice per day for 6–12 months
- Note: Oral Itraconazole, 200 mg 3 times per day for 3 days and then once or twice per day for 6–12 months, is recommended
- 2.Moderately severe to severe pulmonary blastomycosis
- Preferred regimen(1): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg per day for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
- Preferred regimen(2): Amphotericin B deoxycholate 0.7–1 mg/kg per day for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
- Note: Oral Itraconazole, 200 mg 3 times per day for 3 days and then 200 mg twice per day, for a total of 6–12 months, is recommended
- 3.Mild to moderate disseminated blastomycosis
- Preferred regimen: Itraconazole 200 mg PO once or twice per day for 6–12 months
- Note(1): Treat osteoarticular disease for 12 months
- Note(2): Oral Itraconazole, 200 mg 3 times per day for 3 days and then 200 mg twice per day, for a total of 6–12 months, is recommended
- 4.Moderately severe to severe disseminated blastomycosis
- Preferred regimen(1): Lipid amphotericin B(Lipid AmB) 3–5 mg/kg per day, for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
- Preferred regimen(2): Amphotericin B deoxycholate 0.7–1 mg/kg per day, for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
- Note: oral Itraconazole, 200 mg 3 times per day for 3 days and then 200 mg twice per day, for a total of 6–12 months, is recommended
- 5.CNS disease
- Preferred regimen: Lipid amphotericin B (Lipid AmB) 5 mg/kg per day for 4–6 weeks AND an oral azole for at least 1 year
- Note(1): Step-down therapy can be with Fluconazole, 800 mg per day OR Itraconazole, 200 mg 2–3 times per day OR voriconazole, 200–400 mg twice per day.
- Note(2): Longer treatment may be required for immunosuppressed patients.
- 6.Immunosuppressed patients
- Preferred regimen(1): Lipid amphotericin B (Lipid AmB), 3–5 mg/kg per day, for 1–2 weeks, AND Itraconazole, 200 mg PO bid for 12 months
- Preferred regimen(2): Amphotericin B deoxycholate, 0.7–1 mg/kg per day, for 1–2 weeks, AND Itraconazole, 200 mg PO bid for 12 months
- Note(1): Oral Itraconazole, 200 mg 3 times per day for 3 days and then 200 mg twice per day, for a total of 12 months, is recommended
- Note(2): Life-long suppressive treatment may be required if immunosuppression cannot be reversed.
- 7.Pregnant women
- Preferred regimen: Lipid amphotericin B (Lipid AmB) 3–5 mg/kg per day
- Note(1): Azoles should be avoided because of possible teratogenicity
- Note(2): If the newborn shows evidence of infection, treatment is recommended with Amphotericin B deoxycholate, 1.0 mg/kg per day
- 8.Children with mild to moderate disease
- Preferred regimen: Itraconazole 10 mg/kg PO per day for 6–12 months
- Note: Maximum dose 400 mg per day
- 9.Children with moderately severe to severe disease
- Preferred regimen(1): Amphotericin B deoxycholate 0.7–1 mg/kg per day for 1–2 weeks AND Itraconazole 10 mg/kg PO per day to a maximum of 400 mg per day for 6–12 months
- Preferred regimen(2): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg per day for 1–2 weeks AND Itraconazole 10 mg/kg PO per day to a maximum of 400 mg per day for 6–12 months
- Note: Children tolerate Amphotericin B deoxycholate better than adults do.
- Paracoccidioidomycosis
- Preferred regimen(1):
- Adults Trimethoprim/sulfamethoxazole (TMP/SMX) TMP: 160-240 mg/day PO/IV, SMX: 800-1200 mg/day PO/IV divided into two doses per day
- Children Trimethoprim/sulfamethoxazole (TMP/SMX) TMP: 8-10 mg/kg PO/IV, SMX: 40-50 mg/kg PO/IV, divided into two doses per day
- Note: Treatment duration based on organ involvement:
- Minor involvement: 12 months
- Moderate involvement: 18-24 months
- Preferred regimen(2): Ketoconazole 200-400 mg/day PO for 9-12 months
- Preferred regimen(3):
- Adults: Itraconazole 600 mg/day PO for 3 days; continue 200 mg/day PO for 6-9 months
- Children: Itraconazole (5 yr) 5-10 mg/kg/day PO for 6-9 months
- Preferred regimen(4): Voriconazole initial dose 400 mg PO/IV each 12 hr for one day, then 200 mg each 12 hr for 6 months
- Note: Diminish the dose to 50% if weight is <40 kg
- Preferred regimen(5): Amphotericin B deoxycholate mg/kg/day IV until patient improves and can be treated by the oral route
- Candidiasis
- Chromoblastomycosis
- Coccidioidomycosis
- Cryptococcosis
- Dermatophytosis
- Onychomycosis
- Fingernail Treatment Options
- Preferred regimen: Terbinafine 250 mg PO q24h (children 40 kg: 250 mg/day) for 6 weeks OR Itraconazole 200 mg PO q24h for 3 months OR Itraconazole 200 mg PO bid for 1 week/month for 2 months OR Fluconazole 150–300 mg PO q week for 3–6 months
- Toenail Treatment Options
- Preferred regimen: Terbinafine 250 mg PO q24h (children 40 kg: 250 mg/day) for 12 weeks OR Itraconazole 200 mg PO q24h for 3 months OR Itraconazole 200 mg bid for 1 week/month for 3–4 months OR Fluconazole 150–300 mg PO q week for 6–12 months
- Tinea capitis
- Preferred regimen(1): Griseofulvin 10-20 mg/kg/day for minimum 6 weeks
- Preferred regimen(2): Itraconazole 4-6 mg/kg pulsed dose weekly
- Preferred regimen(3): Terbinafine if 40 kg: 250 mg/day
- Tinea corporis
- Small, well-defined lesions
- Preferred regimen: Topical cream/ointment Terbinafine OR Miconazole OR Econazole OR Clotrimazole
- Larger lesionss
- Preferred regimen: Terbinafine 250 mg/day PO for 2 weeks OR Itraconazole 200 mg/day PO for 1 wk OR Fluconazole 250 mg PO weekly for 2-4 weeks
- Tinea pedis
- Athlete's foot
- Interdigital
- Preferred regimen: Topical cream/ointment Terbinafine OR Miconazole OR Econazole OR Clotrimazole
- “Dry type”
- Preferred regimen: Terbinafine 250 mg/day PO for 2-4 weeks OR Itraconazole 400 mg/day PO for 1 week per month (repeated if necessary) OR Fluconazole 200 mg PO weekly for 4-8 weeks
- Tinea cruris
- Tinea versicolor
- Preferred regimen: Ketoconazole 400 mg PO single dose OR 200 mg q24h for 7 days OR 2% cream once q24h for 2 weeks
- Alternative regimen: Fluconazole 400 mg PO single dose OR Itraconazole 400 mg PO q24h for 3–7 days
- Histoplasmosis
- Acute pulmonary histoplasmosis
- Moderately severe or severe
- Preferred regimen: Lipid amphotericin B (Lipid AmB) 3.0–5.0 mg/kg daily for 1–2 weeks OR Amphotericin B deoxycholate 0.7–1.0 mg/kg daily for 1–2 weeks, followed by Itraconazole 200 mg 3 times daily for 3 days and then 200 mg twice daily, for a total of 12 weeks
- Note: Methylprednisolone 0.5–1.0 mg/kg daily IV during the first 1–2 weeks of antifungal therapy is recommended for patients who develop respiratory complications, including hypoxemia or significant respiratory distress.
- Mild to moderate
- Preferred regimen:
- For symptoms of <4 weeks, none
- For symptoms of >4 weeks, Itraconazole 200 mg PO 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks
- Chronic cavitary pulmonary histoplasmosis
- Preferred regimen: Itraconazole 200 mg PO 3 times daily for 3 days and then once or twice daily for at least 1 year
- Pericarditis
- Moderately severe to severe
- Preferred regimen(1): Prednisone 0.5–1.0 mg/kg daily (maximum, 80 mg daily) in tapering doses over 1–2 weeks
- Note(1): Itraconazole 200 mg PO 3 times daily for 3 days and then once or twice daily for 6–12 weeks is recommended if corticosteroids are administered
- Note(2): Tamponade requires drainage of pericardial fluid
- Note(3): Antifungal therapy is given to reduce possible dissemination caused by prednisone induced immunosuppression
- Mild
- Preferred regimen: Nonsteroidal anti-inflammatory agents
- Rheumatologic histoplasmosis
- severe
- Preferred regimen: Prednisone 0.5–1.0 mg/kg daily (maximum, 80 mg daily) in tapering doses over 1–2 weeks is recommended in severe cases
- Note: Itraconazole 200 mg 3 times daily for 3 days and then once or twice daily for 6–12 weeks is recommended if corticosteroids are administered
- Mild
- Preferred regimen: Nonsteroidal anti-inflammatory agents
- Note: Corticosteroids are rarely needed
- Mediastinal lymphadenitis
- Mild symptoms of <4 weeks
- Preferred regimen: None
- Symptoms of >4 weeks
- Preferred regimen: Itraconazole 200 mg 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks
- Symptoms warranting treatment
- Preferred regimen: Prednisone 0.5–1.0 mg/kg daily in tapering doses over 1–2 weeks AND Itraconazole 200 mg 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks
- Mediastinal granuloma
- Asymptomatic
- Preferred regimen: None
- Symptomatic
- Preferred regimen: Itraconazole 200 mg PO 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks
- Mediastinal fibrosis
- Preferred regimen: The placement of intravascular stents is recommended for selected patients with pulmonary vessel obstruction
- Note(1): Antifungal treatment is not recommended
- Note(2): Itraconazole 200 mg PO once or twice daily for 12 weeks is recommended if clinical findings cannot differentiate mediastinal fibrosis from mediastinal granuloma
- Broncholithiasis
- Preferred regimen: Antifungal treatment is not recommended
- Bronchoscopic or surgical removal of the broncholith is recommended
- Pulmonary Nodules (Histoplasmomas)
- Preferred regimen: Antifungal treatment is not recommended
- Note: Must be differentiated from malignancy
- Progressive disseminated histoplasmosis
- Moderately severe to severe
- Preferred regimen: Liposomal amphotericin B 3.0 mg/kg daily for 1–2 weeks, followed by Itraconazole 200 mg PO 3 times daily for 3 days and then 200 mg twice daily for a total of at least 12 months
- Alternative regimen: Amphotericin B deoxycholate 0.7–1.0 mg/kg daily for 1–2 weeks, followed by Itraconazole 200 mg PO 3 times daily for 3 days and then 200 mg twice daily for a total of at least 12 months
- Note: Longer treatment may be required in patients with persistent immunodeficiency
- Mild to moderate
- Preferred regimen: Itraconazole 200 mg PO 3 times daily for 3 days and then twice daily for at least 12 months.
- Note: Longer treatment may be required in patients with persistent immunodeficiency.
- CNS histoplasmosis
- Preferred regimen: Liposomal amphotericin B 5.0 mg/kg daily for a total of 175 mg/kg given over 4–6 weeks followed by Itraconazole 200 mg PO 2 or 3 times daily for at least 12 months and until resolution of CSF abnormalities, including Histoplasma antigen levels.
- Note: Blood levels of itraconazole should be obtained to ensure adequate drug exposure
- Mucormycosis
- Penicilliosis
- Sporotrichosis:
- Lymphocutaneous/cutaneous
- Preferred regimen: Itraconazole 200mg PO/day
- Alternative regimen: Itraconazole 200 mg PO bid OR Terbinafine 500 mg bid OR Saturated solution potassium iodide(SSKI) with increasing doses OR Fluconazole 400–800 mg/day OR local hyperthermia
- Note(1): Treat for 2–4 weeks after lesions resolved
- Note(2): SSKI initiated at a dosage of 5 drops (using a standard eyedropper) 3 times daily, increasing as tolerated to 40–50 drops 3 times daily
- Osteoarticular
- Preferred regimen: Itraconazole 200mg PO bid for 12 months
- Alternative regimen: Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day OR Amphotericin B deoxycholate 0.7–1 mg/kg/day
- Note(1): Switch to Itraconazole after favorable response if AmB used
- Note(2): Treat for a total of at least 12 months
- Pulmonary
- Preferred regimen(1): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day for severe or life-threatening pulmonary sporotrichosis, then Itraconazole 200 mg PO bid
- Preferred regimen(2): Itraconazole 200 mg PO bid for 12 months for less severe disease
- Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/d, then Itraconazole 200 mg PO bid OR surgical removal
- Note(1): Treat severe disease with an AmB formulation followed by Itraconazole
- Note(2): Treat less severe disease with Itraconazole
- Note(3): Treat for a total of at least 12 monthsSurgery combined with amphotericin B therapy is rec- ommended for localized pulmonary disease
- Meningitis
- Preferred regimen: Lipid amphotericin B (Lipid AmB) 5 mg/kg daily for 4–6 weeks, then Itraconazole 200 mg PO bid
- Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/d, then Itraconazole 200 mg PO bid
- Note(1): Length of therapy with AmB not established, but therapy for at least 4–6 weeks is recommended.
- Note(2): Treat for a total of at least 12 months.
- Note(3): May require long-term suppression with Itraconazole.
- Disseminated
- Preferred regimen: Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day, then Itraconazole 200 mg PO bid
- Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/day, then Itraconazole 200 mg PO bid
- Note(1): Therapy with AmB should be continued until the patient shows objective evidence of improvement.
- Note(2): Treat for a total of at least 12 months.
- Note(3): May require long-term suppression with Itraconazole.
- Pregnant women
- Preferred regimen(1): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day OR Amphotericin B deoxycholate 0.7–1 mg/kg/day for severe sporotrichosis
- Preferred regimen(2): Local hyperthermia for cutaneous disease.
- Note(1): It is preferable to wait until after delivery to treat non–life-threatening forms of sporotrichosis.
- Note(2): Azoles should be avoided.
- Children
- Preferred regimen:
- Mild disease: Itraconazole 6–10 mg/kg/day (400 mg/day maximum)
- Severe disease: Amphotericin B deoxycholate 0.7 mg/kg/day followed by Itraconazole 6–10 mg/kg up to a maximum of 400 mg PO daily, as step-down therapy
- Alternative regimen: Saturated solution potassium iodide(SSKI) with increasing doses for mild disease initiated at a dosage of 1 drop (using a standard eyedropper) 3 times daily and increased as tolerated up to a maximum of 1 drop/kg or 40–50 drops 3 times daily, whichever is lowest
- Pneumocystis jiroveci
# Mycobacteria
- Mycobacterium tuberculosis
- Mycobacterium abscessus
- Mycobacterium bovis
- Mycobacterium avium-intracellulare
- Mycobacterium celatum
- Mycobacterium chelonae
- Mycobacterium foruitum
- Mycobacterium haemophilum
- Mycobacterium genavense
- Mycobacterium gordonae
- Mycobacterium kansasii
- Mycobacterium marinum
- Mycobacterium scrofulaceum
- Mycobacterium simiae
- Mycobacterium ulcerans
- Mycobacterium xenopi
- Mycobacterium leprae
# Parasites – Intestinal Protozoa
- Balantidium coli
- Preferred regimen: Tetracycline 500 mg PO qid for 10 days OR Metronidazole 750 mg PO tid for 5 days OR Iodoquinol 650 mg PO tid for 20 days
- Blastocystis hominis
- Preferred regimen: Metronidazole 750 mg PO tid or 1.5 g daily, for 10 days OR Trimethoprim-sulfamethoxazole One double strength tablet bid or two double strength tablets daily for 7 days OR Iodoquinol 650 mg PO tid for 20 days OR Nitazoxanide 500 mg bid for 3 days OR Paromomycin 25-35 mg/kg divided tid for 7 days
- Note(1): Treatment of asymptomatic infections is unnecessary
- Note(2): One double strength tablet contains 160 mg trimethoprim/800 mg sulfamethoxazole
- Cryptosporidium parvum
- Cryptosporidium hominis
- Cyclospora cayetanensis
- Dientamoeba fragilis
- Preferred regimen: Iodoquinol 650 mg PO tid for 20d ays
- Alternative regimen: Tetracycline 500 mg PO qid for 10 days OR Metronidazole 500-750 mg PO tid for 10 days
- Entamoeba histolytica
- Giardia lamblia
- Preferred regimen(1):
- Adult: Tinidazole 2 g, single dose
- Pediatric: Tinidazole 50 mg/kg, single dose (maximum, 2 g)
- Preferred regimen(2):
- Adult: Metronidazole 250 mg tid for 5-7 days
- Pediatric: Metronidazole 5 mg/kg tid for 7 days
- Preferred regimen(3):
- Adult: Nitazoxanide 500 mg bid for 3 days
- Pediatric: Nitazoxanide Age 12-47 months: 100 mg bid for 3 days and for Age 4-11 years: 200 mg bid for 3 days
- Preferred regimen(4):
- Adult: Albendazole 400 mg qd for 5 days
- Pediatric: Albendazole 15 mg/kg/day for 5-7 days (maximum, 400 mg)
- Preferred regimen(5):
- Adult: Paromomycin 500 mg tid for 5-10 days
- Pediatric: Paromomycin 30 mg/kg/day in 3 doses for 5-10 days
- Preferred regimen(6):
- Adult: Quinacrine 100 mg tid for 5-7 days
- Pediatric: Quinacrine 2 mg/kg tid for 7 days
- Preferred regimen(7):
- Adult: Furazolidone 100 mg qid for 7-10 days
- Pediatric: Furazolidone 2 mg/kg qid for 10 days
- Isospora belli
- Microsporidiosis
# Parasites – Extraintestinal Protozoa
- Primary amoebic meningoencephalitis
- Acanthamoeba
- Balamuthia mandrillaris
- Naegleria fowleri
- Babesia microti
- Leishmaniasis
- Plasmodium
- Toxoplasma gondii
- Trichomonas vaginalis
- African trypanosomiasis
- American trypanosomiasis
# Parasites – Intestinal Nematodes (Roundworms)
- Ascaris lumbricoides
- Capillaria philippinensis
- Enterobius vermicularis
- Necator americanus
- Ancylostoma duodenale
- Strongyloides stercoralis
- Trichuris trichiura
# Parasites – Extraintestinal Nematodes (Roundworms)
- Ancylostoma braziliense
- Angiostrongylus cantonensis
- Filariasis
- Onchocerciasis
- Wuchereria bancrofti
- Brugia malayi
- Gnathostoma spinigerum
- Toxocariasis
- Trichinella spiralis
# Parasites – Trematodes (Flukes)
- Clonorchis sinensis
- Dicrocoelium dendriticum
- Fasciola hepatica
- Paragonimus westermani
- Schistosomiasis
# Parasites – Cestodes (Tapeworms)
- Echinococcus
- Neurocysticercosis
- Sparganosis
# Parasites – Ectoparasites
- Body lice
- Head lice
- Pubic lice
- Scabies
- Myiasis
# Viruses
- Adenovirus
- SARS
- Cytomegalovirus
- Enterovirus D68
- Ebola virus
- Marburg virus
- Hantavirus
- Dengue virus
- West Nile virus
- Yellow Fever
- Chikungunya virus
- Hepatitis A virus
- Hepatitis B virus
- Hepatitis C virus
- Hepatitis D virus
- Hepatitis E virus
- Epstein-Barr virus
- Human herpesvirus 6
- Human herpesvirus 7
- Human herpesvirus 8 (KSHV)
- Herpes simplex virus
- Varicella-zoster virus
- Human papillomavirus
- Influenza A
- Influenza B
- Avian influenza
- Swine influenza
- Measles
- Middle East respiratory syndrome
- Paramyxovirus
- Parvovirus B19
- BK virus
- JC virus
- Rabies
- Respiratory Syncytial Virus
- Rhinovirus
- Rotavirus
- Smallpox
- HIV/AIDS | Sandbox ID2
### Bacteria – Gram-Positive Cocci
- Enterococci
- Enterococcus faecalis
- Bacteremia[1]
- Ampicillin or Penicillin susceptible : Ampicillin 2 g IV q4-6h OR (Ampicillin AND Gentamicin 1 mg/kg q8h).
- Ampicillin resistant and vancomycin susceptible or Penicillin allergy : (Vancomycin 15 mg/kg IV q12h AND Gentamicin 1 mg/kg q8h) OR Linezolid 600 mg q12h OR Daptomycin 6 mg/kg per day.
- Ampicillin and Vancomycin resistant : Linezolid 600 mg q12h OR Daptomycin 6 mg/kg IV per day
- Endocarditis in Adults [2]
- Strains Susceptible to Penicillin, Gentamicin, and Vancomycin
- Preferred regimen : (Ampicillin 12 g/day IV for 4–6weeks OR Aqueous crystalline penicillin G sodium 18–30 MU/day IV for 4–6weeks) AND Gentamicin sulfate 3 mg/kg/day IV/IM for 4–6 weeks
- Note : In case of native valve endocarditis, 4-wk therapy recommended for patients with symptoms of illness ≤3 months and 6-wk therapy recommended for patients with symptoms >3 months and prosthetic valve or other prosthetic cardiac material a minimum of 6 wk of therapy recommended
- Alternate regimen : Vancomycin hydrochloride 30 mg/kg/day IV for 6 weeks AND Gentamicin sulfate 3 mg/kg/day IV/IM for 6weeks
- Strains Susceptible to Penicillin, Streptomycin, and Vancomycin and Resistant to Gentamicin
- Preferred regimen : (Ampicillin 12 g/day IV for 4–6 weeks OR Aqueous crystalline penicillin G sodium 24 MU/day IV for 4–6weeks)AND Streptomycin sulfate 15 mg/kg/day IV/IM for 4–6weeks
- Alternate regimen: Vancomycin hydrochloride 30 mg/kg/day IV 6weeks AND Streptomycin sulfate 15 mg/kg per 24 h IV/IM for 6weeks
- Strains Resistant to Penicillin and Susceptible to Aminoglycoside and Vancomycin
- β Lactamase–producing strain
- Preferred regimen : Ampicillin-sulbactam 12 g/day IV for 6weeks AND Gentamicin sulfate 3 mg/kg/day IV/IM 6weeks
- Alternate regimen : Vancomycin hydrochloride 30 mg/kg/day IV for 6weeks AND Gentamicin sulfate 3 mg/kg/day IV/IM for 6weeks
- Intrinsic penicillin resistance : Vancomycin hydrochloride 30 mg/kg/day IV for 6weeks AND Gentamicin sulfate 3 mg/kg/day IV/IM for 6weeks
- Strains Resistant to Penicillin, Aminoglycoside, and Vancomycin
- Preferred regimen : (Imipenem OR Cilastatin 2 g/day IV for ≥ 8weeks AND Ampicillin 12 g/day IV for ≥ 8weeks) OR (Ceftriaxone sodium 4 g/day IV/IM for ≥ 8weeks AND Ampicillin 12 g/day IV for ≥ 8weeks)
- Endocarditis in Pediatrics
- Strains Susceptible to Penicillin, Gentamicin, and Vancomycin
- Preferred regimen : (Ampicillin 300 mg/kg/day IV for 4–6 weeks OR Penicillin 300,000U/kg/day IV for 4–6 weeks) AND Gentamicin 3 mg/kg per 24 h IV/IM 4–6 weeks
- Note : In case of native valve endocarditis, 4-wk therapy recommended for patients with symptoms of illness ≤3 months and 6-wk therapy recommended for patients with symptoms >3 months and prosthetic valve or other prosthetic cardiac material a minimum of 6 wk of therapy recommended
- Alternate regimen : Vancomycin 40 mg/kg/day IV for 6weeks AND Gentamicin 3 mg/kg/day IV/IM for 6weeks
- Strains Susceptible to Penicillin, Streptomycin, and Vancomycin and Resistant to Gentamicin
- Preferred regimen : (Ampicillin 300 mg/kg/day IV for 4–6 weeks OR Penicillin 300,000 U/kg/day IV for 4–6 weeks) AND Streptomycin 20–30 mg/kg/day IV/IM for 4–6 weeks
- Alternate regimen: Vancomycin hydrochloride 40 mg/kg/day IV for 6weeks AND Streptomycin sulfate 15 mg/kg/day IV/IM for 6weeks
- Strains Resistant to Penicillin and Susceptible to Aminoglycoside and Vancomycin
- β Lactamase–producing strain
- Preferred regimen : Ampicillin-sulbactam 300 mg/kg/day IV for 6weeks AND Gentamicin 3 mg/kg/day IV/IM for 6weeks
- Alternate regimen : Vancomycin 40 mg/kg/day IV for 6weeks AND Gentamicin 3 mg/kg/day IV/IM for 6weeks
- Intrinsic penicillin resistance : Vancomycin 40 mg/kg/day IV AND Gentamicin 3 mg/kg/day IV/IM for 6weeks
- Strains Resistant to Penicillin, Aminoglycoside, and Vancomycin
- Preferred regimen : Imipenem/cilastatin 60–100 mg/kg/day IV for ≥ 8weeks AND Ampicillin 300 mg/kg/day IVfor ≥ 8weeks
- Alternate regimen : Ceftriaxone 100 mg/kg/day IV/IM AND Ampicillin 300 mg/kg/day IV for ≥ 8weeks
- Meningitis[3]
- Ampicillin susceptible
- Preferred regimen: Ampicillin 12 g/day IV q4h AND Gentamicin 5 mg/kg/day IV q8h
- Ampicillin resistant
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Gentamicin 5 mg/kg/day IV q8h
- Ampicillin and vancomycin resistant
- Preferred regimen: Linezolid 600 mg IV q12h
- Urinary tract infections [4]
- Preferred regimen : Nitrofurantoin 100 mg PO q6h for 5 days OR Fosfomycin 3 g PO single dose OR Amoxicillin 875 mg-1 g PO q12h for 5 days
- Intra abdominal or Wound infections [5]
- Penicillin or Ampicillin are preferred agents, Vancomycin in setting of penicillin allergy or high-level penicillin resistance.
- For complicated skin-skin structure and intra-abdominal infection : Tigecycline 100 mg IV single dose and 50 mg IV q12h
- Enterococcus faecium
- Bacteremia[6]
- Ampicillin or Penicillin susceptible : Ampicillin 2 g IV q4-6h OR (Ampicillin AND Gentamicin 1 mg/kg q8h).
- Ampicillin resistant and vancomycin susceptible or Penicillin allergy : (Vancomycin 15 mg/kg IV q12h AND Gentamicin 1 mg/kg q8h) OR Linezolid 600 mg q12h OR Daptomycin 6 mg/kg per day.
- Ampicillin and Vancomycin resistant : Linezolid 600 mg q12h OR Daptomycin 6 mg/kg IV per day
- Endocarditis in Adults [2]
- Strains Susceptible to Penicillin, Gentamicin, and Vancomycin
- Preferred regimen : (Ampicillin 12 g/day IV for 4–6weeks OR Aqueous crystalline penicillin G sodium 18–30 MU/day IV for 4–6weeks) AND Gentamicin sulfate 3 mg/kg/day IV/IM for 4–6 weeks
- Note : In case of native valve endocarditis, 4-wk therapy recommended for patients with symptoms of illness ≤3 months and 6-wk therapy recommended for patients with symptoms >3 months and prosthetic valve or other prosthetic cardiac material a minimum of 6 wk of therapy recommended
- Alternate regimen : Vancomycin hydrochloride 30 mg/kg/day IV for 6 weeks AND Gentamicin sulfate 3 mg/kg/day IV/IM for 6weeks
- Strains Susceptible to Penicillin, Streptomycin, and Vancomycin and Resistant to Gentamicin
- Preferred regimen : (Ampicillin 12 g/day IV for 4–6 weeks OR Aqueous crystalline penicillin G sodium 24 MU/day IV for 4–6weeks)AND Streptomycin sulfate 15 mg/kg/day IV/IM for 4–6weeks
- Alternate regimen: Vancomycin hydrochloride 30 mg/kg/day IV 6weeks AND Streptomycin sulfate 15 mg/kg per 24 h IV/IM for 6weeks
- Strains Resistant to Penicillin and Susceptible to Aminoglycoside and Vancomycin
- β Lactamase–producing strain
- Preferred regimen : Ampicillin-sulbactam 12 g/day IV for 6weeks AND Gentamicin sulfate 3 mg/kg/day IV/IM 6weeks
- Alternate regimen : Vancomycin hydrochloride 30 mg/kg/day IV for 6weeks AND Gentamicin sulfate 3 mg/kg/day IV/IM for 6weeks
- Intrinsic penicillin resistance : Vancomycin hydrochloride 30 mg/kg/day IV for 6weeks AND Gentamicin sulfate 3 mg/kg/day IV/IM for 6weeks
- Strains Resistant to Penicillin, Aminoglycoside, and Vancomycin
- Preferred regimen : Linezolid 1200 mg/day IV/PO ≥8weeks OR Quinupristin-Dalfopristin22.5 mg/kg/day IV ≥8weeks
- Endocarditis in Pediatrics
- Strains Susceptible to Penicillin, Gentamicin, and Vancomycin
- Preferred regimen : (Ampicillin 300 mg/kg/day IV for 4–6 weeks OR Penicillin 300,000U/kg/day IV for 4–6 weeks) AND Gentamicin 3 mg/kg per 24 h IV/IM 4–6 weeks
- Note : In case of native valve endocarditis, 4-wk therapy recommended for patients with symptoms of illness ≤3 months and 6-wk therapy recommended for patients with symptoms >3 months and prosthetic valve or other prosthetic cardiac material a minimum of 6 wk of therapy recommended
- Alternate regimen : Vancomycin 40 mg/kg/day IV for 6weeks AND Gentamicin 3 mg/kg/day IV/IM for 6weeks
- Strains Susceptible to Penicillin, Streptomycin, and Vancomycin and Resistant to Gentamicin
- Preferred regimen : (Ampicillin 300 mg/kg/day IV for 4–6 weeks OR Penicillin 300,000 U/kg/day IV for 4–6 weeks) AND Streptomycin 20–30 mg/kg/day IV/IM for 4–6 weeks
- Alternate regimen: Vancomycin hydrochloride 40 mg/kg/day IV for 6weeks AND Streptomycin sulfate 15 mg/kg/day IV/IM for 6weeks
- Strains Resistant to Penicillin and Susceptible to Aminoglycoside and Vancomycin
- β Lactamase–producing strain
- Preferred regimen : Ampicillin-sulbactam 300 mg/kg/day IV for 6weeks AND Gentamicin 3 mg/kg/day IV/IM for 6weeks
- Alternate regimen : Vancomycin 40 mg/kg/day IV for 6weeks AND Gentamicin 3 mg/kg/day IV/IM for 6weeks
- Intrinsic penicillin resistance : Vancomycin 40 mg/kg/day IV AND Gentamicin 3 mg/kg/day IV/IM for 6weeks
- Strains Resistant to Penicillin, Aminoglycoside, and Vancomycin
- Preferred regimen : Linezolid 30 mg/kg/day IV/PO ≥ 8weeks OR Quinupristin-Dalfopristin22.5 mg/kg/day IV ≥ 8weeks
- Meningitis[3]
- Ampicillin susceptible
- Preferred regimen: Ampicillin 12 g/day IV q4h AND Gentamicin 5 mg/kg/day IV q8h
- Ampicillin resistant
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Gentamicin 5 mg/kg/day IV q8h
- Ampicillin and vancomycin resistant
- Preferred regimen: Linezolid 600 mg IV q12h
- Urinary tract infections [7]
- Preferred regimen : Nitrofurantoin 100 mg PO q6h for 5 days OR Fosfomycin 3 g PO single dose OR Amoxicillin 875 mg-1 g PO q12h for 5 days
- Intra abdominal or Wound infections [8]
- Penicillin or Ampicillin are preferred agents, Vancomycin in setting of penicillin allergy or high-level penicillin resistance.
- For complicated skin-skin structure and intra-abdominal infection : Tigecycline 100 mg IV single dose and 50 mg IV q12h
- Staphylococci
- Staphylococcus aureus
- (1)Infectious endocarditis
- In adults
- Preferred regimen: Vancomycin, 15-20 mg/kg IV q8-12h OR Daptomycin 6mg/kg/dose IV qd
- (2) Intravascular catheter-related infections[9]
- Methicillin susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Nafcillin 2 g IV q6h OR Oxacillin, 2 g IV q6h.
- Alternative regimen: Cefazolin, 2 g IV q8h OR Vancomycin, 15 mg/kg IV q12h.
- Pediatric dose:
- Nafcillin
- Neonates
- 0–4 weeks of age and 1200 g- 50 mg/kg/day q12h.
- ≤7 days and 1200–2000 g- 50 mg/kg/day q12h.
- >7 days of age and <2000g- 75 mg/kg/day q8h.
- >7 days of age and >1200 g - 100 mg/kg/day q6h.
- Oxacillin
- Neonates
- 0–4 weeks of age and 1200 g - 50 mg/kg/day q12h.
- Postnatal age <7 days and 1200–2000 g- 50–100 mg/kg/day q12h.
- Postnatal age <7 days and >2000 g, 75–150 mg/kg/day q8h.
- Postnatal age ≥7 days and 1200–2000 g- 75–150 mg/kg/day q8h.
- Postnatal age ≥7 days and >2000 g, 100–200 mg/kg/day q6h.
- Infants and children Nafcillin 100–200 mg/kg/day q4–6h.
- Cefazolin
- Neonates
- Postnatal age ≤7 days: 40 mg/kg/day q12h.
- Postnatal age >7 days and 2000 g: 40 mg/kg/day q12h.
- Postnatal age >7 days and 12000 g: 60 mg/kg/day q8h.
- Infants and children: 50 mg/kg/day q8h.
- Vancomycin
- Neonates
- Postnatal age ≤7 days and <1200 g, 15 mg/kg/day q24h.
- Postnatal age ≤7 days and 1200–2000 g, 10–15 mg/kg q12–18h.
- Postnatal age ≤7 days and >2000 g, 10–15 mg/kg q8–12h.
- Postnatal age >7 days and <1200 g, 15 mg/kg/day q24h.
- Postnatal age >7 days and 1200–2000 g, 10–15 mg/kg q8–12h.
- Postnatal age >7 days and >2000 g, 15–20 mg/kg q8h.
- Infants and children: 40 mg/kg/day q6–8h.
- Methicillin resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin, 15 mg/kg IV q12h OR Daptomycin, 6–8 mg/kg per day IV, or Linezolid 10 mg/kg q 12 hr IV or PO ; OR Vancomycin 15 mg/kg IV q12h AND (Rifampicin IV or Gentamycin IV); or Trimethoprim-Sulfamethoxazole 6–12 mg TMP/kg/day in divided doses q12h alone (if susceptible).
- Pediatric dose
- Linezolid 10 mg/kg IV or PO q12h
- Neonates
- 0–4 weeks of age and birthweight <1200 g: 10 mg/kg q8–12h (note: q12h in patients <34 weeks gestation and <1 week of age).
- <7 days of age and birthweight >1200 g, 10 mg/kg q8–12h (note: q12h in patients <34 weeks gestation and <1 week of age).
- 7 days and birthweight >1200 g, 10 mg/kg q8h.
- Infants and children <12 years of age: 10 mg/kg q8h Children 12 years of age and adolescents: 10 mg/kg q12h.
- Gentamycin
- Neonates
- Premature neonates and <1000 g, 3.5 mg/kg q24h; 0–4 weeks and <1200 g, 2.5 mg/kg q18-24h.
- Postnatal age 7 days: 2.5 mg/kg q12h.
- Postnatal age 17 days and 1200–2000 g, 2.5 mg/kg q8-12h.
- Postnatal age 17 days and 12000 g, 2.5 mg/kg q8h.
- Once daily dosing for premature neonates with normal renal function, 3.5–4 mg/kg q24h.
- Once daily dosing for term neonates with normal renal function, 3.5–5 mg/kg q24h.
- Infants and children <5 years of age: 2.5 mg/kg q8h; qd dosing in patients with normal renal function, 5–7.5 mg/kg q24h.
- Children >5 years of age: 2–2.5 mg/kg q8h; qd s with normal renal function, 5–7.5 mg/kg every 24 h.
- Trimethoprim-Sulfamethoxazole
- Infants 12 months of age and children: mild-to-moderate infections, 6–12 mg TMP/kg/day q12h; serious infection, 15–20 mg TMP/kg/day q6-8h.
- (3) Purulent cellulitis (defined as cellulitis associated with purulent drainage or exudate in the absence of a drainable abscess)
- In adults
- Preferred regimen: Clindamycin 300–450 mg PO TID OR Trimethoprim-Sulfamethoxazole 1–2 DS tab PO BID OR Doxycycline 100 mg PO BID OR Minocycline 200 mg as a single dose, then 100 mg PO BID OR Linezolid 600 mg PO BID
- In childern
- Preferred regimen: Clindamycin 10–13 mg/kg/dose PO q6–8 h, not to exceed 40 mg/kg/day OR Trimethoprim 4–6 mg/kg, Sulfamethoxazole 20–30 mg/kg PO q12h OR Doxycycline If patient body weight <45kg: 2 mg/kg/dose PO q12 h.
- Nonpurulent cellulitis (defined as cellulitis with no purulent drainage or exudate and no associated abscess)
- In adults
- Preferred regimen: Beta-lactam (eg, Cephalexin and Dicloxacillin) 500 mg PO QID OR Clindamycin 300–450 mg PO TID OR Amoxicillin 500 PO mg TID OR Linezolid 600 mg PO BID
- In childern
- Preferred regimen: Clindamycin 10–13 mg/kg PO q6–8 h, not to exceed 40 mg/kg/day OR Trimethoprim 4–6 mg/kg, Sulfamethoxazole 20–30 mg/kg PO q12h OR Linezolid 10 mg/kg PO q8h, not to exceed 600 mg
- (4) Brain abscess[10][11][12]
- Methicillin-resistant Staphylococcus aureus (MRSA)
- In adults
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 4–6 weeks
- Alternative regimen: Linezolid 600 mg PO/IV q12h for 4–6 weeks OR Trimethoprim-Sulfamethoxazole 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks
- In childern
- Preferred regimen: Vancomycin15 mg/kg/dose IV q6h OR Linezolid 10 mg/kg/dose PO/IV q8h
- Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Nafcillin 2 g IV q4h OR Oxacillin 2 g IV q4h
- Alternative regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
- (5) Cerebrospinal fluid shunt infection [13][14]
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND/OR Rifampin 600 mg IV or PO q24h
- Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: (Nafcillin 2 g IV q4h OR Oxacillin 2 g IV q4h) AND/OR Rifampin 600 mg IV/PO q24h
- (6) Spinal epidural abscess [15][16][17][18]
- Penicillin-susceptible Staphylococcus aureus or Streptococcus
- Preferred regimen: Penicillin G 4 MU IV q4h for 2–4 weeks, then PO to complete 6–8 weeks
- Methicillin-susceptible Staphylococcus aureus or Streptococcus
- Preferred regimen: Cefazolin 2 g IV q8h for 2–4 weeks, then PO to complete 6–8 weeks OR Nafcillin 2 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks OR Oxacillin 2 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks
- Alternative regimen: Clindamycin 600 mg IV q6h for 2–4 weeks, then PO to complete 6–8 weeks
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin loading dose 25–30 mg/kg IV followed by 15–20 mg/kg IV q8–12h for 2–4 weeks, then PO to complete 6–8 weeks
- Alternative regimen: Linezolid 600 mg PO or IV q12h for 4–6 weeks OR TMP-SMX 5 mg/kg PO or IV q8–12h for 4–6 weeks
- Pediatric dose: Vancomycin 15 mg/kg IV q6h OR Linezolid 10 mg/kg PO or IV q8h
- (7) Bacterial meningitis
- Methicillin susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Nafcillin 9–12 g/day IV q4h OR Oxacillin 9–12 g/day IV q4h
- Alternative regimen: Vancomycin 30–45 mg/kg/day IV q8–12h OR Meropenem 6 g/day IV q8h
- Methicillin resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
- Alternative regimen: Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h OR Linezolid 600 mg IV q12h
- (8) Septic thrombosis of cavernous or dural venous sinus[19]
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h for 4–6 weeks
- Alternative regimen: Linezolid 600 mg PO IV q12h for 4–6 weeks OR TMP-SMX 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks
- Pediatric dose: Vancomycin 15 mg/kg IV q6h OR Linezolid 10 mg/kg PO or IV q8h
- (9) Subdural empyema
- Methicillin-resistant Staphylococcus aureus (MRSA)[20]
- In adults
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 4–6 weeks
- Alternative regimen: Linezolid 600 mg PO or IV q12h for 4–6 weeks OR TMP-SMX 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks
- In childern
- Preferred regimen: Vancomycin 15 mg/kg/dose IV q6h OR Linezolid 10 mg/kg/dose PO/IV q8h
- (10) Acute conjunctivitis [21]
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin ointment 1% qid
- (11) Appendicitis
- (12) Diverticulitis
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h.
- (13) Peritonitis secondary to bowel perforation, peritonitis secondary to ruptured appendix, peritonitis secondary to ruptured appendix, typhlitis
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h
- (14) Cystic fibrosis [23]
- Preferred Regimen (Adult)
- If methicillin sensitive staphylococcus aureus: Nafcillin 2 gm IV q4hs OR Oxacillin 2 gm IV q4hs
- If methicillin resistant staphylococcus aureus: Vancomycin 15-20 mg/kg IV q8-12h OR Linezolid 600 mg po/IV q12h
- Preferred regimen (Pediatric)
- If methicillin sensitive staphylococcus aureus: Nafcillin 5 mg/kg q6h (Age >28 days) OR Oxacillin 75 mg/kg q6h (Age >28 days)]]
- If methicillin resistant staphylococcus aureus: Vancomycin 40 mg/kg q6-8h (Age >28 days) OR Linezolid 10 mg/kg po or IV q8h (up to age 12)
- (15) Bronchiectasis [24]
- (a) Preferred Regimen in adults
- Recommended first-line treatment and length of treatment
- Recommended second-line treatment and length of treatment
- (b) Preferred Regimen in children
- Recommended first-line treatment and length of treatment
- Recommended second-line treatment and length of treatment
- (B)Long-term oral antibiotic treatment
- (a) Preferred Regimen in adults
- Recommended first-line treatment and length of treatment
- Recommended second-line treatment and length of treatment
- (16) Empyema
- Preferred regimen: Nafcillin 2 gm IV q4h OR oxacillin 2 gm IV q4h if MSSA
- Alternate regimen: Vancomycin 1 gm IV q12h OR Linezolid 600 mg po bid if MRSA
- (17) Community-acquired pneumonia
- Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred Regimen : Nafcillin 1000-2000 mg q4h OR Oxacillin 2 g IV q4h OR Flucloxacillin 250 mg IM/IV q6h
- Alternative Regimen : Cefazolin 500 mg IV q12h OR Clindamycin 150-450 mg PO q6-8h
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred Regimen : Vancomycin 45-60 mg/kg/day divided q8-12h (max: 2000 mg/dose) for 7-21 days OR Linezolid 600 mg PO/IV q12h for 10-14 days
- Alternative Regimen: Trimethoprim-Sulfamethoxazole 1-2 double-strength tablets (800/160 mg) q12-24h
- (18) Olecranon bursitis or prepatellar bursitis
- Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Nafcillin 2 g IV q4h OR Oxacillin 2 g IV q4h OR Dicloxacillin 500 mg PO qid
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 1 g IV q12h OR Linezolid 600 mg PO qd
- (19) Septic arthritis
- In adults
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regime: Vancomycin 15–20 mg/kg IV q8–12h
- Alternative regimen (1): Daptomycin 6 mg/kg IV q24h in adults
- Alternative regimen (2): Linezolid 600 mg PO/IV q12h
- Alternative regimen (3): Clindamycin 600 mg PO/IV q8h
- Alternative regimen (4): TMP-SMX 3.5–4.0 mg/kg PO/IV q8–12h
- In childern
- Preferred regimen: Vancomycin 15 mg/kg IV q6h OR Daptomycin 6–10 mg/kg IV q24h OR Linezolid 10 mg/kg PO/IV q8h OR Clindamycin 10–13 mg/kg/dose PO/IV q6–8h
- Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regime: Nafcillin 2 g IV q6h OR Clindamycin 900 mg IV q8h
- Alternative regime: Cefazolin 0.25–1 g IV/IM q6–8h OR Vancomycin 500 mg IV q6h or 1 g IV q12h
- (20) Septic arthritis, prosthetic joint infection (device-related osteoarticular infections)
- Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Nafcillin 2 g IV q4–6h OR Oxacillin 2 g IV q4–6h
- Alternative regimen: Cefazolin 1–2 g IV q8h OR Ceftriaxone 2 g IV q24h
- Alternative regimen (if allergic to penicillins): Clindamycin 900 mg IV q8h OR Vancomycin 15–20 mg/kg IV q8–12 hours, not to exceed 2 g per dose
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Early-onset (< 2 months after surgery) or acute hematogenous prosthetic joint infections involving a stable implant with short duration (< 3 weeks) of symptoms and debridement (but device retention)
- Preferred regimen: Vancomycin AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks
- Alternative regimen: (Daptomycin 6 mg/kg IV q24h OR Linezolid 600 IV q8h) AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks
- (21) Hematogenous osteomyelitis
- Adult (>21 yrs)
- Methicillin-resistant Staphylococcus aureus (MRSA) possible
- Preferred regimen: Vancomycin 1 gm IV q12h (if over 100 kg, 1.5 gm IV q12h)
- Methicillin-resistant Staphylococcus aureus (MRSA) unlikely
- Preferred regimen: Nafcillin OR Oxacillin 2 gm IV q4h
- Children (>4 mos.)-Adult
- Methicillin-resistant Staphylococcus aureus (MRSA) possible
- Preferred regimen: Vancomycin 40 div q6–8h
- Methicillin-resistant Staphylococcus aureus (MRSA) unlikely
- Preferred regimen: Nafcillin OR Oxacillin 37 q6h (to max. 8–12 gm per day)
- Newborn (<4 mos.)
- Methicillin-resistant Staphylococcus aureus (MRSA) possible
- Preferred regimen: Vancomycin AND (Ceftazidime 2 gm IV q8h or Cefepime 2 gm IV q12h)
- Methicillin-resistant Staphylococcus aureus (MRSA) unlikely
- Preferred regimen: (Nafcillin OR Oxacillin) AND (Ceftazidime OR Cefepime)
- Specific therapy
- Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Nafcillin OR Oxacillin 2 gm IV q4h OR Cefazolin 2 gm IV q8h
- Alternative regimen: Vancomycin 1 gm IV q12h (if over 100 kg, 1.5 gm IV q12h)
- Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 1 gm IV q12h
- Alternative regimen: Linezolid 600 mg q12h IV/po ± Rifampin 300 mg po/IV bid
- (22) Diabetic foot osteomyelitis
- High Risk for MRSA
- Preferred regimen: Linezolid 600 mg IV/PO q12h OR Daptomycin 4 mg/kg IV q24h OR Vancomycin 15–20 mg/kg IV q8–12h (trough: 10–20 mg/L)
- (23) Necrotizing fasciitis[25]
- In adult
- Preferred regimen (1): Nafcillin 1–2 g IV q4h (Severe Pencillin allergy: Vancomycin, linezolid, quinupristin/dalfopristin, daptomycin)
- Preferred regimen (2): Oxacillin 1–2 g IV q4h
- Preferred regimen (3): Cefazolin 1 g IV q8h
- Preferred regimen (4): Vancomycin 15 mg/kg IV bid
- Preferred regimen (5): Clindamycin 600–900 mg IV q8h
- In childern
- Preferred regimen (1): Nafcillin 50 mg/kg/dose IV q6h (Severe Pencillin allergy: Vancomycin, linezolid, quinupristin/dalfopristin, daptomycin)
- Preferred regimen (2): Oxacillin 50 mg/kg/dose IV q6h
- Preferred regimen (3): Cefazolin 33 mg/kg/dose IV q8h
- Preferred regimen (4): Vancomycin 15 mg/kg/dose IV q6h
- Preferred regimen (5): Clindamycin 10–13 mg/kg/dose IV q8h (Bacteriostatic; potential cross-resistance and emergence of resistance in erythromycin-resistant strains; inducible resistance in methicillin resistent staphylococcus aureus)
- (24) Staphylococcal toxic shock syndrome [26]
- Methicillin sensitive Staphylococcus aureus
- Preferred regimen: Cloxacillin 250-500 mg PO q6h (max dose: 4 g/24 hr) OR Nafcillin 4-12 g/24 hr divided IV q4-6hr (max dose: 12 g/24 hr) OR Cefazolin 0.5-2g IV or IM q8h (max dose: 12 g/24 hr), AND Clindamycin 150-600 mg IV, IM, or PO q6-8h (max dose: 5 g/24 hr IV or IM or 2 g/24 hr PO)
- Alternative regimen (1):Clarithromycin 250-500 mg PO q12h (max dose: 1 g/24 hr) AND Clindamycin 150-600 mg IV, IM, or PO q6-8h (max dose: 5 g/24 hr IV or IM or 2 g/24 hr PO)
- Alternative regimen (1):Rifampicin, AND Linezolid 600 mg IV or PO q12h OR Daptomycin OR Tigecycline 100 mg loading dose followed by 50 mg IV q12h
- Methicillin resistant Staphylococcus aureus
- Preferred regimen: Clindamycin 150-600 mg IV, IM, or PO q6-8h (max dose: 5 g/24 hr IV or IM or 2 g/24 hr PO) OR Linezolid 600 mg IV or PO q12h AND Vancomycin 15 to 20 mg/kg IV q8-12h, not to exceed 2 g per dose or Teicoplanin
- Alternative regimen (1):Rifampicin, AND Linezolid 600 mg q12h IV or PO OR Daptomycin OR Tigecycline 100 mg loading dose followed by 50 mg q12h IV
- Glycopeptide resistant or intermediate Staphylococcus aureus
- Preferred regimen: Linezolid 600 mg IV or PO q12h AND Clindamycin 150-600 mg IV, IM, or PO q6-8h (max dose: 5 g/24 hr IV or IM or 2 g/24 hr PO) (if sensitive)
- Alternative regimen (1):Daptomycin OR Tigecycline 100 mg loading dose followed by 50 mg IV q12h
- Prophylaxis for coronary artery bypass graft-associated acute mediastinitis[27]
- Methicillin susceptible staphylococcus aureus (MSSA)
- Preferred regimen: A first- or second-generation Cephalosporin is recommended for prophylaxis in patients without methicillin-resistant Staphylococcus aureus colonization.
- Methicillin resistant staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin alone or in combination with other antibiotics to achieve broader coverage is recommended for prophylaxis in patients with proven or suspected methicillin-resistant S. aureus colonization
- Staphylococcus, coagulase-negative species (CoNS)
- Staphylococcus epidermidis group (Staphylococcus epidermidis, Staphylococcus haemolyticus)
- 1. Bacteremia: most often due to IV lines, vascular grafts, cardiac valves (30-40% of all coagulase-negative staphylococcus infections)
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h AND Vancomycin AND Rifampin 300 mg q8h IV/PO for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg q8h IV/PO.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- 2. CSF shunt: meningitis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h added to Vancomycin AND Rifampin 300 mg IV/PO q8h for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg IV/PO q8h.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- 3. Peritoneal dialysis catheter: peritonitis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h added to Vancomycin AND Rifampin 300 mg q8h IV/PO for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg q8h IV/PO.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- 4. Prosthetic joint: septic arthritis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h added to Vancomycin AND Rifampin 300 mg q8h IV/PO for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg q8h IV/PO.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- 5. Prosthetic or natural cardiac valve: endocarditis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h added to Vancomycin AND Rifampin 300 mg q8h IV/PO for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg q8h IV/PO.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- 6. Post-sternotomy: osteomyelitis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h added to Vancomycin AND Rifampin 300 mg q8h IV/PO for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg q8h IV/PO.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- 7. Implants (breast, penile, pacemaker) and other prosthetic devices: local infection
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h added to Vancomycin AND Rifampin 300 mg q8h IV/PO for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg q8h IV/PO.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- 8. Post-ocular surgery: endophthalmitis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h added to Vancomycin AND Rifampin 300 mg q8h IV/PO for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg q8h IV/PO.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- 9. Surgical site infections
- Preferred regimen: Vancomycin 15 mg/kg IV q12h with or without Rifampin 300 mg q8h IV/PO OR Gentamicin 3 mg/kg/day IV q8h added to Vancomycin AND Rifampin 300 mg q8h IV/PO for prosthetic valve IE.
- Alternative regimen (methicillin resistent Staphylococcus epidermidis) (1): Linezolid 600 mg IV/PO bd OR Daptomycin IV 6 mg/kg/day with or without Rifampin 300 mg q8h IV/PO.
- Alternative regimen (methicillin-sensitive Staphylococcus epidermidis) (2): (Oxacillin 1.5-3 g IV q6h OR Nafcillin 1.5-3 g IV q6h), OR Cefazolin 1-2 g IV q8h OR Ciprofloxacin 400 mg IV q12h OR Clindamycin 600 mg IV q8h OR Trimethoprim-Sulfamethoxazole.
- Staphylococcus lugdunensis
- 1. Postpartum mastitis with or without abscess [28]
- Preferred regimen: In outpatient is Dicloxacillin 500 mg po qid OR Cephalexin 500 mg po qid and in inpatient is Oxacillin OR Nafcillin 2 gm IV q4h
- Alternative regimen: In outpatient is Trimethoprim-Sulfamethoxazole-DS tabs 1-2 po bid or, if susceptible, Clindamycin 300 mg po qid and in inpatient is Vancomycin 1 gm IV q12h; if over 100 kg, 1.5 gm IV q12h.
- 2. Non-puerperal mastitis with abscess
- Preferred regimen: In outpatient is Dicloxacillin 500 mg po qid OR Cephalexin 500 mg po qid and in inpatient is Oxacillin OR Nafcillin 2 gm IV q4h
- Alternative regimen: In outpatient is Trimethoprim-Sulfamethoxazole-DS tabs 1-2 po bid or, if susceptible, Clindamycin 300 mg po qid and in inpatient is Vancomycin 1 gm IV q12h; if over 100 kg, 1.5 gm IV q12h.
- Staphylococcus saprophyticus
- 1. Urinary tract infection [29]
- 1.1 Acute uncomplicated urinary tract infection (cystitis-urethritis) in females
- Preferred regimen : Cephalosporin PO OR Amoxicillin-Clavulanate 625 mg PO OR Trimethoprim-Sulfamethoxazole-DS bid for 3 days; if sulfa allergy, Nitrofurantoin 100 mg po bid for 5 days OR Fosfomycin 3 gm po as a single dose AND Pyridium.
- Alternative regimen (in sulfa allergy): then 3 days of Ciprofloxacin 250 mg bid OR Ciprofloxacin-Erythromycin 500 mg q24h OR Levofloxacin 250 mg q24h OR Moxifloxacin 400 mg q24h OR Nitrofurantoin 100 mg bid OR Fosfomycin single 3 gm dose AND Phenazopyridine Pyridium 200 mg po tid times 2 days.
- 1.2 Recurrent urinary tract infection in postmenopausal women
- Preferred regimen : Trimethoprim-Sulfamethoxazole-DS bid for 3 days; if sulfa allergy, Nitrofurantoin 100 mg po bid for 5 days OR Fosfomycin 3 gm po as a single dose AND Pyridium.
- Alternative regimen (in sulfa allergy): then 3 days of Ciprofloxacin 250 mg bid OR Ciprofloxacin-Erythromycin 500 mg q24h OR Levofloxacin 250 mg q24h OR Moxifloxacin 400 mg q24h OR Nitrofurantoin 100 mg bid OR Fosfomycin single 3 gm dose AND Phenazopyridine Pyridium 200 mg po tid times 2 days.
- Streptococci
- Streptobacillus moniliformis
- Streptococcus moniliformis treatment[30]
- 1. Migratory arthropathy and arthritis
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 2. Diarrhea, (especially kids) liver or spleen abscess
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 3. Undifferentiated fever
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 4. Endocarditis, myocarditis, pericarditis (cardiac)
- Preferred regimen: Penicillin 20 MU/day IV divided q4h. Optimal duration recommendation for infective endocarditis is 4 weeks.
- Alternative regimen: Cephalosporins-Ceftriaxone OR Clindamycin OR Erythromycin OR Chloramphenicol AND Streptomycin.
- 5. Meningitis, brain abscess
- Preferred regimen: Penicillin 20 MU/day IV divided q4h.
- Alternative regimen: Cephalosporins-Ceftriaxone OR Clindamycin OR Erythromycin OR Chloramphenicol AND Streptomycin.
- 6. Anemia
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 7. Pneumonia
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 8. Amnionitis (pregnancy)
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 9. Renal abscess
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- Streptococcus anginosus
Group comprises 3-15% of streptococcal isolates of endocarditis. See Diagnosis section for Endocarditis module for management, follow viridans Streptococci recommendations.
Dental abscesses, sinusitis, fasciitis of head and neck: can be life threatening and require aggressive surgical management. See appropriate HEENT module for specific management.
Bacteremia often associated with deep-seated abscess. Investigate for abscess—most often intraabdominal. Drainage is usually recommended.
Brain abscesses often polymicrobial, but S. intermedius found in 50-80%. See Brain abscess module for management.
Implicated in aspiration pneumonia, lung abscess and empyema.
- Preferred regimen: Penicillin G 2-4 MU IV q4h .
- Alternative regimen: Ceftriaxone 2 g IV qd; Clindamycin 600-900 mg IV q8h or 300-450 mg PO qid OR Vancomycin 15 mg/kg IV q12h ([[Penicillin-allergic).
- Streptococcus pneumoniae
- Streptococcus pneumonia treatment[31]
- 1. Lung (pneumonia)
- Community-acquired pneumonia
- Penicillin sensitive (minimum inhibitory concentration ≤ 2)
- Preferred regimen: Penicillin G 1-2 MU q6h IV OR Ceftriaxone 2 g IV q24h OR Cefotaxime 1-2 g IV q6-8h.
- Penicillin-resistant (Penicillin minimum inhibitory concentration >8)
- Preferred regimen:: Levofloxacin (Levaquin) 750 mg OR Moxifloxacin (Avelox) 400 mg IV/PO q24h, Telithromycin (Ketek) 800 mg PO qd, Ceftriaxone IV, Cefotaxime IV, Vancomycin 15 mg/kg IV q12h OR Linezolid 600 mg IV/PO q12h.
- 2. Sinuses (sinusitis)
- Sinusitis (empiric therapy)
- Preferred regimen: amoxicillin 500-1000 mg PO tid OR Amoxicillin/Clavulanate 875/125 mg PO bd.
- 3. Middle ear (otitis media)
- (4)Bronchi (acute exacerbation of chronic bronchitis)
- Preferred regimen: amoxicillin 2-3 PO g/day OR Doxycycline 100 mg PO bd.
- (5)CNS (meningitis)
- Empiric therapy
- In age group of 1 months– 50 years
Adult dosage: (Cefotaxime 2 gm IV q4–6h OR Ceftriaxone 2 gm IV q12h) AND Dexamethasone AND Vancomycin 15 mg/kg/day IV q12h
- Preferred regimen: Vancomycin 15 mg/kg/day IV q12h AND Ceftriaxone 2 g IV q12h OR Cefotaxime 2 g IV q4h or 3 g q6h.
- Penicillin sensitive (minimum inhibitory concentration ≤ 0.06)
- Preferred regimen: Ceftriaxone 2 g IV q12h, OR Cefotaxime 2 g IV q4h or 3 g IV q6h.
- Penicillin resistant (minimum inhibitory concentration ≥ 0.12) or beta-lactam hypersensitivity
- Preferred regimen: Vancomycin 30-45 mg/kg/day IV.
- (6)Peritoneum (spontaneous bacterial peritonitis)
- (7)Pericardium (purulent pericarditis)
- (8)Skin (cellulitis)
- (9)Eye (conjunctivitis)
- Streptococcus pyogenes[32]
- (1) Pharyngitis
- Preferred regimen: Penicillin-benzathine]] Penicillin 1.2 mU IM once OR Penicillin VK 500 mg PO bd or tid for 10 days.
- Alternative regimen (1): Amoxicillin 750 PO bd or tid for 10 days.
- Alternative regimen (Penicillin allergy): Erythromycin 500 mg PO bd or tid for 10 days OR (Azithromycin 500 mg, then 250 mg for 5 days, Clarithromycin (Biaxin) 1 g XR/day or 500 mg bd for 10 days. Note: 5-10% isolates are macrolide resistant) OR Cefpodoxime proxetil (Vantin) 200 mg bd for 5 days OR Cefdinir 300 mg bd PO for 5 days OR Cefadroxil 500 mg bd PO for 5 days OR Loracarbef 200 mg PO bd for 5 days.
- (2) Skin: erysipelas, lymphangitis, cellulitis
- Preferred regimen: Clindamycin 600 mg IV q8h AND Penicillin G G 4 mU IV q4h. (clindamycin to stop toxin production).
- Alternative regimen: Penicillin G 2-4 mU IV q4h OR Clindamycin 600 mg IV q8h OR Cefazolin 1-2 g IV q6-8h OR Cefotaxime 2-3 g IV q6-8h OR Ceftriaxone 2 g/day IV OR Vancomycin 15 mg/kg IV q12h.
- (3) Soft tissue
- Necrotizing fasciitis: surgical consultation for emergent fasciotomy and debridement; repeat debridements usually necessary.
- (4) Muscle
- Myositis: debirdement
- (5) Endometrium
- (6) Puerperal sepsis
- (7) Lung
- pneumonia with or without early bloody effusion Bacteremia
- (8) Cardiac are endocarditis (very rare in antibiotic era)
- (9) Toxin mediated
- Scarlet fever
- Toxic shock syndrome
- Preferred regimen: Immunoglobulin-G 2 or more doses IV , massive IV fluids (10-20 L/day), Albumin if <2 g/dL, debridement of necrotic tissue.
- (10)Non-suppurative complications are rheumatic fever and glomerulonephritis
- Prophylaxis
- Acute rheumatic fever prophylaxis
- Preferred regimen: Benzathine Penicillin 1.2 mu IM q mo, Penicillin V 250 mg PO bd, Erythromycin 250 mg PO bd until >5 yrs post-acute rheumatic fever and age in 20years.
- Recurrent cellulitis, chronic lymphedema prophylaxis
- Preferred regimen: Clindamycin 150 mg PO qd OR Trimethoprim-Sulfamethoxaole 1 DS PO qd OR “stand-by therapy” immediate treatment with Penicillin V OR Amoxicillin 500-750 mg PO bd at onset of symptoms.
- Streptococcus agalactiae
### Bacteria – Gram-Positive Bacilli
- Actinomyces israelii
- Arcanobacterium haemolyticum
- Bacillus
- Bacillus anthracis, treatment
- (A) Treatment for cutaneous anthrax, without systemic involvement[33]
- Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown): Ciprofloxacin 500 mg PO q12h OR Doxycycline 100 mg PO q12h OR Levofloxacin 750 mg PO q24h OR Moxifloxacin 400 mg PO q24h
- Alternative regimen: Clindamycin 600 mg PO q8h OR Amoxicillin 1 g PO q8h (for penicillin-susceptible strains) OR Penicillin VK 500 mg PO q6h (for penicillin-susceptible strains)
- (B) Treatment for systemic anthrax including anthrax meningitis, inhalational anthrax, injectional anthrax, and gastrointestinal anthrax; and cutaneous anthrax with systemic involvement, extensive edema, or lesions of the head or neck[33]
- (B-1) Systemic anthrax with possible/confirmed meningitis
- (1) Bactericidal agent (fluoroquinolone): Ciprofloxacin 400 mg IV q8h (OR Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h) AND
- (2) Bactericidal agent (β-lactam) for all strains, regardless of penicillin susceptibility or if susceptibility is unknown: Meropenem 2 g IV q8h OR Imipenem 1 g IV q6h OR Doripenem 500 mg IV q8h OR Penicillin G 4 MU IV q4h (for penicillin-susceptible strains) OR Ampicillin 3 g IV q6h (for penicillin-susceptible strains) AND
- (3) Protein synthesis inhibitor: Linezolid 600 mg IV q12h OR Clindamycin 900 mg IV q8h OR Rifampin 600 mg IV q12h OR Chloramphenicol 1 g IV q6-8h
- (B-2) Systemic anthrax when meningitis has been excluded
- (1) Bactericidal agent: Ciprofloxacin 400 mg IV q8h OR Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg q24h OR Meropenem 2 g IV q8h OR Imipenem 1 g IV q6h OR Doripenem 500 mg IV q8h OR Vancomycin 20 mg/kg IV q8h (maintain serum trough concentrations of 15-20 µg/mL) OR Penicillin G 4 MU IV q4h (penicillin-susceptible strains) OR Ampicillin 3 g IV q6h (penicillin-susceptible strains) AND
- (2) Protein synthesis inhibitor: Clindamycin 900 mg IV q8h OR Linezolid 600 mg IV q12h OR Doxycycline 200 mg IV initially, then 100 mg IV q12h OR Rifampin 600 mg IV q12h
- Specific considerations
- Treatment of anthrax for pregnant Women
- (A) Intravenous antimicrobial treatment for systemic anthrax with possible/confirmed meningitis [34]
- (1) A Bactericidal Agent (Fluoroquinolone): Ciprofloxacin 400 mg IV q8h is preferred, OR Levofloxacin 750 mg IV q24h, OR
- (2). A Bactericidal Agent (β-lactam)
- (a). For all strains, regardless of penicillin susceptibility or if susceptibility is unknown : Meropenem 2 g q8h,OR
- (b). Alternatives for penicillin-susceptible strains: Ampicillin 3 g IV q6h,OR Penicillin G 4 million units IV q4h, OR
- (3). A Protein Synthesis Inhibitor: Clindamycin 900 IV mg q8h,OR Rifampin 600 IV mg q12h
- (B) Intravenous antimicrobial treatment for systemic anthrax when meningitis has been excluded
- (1). A Bactericidal Antimicrobial: Ciprofloxacin 400 mg IV q8h is preferred, OR Levofloxacin 750 mg IV q24h, OR
- (2). A Bactericidal Agent (β-lactam)
- (a). For all strains, regardless of penicillin susceptibility or if susceptibility is unknown : Meropenem 2 g q8h,OR
- (b). Alternatives for penicillin-susceptible strains:Ampicillin 3 g IV q6h,OR Penicillin G 4 million units IV q4h, OR
- (3). A Protein Synthesis Inhibitor:Clindamycin 900 IV mg q8h,OR Rifampin 600 IV mg q12h
- (C) Oral antimicrobial treatment for cutaneous anthrax without systemic involvement
- (a).For all strains, regardless of penicillin susceptibility or if susceptibility is unknown: Ciprofloxacin 400 mg IV q8h is preferred.
- Treatment for anthrax in children [35]
- (1). Treatment of cutaneous anthrax without systemic involvement (for children 1 month of age and older)
- (A). For all strains, regardless of penicillin susceptibility or if susceptibility is unknown : Ciprofloxacin, 30 mg/kg/day, by mouth (PO), divided q12h (not to exceed 500 mg/dose) OR Doxycycline, <45 kg: 4.4 mg/kg/day, PO, divided q12h (not to exceed 100 mg/dose) ≥45 kg: 100 mg/dose, PO, given q12h OR Clindamycin, 30 mg/kg/day, PO, divided q8h (not to exceed 600 mg/dose) OR Levofloxacin <50 kg: 16 mg/kg/day, PO, divided q12h (not to exceed 250 mg/dose) >50 kg: 500 mg, PO, given q24h OR
- (B). Alternatives for penicillin-susceptible strains: Amoxicillin, 75 mg/kg/day, PO, divided q8h (not to exceed 1 g/dose) OR Penicillin VK, 50-75 mg/kg/day, PO, divided q6h to q8h
- (2). Combination therapy for systemic anthrax when meningitis can be ruled out (for children 1 month of age and older)
- (A). A bactericidal antimicrobial
- (a). For all strains, regardless of penicillin susceptibility or if susceptibility is unknown: Ciprofloxacin, 30 mg/kg/day, intravenously (IV), divided q8h (not to exceed 400 mg/dose) OR Meropenem, 60 mg/kg/day, IV, divided q8h (not to exceed 2 g/dose) OR Levofloxacin <50 kg: 20 mg/kg/day, IV, divided q12h (not to exceed 250 mg/dose >50 kg: 500 mg, IV, q24h OR Imipenem/Cilastatin,a 100 mg/kg/day, IV, divided q6h (not to exceed 1 g/dose) OR Vancomycin, 60 mg/kg/day, IV, divided q8h (follow serum concentrations)
- (b). Alternatives for penicillin-susceptible strains: Penicillin G, 400 000 U/kg/day, IV, divided q4h (not to exceed 4 MU/dose) OR Ampicillin, 200 mg/kg/day, IV, divided q6h (not to exceed 3 g/dose) AND
- (B). A Protein Synthesis Inhibitor: Clindamycin, 40 mg/kg/day, IV, divided q8h (not to exceed 900 mg/dose) OR Linezolid (non-CNS infection dose): <12 y old: 30 mg/kg/day, IV, divided q8h ≥12 y old: 30 mg/kg/day, IV, divided q12h (not to exceed 600 mg/dose) OR Doxycycline <45 kg: 4.4 mg/kg/day, IV, loading dose (not to exceed 200 mg); ≥45 kg: 200 mg, IV, loading dose then <45 kg: 4.4 mg/kg/day, IV, divided q12h (not to exceed 100 mg/dose); ≥45 kg: 100 mg, IV, given q12h OR Rifampin,d 20 mg/kg/day, IV, divided q12h (not to exceed 300 mg/dose)
- (3).Triple therapy for systemic anthrax (anthrax meningitis or disseminated infection and meningitis cannot be ruled out) for Children 1 Month of Age and Older
- (A). A bactericidal antimicrobial (fluoroquinolone): Ciprofloxacin, 30 mg/kg/day, intravenously (IV), divided q8h (not to exceed 400 mg/dose)OR Levofloxacin <50 kg: 16 mg/kg/day, IV, divided q12h (not to exceed 250 mg/dose); >50 kg: 500 mg, IV, q24h OR Moxifloxacin 3 months to <2 years: 12 mg/kg/day, IV, divided q12h (not to exceed 200 mg/dose)
- (B). A bactericidal antimicrobial (β-lactam or glycopeptide)
- (a). For all strains, regardless of penicillin susceptibility testing or if susceptibility is unknown : Meropenem, 120 mg/kg/day, IV, divided q8h (not to exceed 2 g/dose) OR Imipenem/Cilastatin, 100 mg/kg/day, IV, divided q6h (not to exceed 1 g/dose) OR Doripenem, 120 mg/kg/day, IV, divided q8h (not to exceed 1 g/dose) OR Vancomycin, 60 mg/kg/day, IV, divided q8h
- (b). Alternatives for penicillin-susceptible strains: Penicillin G, 400 000 U/kg/day, IV, divided q4h (not to exceed 4 MU/dose) OR Ampicillin, 400 mg/kg/day, IV, divided q6h (not to exceed 3 g/dose) AND
- (C). A Protein Synthesis Inhibitor: Linezolid <12 y old: 30 mg/kg/day, IV, divided every 8 h≥12 y old: 30 mg/kg/day, IV, divided q12h (not to exceed 600 mg/dose) OR Clindamycin, 40 mg/kg/day, IV, divided q8h (not to exceed 900 mg/dose) OR Rifampin, 20 mg/kg/day, IV, divided q12h (not to exceed 300 mg/dose) OR Chloramphenicol, 100 mg/kg/day, IV, divided q6h
- (4).Oral follow-up combination therapy for severe anthrax (for Children 1 Month of Age and Older)
- (A). A bactericidal antimicrobial
- (B). A protein synthesis inhibitor: Clindamycin 30 mg/kg/day, PO, divided q8h (not to exceed 600 mg/dose) OR Doxycycline <45 kg: 4.4 mg/kg/day, PO, divided q12h (not exceed 100 mg/dose) ≥45 kg: 100 mg, PO, given q12h OR Linezolid (non-CNS infection dose):
- (5). Dosing in preterm and term neonates 32 to 44 Weeks postmenstrual Age (Gestational Age Plus Chronologic Age)
- (A). Triple therapy for severe anthrax(anthrax meningitis or disseminated infection and meningitis cannot be ruled out)
- (1). Bactericidal antimicrobial (fluoroquinolone) therapy
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (2). A bactericidal antimicrobial (β-lactam)
- a. For all strains, regardless of penicillin susceptibility or if susceptibility is unknown :
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- b. Alternatives for penicillin-susceptible strains
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (3).A protein synthesis inhibitor
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (B). Therapy for severe anthrax when meningitis can be ruled out
- (1).A bactericidal antimicrobial
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (2).A protein synthesis inhibitor
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (C). Oral follow-up combination therapy for severe anthrax
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (D).Treatment of cutaneous anthrax without systemic involvement
- (1).For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (2).Alternatives for penicillin-susceptible strains
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- Bacillus anthracis, postexposure prophylaxis
- For adults[33]
- (1) For all strains, regardless of penicillin susceptibility or if susceptibility is unknown: Ciprofloxacin, 500 mg q12h OR Doxycycline, 100 mg q12h OR Levofloxacin, 750 mg q24h OR Moxifloxacin, 400 mg q24h OR Clindamycin, 600 mg q8h OR
- (2) Alternatives for penicillin-susceptible strain Amoxicillin, 1 g q8h OR Penicillin VK, 500 mg q6h
- For children ≥ 1 month[35]
- (1) For penicillin-resistant strains or prior to susceptibility testing: Ciprofloxacin, 30 mg/kg/day, by mouth (PO), divided q12h (not to exceed 500 mg/dose) OR Doxycycline, <45 kg: 4.4 mg/kg/day, PO, divided q12h (not to exceed 100 mg/dose) >45 kg: 100 mg/dose, PO, given q12h OR Clindamycin, 30 mg/kg/day, PO, divided q8h (not to exceed 900 mg/dose) OR Levofloxacin, <50 kg: 16 mg/kg/day, PO, divided q12h (not to exceed 250 mg/dose) >50 kg: 500 mg, PO, given q24h OR
- (2) For penicillin-susceptible strains: Amoxicillin, 75 mg/kg/day, PO, divided every q8h (not to exceed 1 g/dose) OR Penicillin VK, 50-75 mg/kg/day, PO, divided q6h to q8h
- For children < 1 month
- (1) For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- (2) Alternatives for penicillin-susceptible strains
- (a) For 32–34 weeks gestational age
- (b) For 34–37 week gestational age
- (c) Term Newborn Infant
- Bacillus cereus
- Bacillus cereus [36]
- (1) Food poisoning
- Preferred treatment: Food poisoning is self-limited, no antibiotics necessary. Treatment is Supportive therapy, hydration, and anti-emetics. Prevention is by fried/boiled rice should be maintained >60° C or rapidly cooled <8 ° C to avoid room temperature germination of spores and toxin.
- (2) Bacteremia
- Preferred regimen: Vancomycin 15 mg/kg IV q12h.
- Alternative regimen: Clindamycin 600 mg IV q8h
- (3) Meningitis, brain abscess
- Preferred regimen: Vancomycin 15 mg/kg IV q12h.
- Alternative regimen: Clindamycin 600 mg IV q8h.
- (4) Endophthalmitis
- Preferred regimen: Clindamycin 450 mcg intravitreal AND Gentamicin 400 mcg intravitreal OR Dexamethasone intravitreal AND Vancomycin 15 mg/kg IV q12h.
- Alternative regimen: Clindamycin 600 mg IV q8h
- (5) Endocarditis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h OR Clindamycin 600 mg IV q8h.
- (6) Soft tissue
- Preferred regimen: Vancomycin 15 mg/kg IV q12h.
- Alternative regimen: Clindamycin 600 mg IV q8h.
- (7) Pneumonia
- Preferred regimen: Vancomycin 15 mg/kg IV q12h.
- Alternative regimen: Clindamycin 600 mg IV q8h.
- Bacillus subtilis[37][38][39]
- 1. Food poisoning
- Preferred regimen: supportive treatment
- 2. Other infections
- Preferred regimen: Vancomycin OR Clindamycin
- Alternative regimen: Ciprofloxacin OR Imipenem
- Clostridium
- Clostridium botulinum
- Clostridium difficile
- Clostridium perfringens
- Clostridium tetani
- Corynebacterium
- Corynebacterium diphtheriae
- Diphtheria treatment
- Antitoxin
- Preferred regimen: 20,000-40,000 U pharyngeal disease <48 hrs; 40-60,000 U nasopharyngeal; 80-120,000 U for extensive disease, brawny neck or sx >72 hrs; Adiminister IV (severe disease) or IM
- Antibiotics:
- Preferred regimen: Procaine Penicillin G (<20 lbs: 300,000 U; >20 lbs: 600,000 U) IM q12h until patient can swallow then Penicillin VK 125-250 mg PO QID OR Erythromycin 125-500 mg PO QID for 14 days total.
- Alternative regimen (1): Erythromycin 20-25mg/kg IV q6h (max 4g/day; β-lactam allergic patients)
- Alternative regimen (2): Clindamycin 600 mg IV q8h
- C. diphtheriae carrier
- Preferred regimen: Erythromycin 250-500 mg PO QID
- Alternative regimen: Benzathine Penicillin G 600,000-1,200,000 units IM single dose
- Endocarditis treatment
- Preferred regimen: Penicillin G OR Ampicillin IV for 4-6 weeks ± Aminoglycoside
- Corynebacterium jeikeium
- Corynebacterium urealyticum
- Coxiella burnetii
- Adults:
- Preferred Regimen: DoxycyclinePO 100 mg bid for 14 days
- Children
- Children with age ≥8 years:
- Preferred regimen:Doxycycline PO 2.2 mg/kg per dose bid for 14 days (maximum 100 mg per dose)
- children with age <8 years with high risk criteria
- Preferred regimen:Doxycycline PO 2.2 mg/kg per dose bid for 14 days (maximum: 100 mg per dose)
- children with age < 8 years with mild or uncomplicated illness:
- Preferred regimen:Doxycycline PO 2.2 mg/kg per dose bid for 5 days (maximum 100 mg per dose). If patient remains febrile past 5 days of treatment: Trimethoprim/Sulfamethoxazole 4-20 mg/kg bid for 14 days (maximum: 800 mg per dose)
- Pregnant women
- Preferred regimen: Trimethoprim/sulfamethoxazole PO 160 mg/800 mg bid a day throughout pregnancy
- Endocarditis or vascular infection
- Preferred regimen:Doxycycline PO 100 mg bid and hydroxychloroquine PO 200 mg tid for ≥18 months
- Note: childern and pregnant women- consultation Recommended
- Noncardiac organ disease
- Preferred regimen: Doxycycline PO 100 mg bid and hydroxychloroquine PO 200 mg tid
- Note: childern and pregnant women- consultation Recommended
- Postpartumwith serologic profile for chronic Q fever
- Preferred regimen:Doxycycline PO 100 mg bid and hydroxychloroquine PO 200 mg tid for 12 months
- Note: Women should only be treated postpartum if serologic titers remain elevated >12 months after delivery (immunoglobulin G phase I titer ≥1:1024). Women treated during pregnancy for acute Q fever should be monitored similarly to other patients who are at high risk for progression to chronic disease (e.g., serologic monitoring at 3, 6, 12, 18, and 24 months after delivery)
- Note:Post-Q fever fatigue syndrome- no current recommendation
- Ehrlichia
- Human Monocytic Ehrlichiosis or Human Granulocytic Anaplasmosis (adult) [41]
- Preferred regimen: Doxycycline 100 mg PO/IV q12h for 7-14 days
- NOTE: Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement
- Alternative regimen: Chloramphenicol 500mg QID OR Rifampin 600 mg PO/IV daily for 7-10 days
- Human Monocytic Ehrlichiosis or Human Granulocytic Anaplasmosis (pediatric)
- ≥8 years old
- Preferred regimen: Doxycycline 2 mg/kg IV/PO q12h (max 200 mg/day) for 10 days
- <8 years old without Lyme disease
- Preferred regimen: Doxycycline 2 mg/kg IV/PO q12h (max 200 mg/day) for 4-5 days (or 3 days after resolution of fever)
- co-infected with Lyme disease
- Preferred regimen: At the conclusion of Doxycycline then give Amoxicillin 50 mg/kg in 3 divided doses (max 500 mg/dose) OR Cefuroxime 30 mg/kg in 2 divided doses (max 500 mg/dose) for 14 days
- Erysipelothrix rhusiopathiae
- Erysipeloid of Rosenbach (localized cutaneous infection)[42]
- Preferred regimen (1): Penicillin G benzathine 1.2 MU IV as a single dose
- Preferred regimen (2): Penicillin VK 250 mg PO qid for 5-7 days
- Preferred regimen (3): Procaine penicillin 0.6-1.2 MU IM qd for 5-7 days
- Alternative regimen (1): Erythromycin 250 mg PO qid for 5-7 days
- Alternative regimen (2): Doxycycline 100 mg PO bid for 5-7 days
- Diffuse cutaneous infection
- Preferred regimen: As for localized infection
- Bacteremia or endocarditis
- Preferred regimen: Penicillin G benzathine 2-4 MU IV q4h for 4-6 weeks
- Alternative regimen (1): Ceftriaxone 2 g IV q24h for 4-6 weeks
- Alternative regimen (2): Imipenem 500 mg IV q6h for 4-6 weeks
- Alternative regimen (3): Ciprofloxacin 400 mg IV q12h for 4-6 weeks
- Alternative regimen (4): Daptomycin 6 mg/kg IV q24h for 4-6 weeks
- Listeria monocytogenes
- Meningitis [43]
- Preferred regimen: Ampicillin 2g IV q4-6h ± Gentamicin 1.7 mg/kg IV q8h for more than 3 weeks
- Alternative regimen: TMP-SMX 3-5 mg/kg (trimethoprim) q6h IV for more than 3 weeks
- Bacteremia
- Preferred regimen: Ampicillin 2g IV q4-6h ± Gentamicin 1.7 mg/kg IV q8h for 2 weeks
- Alternative regimen: TMP-SMX 3-5 mg/kg (trimethoprim) q6h IV for 2 weeks
- Brain abscess or rhomboencephalitis
- Preferred regimen: Ampicillin 2g IV q4-6h ± Gentamicin 1.7 mg/kg IV q8h for 4-6 weeks
- Alternative regimen: TMP-SMX 3-5 mg/kg (trimethoprim) q6h IV for 4-6 weeks
- Gastroenteritis
- Preferred regimen: Amoxicillin OR TMP-SMX for 7 days
- Lactobacillus
- Endovascular Infection [44]
- Preferred regiemn (1): Penicillin G 20 Million units/day for 6 weeks
- Preferred regiemn (2): Gentamicin 1.3 mg/kg IV q8h (trough <1.5 mg/L) AND Polychlorinated naphthalene
- Odontogenic Infection
- Preferred regiemn: Clindamycin 450 mg PO q6h
- Intrabdominal Abscess
- Preferred regiemn: Clindamycin 450 mg PO q6h
- Leuconostoc
- Preferred regimen: Penicillin G OR Ampicillin
- Alternative regimen: Clindamycin OR Erythromycin OR Minocycline
- Nocardia
- Sulfonamide-based therapies [45]
- Pulmonary
- Preferred regimen: TMP-SMX 10 mg/kg/day (TMP) in 2-4 doses IV for 3-6 weeks, then PO (2 DS BID) for >5 months
- Pulmonary alternatives
- Preferred regimen: Sulfisoxazole OR Sulfadiazine OR Trisulfapyrimidine 3-6 g/day PO 2- 4 doses OR TMP-SMX 2 DS twice daily up to 2 DS TID
- CNS (AIDS, severe or disseminated disease)
- Preferred regimen: TMP-SMX 15 mg/kg/day (TMP) IV for 3-6 weeks, then PO (3 DS BID) for 6-12 months
- CNS alternatives
- Preferred regimen: Imipenem 1000 mg IV q8h OR Ceftriaxone 2 g IV q12h OR Cefotaxime 2-3 g IV q6h AND Amikacin
- Severe disease, compromised host, multiple sites
- Preferred regimen: TMP-SMX IV (above doses) AND Amikacin 7.5 mg/kg q12h (adjust per levels) OR Sulfonamide PO 6-12 m/day
- Sporotrichoid (cutaneous)
- Preferred regimen: TMP-SMX 1 DS BID for 4-6 months
- NOTE(1): Immunocompetent medicine use for 6 months; Immunosuppressed medicine for 12 months
- NOTE(2): Treat based on host, site of disease and in vitro activity; Sulfonamide usually preferred, must treat for 6-12 months; Preferred drugs for resistant strains are Amikacin and/or Imipenem
- NOTE(3): Seriously ill usually treated with IV Imipenem or Sulfonamide or Cefotaxime all potentially combined with Amikacin; less seriously ill treated with oral agents— especially TMP-SMX or Minocycline
- Sulfonamide alternatives
- Severe
- Preferred regimen(1): (AIDS) (Imipenem 1000mg IV q8h OR Meropenem (CNS) 2g q8h) AND Amikacin 7.5 mg/kg q12h IV
- Preferred regimen(2): Cefotaxime 2-3g q6-8h OR Ceftriaxone 2 g/day IV ± Amikacin
- Mild
- Preferred regimen: Minocycline 100 mg BID for > 6 months (initial treatment of local disease or maintenance)
- Alternative regimen: Amoxicillin/Clavulanate 875/125 mg BID OR Doxycycline OR Erythromycin OR Clarithromycin OR Linezolid OR Fluoroquinolone OR combinations for >6 months
- Propionibacterium acnes
- Systemic infection[46]
- Preferred regimen: Penicillin G 2 MU IV q4h for 2-4 weeks
- Alternative regimen: Clindamycin 600 mg IV q8h for 2-4 weeks OR Vancomycin 15 mg/kg IV q12h for 2-4 weeks
- Shoulder prosthesis infection
- Preferred regimen: Amoxicillin AND Rifampin for 3-6 months
- Acne vulgaris
- Topical antibiotics: Erythromycin OR Clindamycin
- Systemic antibiotics: Minocycline OR Doxycycline OR Trimethoprim-Sulfamethoxazole
- Rhodococcus equi
- Rhodococcus equi [47]
- Preferred regimen:
- First line: vancomycin 1 g IV q12h (15 mg/kg q12 for >70 kg) OR Imipenem 500 mg IV q6h AND Rifampin 600 mg PO once daily OR Ciprofloxacin 750 mg PO twice daily OR Erythromycin 500 mg PO four times a day for at least 4 weeks or until infiltrate disappears (at least 8 weeks in immunocompromised patients)
- Oral/maintenance therapy (after infiltrate clears): Ciprofloxacin 750 mg PO twice daily OR Erythromycin 500 mg PO four times a day
- Alternative regimen: Azithromycin OR TMP-SMX OR Chloramphenicol OR Clindamycin
- NOTE: Avoid Penicillins/Cephalosporins due to development of resistance; Linezolid effective in vitro, but no clinical reports of use
- Rickettsia
- Rickettsia rickettsii [48]
- Preferred regimen: Doxycycline 200 mg load (severe disease) and then 100 mg PO/IV BID for 3-7 days after defervescence
- Alternative regimen: Chloramphenicol 500 mg PO QID for 3-7 days after defervescence
- Pediatric regimen: Doxycycline 2-4 mg/kg/day (up to 200 mg/day) q12h OR Tetracycline 25-50 mg/kg/day PO in 4 divided doses OR Chloramphenicol 50-75 mg/kg/day PO in 4 divided doses
### Bacteria – Gram-Negative Cocci and Coccobacilli
- Aggregatibacter aphrophilus
- Bordetella pertussis
- Brucella
- Eikenella corrodens
- Haemophilus ducreyi
- Chancroid Treatment [49]
- Preferred Regimen: Azithromycin 1 g PO in a single dose OR Ceftriaxone 250 mg IM in a single dose OR Ciprofloxacin 500 mg PO bid for 3 days OR Erythromycin base 500 mg PO three tid for 7 days
- Note(1): Regardless of whether symptoms of the disease are present, sex partners of patients who have chancroid should be examined and treated if they had sexual contact with the patient during the 10 days preceding the patient’s onset of symptoms.
- Note(2):Persons with HIV infection might require repeated or longer courses of therapy, and treatment failures can occur with any regimen.
- Haemophilus influenzae
- Neisseria gonorrhoeae
- Neisseria gonorrhoeae, treatment[50]
- 1. Gonococcal infections in adolescents and adults
- 1.1 Uncomplicated gonococcal infections of the cervix, urethra, and rectum
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- Alternative regimen: Cefixime 400 mg PO in a single dose AND Azithromycin 1 g PO in a single dose (if ceftriaxone is not available)
- 1.2 Uncomplicated gonococcal infections of the pharynx
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.2.1 Management of sex partners
- Expedited partner therapy: Cefixime 400 mg PO in a single dose AND Azithromycin 1 g PO in a single dose
- 1.2.2 Allergy, intolerance, and adverse reactions
- Preferred regimen (1): Gemifloxacin 320 mg PO in a single dose AND Azithromycin 2 g PO in a single dose
- Preferred regimen (2): Gentamicin 240 mg IM in a single dose AND Azithromycin 2 g PO in a single dose
- 1.2.3 Pregnancy
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.2.4 Suspected cephalosporin treatment failure
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Gemifloxacin 320 mg PO single dose AND Azithromycin 2 g PO single dose (when isolates have elevated cephalosporin MICs)
- Alternative regimen (2): Gentamicin 240 mg IM single dose AND Azithromycin 2 g PO single dose (when isolates have elevated cephalosporin MICs)
- Alternative regimen (3): Ceftriaxone 250 mg IM as a single dose AND Azithromycin 2 g PO as a single dose (failure after treatment with cefixime and azithromycin)
- 1.3 Gonococcal conjunctivitis
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.3.1 Management of sex partners
- Patients should be instructed to refer their sex partners for evaluation and treatment.
- 1.4 Disseminated gonococcal infection
- 1.4.1 Arthritis and arthritis-dermatitis syndrome
- Preferred regimen: Ceftriaxone 1 g IM/IV q24h for 7 days AND Azithromycin 1 g PO in a single dose
- Alternative regimen: Cefotaxime 1 g IV q8h for 7 days OR Ceftizoxime 1 g IV q 8 h for 7 days AND Azithromycin 1 g PO in a single dose
- 1.4.2 Gonococcal meningitis and endocarditis
- Preferred regimen : Ceftriaxone 1-2 g IV q 12-24 h for 10-14 days AND Azithromycin 1 g PO in a single dose
- 2. Gonococcal infections among neonates
- 2.1 Ophthalmia neonatorum caused by N. gonorrhoeae
- Preferred regimen: Ceftriaxone 25-50 mg/kg IV or IM in a single dose, not to exceed 125 mg
- 2.1.1 Management of mothers and their sex partners
- Mothers of infants with ophthalmia neonatorum caused by N. gonorrhoeae should be evaluated, tested, and presumptively treated for gonorrhea, along with their sex partner(s).
- 2.2 Disseminated gonococcal infection and gonococcal scalp abscesses in neonates
- Preferred regimen: Ceftriaxone 25-50 mg/kg/day IM/IV qd for 7 days OR Cefotaxime 25 mg/kg IV /IM q12h for 7 days.
- 2.2.1 Management of mothers and their sex partners
- Mothers of infants who have DGI or scalp abscesses caused by N. gonorrhoeae should be evaluated, tested, and presumptively treated for gonorrhea, along with their sex partner(s).
- 2.3 Neonates born to mothers who have gonococcal infection
- Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg
- 2.3.1 Management of mothers and their sex partners
- Mothers who have gonorrhea and their sex partners should be evaluated, tested, and presumptively treated for gonorrhea.
- 3. Gonococcal infections among infants and children
- 3.1 Infants and children who weigh ≤ 45 kg and who have uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis
- Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg
- 3.2 Children who weigh > 45 kg and who have uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1g PO in a single dose
- Alternative regimen: Cefixime 400 mg PO single dose AND Azithromycin 1 g PO single dose.(If ceftriaxone is not available)
- 3.3 Children who weigh ≤ 45 kg and who have bacteremia or arthritis
- Preferred regimen: Ceftriaxone 50 mg/kg (maximum dose: 1 g) IM/IV q24h for 7 days
- 3.4 Children who weigh > 45 kg and who have bacteremia or arthritis
- Preferred regimen: Ceftriaxone 1 g IM/IV q24h for 7 days
- Neisseria gonorrhoeae, prophylaxis[51]
- 1. Ophthalmia neonatorum
- Preferred regimen: Erythromycin 0.5% ophthalmic ointment in each eye in a single application at birth
- Alternative regimen: Ceftriaxone 25–50 mg/kg IV/IM in a single dose, not to exceed 125 mg (if erythromycin ointment is not available)
- Neisseria meningitidis
- Meningococcal Meningitis or Bacteremia [52]
- Antimicrobials:
- Preferred regimen : Ceftriaxone 2 g IV q24h OR Cefotaxime 2 g IV q4-6h for 7-10 days.
- Alternatives regimen (1): Chloramphenicol 4-6 g/day for 7-10 days
- Alternatives regimen (2): Penicillin 18-24 MU/day IV
- Alternatives regimen (3): Ampicillin 12 g/day IV
- Alternatives regimen (4): Aztreonam 6-8 g/day IV OR moxifloxacin 400 mg/day IV.
- Steroids: Dexamethasone 10 mg IV q6h for 2-4 days starting before or with first dose.
- Moraxella catarrhalis
- Pasteurella multocida
### Bacteria – Spirochetes
- Borrelia
- Borrelia burgdorferi
- Lyme disease
- Early Lyme Disease
- Erythema migrans
- Preferred regimen: Doxycycline 100 mg twice per day for 10-21 days OR Amoxicillin 500 mg 3 times per day for 14-21 days OR Cefuroxime axetil 500 mg twice per day for 14-21 days
- Alternatie regimen: : Azithromycin 500 mg PO per day for 7–10 days OR Clarithromycin 500 mg PO twice per day for 14–21 days (if the patient is not pregnant) OR Erythromycin 500 mg PO 4 times per day for 14–21 days
- Pediatric regimen (1): (children <8 years of age) Amoxicillin 50 mg/kg per day in 3 divided doses [maximum of 500 mg per dose] OR Cefuroxime axetil 30 mg/kg per day in 2 divided doses （maximum of 500 mg per dose)
- Pediatric regimen (2):（children ≥8 years of age）Doxycycline 4 mg/kg per day in 2 divided doses（maximum of 100 mg per dose）
- Pediatric regimen (3): Azithromycin 10 mg/kg per day (maximum of 500 mg per day) OR Clarithromycin 7.5 mg/kg twice per day (maximum of 500 mg per dose) OR Erythromycin 12.5 mg/kg 4 times per day (maximum of 500 mg per dose)
- When erythema migrans cannot be reliably distinguished from community-acquired bacterial cellulitis
- Preferred regimen: Amoxicillin–clavulanic acid 500 mg 3 times per day;
- Pediatric regimen；Amoxicillin–clavulanic acid 50 mg/kg per day in 3 divided doses (maximum of 500 mg per dose)
- Lyme meningitis and other manifestations of early neurologic Lyme disease
- Preferred regimen: Ceftriaxone 2g once per day IV for 10–28 days
- Alternative regimen (1): Cefotaxime 2 g IV q8h OR Penicillin G 18–24 million U q4h per day for patients with normal renal function
- Alternative regimen (2): Doxycycline 200–400 mg per day in 2 divided doses PO for 10–28 days
- Pediatric regimen (1): Ceftriaxone 50–75 mg/kg per day in a single daily intravenous dose (maximum, 2g)
- Pediatric regimen (2): Cefotaxime 150–200 mg/kg per day divided into 3 or 4 intravenous doses per day (maximum, 6 g per day)
- Pediatric regimen (3): Penicillin G 200,000–400,000 units/kg per day (maximum, 18–24 million U per day) divided into doses given intravenously q4h for those with normal renal function
- Pediatric regimen (4): (≥8 years old) Doxycycline 4–8 mg/kg PO per day in 2 divided doses (maximum, 100–200 mg per dose)
- Lyme carditis
- Preferred regimen: Ceftriaxone 2g once per day IV for 10–28 days
- NOTE: patients with advanced heart block, a temporary pacemaker may be required; expert consultation with a cardiologist is recommended; Use of the pacemaker may be discontinued when the advanced heart block has resolved; An oral antibiotic treatment regimen should be used for completion of therapy and for outpatients, as is used for patients with erythema migrans without carditis (see above)
- Borrelial lymphocytoma
- Preferred regimen: The same regimens used to treat patients with erythema migrans (see above)
- Late Lyme Disease
- Lyme arthritis
- Preferred regimen: Doxycycline 100 mg twice per day OR Amoxicillin 500 mg 3 times per day
- Alternative regimen: Cefuroxime axetil 500 mg twice per day for 28 days
- Pediatric regimen: Amoxicillin 50 mg/kg per day in 3 divided doses (maximum of 500 mg per dose) OR Cefuroxime axetil 30 mg/kg per day in 2 divided doses (maximum of 500 mg per dose) OR (≥8 years of age) Doxycycline 4 mg/ kg per day in 2 divided doses (maximum of 100 mg per dose)
- NOTE: For patients who have persistent or recurrent joint swelling after a recommended course of oral antibiotic therapy, we recommend re-treatment with another 4-week course of oral antibiotics or with a 2–4-week course of Ceftriaxone IV
- patients with arthritis and objective evidence of neurologic disease
- Preferred regimen: Ceftriaxone IV for 2–4 weeks
- Alternative regimen: Cefotaxime OR Penicillin G IV
- Pediatric regime: Ceftriaxone OR Cefotaxime OR Penicillin G IV
- Late neurologic Lyme disease
- Preferred regimen: Ceftriaxone IV for 2 to 4 weeks
- Alternative regimen: Cefotaxime OR Penicillin G IV
- Pediatric regimen: Ceftriaxone OR Cefotaxime OR Penicillin G
- Acrodermatitis chronica atrophicans
- Preferred regimen: Doxycycline 100 mg twice per day OR Amoxicillin 500 mg 3 times per day OR Cefuroxime axetil 500 mg twice per day for 21 days
- Post–Lyme Disease Syndromes
- Preferred regimen: Further antibiotic therapy for Lyme disease should not be given unless there are objective findings of active disease (including physical findings, abnormalities on cerebrospinal or synovial fluid analysis, or changes on formal neuropsychologic testing)
- Borrelia recurrentis
- Tick-Borne Relapsing Fever [53]
- Preferred regimen: Doxycycline 100 mg PO twice daily for 5-10 days
- Alternative regimen: Erythromycin 500 mg PO four times a day for 5-10 days
- NOTE: If meningitis/encephalitis present, use Ceftriaxone 2 g IV q12h for 14 days
- Louse-Borne Relapsing Fever
- Preferred regimen: single dose Tetracycline 500 mg PO
- Alternative regimen: single dose Erythromycin 500 mg PO
- Leptospira
- Treatment
- Severe [54] [55]
- Preferred regimen: Penicillin 1.5 million units IV q6hr for 5-7 days
- Less severe
- Preferred regimen: Amoxycillin OR Ampicillin OR Doxycycline 100 mg BID IV or PO for 5-7 days OR Erythromycin OR Ceftriaxone 1g IV per day for 5-7 days OR Cefotaxime OR Quinolone PO
- Prophylaxis
- Leptospira interrogans [56]
- Preferred regimen: Doxycycline 200 mg PO once per week
- Treponema pallidum
- Syphilis Among non-HIV-Infected Persons[57]
- Primary and Secondary Syphilis
- Preferred regimen (adult): Benzathine penicillin G 2.4 million units IM in a single dose
- Preferred regimen (pediatric): Benzathine penicillin G 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose
- Latent Syphilis
- Early Latent Syphilis
- Preferred regimen: Benzathine penicillin G 2.4 million units IM in a single dose
- Pediatric regimen: Benzathine penicillin G 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose
- Late Latent Syphilis or Latent Syphilis of Unknown Duration
- Preferred regimen: Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervalspediatric
- Pediatric regimen: Benzathine penicillin G 50,000 units/kg IM, up to the adult dose of 2.4 million units, administered as 3 doses at 1-week intervals (total 150,000 units/kg up to the adult total dose of 7.2 million units)
- Tertiary Syphilis
- Preferred regimen: Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals
- Neurosyphilis and ocular syphilis
- Preferred regimen: Aqueous crystalline penicillin G 18--24 million units per day, administered as 3--4 million units IV every 4 hours or continuous infusion, for 10--14 days
- Alternative regimen: Procaine penicillin 2.4 million units IM once daily AND Probenecid 500 mg orally four times a day, both for 10--14 days
- Syphilis Among HIV-Infected Persons
- Primary and Secondary Syphilis Among HIV-Infected Persons
- Preferred regimen: Benzathine penicillin G 2.4 million units IM in a single dose.
- Latent Syphilis Among HIV-Infected Persons
- early latent
- Preferred regimen: Benzathine penicillin G 2.4 million units IM in a single dose.
- late latent
- Preferred regimen: Benzathine penicillin G at weekly doses of 2.4 million units for 3 weeks.
- Neurosyphilis Among HIV-Infected Persons
- Preferred regimen: Aqueous crystalline penicillin G 18--24 million units per day, administered as 3--4 million units IV every 4 hours or continuous infusion, for 10--14 days
- Alternative regimen: Procaine penicillin 2.4 million units IM once daily AND Probenecid 500 mg orally four times a day, both for 10--14 days
- Syphilis During Pregnancy
- Preferred regimen: Pregnant women should be treated with the penicillin regimen appropriate for their stage of infection
- Congenital Syphilis in neonates
- condition 1 : Infants with proven or highly probable disease and (1)an abnormal physical examination that is consistent with congenital syphilis;（2）a serum quantitative nontreponemal serologic titer that is fourfold higher than the mother's titer;¶ or（3）a positive darkfield test of body fluid(s).
- Preferred regimen: Aqueous crystalline penicillin G 100,000--150,000 units/kg/day, administered as 50,000 units/kg/dose IV every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days OR Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days
- NOTE: If more than 1 day of therapy is missed, the entire course should be restarted. Data are insufficient regarding the use of other antimicrobial agents (e.g., ampicillin). When possible, a full 10-day course of penicillin is preferred, even if ampicillin was initially provided for possible sepsis. The use of agents other than penicillin requires close serologic follow-up to assess adequacy of therapy. In all other situations, the maternal history of infection with T. pallidum and treatment for syphilis must be considered when evaluating and treating the infant.
- condition 2: Infants who have a normal physical examination and a serum quantitive nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1)mother was not treated, inadequately treated, or has no documentation of having received treatment; (2)mother was treated with erythromycin or another nonpenicillin regimen;†† or (3)mother received treatment < 4 weeks before delivery.
- Preferred regimen: Aqueous crystalline penicillin G 100,000--150,000 units/kg/day, administered as 50,000 units/kg/dose IV every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days OR Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days OR Benzathine penicillin G 50,000 units/kg/dose IM in a single dose
- NOTE:If the mother has untreated early syphilis at delivery, 10 days of parenteral therapy can be considered.
- condition 3:Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1)mother was treated during pregnancy, treatment was appropriate for the stage of infection, and treatment was administered >4 weeks before delivery and (2)mother has no evidence of reinfection or relapse.
- Preferred regimen: Benzathine penicillin G 50,000 units/kg/dose IM in a single dose
- condition 4: Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1)mother's treatment was adequate before pregnancy and (2)mother's nontreponemal serologic titer remained low and stable before and during pregnancy and at delivery (VDRL <1:2; RPR <1:4).
- Preferred regimen: No treatment is required; however, benzathine penicillin G 50,000 units/kg as a single IM injection might be considered, particularly if follow-up is uncertain.
- Congenital Syphilis in infants and children
- Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg q4–6h for 10 days
### Bacteria – Gram-Negative Bacilli
- Enteric flora
- Aeromonas hydrophila
- Preferred regimen: (consider if not self-limiting, or if severe), Ciprofloxacin 500 mg PO BID.
- Alternate regimen: TMP-SMX single dose PO BID
- Preferred regimen (mild infection) : Ciprofloxacin 500 mg PO BID OR Levofloxacin 500 mg OD.
- Preferred regimen (severe infection) or sepsis: Ciprofloxacin 400 mg IV q8h OR Levofloxacin 750 mg IV q24
- Citrobacter koseri
- Preferred regimen: Ceftriaxone 1-2 g IV q12-24 OR Cefotaxime 1-2 g IV q6h OR Cefepime 1-2 IV q8h.
- Alternate regimen: Ciprofloxacin 400 mg IV q12h (or 500 mg PO q12h for UTI)OR Imipenem 1 g IV q6h OR Doripenem 500 mg IV q8h OR Meropenem 1-2 g IV q8h OR Aztreonam 1-2 g IV q6hOR TMP-SMX 5 mg/kg q6h IV (or DS PO twice daily for UTI).
- Citrobacter freundii
- Preferred regimen: Meropenem 1-2 g IV q8h OR Imipenem 1 g IV q6h OR Doripenem 500 mg IVq8hOR Cefepime 1-2 g IV q8h, Ciprofloxacin 400 mg IV q12h(or 500 mg PO twice daily for UTI) OR Gentamicin 5 mg/kg/day.
- Alternate regimen: Piperacillin/tazobactam 3.375 mg q6h IV OR Aztreonam 1-2 g IV q6h OR TMP-SMX 5 mg/kg q6h IV (or DS PO twice daily for UTI).
- Enterobacter cloacae
- UTI
- Preferred regimen: Ciprofloxacin 250 mg PO bid
- Enterobacter aerogenes
- UTI
- Preferred regimen: Ciprofloxacin 250 mg PO bid
- Escherichia coli
- 1.Meningitits
- 1.1.Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- 1.2.Alternative regimen: Aztreonam 6–8 g/day IV q6–8h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h OR Meropenem 6 g/day IV q8h OR Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h OR Ampicillin 12 g/day IV q4h
- 2.Uncomplicated urinary tract infection
- 2.1.Preferred agents (IDSA/AUA Guidelines): TMP-SMX DS PO bid for 3-day
- 2.2.Alternative regimen(1): Ciprofloxacin 250 mg PO bid OR Ciprofloxacin 500 mg XR once daily for 3 days OR Levofloxacin 250 mg PO OD for 3 days.
- 2.3.Alternative regimen(2): Nitrofurantoin 100 mg PO q6h OR Nitrofurantoin macrocrystals (Macrobid) 100 mg PO bid for 7 days.
- 2.4.Alternative regimen(3): Fosfomycin 3 g sachet PO single dose.
- 3.Pyelonephritis
- 3.1.1.Acute uncomplicated pyelonephritis
- Preferred regimen: Ciprofloxacin 500 mg bid PO for 5-7 days OR Ciprofloxacin-Erythromycin 1000 mg q24h OR Levofloxacin 750 mg q24h OR Ofloxacin 400 mg bid, Moxifloxacin 400 mg q24h
- Alternative regimen: Amoxicillin-Clavulanic acid875/125 mg PO q12h or 500/125 mg PO tid or 1000 /125 mg PO bid OR Oral Cephalosporins OR TMP-SMX 2 mg/kg IV q6h PO for 14 days
- 3.1.2.Acute pyelonephritis (Hospitalized)
- Preferred regimen: Ciprofloxacin 400 mg IV q12h OR (Ampicillin Gentami-cin) OR Piperacillin-Tazobactam 3.375 gm IV q4-6h for 14 days.
- Alternative regimen: Ticarcillin-Clavulanate3.1 gm IV q6h or Ampicillin-Salbactam 3 gm IV q6h or Piperacillin-Tazobactam 3.375 gm IV q4-6h OR Ertapenem 1 gm IV q24h or Doripenem 500 mg q8h for 14 days.
- 4.Traveler’s diarrhea
- Preferred regimen : Ciprofloxacin 750 mg PO OD for 1-3 days or other Fluoroquinolones
- Pediatrics & pregnancy: Azithromycin 10 mg/kg/day single dose OR Ceftriaxone 50 mg/kg/day IV OD for 3 days.
- 5.Malacoplakia
- Bethanechol chloride AND (Ciprofloxacin 400 mg IV q12h OR TMP-SMX 2 mg/kg (TMP component) IV q6h)
- 6.Bacteremia/Pneumonia
- Preferred regimen : Ceftriaxone 1-2g IV q24h OR other third or fourth generation cephalosporin OR Ciprofloxacin 400mg IV q12h or 500mg PO q12h OR Levofloxacin 500mg PO/IV q24h OR Moxifloxacin 400mg IV/PO q24h OR Ampicillin(if sensitive) 2g IV q6h OR TMP-SMX(if sensitive) 5-10mg/kg/day for q6-8hIV
- Alternative regimen : Imipenem, Meropenem, Ertapenem, Doripenem, Ceftazidime, Cefepime, Cefazolin or Cefuroxime(ifsensitive), Aztreonam, Ticarcillin, Piperacillin, Piperacillin-Tazobactam, Aminoglycosides, Tigecycline(intra-abdorskin/softtissue).
- Alternative regimen : Ampicillin-sulbactam 3g IV q6h ANDGentamicin 1.5mg/kg/q8h or 5-7mg/kg/dayIV OR Gentamicin 5mg/kg/day OR Tobramycin 5mg/kg/dayIV for 7-14days
- Klebsiella pneumoniae
- Aspiration Pneumonia
- Preferred regimen : Piperacillin-Tazobactam 3.375 gm IV q6h or 4-hr infusion of 3.375 gm q8h
- Alternate regimen : (Ceftriaxone 1 gm IV q24h AND Metronidazole 500 mg IV q6h or 1 gm IV q12h) OR Moxifloxacin 400 mg IV/po q24h
- Klebsiella rhinoscleromatis
- Morganella morganii
- Proteus vulgaris
- Providencia
- Salmonella
- Serratia marcescens
- Shigella
- Non-fermenters
- Acinetobacter baumannii
- Achromobacter xylosoxidans
- Bordetella pertussis
- Burkholderia cepacia
- Burkholderia pseudomallei
- Stenotrophomonas maltophilia
- Elizabethkingia meningoseptica
- Moraxella catarrhalis
- Bartonella
- Campylobacter
- Campylobacter fetus
- Campylobacter jejuni
- Capnocytophaga
- Francisella tularensis
- Helicobacter pylori
- Legionella
- Plesiomonas shigelloides
- Pseudomonas aeruginosa
- Vibrio
- Vibrio cholerae
- Vibrio parahaemolyticus
- Vibrio vulnificus
### Bacteria – Atypical Organisms
- Chlamydophila pneumoniae
- 1. Pneumonia[58]
- 1.1 Adult
- Preferred regimen (1): Doxycycline 100 mg PO bid for 14-21 days
- Preferred regimen (2): Tetracycline 250 mg PO qid for 14-21 days
- Preferred regimen (3): Azithromycin 500 mg PO as a single dose, followed by 250 mg PO qd for 4 days
- Preferred regimen (4): Clarithromycin 500 mg PO bid for 10 days
- Preferred regimen (5): Levofloxacin 500 mg IV or PO qd for 7 to 14 days
- Preferred regimen (6): Moxifloxacin 400 mg PO qd for 10 days.
- 1.2 Pediatric
- Preferred regimen (1):Erythromycin suspension,PO 50 mg/kg/day for 10 to 14 days
- Preferred regimen (2):Clarithromycin suspension, 15 mg/kg/day for 10 days
- Preferred regimen (3): Azithromycin suspension, PO 10 mg/kg once on the first day, followed by 5 mg/kg qd daily for 4 days
- 2.Upper respiratory tract infection[59]
- Bronchitis
- Antibiotic therapy for C. pneumoniae is not required.
- Pharyngitis
- Antibiotic therapy for C. pneumoniae is not required.
- Sinusitis
- Antibiotic therapy is advisable if symptoms remain beyond 7-10 days.
- Chlamydia trachomatis
- Chlaymydial infections [60]
- 1. Chlamydial Infections in Adolescents and Adults
- Preferred regimen : Doxycycline 100 mg PO bid for 7 days OR Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days OR Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (2): Levofloxacin 500 mg PO qd for 7 days OR Ofloxacin 300 mg PO bid for 7 days.
- Note: Patients should be instructed to refer their sex partners for evaluation, testing, and treatment if they had sexual contact with the patient during the 60 days preceding onset of the patient's symptoms or chlamydia diagnosis.
- 1.1 Chlamydial Infections in patients with HIV Infection
- Preferred regimen : Doxycycline 100 mg PO bid for 7 days OR Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days OR Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (2): Levofloxacin 500 mg PO qd for 7 days OR Ofloxacin 300 mg PO bid for 7 days.
- 1.2Pregancy
- Preferred regimen :Azithromycin 1 g PO in a single dose
- Alternative regimen (1):Amoxicillin 500 mg PO tid for 7 days
- Alternative regimen (2):Erythromycin base 500 mg PO qid for 7 days OR Erythromycinbase 250 mg PO qid for 14 days
- Alternative regimen (3):Erythromycin ethylsuccinate 800 mg PO qid for 7 days OR Erythromycin ethylsuccinate 400 mg PO four qid for 14days
- Note:Doxycycline, Ofloxacin, and Levofloxacin are contraindicated in pregnant women.
- 2 Chlamydial infection among neonates
- 2.1 Ophthalmia Neonatorumcaused by C. trachomatis
- Preferred regimen :Erythromycin base or ethylsuccinate ,PO 50 mg/kg/ day divided into 4 doses daily for 14 days
- Alternative regimen : Azithromycin suspension, PO 20 mg/kg /day qd for 3 days
- Note: The mothers of infants who have chlamydial infection and the sex partners of these women should be evaluated and treated.
- 2.2Infant Pneumonia
- Preferred regimen :Erythromycin base or ethylsuccinate PO 50 mg/kg/ day divided into 4 doses daily for 14 days
- Alternative regimen : Azithromycin suspension, PO 20 mg/kg /day qd for 3 days
- 3.Chlamydial infection among infants and childern
- 3.1 Infants and childern who weigh < 45 kg
- Preferred regimen :Erythromycin base or ethylsuccinate PO 50 mg/kg/ day divided into 4 doses daily for 14 days
- 3.2 Infants and childern who weigh ≥45 kg but who are aged <8 years
- Preferred regimen :Azithromycin 1 g PO in a single dose
- 3.3 Infants and childern aged ≥8 years
- Preferred regimen :Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
- Lymphogranuloma venereum (LGV)
- Lymphogranuloma venereum (LGV) is caused by C. trachomatis serovars L1, L2, or L3[61]
- Preferred regimen : Doxycycline 100 mg PO bid for 21 days
- Alternative regimen: Erythromycin base 500 mg PO qid for 21 days
- Note (1): azithromycin 1 g orally once weekly for 3 weeks is probably effective based on its chlamydial antimicrobial activity. Fluoroquinolone-based treatments might also be effective, but extended treatment intervals are likely required.
- Note (2): Patients should be followed clinically until signs and symptoms have resolved.
- Note (2): Pregnant and lactating women should be treated with erythromycin. Azithromycin might prove useful for treatment of LGV in pregnancy, but no published data are available regarding its safety and efficacy. Doxycycline is contraindicated in pregnant women.
- Note (3): Persons with both LGV and HIV infection should receive the same regimens as those who are HIV negative. Prolonged therapy might be required, and delay in resolution of symptoms might occur.
- Note(4): Persons who have had sexual contact with a patient who has LGV within the 60 days before onset of the patient’s symptoms should be examined and tested for urethral, cervical, or rectal chlamydial infection depending on anatomic site of exposure. They should be presumptively treated with a chlamydia regimen ( Azithromycin 1 g PO single dose OR Doxycycline 100 mg PO bid for 7 days).
- Chlamydophila psittaci
- 1. Pneumonia[62]
- 1.1 Adult
- Preferred regimen : Doxycycline 100 mg PO bid daily OR Tetracycline 500 mg PO qid for 10-21 days
- Alternative regimen :Minocycline
- 1.2 Pediatric
- Preferred regimen: Azithromycin
- Alternative regimen: fluoroquinolones
- 1.3 Pregnant Patients
- Preferred regimen : Azithromycin
- Alternative regimen: fluoroquinolones
- 2.Endocarditis in valve replacement patients
- Preferred regimen : Doxycycline
- Alternative regimen : fluoroquinolones.
- Coxiella burnetii
- Q fever [63]
- 1.Acute Q fever
- 1.1 Adults:
- Preferred Regimen: DoxycyclinePO 100 mg bid for 14 days
- 1.2 Children
- 1.2.1Children with age ≥8 years:
- Preferred regimen:Doxycycline PO 2.2 mg/kg per dose bid for 14 days (maximum 100 mg per dose)
- 1.2.2 children with age <8 years with high risk criteria
- Preferred regimen:Doxycycline PO 2.2 mg/kg per dose bid for 14 days (maximum: 100 mg per dose)
- 1.2.3 children with age <8 years with mild or uncomplicated illness:
- Preferred regimen:Doxycycline PO 2.2 mg/kg per dose bid for 5 days (maximum 100 mg per dose). If patient remains febrile past 5 days of treatment: Trimethoprim/Sulfamethoxazole 4-20 mg/kg bid for 14 days (maximum: 800 mg per dose)
- 1.3 Pregnant women
- Preferred regimen: Trimethoprim/Sulfamethoxazole PO 160 mg/800 mg bid a day throughout pregnancy
- 2. Chronic Q fever
- 2.1 Endocarditis or vascular infection
- Preferred regimen:Doxycycline PO 100 mg bid and Hydroxychloroquine PO 200 mg tid for ≥18 months
- Note: childern and pregnant women- consultation Recommended
- 2.2 Noncardiac organ disease
- Preferred regimen: Doxycycline PO 100 mg bid and Hydroxychloroquine PO 200 mg tid
- Note: childern and pregnant women- consultation Recommended
- 2.3 Postpartumwith serologic profile for chronic Q fever
- Preferred regimen:Doxycycline PO 100 mg bid and Hydroxychloroquine PO 200 mg tid for 12 months
- Note: Women should only be treated postpartum if serologic titers remain elevated >12 months after delivery (immunoglobulin G phase I titer ≥1:1024). Women treated during pregnancy for acute Q fever should be monitored similarly to other patients who are at high risk for progression to chronic disease (e.g., serologic monitoring at 3, 6, 12, 18, and 24 months after delivery)
- Note:Post-Q fever fatigue syndrome- no current recommendation
- Legionella
- Legionella pneumonia (atypical bacterial pneumonia) [64]
- Preferred Regimen: Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h OR Azithromycin 500 mg PO on day 1 followed by 250 mg q24h
- Alternate Regimen: Doxycycline 100 mg PO/IV q12h
- Mycoplasma pneumoniae
- Atypical pneumonia caused by Mycoplasma pneumoniae[65]
- Preferred regimen (1): Azithromycin 500 mg PO day 1 and 250 mg day 2 to 5
- Preferred regimen (2): Doxycycline 100 mg PO bid for 14 days
- Preferred regimen (3): Moxifloxacin 400 mg PO qd for 14 days
- Mycoplasma genitalium
- 1.Urethritis and cervicitis caused due to Mycoplasma Genitalium[66]
- Preferred regimen: Azithromycin 1 g PO single dose
- Note(1): Resistant strains -Azithromycin PO in 500 mg single dose followed by 250 mg qd for 4 days
- Note(2): previous treatment failures- Moxifloxacin PO 400 mg qd for 7, 10 or 14 days) has been successfully used to treat both men and women
- 2. PID caused due to Mycoplasma Genitalium
- Preferred regimen: Moxifloxacin PO 400 mg/day for 14 days
### Bacteria – Miscellaneous
- Gardnerella vaginalis
- Eikenella corrodens
- Human bite/soft tissue infections [67]
- Severe
- Preferred regimen: Ampicillin/Sulbactam 1.5-3 g IV q6h
- Alternative regimen: Doxycycline 100 mg IV BID OR Moxifloxacin 400 mg IV OD OR Levofloxacin 500 mg IV OD
- Mild
- Preferred regimen: Amoxicillin/Clavulanate 250-500 mg TID or 875/125 mg PO BID
- Alternative regimen: Doxycycline 100 mg PO BID OR Moxifloxacin 400 mg PO OD OR Levofloxacin 500 mg PO OD
- Head and neck infections
- Severe
- Preferred regimen: Ampicillin/Sulbactam 1.5-3 g IV q6h
- Alternative regimen: Doxycycline 100 mg IV BID OR Moxifloxacin 400 mg IV OD OR Levofloxacin 500 mg IV OD
- Mild
- Preferred regimen: Amoxicillin/Clavulanate 250-500 mg TID or 875/125 mg PO BID
- Alternative regimen: Doxycycline 100 mg PO BID OR Moxifloxacin 400 mg PO OD OR Levofloxacin 500 mg PO OD
- Endocarditis
- Preferred regimen: Ceftriaxone 1g IV q12h OR Cefotaxime 1-2 g IV q8h OR Cefepime 1-2g IV q8h
- Bordetella pertussis
- Bartonella
- Stenotrophomonas maltophilia
- Acinetobacter baumannii
- Preferred regimen: Imipenem (Primaxin) 0.5-1 g IV q6h OR Ampicillin/sulbactam (Unasyn) 3g q4h OR Cefepime (Maxipime) 1-2 g IV q8h OR Colistin 2.5 mg/kg IV q12h OR Tigecycline (Tygacil) 100 mg IV, then 50 mg IV q12h OR Amikacin 7.5 mg/kg q12h IV or 15 mg/kg/day IV
- Alternative regimen: Ceftriaxone 1-2g IV every day OR Cefotaxime 2-3g IV q6-8h OR Ciprofloxacin (Cipro) 400 mg IV q8-12h or 750 mg PO BID OR TMP-SMX 15-20 mg (TMP)/kg/day IV divided 3 or 4 doses/day or 2 DS PO BID
### Bacteria – Anaerobic Gram-Negative Bacilli
- Bacteroides fragilis
- Monotherapy [68]
- Preferred regimen: Imipenem (Primaxin) OR Ertapenem OR Meropenem OR Doripenem 0.5-1.0 g IV q6h OR Piperacillin-tazobactam (Zosyn) 3.375 g IV q6h OR Ampicillin-sulbactam (Unasyn) 1-2 g IV q6h OR Tigecycline (Tygacil) 100 mg IV, then 50 mg IV q12h
- Combination therapy
- Preferred regimen: Metronidazole 0.75-1.0 g IV q12h AND Cefotaxime 1.5-2 g IV q6h OR Aztreonam 1-2 g IV q8h OR Ceftriaxone 1 g IV q12h
- Fusobacterium necrophorum
### Fungi
- Aspergillosis
- Blastomycosis[69]
- 1.Mild to moderate pulmonary blastomycosis
- Preferred regimen: Itraconazole 200 mg PO once or twice per day for 6–12 months
- Note: Oral Itraconazole, 200 mg 3 times per day for 3 days and then once or twice per day for 6–12 months, is recommended
- 2.Moderately severe to severe pulmonary blastomycosis
- Preferred regimen(1): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg per day for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
- Preferred regimen(2): Amphotericin B deoxycholate 0.7–1 mg/kg per day for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
- Note: Oral Itraconazole, 200 mg 3 times per day for 3 days and then 200 mg twice per day, for a total of 6–12 months, is recommended
- 3.Mild to moderate disseminated blastomycosis
- Preferred regimen: Itraconazole 200 mg PO once or twice per day for 6–12 months
- Note(1): Treat osteoarticular disease for 12 months
- Note(2): Oral Itraconazole, 200 mg 3 times per day for 3 days and then 200 mg twice per day, for a total of 6–12 months, is recommended
- 4.Moderately severe to severe disseminated blastomycosis
- Preferred regimen(1): Lipid amphotericin B(Lipid AmB) 3–5 mg/kg per day, for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
- Preferred regimen(2): Amphotericin B deoxycholate 0.7–1 mg/kg per day, for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
- Note: oral Itraconazole, 200 mg 3 times per day for 3 days and then 200 mg twice per day, for a total of 6–12 months, is recommended
- 5.CNS disease
- Preferred regimen: Lipid amphotericin B (Lipid AmB) 5 mg/kg per day for 4–6 weeks AND an oral azole for at least 1 year
- Note(1): Step-down therapy can be with Fluconazole, 800 mg per day OR Itraconazole, 200 mg 2–3 times per day OR voriconazole, 200–400 mg twice per day.
- Note(2): Longer treatment may be required for immunosuppressed patients.
- 6.Immunosuppressed patients
- Preferred regimen(1): Lipid amphotericin B (Lipid AmB), 3–5 mg/kg per day, for 1–2 weeks, AND Itraconazole, 200 mg PO bid for 12 months
- Preferred regimen(2): Amphotericin B deoxycholate, 0.7–1 mg/kg per day, for 1–2 weeks, AND Itraconazole, 200 mg PO bid for 12 months
- Note(1): Oral Itraconazole, 200 mg 3 times per day for 3 days and then 200 mg twice per day, for a total of 12 months, is recommended
- Note(2): Life-long suppressive treatment may be required if immunosuppression cannot be reversed.
- 7.Pregnant women
- Preferred regimen: Lipid amphotericin B (Lipid AmB) 3–5 mg/kg per day
- Note(1): Azoles should be avoided because of possible teratogenicity
- Note(2): If the newborn shows evidence of infection, treatment is recommended with Amphotericin B deoxycholate, 1.0 mg/kg per day
- 8.Children with mild to moderate disease
- Preferred regimen: Itraconazole 10 mg/kg PO per day for 6–12 months
- Note: Maximum dose 400 mg per day
- 9.Children with moderately severe to severe disease
- Preferred regimen(1): Amphotericin B deoxycholate 0.7–1 mg/kg per day for 1–2 weeks AND Itraconazole 10 mg/kg PO per day to a maximum of 400 mg per day for 6–12 months
- Preferred regimen(2): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg per day for 1–2 weeks AND Itraconazole 10 mg/kg PO per day to a maximum of 400 mg per day for 6–12 months
- Note: Children tolerate Amphotericin B deoxycholate better than adults do.
- Paracoccidioidomycosis[70]
- Preferred regimen(1):
- Adults Trimethoprim/sulfamethoxazole (TMP/SMX) TMP: 160-240 mg/day PO/IV, SMX: 800-1200 mg/day PO/IV divided into two doses per day
- Children Trimethoprim/sulfamethoxazole (TMP/SMX) TMP: 8-10 mg/kg PO/IV, SMX: 40-50 mg/kg PO/IV, divided into two doses per day
- Note: Treatment duration based on organ involvement:
- Minor involvement: 12 months
- Moderate involvement: 18-24 months
- Preferred regimen(2): Ketoconazole 200-400 mg/day PO for 9-12 months
- Preferred regimen(3):
- Adults: Itraconazole 600 mg/day PO for 3 days; continue 200 mg/day PO for 6-9 months
- Children: Itraconazole (<30/kg and >5 yr) 5-10 mg/kg/day PO for 6-9 months
- Preferred regimen(4): Voriconazole initial dose 400 mg PO/IV each 12 hr for one day, then 200 mg each 12 hr for 6 months
- Note: Diminish the dose to 50% if weight is <40 kg
- Preferred regimen(5): Amphotericin B deoxycholate mg/kg/day IV until patient improves and can be treated by the oral route
- Candidiasis
- Chromoblastomycosis
- Coccidioidomycosis
- Cryptococcosis
- Dermatophytosis
- Onychomycosis[71]
- Fingernail Treatment Options
- Preferred regimen: Terbinafine 250 mg PO q24h (children <20 kg: 67.5 mg/day, 20–40 kg: 125 mg/day, >40 kg: 250 mg/day) for 6 weeks OR Itraconazole 200 mg PO q24h for 3 months OR Itraconazole 200 mg PO bid for 1 week/month for 2 months OR Fluconazole 150–300 mg PO q week for 3–6 months
- Toenail Treatment Options
- Preferred regimen: Terbinafine 250 mg PO q24h (children <20 kg: 67.5 mg/day, 20–40 kg:125 mg/day, >40 kg: 250 mg/day) for 12 weeks OR Itraconazole 200 mg PO q24h for 3 months OR Itraconazole 200 mg bid for 1 week/month for 3–4 months OR Fluconazole 150–300 mg PO q week for 6–12 months
- Tinea capitis[72]
- Preferred regimen(1): Griseofulvin 10-20 mg/kg/day for minimum 6 weeks
- Preferred regimen(2): Itraconazole 4-6 mg/kg pulsed dose weekly
- Preferred regimen(3): Terbinafine if <20 kg: 62.5 mg/day, if 20-40 kg: 125 mg/day, if >40 kg: 250 mg/day
- Tinea corporis[73]
- Small, well-defined lesions
- Preferred regimen: Topical cream/ointment Terbinafine OR Miconazole OR Econazole OR Clotrimazole
- Larger lesionss
- Preferred regimen: Terbinafine 250 mg/day PO for 2 weeks OR Itraconazole 200 mg/day PO for 1 wk OR Fluconazole 250 mg PO weekly for 2-4 weeks
- Tinea pedis[74]
- Athlete's foot
- Interdigital
- Preferred regimen: Topical cream/ointment Terbinafine OR Miconazole OR Econazole OR Clotrimazole
- “Dry type”
- Preferred regimen: Terbinafine 250 mg/day PO for 2-4 weeks OR Itraconazole 400 mg/day PO for 1 week per month (repeated if necessary) OR Fluconazole 200 mg PO weekly for 4-8 weeks
- Tinea cruris
- Tinea versicolor[75]
- Preferred regimen: Ketoconazole 400 mg PO single dose OR 200 mg q24h for 7 days OR 2% cream once q24h for 2 weeks
- Alternative regimen: Fluconazole 400 mg PO single dose OR Itraconazole 400 mg PO q24h for 3–7 days
- Histoplasmosis[76]
- Acute pulmonary histoplasmosis
- Moderately severe or severe
- Preferred regimen: Lipid amphotericin B (Lipid AmB) 3.0–5.0 mg/kg daily for 1–2 weeks OR Amphotericin B deoxycholate 0.7–1.0 mg/kg daily for 1–2 weeks, followed by Itraconazole 200 mg 3 times daily for 3 days and then 200 mg twice daily, for a total of 12 weeks
- Note: Methylprednisolone 0.5–1.0 mg/kg daily IV during the first 1–2 weeks of antifungal therapy is recommended for patients who develop respiratory complications, including hypoxemia or significant respiratory distress.
- Mild to moderate
- Preferred regimen:
- For symptoms of <4 weeks, none
- For symptoms of >4 weeks, Itraconazole 200 mg PO 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks
- Chronic cavitary pulmonary histoplasmosis
- Preferred regimen: Itraconazole 200 mg PO 3 times daily for 3 days and then once or twice daily for at least 1 year
- Pericarditis
- Moderately severe to severe
- Preferred regimen(1): Prednisone 0.5–1.0 mg/kg daily (maximum, 80 mg daily) in tapering doses over 1–2 weeks
- Note(1): Itraconazole 200 mg PO 3 times daily for 3 days and then once or twice daily for 6–12 weeks is recommended if corticosteroids are administered
- Note(2): Tamponade requires drainage of pericardial fluid
- Note(3): Antifungal therapy is given to reduce possible dissemination caused by prednisone induced immunosuppression
- Mild
- Preferred regimen: Nonsteroidal anti-inflammatory agents
- Rheumatologic histoplasmosis
- severe
- Preferred regimen: Prednisone 0.5–1.0 mg/kg daily (maximum, 80 mg daily) in tapering doses over 1–2 weeks is recommended in severe cases
- Note: Itraconazole 200 mg 3 times daily for 3 days and then once or twice daily for 6–12 weeks is recommended if corticosteroids are administered
- Mild
- Preferred regimen: Nonsteroidal anti-inflammatory agents
- Note: Corticosteroids are rarely needed
- Mediastinal lymphadenitis
- Mild symptoms of <4 weeks
- Preferred regimen: None
- Symptoms of >4 weeks
- Preferred regimen: Itraconazole 200 mg 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks
- Symptoms warranting treatment
- Preferred regimen: Prednisone 0.5–1.0 mg/kg daily in tapering doses over 1–2 weeks AND Itraconazole 200 mg 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks
- Mediastinal granuloma
- Asymptomatic
- Preferred regimen: None
- Symptomatic
- Preferred regimen: Itraconazole 200 mg PO 3 times daily for 3 days and then 200 mg once or twice daily for 6–12 weeks
- Mediastinal fibrosis
- Preferred regimen: The placement of intravascular stents is recommended for selected patients with pulmonary vessel obstruction
- Note(1): Antifungal treatment is not recommended
- Note(2): Itraconazole 200 mg PO once or twice daily for 12 weeks is recommended if clinical findings cannot differentiate mediastinal fibrosis from mediastinal granuloma
- Broncholithiasis
- Preferred regimen: Antifungal treatment is not recommended
- Bronchoscopic or surgical removal of the broncholith is recommended
- Pulmonary Nodules (Histoplasmomas)
- Preferred regimen: Antifungal treatment is not recommended
- Note: Must be differentiated from malignancy
- Progressive disseminated histoplasmosis
- Moderately severe to severe
- Preferred regimen: Liposomal amphotericin B 3.0 mg/kg daily for 1–2 weeks, followed by Itraconazole 200 mg PO 3 times daily for 3 days and then 200 mg twice daily for a total of at least 12 months
- Alternative regimen: Amphotericin B deoxycholate 0.7–1.0 mg/kg daily for 1–2 weeks, followed by Itraconazole 200 mg PO 3 times daily for 3 days and then 200 mg twice daily for a total of at least 12 months
- Note: Longer treatment may be required in patients with persistent immunodeficiency
- Mild to moderate
- Preferred regimen: Itraconazole 200 mg PO 3 times daily for 3 days and then twice daily for at least 12 months.
- Note: Longer treatment may be required in patients with persistent immunodeficiency.
- CNS histoplasmosis
- Preferred regimen: Liposomal amphotericin B 5.0 mg/kg daily for a total of 175 mg/kg given over 4–6 weeks followed by Itraconazole 200 mg PO 2 or 3 times daily for at least 12 months and until resolution of CSF abnormalities, including Histoplasma antigen levels.
- Note: Blood levels of itraconazole should be obtained to ensure adequate drug exposure
- Mucormycosis
- Penicilliosis
- Sporotrichosis[77]:
- Lymphocutaneous/cutaneous
- Preferred regimen: Itraconazole 200mg PO/day
- Alternative regimen: Itraconazole 200 mg PO bid OR Terbinafine 500 mg bid OR Saturated solution potassium iodide(SSKI) with increasing doses OR Fluconazole 400–800 mg/day OR local hyperthermia
- Note(1): Treat for 2–4 weeks after lesions resolved
- Note(2): SSKI initiated at a dosage of 5 drops (using a standard eyedropper) 3 times daily, increasing as tolerated to 40–50 drops 3 times daily
- Osteoarticular
- Preferred regimen: Itraconazole 200mg PO bid for 12 months
- Alternative regimen: Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day OR Amphotericin B deoxycholate 0.7–1 mg/kg/day
- Note(1): Switch to Itraconazole after favorable response if AmB used
- Note(2): Treat for a total of at least 12 months
- Pulmonary
- Preferred regimen(1): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day for severe or life-threatening pulmonary sporotrichosis, then Itraconazole 200 mg PO bid
- Preferred regimen(2): Itraconazole 200 mg PO bid for 12 months for less severe disease
- Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/d, then Itraconazole 200 mg PO bid OR surgical removal
- Note(1): Treat severe disease with an AmB formulation followed by Itraconazole
- Note(2): Treat less severe disease with Itraconazole
- Note(3): Treat for a total of at least 12 monthsSurgery combined with amphotericin B therapy is rec- ommended for localized pulmonary disease
- Meningitis
- Preferred regimen: Lipid amphotericin B (Lipid AmB) 5 mg/kg daily for 4–6 weeks, then Itraconazole 200 mg PO bid
- Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/d, then Itraconazole 200 mg PO bid
- Note(1): Length of therapy with AmB not established, but therapy for at least 4–6 weeks is recommended.
- Note(2): Treat for a total of at least 12 months.
- Note(3): May require long-term suppression with Itraconazole.
- Disseminated
- Preferred regimen: Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day, then Itraconazole 200 mg PO bid
- Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/day, then Itraconazole 200 mg PO bid
- Note(1): Therapy with AmB should be continued until the patient shows objective evidence of improvement.
- Note(2): Treat for a total of at least 12 months.
- Note(3): May require long-term suppression with Itraconazole.
- Pregnant women
- Preferred regimen(1): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day OR Amphotericin B deoxycholate 0.7–1 mg/kg/day for severe sporotrichosis
- Preferred regimen(2): Local hyperthermia for cutaneous disease.
- Note(1): It is preferable to wait until after delivery to treat non–life-threatening forms of sporotrichosis.
- Note(2): Azoles should be avoided.
- Children
- Preferred regimen:
- Mild disease: Itraconazole 6–10 mg/kg/day (400 mg/day maximum)
- Severe disease: Amphotericin B deoxycholate 0.7 mg/kg/day followed by Itraconazole 6–10 mg/kg up to a maximum of 400 mg PO daily, as step-down therapy
- Alternative regimen: Saturated solution potassium iodide(SSKI) with increasing doses for mild disease initiated at a dosage of 1 drop (using a standard eyedropper) 3 times daily and increased as tolerated up to a maximum of 1 drop/kg or 40–50 drops 3 times daily, whichever is lowest
- Pneumocystis jiroveci
### Mycobacteria
- Mycobacterium tuberculosis
- Mycobacterium abscessus
- Mycobacterium bovis
- Mycobacterium avium-intracellulare
- Mycobacterium celatum
- Mycobacterium chelonae
- Mycobacterium foruitum
- Mycobacterium haemophilum
- Mycobacterium genavense
- Mycobacterium gordonae
- Mycobacterium kansasii
- Mycobacterium marinum
- Mycobacterium scrofulaceum
- Mycobacterium simiae
- Mycobacterium ulcerans
- Mycobacterium xenopi
- Mycobacterium leprae
### Parasites – Intestinal Protozoa
- Balantidium coli[78]
- Preferred regimen: Tetracycline 500 mg PO qid for 10 days OR Metronidazole 750 mg PO tid for 5 days OR Iodoquinol 650 mg PO tid for 20 days
- Blastocystis hominis[79]
- Preferred regimen: Metronidazole 750 mg PO tid or 1.5 g daily, for 10 days OR Trimethoprim-sulfamethoxazole One double strength tablet bid or two double strength tablets daily for 7 days OR Iodoquinol 650 mg PO tid for 20 days OR Nitazoxanide 500 mg bid for 3 days OR Paromomycin 25-35 mg/kg divided tid for 7 days
- Note(1): Treatment of asymptomatic infections is unnecessary
- Note(2): One double strength tablet contains 160 mg trimethoprim/800 mg sulfamethoxazole
- Cryptosporidium parvum
- Cryptosporidium hominis
- Cyclospora cayetanensis
- Dientamoeba fragilis[80]
- Preferred regimen: Iodoquinol 650 mg PO tid for 20d ays
- Alternative regimen: Tetracycline 500 mg PO qid for 10 days OR Metronidazole 500-750 mg PO tid for 10 days
- Entamoeba histolytica
- Giardia lamblia[81]
- Preferred regimen(1):
- Adult: Tinidazole 2 g, single dose
- Pediatric: Tinidazole 50 mg/kg, single dose (maximum, 2 g)
- Preferred regimen(2):
- Adult: Metronidazole 250 mg tid for 5-7 days
- Pediatric: Metronidazole 5 mg/kg tid for 7 days
- Preferred regimen(3):
- Adult: Nitazoxanide 500 mg bid for 3 days
- Pediatric: Nitazoxanide Age 12-47 months: 100 mg bid for 3 days and for Age 4-11 years: 200 mg bid for 3 days
- Preferred regimen(4):
- Adult: Albendazole 400 mg qd for 5 days
- Pediatric: Albendazole 15 mg/kg/day for 5-7 days (maximum, 400 mg)
- Preferred regimen(5):
- Adult: Paromomycin 500 mg tid for 5-10 days
- Pediatric: Paromomycin 30 mg/kg/day in 3 doses for 5-10 days
- Preferred regimen(6):
- Adult: Quinacrine 100 mg tid for 5-7 days
- Pediatric: Quinacrine 2 mg/kg tid for 7 days
- Preferred regimen(7):
- Adult: Furazolidone 100 mg qid for 7-10 days
- Pediatric: Furazolidone 2 mg/kg qid for 10 days
- Isospora belli
- Microsporidiosis
### Parasites – Extraintestinal Protozoa
- Primary amoebic meningoencephalitis
- Acanthamoeba
- Balamuthia mandrillaris
- Naegleria fowleri
- Babesia microti
- Leishmaniasis
- Plasmodium
- Toxoplasma gondii
- Trichomonas vaginalis
- African trypanosomiasis
- American trypanosomiasis
### Parasites – Intestinal Nematodes (Roundworms)
- Ascaris lumbricoides
- Capillaria philippinensis
- Enterobius vermicularis
- Necator americanus
- Ancylostoma duodenale
- Strongyloides stercoralis
- Trichuris trichiura
### Parasites – Extraintestinal Nematodes (Roundworms)
- Ancylostoma braziliense
- Angiostrongylus cantonensis
- Filariasis
- Onchocerciasis
- Wuchereria bancrofti
- Brugia malayi
- Gnathostoma spinigerum
- Toxocariasis
- Trichinella spiralis
### Parasites – Trematodes (Flukes)
- Clonorchis sinensis
- Dicrocoelium dendriticum
- Fasciola hepatica
- Paragonimus westermani
- Schistosomiasis
### Parasites – Cestodes (Tapeworms)
- Echinococcus
- Neurocysticercosis
- Sparganosis
### Parasites – Ectoparasites
- Body lice
- Head lice
- Pubic lice
- Scabies
- Myiasis
### Viruses
- Adenovirus
- SARS
- Cytomegalovirus
- Enterovirus D68
- Ebola virus
- Marburg virus
- Hantavirus
- Dengue virus
- West Nile virus
- Yellow Fever
- Chikungunya virus
- Hepatitis A virus
- Hepatitis B virus
- Hepatitis C virus
- Hepatitis D virus
- Hepatitis E virus
- Epstein-Barr virus
- Human herpesvirus 6
- Human herpesvirus 7
- Human herpesvirus 8 (KSHV)
- Herpes simplex virus
- Varicella-zoster virus
- Human papillomavirus
- Influenza A
- Influenza B
- Avian influenza
- Swine influenza
- Measles
- Middle East respiratory syndrome
- Paramyxovirus
- Parvovirus B19
- BK virus
- JC virus
- Rabies
- Respiratory Syncytial Virus
- Rhinovirus
- Rotavirus
- Smallpox
- HIV/AIDS | https://www.wikidoc.org/index.php/Sandbox_ID2 | |
cb60a7693a281fc649c55b4ed128661c84aceded | wikidoc | Sandbox ID3 | Sandbox ID3
# WikiDoc Infectious Disease Project — Pathogen-Based Infections
## Pathogens of Public Health Significance
## Pathogens of Clinical Significance
### Bacteria – Gram-Positive Cocci
# Enterococcus faecalis
- Enterococcus faecalis Return to Top
- 1. Bacteremia
- 1.1 Ampicillin or penicillin susceptible
- Preferred regimen (1): Ampicillin 2 g IV q4-6h
- Preferred regimen (2): Ampicillin 2 g IV q4-6h AND Gentamicin 1 mg/kg IV/IM q8h
- 1.2 Ampicillin resistant and vancomycin susceptible or penicillin allergy
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h AND Gentamicin 1 mg/kg IV/IM q8h
- Preferred regimen (2): Linezolid 600 mg IV q12h
- Preferred regimen (3): Daptomycin 6 mg/kg IV q24h
- 1.3 Ampicillin and vancomycin resistant
- Preferred regimen (1): Linezolid 600 mg IV q12h
- Preferred regimen (2): Daptomycin 6 mg/kg IV q24h
- 2. Endocarditis
- 2.1 Endocarditis in adults
- 2.1.1 Strains susceptible to penicillin, gentamicin, and vancomycin
- Preferred regimen: (Ampicillin 12 g IV q24h for 4–6 weeks OR Aqueous crystalline penicillin G sodium 18–30 MU IV q24h for 4–6 weeks) AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 4–6 weeks
- Alternative regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
- Note (1): In case of native valve endocarditis with symptoms ≤ 3 months, a 4-week course of therapy is recommended.
- Note (2): In case of native valve endocarditis with symptoms > 3 months, a 6-week course of therapy is recommended.
- Note (3): In case of prosthetic valve or other prosthetic cardiac material, a minimum of 6-week course of therapy is recommended.
- 2.1.2 Strains susceptible to penicillin, streptomycin, and vancomycin and resistant to gentamicin
- Preferred regimen: (Ampicillin 12 g IV q24h for 4–6 weeks OR Aqueous crystalline penicillin G sodium 24 MU IV q24h for 4–6 weeks) AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 4–6 weeks
- Alternate regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 6 weeks
- 2.1.3 Strains resistant to penicillin and susceptible to aminoglycoside and vancomycin
- 2.1.3.1 β Lactamase–producing strain
- Preferred regimen: Ampicillin-sulbactam 12 g IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h 6 weeks
- Alternate regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
- 2.1.3.2 Intrinsic penicillin resistance
- Preferred regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
- 2.1.4 Strains resistant to penicillin, aminoglycoside, and vancomycin
- Preferred regimen (1): (Imipenem OR Cilastatin 2 g/day IV for ≥ 8weeks) AND Ampicillin 12 g/day IV for ≥ 8 weeks
- Preferred regimen (2): Ceftriaxone sodium 4 g IV/IM q24h for ≥ 8weeks AND Ampicillin 12 g IV q24h for ≥ 8 weeks
- 2.2 Endocarditis in pediatrics
- 2.2.1 Strains susceptible to penicillin, gentamicin, and vancomycin
- Preferred regimen: (Ampicillin 300 mg/kg IV q24h for 4–6 weeks OR Penicillin 0.3 MU/kg IV q24h for 4–6 weeks) AND Gentamicin 3 mg/kg IV/IM q24h 4–6 weeks
- Note (1): In case of native valve endocarditis with symptoms ≤ 3 months, a 4-week course of therapy is recommended.
- Note (2): In case of native valve endocarditis with symptoms > 3 months, a 6-week course of therapy is recommended.
- Note (3): In case of prosthetic valve or other prosthetic cardiac material, a minimum of 6-week course of therapy is recommended.
- Alternate regimen : Vancomycin 40 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
- 2.2.2 Strains susceptible to penicillin, streptomycin, and vancomycin and resistant to gentamicin
- Preferred regimen: (Ampicillin 300 mg/kg IV q24h for 4–6 weeks OR Penicillin 0.3 MU/kg IV q24h for 4–6 weeks) AND Streptomycin 20–30 mg/kg IV/IM q24h for 4–6 weeks
- Alternate regimen: Vancomycin hydrochloride 40 mg/kg IV q24h for 6 weeks AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 6 weeks
- 2.2.3 Strains resistant to penicillin and susceptible to aminoglycoside and vancomycin
- 2.2.3.1 β Lactamase–producing strain
- Preferred regimen: Ampicillin-sulbactam 300 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
- Alternate regimen: Vancomycin 40 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
- 2.2.3.2 Intrinsic penicillin resistance
- Preferred regimen: Vancomycin 40 mg/kg IV q24h AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
- 2.2.4 Strains resistant to penicillin, aminoglycoside, and vancomycin
- Preferred regimen: Imipenem/Cilastatin 60–100 mg/kg IV q24h for ≥ 8 weeks AND Ampicillin 300 mg/kg IV q24h for ≥ 8 weeks
- Alternate regimen: Ceftriaxone 100 mg/kg IV/IM q24h AND Ampicillin 300 mg/kg IV q24h for ≥ 8 weeks
- 3. Meningitis
- 3.1 Ampicillin susceptible
- Preferred regimen: Ampicillin 12 g/day IV q4h AND Gentamicin 5 mg/kg/day IV q8h
- 3.2 Ampicillin resistant
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Gentamicin 5 mg/kg/day IV q8h
- 3.3 Ampicillin and vancomycin resistant
- Preferred regimen: Linezolid 600 mg IV q12h
- 4. Urinary tract infections
- Preferred regimen (1): Nitrofurantoin 100 mg PO q6h for 5 days
- Preferred regimen (2): Fosfomycin 3 g PO single dose
- Preferred regimen (3): Amoxicillin 875 mg to 1 g PO q12h for 5 days
- 5. Intra abdominal or wound infections
- Preferred regimen (1): Penicillin
- Preferred regimen (2): Ampicillin
- Alternative regimen (Penicillin allergy or high-level Penicillin resistance): Vancomycin
- Alternative regimen (For complicated skin-skin structure and intra-abdominal infection): Tigecycline 100 mg IV single dose and 50 mg IV q12h
- Enterococcus faecium Return to Top
- 1. Bacteremia
- 1.1 Ampicillin or penicillin susceptible
- Preferred regimen (1): Ampicillin 2 g IV q4-6h
- Preferred regimen (2): Ampicillin 2 g IV q4-6h AND Gentamicin 1 mg/kg IV/IM q8h
- 1.2 Ampicillin resistant and vancomycin susceptible or penicillin allergy
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h AND Gentamicin 1 mg/kg IV/IM q8h
- Preferred regimen (2): Linezolid 600 mg IV q12h
- Preferred regimen (3): Daptomycin 6 mg/kg IV q24h.
- 1.3 Ampicillin and vancomycin resistant
- Preferred regimen (1): Linezolid 600 mg IV q12h
- Preferred regimen (2): Daptomycin 6 mg/kg IV q24h
- 2. Endocarditis
- 2.1 Endocarditis in adults
- 2.1.1 Strains susceptible to penicillin, gentamicin, and vancomycin
- Preferred regimen: (Ampicillin 12 g IV q24h for 4–6 weeks OR Aqueous crystalline penicillin G sodium 18–30 MU IV q24h for 4–6 weeks) AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 4–6 weeks
- Alternative regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
- Alternate regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
- Note (1): In case of native valve endocarditis with symptoms ≤ 3 months, a 4-week course of therapy is recommended.
- Note (2): In case of native valve endocarditis with symptoms > 3 months, a 6-week course of therapy is recommended.
- Note (3): In case of prosthetic valve or other prosthetic cardiac material, a minimum of 6-week course of therapy is recommended.
- 2.1.2 Strains susceptible to penicillin, streptomycin, and vancomycin and resistant to gentamicin
- Preferred regimen: (Ampicillin 12 g IV q24h for 4–6 weeks OR Aqueous crystalline penicillin G sodium 24 MU/day IV q24h for 4–6 weeks) AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 4–6 weeks
- Alternate regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 6 weeks
- 2.1.3 Strains resistant to penicillin and susceptible to aminoglycoside and vancomycin
- 2.1.3.1 β Lactamase–producing strain
- Preferred regimen: Ampicillin-sulbactam 12 g IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
- Alternate regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
- 2.1.3.2 Intrinsic penicillin resistance
- Preferred regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
- 2.1.4 Strains resistant to penicillin, aminoglycoside, and vancomycin
- Preferred regimen (1): Linezolid 1200 mg IV/PO q24h ≥ 8 weeks
- Preferred regimen (2): Quinupristin-Dalfopristin 22.5 mg/kg IV q24h ≥ 8 weeks
- 2.2 Endocarditis in pediatrics
- 2.2.1 Strains susceptible to penicillin, gentamicin, and vancomycin
- Preferred regimen: (Ampicillin 300 mg/kg IV q24h for 4–6 weeks OR Penicillin 0.3MU/kg IV q24h for 4–6 weeks) AND Gentamicin 3 mg/kg IV/IM q24h 4–6 weeks
- Alternate regimen: Vancomycin 40 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
- Note (1): In case of native valve endocarditis with symptoms ≤ 3 months, a 4-week course of therapy is recommended.
- Note (2): In case of native valve endocarditis with symptoms > 3 months, a 6-week course of therapy is recommended.
- Note (3): In case of prosthetic valve or other prosthetic cardiac material, a minimum of 6-week course of therapy is recommended.
- 2.2.2 Strains Susceptible to penicillin, streptomycin, and vancomycin and resistant to gentamicin
- Preferred regimen: (Ampicillin 300 mg/kg IV q24h for 4–6 weeks OR Penicillin 0.3MU/kg IV q24h for 4–6 weeks) AND Streptomycin 20–30 mg/kg IV/IM q24h for 4–6 weeks
- Alternate regimen: Vancomycin hydrochloride 40 mg/kg IV q24h for 6 weeks AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 6 weeks
- 2.2.3 Strains resistant to penicillin and susceptible to aminoglycoside and vancomycin
- 2.2.3.1 β Lactamase–producing strain
- Preferred regimen: Ampicillin-sulbactam 300 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
- Alternate regimen: Vancomycin 40 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
- 2.2.3.2 Intrinsic penicillin resistance
- Preferred regimen: Vancomycin 40 mg/kg IV q24h AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
- 2.2.4 Strains resistant to penicillin, aminoglycoside, and vancomycin
- Preferred regimen (1): Linezolid 30 mg/kg IV/PO q24h ≥ 8 weeks
- Preferred regimen (2): Quinupristin-Dalfopristin 22.5 mg/kg IV q24h ≥ 8 weeks
- 3. Meningitis
- 3.1 Ampicillin susceptible
- Preferred regimen: Ampicillin 12 g/day IV q4h AND Gentamicin 5 mg/kg/day IV q8h
- 3.2 Ampicillin resistant
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Gentamicin 5 mg/kg/day IV q8h
- 3.3 Ampicillin and vancomycin resistant
- Preferred regimen: Linezolid 600 mg IV q12h
- 4. Urinary tract infections
- Preferred regimen (1): Nitrofurantoin 100 mg PO q6h for 5 days
- Preferred regimen (2): Fosfomycin 3 g PO single dose
- Preferred regimen (3): Amoxicillin 875 mg to 1 g PO q12h for 5 days
- 5. Intra abdominal or wound infections
- Preferred regimen (1): Penicillin
- Preferred regimen (2): Ampicillin
- Alternative regimen (penicillin allergy or high-level penicillin resistance): Vancomycin
- Alternative regimen (for complicated skin-skin structure and intra-abdominal infection): Tigecycline 100 mg IV single dose and 50 mg IV q12h
- Staphylococcus aureus Return to Top
- Staphylococcus aureus treatment
- 1. Infectious endocarditis
- 1.1 In adults
- Preferred regimen (1): Vancomycin 15-20 mg/kg IV q8-12h
- Preferred regimen (2): Daptomycin 6mg/kg/dose IV qd
- 2. Intravascular catheter-related infections
- 2.1 Methicillin susceptible Staphylococcus aureus (MSSA)
- Preferred regimen (1): Nafcillin 2 g IV q6h
- Preferred regimen (2): Oxacillin 2 g IV q6h
- Alternative regimen (1): Cefazolin 2 g IV q8h
- Alternative regimen (2): Vancomycin 15 mg/kg IV q12h
- 2.1.1 Pediatric dose of Nafcillin
- 2.1.1.1 Neonates (< 4 weeks)
- For < 1200 g: Nafcillin 50 mg/kg/day q12h
- For ≤ 7 days of age and 1200–2000 g: Nafcillin 50 mg/kg/day q12h
- For ≤ 7 days of age and > 2000 g: Nafcillin 75 mg/kg/day q8h
- For > 7 days of age and 1200–2000 g: Nafcillin 75 mg/kg/day q8h
- For > 7 days of age and > 2000 g: Nafcillin 100 mg/kg/day q6h
- 2.1.1.2 Infants and children (> 4 weeks)
- Nafcillin 100–200 mg/kg/day q4–6h
- 2.1.2 Pediatric dose of Oxacillin
- 2.1.2.1 Neonates (< 4 weeks)
- For < 1200 g: Oxacillin 50 mg/kg/day q12h
- For Postnatal age < 7 days and 1200–2000 g: Oxacillin 50–100 mg/kg/day q12h
- For Postnatal age 2000 g: Oxacillin 75–150 mg/kg/day q8h
- For Postnatal age ≥ 7 days and 1200–2000 g: Oxacillin 75–150 mg/kg/day q8h
- For Postnatal age ≥ 7 days and > 2000 g: Oxacillin 100–200 mg/kg/day q6h
- 2.1.2.2 Infants and children(> 4weeks)
- Oxacillin 150–200 mg/kg/day q4–6h
- 2.1.3 Pediatric dose of Cefazolin
- 2.1.3.1 Neonates (< 4 weeks)
- Postnatal age ≤ 7 days: Cefazolin 40 mg/kg/day q12h
- Postnatal age > 7 days and ≤ 2000 g: Cefazolin 40 mg/kg/day q12h
- Postnatal age > 7 days and > 2000 g: Cefazolin 60 mg/kg/day q8h
- 2.1.3.2 Infants and children (> 4 weeks)
- Cefazolin 50 mg/kg/day q8h.
- 2.1.4 Pediatric dose of Vancomycin
- 2.1.4.1 Neonates (< 4 weeks)
- Postnatal age ≤ 7 days and < 1200 g: Vancomycin 15 mg/kg/day q24h.
- Postnatal age ≤ 7 days and 1200–2000 g: Vancomycin 10–15 mg/kg q12–18h.
- Postnatal age ≤ 7 days and > 2000 g: Vancomycin 10–15 mg/kg q8–12h.
- Postnatal age > 7 days and < 1200 g: Vancomycin 15 mg/kg/day q24h.
- Postnatal age > 7 days and 1200–2000 g: Vancomycin 10–15 mg/kg q8–12h.
- Postnatal age > 7 days and > 2000 g: Vancomycin 15–20 mg/kg q8h.
- 2.1.4.2 Infants and children (> 4 weeks)
- Vancomycin 40 mg/kg/day q6–8h.
- 2.2 Methicillin resistant Staphylococcus aureus (MRSA)
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h
- Preferred regimen (2): Daptomycin 6–8 mg/kg/day IV
- Preferred regimen (3): Linezolid 10 mg/kg IV/PO q12h
- Preferred regimen (4): Vancomycin 15 mg/kg IV q12h AND (Rifampicin IV or Gentamycin IV)
- Preferred regimen (5): Trimethoprim-Sulfamethoxazole 6–12 mg TMP/kg/day q12h alone (if susceptible)
- 2.2.1 Pediatric dose of Linezolid
- 2.2.1.1 Neonates (< 4 weeks)
- For < 1200 g: Linezolid 10 mg/kg q8–12h (note: q12h in patients < 34 weeks gestation and < 1 week of age).
- For < 7 days of age and ≥ 1200 g: Linezolid 10 mg/kg q8–12h (note: q12h in patients < 34 weeks gestation and < 1 week of age).
- For ≥ 7 days and ≥ 1200 g: Linezolid 10 mg/kg q8h
- 2.2.1.2 Infants and children 4 weeks)
- Linezolid 10 mg/kg q8h
- 2.2.1.3 Children ≥ 12 years and adolescents
- Linezolid 10 mg/kg q12h
- 2.2.2 Pediatric dose of Gentamycin
- 2.2.2.1 Neonates (< 4 weeks)
- Premature neonates and < 1000 g: Gentamycin 3.5 mg/kg q24h
- < 1200 g: Gentamycin 2.5 mg/kg q18-24h.
- Postnatal age ≤ 7 days: Gentamycin 2.5 mg/kg q12h.
- Postnatal age > 7 days and 1200–2000 g: Gentamycin 2.5 mg/kg q8-12h.
- Postnatal age > 7 days and > 1200 g: Gentamycin 2.5 mg/kg q8h.
- Premature neonates with normal renal function: Gentamycin 3.5–4 mg/kg q24h.
- Term neonates with normal renal function: Gentamycin 3.5–5 mg/kg q24h.
- 2.2.2.2 Infants and children 4 weeks)
- Gentamycin 2.5 mg/kg q8h; qd dosing in patients with normal renal function, Gentamycin 5–7.5 mg/kg q24h.
- 2.2.2.3 Children ≥ 5 years
- Gentamycin 2–2.5 mg/kg q8h; qd with normal renal function, Gentamycin 5–7.5 mg/kg q24h.
- 2.2.3 Pediatric dose of Trimethoprim-Sulfamethoxazole
- 2.2.3.1 Infants > 2 months of age and children of mild-to-moderate infections
- Trimethoprim-Sulfamethoxazole 6–12 mg TMP/kg/day q12h; serious infection- Trimethoprim-Sulfamethoxazole 15–20 mg TMP/kg/day q6-8h.
- 3. Cellulitis
- 3.1.1 In adults
- Preferred regimen (1): Clindamycin 300–450 mg PO tid
- Preferred regimen (2): Trimethoprim-Sulfamethoxazole 1–2 DS (double strength) tab PO bid
- Preferred regimen (3): Doxycycline 100 mg PO bid
- Preferred regimen (4): Minocycline 200 mg as a single dose THEN 100 mg PO bid
- Preferred regimen (5): Linezolid 600 mg PO bid
- 3.1.2 In children
- Preferred regimen (1): Clindamycin 10–13 mg/kg PO q6–8h, not to exceed 40 mg/kg/day
- Preferred regimen (2): Trimethoprim 4–6 mg/kg, Sulfamethoxazole 20–30 mg/kg PO q12h
- Preferred regimen (3)
- 3.1 If patient body weight < 45kg then Doxycycline 2 mg/kg PO q12h
- 3.2 If patient body weight 45kg then Doxycycline adult dose
- Preferred regimen (4): Minocycline 4 mg/kg PO 200 mg as a single dose, THEN Minocycline 2 mg/kg PO q12h
- Preferred regimen (5): Linezolid 10 mg/kg PO q8h, (max: 600 mg)
- 3.2 Nonpurulent cellulitis (defined as cellulitis with no purulent drainage or exudate and no associated abscess)
- 3.2.1 In adults
- Preferred regimen (1): Beta-lactam (eg, Cephalexin and Dicloxacillin) 500 mg PO qid
- Preferred regimen (2): Clindamycin 300–450 mg PO tid
- Preferred regimen (3): Amoxicillin 500 PO mg tid
- Preferred regimen (4): Linezolid 600 mg PO bid
- Note (1): Empirical therapy for beta-hemolytic streptococci is recommended. Empirical coverage for CA-MRSA is recommended in patients who do not respond to beta-lactam therapy and may be considered in those with systemic toxicity.
- Note (2): Provide coverage for both beta-hemolytic streptococci and CA-MRSA beta-lactam (eg, Amoxicillin) with or without Trimethoprim-Sulfamethoxazole or a Tetracycline
- 3.2.2 In children
- Preferred regimen (1): Clindamycin 10–13 mg/kg PO q6–8h, not to exceed 40 mg/kg/day
- Preferred regimen (2): Trimethoprim 4–6 mg/kg, Sulfamethoxazole 20–30 mg/kg PO q12h
- Preferred regimen (3): Linezolid 10 mg/kg PO q8h, not to exceed 600 mg
- Note (1): Clindamycin causes Clostridium difficile–associated disease may occur more frequently, compared with other oral agents.
- Note (2): Trimethoprim-Sulfamethoxazole not recommended for women in the third trimester of pregnancy and for children ,2 months of age.
- Note (3): Tetracyclines are not recommended for children under 8 years of age and are pregnancy category D.
- 4. Brain abscess
- 4.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- 4.1.1 In adults
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 4–6 weeks
- Alternative regimen (1): Linezolid 600 mg PO/IV q12h for 4–6 weeks
- Alternative regimen (2): Trimethoprim-Sulfamethoxazole 5 mg/kg PO/IV q8–12h for 4–6 weeks
- 4.1.2 In children
- Preferred regimen (1): Vancomycin15 mg/kg/dose IV q6h
- Preferred regimen (2): Linezolid 10 mg/kg/dose PO/IV q8h
- Note: Consider the addition of Rifampin 600 mg qd OR 300–450 mg bid to Vancomycin.
- 4.2 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen (1): Nafcillin 2 g IV q4h
- Preferred regimen (2): Oxacillin 2 g IV q4h
- Alternative regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
- 5. Cerebrospinal fluid shunt infection
- 5.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h with or without Rifampin 600 mg IV or PO q24h
- Note: Shunt removal is recommended, and it should not be replaced until cerebrospinal fluid cultures are repeatedly negative.
- 5.2 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen (1): Nafcillin 2 g IV q4h with or without Rifampin 600 mg IV/PO q24h
- Preferred regimen (2): Oxacillin 2 g IV q4h
- 6. Spinal epidural abscess
- 6.1 Penicillin-susceptible Staphylococcus aureus or Streptococcus
- Preferred regimen: Penicillin G 4 MU IV q4h for 2–4 weeks, THEN PO to complete 6–8 weeks
- 6.2 Methicillin-susceptible Staphylococcus aureus or Streptococcus
- Preferred regimen (1): Cefazolin 2 g IV q8h for 2–4 weeks, THEN PO to complete 6–8 weeks
- Preferred regimen (2): Nafcillin 2 g IV q4h for 2–4 weeks, THEN PO to complete 6–8 weeks
- Preferred regimen (3): Oxacillin 2 g IV q4h for 2–4 weeks, THEN PO to complete 6–8 weeks
- Alternative regimen: Clindamycin 600 mg IV q6h for 2–4 weeks, THEN PO to complete 6–8 weeks
- 6.3 Methicillin-resistant Staphylococcus aureus (MRSA)
- 6.3.1 In adults
- Preferred regimen: Vancomycin loading dose 25–30 mg/kg IV THEN Vancomycin 15–20 mg/kg IV q8–12h for 2–4 weeks, THEN PO to complete 6–8 weeks
- Alternative regimen (1): Linezolid 600 mg PO/IV q12h for 4–6 weeks
- Alternative regimen (2): Trimethoprim-Sulfamethoxazole 5 mg/kg PO/IV q8–12h for 4–6 weeks
- 6.3.2 Pediatric dose
- Preferred regimen (1): Vancomycin 15 mg/kg IV q6h
- Preferred regimen (2): Linezolid 10 mg/kg PO/IV q8h
- Note: Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to Vancomycin in adult patients.
- 7. Bacterial meningitis
- 7.1 Methicillin susceptible Staphylococcus aureus (MSSA)
- Preferred regimen (1): Nafcillin 9–12 g/day IV q4h
- Preferred regimen (2): Oxacillin 9–12 g/day IV q4h
- Alternative regimen (1): Vancomycin 30–45 mg/kg/day IV q8–12h
- Alternative regimen (2): Meropenem 6 g/day IV q8h
- 7.2 Methicillin resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
- Alternative regimen (1): Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h
- Alternative regimen (2): Linezolid 600 mg IV q12h
- Note: Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to Vancomycin in adult patients.
- 8. Septic thrombosis of cavernous or dural venous sinus
- 8.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- 8.1.1 In adults
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h for 4–6 weeks
- Alternative regimen (1): Linezolid 600 mg PO/IV q12h for 4–6 weeks
- Alternative regimen (2): Trimethoprim-Sulfamethoxazole 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks
- 8.1.2 Pediatric dose
- Preferred regimen (1): Vancomycin 15 mg/kg IV q6h
- Preferred regimen (2): Linezolid 10 mg/kg PO/IV q8h
- Note (1): Surgical evaluation for incision and drainage of contiguous sites of infection or abscess is recommended whenever possible.
- Note (2): Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to Vancomycin.
- 9. Subdural empyema
- 9.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- 9.1.1 In adults
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 4–6 weeks
- Alternative regimen (1): Linezolid 600 mg PO/IV q12h for 4–6 weeks
- Alternative regimen (2): Trimethoprim-Sulfamethoxazole 5 mg/kg PO/IV q8–12h for 4–6 weeks
- 9.1.2 In children
- Preferred regimen (1): Vancomycin 15 mg/kg IV q6h
- Preferred regimen (2): Linezolid 10 mg/kg PO/IV q8h
- Note: Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to Vancomycin.
- 10. Acute conjunctivitis
- 10.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin ointment 1% qid
- 11. Appendicitis
- 11.1 Health care–associated complicated intra-abdominal infection
- 11.1.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h
- 12. Diverticulitis
- 12.1 Health care–associated complicated intra-abdominal infection
- 12.1.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h.
- 13. Peritonitis secondary to bowel perforation, peritonitis secondary to ruptured appendix, peritonitis secondary to ruptured appendix, typhlitis
- 13.1 Health care–associated complicated intra-abdominal infection
- 13.1.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h
- 14. Cystic fibrosis
- 14.1 Adults
- 14.1.1 If methicillin sensitive staphylococcus aureus
- Preferred Regimen (1): Nafcillin 2 gm IV q4h
- Preferred Regimen (2): Oxacillin 2 gm IV q4h
- 14.1.2 If methicillin resistant staphylococcus aureus
- Preferred Regimen (1): Vancomycin 15-20 mg/kg IV q8-12h
- Preferred Regimen (2): Linezolid 600 mg PO/IV q12h
- 14.2 Pediatric
- 14.2.1 If methicillin sensitive staphylococcus aureus
- Preferred Regimen (1): Nafcillin 5 mg/kg q6h (Age >28 days)
- Preferred Regimen (2): Oxacillin 75 mg/kg q6h (Age >28 days)
- 14.2.2 If methicillin resistant staphylococcus aureus
- Preferred Regimen (1): Vancomycin 40 mg/kg q6-8h (Age >28 days)
- Preferred Regimen (2): Linezolid 10 mg/kg PO/IV q8h (up to age 12)
- 15. Bronchiectasis
- 15.1 In adults
- 15.1.1 Recommended first-line treatment and length of treatment
- 15.1.1.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Flucloxacillin 500 mg PO qds for 14 days
- 15.1.1.2 Methicillin-resistant Staphylococcus aureus (MRSA)
- Patient's body weight is < 50 kg
- Preferred regimen: Rifampicin 450 mg PO qd AND Trimethoprim 200 mg PO bd for 14 days
- Patient's body weight is > 50 kg
- Preferred regimen: Rifampicin 600 mg PO qd AND Trimethoprim 200 mg PO bd for 14 days
- 15.1.1.3 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen (1): Vancomycin 1 g IV bd (monitor serum levels and adjust dose accordingly)
- Preferred regimen (2): Teicoplanin 400 mg qd for 14 days
- 15.1.2 Recommended second-line treatment and length of treatment
- 15.1.2.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Clarithromycin 500 mg PO bd 14 days
- 15.1.2.2 Methicillin-resistant Staphylococcus aureus (MRSA)
- Patient's body weight is < 50 kg
- Preferred regimen: Rifampicin 450 mg PO qd AND Doxycycline 200 mg PO qd for 14 days
- Patient's body weight is > 50 kg
- Preferred regimen: Rifampicin 600 mg PO qd AND Doxycycline 200 mg PO qd for 14 days
- Third-line: Linezolid 600 mg bd for 14 days
- 15.1.2.3 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Linezolid 600 mg IV bd for 14 days
- 15.2 In children
- 15.2.1 Recommended first-line treatment and length of treatment
- 15.2.1.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Flucloxacillin
- 15.2.1.2 Methicillin-resistant Staphylococcus aureus (MRSA)
- 15.2.1.2.1 Children (< 12 yr)
- Preferred regimen: Trimethoprim 4-6 mg/kg/day PO q12h
- 15.2.1.2.2 Children (> 12 yr)
- Preferred regimen (1): Trimethoprim 100-200 mg PO q12h
- Preferred regimen (2): Rifampicin 450 mg PO od (or Rifampicin 600 mg PO od)
- 15.2.1.3 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen (1): Vancomycin 45-60 mg/kg/day IV q8-12h
- Preferred regimen (2): Teicoplanin 400 mg qd for 14 days
- 15.2.2 Recommended second-line treatment and length of treatment
- 15.2.2.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Clarithromycin 15 mg/kg/day PO q12h
- 15.2.2.2 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen (1): Rifampicin AND Doxycycline 2-5 mg/kg/day PO/IV q12-24h (max dose: 200 mg/24 hr)
- Preferred regimen (2): Rifampicin AND Doxycycline 2-5 mg/kg/day PO/IV q12-24h (max dose: 200 mg/24 hr)
- Third-line: Linezolid 10 mg/kg PO/IV q12h
- 15.2.2.3 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Linezolid 10 mg/kg PO/IV q12h
- 15.3 Long-term oral antibiotic treatment
- 15.3.1 In adults
- 15.3.1.1 Recommended first-line treatment and length of treatment
- 15.3.1.1.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Flucloxacillin 500 mg PO bd
- 15.3.1.2 Recommended second-line treatment and length of treatment
- 15.3.1.2.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Clarithromycin 250 mg PO bd
- 16. Empyema
- Preferred regimen (1): Nafcillin 2 gm IV q4h
- Preferred regimen (2): oxacillin 2 gm IV q4h (if MSSA)
- Alternative regimen (1): Vancomycin 1 gm IV q12h
- Alternative regimen (2): Linezolid 600 mg PO bid (if MRSA)
- 17. Community-acquired pneumonia
- 17.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred Regimen (1): Nafcillin 1000-2000 mg q4h
- Preferred Regimen (2): Oxacillin 2 g IV q4h
- Preferred Regimen (3): Flucloxacillin 250 mg IM/IV q6h
- Alternative Regimen (1): Cefazolin 500 mg IV q12h
- Alternative Regimen (2): Clindamycin 150-450 mg PO q6-8h
- 17.2 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred Regimen (1): Vancomycin 45-60 mg/kg/day q8-12h (max: 2000 mg/dose) for 7-21 days
- Preferred Regimen (2): Linezolid 600 mg PO/IV q12h for 10-14 days
- Alternative Regimen: Trimethoprim-Sulfamethoxazole 1-2 double-strength tablets (800/160 mg) q12-24h
- 18. Olecranon bursitis or prepatellar bursitis
- 18.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen (1): Nafcillin 2 g IV q4h
- Preferred regimen (2): Oxacillin 2 g IV q4h
- Preferred regimen (3): Dicloxacillin 500 mg PO qid
- 18.2 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen (1): Vancomycin 1 g IV q12h
- Preferred regimen (2): Linezolid 600 mg PO qd
- Note: Initially aspirate q24h and treat for a minimum of 2–3 weeks.
- 19. Septic arthritis
- 19.1 In adults
- 19.1.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h
- Alternative regimen (1): Daptomycin 6 mg/kg IV q24h in adults
- Alternative regimen (2): Linezolid 600 mg PO/IV q12h
- Alternative regimen (3): Clindamycin 600 mg PO/IV q8h
- Alternative regimen (4): TMP-SMX 3.5–4.0 mg/kg PO/IV q8–12h
- 19.2.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen (1): Nafcillin 2 g IV q6h
- Preferred regimen (2): Clindamycin 900 mg IV q8h
- Alternative regimen (1): Cefazolin 0.25–1 g IV/IM q6–8h
- Alternative regimen (2): Vancomycin 500 mg IV q6h or 1 g IV q12h
- 19.2 In childern
- Preferred regimen (1): Vancomycin 15 mg/kg IV q6h
- Preferred regimen (2): Daptomycin 6–10 mg/kg IV q24h
- Preferred regimen (3): Linezolid 10 mg/kg PO/IV q8h
- Preferred regimen (4): Clindamycin 10–13 mg/kg PO/IV q6–8h
- 20. Septic arthritis, prosthetic joint infection (device-related osteoarticular infections)
- 20.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen (1): Nafcillin 2 g IV q4–6h
- Preferred regimen (2): Oxacillin 2 g IV q4–6h
- Alternative regimen (1): Cefazolin 1–2 g IV q8h
- Alternative regimen (2): Ceftriaxone 2 g IV q24h
- Alternative regimen (if allergic to penicillins) (3): Clindamycin 900 mg IV q8h
- Alternative regimen (if allergic to penicillins) (4): Vancomycin 15–20 mg/kg IV q8–12h, (max: 2 g per dose)
- 20.2 Methicillin-resistant Staphylococcus aureus (MRSA)
- Early-onset (2 months after surgery) or acute hematogenous prosthetic joint infections involving a stable implant with short duration (< 3 weeks) of symptoms and debridement (but device retention)
- Preferred regimen: Vancomycin AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks
- Alternative regimen (1): Daptomycin 6 mg/kg IV q24h AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks
- Alternative regimen (2): Linezolid 600 IV q8h AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks
- Note: The above regimen should be followed by Rifampin and a Fluoroquinolone, TMP/SMX, a Tetracycline or Clindamycin for 3-6 months for hips and knees, respectively.
- 21. Hematogenous osteomyelitis
- 21.1 Adult (> 21 yrs)
- 21.1.1 Methicillin-resistant Staphylococcus aureus (MRSA) possible
- Preferred regimen: Vancomycin 1 gm IV q12h (if over 100 kg, 1.5 gm IV q12h)
- 21.1.2 Methicillin-resistant Staphylococcus aureus (MRSA) unlikely
- Preferred regimen (1): Nafcillin
- Preferred regimen (2): Oxacillin 2 gm IV q4h
- 21.2 Children (> 4 months)-Adult
- 21.2.1 Methicillin-resistant Staphylococcus aureus (MRSA) possible
- Preferred regimen: Vancomycin 40 mg IV q6–8h
- 21.2.2 Methicillin-resistant Staphylococcus aureus (MRSA) unlikely
- Preferred regimen (1): Nafcillin
- Preferred regimen (2): Oxacillin q6h (max. 8–12 gm per day)
- Note: Add Ceftazidime 50 mg q8h or Cefepime 150 mg q8h if Gram negative bacilli on Gram stain
- 21.3 Newborn (< 4 months.)
- 21.3.1 Methicillin-resistant Staphylococcus aureus (MRSA) possible
- Preferred regimen (1): Vancomycin AND Ceftazidime 2 gm IV q8h
- Preferred regimen (2): Vancomycin AND Cefepime 2 gm IV q12h
- 21.3.2 Methicillin-resistant Staphylococcus aureus (MRSA) unlikely
- Preferred regimen (1): Nafcillin AND Ceftazidime
- Preferred regimen (2): Oxacillin AND Cefepime
- 21.4 Specific therapy
- 21.4.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen (1): Nafcillin
- Preferred regimen (2): Oxacillin 2 gm IV q4h
- Preferred regimen (3): Cefazolin 2 gm IV q8h
- Alternative regimen: Vancomycin 1 gm IV q12h (if over 100 kg, 1.5 gm IV q12h)
- 21.4.2 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 1 gm IV q12h
- Alternative regimen: Linezolid 600 mg q12h PO/IV with or without Rifampin 300 mg PO/IV bid
- 22. Diabetic foot osteomyelitis
- High risk for MRSA
- Preferred regimen (1): Linezolid 600 mg IV or PO q12h
- Preferred regimen (2): Daptomycin 4 mg/kg IV q24h
- Preferred regimen (3): Vancomycin 15–20 mg/kg IV q8–12h (trough: 10–20 mg/L)
- 23. Necrotizing fasciitis
- 23.1 In adult
- Preferred regimen (1): Nafcillin 1–2 g IV q4h (severe Pencillin allergy: Vancomycin, linezolid, quinupristin/dalfopristin, daptomycin)
- Preferred regimen (2): Oxacillin 1–2 g IV q4h
- Preferred regimen (3): Cefazolin 1 g IV q8h
- Preferred regimen (4): Vancomycin 15 mg/kg IV bid
- Preferred regimen (5): Clindamycin 600–900 mg IV q8h
- 23.2 In childern
- Preferred regimen (1): Nafcillin 50 mg/kg/dose IV q6h (severe Pencillin allergy: Vancomycin, linezolid, quinupristin/dalfopristin, daptomycin)
- Preferred regimen (2): Oxacillin 50 mg/kg/dose IV q6h
- Preferred regimen (3): Cefazolin 33 mg/kg/dose IV q8h
- Preferred regimen (4): Vancomycin 15 mg/kg/dose IV q6h
- Preferred regimen (5): Clindamycin 10–13 mg/kg/dose IV q8h (Bacteriostatic; potential cross-resistance and emergence of resistance in erythromycin-resistant strains; inducible resistance in methicillin resistent staphylococcus aureus)
- 24. Staphylococcal toxic shock syndrome
- 24.1 Methicillin sensitive Staphylococcus aureus
- Preferred regimen (1): Cloxacillin 250-500 mg PO q6h (max dose: 4 g/24 hr)
- Preferred regimen (2): Nafcillin 4-12 g/24 hr IV q4-6hr (max dose: 12 g/24 hr)
- Preferred regimen (3): Cefazolin 0.5-2g IV/IM q8h (max dose: 12 g/24 hr) AND Clindamycin 150-600 mg IV, IM/PO q6-8h (max dose: 5 g/24 hr IV or IM or 2 g/24 hr PO)
- Alternative regimen (1): Clarithromycin 250-500 mg PO q12h (max dose: 1 g/24 hr) AND Clindamycin 150-600 mg IV, IM/PO q6-8h (max dose: 5 g/24 hr IV/IM or 2 g/24h PO)
- Alternative regimen (2): Rifampicin AND Linezolid 600 mg IV/PO q12h
- Alternative regimen (3): Daptomycin
- Alternative regimen (4): Tigecycline 100 mg loading dose THEN 50 mg IV q12h
- 24.2 Methicillin resistant Staphylococcus aureus
- Preferred regimen (1): Clindamycin 150-600 mg IV, IM/PO q6-8h (max dose: 5 g/24h IV/IM or 2 g/24h PO)
- Preferred regimen (2): Linezolid 600 mg IV/PO q12h AND Vancomycin 15-20 mg/kg IV q8-12h, (max: 2 g per dose)
- Preferred regimen (3): Teicoplanin
- Alternative regimen (1): Rifampicin AND Linezolid 600 mg IV/PO q12h
- Alternative regimen (2): Daptomycin
- Alternative regimen (3): Tigecycline 100 mg loading dose THEN 50 mg IV q12h
- 24.3 Glycopeptide resistant or intermediate Staphylococcus aureus
- Preferred regimen: Linezolid 600 mg IV/PO q12h AND Clindamycin 150-600 mg IV, IM/PO q6-8h (max dose: 5 g/24 hr IV/IM or 2 g/24h PO) (if sensitive)
- Alternative regimen (1): Daptomycin
- Alternative regimen (2): Tigecycline 100 mg loading dose THEN 50 mg IV q12h
- Staphylococcus aureus ,prophylaxis
- 1. Prophylaxis for coronary artery bypass graft-associated acute mediastinitis
- 1.1 Methicillin susceptible staphylococcus aureus (MSSA)
- Preferred regimen: A first- or second-generation Cephalosporin is recommended for prophylaxis in patients without MRSA colonization.
- 1.2 Methicillin resistant staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin alone or in combination with other antibiotics to achieve broader coverage is recommended for prophylaxis in patients with proven or suspected MRSA colonization
- Note (1): Preoperative antibiotics should be administered to all patients to reduce the risk of mediastinitis in cardiac surgery.
- Note (2): The use of intranasal Mupirocin is reasonable in nasal carriers of Staphylococcus aureus.
- Staphylococcus haemolyticus Return to Top
- 1. Methicillin-susceptible strain
- Preferred regimen (1): Nafcillin 1–2 g IV q4-6h (maximum 12 g/day)
- Preferred regimen (2): Oxacillin 1–2 g IVq4-6h (maximum 12 g/day)
- Preferred regimen (3): Cefazolin 0.5–2 g IV q6-8h
- Alternative regimen (1): TMP-SMX 4–5 mg/kg IV q6–12h
- Alternative regimen (2): Doxycycline 100–200 mg IV q12-24h
- 2. Methicillin-resistant, Glycopeptide-susceptible strain
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h
- 3. Methicillin-resistant, Glycopeptide-resistant strain
- Preferred regimen (1): Daptomycin 4–6 mg/kg IV q24h
- Preferred regimen (2): Linezolid 600 mg PO/IV q12h
- Staphylococcus epidermidis Return to Top
- Staphylococcus epidermidis
- 1. Methicillin-sensitive Staphylococcus epidermidis
- Preferred regimen (1): Oxacillin 1-2 g IV q4h
- Preferred regimen (2): Nafcillin 1-2 g IV q4h
- Preferred regimen (3): Cephalothin
- Alternative regimen: Rifampin 600 mg/day PO qd AND Sulfamethoxazole and Trimethoprim ((or) Fluoroquinolones) AND Daptomycin 600 mg PO or IV q12h
- Note: 75% of the S. epidermidis are methicillin-resistant.
- 2. Methicillin-resistant Staphylococcus epidermidis
- Preferred regimen: Vancomycin 1 g IV q12h with or without Rifampin 600 mg/day PO qd
- Note: For deep-seated infections consider adding Gentamicin with or without Rifampin 600 mg/day PO qd to the regimen
- 3. Prosthetic device infections
- Preferred regimen: Oxacillin 1-2 g IV q4h ((or) Vancomycin 1 g IV q12h) AND Rifampin 600 mg/day PO qd AND Gentamicin 3 mg/kg/day IV/IM q8-24h is appropriate
- Note: Duration depends on site of infection and severity.
- Staphylococcus lugdunensis Return to Top
- Staphylococcus lugdunensis treatment
- 1. Skin and soft tissue infections
- Preferred regimen: Oxacillin 1-2 g IV q4h for 1-2 weeks
- Note: Abscesses should be drained if possible.
- 2. Endocarditis
- 2.1 Native valve infectious endocarditis
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h (target trough concentration, 10 to 15 mcg/mL)
- Preferred regimen (for most patients with normal renal function) (2): Vancomycin 15 to 20 mg/kg (actual body weight) IV q8-12h -for trough concentration of 15 to 20 mcg/mL (minimum inhibitory concentration, 1 mcg/mL or less)
- Note: should consist of 6 weeks of parenteral beta-lactam therapy or Vancomycin (depending on susceptibility testing and beta-lactam hypersensitivity).
- 2.2 Prosthetic valve infective endocarditis
- Preferred regimen: Combination therapy including a beta-lactam (or Vancomycin) with an Aminoglycoside- Gentamicin 3 mg/kg/day in 1-3 divided doses and Rifampin 300 mg PO/IV q8h for at least 6 weeks
- Note (1): Combine with Vancomycin for the entire duration of therapy and Gentamicin for the first 2 weeks.
- Note (2): The Gentamicin should be administered for the first 2 weeks of therapy; the beta-lactam (or Vancomycin) and Rifampin should be continued for 6 weeks.
- Note (3): Surgery must be considered given the frequency of valvular compromise in the setting of Staphylococcus lugdunensis infective endocarditis.
- Note (4): The treatment of Staphylococcus lugdunensis pacemaker endocarditis includes antibiotic therapy as well as removal of the pacer system
- 3. Bacteremia
- Preferred regimen: Oxacillin 1-2 g IV q4h for 1-2 weeks
- Note (1): Bacteremia without endocarditis (often related to an intravascular catheter) appears to have a good prognosis.
- Note (2): For intravascular catheter-related Staphylococcus lugdunensis bacteremia, the catheter should be removed, followed by 14 days of antibiotics, provided that all of the following are applicable
- 2.1 The patient is not diabetic or immunosuppressed.
- 2.2 There is no prosthetic material, thrombophlebitis, infective endocarditis, evidence of metastatic infection.
- 2.3 The patient’s fever and bacteremia resolve within 72 hours after initiation of appropriate antibiotic therapy.
- 4. Prosthetic devices,
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h (target trough concentration, 10 to 15 mcg/mL)
- Preferred regimen (for most patients with normal renal function) (2): Vancomycin 15 to 20 mg/kg (actual body weight) IV q8-12h -for trough concentration of 15 to 20 mcg/mL (minimum inhibitory concentration, 1 mcg/mL or less)
- Preferred regimen (3): Daptomycin 6 mg/kg IV qd for 3 to 4 weeks
- Preferred regimen (4): Linezolid 600 mg IV q12h
- 5. Vertebral osteomyelitis, discitis
- Preferred regimen: Vancomycin 15 to 20 mg/kg IV q8-12h, not to exceed 2 g per dose
- 6. Septic arthritis in adults
- Preferred regimen: Vancomycin 15 mg/kg IV bd, not to exceed 2 g per 24 hours (unless cncentrations in serum are inappropriately low) for 4 weeks.
- Staphylococcus lugdunensis treatment
- 1. Skin and soft tissue infections
- Preferred regimen: Oxacillin 1-2 g IV q4h for 1-2 weeks
- Note: Abscesses should be drained if possible.
- 2. Endocarditis
- 2.1 Native valve infectious endocarditis
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h (target trough concentration, 10 to 15 mcg/mL)
- Preferred regimen (for most patients with normal renal function) (2): Vancomycin 15 to 20 mg/kg (actual body weight) IV q8-12h -for trough concentration of 15 to 20 mcg/mL (minimum inhibitory concentration, 1 mcg/mL or less)
- Note: should consist of 6 weeks of parenteral beta-lactam therapy or Vancomycin (depending on susceptibility testing and beta-lactam hypersensitivity).
- 2.2 Prosthetic valve infective endocarditis
- Preferred regimen: Combination therapy including a beta-lactam (or Vancomycin) with an Aminoglycoside- Gentamicin 3 mg/kg/day in 1-3 divided doses and Rifampin 300 mg PO/IV q8h for at least 6 weeks
- Note (1): Combine with Vancomycin for the entire duration of therapy and Gentamicin for the first 2 weeks.
- Note (2): The Gentamicin should be administered for the first 2 weeks of therapy; the beta-lactam (or Vancomycin) and Rifampin should be continued for 6 weeks.
- Note (3): Surgery must be considered given the frequency of valvular compromise in the setting of Staphylococcus lugdunensis infective endocarditis.
- Note (4): The treatment of Staphylococcus lugdunensis pacemaker endocarditis includes antibiotic therapy as well as removal of the pacer system
- 3. Bacteremia
- Preferred regimen: Oxacillin 1-2 g IV q4h for 1-2 weeks
- Note (1): Bacteremia without endocarditis (often related to an intravascular catheter) appears to have a good prognosis.
- Note (2): For intravascular catheter-related Staphylococcus lugdunensis bacteremia, the catheter should be removed, followed by 14 days of antibiotics, provided that all of the following are applicable
- 2.1 The patient is not diabetic or immunosuppressed.
- 2.2 There is no prosthetic material, thrombophlebitis, infective endocarditis, evidence of metastatic infection.
- 2.3 The patient’s fever and bacteremia resolve within 72 hours after initiation of appropriate antibiotic therapy.
- 4. Prosthetic devices,
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h (target trough concentration, 10 to 15 mcg/mL)
- Preferred regimen (for most patients with normal renal function) (2): Vancomycin 15 to 20 mg/kg (actual body weight) IV q8-12h -for trough concentration of 15 to 20 mcg/mL (minimum inhibitory concentration, 1 mcg/mL or less)
- Preferred regimen (3): Daptomycin 6 mg/kg IV qd for 3 to 4 weeks
- Preferred regimen (4): Linezolid 600 mg IV q12h
- 5. Vertebral osteomyelitis, discitis
- Preferred regimen: Vancomycin 15 to 20 mg/kg IV q8-12h, not to exceed 2 g per dose
- 6. Septic arthritis in adults
- Preferred regimen: Vancomycin 15 mg/kg IV bd, not to exceed 2 g per 24 hours (unless cncentrations in serum are inappropriately low) for 4 weeks.
- Staphylococcus lugdunensis treatment
- 1. Skin and soft tissue infections
- Preferred regimen: Oxacillin 1-2 g IV q4h for 1-2 weeks
- Note: Abscesses should be drained if possible.
- 2. Endocarditis
- 2.1 Native valve infectious endocarditis
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h (target trough concentration, 10 to 15 mcg/mL)
- Preferred regimen (for most patients with normal renal function) (2): Vancomycin 15 to 20 mg/kg (actual body weight) IV q8-12h -for trough concentration of 15 to 20 mcg/mL (minimum inhibitory concentration, 1 mcg/mL or less)
- Note: should consist of 6 weeks of parenteral beta-lactam therapy or Vancomycin (depending on susceptibility testing and beta-lactam hypersensitivity).
- 2.2 Prosthetic valve infective endocarditis
- Preferred regimen: Combination therapy including a beta-lactam (or Vancomycin) with an Aminoglycoside- Gentamicin 3 mg/kg/day in 1-3 divided doses and Rifampin 300 mg PO/IV q8h for at least 6 weeks
- Note (1): Combine with Vancomycin for the entire duration of therapy and Gentamicin for the first 2 weeks.
- Note (2): The Gentamicin should be administered for the first 2 weeks of therapy; the beta-lactam (or Vancomycin) and Rifampin should be continued for 6 weeks.
- Note (3): Surgery must be considered given the frequency of valvular compromise in the setting of Staphylococcus lugdunensis infective endocarditis.
- Note (4): The treatment of Staphylococcus lugdunensis pacemaker endocarditis includes antibiotic therapy as well as removal of the pacer system
- 3. Bacteremia
- Preferred regimen: Oxacillin 1-2 g IV q4h for 1-2 weeks
- Note (1): Bacteremia without endocarditis (often related to an intravascular catheter) appears to have a good prognosis.
- Note (2): For intravascular catheter-related Staphylococcus lugdunensis bacteremia, the catheter should be removed, followed by 14 days of antibiotics, provided that all of the following are applicable
- 2.1 The patient is not diabetic or immunosuppressed.
- 2.2 There is no prosthetic material, thrombophlebitis, infective endocarditis, evidence of metastatic infection.
- 2.3 The patient’s fever and bacteremia resolve within 72 hours after initiation of appropriate antibiotic therapy.
- 4. Prosthetic devices,
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h (target trough concentration, 10 to 15 mcg/mL)
- Preferred regimen (for most patients with normal renal function) (2): Vancomycin 15 to 20 mg/kg (actual body weight) IV q8-12h -for trough concentration of 15 to 20 mcg/mL (minimum inhibitory concentration, 1 mcg/mL or less)
- Preferred regimen (3): Daptomycin 6 mg/kg IV qd for 3 to 4 weeks
- Preferred regimen (4): Linezolid 600 mg IV q12h
- 5. Vertebral osteomyelitis, discitis
- Preferred regimen: Vancomycin 15 to 20 mg/kg IV q8-12h, not to exceed 2 g per dose
- 6. Septic arthritis in adults
- Preferred regimen: Vancomycin 15 mg/kg IV bd, not to exceed 2 g per 24 hours (unless cncentrations in serum are inappropriately low) for 4 weeks.
eeks
- Staphylococcus saprophyticus Return to Top
- Urinary tract infections
- Preferred regimen (1): Cephalexin 500 mg PO qid
- Preferred regimen (2): Amoxicillin-Clavulanate 875/125 mg PO bid
- Preferred regimen (3): TMP-SMX 160–800 mg PO bid
- Alternative regimen: Levofloxacin 500 mg PO qd
- Streptobacillus moniliformis Return to Top
- Streptobacillus moniliformis treatment
- 1. Migratory arthropathy and arthritis
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 2. Diarrhea, (especially kids) liver or spleen abscess
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 3. Undifferentiated fever
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 4. Endocarditis, myocarditis, pericarditis (cardiac)
- Preferred regimen: Penicillin 20 MU/day IV divided q4h. Optimal duration recommendation for infective endocarditis is 4 weeks.
- Alternative regimen: Cephalosporins-Ceftriaxone OR Clindamycin OR Erythromycin OR Chloramphenicol AND Streptomycin.
- 5. Meningitis, brain abscess
- Preferred regimen: Penicillin 20 MU/day IV divided q4h.
- Alternative regimen: Cephalosporins-Ceftriaxone OR Clindamycin OR Erythromycin OR Chloramphenicol AND Streptomycin.
- 6. Anemia
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 7. Pneumonia
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 8. Amnionitis (pregnancy)
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 9. Renal abscess
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- Streptococcus anginosus Return to Top
- 1. Dental abscess
- Preferred regimen: Penicillin V 500 mg PO qid
- Alternative regimen: Vancomycin 15–20 mg/kg IV q8–12h
- 2. Brain abscess
- Preferred regimen (1): Penicillin G 18–24 MU/day IV q4–6h
- Preferred regimen (2): Ceftriaxone 2 g IV q12h
- Alternative regimen: Vancomycin 15–20 mg/kg IV q8–12h
- Streptococcus pneumoniae Return to Top
- Streptococcus pneumonia treatment
- 1. Lung (Community-acquired pneumonia)
- 1.1 Penicillin sensitive (minimum inhibitory concentration < 2 mcg/ml)
- Preferred regimen: Penicillin G 5 to 24 MU IV in equally divided doses q4-6h, Amoxicillin 1 g PO tid (+/- macrolide)
- Alternative regimen: Macrolides (Azithromycin (IV) 500 mg IV qd for at least 2 days followed by 500 mg PO qd 7 to 10 days or Clarithromycin extended-release tablets 1000 mg PO qd for 7 days) and Oral Cephalosporins-Cefpodoxime 200 mg PO bd, (Cefprozil 500 mg PO bd, Cefditoren 400 mg PO bd, Cefdinir 300 mg PO bd), OR parenteral Cephalosporins-Ceftriaxone 2 g IV q24h (or Cefotaxime 1-2 g IV q6-8h), Clindamycin 600 to 1200 mg IV or IM q6-12h, do not give single IM doses >600 mg; IV infusion rates should not exceed 30 mg/min , Doxycycline 100 mg PO bd, respiratory flouroquniolones.
- 1.2 Penicillin-resistant (Penicillin minimum inhibitory concentration ≥2)
- Preferred regimen: Ceftriaxone 2 g IV q24h (or Cefotaxime 1-2 g IV q6-8h), respiratory Flouroquniolones Levofloxacin (Levaquin) 500 mg IV/PO q24h for 7 to 14 days or 750 mg IV/PO q24h for 5 days (or Moxifloxacin (Avelox) 400 mg PO/IV over 60 minutes q24h for 7 to 14 days)
- Alternative regimen: Vancomycin 2 g/day IV q6-12h over at least 60 minutes, Linezolid 600 mg IV/PO q12h for 7 to 21 days , high-dose Amoxicillin (3 g qd with Penicillin minimum concentration of inhibitory <4 mcg/mL).
- 2.Endocarditis
- Preferred regimen (1): Aqueous crystalline Penicillin-G 6 MU q4-6h IV for 4 weeks
- Preferred regimen (2) (who are unable to tolerate beta lactams therapy): Vancomycin 15 mg/kg IV every 12 hours (target trough concentration, 10 to 15 mcg/mL) ; for troughs of 15 to 20 mcg/mL (MIC, 1 mcg/mL or less), dose 15 to 20 mg/kg (actual body weight) IV every 8 to 12 hours for most patients with normal renal function
- Preferred regimen (3) (If the isolate is resistant (MIC 2 g/mL) to cefotaxime): Cefotaxime 1-2 g q8-12h IV or IM (max dose: 12 g/24 hr) AND Vancomycin 15 mg/kg/day IV q12h AND Rifampin 300 mg IV/PO q8h for 6 weeks, in combination with appropriate antimicrobial therapy
- Alternative regimen (1): Cefazolin 0.5-2 g q8h IV or IM (max dose: 12 g/24 hr)
- Alternative regimen (2): Ceftriaxone 2 g IV q12h
- Note : Streptococcus pneumoniae with intermediate doses minimum inhibitory concentration (MIC) 0.12 g/mL–0.5 g/mL Penicillin resistance (MIC 0.1 to 1.0 g/mL) or high Penicillin resistance (MIC 2.0 g/mL) is being recovered from patients with bacteremia.
- 3. Sinuses (sinusitis)
- Empiric therapy
- 3.1 For initial empiric treatment of acute bacterial rhinosinusitis in adults
- Preferred regimen: Amoxicillin 500 mg/Clavulanate 125 mg PO tid or Amoxicillin 875 mg/Clavulanate 125 mg PO bid for 5 to 7 days recommended by the Infectious Disease Society of America (IDSA)
- Alternative regimen (1): Doxycycline 100 mg PO q12h
- Note: Doxycycline can be used in patients with Penicillin allergy.
- Alternative regimen (2): A respiratory Fluoroquinolone (Levofloxacin or Moxifloxacin) is another recommended drug for Penicillin-allergic patients.
- 3.2 For second-line high-dose therapy for acute bacterial rhinosinusitis in adults
- Preferred regimen: Amoxicillin 2 g/Clavulanate 125 mg PO bid recommended by the Infectious Disease Society of America (IDSA).
- Note: The second line high dose therapy is recommended in adults who have failed initial therapy, in regions of high endemic rates (10% or greater) of invasive Penicillin-nonsusceptible Streptococcus pneumoniae, severe infection.
- 4. Bronchi (acute exacerbation of chronic bronchitis)
- Preferred regimen (1): Amoxicillin 875 mg PO q12h or 500 mg PO q8h
- Preferred regimen (2): Doxycycline 100 mg PO q12h
- 5. CNS (meningitis)
- Empiric therapy
- Preferred regimen: Vancomycin 15 mg/kg/day IV q12h AND a third-generation cephalosporin (Ceftriaxone 2 g IV q12h OR Cefotaxime 2 g IV q4h or 3 g q6h) AND Rifampin 600 mg IV qd in combination with Vancomycin
- Alternative regimen: Meropenem, fluoroquinolones
- Prevention
- 1. Pneumovax (23-valent) prevents bacteremia; impact on rates of CAP are modest or nil.
- 2. Prevnar vaccine for children <2 yrs age prevents invasive pneumococcal infection in adults by herd effect. Impact is impressive with rates of invasive pneumococcal infection down 80% in peds and 20-40% in adults.
- 3. Risk for bacteremia in splenectomy, HIV, smokers, black race, multiple myeloma, asthma.
- Streptococcus pyogenes Return to Top
- 1. Streptococcus pyogenes tonsilitis
- Preferred regimen (1): Penicillin V 250 mg PO bid or tid (for children) 250 mg PO qid or 500 mg PO bid (for adults) for 10 days
- Preferred regimen (2): Benzathine penicillin G if 27kg 1,200,000 U IM single-dose
- Alternative regimen (1): Amoxicillin 50 mg/kg/day PO qd for 10 days OR 25 mg/kg/day PO bid for 10 days. Its oral suspension is more tolerable to children and it is better absorbed by the GI tract
- Alternative regimen (2): first generation Cephalosporins are acceptable for treating recurrent group A streptococcus infection but not as first-line therapy
- Alternative regimen (3): Clarithromycin 250 mg PO bid for 10 days OR Azithromycin 12 mg/kg maximum 500 mg PO on day 1 THEN 6 mg/kg maximum 250 mg PO qd on days 2 through 5 OR Erythromycin 20 mg/kg/day PO or 40 mg/kg/day (ethylsuccinate) PO bid for 10 days.
- Alternative regimen (4): Clindamycin for penicillin-intolerant patients with erythromycin-resistant strains.
- Note: Intramuscular penicillin is the only therapy that has been shown to prevent initial attacks of rheumatic fever in controlled studies
- 2. Recurrent Streptococcus pyogenes tonsilitis
- Preferred regimen (1): Clindamycin 20-30 mg/kg/day PO tid (for children), 600 mg/day bid, tid or qid (for adults) for 10 days
- Preferred regimen (2): Amoxicillin-clavulanic acid 40 mg/kg/day PO tid (for children), 500 mg bid (for adults) for 10 days
- Alternative regimen: Benzathine penicillin G if 27kg 1,200,000 U IM single-dose ± Rifampin 20 mg/kg/day PO bid for 4 days
- 3. Secondary prophylaxis for rheumatic fever
- Preferred regimen (1): Benzathine penicillin G if 27kg 1,200,000 U IM every 4 weeks
- Alternative regimen (1): Penicillin V potassium 250 mg PO bid
- Alternative regimen (2): Sulfadiazine if 27kg 1 g PO qd
- Duration of treatment: if residual cardiac disease, keep treatment until 40 patient is 40 years old or for 10 years (whichever is longer); if there's no residual cardiac disease keep treatment for 10 years or until age 21 years (whichever is longer); if there's rheumatic fever without carditis keep it for 5 years or until age 21 years (whichever is longer).
- Note: For patients allergic to penicillin and sulfadiazine, consider a macrolide or azalide antibiotic
- 4. Streptococcus pyogenes bacteremia
- Preferred regimen: Penicillin G 4 million units IV q4h AND Clindamycin 900 mg IV q8h for at least 14 days
- Penicillin is added to the regimen to cover any other group A streptococcus which might be resistant to Clindamycin.
- Alternative regimen (1): Erythromycin
- Alternative regimen (2): Azithromycin
- Alternative regimen (3): Clarithromycin
- Alternative regimen (4): any other β-lactam
- Note (1): Macrolide resistance is increasing.
- Note (2): Consider using intravenous immune globulin in patients with invasive infection and signs of shock. Immunoglobulin-G IV 1 g/kg day 1, then 0.5 g/kg days 2 & 3.
- Note (3): If shock, administer massive IV fluids (10-20 L/day), Albumin if <2 g/dL, debridement of necrotic tissue.
- 5. Streptococcus pyogenes celulitis
- Preferred regimen: treat as Streptococcus pyogenes bacteremia
- 6 Epiglottitis in childern
- Preferred regimen (1): Cefotaxime 50 mg/kg IV q8h
- Preferred regimen (2): Ceftriaxone 50 mg/kg IV q24h
- Alternative regimen (1): Amoxicillin-SB 100–200 mg/kg qd q6h
- Alternative regimen (2): Trimethoprim-Sulfamethoxazole 8–12 mg/kg bid
- Note: Have tracheostomy set “at bedside.” Chloro is effective, but potentially less toxic alternative agents available.
- 7 Burn wound sepsis
- Preferred regimen: Vancomycin 1 gm IV q12h AND (Amikacin 10 mg/kg IV loading dose then 7.5 mg/kg IV q12h) AND . Can use Piperacillin-Tazobactam if Piperacillin not available.
- 8. Soft tissue
- Note: For necrotizing fasciitis, surgical consultation for emergent fasciotomy and debridement; repeat debridements usually necessary.
- 9. Muscle
- Note: For myositis-debirdement is recommended.
- 10. Eye
- 10.1 Keratitis
- 10.1.1 Acute bacterial keratitis
- Preferred regimen: Moxifloxacin eye gtts. 1 gtt tid for 7 days
- Alternative therapy: Gatifloxacin eye gtts. 1-2 gtts q2h while awake for 2 days, then q4h for 3-7 days.
- Note: Prefer Moxifloxacin due to enhanced lipophilicity and penetration into aqueous humor (1 gtt = 1 drop).
- 10.1.2 Keratitis due to dry cornea, diabetes, immunosuppression
- Preferred regimen: Cefazolin (50 mg/mL) AND (Gentamicin OR Tobramycin (14 mg/mL) q15–60 min around clock for 24–72 hrs, then slow reduction)
- Alternative therapy: Vancomycin (50 mg/mL) AND Ceftazidime (50 mg/mL) q15–60 min around clock for 24–72 hrs, then slow reduction.
- Note: Specific therapy guided by results of alginate swab culture and sensitivity. Ciprofloxacin 0.3% found clinically equivalent to CefazolinAND Tobramycin; only concern was efficacy of Ciprofloxacin vs S. pneumoniae
- 10.2 Dacryocystitis (lacrimal sac)
- Preferred regimen: Moxifloxacin 1 gtt tid for 7 days OR Cefazolin (50 mg/mL) (1 gtt = 1 drop)
- 11. Suppurative phlebitis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h (normal weight)
- Alternative regimen: Daptomycin 6 mg/kg IV q12h
- Note: Retrospective study for suppurative phlebitis recommends 2-3 weeks IV therapy and 2 weeks PO therapy.
- 12. Infected prosthetic joint
- Preferred regimen: Penicillin G 2 million units IV q4h OR Ceftriaxone 2 g IV q24h for 4 weeks
- Note: Debridement & prosthesis retention with intravenous antibiotics.
- 13. “Hot” tender parotid swelling
- Preferred regimen: Nafcillin OR Oxacillin 2 g IV q4h
- Note: Predisposing factors are stone(s) in Stensen’s duct, dehydration. Therapy depends on ID of specific etiologic organism.
- 14. Diabetic foot ulcer (ulcer with <2 cm of superficial inflammation)
- Preferred regimen: (Trimethoprim-Sulfamethoxazole 800/160 mg 1-2 tabs PO bid OR Minocycline 100 mg PO bid) AND (Penicillin VK 500 mg PO qid OR selected Cephalosporins 2nd, 3rd generation - cefprozil 500 mg PO bid OR cefuroxime axetil 500 mg PO bid OR cefdinir 300 mg PO bid or 600 mg PO qd OR cefpodoxime 200 mg PO bid OR Fluoroquinolones Levofloxacin 750 mg PO qd).
- 15. Recurrent cellulitis, chronic lymphedema prophylaxis
- Preferred regimen: Clindamycin 150 mg PO qd OR Trimethoprim-Sulfamethoxazole 800/160 mg 1 tablet PO qd OR “stand-by therapy” immediate treatment with Penicillin V OR Amoxicillin 500-750 mg PO bd at onset of symptoms.
- Streptococcus agalactiae Return to Top
- Streptococcus agalactiae treatment (GBS-group B Streptococcus)
- 1. Early onset group B streptococcal infections
- 1.1 Bacteremia or sepsis or pneumonia
- 1.1.1 Empiric therapy
- Preferred regimen: Ampicillin 150 mg/kg IV q12h for 10 days AND Gentamicin 4 mg/kg IV q12h for 10 days-for infants born at ≥ 35 weeks gestation; Gentamicin 3 mg/kg IV q24h for 10 days-for infants born at < 35 weeks gestation
- 1.1.2 Definitive therapy
- Preferred regimen: Penicillin G 50,000-100,000 units/kg per day IV divided q12h for 10 days
- 1.2 Meningitis
- 1.2.1 Empiric therapy
- Preferred regimen: Ampicillin 100-150 mg/kg IV q8h for 14-21 days AND Gentamicin 4 mg/kg IV q24h for 14-21 days-for infants born at ≥ 35 weeks gestation; Gentamicin 3 mg/kg IV q24h for 14-21 days-for infants born at < 35 weeks gestation
- 1.2.2 Definitive therapy
- Preferred regimen: Penicillin G 250,000-450,000 units/kg per day IV divided q8h for 14-21 days
- Note: Cellulitis is the most frequent clinical manifestation of GBS-associated skin and soft tissue infections.
- 2. Late onset group b streptococcus infections in neonates and young infants (age > 1 week and body weight ≥ 1 kg with normal renal function)
- 2.1 Bacteremia without a focus
- 2.1.1 Empiric therapy
- Preferred regimen: Ampicillin IV for 10 days, Nafcillin IV for 10 days, (OR Vancomycin IV for 10 days) AND Gentamicin IV for 10 days (OR Cefotaxime IV for 10 days)
- 2.1.2 Definitive therapy
- Preferred regimen: Penicillin G 75,000-150,000 units/kg per day IV divided q8h for 10 days
- 2.2 Meningitis
- 2.2.1 Empiric therapy
- Preferred regimen: Ampicillin IV for 14-21 days with or without Vancomycin IV for 14-21 day AND Gentamicin IV for 14-21 days OR Cefotaxime IV for 14-21 day
- 2.2.2 Definitive therapy
- Preferred regimen: Penicillin G 450,000-500,000 units/kg per day IV divided q6h for 14-21 days
- 2.3 Cellulitis or adenitis
- 2.3.1 Empiric therapy
- Preferred regimen: Nafcillin IV for 10-14 days (OR [[Vancomycin IV for 10-14 days) AND Gentamicin IV for 10-14 days (OR Cefotaxime IV for 10-14 days)
- 2.3.2 Definitive therapy
- Preferred regimen: Penicillin-G 75,000-150,000 units/kg per day IV divided q8h for 10-14 days
- 2.4 Septic arthritis
- 2.4.1 Empiric therapy
- Preferred regimen: Nafcillin IV for 14-21 days OR Vancomycin IV for 14-21 days AND Cefotaxime IV for 14-21 days
- 2.4.2 Definitive therapy
- Preferred regimen: Penicillin-G 75,000-150,000 units/kg per day IV divided q8h for 14-21 days
- 2.5 Osteomyelitis
- 2.5.1 Empiric therapy
- Preferred regimen: Nafcillin IV for 21-28 days OR Vancomycin IV for 21-28 days AND Cefotaxime IV for 21-28 days
- 2.5.2 Definitive therapy
- Preferred regimen: Penicillin-G 75,000-150,000 units/kg per day IV divided q8h for 21-28 days
- 2.6 Urinary tract infection
- 2.6.1 Empiric therapy
- Preferred regimen: Ampicillin IV for 10 days, Nafcillin IV for 10 days, (OR Vancomycin IV for 10 days) AND Gentamicin IV for 10 days (OR Cefotaxime IV for 10 days)
- 2.6.2 Definitive therapy
- Preferred regimen: Penicillin-G 75,000-150,000 units/kg per day IV divided q8h for 10 days
- Neonatal prophylaxis
- Group B streptococcus infection (maternal dose for neonatal prophylaxis)
- Preferred regimen: Penicillin-G, Ampicillin 2 g IV initial dose, THEN 1 g q4h until delivery, Cefazolin ≥ 4h prior to delivery
### Bacteria – Gram-Positive Bacilli
- Actinomycosis Return to Top
- Actinomyces species including A. israeli
- Preferred regimen: Penicillin 3-4 million units IV q4h for 2-6 weeks THEN Penicillin V 2-4 g/day PO qid for 6-12 months
- Alternative regimen (1): Erythromycin 500-1000 mg IV q6h OR 500 mg PO qid
- Alternative regimen (2): Tetracyclin 500 mg PO qid
- Alternative regimen (3): Doxycycline 100 mg IV q12h OR 100 mg PO bid
- Alternative regimen (4): Clindamycin 900 mg IV q8h OR 300-450 mg PO qd
- Alternative regimen (5): Minocycline 100 mg IV q12h OR 100 mg PO bid
- Arcanobacterium haemolyticum Return to Top
- Arcanobacterium haemolyticum treatment
- Preferred regimen: Erythromycin Base: 333 mg PO q8h; estolate/stearate/base: 250-500 mg q6h PO
- Alternative regimen: Benzathine Penicillin G 1.2 MU IM q3-4 weeks
# Anthracis
- Bacillus anthracis Return to Top
- Bacillus anthracis treatment
- 1. Treatment for cutaneous anthrax, without systemic involvement
- Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown) (1): Ciprofloxacin 500 mg PO bid for 7-10 days
- Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown) (2): Doxycycline 100 mg PO bid for 7-10 days
- Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown) (3): Levofloxacin 750 mg PO qd for 7-10 days
- Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown) (4): Moxifloxacin 400 mg PO qd for 7-10 days
- Alternative regimen (1): Clindamycin 600 mg PO tid for 7-10 days
- Alternative regimen (2): Amoxicillin 1 g PO tid (for penicillin-susceptible strains) for 7-10 days
- Alternative regimen (3): Penicillin VK 500 mg PO qid (for penicillin-susceptible strains) for 7-10 days
- Note: Duration of treatment is 60 days for bioterrorism-related cases and 7-10 days for naturally acquired cases.
- 2. Treatment for systemic anthrax including anthrax meningitis, inhalational anthrax, injectional anthrax, and gastrointestinal anthrax; and cutaneous anthrax with systemic involvement, extensive edema, or lesions of the head or neck
- 2.1 Systemic anthrax with possible/confirmed meningitis
- 2.1.1 Bactericidal agent (fluoroquinolone)
- Preferred regimen (1): Ciprofloxacin 400 mg IV q8h for 2-3 weeks
- Preferred regimen (2): Levofloxacin 750 mg IV q24h for 2-3 weeks
- Preferred regimen (3): Moxifloxacin 400 mg IV q24h for 2-3 weeks AND
- 2.1.2 Bactericidal agent (ß-lactam) for all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- Preferred regimen (1): Meropenem 2 g IV q8h for 2-3 weeks
- Preferred regimen (2): Imipenem 1 g IV q6h for 2-3 weeks
- Preferred regimen (3): Doripenem 500 mg IV q8h for 2-3 weeks
- Preferred regimen (4): Penicillin G 4 MU IV q4h (for penicillin-susceptible strains) for 2-3 weeks
- Preferred regimen (5): Ampicillin 3 g IV q6h (for penicillin-susceptible strains) for 2-3 weeks AND
- 2.1.3 Protein synthesis inhibitor
- Preferred regimen (1): Linezolid 600 mg IV q12h for 2-3 weeks
- Preferred regimen (2): Clindamycin 900 mg IV q8h for 2-3 weeks
- Preferred regimen (3): Rifampin 600 mg IV q12h for 2-3 weeks
- Preferred regimen (4): Chloramphenicol 1 g IV q6-8h for 2-3 weeks
- Note (1): Patients exposed to aerosolized spores will require prophylaxis to complete an antimicrobial drug course of 60 days from onset of illness.
- Note (2): Increased risk for seizures associated with Imipenem/Cilastatin treatment.
- Note (3): Linezolid should be used with caution in patients with thrombocytopenia because it might exacerbate it. Linezolid use for > 14 days has additional hematopoietic toxicity.
- Note (4): Rifampin is not a protein synthesis inhibitor. However, it may be used in combination with other antimicrobial drugs on the basis of its in vitro synergy.
- 2.2 Systemic anthrax when meningitis has been excluded
- 2.2.1 Bactericidal agent
- Preferred regimen (1): Ciprofloxacin 400 mg IV q8h for 2 weeks
- Preferred regimen (2): Levofloxacin 750 mg IV q24h for 2 weeks
- Preferred regimen (3): Moxifloxacin 400 mg q24h for 2 weeks
- Preferred regimen (4): Meropenem 2 g IV q8h for 2 weeks
- Preferred regimen (5): Imipenem 1 g IV q6h for 2 weeks
- Preferred regimen (6): Doripenem 500 mg IV q8h for 2 weeks
- Preferred regimen (7): Vancomycin 20 mg/kg IV q8h (maintain serum trough concentrations of 15-20 µg/mL) for 2 weeks
- Preferred regimen (8): Penicillin G 4 MU IV q4h (penicillin-susceptible strains) for 2 weeks
- Preferred regimen (9): Ampicillin 3 g IV q6h (penicillin-susceptible strains) for 2 weeks AND
- 2.2.2 Protein synthesis inhibitor
- Preferred regimen (1): Clindamycin 900 mg IV q8h for 2 weeks
- Preferred regimen (2): Linezolid 600 mg IV q12h for 2 weeks
- Preferred regimen (3): Doxycycline 200 mg IV initially, then 100 mg IV q12h for 2 weeks
- Preferred regimen (4): Rifampin 600 mg IV q12h for 2 weeks
- Note: Patients exposed to aerosolized spores will require prophylaxis to complete an antimicrobial drug course of 60 days from onset of illness.
- 3. Specific considerations
- 3.1 Treatment of anthrax for pregnant Women
- 3.1.1 Intravenous antimicrobial treatment for systemic anthrax with possible/confirmed meningitis
- 3.1.1.1 A Bactericidal Agent (Fluoroquinolone)
- Preferred regimen (1): Ciprofloxacin 400 mg IV q8h for 2–3 weeks OR
- Preferred regimen (2): Levofloxacin 750 mg IV q24h for 2–3 weeksOR
- 3.1.1.2 A Bactericidal Agent (ß-lactam)
- 3.1.1.2.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- Preferred regimen: Meropenem 2 g q8h for 2–3 weeks
- 3.1.1.2.2 Alternatives for penicillin-susceptible strains
- Alternative regimen (1): Ampicillin 3 g IV q6h for 2–3 weeks
- Alternative regimen (2): Penicillin G 4 MU IV q4h for 2–3 weeks OR
- 3.1.1.3 A Protein Synthesis Inhibitor
- Preferred regimen (1): Clindamycin 900 IV mg q8h for 2–3 weeks
- Preferred regimen (2): Rifampin 600 IV mg q12h for 2–3 weeks
- Note: At least one antibiotic with transplacental passage is recommended.
- 3.1.2 Intravenous antimicrobial treatment for systemic anthrax when meningitis has been excluded
- 3.1.2.1 A Bactericidal Antimicrobial
- Preferred regimen (1): Ciprofloxacin 400 mg IV q8h for 2 weeks
- Preferred regimen (2): Levofloxacin 750 mg IV q24h for 2 weeks OR
- 3.1.2.2 A Bactericidal Agent (ß-lactam)
- 3.1.2.2.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- Preferred regimen: Meropenem 2 g q8h for 2 weeks OR
- 3.1.2.2.2 Alternatives for penicillin-susceptible strains
- Alternative regimen (1): Ampicillin 3 g IV q6h for 2 weeks
- Alternative regimen (2): Penicillin G 4 MU IV q4h for 2 weeks OR
- 3.1.2.3 A Protein Synthesis Inhibitor
- Preferred regimen (1): Clindamycin 900 IV mg q8h for 2 weeks
- Preferred regimen (2): Rifampin 600 IV mg q12h for 2 weeks
- 3.1.3 Oral antimicrobial treatment for cutaneous anthrax without systemic involvement
- 3.1.3.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- Preferred regimen: Ciprofloxacin 400 mg IV q8h
- Note: Duration of treatment is 60 days
- 3.2 Treatment for anthrax in childern
- 3.2.1 Treatment of cutaneous anthrax without systemic involvement (for children 1 month of age and older)
- 3.2.1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day PO bid (not to exceed 500 mg/dose) for 7-10 days
- Preferred regimen (2):
- If patients body weight is < 45 kg: Doxycycline 4.4 mg/kg/day PO bid (not to exceed 100 mg/dose) for 7-10 days
- If patients body weight is = 45 kg: Doxycycline 100 mg/dose PO bid for 7-10 days
- Preferred regimen (3): Clindamycin 30 mg/kg/day PO tid (not to exceed 600 mg/dose) for 7-10 days
- Preferred regimen (4):
- If patients body weight is < 50 kg: Levofloxacin 16 mg/kg/day PO bid (not to exceed 250 mg/dose) for 7-10 days
- If patients body weight is > 50 kg: Levofloxacin 500 mg PO qd for 7-10 days
- 3.2.1.2 Alternatives for penicillin-susceptible strains
- Alternative regimen (1):Amoxicillin 75 mg/kg/day PO tid (not to exceed 1 g/dose) for 7-10 days
- Alternative regimen (2): Penicillin VK 50-75 mg/kg/day PO tid or qid for 7-10 days
- 3.2.2 Combination therapy for systemic anthrax when meningitis can be ruled out (for children 1 month of age and older)
- 3.2.2.1 A bactericidal antimicrobial
- 3.2.2.1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q8h (not to exceed 400 mg/dose) for 14 days
- Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h (not to exceed 2 g/dose) for 14 days
- Preferred regimen (3):
- If patients body weight is < 50 kg: Levofloxacin 20 mg/kg/day IV divided q12h (not to exceed 250 mg/dose) for 14 days
- If patients body weight is > 50 kg: Levofloxacin 500 mg IV q24h for 14 days
- Preferred regimen (4): Imipenem/Cilastatin 100 mg/kg/day IV divided q6h (not to exceed 1 g/dose) for 14 days
- Preferred regimen (5): Vancomycin 60 mg/kg/day IV divided q8h (follow serum concentrations) for 14 days
- 3.2.2.1.2 Alternatives for penicillin-susceptible strains
- Alternative regimen (1): Penicillin G 400 000 U/kg/day IV divided q4h (not to exceed 4 MU/dose) for 14 days
- Alternative regimen (2): Ampicillin 200 mg/kg/day IV divided q6h (not to exceed 3 g/dose) for 14 days AND
- 3.2.2.2 A Protein Synthesis Inhibitor
- Preferred regimen (1): Clindamycin, 40 mg/kg/day IV divided q8h (not to exceed 900 mg/dose) for 14 days
- Preferred regimen (2): (non-CNS infection dose)
- If patient is < 12 y old: Linezolid 30 mg/kg/day IV divided q8h for 14 days
- If patient is = 12 y old: Linezolid 30 mg/kg/day IV divided q12h (not to exceed 600 mg/dose) for 14 days
- Preferred regimen (3):
- If patients body weight is < 45 kg: Doxycycline 4.4 mg/kg/day IV loading dose (not to exceed 200 mg) THEN Doxycycline 4.4 mg/kg/day IV divided q12h (not to exceed 100 mg/dose) for 14 days
- If patients body weight is =45 kg: Doxycycline 200 mg IV loading dose THEN Doxycycline 100 mg IV given q12h for 14 days
- Preferred regimen (4): Rifampin 20 mg/kg/day IV divided q12h (not to exceed 300 mg/dose) for 14 days
- Note: Duration of therapy for 14 days or longer until clinical criteria for stability are met. Will require prophylaxis to complete an antimicrobial course of up to 60 days from onset of illness.
- 3.2.3 Triple therapy for systemic anthrax (anthrax meningitis or disseminated infection and meningitis cannot be ruled out) for Children 1 Month of Age and Older
- 3.2.3.1 A bactericidal antimicrobial (fluoroquinolone)
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q8h (not to exceed 400 mg/dose) for 2–3 wks
- Preferred regimen (2):
- If patients body weight is < 50 kg: Levofloxacin 16 mg/kg/day IV divided q12h (not to exceed 250 mg/dose) for 2–3 wks
- If patients body weight is > 50 kg: Levofloxacin 500 mg IV q24h for 2–3 wks
- Preferred regimen (3):
- If patients age is 3 months to < 2 years: Moxifloxacin 12 mg/kg/day IV, divided q12h (not to exceed 200 mg/dose) for 2–3 wks
- If patients age is 2-5 years: Moxifloxacin 10 mg/kg/day IV divided q1h (not to exceed 200 mg/dose) for 2–3 wks
- If patients age is 6–11 years: Moxifloxacin 8 mg/kg/day IV divided q12h (not to exceed 200 mg/dose) for 2–3 wks
- If patients age is 12–17 years, = 45 kg body weight: Moxifloxacin 400 mg IV q24h for 2–3 wks
- If patients age is 12–17 years, < 45 kg body weight: Moxifloxacin 8 mg/kg/day IV divided q12h (not to exceed 200 mg/dose) for 2–3 wks AND
- 3.2.3.2 A bactericidal antimicrobial (ß-lactam or glycopeptide)
- 3.2.3.2.1 For all strains, regardless of penicillin susceptibility testing or if susceptibility is unknown:
- Preferred regimen (1): Meropenem 120 mg/kg/day IV divided q8h (not to exceed 2 g/dose) for 2–3 wks
- Preferred regimen (2): Imipenem/Cilastatin 100 mg/kg/day IV divided q6h (not to exceed 1 g/dose) for 2–3 wks
- Preferred regimen (3): Doripenem 120 mg/kg/day IV divided q8h (not to exceed 1 g/dose) for 2–3 wks
- Preferred regimen (4): Vancomycin 60 mg/kg/day IV divided q8h for 2–3 wks
- 3.2.3.2.2 Alternatives for penicillin-susceptible strains
- Alternative regimen (1): Penicillin G 400 000 U/kg/day IV divided q4h (not to exceed 4 MU/dose) for 2–3 wks
- Alternative regimen (2): Ampicillin 400 mg/kg/day IV divided q6h (not to exceed 3 g/dose) for 2–3 wks AND
- 3.2.3.3 A Protein Synthesis Inhibitor
- Preferred regimen (1):
- If patients age is < 12 y old: Linezolid 30 mg/kg/day IV divided q8h for 2–3 wk
- If patients age is = 12 y old: Linezolid 30 mg/kg/day,IV divided q12h (not to exceed 600 mg/dose) for 2–3 wk
- Preferred regimen (2): Clindamycin 40 mg/kg/day IV divided q8h (not to exceed 900 mg/dose) for 2–3 wk
- Preferred regimen (3): Rifampin 20 mg/kg/day IV divided q12h (not to exceed 300 mg/dose) for 2–3 wk
- Preferred regimen (4): Chloramphenicol 100 mg/kg/day IV divided q6h for 2–3 wk
- 3.2.4 Oral follow-up combination therapy for severe anthrax (for Children 1 Month of Age and Older)
- 3.2.4.1 A bactericidal antimicrobial
- 3.2.4.1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day PO bid (not to exceed 500 mg/dose)
- Preferred regimen (2):
- If patients body weight is < 50 kg: Levofloxacin 16 mg/kg/day PO bid (not to exceed 250 mg/dose)
- If patients body weight is = 50 kg: Levofloxacin 500 mg PO qd
- 3.2.4.1.2 Alternatives for penicillin-susceptible strains
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid (not to exceed 1 g/dose)
- Alternative regimen (2): Penicillin VK 50–75 mg/kg/day PO tid or qds AND
- 3.2.4.2 A protein synthesis inhibitor:
- Preferred regimen (1):Clindamycin 30 mg/kg/day PO tid (not to exceed 600 mg/dose)
- Preferred regimen (2):
- If the patients body weight is < 45 kg: Doxycycline 4.4 mg/kg/day PO bid (not exceed 100 mg/dose)
- If the patients body weight is = 45 kg: Doxycycline 100 mg PO bid
- Preferred regimen (3): (non-CNS infection dose):
- If the patients age is < 12 yrs old: Linezolid 30 mg/kg/day PO tid
- If the patients age is = 12 yrs old: Linezolid 30 mg/kg/day PO bid (not to exceed 600 mg/dose)
- Note: Duration of therapy to complete a treatment course of 14 days or greater. May require prophylaxis to complete an antimicrobial course of up to 60 days from onset of illness.
- 3.2.5 Dosing in preterm and term neonates 32 to 44 Weeks postmenstrual Age (Gestational Age Plus Chronologic Age)
- 3.2.5.1 Triple therapy for severe anthrax(anthrax meningitis or disseminated infection and meningitis cannot be ruled out)
- 3.2.5.1.1 Bactericidal antimicrobial (fluoroquinolone) therapy
- 3.2.5.1.1.1 For 32–34 weeks gestational age
- For 0–1 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (2): Moxifloxacin 5 mg/kg/day IV q24h for 2–3 weeks
- For 1–4 weeks of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (2): Moxifloxacin 5 mg/kg/day IV q24h for 2–3 weeks
- 3.2.5.1.1.2 For 34–37 week gestational age
- For 0–1 wk of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (2):Moxifloxacin 5 mg/kg/day IV q24h for 2–3 weeks
- For 1–4 wk of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (2): Moxifloxacin 5 mg/kg/day IV q24h for 2–3 weeks
- 3.2.5.1.1.3 Term newborn infant
- For 0–1 week of age
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (2): Moxifloxacin 10 mg/kg/day IV q24h for 2–3 weeks
- For 1–4 weeks of age
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (2): Moxifloxacin 10 mg/kg/day IV q24h for 2–3 weeks AND
- 3.2.5.1.2 A bactericidal antimicrobial (ß-lactam)
- 3.2.5.1.2.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown:
- 3.2.5.1.2.1.1 For 32–34 weeks gestational age
- For 0–1 week of Age :
- Preferred regimen (1): Meropenem 60 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Imipenem 50 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (3): Doripenem 20 mg/kg/day IV divided q12h for 2–3 weeks
- For 1–4 wk of Age :
- Preferred regimen (1): Meropenem 90 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Imipenem 75 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (3): Doripenem 30 mg/kg/day IV divided q8h for 2–3 weeks
- 3.2.5.1.2.1.2 For 34–37 week gestational age
- For 0–1 week of Age :
- Preferred regimen (1): Meropenem 60 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Imipenem 50 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (3): Doripenem 20 mg/kg/day IV divided q12h for 2–3 weeks
- For 1–4 week of Age :
- Preferred regimen (1): Meropenem 90 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Imipenem 75 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (3): Doripenem 30 mg/kg/day IV divided q8h for 2–3 weeks
- 3.2.5.1.2.1.3 Term newborn infant
- For < 1 week of age
- Preferred regimen (1): Meropenem 60 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Imipenem 50 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (3): Doripenem 20 mg/kg/day IV divided q12h for 2–3 weeks
- For 1–4 week of age
- Preferred regimen (1): Meropenem 90 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Imipenem 75 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (3): Doripenem 30 mg/kg/day IV divided q8h for 2–3 weeks
- 3.2.5.1.2.2 Alternatives for penicillin-susceptible strains
- 3.2.5.1.2.2.1 For 32–34 weeks gestational age
- For 0–1 week of age
- Alternative regimen (1): Penicillin G 200000 Units/kg/day IV divided q12h for 2–3 weeks
- Alternative regimen (2): Ampicillin 100 mg/kg/day IV divided q12h for 2–3 weeks
- For 1–4 week of age :
- Alternative regimen (1): Penicillin G 300000 Units/kg/day IV divided q12h for 2–3 weeks
- Alternative regimen (2): Ampicillin 150 mg/kg/day divided IV q12h for 2–3 weeks
- 3.2.5.1.2.2.2 For 34–37 week gestational age
- For < 1 week of age
- Alternative regimen (1): Penicillin G 300000 Units/kg/day IV divided q12h for 2–3 weeks
- Alternative regimen (2): Ampicillin 150 mg/kg/day IV divided q12h for 2–3 weeks
- For 1–4 week of age
- Alternative regimen (1): Penicillin G 400000 Units/kg/day IV divided q12h for 2–3 weeks
- Alternative regimen (2): Ampicillin 200 mg/kg/day IV divided q12h for 2–3 weeks
- 3.2.5.1.2.2.3 Term newborn infant
- For 0–1 week of age
- Alternative regimen (1): Penicillin G 300000 Units/kg/day IV divided q12h for 2–3 weeks
- Alternative regimen (2): Ampicillin 150 mg/kg/day IV divided q12h for 2–3 weeks
- For 1–4 week of age
- Alternative regimen (1): Penicillin G 400000 Units/kg/day IV divided q12h for 2–3 weeks
- Alternative regimen (2): Ampicillin 200 mg/kg/day IV divided q12h for 2–3 weeks AND
- 3.2.5.1.3 A protein synthesis inhibitor
- 3.2.5.1.3.1 For 32–34 weeks gestational age
- For < 1 week of age
- Preferred regimen (1): Linezolid 20 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (2): Clindamycin 10 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (4): Chloramphenicol 25 mg/kg/day IV q24h for 2–3 weeks
- For 1–4 week of age
- Preferred regimen (1): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (4): Chloramphenicol 50 mg/kg/day IV q12h for 2–3 weeks
- 3.2.5.1.3.2 For 34–37 week gestational age
- For < 1 week of age
- Preferred regimen (1): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (4): Chloramphenicol 25 mg/kg/day IV q24h for 2–3 weeks
- For 1–4 week of age
- Preferred regimen (1): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Clindamycin 20 mg/kg/day IV divided q6h for 2–3 weeks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (4): Chloramphenicol 50 mg/kg/day IV q12h for 2–3 weeks
- 3.2.5.1.3.3 Term newborn infant
- For < 1 week of age
- Preferred regimen (1): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (4): Chloramphenicol 25 mg/kg/day IV q24h for 2–3 weeks
- For 1–4 week of age
- Preferred regimen (1): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Clindamycin 20 mg/kg/day IV divided q6h for 2–3 weeks
- Preferred regimen (3): Rifampin 20 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (4): Chloramphenicol 50 mg/kg/day IV q12h for 2–3 weeks
- Note :Duration of therapy for 2–3 weeks, until clinical criteria for stability are met. Will require prophylaxis to complete an antibiotic course of upto 60 days from onset of illness.
- 3.2.5.2 Therapy for severe anthrax when meningitis can be ruled out
- 3.2.5.2.1 A bactericidal antimicrobial
- 3.2.5.2.1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- 3.2.5.2.1.1.1 For 32–34 weeks gestational age
- For < 1 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2-3 weeks
- Preferred regimen (2): Meropenem 40 mg/kg/day IV divided q8h for 2-3 weeks
- Preferred regimen (3): Imipenem 40 mg/kg/day IV divided q12h for 2-3 weeks
- For 1–4 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2-3 weeks
- Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h for 2-3 weeks
- Preferred regimen (3): Imipenem 50 mg/kg/day IV divided q12h for 2-3 weeks
- 3.2.5.2.1.1.2 For 34–37 week gestational age
- For < 1 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2-3 weeks
- Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h for 2-3 weeks
- Preferred regimen (3): Imipenem 50 mg/kg/day IV divided q12h for 2-3 weeks
- For 1–4 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2-3 weeks
- Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h for 2-3 weeks
- Preferred regimen (3): Imipenem 75 mg/kg/day IV divided q8h for 2-3 weeks
- 3.2.5.2.1.1.3 Term Newborn Infant
- For < 1 week of age
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q12h for 2-3 weeks
- Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h for 2-3 weeks
- Preferred regimen (3): Imipenem 50 mg/kg/day IV divided q12h for 2-3 weeks
- For 1–4 week of age
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q12h for 2-3 weeks
- Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h for 2-3 weeks
- Preferred regimen (3): Imipenem 75 mg/kg/day IV divided q8h for 2-3 weeks
- Vancomycin IV (dosing based on serum creatinine for infants of 32 wk gestational age). Follow vancomycin serum concentrations to modify dose.
- If Serum creatinine < 0.7 then Vancomycin 15 mg/kg/dose IV q12h for 2-3 weeks
- If Serum creatinine 0.7 -0.9 then Vancomycin 20 mg/kg/dose IV q24h for 2-3 weeks
- If Serum creatinine 1–1.2 then Vancomycin 15 mg/kg/dose IV q24h for 2-3 weeks
- If Serum creatinine 1.3–1.6 then Vancomycin 10 mg/kg/dose IV q24h for 2-3 weeks
- If Serum creatinine > 1.6 then Vancomycin mg/kg/dose IV q48h for 2-3 weeks
- Note: Begin treatment with a 20 mg/kg loading dose OR
- 3.2.5.2.1.2 Alternatives for penicillin-susceptible strains
- 3.2.5.2.1.2.1 For 32–34 weeks gestational age
- For < 1 week of age
- Alternative regimen (1): Penicillin G 200000 U/kg/day IV divided q12h for 2-3 weeks
- Alternative regimen (2): Ampicillin 100 mg/kg/day IV divided q12h for 2-3 weeks
- For 1–4 week of age
- Alternative regimen (1): Penicillin G 300000 U/kg/day IV divided q8h for 2-3 weeks
- Alternative regimen (2): Ampicillin 150 mg/kg/day IV divided q8h for 2-3 weeks
- 3.2.5.2.1.2.2 For 34–37 week gestational age
- For < 1 week of age
- Alternative regimen (1): Penicillin G 300000 U/kg/day IV divided q8h for 2-3 weeks
- Alternative regimen (2): Ampicillin 150 mg/kg/day IV divided q8h for 2-3 weeks
- For 1–4 week of age
- Alternative regimen (1): Penicillin G 400000 U/kg/day IV divided q6h for 2-3 weeks
- Alternative regimen (2): Ampicillin 200 mg/kg/day IV divided q6h for 2-3 weeks
- 3.2.5.2.1.2.3 Term newborn infant
- For < 1 week of age
- Alternative regimen (1): Penicillin G 300000 U/kg/day IV divided q8h for 2-3 weeks
- Alternative regimen (2): Ampicillin 150 mg/kg/day IV divided q8h for 2-3 weeks
- For 1–4 week of age
- Alternative regimen (1): Penicillin G 400000 U/kg/day IV divided q6h for 2-3 weeks
- Alternative regimen (2):Ampicillin 200 mg/kg/day IV divided q6h for 2-3 weeks
- 3.2.5.2.2 A protein synthesis inhibitor
- 3.2.5.2.2.1 For 32–34 weeks gestational age
- For < 1 week of age
- Preferred regimen (1): Clindamycin 10 mg/kg/day IV divided q12h for 2–3 wks
- Preferred regimen (2): Linezolid 20 mg/kg/day IV divided q12h for 2–3 wks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV q24h for 2–3 wks
- For 1–4 week of age
- Preferred regimen (1): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 wks
- Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 wks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV q24h for 2–3 wks
- 3.2.5.2.2.2 For 34–37 week gestational age
- For < 1 week of age
- Preferred regimen (1): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 wks
- Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 wks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV q24h for 2–3 wks
- For 1–4 week of age
- Preferred regimen (1): Clindamycin 20 mg/kg/day IV divided q6h for 2–3 wks
- Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 wks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV q24h for 2–3 wks
- 3.2.5.2.2.3 Term newborn infant
- For 0–1 week of age :
- Preferred regimen (1): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 wks
- Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 wks
- Preferred regimen (3): Doxycycline 4.4 mg/kg/day IV divided q12h, (loading dose 4.4 mg/kg) for 2–3 wks
- Preferred regimen (4): Rifampin 10 mg/kg/day IV q24h for 2–3 wks
- For 1–4 week of age :
- Preferred regimen (1): Clindamycin 20 mg/kg/day IV divided q6h for 2–3 wks
- Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 wks
- Preferred regimen (3): Doxycycline 4.4 mg/kg/day IV divided q12h, (loading dose 4.4 mg/kg) for 2–3 wks
- Preferred regimen (4): Rifampin 10 mg/kg/day IV q24h for 2–3 wks
- Note: Duration of therapy for 2–3 wks, until clinical criteria for stability are met (see text). Will require prophylaxis to complete an antimicrobial course of upto 60 days from onset of illness
- 3.2.5.3 Oral follow-up combination therapy for severe anthrax
- 3.2.5.3.1 A bactericidal antimicrobial
- 3.2.5.3.1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- 3.2.5.3.1.1.1 For 32–34 weeks gestational age
- For < 1 week of age
- Preferred regimen: Ciprofloxacin 20 mg/kg/day PO bid
- For 1–4 week of age
- Preferred regimen: Ciprofloxacin 20 mg/kg/day PO bid
- 3.2.5.3.1.1.2 For 34–37 week gestational age
- For < 1 week of age
- Preferred regimen: Ciprofloxacin 20 mg/kg/day PO bid
- For 1–4 week of age
- Preferred regimen: Ciprofloxacin 20 mg/kg/day PO bid
- 3.2.5.3.1.1.3 Term newborn infant
- For < 1 week of age
- Preferred regimen: Ciprofloxacin 30 mg/kg/day PO bid
- For 1–4 week of age
- Preferred regimen: Ciprofloxacin 30 mg/kg/day PO bid OR
- 3.2.5.3.1.2 Alternatives for penicillin-susceptible strains
- 3.2.5.3.1.2.1 For 32–34 weeks gestational age
- For < 1 week of age
- Alternative regimen (1): Amoxicillin 50 mg/kg/day PO bid
- Alternative regimen (2): Penicillin VK 50 mg/kg/day PO bid
- For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO bid
- Alternative regimen (2): Penicillin VK 75 mg/kg/day PO bid
- 3.2.5.3.1.2.2 For 34–37 week gestational age
- For < 1 week of age
- Alternative regimen (1): Amoxicillin 50 mg/kg/day PO bid
- Alternative regimen (2): Penicillin VK 50 mg/kg/day PO bid
- For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO bid
- Alternative regimen (2): Penicillin VK 75 mg/kg/day PO tid
- 3.2.5.3.1.2.3 Term newborn infant
- For < 1 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid
- Alternative regimen (2): Penicillin VK 75 mg/kg/day PO tid
- For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid
- Alternative regimen (2): Penicillin VK 75 mg/kg/day PO tid or qid
- 3.2.5.3.2 A protein synthesis inhibitor
- 3.2.5.3.2.1 For 32–34 weeks gestational age
- For < 1 week of age
- Preferred regimen (1): Clindamycin 10 mg/kg/day PO bid
- Preferred regimen (2): Linezolid 20 mg/kg/day PO bid
- For 1–4 week of age
- Preferred regimen (1): Clindamycin 15 mg/kg/day PO bid
- Preferred regimen (2): Linezolid 30 mg/kg/day PO bid
- 3.2.5.3.2.2 For 34–37 week gestational age
- For < 1 week of age
- Preferred regimen (1): Clindamycin 15 mg/kg/day PO tid
- Preferred regimen (2): Linezolid 30 mg/kg/day PO tid
- For 1–4 week of age
- Preferred regimen (1): Clindamycin 20 mg/kg/day PO qid
- Preferred regimen (2): Linezolid 30 mg/kg/day PO tid
- 3.2.5.3.2.3 Term newborn infant
- For < 1 week of age
- Preferred regimen (1): Clindamycin 15 mg/kg/day PO tid
- Preferred regimen (2): Doxycycline 4.4 mg/kg/day PO bid (loading dose 4.4 mg/kg)
- Preferred regimen (3): Linezolid 30 mg/kg/day PO tid
- For 1–4 week of age
- Preferred regimen (1): Clindamycin 20 mg/kg/day PO qid
- Preferred regimen (2): Doxycycline 4.4 mg/kg/day PO bid (loading dose 4.4 mg/kg)
- Preferred regimen (3): Linezolid 30 mg/kg/day PO tid
- Note: Duration of therapy to complete a treatment course of 10–14 days or greater. May require prophylaxis to complete an antimicrobial course of upto 60 days from onset of illness.
- 3.2.5.4 Treatment of cutaneous anthrax without systemic involvement
- 3.2.5.4.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- 3.2.5.4.1.1 For 32–34 weeks gestational age
- For < 1 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day PO bid
- Preferred regimen (2): Clindamycin 10 mg/kg/day PO bid
- For 1–4 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day PO bid
- Preferred regimen (2): Clindamycin 15 mg/kg/day PO tid
- 3.2.5.4.1.2 For 34–37 week gestational age
- For < 1 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day PO bid
- Preferred regimen (2): Clindamycin 15 mg/kg/day PO tid
- For 1–4 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day PO bid
- Preferred regimen (2): Clindamycin 20 mg/kg/day PO qid
- 3.2.5.4.1.3 Term newborn infant
- For < 1 week of age
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day PO bid
- Preferred regimen (2): Doxycycline 4.4 mg/kg/day PO bid (Loading dose 4.4 mg/kg)
- Preferred regimen (3): Clindamycin 15 mg/kg/day PO tid
- For 1–4 week of age
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day PO bid
- Preferred regimen (2): Doxycycline 4.4 mg/kg/day PO bid (Loading dose 4.4 mg/kg)
- Preferred regimen (3): Clindamycin 20 mg/kg/day PO qid
- 3.2.5.4.2 Alternatives for penicillin-susceptible strains
- 3.2.5.4.2.1 For 32–34 weeks gestational age
- For < 1 week of age
- Alternative regimen (1): Amoxicillin 50 mg/kg/day PO bid
- Alternative regimen (2): Penicillin Vk 50 mg/kg/day PO bid
- For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid
- Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO tid
- 3.2.5.4.2.2 For 34–37 week gestational age
- For < 1 week of age
- Alternative regimen (1): Amoxicillin 50 mg/kg/day PO bid
- Alternative regimen (2): Penicillin Vk 50 mg/kg/day PO bid
- For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO bid
- Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO bid
- 3.2.5.4.2.3 Term newborn infant
- For < 1 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid
- Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO tid
- For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid
- Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO tid or qid
- Note : Duration of therapy for naturally acquired infection is 7–10 days and for a biological weapon–related event,may require additional prophylaxis for inhaled spores to complete an antimicrobial course of up to 60 days from onset of illness.
- Bacillus anthracis, postexposure prophylaxis
- 1. For adults
- 1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- Preferred regimen (1): Ciprofloxacin 500 mg IV q12h
- Preferred regimen (2): Doxycycline 100 mg IV q12h
- Preferred regimen (3): Levofloxacin 750 mg IV q24h
- Preferred regimen (4): Moxifloxacin 400 mg IV q24h
- Preferred regimen (5): Clindamycin 600 mg IV q8h
- 1.2 Alternatives for penicillin-susceptible strain
- Preferred regimen (1): Amoxicillin 1 g IV q8h
- Preferred regimen (2): Penicillin VK 500 mg IV q6h
- 2. For children = 1 month
- 2.1 For penicillin-resistant strains or prior to susceptibility testing
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day, PO, bid (not to exceed 500 mg/dose)
- Preferred regimen (2):
- If patients body weight < 45 kg: Doxycycline 4.4 mg/kg/day, PO, bid (not to exceed 100 mg/dose)
- If patients body weight > 45 kg: Doxycycline 100 mg/dose, PO, bid
- Preferred regimen (3): Clindamycin 30 mg/kg/day, PO, tid (not to exceed 900 mg/dose)
- Preferred regimen (4):
- If patients body weight < 50 kg: Levofloxacin 16 mg/kg/day, PO, bid (not to exceed 250 mg/dose)
- If patients body weight > 50 kg: Levofloxacin 500 mg, PO, qd
- 2.2 For penicillin-susceptible strains
- Preferred regimen (1): Amoxicillin 75 mg/kg/day, PO, tid (not to exceed 1 g/dose)
- Preferred regimen (2): Penicillin VK 50-75 mg/kg/day, PO, id or tid
- Note: Duration of Therapy is 60 days after exposure
- 3. For children < 1 month
- 3.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- 3.1.1 For 32–34 weeks gestational age
- 3.1.1.1 For < 1 week of Age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day, PO, bid
- Preferred regimen (2): Clindamycin 10 mg/kg/day, PO, bid
- 3.1.1.2 For 1–4 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day, PO,bid
- Preferred regimen (2): Clindamycin 15 mg/kg/day, PO, tid
- 3.1.2 For 34–37 week gestational age
- 3.1.2.1 For < 1 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day, PO, bid
- Preferred regimen (2): Clindamycin 15 mg/kg/day, PO, tid
- 3.1.2.2 For 1–4 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day, PO, bid
- Preferred regimen (2): Clindamycin 20 mg/kg/day, PO, id
- 3.1.3 Term newborn infant
- 3.1.3.1 For < 1 week of age
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day, PO, bid
- Preferred regimen (2): Doxycycline 4.4 mg/kg/day, PO, bid (Loading dose 4.4 mg/kg)
- Preferred regimen (3): Clindamycin 15 mg/kg/day, PO, tid
- 3.1.3.2 For 1–4 week of Age
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day, PO, bid
- Preferred regimen (2): Doxycycline 4.4 mg/kg/day, PO, bid (Loading dose 4.4 mg/kg)
- Preferred regimen (3): Clindamycin 20 mg/kg/day, PO, qid
- 3.2 Alternatives for penicillin-susceptible strains
- 3.2.1 For 32–34 weeks gestational age
- 3.2.1.1 For < 1 week of age
- Alternative regimen (1): Amoxicillin 50 mg/kg/day, PO, bid
- Alternative regimen (2): Penicillin Vk 50 mg/kg/day, PO, bid
- 3.2.1.2 For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day, PO, tid
- Alternative regimen (2): Penicillin Vk 75 mg/kg/day, PO, tid
- 3.2.2 For 34–37 week gestational age
- 3.2.2.1 For < 1 week of age
- Alternative regimen (1): Amoxicillin 50 mg/kg/day, PO, bid
- Alternative regimen (2): Penicillin Vk 50 mg/kg/day, PO, bid
- 3.2.2.2 For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day, PO, tid
- Alternative regimen (2): Penicillin Vk 75 mg/kg/day, PO, tid
- 3.2.3 Term newborn infant
- 3.2.3.1 For < 1 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day, PO, tid
- Alternative regimen (2): Penicillin Vk 75 mg/kg/day, PO, tid
- 3.2.3.2 For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day, PO, tid
- Alternative regimen (2): Penicillin Vk 75 mg/kg/day, PO, id or tid
- Note: Duration of therapy is 60 days from exposure
- Bacillus cereus Return to Top
- 1. Food poisoning
- Preferred regimen: Food poisoning is usually self-limited and requires no antibiotic therapy.
- 2. Bacteremia
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- Note (1): Bacillus cereus is commonly resistant to beta-lactams.
- Note (2): Pseudobacteremia is transient and usually results from contaminated blood cultures, gloves, or syringes.
- 3. Meningitis or brain abscess
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- Note: Blood culture isolates are mostly contaminates until proven otherwise, especially in intravenous drug user population.
- 4. Endophthalmitis
- Preferred regimen: Clindamycin 450 μg intravitreal AND Gentamicin 400 μg intravitreal OR Dexamethasone intravitreal AND Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- Note: Ophthalmological consultation, culture ocular fluids, early vitrectomy, and intravitreal antibiotics are necessary.
- 5. Endocarditis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Note: Most blood cultures in intravenous drug users are contaminates or represent transient bacteremia.
- 6. Soft tissue infection
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- 7. Pneumonia
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- Bacillus subtilis Return to Top
- Bacillus subtilis infection treatment
- 1. Food poisoning
- Preferred regimen: supportive treatment
- 2. Other infections
- Preferred regimen: Vancomycin OR Clindamycin
- Alternative regimen: Ciprofloxacin OR Imipenem
- Note: Distinguish clinically significant infection from contamination before administering antibiotics.
- Clostridium botulinum Return to Top
- Botulism
- 1.Foodborne botulism
- 1.1 Adult
- Preferred regimen: Heptavalent botulism antitoxin IV starting infusion rate (first 30 minutes): 0.5 mL/min; incremental infusion rate if tolerated (every 30 minutes): double the rate; maximum infusion rate: 2 mL/min
- 1.2 Children
- 1.2.1 Children < 1 year
- Preferred regimen: Heptavalent botulism antitoxin IV starting infusion rate (first 30 minutes): 0.01 mL/kg/min; incremental infusion rate if tolerated (every 30 minutes): 0.01 mL/kg/min ; maximum infusion rate: 0.03 mL/kg/min (10% of adult dose regardless of body weight)
- 1.2.1 Children 1-17 years
- Preferred regimen: Heptavalent botulism antitoxin IV starting infusion rate (first 30 minutes): 0.01 mL/kg/min; incremental infusion rate if tolerated (every 30 minutes): 0.01 mL/kg/min ; maximum infusion rate: 0.03 mL/kg/min (20 – 100% of adult dose)
- Note:Physicians may try to remove contaminated food still in the gut by inducing vomiting or by using enemas. A patient with severe botulism may require a ventilator as well as intensive medical and nursing care for several months.
- 2. Infant botulism
- Preferred regimen: BabyBIG, Botulism Immune Globulin Intravenous (Human) (BIG-IV) is for the treatment of patients below one year of age.The recommended total dosage is 1mL/kg (50mg/kg), given as a single IV infusion as soon as the clinical diagnosis of infant botulism is made
- Note: infant with botulism must receive supportive care during their recovery. This includes ensuring proper nutrition,keeping the airway clear,watching for respiratory failure and if it develops,ventilator may be needed.
- 3. Wound botulism
- 3.1 Adult
- Preferred regimen (adult): Heptavalent botulism antitoxin IV starting infusion rate (first 30 minutes): 0.5 mL/min; incremental infusion rate if tolerated (every 30 minutes): double the rate; maximum infusion rate: 2 mL/min
- 3.2 Children
- 3.2.1 Children < 1 year
- Preferred regimen: Heptavalent botulism antitoxin IV starting infusion rate (first 30 minutes): 0.01 mL/kg/min; incremental infusion rate if tolerated (every 30 minutes): 0.01 mL/kg/min ; maximum infusion rate: 0.03 mL/kg/min (10% of adult dose regardless of body weight)
- 3.2.2 Children 1-17 years
- Preferred regimen: Heptavalent botulism antitoxin IV starting infusion rate (first 30 minutes): 0.01 mL/kg/min; incremental infusion rate if tolerated (every 30 minutes): 0.01 mL/kg/min ; maximum infusion rate: 0.03 mL/kg/min (20 – 100% of adult dose)
- Note (1): Physicians may try to remove contaminated food still in the gut by inducing vomiting or by using enemas. A patient with severe botulism may require a ventilator as well as intensive medical and nursing care for several months.
- Note (2): For wound botulism, antibiotics are used in addition to appropriate debridement.
- Note (3): Antibiotic therapy is recommended for wound botulism after antitoxin has been administered. Penicillin G 3 MU IV q4h in adults is frequently used. Metronidazole 500 mg IV q8h may be used as an alternative for penicillin-allergic patients.
- Clostridium perfringens Return to Top
- Clostridium perfringens
- Gas gangrene
- Preferred regimen: Penicillin G 3-4 million units IV q4h AND (Clindamycin 900 mg IV q8h OR Tetracycline 500 mg IV q6h)
- Clostridium tetani Return to Top
- 1. General measures
- Preferred regimen: Patients should be placed in a quiet shaded area and protected from tactile and auditory stimulation as much as possible; All wounds should be cleaned and debrided as indicated
- 2. Immunotherapy
- Preferred regimen: Human TIG 500 units IV/IM as soon as possible AND Age-appropriate TT-containing vaccine, 0.5 cc IM at a separate site
- Note: patients without a history of primary TT vaccination should receive a second dose 1–2 months after the first dose and a third dose 6–12 months later
- 3. Antibiotic treatment
- Preferred regimen: Metronidazole 500 mg IV/PO q6h OR Penicillin G 100,000–200,000 IU/kg/day IV, administered in 2–4 divided doses
- Alternative regimen: Tetracyclines OR Macrolides OR Clindamycin OR Cephalosporins OR Chloramphenicol
- 4. Muscle spasm control
- Preferred regimen: Diazepam 5 mg IV OR Lorazepam 2 mg IV titrating to achieve spasm control without excessive sedation and hypoventilation
- Alternative regimen (1): Magnesium sulphate 5 g (or 75mg/kg) IV loading dose, then 2–3 g per hour until spasm control is achieved ± Benzodiazepines
- Note: Monitor patellar reflex as areflexia (absence of patellar reflex) occurs at the upper end of the therapeutic range (4mmol/L). If areflexia develops, dose should be decreased
- Alternative regimen (2): Baclofen OR Dantrolene 1–2 mg/kg IV/PO q4h
- Alternative regimen (3): Barbiturates 100–150 mg q1-4h by any route
- Alternative regimen (4): Chlorpromazine 50–150 mg IM q4–8h
- Pediatric regimen: Lorazepam 0.1–0.2 mg/kg IV q2–6h, titrating upward as needed; Barbiturates 6–10 mg/kg in children by any route; Chlorpromazine 4–12 mg IM every q4–8h
- Note: As for Benzodiazepines, large amounts may be required (up to 600 mg/day); oral preparations could be used but must be accompanied by careful monitoring to avoid respiratory depression or arrest
- 5. Autonomic dysfunction control
- Preferred regimen: Magnesium sulphate OR Morphine OR Esmolol
- 6. Airway/respiratory control
- Note: Drugs used to control spasm and provide sedation can result in respiratory depression. If spasm, including laryngeal spasm, is impeding or threatening adequate ventilation, mechanical ventilation is recommended when possible. Early tracheostomy is preferred as endotracheal tubes can provoke spasm and exacerbate airway compromise.
- Clostridium difficile Return to Top
- 1. Pseudomembranous colitis - mild to moderate
- Preferred regimen:Metronidazole 500 mg PO tid for 10-14 days
- Alternative regimen: Vancomycin 125 mg PO qid for 10-14 days
- Note: If significant risk of recurrence: Vancomycin 125 mg PO qid for 10-14 days OR Fidaxomicin 200 mg PO bid for 10 days
- 2. Pseudomembranous colitis - severe
- Preferred regimen: Vancomycin 125 mg PO qid for 10-14 days
- Note: If significant risk of recurrence: Vancomycin 125 mg PO qid for 10-14 days OR Fidaxomicin 200 mg PO bid for 10 days
- 3. Pseudomembranous colitis - severe, complicated
- Preferred regimen: Vancomycin 125-500 mg PO qid for 10-14 days AND Vancomycin 500 mg diluted in 500 ml of saline as enema per rectum q6h AND Metronidazole 500 mg IV q8h
- Note: Consider urgent surgical consult
- 4. Recurrent pseudomembranous colitis
- First recurrence treatment
- Preferred regimen: same as first episode or ] 200 mg PO bid for 10 days
- Second or more recurrence treatment
- Preferred regimen: Vancomycin 125 mg PO qid for 14 days THEN Vancomycin 125 mg PO tid for 7 days THEN Vancomycin 125 mg PO bid for 7 days THEN Vancomycin 125 mg PO qd for 7 days THEN Vancomycin 125 mg PO q48h for 7 days THEN Vancomycin 125 mg PO q72h for 7 days OR Fidaxomicin 200 mg PO bid for 10 days
- Note: Consider expert consult for fecal microbiota transplantation
# Corynebacterium
- Corynebacterium diphtheriae Return to Top
- Diphtheria treatment
- 1. Antitoxin
- 1.1 Pharyngeal disease <48 hrs
- Preferred regimen: 20,000-40,000 U IV/IM
- 1.2 Nasopharyngeal
- Preferred regimen: 40-60,000 U IV/IM
- 1.3 Extensive disease, or > 72 hrs
- Preferred regimen: 80-120,000 U IV/IM
- Note: IV administration for severe disease
- 2. Antibiotics
- Preferred regimen: Erythromycin 40 mg/kg/day (Maximum, 2 gm/day) PO/IV for 14 days
- Alternative regimen: Procaine penicillin G 600,000 U/day IM qd for 14 days
- Note: Procaine penicillin G 300,000 U/day for those weighing 10 kg or less
- 3. Preventive antibiotic use
- Note: For close contacts, especially household contacts, a diphtheria booster, appropriate for age, should be given
- Preferred regimen: Benzathine penicillin G
- younger than 6 years old: 600,000 U IM
- 6 years old and older: 1,200,000 U IM
- Alternative regimen: Erythromycin
- Adult: 1 g/day PO 7-10 days
- Pediatric: 40 mg/kg/day PO 7-10 days
- Note (1): If surveillance of contacts cannot be maintained, they should receive benzathine penicillin G
- Note (2): Maintain close surveillance and begin antitoxin at the first signs of illness
- Corynebacterium jeikeium Return to Top
- Corynebacterium jeikeium
- Preferred regimen : Vancomycin 1 gm IV q12h
- Alternative regimen : Penicillin G AND Anti pseudomonal aminoglycosides like Tobramycin, Gentamicin, Amikacin
- Corynebacterium urealyticum Return to Top
- Corynebacterium urealyticum
- 1. Post renal transplant obstructive uropathy
- Preferred regimen (1): Vancomycin 1 gm IV q12h
- Preferred regimen (2): Teicoplanin 6 mg/kg/day IV q24h
- Coxiella burnetii Return to Top
- Q fever
- 1. Acute Q fever
- 1.1 Adults
- Preferred Regimen: Doxycycline 100 mg PO bid for 14 days
- 1.2 Children
- 1.2.1 Children with age ≥8 years
- Preferred regimen: Doxycycline 2.2 mg/kg PO bid for 14 days (maximum 100 mg per dose)
- 1.2.2 Children with age <8 years with high risk criteria
- Preferred regimen: Doxycycline 2.2 mg/kg PO bid for 14 days (maximum: 100 mg per dose)
- 1.2.3 Children with age <8 years with mild or uncomplicated illness
- Preferred regimen: Doxycycline 2.2 mg/kg PO bid for 5 days (maximum 100 mg per dose).
- 1.2.3 Children with age < 8 years with mild or uncomplicated illness,who remains febrile past 5 days of treatment
- Preferred regimen: Trimethoprim/Sulfamethoxazole 4-20 mg/kg PO bid for 14 days (maximum: 800 mg per dose)
- 1.3 Pregnant women
- Preferred regimen: Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO bid a day throughout pregnancy
- 2. Chronic Q fever
- 2.1 Endocarditis or vascular infection
- Preferred regimen: Doxycycline 100 mg PO bid AND Hydroxychloroquine 200 mg PO tid for ≥18 months
- Note: childern and pregnant women- consultation Recommended
- 2.2 Noncardiac organ disease
- Preferred regimen: Doxycycline 100 mg PO bid AND Hydroxychloroquine 200 mg PO tid
- Note: childern and pregnant women- consultation Recommended
- 2.3 Postpartum with serologic profile for chronic Q fever
- Preferred regimen: Doxycycline 100 mg PO bid AND Hydroxychloroquine 200 mg PO tid for 12 months
- Note (1): Women should only be treated postpartum if serologic titers remain elevated >12 months after delivery (immunoglobulin G phase I titer ≥1:1024). Women treated during pregnancy for acute Q fever should be monitored similarly to other patients who are at high risk for progression to chronic disease (e.g., serologic monitoring at 3, 6, 12, 18, and 24 months after delivery)
- Note (2): Post-Q fever fatigue syndrome- no current recommendation.
- Ehrlichia Return to Top
- 1. Human Monocytic Ehrlichiosis or Human Granulocytic Anaplasmosis (adult)
- Preferred regimen: Doxycycline 100 mg PO/IV q12h for 7-14 days
- Note: Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement
- Alternative regimen (1): Chloramphenicol 500mg PO qid
- Alternative regimen (2): Rifampin 600 mg PO/IV qd for 7-10 days
- 2. Human Monocytic Ehrlichiosis or Human Granulocytic Anaplasmosis (pediatric)
- 2.1 ≥ 8 years old
- Preferred regimen: Doxycycline 2 mg/kg IV/PO q12h (Maximum, 200 mg/day) for 10 days
- 2.2 < 8 years old without Lyme disease
- Preferred regimen: Doxycycline 2 mg/kg IV/PO q12h (Maximum, 200 mg/day) for 4-5 days (or 3 days after resolution of fever)
- 2.3 co-infected with Lyme disease
- Preferred regimen: Doxycycline (see above) THEN Amoxicillin 50 mg/kg/day tid (Maximum, 500 mg/dose) OR Cefuroxime 30 mg/kg/day bid (Maximum, 500 mg/dose) for 14 days
- Erysipelothrix rhusiopathiae Return to Top
- Erysipelothrix rhusiopathiae
- 1. Erysipeloid of Rosenbach (localized cutaneous infection)
- Preferred regimen (1): Penicillin G benzathine 1.2 MU IV single dose
- Preferred regimen (2): Penicillin VK 250 mg PO qid for 5-7 days
- Preferred regimen (3): Procaine penicillin 0.6-1.2 MU IM qd for 5-7 days
- Alternative regimen (1): Erythromycin 250 mg PO qid for 5-7 days
- Alternative regimen (2): Doxycycline 100 mg PO bid for 5-7 days
- 2. Diffuse cutaneous infection
- Preferred regimen: See localized infection
- 3. Bacteremia or endocarditis
- Preferred regimen: Penicillin G benzathine 2-4 MU IV q4h for 4-6 weeks
- Alternative regimen (1): Ceftriaxone 2 g IV q24h for 4-6 weeks
- Alternative regimen (2): Imipenem 500 mg IV q6h for 4-6 weeks
- Alternative regimen (3): Ciprofloxacin 400 mg IV q12h for 4-6 weeks
- Alternative regimen (4): Daptomycin 6 mg/kg IV q24h for 4-6 weeks
- Note: Recommended duration of therapy for endocarditis is 4 to 6 weeks, although shorter courses consisting of 2 weeks of intravenous therapy followed by 2 to 4 weeks of oral therapy have been successful
- Listeria monocytogenes Return to Top
- 1. Meningitis
- Preferred regimen: Ampicillin 2g IV q4-6h ± Gentamicin 1.7 mg/kg IV q8h for more than 3 weeks
- Alternative regimen: TMP-SMX 3-5 mg/kg (trimethoprim) IV q6h for more than 3 weeks
- 2. Bacteremia
- Preferred regimen: Ampicillin 2g IV q4-6h ± Gentamicin 1.7 mg/kg IV q8h for 2 weeks
- Alternative regimen: TMP-SMX 3-5 mg/kg (trimethoprim) q6h IV for 2 weeks
- 3. Brain abscess or rhomboencephalitis
- Preferred regimen: Ampicillin 2g IV q4-6h ± Gentamicin 1.7 mg/kg IV q8h for 4-6 weeks
- Alternative regimen: TMP-SMX 3-5 mg/kg (trimethoprim) q6h IV for 4-6 weeks
- 4. Gastroenteritis
- Preferred regimen (1): Amoxicillin 2g IV q4-6h
- Preferred regimen (2): TMP-SMX 3-5 mg/kg (trimethoprim) q6h IV for 7 days
- Lactobacillus Return to Top
- 1. Endovascular Infection
- Preferred regiemn (1): Penicillin G 20 MU/day for 6 weeks
- Preferred regiemn (2): Gentamicin 1.3 mg/kg IV q8h (trough <1.5 mg/L) AND Polychlorinated naphthalene
- 2. Odontogenic Infection
- Preferred regiemn: Clindamycin 450 mg PO qid
- 3. Intrabdominal Abscess
- Preferred regiemn: Clindamycin 450 mg PO qid
- Leuconostoc Return to Top
- Leuconostoc
- Preferred regimen (1): Penicillin G
- Preferred regimen (2): Ampicillin
- Alternative regimen (1): Clindamycin
- Alternative regimen (2): Erythromycin
- Alternative regimen (3): Minocycline
- Nocardia Return to Top
- 1. Sulfonamide-based therapies
- 1.1 Pulmonary
- Preferred regimen: TMP-SMX 10 mg/kg/day (TMP) IV q6-12h for 3-6 weeks THEN 2 DS PO bid for at least 5 months
- 1.2 Pulmonary alternatives
- Preferred regimen: Sulfisoxazole OR Sulfadiazine OR Trisulfapyrimidine 3-6 g/day PO bid-qid OR TMP-SMX 2 DS bid up to 2 DS tid
- 1.3 CNS (AIDS, severe or disseminated disease)
- Preferred regimen: TMP-SMX 15 mg/kg/day (TMP) IV for 3-6 weeks THEN 3 DS PO bid for 6-12 months
- 1.4 CNS alternatives
- Preferred regimen: Imipenem 1000 mg IV q8h OR Ceftriaxone 2 g IV q12h OR Cefotaxime 2-3 g IV q6h AND Amikacin
- 1.5 Severe disease, compromised host, multiple sites
- Preferred regimen: TMP-SMX 15 mg/kg/day (TMP) IV AND Amikacin 7.5 mg/kg q12h OR Sulfonamide 6-12 mg/day PO
- 1.6 Sporotrichoid (cutaneous)
- Preferred regimen: TMP-SMX 1 DS bid for 4-6 months
- Note (1): Immunocompetent medicine use for 6 months; Immunosuppressed medicine for 12 months
- Note (2): Treat based on host, site of disease and in vitro activity; Sulfonamide usually preferred, must treat for 6-12 months; Preferred drugs for resistant strains are Amikacin and/or Imipenem
- Note (3): Seriously ill usually treated with IV Imipenem or Sulfonamide or Cefotaxime all potentially combined with Amikacin; less seriously ill treated with oral agents— especially TMP-SMX or Minocycline
- 2. Sulfonamide alternatives
- 2.1 Severe
- Preferred regimen (1): (For AIDS) (Imipenem 1000 mg IV q8h OR Meropenem 2 g q8h AND Amikacin 7.5 mg/kg q12h IV
- Preferred regimen (2): Cefotaxime 2-3 g q6-8h OR Ceftriaxone 2 g/day IV ± Amikacin
- 2.2 Mild
- Preferred regimen: Minocycline 100 mg bid for at least 6 months (initial treatment of local disease or maintenance)
- Alternative regimen: Amoxicillin clavulanate 875/125 mg bid OR Doxycycline OR Erythromycin OR Clarithromycin OR Linezolid OR Fluoroquinolone OR combinations for at least 6 months
- Propionibacterium acnes Return to Top
- Propiobacterium acnes
- 1. Systemic infection
- Preferred regimen: Penicillin G 2 MU IV q4h for 2-4 weeks
- Alternative regimen (1): Clindamycin 600 mg IV q8h for 2-4 weeks
- Alternative regimen (2): Vancomycin 15 mg/kg IV q12h for 2-4 weeks
- 2. Shoulder prosthesis infection
- Preferred regimen: Amoxicillin AND Rifampin for 3-6 months
- 3. Acne vulgaris
- Topical antibiotics: Erythromycin OR Clindamycin
- Systemic antibiotics: Minocycline OR Doxycycline OR Trimethoprim-Sulfamethoxazole
- Rhodococcus equi Return to Top
- Rhodococcus equi
- First line:
- Preferred regimen: Vancomycin 1 g IV q12h (15 mg/kg q12 for >70 kg) OR Imipenem 500 mg IV q6h AND Rifampin 600 mg PO qd OR Ciprofloxacin 750 mg PO bid OR Erythromycin 500 mg PO qid for at least 4 weeks or until infiltrate disappears
- Note: Should be administrated at least 8 weeks in immunocompromised patients
- Oral/maintenance therapy (after infiltrate clears):
- Preferred regimen (1): Ciprofloxacin 750 mg PO bid
- Preferred regimen (2): Erythromycin 500 mg PO qid
- Alternative regimen: Azithromycin OR TMP-SMX OR Chloramphenicol OR Clindamycin
- Note: Avoid Penicillins/Cephalosporins due to development of resistance; Linezolid effective in vitro, but no clinical reports of use
- Rickettsia prowazekii Return to Top
- Rickettsia rickettsii Return to Top
- 1. Adult
- Preferred regimen: Doxycycline 100 mg q12h
- Note: Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement. Standard duration of treatment is 7-14 days
- Alternative regimen: Chloramphenicol 500 mg PO qid for 7 days or stop 3 days after defervescence
- 2. Pediatric (under 45 kg (100 lbs))
- Preferred regimen: Doxycycline 2.2 mg/kg bid
- Note: The recommended dose and duration of medication needed to treat RMSF has not been shown to cause staining of permanent teeth, even when five courses are given before the age of eight. Healthcare providers should use doxycycline as the first-line treatment for suspected Rocky Mountain spotted fever in patients of all ages
- Rickettsia typhi Return to Top
### Bacteria – Gram-Negative Cocci and Coccobacilli
- Aggregatibacter aphrophilus Return to Top
- 1. Endocarditis
- 1.1 Adults
- Preferred regimen (1): Ceftriaxone 2 g/day TV/IM q24h for 4 weeks
- Preferred regimen (2): Ampicillin-sulbactam 12 g/day TV q6h for 4 weeks
- Preferred regimen (3): Ciprofloxacin 1000 mg PO q24h OR 800 mg/day IV q12h for 4 weeks
- 1.2 Pediatrics
- Preferred regimen (1): Ceftriaxone 100 mg/kg/day TV/IM q24h for 4 weeks
- Preferred regimen (2): Ampicillin-sulbactam 300 mg/kg/day TV q6h/q4h for 4 weeks
- Preferred regimen (3): Ciprofloxacin 20-30 mg/kg/day IV/PO bid for 4 weeks
- Note (1): Floroquinolone therapy recommended for patients unable to tolerate Cephalosporin and ampicillin thearpy
- Note (2): For patients < 18 years, Flourouinolones are generally not recommended
- Note (3): For patients with endocarditis involving the prosthetic cardiac valve or other prosthetic cardiac material should be treated for 6 weeks
- 2. Abscess
- Note: The small number of patients reported and the variety of antibiotics used, do not permit identification of the optimal therapeutic regimen for this organism.
# Bordetella pertusis
- Bordetella pertussis Return to Top
- Bordetella pertussis
- 1. Whooping cough
- 1.1. Adults
- Preferred regimen (1): Azithromycin 500 mg PO single dose on day 1 THEN 250 mg PO qd on 2-5 days
- Preferred regimen (2): Erythromycin 2 g/day PO qid for 14 days
- Preferred regimen (3): Clarithromycin 1 g PO bid for 7 days.
- Alternative regimen (intolerant of macrolides): Trimethoprim 320 mg/day AND Sulfamethoxazole 1600 mg/day PO bid for 14 days
- 1.2. Infants <6 months of age
- 1.2.1. Infants <1 month
- Preferred regimen (1): Azithromycin 10 mg/kg PO qd for 5 days
- Preferred regimen (2) (if azithromycin unavailable): Erythromycin 40-50 mg/kg/day PO q6h for 14 days
- Note: TMP-SMX contraindicated for infants aged < 2 months
- 1.2.2. Infants of 1-5 months of age
- Preferred regimen (1): Azithromycin 10 mg/kg PO qd for 5 days
- Preferred regimen (2): Erythromycin 40-50 mg/kg/day PO qid for 14 days
- Preferred regimen (3): Clarithromycin 15 mg/kg PO bid for 7 days
- Alternative regimen: For infants aged ≥ 2 months TMP 8 mg/kg q24h AND SMX 40 mg/kg/day PO bid for 14 days
- 1.3. Infants ≥6 months of age-children
- Preferred regimen (1): Azithromycin 10 mg/kg single dose THEN 5 mg/kg (500 mg Maximum) qd for 2-5 days
- Preferred regimen (2): Erythromycin 40-50 mg/kg PO (2 g daily Maximum) qid for 14 days
- Preferred regimen (3): Clarithromycin 15 mg/kg PO (1 g daily Maximum) bid for 7 days
- Preferred regimen (4): TMP 8 mg/kg/day AND SMX 40 mg/kg/day bid for 14 days
- 2. Post exposure prophylaxis
- Preferred regimen: The antibiotic regimens for post exposure prophylaxis are similar to the regimens used for the treatment of pertussis
- Note (1): Post exposure prophylaxis to an asymptomatic contacts within 21 days of onset of cough in the index patient can potentially prevent symptomatic infection
- Note (2): Close contacts include persons who have direct contact with respiratory, oral or nasal secretions from a symptomatic patient (eg: cough, sneeze, sharing food, eating utensils, mouth to mouth resuscitation, or performing a medical examination of the mouth, nose, throat.
- Note (3): Some close contacts are at high risk for acquiring severe disease following exposure to pertussis. These contacts include infants aged < 1 year , persons with some immunodeficiency conditions, or other underlying medical conditions such as chronic lung disease, respiratory insufficiency and cystic fibrosis.
# Brucella
- Brucella Return to Top
- Brucellosis ,
- 1.Uncomplicated brucellosis in adults and children ≥8yrs of age
- Preferred regimen: Doxycycline 100 mg PO bid for 6 weeks AND Streptomycin 1 g/day IM for 2-3 weeks
- Alternative regimen (1): Doxycycline 100 mg/day PO for six weeks AND Gentamicin 5mg/kg IM for 7-days
- Alternative regimen (2): Gentamicin 5mg/kg/day IV/ IM for 7-10 days AND Rifampicin 600–900 mg/day PO for six weeks
- 2. Complications of brucellosis
- 2.1 Spondylitis
- Preferred regimen:Doxycycline for 3 months AND Streptomycin for 2 to 3 weeks.
- 2.2 Neurobrucellosis
- Preferred regimen: Ceftriaxone 2 mg IV q12h for 1 month AND Doxycycline 100 mg PO bid for 4-5 month AND Rifampicin 600–900 mg/day PO for 4-5 month
- 2.3 Brucella endocarditis
- Preferred regimen: Doxycycline AND an Aminoglycoside for at least 8 weeks, and therapy should be continued for several weeks after surgery when valve replacement is necessary
- Note: Rifampicin OR Trimethoprim/sulfamethoxazole are used for their ability to penetrate cell membranes
- 3. Pregnancy
- Preferred regimen: Rifampin 900 mg PO qd for 6 weeks
- Note: Adding Trimethoprim-sulfamethoxazole can be considered, but this option should probably be avoided preceding the 13th week and after the 36th week of gestation because of concern about teratogenicity and kernicterus.
- 4.For children < 8 yrs of age
- Preferred regimen (1): TMP/SMZ 8/40 mg/ kg/day PO bid for 6 weeks AND Streptomycin 30 mg/kg/day IM q24h for 3 weeks
- Preferred regimen (2): Gentamicin 5 mg/kg/day IM/ IV q24h for 7-10 days
- Alternative regimen (1): TMP/SMZ AND Rifampicin 15 mg/kg/day PO for 6 weeks
- Alternative regimen (2): Rifampicin AND an Aminoglycoside
- Eikenella corrodens Return to Top
- 1. Human bite/soft tissue infections
- 1.1 Severe
- Preferred regimen: Ampicillin sulbactam 1.5-3 g IV q6h
- Alternative regimen (1): Doxycycline 100 mg IV bid
- Alternative regimen (2): Moxifloxacin 400 mg IV q24h
- Alternative regimen (3): Levofloxacin 500 mg IV q24h
- 1.2 Mild
- Preferred regimen: Amoxicillin clavulanate 250-500 mg tid or 875/125 mg PO bid
- Alternative regimen (1): Doxycycline 100 mg PO bid
- Alternative regimen (2): Moxifloxacin 400 mg PO qd
- Alternative regimen (3): Levofloxacin 500 mg PO qd
- 2. Head and neck infections
- 2.1 Severe
- Preferred regimen: Ampicillin sulbactam 1.5-3 g IV q6h
- Alternative regimen (1): Doxycycline 100 mg IV bid
- Alternative regimen (2): Moxifloxacin 400 mg IV q24h
- Alternative regimen (3): Levofloxacin 500 mg IV q24h
- 2.2 Mild
- Preferred regimen: Amoxicillin clavulanate 250-500 mg tid or 875/125 mg PO bid
- Alternative regimen (1): Doxycycline 100 mg PO bid
- Alternative regimen (2): Moxifloxacin 400 mg PO qd
- Alternative regimen (3): Levofloxacin 500 mg PO qd
- 3. Endocarditis
- Preferred regimen (1): Ceftriaxone 1 g IV q12h
- Preferred regimen (1): Cefotaxime 1-2 g IV q8h
- Preferred regimen (1): Cefepime 1-2g IV q8h
# Haemophilus ducreyi
- Haemophilus ducreyi Return to Top
- 1. Chancroid
- Preferred Regimen (1): Azithromycin 1 g PO in a single dose
- Preferred Regimen (2): Ceftriaxone 250 mg IM in a single dose
- Preferred Regimen (3): Ciprofloxacin 500 mg PO bid for 3 days
- Preferred Regimen (4): Erythromycin base 500 mg PO tid for 7 days
- Note: Patients should be tested for HIV infection at the time chancroid is diagnosed. If the initial test results were negative, a serologic test for syphilis and HIV infection should be performed 3 months after the diagnosis of chancroid.
- 1.1 Follow-up
- Patients should be re-examined 3–7 days after initiation of therapy. If treatment is successful, ulcers usually improve symptomatically within 3 days and objectively within 7 days after therapy. If no clinical improvement is evident, the clinician must consider whether 1) the diagnosis is correct, 2) the patient is coinfected with another STD, 3) the patient is infected with HIV, 4) the treatment was not used as instructed, or 5) the H. ducreyi strain causing the infection is resistant to the prescribed antimicrobial.
- Clinical resolution of fluctuant lymphadenopathy is slower than that of ulcers and might require needle aspiration or incision and drainage, despite otherwise successful therapy. Although needle aspiration of buboes is a simpler procedure, incision and drainage might be preferred because of reduced need for subsequent drainage procedures.
- 1.2 Management of sex partners
- Regardless of whether symptoms of the disease are present, sex partners of patients who have chancroid should be examined and treated if they had sexual contact with the patient during the 10 days preceding the patient’s onset of symptoms.
- 1.3 Pregnancy
- Ciprofloxacin presents a low risk to the fetus during pregnancy, with a potential for toxicity during breastfeeding. Alternative drugs should be used during pregnancy and lactation
- 1.4 HIV Infection
- Persons with HIV infection who have chancroid should be monitored closely because they are more likely to experience treatment failure and to have ulcers that heal slowly. Persons with HIV infection might require repeated or longer courses of therapy, and treatment failures can occur with any regimen.
# Haemophilus influenzae
- Haemophilus influenzae Return to Top
- Haemophilus influenzae
- 1. Non- life threatening infections
- 1.1 Adults
- Preferred regimen (1): Amoxicillin-clavulanate 500 mg PO tid or 875 mg PO bid
- Preferred regimen (2): Amoxicillin 500 mg PO tid
- Preferred regimen (3): TMP-SMX DS PO bid
- Preferred regimen (4): Cefuroxime 250-500 mg PO bid
- Preferred regimen (5): Moxifloxacin 400 mg PO qd
- Preferred regimen (6): Levofloxacin 500 mg PO qd
- Preferred regimen (7): Azithromycin 500 mg PO single dose then 250 mg for 4 days
- Preferred regimen (8): Clarithromycin 500 mg PO bid or XL 500 mg PO q24h
- Note: Treatment duration of otitis media is 10-14 days, acute exacerbation of chronic bronchitis is 5 days (quinolone - 14 days), sinusitis is 10-14 days.
- 2. Meningitis
- Dexamethasone 0.15 mg/kg 15-20 mins before first dose of antibiotic and then q6h for 4 days
- 2.1 Adults
- Preferred regimen (1): Ceftriaxone 2 g IV q12h (4 g maximum)
- Preferred regimen (2): Cefotaxime 2 g IV q4-6h (12 g maximum)
- Preferred regimen (3): Ampicillin 2 g IV q4h if sensitive
- Alternative regimen: Ciprofloxacin 400 mg IV q8h OR other Fluoroquinolones
- 2.2 Pediatric
- 2.2.1 Neonates < 7 days
- 2.2.1.1 Weight < 2 kg
- Preferred regimen: Cefotaxime 50 mg/kg IV q12h for 10-14 days
- 2.2.1.2 Weight > 2 kg
- Preferred regimen (1): Cefotaxime 50 mg/kg IV q8h
- Preferred regimen (2): Ceftriaxone 50 mg/kg IV q24h for 10-14 days
- 2.2.2 Neonates >7 days
- 2.2.2.1 Weight > 2 kg
- Preferred regimen (1): Cefotaxime 50 mg/kg IV q6-8h
- Preferred regimen (2): Ceftriaxone 75 mg/kg IV q24h for 10-14 days
- 2.2.3 Children
- Preferred regimen (1): Cefotaxime 200 mg/kg/day IV q6h
- Preferred regimen (2): Ceftriaxone 100 mg/kg IV q12-24h for 10-14 days
- 2.3 Post-meningitis exposure prophylaxis
- Preferred regimen (1): Rifampin 600 mg PO qd for 4 days
- 3. Severe infections
- 3.1 Adults
- Preferred regimen (1): Ceftriaxone 1-2 g IV q24 or q12h
- Preferred regimen (2): Cefotaxime 2 g IV q6h
- Alternative regimen (1): Ciprofloxacin 400 mg IV q8h or other Fluoroquinolones
- Alternative regimen (2): Ampicillin 2 g IV q6h if sensitive
# Neisseria gonorrhoeae
- Neisseria gonorrhoeae Return to Top
- Neisseria gonorrhoeae treatment
- 1. Gonococcal infections in adolescents and adults
- 1.1 Uncomplicated gonococcal infections of the cervix, urethra, and rectum
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- Alternative regimen: Cefixime 400 mg PO in a single dose AND Azithromycin 1 g PO in a single dose (if ceftriaxone is not available)
- 1.2 Uncomplicated gonococcal infections of the pharynx
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.2.1 Management of sex partners
- Expedited partner therapy: Cefixime 400 mg PO in a single dose AND Azithromycin 1 g PO in a single dose
- Note (1): Recent sex partners (i.e., persons having sexual contact with the infected patient within the 60 days preceding onset of symptoms or gonorrhea diagnosis) should be referred for evaluation, testing, and presumptive dual treatment.
- Note (2): If the patient’s last potential sexual exposure was >60 days before onset of symptoms or diagnosis, the most recent sex partner should be treated.
- Note (3): To avoid reinfection, sex partners should be instructed to abstain from unprotected sexual intercourse for 7 days after they and their sexual partner(s) have completed treatment and after resolution of symptoms, if present.
- 1.2.2 Allergy, intolerance, and adverse reactions
- Preferred regimen (1): Gemifloxacin 320 mg PO in a single dose AND Azithromycin 2 g PO in a single dose
- Preferred regimen (2): Gentamicin 240 mg IM in a single dose AND Azithromycin 2 g PO in a single dose
- Note: Use of ceftriaxone or cefixime is contraindicated in persons with a history of an IgE-mediated penicillin allergy (e.g., anaphylaxis, Stevens Johnson syndrome, and toxic epidermal necrolysis).
- 1.2.3 Pregnancy
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.2.4 Suspected cephalosporin treatment failure
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Gemifloxacin 320 mg PO single dose AND Azithromycin 2 g PO single dose (when isolates have elevated cephalosporin MICs)
- Alternative regimen (2): Gentamicin 240 mg IM single dose AND Azithromycin 2 g PO single dose (when isolates have elevated cephalosporin MICs)
- Alternative regimen (3): Ceftriaxone 250 mg IM as a single dose AND Azithromycin 2 g PO as a single dose (failure after treatment with cefixime and azithromycin)
- Note: Treatment failure should be considered in: (1) persons whose symptoms do not resolve within 3–5 days after appropriate treatment and report no sexual contact during the post-treatment follow-up period; (2) persons with a positive test-of-cure (i.e., positive culture ≥ 72 hours or positive NAAT ≥ 7 days after receiving recommended treatment) when no sexual contact is reported during the post-treatment follow-up period; (3) persons who have a positive culture on test-of-cure (if obtained) if there is evidence of decreased susceptibility to cephalosporins on antimicrobial susceptibility testing, regardless of whether sexual contact is reported during the post-treatment follow-up period.
- 1.3 Gonococcal conjunctivitis
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.3.1 Management of sex partners
- Patients should be instructed to refer their sex partners for evaluation and treatment.
- 1.4 Disseminated gonococcal infection
- 1.4.1 Arthritis and arthritis-dermatitis syndrome
- Preferred regimen: Ceftriaxone 1 g IM/IV q24h for 7 days AND Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Cefotaxime 1 g IV q8h for 7 days
- Alternative regimen (2): Ceftizoxime 1 g IV q8h for 7 days AND Azithromycin 1 g PO in a single dose
- 1.4.2 Gonococcal meningitis and endocarditis
- Preferred regimen: Ceftriaxone 1-2 g IV q 12-24 h for 10-14 days AND Azithromycin 1 g PO in a single dose
- 2. Gonococcal infections among neonates
- 2.1 Ophthalmia neonatorum caused by N. gonorrhoeae
- Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg
- 2.1.1 Management of mothers and their sex partners
- Mothers of infants with ophthalmia neonatorum caused by N. gonorrhoeae should be evaluated, tested, and presumptively treated for gonorrhea, along with their sex partner(s).
- 2.2 Disseminated gonococcal infection and gonococcal scalp abscesses in neonates
- Preferred regimen (1): Ceftriaxone 25-50 mg/kg/day IM/IV q24h for 7 days
- Preferred regimen (2): Cefotaxime 25 mg/kg IM/IV q12h for 7 days.
- Note (1): The duration of treatment is 10-14 days if meningitis is documented.
- Note (2): Ceftriaxone should be administered cautiously to hyperbilirubinemic infants, especially those born prematurely.
- 2.2.1 Management of mothers and their sex partners
- Mothers of infants who have DGI or scalp abscesses caused by N. gonorrhoeae should be evaluated, tested, and presumptively treated for gonorrhea, along with their sex partner(s).
- 2.3 Neonates born to mothers who have gonococcal infection
- Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg
- 2.3.1 Management of mothers and their sex partners
- Mothers who have gonorrhea and their sex partners should be evaluated, tested, and presumptively treated for gonorrhea.
- 3. Gonococcal infections among infants and children
- 3.1 Infants and children who weigh ≤ 45 kg and who have uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis
- Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg
- 3.2 Children who weigh > 45 kg and who have uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1g PO in a single dose
- Alternative regimen: Cefixime 400 mg PO single dose AND Azithromycin 1 g PO single dose.(If ceftriaxone is not available)
- 3.3 Children who weigh ≤ 45 kg and who have bacteremia or arthritis
- Preferred regimen: Ceftriaxone 50 mg/kg (maximum dose: 1 g) IM/IV q24h for 7 days
- 3.4 Children who weigh > 45 kg and who have bacteremia or arthritis
- Preferred regimen: Ceftriaxone 1 g IM/IV q24h for 7 days
# Neisseria meningitidis
- Neisseria meningitidis Return to Top
- 1. Meningococcal meningitis or meningococcemia, treatment
- 1.1 Adults
- 1.1.1 Penicillin MIC < 0.1 mcg/mL
- Preferred regimen (1): Penicillin G 4 MU IV q4h for 7 days
- Preferred regimen (2): Ampicillin 2 g IV q4h for 7 days
- Alternative regimen (1): Ceftriaxone 4 g/day IV q12-24h for 7 days
- Alternative regimen (2): Cefotaxime 8-12 g/day IV q4-6h for 7 days
- Alternative regimen (3): Chloramphenicol 4-6 g/day IV q6h for 7 days
- 1.1.2 Penicillin MIC 0.1-1.0 mcg/mL
- Preferred regimen (1): Ceftriaxone 4 g/day IV q12-24h for 7 days
- Preferred regimen (2): Cefotaxime 8-12 g/day IV q4-6h for 7 days
- Alternative regimen (1): Cefepime 2 g IV q8h for 7 days
- Alternative regimen (2): Chloramphenicol 4-6 g/day IV q6h for 7 days
- Alternative regimen (3): Moxifloxacin 400 mg IV q24h for 7 days
- Alternative regimen (4): Meropenem 2 g IV q8h for 7 days
- 1.2 Neonates (birth-7 days old)
- 1.2.1 Penicillin MIC < 0.1 mcg/mL
- Preferred regimen (1): Penicillin G 0.15 MU/kg/day IV q8-12h for 7 days
- Preferred regimen (2): Ampicillin 150 mg/kg/day IV q8h for 7 days
- Alternative regimen (1): Cefotaxime 100-150 mg/kg/day IV q8-12h for 7 days
- Alternative regimen (2): Chloramphenicol 25 mg/kg/day IV q24h for 7 days
- 1.2.2 Penicillin MIC 0.1-1.0 mcg/mL
- Preferred regimen: Cefotaxime 100-150 mg/kg/day IV q8-12h for 7 days
- Alternative regimen: Chloramphenicol 25 mg/kg/day IV q24h for 7 days
- 1.3 Neonates (8-28 days old)
- 1.3.1 Penicillin MIC < 0.1 mcg/mL
- Preferred regimen (1): Penicillin G 0.2 MU/kg/day IV q6-8h for 7 days
- Preferred regimen (2): Ampicillin 200 mg/kg/day IV q6-8h for 7 days
- Alternative regimen (1): Cefotaxime 150-200 mg/kg/day IV q6-8h for 7 days
- Alternative regimen (2): Chloramphenicol 50 mg/kg/day IV q12-24h for 7 days
- 1.3.2 Penicillin MIC 0.1-1.0 mcg/mL
- Preferred regimen : Cefotaxime 150-200 mg/kg/day IV q6-8h for 7 days
- Alternative regimen : Chloramphenicol 50 mg/kg/day IV q12-24h for 7 days
- 1.4 Infants and children
- 1.4.1 Penicillin MIC < 0.1 mcg/mL
- Preferred regimen (1): Penicillin G 0.3 MU/kg/day IV q4-6h for 7 days
- Preferred regimen (2): Ampicillin 300 mg/kg/day IV q6h for 7 days
- Alternative regimen (1): Ceftriaxone 80-100 mg/kg/day IV q12-24h for 7 days
- Alternative regimen (2): Cefotaxime 225-300 mg/kg/day IV q6-8h for 7 days
- Alternative regimen (3): Chloramphenicol 75-100 mg/kg/day IV q6h for 7 days
- 1.4.2 Penicillin MIC 0.1-1.0 mcg/mL
- Preferred regimen (1): Ceftriaxone 80-100 mg/kg/day IV q12-24h for 7 days
- Preferred regimen (2): Cefotaxime 225-300 mg/kg/day IV q6-8h for 7 days
- Alternative regimen (1): Cefepime 150 mg/kg/day IV q8h for 7 days
- Alternative regimen (2): Chloramphenicol 75-100 mg/kg/day q6h for 7 days
- Alternative regimen (3): Meropenem 120 mg/kg/day IV q8h for 7 days
- Note (1): Dexamethasone has not been shown to be beneficial in meningococcal meningitis and should be discontinued once this diagnosis is established.
- Note (2): Clinical data are limited on the use of fluoroquinolones for therapy for meningococcal meningitis but may be considered in patients not responding to standard therapy or when disease is caused by resistant organisms.
- 2. Meningococcal meningitis, prophylaxis for household and close contacts
- 2.1 Adults
- Preferred regimen (1): Rifampin 600 mg PO bid for 2 days
- Preferred regimen (2): Ciprofloxacin 500 mg PO single dose
- Preferred regimen (3): Ceftriaxone 250 mg IM single dose
- 2.2 Children < 15 years
- Preferred regimen: Ceftriaxone 12 mg IM single dose
- 2.3 Children ≥ 1 month
- Preferred regimen: Rifampin 10 mg /kg PO bid for 2 days
- 2.4 Children < 1 month
- Preferred regimen: Rifampin 5 mg/kg PO bid for 2 days
- Moraxella catarrhalis Return to Top
- Moraxella catarrhalis
- Preferred regimen(1): TMP-SMX 1DS PO bid
- Preferred regimen(2): Erythromycin 500 mg PO qid
- Preferred regimen(3): Clarithromycin 500 mg PO bid or XL 1 g PO qd
- Preferred regimen(4): Azithromycin 500 mg PO single dose THEN 250 mg PO qd
- Preferred regimen(5): Doxycycline 100 mg PO/IV bid/q12h
- Preferred regimen(6): Cefprozil 200-500 mg PO bid
- Preferred regimen(7): Cefpodoxime 200-400 mg PO bid
- Preferred regimen(8): Cefuroxime 250-500 mg PO bid
- Preferred regimen(9): Cefdinir 300 mg PO bid
- Preferred regimen(10): Moxifloxacin 400 mg IV/PO qd
- Preferred regimen(11): Levofloxacin 500 mg IV/PO qd
- Preferred regimen(12): Amoxicillin clavulanate 875/125 mg PO bid or XL 2000/125 PO bid
- Pasteurella multocida Return to Top
- Pasteurella multocida
- Preferred regimen (1): Amoxicillin clavulanate 500 mg PO tid or 875 mg PO bid with food
- Note: Its also a preferred empirical coverage of animal bite wounds
- Preferred regimen (2): Ampicillin sulbactam 3 g IV q6h
- Preferred regimen (3): Ciprofloxacin 500 mg PO bid or 400 mg IV q12h
- Preferred regimen (4): Levofloxacin 500 mg PO qd or IV q24h
- Alternative regimen (1): Doxycycline 100 mg PO bid
- Alternative regimen (2): TMP-SMX DS PO bid (for beta-lactam allergic patients )
- Alternative regimen (3): Penicillin 500 mg PO qid or 4 MU IV q4h (use only if isolate known to be susceptible)
### Bacteria – Spirochetes
- Borrelia burgdorferi Return to Top
- Lyme disease
- 1. Early Lyme Disease
- 1.1 Erythema migrans
- 1.1.1 Adult
- Preferred regimen (1): Doxycycline 100 mg PO bid for 10-21 days
- Preferred regimen (2): Amoxicillin 500 mg PO tid for 14-21 days
- Preferred regimen (3): Cefuroxime axetil 500 mg bid for 14-21 days
- Alternatie regimen (1): Azithromycin 500 mg PO qd for 7–10 days
- Alternatie regimen (2): Clarithromycin 500 mg PO bid for 14–21 days (if the patient is not pregnant)
- Alternatie regimen (3): Erythromycin 500 mg PO qid for 14–21 days
- 1.1.2 Pediatric
- 1.1.2.1 children <8 years of age
- Preferred regimen (1): Amoxicillin 50 mg/kg/day PO q8h (Maximum of 500 mg per dose)
- Preferred regimen (2): Cefuroxime axetil 30 mg/kg/day PO q12h（Maximum, 500 mg per dose)
- 1.1.2.2 children ≥8 years of age
- Preferred regimen (1): Doxycycline 4 mg/kg/day PO q12h（Maximum, 100 mg per dose）
- Preferred regimen (2): Azithromycin 10 mg/kg PO qd (Maximum, 500 mg qd)
- Preferred regimen (3): Clarithromycin 7.5 mg/kg PO bid (Maximum, 500 mg per dose)
- Preferred regimen (4): Erythromycin 12.5 mg/kg PO qid (Maximum, 500 mg per dose)
- 1.2 When erythema migrans cannot be reliably distinguished from community-acquired bacterial cellulitis
- Preferred regimen: Amoxicillin-Clavulanate 500 mg PO tid
- Pediatric regimen: Amoxicillin-Clavulanate 50 mg/kg/day q8h (Maximum, 500 mg per dose)
- 1.3 Lyme meningitis and other manifestations of early neurologic Lyme disease
- 1.3.1 Adult
- Preferred regimen: Ceftriaxone 2 g IV q24h for 10–28 days
- Alternative regimen (1): Cefotaxime 2 g IV q8h
- Alternative regimen (2): Penicillin G 18–24 MU q4h (for patients with normal renal function)
- Alternative regimen (3): Doxycycline 200–400 mg/day PO bid for 10–28 days
- 1.3.2 Pediatric
- Preferred regimen (1): Ceftriaxone 50–75 mg/kg IV single dose (Maximum, 2 g)
- Preferred regimen (2): Cefotaxime 150–200 mg/kg/day IV q6-8h (Maximum, 6 g per day)
- Alternative regimen (1): Penicillin G 200,000–400,000 units/kg/day IV q4h (for normal renal function) (maximum, 18–24 MU per day)
- Alternative regimen (2): Doxycycline 4–8 mg/kg/day PO bid (maximum, 100–200 mg per dose) (≥8 years old)
- 1.4 Lyme carditis
- Preferred regimen: Ceftriaxone 2 g IV q24h for 10–28 days
- Note: patients with advanced heart block, a temporary pacemaker may be required; expert consultation with a cardiologist is recommended; Use of the pacemaker may be discontinued when the advanced heart block has resolved; An oral antibiotic treatment regimen should be used for completion of therapy and for outpatients, as is used for patients with erythema migrans without carditis (see above)
- 1.5 Borrelial lymphocytoma
- Preferred regimen: The same regimens used to treat patients with erythema migrans (see above)
- 2. Late Lyme Disease
- 2.1 Lyme arthritis
- Preferred regimen (1): Doxycycline 100 mg PO bid
- Preferred regimen (2): Amoxicillin 500 mg PO tid
- Alternative regimen: Cefuroxime axetil 500 mg PO bid for 28 days
- Pediatric regimen: Amoxicillin 50 mg/kg/day tid (Maximum, 500 mg per dose); Cefuroxime axetil 30 mg/kg/day bid (Maximum,500 mg per dose); (≥8 years of age) Doxycycline 4 mg/kg/day bid (Maximum, 100 mg per dose)
- Note: For patients who have persistent or recurrent joint swelling after a recommended course of oral antibiotic therapy, we recommend re-treatment with another 4-week course of oral antibiotics or with a 2–4 weeks course of Ceftriaxone IV
- 2.2 patients with arthritis and objective evidence of neurologic disease
- Preferred regimen: Ceftriaxone IV for 2–4 weeks
- Alternative regimen (1): Cefotaxime IV
- Alternative regimen (1): Penicillin G IV
- Pediatric regime: Ceftriaxone; Cefotaxime; Penicillin G IV
- 2.3 Late neurologic Lyme disease
- Preferred regimen: Ceftriaxone IV for 2 to 4 weeks
- Alternative regimen (1): Cefotaxime IV
- Alternative regimen (2): Penicillin G IV
- Pediatric regimen: Ceftriaxone; Cefotaxime; Penicillin G
- 2.4 Acrodermatitis chronica atrophicans
- Preferred regimen (1): Doxycycline 100 mg PO bid for 21 days
- Preferred regimen (2): Amoxicillin 500 mg PO tid for 21 days
- Preferred regimen (3): Cefuroxime axetil 500 mg PO bid for 21 days
- 3. Post–Lyme Disease Syndromes
- Preferred regimen: Further antibiotic therapy for Lyme disease should not be given unless there are objective findings of active disease (including physical findings, abnormalities on cerebrospinal or synovial fluid analysis, or changes on formal neuropsychologic testing)
- Borrelia recurrentis Return to Top
- 1. Tick-Borne Relapsing Fever
- Preferred regimen: Doxycycline 100 mg PO bid for 5-10 days
- Alternative regimen: Erythromycin 500 mg PO qid for 5-10 days
- Note: If meningitis/encephalitis present, use Ceftriaxone 2 g IV q12h for 14 days
- 2. Louse-Borne Relapsing Fever
- Preferred regimen: Tetracycline 500 mg PO single dose
- Alternative regimen: Erythromycin 500 mg PO single dose
- Leptospira Return to Top
- 1. Severe
- Preferred regimen: Penicillin 1.5 MU IV q6h for 5-7 days
- 2. Less severe
- Preferred regimen (1): Amoxycillin
- Preferred regimen (2): Ampicillin
- Preferred regimen (3): Doxycycline 100 mg IV/PO q12h/bid for 5-7 days
- Preferred regimen (4): Erythromycin
- Preferred regimen (5): Ceftriaxone 1 g IV q24h for 5-7 days
- Preferred regimen (6): Cefotaxime
- Preferred regimen (7): Quinolone PO
- Treponema pallidum Return to Top
- 1. Syphilis Among non-HIV-Infected Persons
- 1.1 Primary and Secondary Syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM single dose
- Pediatric regimen: Benzathine penicillin G 50,000 U/kg (Maximum, 2.4 MU) IM single dose
- 1.2 Latent Syphilis
- 1.2.1 Early Latent Syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM in a single dose
- Pediatric regimen: Benzathine penicillin G 50,000 U/kg (Maximum, 2.4 MU) IM single dose
- 1.2.2 Late Latent Syphilis or Latent Syphilis of Unknown Duration
- Preferred regimen: Benzathine penicillin G 7.2 MU total, administered as 3 doses of 2.4 MU IM each at 1 week intervals
- Pediatric regimen: Benzathine penicillin G 50,000 U/kg IM (Maximum, 2.4 MU), administered as 3 doses at 1 week intervals (total 150,000 U/kg up to the adult total dose of 7.2 MU)
- 1.3 Tertiary Syphilis
- Preferred regimen: Benzathine penicillin G 7.2 MU total, administered as 3 doses of 2.4 MU IM each at 1 week intervals
- 1.4 Neurosyphilis and ocular syphilis
- Preferred regimen: Aqueous crystalline penicillin G 18-24 MU per day, administered as 3-4 MU IV q4h or continuous infusion, for 10-14 days
- Alternative regimen: Procaine penicillin 2.4 MU IM q24h AND Probenecid 500 mg PO qid for 10-14 days
- 2. Syphilis Among HIV-Infected Persons
- 2.1 Primary and Secondary Syphilis Among HIV-Infected Persons
- Preferred regimen: Benzathine penicillin G 2.4 MU IM single dose
- 2.2 Latent Syphilis Among HIV-Infected Persons
- 2.2.1 early latent
- Preferred regimen: Benzathine penicillin G 2.4 MU IM single dose
- 2.2.2 late latent
- Preferred regimen: Benzathine penicillin G 2.4 MU once a week for 3 weeks
- 2.3 Neurosyphilis Among HIV-Infected Persons
- Preferred regimen: Aqueous crystalline penicillin G 18-24 MU per day, administered as 3-4 MU IV q4h or continuous infusion, for 10-14 days
- Alternative regimen: Procaine penicillin 2.4 MU IM q24h AND Probenecid 500 mg PO qid for 10-14 days
- 3. Syphilis During Pregnancy
- Pregnant women should be treated with the penicillin regimen appropriate for their stage of infection
- 4. Congenital Syphilis in neonates
- 4.1 condition1: Infants with proven or highly probable disease and (1) an abnormal physical examination that is consistent with congenital syphilis;（2）a serum quantitative nontreponemal serologic titer that is fourfold higher than the mother's titer; or（3）a positive darkfield test of body fluid(s).
- Preferred regimen (1): Aqueous crystalline penicillin G 100,000-150,000 U/kg/day, administered as 50,000 U/kg/dose IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days
- Preferred regimen (2): Procaine penicillin G 50,000 U/kg/dose IM q24h for 10 days
- Note: If more than 1 day of therapy is missed, the entire course should be restarted. Data are insufficient regarding the use of other antimicrobial agents (e.g., ampicillin). When possible, a full 10-day course of penicillin is preferred, even if ampicillin was initially provided for possible sepsis. The use of agents other than penicillin requires close serologic follow-up to assess adequacy of therapy. In all other situations, the maternal history of infection with T. pallidum and treatment for syphilis must be considered when evaluating and treating the infant.
- 4.2 condition2: Infants who have a normal physical examination and a serum quantitive nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1) mother was not treated, inadequately treated, or has no documentation of having received treatment; (2) mother was treated with erythromycin or another nonpenicillin regimen; or (3) mother received treatment <4 weeks before delivery.
- Preferred regimen (1): Aqueous crystalline penicillin G 100,000-150,000 U/kg/day, administered as 50,000 U/kg/dose IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days
- Preferred regimen (2): Procaine penicillin G 50,000 U/kg/dose IM q24h for 10 days
- Preferred regimen (3): Benzathine penicillin G 50,000 U/kg/dose IM single dose
- Note: If the mother has untreated early syphilis at delivery, 10 days of parenteral therapy can be considered
- 4.3 condition3: Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1) mother was treated during pregnancy, treatment was appropriate for the stage of infection, and treatment was administered >4 weeks before delivery and (2) mother has no evidence of reinfection or relapse.
- Preferred regimen: Benzathine penicillin G 50,000 U/kg/dose IM single dose
- 4.4 condition4: Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1) mother's treatment was adequate before pregnancy; and (2) mother's nontreponemal serologic titer remained low and stable before and during pregnancy and at delivery (VDRL <1:2; RPR <1:4).
- No treatment is required
- Benzathine penicillin G 50,000 U/kg IM single dose might be considered, particularly if follow-up is uncertain.
- 5. Congenital Syphilis in infants and children
- Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg q4–6h for 10 days
### Bacteria – Gram-Negative Bacilli
- Achromobacter xylosoxidans Return to Top
- Achromobacter xylosoxidans treatment,,,,,
- Preferred regimen: most active agents are Piperacillin-Tazobactam, Meropenem AND Trimethoprim–Sulfamethoxazole whereas Ceftazidime is more active than Cefepime
- Alternative regimen: Colistin inhaled, could also be considered
- Note : Achromobacter (formerly Alcaligenes) xylosoxidans is a newly emerging microorganism isolated with increased frequency from the lungs of patients with cystic fibrosis. Combination therapy has been recommended for the treatment of Achromobacter xylosoxidans pulmonary exacerbations in cystic fibrosis
# Acinetobacter baumannii
- Acinetobacter baumannii Return to Top
- Acinetobacter baumannii
- Preferred regimen (1): Imipenem 0.5-1 g IV q6h
- Preferred regimen (2): Ampicillin/sulbactam 3 g IV q4h
- Preferred regimen (3): Cefepime 1-2 g IV q8h
- Preferred regimen (4): Colistin 2.5 mg/kg IV q12h
- Preferred regimen (5): Tigecycline 100 mg IV single dose THEN 50 mg IV q12h
- Preferred regimen (6): Amikacin 7.5 mg/kg IV q12h or 15 mg/kg IV q24h
- Preferred regimen (7) (pan-resistant isolates): Colistin 5 mg/kg/day IV q12h ± Imipenem
- Preferred regimen (8) (pan-resistant isolates): Ampicillin-sulbactam 3 g IV q4h
- Alternative regimen (1): Ceftriaxone 1-2 g IV qd
- Alternative regimen (2): Cefotaxime 2-3 g IV q6-8h
- Alternative regimen (3): Ciprofloxacin 400 mg IV q8-12h or 750 mg PO bid
- Alternative regimen (4): TMP-SMX 15-20 mg (TMP)/kg/day IV q6-8h or 2 DS PO bid
# Aeromonas hydrophila
- Aeromonas hydrophila Return to Top
- Aeromonas hydrophila
- 1. Diarrhea
- Preferred regimen (if not self-limiting, or if severe): Ciprofloxacin 500 mg PO bid.
- Alternate regimen: TMP-SMX 1 DS PO bid
- Note: High resistance to sulfa agents described in Taiwan and Spain
- 2. Skin and soft tissue infection
- 2.1 Mild infection
- Preferred regimen (1): Ciprofloxacin 500 mg PO bid
- Preferred regimen (2): Levofloxacin 500 mg qd
- 2.2 Severe infection or sepsis
- Preferred regimen (1): Ciprofloxacin 400 mg IV q8h
- Preferred regimen (2): Levofloxacin 750 mg IV q24h
- Note (1): For suspicion of water-based injury,empiric coverage for Vibrio doxycycline 100 mg bid, although flouroquinolones may also cover and vancomycin 15 mg/kg IV q12h with or without clindamycin or linezolid for inhibition of gram-positive toxin production
- Note (2): Alternatives to fluoroquinolones for Aeromonas coverage include carbapenems (ertapenem, doripenem, imipenem or meropenem), ceftriaxone, cefepime and aztreonam
- 3. Prevention
- Preferred regimen: Frequent recommendations include using a Cephalosporin (e.g.,cefuroxime,ceftriaxone or cefixime) OR a Fluoroquinolone (e.g.,ciprofloxacin or levofloxacin) during treatment with medicinal leeches
- Note (1): Duration of antibiotic use is 3-5 days, some recommend continuing until wound or eschar resolves
- Note (2): Aeromonas isolates from leeches have been described as uniformly susceptible to fluoroquinolones
# Bartonella
- Bartonella Return to Top
- Bartonella
- 1. Bartonella quintana
- 1.1 Acute or chronic infections without endocarditis
- Preferred regimen: Doxycycline 200 mg PO qd or 100 mg bid for 4 weeks AND Gentamicin 3 mg/kg IV qd for the first 2 weeks
- 1.2 Endocarditis
- Preferred regimen: Gentamicin 3 mg/kg/day IV q8h for 14 days AND Ceftriaxone 2 g IV q24h for 6 weeks ± Doxycycline 100 mg PO bid for 6 weeks
- 2. Bartonella elizabethae
- 2.1 Endocarditis
- Preferred regimen: Gentamicin 3 mg/kg/day IV q8h for 14 days AND Ceftriaxone 2 g IV q24h for 6 weeks ± Doxycycline 100 mg PO bid for 6 weeks
- 3. Bartonella bacilliformis
- 3.1 Oroya fever
- Preferred regimen: Ciprofloxacin 500 mg PO bid for 14 days
- Note: If severe disease, add Ceftriaxone 1 g IV qd for 14 days
- 3.2 Verruga peruana
- Preferred regimen: Azithromycin 500 mg PO qd for 7 days
- Alternative regimen (1): Rifampin 600 mg PO qd for 14-21 days
- Alternative regimen (2): Ciprofloxacin 500 mg bid for 7-10 days
- 4. Bartonella henselae
- 4.1 Cat scratch disease
- No treatment recommended for typical cat scratch disease, consider treatment if there is an extensive lymphadenopathy
- 4.1.1 If extensive lymphadenopathy
- Preferred regimen (1) (pediatrics): Azithromycin 500 mg PO on day 1 THEN 250 mg PO qd on days 2 to 5
- Preferred regimen (2) (adults): Azithromycin 1 g PO at day 1 THEN 500 mg PO for 4 days
- 4.2 Endocarditis
- Preferred regimen: Gentamicin 3 mg/kg/day IV q8h for 14 days AND Ceftriaxone 2 g/day IV for 6weeks ± Doxycycline 100 mg PO bid for 6 weeks
- 4.3 Retinitis
- Preferred regimen: Doxycycline 100 mg bid AND Rifampin 300 mg bid PO for 4-6 weeks
- 4.4 Bacillary angiomatosis
- Preferred regimen (1): Erythromycin 500 mg PO qid for 2 months at least
- Preferred regimen (2): Doxycycline 100 mg PO bid for 2 months at least
- 4.5 Bacillary Pelliosis
- Preferred regimen (1): Erythromycin 500 mg PO qid for 4 months at least
- Preferred regimen (2): Doxycycline 100 mg PO bid for 4 months at least
# Bordetella pertussis
- Bordetella pertussis Return to Top
- Bordetella pertussis
- 1. Whooping cough
- 1.1 Adults
- Preferred regimen (1): Azithromycin 500 mg PO single dose on day 1 THEN 250 mg PO qd on 2-5 days
- Preferred regimen (2): Erythromycin 2 g/day PO qid for 14 days
- Preferred regimen (3): Clarithromycin 1 g PO bid for 7 days.
- Alternative regimen (intolerant of macrolides): Trimethoprim 320 mg/day AND Sulfamethoxazole 1600 mg/day PO bid for 14 days
- 1.2 Infants <6 months of age
- 1.2.1 Infants <1 month
- Preferred regimen (1): Azithromycin 10 mg/kg PO qd for 5 days
- Preferred regimen (2) (if azithromycin unavailable): Erythromycin 40-50 mg/kg/day PO q6h for 14 days
- Note: TMP-SMX contraindicated for infants aged < 2 months
- 1.2.2 Infants of 1-5 months of age
- Preferred regimen (1): Azithromycin 10 mg/kg PO qd for 5 days
- Preferred regimen (2): Erythromycin 40-50 mg/kg/day PO qid for 14 days
- Preferred regimen (3): Clarithromycin 15 mg/kg PO bid for 7 days
- Alternative regimen: For infants aged ≥ 2 months TMP 8 mg/kg q24h AND SMX 40 mg/kg/day PO bid for 14 days
- 1.3 Infants ≥6 months of age-children
- Preferred regimen(1): Azithromycin 10 mg/kg single dose THEN 5 mg/kg (500 mg Maximum) qd for 2-5 days
- Preferred regimen(2): Erythromycin 40-50 mg/kg PO (2 g daily Maximum) qid for 14 days
- Preferred regimen(3): Clarithromycin 15 mg/kg PO (1 g daily Maximum) bid for 7 days
- Preferred regimen(4): TMP 8 mg/kg/day AND SMX 40 mg/kg/day bid for 14 days
- 2. Post exposure prophylaxis
- Preferred regimen: The antibiotic regimens for post exposure prophylaxis are similar to the regimens used for the treatment of pertussis
- Note (1): Post exposure prophylaxis to an asymptomatic contacts within 21 days of onset of cough in the index patient can potentially prevent symptomatic infection
- Note (2): Close contacts include persons who have direct contact with respiratory, oral or nasal secretions from a symptomatic patient (eg: cough, sneeze, sharing food, eating utensils, mouth to mouth resuscitation, or performing a medical examination of the mouth, nose, throat.
- Note (3): Some close contacts are at high risk for acquiring severe disease following exposure to pertussis. These contacts include infants aged < 1 year , persons with some immunodeficiency conditions, or other underlying medical conditions such as chronic lung disease, respiratory insufficiency and cystic fibrosis.
# Burkholderia cepacia
- Burkholderia cepacia Return to Top
- Burkholderia cepacia complex
- Preferred regimen (1): Ceftazidime 2 g IV q8h
- Preferred regimen (2): Imipenem 1 g IV q6h
- Preferred regimen (3): Meropenem 1-2 g IV q8h
- Preferred regimen (4): Minocycline 100 mg IV/PO bid
# Burkholderia pseudomallei
- Burkholderia pseudomallei Return to Top
- Burkholderia pseudomallei
- 1. Melioidosis
- 1.1 Intial intensive therapy (Minimum of 10-14 days)
- Preferred regimen (1): Ceftazidime 50 mg/kg upto 2 g q6h
- Preferred regimen (2): Meropenem 25 mg/kg upto 1 g q8h
- Preferred regimen (3): Imipenem 25 mg/kg upto 1 g q6h
- Note: Any one of the three may be combined with TMP-SMX 6/30 mg/kg upto 320/1600 mg/kg q12h (recommended for neurologic, bone, joint, cutaneous and prostatic melioidosis)
- 1.2 Eradication therapy (Minimum of 3 months)
- Preferred regimen: TMP-SMX 6/30 mg/kg upto 320/1600 mg/kg q12h
# Campylobacter fetus
- Campylobacter fetus Return to Top
- Campylobacter fetus
- 1. Gastroenteritis
- Preferred regimen: Gentamicin 5 mg/kg IV q24h
- Alternative regimen (1): Ampicillin 100 mg/kg IV q6h
- Alternative regimen (2): Imipenem 500 mg IV q6h
- Campylobacter jejuni Return to Top
- Campylobacter jejuni
- 1. Gastroenteritis
- Most patients donot require antibiotics and symptoms last < 1 week
- 1.1 Indications for the treatment
- Highfevers
- Bloodystools
- Prolonged illness > 1 week
- Pregnancy
- HIV and other immunosuppressed states
- 1.2 Treatment regimen
- Preferred regimen (1):Erythromycin stearate 500 mg PO bid for 5 days
- Preferred regimen (2): Ciprofloxacin 500 mg PO bid for 3–5 days
- Alternative regimen (1): TMP-SMX DS PO bid for 3–5 days
- Note (1): Campylobacter resistance to TMP-SMX common in tropics
- Note (2): Extraintestinal infections should be treated for longer duration (e.g.,2-4 weeks)
# Capnocytophaga canimorsus
- Capnocytophaga canimorsus Return to Top
- Capnocytophaga canimorsus
- 1. Severe cellulitis/sepsis or endocarditis
- Preferred regimen (1) (Beta-lactam/beta-lactamase inhibitor): Ampicillin/sulbactam 3 g IV q6h
- Preferred regimen (2) (Non-beta-lactamase producing): Penicillin G 2-4 MU IV q24h
- Alternative regimen (1): Ceftriaxone 1-2 g IV q24h
- Alternative regimen (2): Meropenem 1 g IV q8h
- Alternative regimen (3) (complicated infections or immunocompromise): Clindamycin 600 mg IV q8h may be combined with above agents
- Note (1): Resistance to aztreonam described, and variable susceptibility reported to TMP-SMX and aminoglycosides
- Note (2): For endocarditis, alternatives to penicillins not well established, treated for duration of 6 weeks
- Note (3): For non-endocarditis infections, duration not well established, but most authorities recommend at least 14-21 days of therapy
- 2. Mild cellulitis/dog or cat bites
- Preferred regimen (1): Amoxicillin/clavulanate 500 mg PO q8h or 875 mg PO bid
- Preferred regimen (2): Amoxicillin 500 mg PO q8h
- Alternative regimen (1): Clindamycin 300 mg PO q6h
- Alternative regimen (2): Doxycycline 100 mg PO bid
- Alternative regimen (3): Clarithromycin 500 mg PO bid
- Alternative regimen (4): Moxifloxacin 400 mg PO qd
- 3. Meningitis or brain abscess
- Preferred regimen (1): Ceftriaxone 2 g IV q12h AND Ampicillin 2 g IV q4h
- Preferred regimen (2) (if beta-lactamase producing or polymicrobial brain abscess): Imipenem/Cilastin 1000 mg q6-8h AND Clindamycin 600 mg IV q8h
- 4. Prevention
- Although no firm data supports this recommendation, many clinicians do give prophylaxis for dog and cat bites in asplenic patients with Amoxicillin/clavulanate for 7-10 days.
# Citrobacter freundii
- Citrobacter freundii Return to Top
- Citrobacter freundii
- Preferred regimen (1): Meropenem 1-2 g IV q8h
- Preferred regimen (2): Imipenem 1 g IV q6h
- Preferred regimen (3): Doripenem 500 mg IV q8h
- Preferred regimen (4): Cefepime 1-2 g IV q8h
- Preferred regimen (5): Ciprofloxacin 400 mg IV q12h or 500 mg PO bid for UTI
- Preferred regimen (6): Gentamicin 5 mg/kg IV q24h
- Alternate regimen (1): Piperacillin-tazobactam 3.375 mg IV q6h
- Alternate regimen (2): Aztreonam 1-2 g IV q6h
- Alternate regimen (3): TMP-SMX 5 mg/kg q6h IV or DS PO bid for UTI
- Note: Usually carbenicillin sensitive, cephalothin resistant
# Citrobacter koseri
- Citrobacter koseri Return to Top
- Citrobacter koseri
- Preferred regimen (1): Ceftriaxone 1-2 g IV q12-24h
- Preferred regimen (2): Cefotaxime 1-2 g IV q6h
- Preferred regimen (3): Cefepime 1-2 IV q8h
- Alternate regimen (1): Ciprofloxacin 400 mg IV q12h or 500 mg PO q12h for UTI
- Alternate regimen (2): Imipenem 1 g IV q6h
- Alternate regimen (3): Doripenem 500 mg IV q8h
- Alternate regimen (4): Meropenem 1-2 g IV q8h
- Alternate regimen (5): Aztreonam 1-2 g IV q6h
- Alternate regimen (6): TMP-SMX 5 mg/kg IV q6h or DS PO bid for UTI
- Note: Usually Ampicillin resistant, but may be sensitive to first generation cephalosporins
- Elizabethkingia meningoseptica Return to Top
- 1. Bacteremia
- Preferred regimen (1): Levofloxacin 750 mg IV/PO q24h
- Preferred regimen (2): TMP-SMX 8–10 mg/kg/day IV divided q6–8h
- Alternative regimen (1): Ciprofloxacin 400 mg IV q12h
- Alternative regimen (2): TMP-SMX 8–10 mg/kg/day IV divided q6–8h
# Enterobacter
- Enterobacter Return to Top
- Enterobacter species including E. aerogenes and E. cloacae
- 1. Empiric antimicrobial therapy pending in vitro susceptibility
- 1.1 Non–life-threatening infections or MDR-GNB prevalence < 20%
- Preferred regimen: Piperacillin-Tazobactam 3.375 g IV q6h ± Aminoglycosides
- Alternative regimen: Ciprofloxacin 400 mg IV q8–12h
- 1.2 Life-threatening infections or MDR-GNB prevalence > 20%
- Preferred regimen: Meropenem 0.5–1 g IV q8h
- Alternative regimen (1): Colistin AND Meropenem 0.5–1 g IV q8h
- Alternative regimen (2): Colistin AND Imipenem 500 mg IV q6h
- Alternative regimen (3): Colistin AND Doripenem 500 mg IV q8h
- Alternative regimen (4): Colistin AND Ertapenem 1 g IV q24h
- Alternative regimen (5): Colistin AND Fosfomycin 6 g IV q6h
- 2. In vitro susceptibility available
- 2.1 Susceptible to all tested agents
- Preferred regimen: Piperacillin-Tazobactam 3.375 g IV q6h
- Alternative regimen (1): Ciprofloxacin 400 mg IV q8–12h
- Alternative regimen (2): Cefepime 2 g IV q8h (if MIC ≤ 1 μg/mL)
- 2.2 Extended spectrum beta-lactamase (ESBL)-producing Enterobacter spp.
- Preferred regimen: Meropenem 0.5–1 g IV q8h
- Alternative regimen (1): Imipenem 500 mg IV q6h
- Alternative regimen (2): Doripenem 500 mg IV q8h
- Alternative regimen (3): Ertapenem 1 g IV q24h
- Alternative regimen (4): Cefepime 2 g IV q8h (if MIC ≤ 1 μg/mL)
- 2.3 Resistant to all tested agents
- Preferred regimen: Colistin AND Meropenem 0.5–1 g IV q8h
- Alternative regimen (1): Colistin AND Imipenem 500 mg IV q6h
- Alternative regimen (2): Colistin AND Doripenem 500 mg IV q8h
- Alternative regimen (3): Colistin AND Ertapenem 1 g IV q24h
- Alternative regimen (4): Colistin AND Minocycline 100 mg IV q12h
# Escherichia coli
- Escherichia coli Return to Top
- Escherichia coli
- 1. Meningitits
- Preferred regimen (1): Ceftriaxone 4 g IV q12–24h
- Preferred regimen (2): Cefotaxime 8–12 g/day IV q4–6h
- Alternative regimen (1): Aztreonam 6–8 g/day IV q6–8h
- Alternative regimen (2): Gatifloxacin 400 mg/day IV q24h
- Alternative regimen (3): Moxifloxacin 400 mg/day IV q24h
- Alternative regimen (4): Meropenem 6 g/day IV q8h
- Alternative regimen (5): Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day IV q6–12h
- Alternative regimen (6): Ampicillin 12 g/day IV q4h
- 2. Uncomplicated urinary tract infection
- Preferred agents (IDSA/AUA Guidelines): TMP-SMX DS PO bid for 3 days
- Alternative regimen (1): Ciprofloxacin 250 mg PO bid
- Alternative regimen (2): Ciprofloxacin 500 mg XR qd for 3 days
- Alternative regimen (3): Levofloxacin 250 mg PO qd for 3 days.
- Alternative regimen (4): Nitrofurantoin 100 mg PO q6h
- Alternative regimen (5): Nitrofurantoin macrocrystals 100 mg PO bid for 7 days
- Alternative regimen (6): Fosfomycin 3 g sachet PO single dose
- Note: For older patients, those with comorbidities (e.g., diabetes mellitus) use 7-10 days course.
- 3. Pyelonephritis
- 3.1 Acute uncomplicated pyelonephritis
- Preferred regimen (1): Ciprofloxacin 500 mg bid PO for 5-7 days
- Preferred regimen (2): Ciprofloxacin-Erythromycin 1000 mg q24h
- Preferred regimen (3): Levofloxacin 750 mg q24h
- Preferred regimen (4): Ofloxacin 400 mg bid
- Preferred regimen (5): Moxifloxacin 400 mg q24h
- Alternative regimen (1): Amoxicillin-Clavulanic acid 875/125 mg PO q12h or 500/125 mg PO tid or 1000 /125 mg PO bid
- Alternative regimen (2): Oral Cephalosporins
- Alternative regimen (3): TMP-SMX 2 mg/kg IV q6h PO for 14 days
- 3.2 Acute pyelonephritis (Hospitalized)
- Preferred regimen (1): Ciprofloxacin 400 mg IV q12h
- Preferred regimen (2): Ampicillin and Gentamicin
- Preferred regimen (3): Piperacillin-Tazobactam 3.375 g IV q4-6h for 14 days
- Alternative regimen (1): Ticarcillin-Clavulanate 3.1 g IV q6h
- Alternative regimen (2): Ampicillin-Sulbactam 3 g IV q6h
- Alternative regimen (3): Piperacillin-Tazobactam 3.375 g IV q4-6h
- Alternative regimen (4): Ertapenem 1 g IV q24h
- Alternative regimen (5): Doripenem 500 mg q8h for 14 days
- 4. Traveler’s diarrhea
- 4.1 Prophylaxis
- Preferred regimen (1): Bismuth subsalicylate two chewable tablets qid
- Preferred regimen (2): Norfloxacin 400 mg PO qd
- Preferred regimen (3): Ciprofloxacin 500 mg PO qd
- Preferred regimen (4): Rifaximin 200 mg PO qd or bid
- 4.2 Symptomatic treatment
- Preferred regimen (1): Bismuth subsalicylate 1 oz PO every 30 min for 8 doses
- Preferred regimen (2): Loperamide 4 mg PO then 2 mg after each loose stool not to exceed 16 mg daily
- 4.3 Antibiotic treatment
- Preferred regimen (1): Fluoroquinolones, Norfloxacin 400 mg PO bid
- Preferred regimen (2): Ciprofloxacin 500 mg PO bid
- Preferred regimen (3): Ofloxacin 200 mg PO bid
- Preferred regimen (4): Levofloxacin 500 mg PO qd
- Preferred regimen (5): Azithromycin 1000 mg PO single dose
- Preferred regimen (6): Rifaximin 200 mg PO tid
- 5. Malacoplakia
- Preferred regimen (1): Bethanechol chloride AND Ciprofloxacin 400 mg IV q12h
- Preferred regimen (2): Bethanechol chloride AND TMP-SMX 2 mg/kg (TMP component IV q6h)
- 6. Bacteremia/pneumonia
- Preferred regimen (1): Ceftriaxone 1-2 g IV q24h
- Preferred regimen (2): Ciprofloxacin 400 mg IV q12h or 500 mg PO q12h
- Preferred regimen (3): Levofloxacin 500 mg PO/IV q24h
- Preferred regimen (4): Moxifloxacin 400 mg IV/PO q24h
- Preferred regimen (5): Ampicillin 2 g IV q6h (if sensitive)
- Preferred regimen (6): TMP-SMX 5-10 mg/kg/day for q6-8h IV (if sensitive)
- Alternative regimen (1): Imipenem, Meropenem, Ertapenem, Doripenem; Ceftazidime, Cefepime; Cefazolin or Cefuroxime (if sensitive); Aztreonam; Ticarcillin, Piperacillin; Piperacillin-Tazobactam
- Alternative regimen (2): Ampicillin-sulbactam 3 g IV q6h AND (Gentamicin 1.5 mg/kg IV q8h or 5-7 mg/kg/day IV OR Tobramycin 5 mg/kg/day IV)
- Note (1): A 7- to 14-day course of antibiotic therapy is usually recommended.
- Note (2): The choice of antimicrobial agents should be based on susceptibility results.
- Note (3): Monotherapy with aminoglycosides is generally not recommended for bacteremia or pneumonia.
# Francisella tularensis
- Francisella tularensis Return to Top
- Francisella tularensis
- 1. Tularemia
- Preferred regimen (1): Streptomycin 1 g IM bid
- Preferred regimen (2): Gentamicin 5 mg/kg IV q24h for 10 days
- Preferred regimen (3) (pregnancy): Gentamicin 5 mg/kg IV q24h for 10 days
- Alternative regimen (1): Doxycycline 100 mg IV bid
- Alternative regimen (2): Chloramphenicol 1 g IV q6h
- Alternative regimen (3): Ciprofloxacin 400 mg IV bid until stable THEN PO for 14-21 days (total)
# Helicobacter pylori
- Helicobacter pylori Return to Top
- 1. Peptic ulcer disease
- In patients aged 55 years or younger with no alarm features, two management options may be considered:
- 1.1 Indications for eradication therapy
- In moderate to high prevalence of H. pylori infection (≥ 10%): Test-and-treat strategy using a validated noninvasive test (urea breathing test or stool antigen test)
- In low prevalence situations: Treatment indicated after the empiric trial of acid suppression with a proton pump inhibitor for 4–8 weeks
- 1.2 Proton pump inhibitors (PPI)
- Preferred regimen (1): Lansoprazole 30 mg q12h
- Preferred regimen (2): Omeprazole 20 mg q12h
- Preferred regimen (3): Esomeprazole 40 mg q24h
- Preferred regimen (4): Rabeprazole 20 mg q12h
- 1.3 Regimens for Initial Treatment
- 1.3.1 Triple therapy
- Preferred regimen (1): Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid AND Clarithromycin 500 mg bid for 7-14 days
- Preferred regimen (2): Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid AND Metronidazole 500 mg bid for 7-14 days
- Preferred regimen (3) (Levofloxacin triple therapy): Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid AND Levofloxacin 500 mg bid for 10 days
- Preferred regimen (4) (Rifabutin triple therapy): Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid AND Rifabutin 150-300 mg/day for 10 days
- 1.3.2 Quadruple therapy
- Preferred regimen (1): Proton pump inhibitor standard dose bid AND Metronidazole 250 mg q6h AND Tetracycline 500 mg q6h AND Bismuth (dose depends on preparation) for 10-14 days
- Preferred regimen (2) non-bismuth quadruple therapy (concomitant therapy): Proton pump inhibitor (standard dose twice daily) for 7–14 days AND Clarithromycin 500 mg bid for 7–14 days AND Amoxicillin 1 g bid for 10 days AND Metronidazole 250 mg qid for 7–14 days
- 1.3.3 Sequential therapy
- Preferred regimen: Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid for 1-5 days followed by Proton pump inhibitor standard dose bid AND Clarithromycin 500 mg bid AND Tinidazole 500 mg bid for 6-10 days
- Note: Alternative triple therapies appropriate for patients with an allergy to Amoxicillin include (Proton pump inhibitor and Clarithromycin and Metronidazole) or (Proton pump inhibitor and Tetracycline and Metronidazole)
- 1.5 Clarithromycin resistance
- 1.5.1 Clarithromycin resistance ≥ 20%
- Preferred regimen (1) (bismuth quadruple therapy): Proton pump inhibitor standard dose bid AND Metronidazole 250 mg q6h AND Tetracycline 500 mg q6h AND Bismuth (dose depends on preparation) for 10-14 days
- Preferred regimen (2) (sequential therapy): Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid for 1-5 days followed by Proton pump inhibitor standard dose bid AND Clarithromycin 500 mg bid AND Tinidazole 500 mg bid for 6-10 days
- Preferred regimen (3) non-bismuth quadruple therapy (concomitant therapy): Proton pump inhibitor (standard dose twice daily) for 7–14 days AND Clarithromycin 500 mg bid for 7–14 days AND Amoxicillin 1 g bid for 10 days AND Metronidazole 250 mg qid for 7–14 days
- Alternative regimen: Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid AND Levofloxacin 500 mg bid for 10 days
- 1.5.2 Clarithromycin resistance < 20%
- Preferred regimen (1): Proton pump inhibitor standard dose bid for 7-14 days AND Clarithromycin 500 mg bid for 7–14 days AND Amoxicillin 1 g bid for 7–14 days OR Metronidazole 250 mg qid for 7–14 days
- Preferred regimen (2): Proton pump inhibitor standard dose bid AND Metronidazole 250 mg q6h AND Tetracycline 500 mg q6h AND Bismuth (dose depends on preparation) for 10-14 days
- Alternative regimen (1):Proton pump inhibitor standard dose bid AND Metronidazole 250 mg q6h AND Tetracycline 500 mg q6h AND Bismuth (dose depends on preparation) for 10-14 days
- Alternative regimen (2): Proton pump inhibitor standard dose bid for 10 days AND Levofloxacin 500 mg bid for 10 days AND Amoxicillin 1 g bid for 10 days
# Klebsiella granulomatis
- Klebsiella granulomatis Return to Top
- Klebsiella granulomatis (formly known as Calymmatobacterium granulomatis)
- 1. Granuloma inguinale (donovanosis)
- Preferred regimen: Azithromycin 1 g PO once a week or 500 mg qd for 3 weeks THEN until all lesions have completely healed
- Alternative regimen (1): Doxycycline 100 mg PO bid for 3 weeks THEN until all lesions have completely healed
- Alternative regimen (2): Ciprofloxacin 750 mg PO bid for at least 3 weeks THEN until all lesions have completely healed
- Alternative regimen (3): Erythromycin base 500 mg PO qid for at least 3 weeks THEN until all lesions have completely healed
- Alternative regimen (4): Trimethoprim-sulfamethoxazole DS (160 mg/800 mg) tablet PO bid for at least 3 weeks THEN until all lesions have completely healed
# Klebsiella pneumoniae
- Klebsiella pneumoniae Return to Top
- Klebsiella pneumoniae
- 1. Severe, nosocomial infections
- 1.1 Non-ESBLs in pneumonia, sepsis, complicated UTI, or intra-abdominal infections
- Preferred regimen (1): Cefepime 2 g IV q8h
- Preferred regimen (2): Ceftazidime 2 g IV q8h
- Preferred regimen (3): Imipenem 500 mg IV q6h
- Preferred regimen (4): Meropenem 1 g IV q8h
- Preferred regimen (5): Piperacillin-tazobactam 4.5 g IV q6h AND Aminoglycoside
- Alternative regimen (1): Ceftriaxone 1 g IV q24h AND Metronidazole 500 mg IV q6h or 1 g IV q12h
- Alternative regimen (2): Moxifloxacin 400 mg IV/PO q24h
- 1.2 ESBLs in pneumonia, sepsis, complicated UTI, or intra-abdominal infections
- Preferred regimen (1): Imipenem 500 mg IV q6h
- Preferred regimen (2): Meropenem 1 g IV q8h
- Preferred regimen (3): Ertapenem 1 g IV q24h
- Preferred regimen (4): Doripenem 500 mg IV q8h
- Note: In ESBLs, inconsistent activity is seen with aminoglycosides, fluoroquinolones, and piperacillin-tazobactam. Avoid cephalosporins.
# Klebsiella rhinoscleromatis
- Klebsiella rhinoscleromatis Return to Top
- 1. Rhinoscleroma
- Preferred regimen (1): Ciprofloxacin 500–750 mg PO bid for 2–3 months
- Preferred regimen (2): Levofloxacin 750 mg PO qd for 2–3 months
- Preferred regimen (3): Trimethoprim-Sulfamethoxazole 1 DS tab PO bid for 3 months AND Rifampicin 300 mg PO bid for 3 months
- Alternative regimen: Tetracycline OR Streptomycin OR Doxycycline OR Ceftriaxone OR Ofloxacin
- Note (1): The optimal duration of antimicrobial therapy remains unclear. A 6-week to 6-month course of antibiotics until histology exams and cultures are negative may be required.
- Note (2): Use of topical antiseptics such as Acriflavinium and Rifampin ointment has been reported with resolution of symptoms.
# Legionella pneumophila
- Legionella pneumophila Return to Top
- 1.Atypical pneumonia (Legionnaires' disease )
- 1.1 Mild pneumonia inpatient or outpatient, non immunocompromised
- Preferred regimen (1): Azithromycin 500 mg PO qd for 3-5 days
- Preferred regimen (2): Levofloxacin 500 mg PO qd for 7-10 days
- Preferred regimen (3): Ciprofloxacin 500 mg PO bid for 7-10 days
- Preferred regimen (4): Moxifloxacin 400 mg PO qd for 7-10 days
- Preferred regimen (5): Clarithromycin 500 mg PO bid for 10-14 days
- Alternative regimen (1): Doxycycline 200 mg PO loading dose, then 100 mg PO bid for 10-14 days
- Alternative regimen (2): Erythromycin 500 mg PO qid for 10-14 days
- Note: Patients with mild disease may be treated entirely with oral therapy.
- 1.2 Moderate to severe pneumonia or immunocompromised
- Preferred regimen (1): Azithromycin 500 mg PO/IV q24h for 5-7 days
- Preferred regimen (2): Levofloxacin 500 mg PO/IV q24h for 7-10 days OR 750 mg PO/IV q24h for 5-7 days
- Alternative regimen (1): Ciprofloxacin 750 mg PO bid for 14 days
- Alternative regimen (2): Moxifloxacin 400 mg PO qd for 14 days
- Alternative regimen (3): Erythromycin 750-1000 mg IV q6h for 3-7 days, then 500 mg PO qid for a total course of 21 days
- Alternative regimen (4): Clarithromycin 500 mg IV q12h for 3-7 days, and then 500 mg PO bid for a total course of 21 days
- Note: Severely ill patients parenteral therapy is advised until improvement is seen and oral absorption is sufficient.
- 2 Pontiac fever
- Pontiac fever is febrile, self-limited form of Legionella infection which requires only symptomatic therapy, such as analgesics for headache. Antibiotics are not indicated.
# Moraxella catarrhalis
- Moraxella catarrhalis Return to Top
- Moraxella catarrhalis
- Preferred regimen (1): TMP-SMX 1DS PO bid
- Preferred regimen (2): Erythromycin 500 mg PO q6h
- Preferred regimen (3): Clarithromycin 500 mg bid or XL 1 g PO qd
- Preferred regimen (4): Azithromycin 500 mg single dose THEN 250 mg PO qd
- Preferred regimen (5): Doxycycline 100 mg PO/IV bid
- Preferred regimen (6): Parenteral cephalosporins such as Cefuroxime OR Cefotaxime OR Ceftriaxone
- Preferred regimen (7): Cefprozil 200-500 mg PO bid
- Preferred regimen (8): Cefpodoxime 200-400 mg PO bid
- Preferred regimen (9): Cefuroxime 250-500 mg PO bid
- Preferred regimen (10): Cefdinir 300 mg bid
- Preferred regimen (11): Moxifloxacin 400 mg IV/PO qd
- Preferred regimen (12): Levofloxacin 500 mg IV/PO qd
- Preferred regimen (13): Amoxicillin-Clavulanate 875/125 mg PO bid or XL 2000/125 PO bid
# Morganella morganii
- Morganella morganii Return to Top
- Morganella morganii
- Preferred regimen (1): Imipenem 500 mg IV q6h
- Preferred regimen (2): Meropenem 1.0 g IV q8h (adjust dose if necessary for renal function).
- Note (1): Carbapenems are considered first line therapy due to inducible cephalosporinases, and presence of extended-spectrum beta-lactamases in some isolates
- Note (2): Duration of treatment for UTI (generally complicated) is 7 days and duration of treatment for bacteremia is 14 days
- Note (3): Tigecycline is not reliably effective
- Alternative Regimen (1): Cefepime 2.0 g IV q8-12h
- Alternative Regimen (2): Ciprofloxacin 500 mg PO/400 mg IV q12h
- Alternative Regimen (3): Piperacillin 3 g IV q6h
- Alternative Regimen (4): Ticarcillin 3 g IV q4h
- Alternative Regimen (5): Gentamicin
- Alternative Regimen (6): Tobramycin 1 mg/kg IV q24h
- Alternative Regimen (7): Amikacin 3 mg/kg IV q24h
- Note: Aminoglycosides can be used alone for treatment of UTI
# Plesiomonas shigelloides
- Plesiomonas shigelloides Return to Top
- Plesiomonas shigelloides
- 1. Immunocompetent hosts or severe Infection
- Preferred regimen: Ciprofloxacin 500 mg PO bid or 400 mg IV q12h
- Alternative regimen (1): Ofloxacin 300 mg PO bid
- Alternative regimen (2): Norfloxacin 400 mg PO bid
- Alternative regimen (3): TMP-SMX DS PO bid for 3 days
- Alternative regimen (4): Ceftriaxone 1-2 g IV qd in severe cases
- 2. Immunocompromised hosts
- Preferred regimen: Ciprofloxacin 500 mg PO bid for 3 days
- Alternative regimen (1): Ofloxacin 300 mg PO bid
- Alternative regimen (2): Norfloxacin 400 mg PO bid
- Alternative regimen (3): TMP-SMX DS PO bid for 3 days if susceptible
# Proteus mirabilis
- Proteus mirabilis Return to Top
- Proteus mirabilis
- Preferred regimen (1): Ampicillin 500 mg PO q6h or 2 g IV q6h
- Preferred regimen (2): Cefuroxime 250 mg PO bid or 750 mg IV q8h
- Preferred regimen (3): Ciprofloxacin 250-500 mg PO bid or 400 mg IV q12h
- Preferred regimen (4): Levofloxacin 500 mg PO OD or 500 mg IV q24h
- Note: Duration of treatment for uncomplicated UTI 3 days, pyelonephritis 7-14 days, complicated UTI 10-21 days and bacteremia is 7-14 days
# Indole positive Proteus species
- Indole positive Proteus species
- Preferred regimen (1): Ceftriaxone 1 g IV q24h
- Preferred regimen (2): Imipenem 500 mg IV q6h
- Preferred regimen (3): Ciprofloxacin 400 mg IV q12h or 250-500 mg PO bid
- Preferred regimen (4): Levofloxacin 500 mg IV/PO q24h
# Providencia
- Providencia Return to Top
- Providencia
- 1. Complicated uti/bacteremia/acute prostatitis
- Preferred regimen (1): Ciprofloxacin 500-750 mg PO q12h or 400 mg IV q8-12h
- Preferred regimen (2): Levofloxacin 500 mg IV/PO q24h
- Preferred regimen (3): Piperacillin-Tazobactam 3.375 mg IV q6h
- Preferred regimen (4): Ceftriaxone 1-2 g IV q24h (donot use if ESBL suspected or critically ill)
- Preferred regimen (5): Meropenem 1 g IV q8h (consider if critically ill or ESBL suspected)
- Preferred regimen (6): Amikacin 7.5 mg/kg IV q12h
- Preferred regimen (7): Gentamicin
- Preferred regimen (8): Tobramycin acceptable if susceptible but many species are resistant
- Note (1): Duration of treatment for (UTI) is 7 days common or 3-5 days after defervescence or control/elimination of complicating factors (e.g.,removal of foreign material catheter).
- Note (2): Duration of treatment for (bacteremia) is 10-14 days or 3-5 days after defervescence or control/elimination of complicating factors
- Note (3): Duration for acute prostatitis (2 weeks), shorter than chronic prostatitis (4-6 weeks)
- Alternative regimen: TMP-SMX DS PO q12h for 10-14 days or TMP 5-10 mg/kg/day IV q6h
# Pseudomonas aeruginosa
- Pseudomonas aeruginosa Return to Top
- Pseudomonas aeruginosa
- Preferred regimen (1): Cefepime 2 g IV q8h
- Preferred regimen (2): Ceftazidime 2 g IV q8h
- Preferred regimen (3): Piperacillin 3-4 g IV q4h in (no benefit for pseudomonas from beta-lactamase inhibitor)
- Preferred regimen (4): Ticarcillin 3-4 g IV q4h (no benefit for pseudomonas from beta-lactamase inhibitor)
- Preferred regimen (5): Imipenem 500 mg—1 g IV q6h
- Preferred regimen (6): Meropenem 1 g IV q8h
- Preferred regimen (7): Doripenem 500 mg IV q8h
- Preferred regimen (8): Ciprofloxacin 400 mg IV q8h or 750 mg PO q12h (for less serious infections)
- Preferred regimen (9): Aztreonam 2 g IV q6-8h
- Preferred regimen (10): Colistin 2.5 mg/kg IV q12h
- Preferred regimen (11): Polymyxin B 0.75-1.25 mg/kg IV q12h
- Preferred regimen (12): Gentamicin
- Preferred regimen (13): Tobramycin 1.7-2.0 mg/Kg IV q8h or 5-7 mg/kg IV
- Preferred regimen (14): Amikacin 2.5 mg/kg IV q12h
- Note: Amikacin > Tobramycin > Gentamicin with respect to P.aeruginosa susceptibility percentages at most institutions.
# Salmonella
- Salmonella Return to Top
- 1. Salmonellosis in immunocompetent hosts
- 1.1 Gastroenteritis
- Antimicrobial therapy is usually not recommended for uncomplicated diarrheal illness.
- 1.1.1 Indications for antimicrobial therapy
- severedisease,
- Age > 50 yrs
- Prosthesis
- Presence of valvular heart disease
- Severe atherosclerosis
- Cancer
- Uremia
- Immunosuppression
- 1.1.2 Treatment regimens
- Preferred regimen (1): TMP-SMX DS PO bid for 5-7 days
- Preferred regimen (2): Ciprofloxacin 500 mg PO bid for 5-7 days
- Preferred regimen (3): Ceftriaxone 2 g IV q24h for 5-7 days
- 1.2 Typhoid fever
- 1.2.1 Uncomplicated typhoid
- Preferred regimen (1) (fully susceptible): Fluoroquinolone (e.g., Ofloxacin 15 mg/kg PO qd for 5–7 days)
- Preferred regimen (2) (multi drug-resistant): Fluoroquinolone (Ofloxacin 15 mg/kg PO qd for 5–7 days)
- Preferred regimen (3) (quinolone-resistant): Azithromycin 8–10 mg/kg PO qd for 7 days
- Preferred regimen (4) (quinolone-resistant): Fluoroquinolone 20 mg/kg PO qd for 10-14 days
- Alternative regimen (1) (fully susceptible): Chloramphenicol 50–75 mg/kg PO qd for 14-21 days
- Alternative regimen (2) (fully susceptible): Amoxicillin 75–100 mg/kg PO qd for 14 days
- Alternative regimen (3) (fully susceptible): Trimethoprim–Sulfamethoxazole, 8 mg/kg (trimethoprim)– 40 mg/kg (sulfamethoxazole) PO qd for 14 days
- Alternative regimen (4) (multi drug-resistant): Azithromycin 8–10 mg/kg PO for 7 days
- Alternative regimen (5) (multi drug-resistant): Third-generation cephalosporin, e.g., Cefixime 20 mg/kg PO qd for 7-14 days
- Alternative regimen (6) (quinolone-resistant): Third-generation cephalosporin, e.g., Cefixime 20 mg/kg PO qd for 7-14 days
- 1.2.2 Severe typhoid
- Preferred regimen (1) (fully susceptible): Fluoroquinolone (e.g., Ofloxacin 15 mg/kg IV qd for 10-14 days)
- Preferred regimen (2) (multi drug-resistant): Fluoroquinolone (Ofloxacin 15 mg/kg IV qd for 10-14 days)
- Preferred regimen (3) (quinolone-resistant): Ceftriaxone 60 mg/kg IV qd for 10-14 days
- Preferred regimen (4) (quinolone-resistant): Cefotaxime 80 mg/kg IV qd for 10-14 days
- Alternative regimen (1) (fully susceptible): Chloramphenicol 100 mg/kg PO qd for 14-21 days
- Alternative regimen (2) (fully susceptible): Ampicillin 100 mg/kg PO qd for 14-21 days
- Alternative regimen (3) (fully susceptible): Trimethoprim–Sulfamethoxazole, 8 mg/kg (trimethoprim)– 40 mg/kg (sulfamethoxazole) IV qd for 10-14 days
- Alternative regimen (4) (multi drug-resistant): Ceftriaxone 60 mg/kg IV qd for 10-14 days
- Alternative regimen (5) (multi drug-resistant): Cefotaxime 80 mg/kg IV qd for 10-14 days
- Alternative regimen (6) (quinolone-resistant): Fluoroquinolone 20 mg/kg IV qd for 10-14 days
- 1.3 Non-typhoid (serious infection)
- Preferred regimen (1): 3rd generation cephalosporin (Ceftriaxone/Cefotaxime)
- Preferred regimen (2): Fluoroquinolone (Ciprofloxacin, Levofloxacin)
- 1.4 Bacteremia
- Preferred regimen (1): Ceftriaxone 2 g IV q24h
- Preferred regimen (2): Cefotaxime 2 g IV q6-8h for 7-14 days
- Preferred regimen (3): Ciprofloxacin 400 mg IV q12h for 7-14 days
- 1.5 Vascular prosthesis infection
- Preferred regimen (1): Ceftriaxone
- Preferred regimen (2): Cefotaxime
- Preferred regimen (3): Ciprofloxacin 400 mg IV q12h for 6 weeks
- 1.6 Osteomyelitis
- Preferred regimen (1): Ceftriaxone 2 g IV q24h
- Preferred regimen (2): Cefotaxime 2 g IV q6-8h
- Preferred regimen (3): Ciprofloxacin 750 mg PO bid for ≥ 4 weeks
- 1.7 Arthritis
- Preferred regimen (1): Ceftriaxone 2 g IV q24h
- Preferred regimen (2): Cefotaxime 2 g IV q6-8h for 6 weeks
- 1.8 Endocarditis
- Preferred regimen (1): Ceftriaxone 2 g IV q24h
- Preferred regimen (2): Cefotaxime 2 g IV q6-8h for 6 weeks
- 1.9 UTI
- Preferred regimen (1): Ceftriaxone
- Preferred regimen (2): Cefotaxime
- Preferred regimen (3): Ciprofloxacin IV for 1-2 weeks THEN (oral Ciprofloxacin OR TMP-SMX for 6 weeks)
- 1.10 Carrier state
- Preferred regimen (1): Ciprofloxacin 500 mg PO bid for 4-6 weeks
- Preferred regimen (2): TMP-SMX 1DS bid PO for 6 weeks
- Preferred regimen (3): Amoxicillin 500 mg PO for 6 weeks
- 2. Salmonellosis in immunocompromised hosts
- 2.1 HIV and salmonellosis
- 2.1.1 Gastroenteritis
- Preferred regimen: Ciprofloxacin 500-750 mg PO bid or 400 mg IV q12h, if susceptible
- Alternative regimen (1): Levofloxacin 750 mg PO/IV q24h
- Alternative regimen (2): Moxifloxacin 400 mg PO/IV q24h
- Alternative regimen (3): TMP 160 mg AND SMX 800 mg PO/IV q12h
- Alternative regimen (4): Ceftriaxone 1 g IV q24h
- Alternative regimen (5): Cefotaxime 1 g IV q8h
- Duration of treatment for gastroenteritis without bacteremia
- If CD4 count ≥ 200 cells/μL: Duration of treatment is 7–14 days
- If CD4 count < 200 cells/μL: Duration of treatment is 2–6 weeks
- Duration of treatment for gastroenteritis with bacteremia
- If CD4 count ≥ 200/μL: Duration of treatment is 14 days; longer duration if bacteremia persists or if the infection is complicated (e.g., if metastatic foci of infection are present)
- If CD4 count < 200 cells/μL: Duration of treatment is 2–6 weeks
- Note: Secondary prophylaxis should be considered for
- Patients with recurrent Salmonella gastroenteritis with or without bacteremia
- Patients with CD4 < 200 cells/μL with severe diarrhea
# Serratia marcescens
- Serratia marcescens Return to Top
- Serratia marcescens
- 1. Bacteremia, pneumonia or serious infections
- Preferred regimen (1): Cefepime 1-2 g IV q8h
- Preferred regimen (2): Imipenem 0.5-1.0 g IV q6h
- Preferred regimen (3): Ciprofloxacin 400 mg IV q8h
- Alternative regimen (1): Aztreonam
- Alternative regimen (2): Gentamicin
- Alternative regimen (3): Amikacin
- Alternative regimen (4): Piperacillin-tazobactam also often effective
- Note: Duration depends on clinical response, usually 7-14 days
- 2. Endocarditis
- Note: Choice dictated by sensitivities, 4 to 6 week duration of parenteral therapy.
- 3. Osteomyelitis
- Note (1): Choice dictated by sensitivity profile, treat for 6-12 weeks depending upon response.
- Note (2): Use IV treatment until stable/clinically improved (10-14 days Minimum) then may convert to oral therapy if appropriate.
- 4. UTI
- Preferred regimen (1): Ciprofloxacin 250 mg PO bid or 400 mg IV q12h
- Preferred regimen (2): Levofloxacin 250 mg PO qd or 500mg IV q24h
- Note: Fluoroquinolones often sensitive but in seriously ill patient consider empiric coverage with two drugs (e.g.,beta-lactam and aminoglycoside or fluoroquinolones and carbapenem) until susceptibilities known.
# Shigella
- Shigella Return to Top
- 1. Shigellosis
- 1.1 Adults
- Preferred regimen (1): Ciprofloxacin 500 mg PO bid for 3 days
- Alternative regimen (1): Pivmecillinam 100 mg PO qid for 5 days
- Alternative regimen (2): Azithromycin 1-1.5 g PO qd for 1 to 5 days
- 1.2 Pediatrics
- Preferred regimen (1): Ciprofloxacin 15 mg/kg PO bid for 3 days
- Alternative regimen (1): Pivmecillinam 20 mg/kg PO qid for 5 days
- Alternative regimen (2): Ceftriaxone 50-100 mg/kg IM qd for 2 to 5 days
- Alternative regimen (3): Azithromycin 6-20 mg/kg PO qd for 1 to 5 days
# Stenotrophomonas maltophilia
- Stenotrophomonas maltophilia Return to Top
- Stenotrophomonas maltophilia
- Preferred treatment: TMP-SMX 15-20 mg/kg/day (TMP component) IV/PO q8h
- Alternative treatment (1): Ceftazidime 2 g IV q8h
- Alternative treatment (2): Ticarcillin-clavulanate 3.1 g IV q4h
- Alternative treatment (3): Tigecycline 100 mg IV single dose THEN 50 mg IV q12h
- Alternative treatment (4): Ciprofloxacin 500-750 mg PO /400 mg IV q12h
- Alternative treatment (5): Moxifloxacin 400 mg PO/IV
- Alternative treatment (6): Levofloxacin 750 mg PO/IV .
- Alternative treatment (7) (Multiply-resistantance): Colistin 2.5 mg/kg q12h IV
- Note: Treatment duration uncertain, but usually ≥ 14 days
- Vibrio cholerae Return to Top
- 1. WHO
- Note: Antibiotic treatment for cholera patients with severe dehydration only
- Adults
- Preferred regimen: Doxycycline 300 mg po single dose
- Alternative regimen: Tetracycline 12.5 mg/kg PO qid for 3 days
- Pediatric
- Under 12 years old
- Preferred regimen: Erythromycin 12.5 mg/kg PO qid for 3 days
- Over 12 years old
- Preferred regimen: Doxycycline 300 mg po single dose
- Alternative regimen: Tetracycline 12.5 mg/kg PO qid for 3 days
- 2. Pan American Health Organization
- Note: Antibiotic treatment for cholera patients with moderate or severe dehydration
- 2.1 Adult
- Preferred regimen: Doxycycline 300 mg po single dose
- Alternative regimen (1): Ciprofloxacin 1 g PO single dose
- Alternative regimen (2): Azithromycin 1 g PO single dose
- 2.2 Pediatric
- 2.2.1 Children over 3 year, who can swallow tablets
- Preferred regimen (1): Erythromycin 12.5 mg/kg/ PO qid for 3 days
- Preferred regimen (2): Azithromycin 20 mg/kg PO in a single dose
- Alternative regimen (1): Ciprofloxacin suspension or tablets 20 mg/kg PO single dose
- Alternative regimen (2): Doxycycline suspension or tablets 2-4 mg/kg PO single dose
- Note: Although doxycycline has been associated with a low risk of yellowing of the teeth in children, its benefits outweigh its risks
- 2.2.2 Children under 3 year, or infants who cannot swallow tablets
- Preferred regimen (1): Erythromycin suspension 12.5 mg/kg/ PO qid for 3 days
- Preferred regimen (2): Azithromycin suspension 20 mg/kg PO single dose
- Alternative regimen (1): Ciprofloxacin suspension 20 mg/kg PO single dose
- Alternative regimen (2): Doxycycline syrup 2-4 mg/kg PO single dose
- 2.3 Pregnancy
- Preferred regimen (!): Erythromycin 500 mg/ PO qid for 3 days
- Preferred regimen (2): Azithromycin 1 g PO single dose
- Vibrio parahaemolyticus Return to Top
- Vibrio parahaemolyticus
- 1. Mild to Moderate
- Treatment is not necessary in most cases of V. parahaemolyticus infection
- There is no evidence that antibiotic treatment decreases the severity or the length of the illness
- Patients should drink plenty of liquids to replace fluids lost through diarrhea
- 2. Severe or prolonged illnesses
- Preferred regimen: Tetracycline OR Ciprofloxacin
- Vibrio vulnificus Return to Top
- Vibrio vulnificus
- Note: If V. vulnificus is suspected, treatment should be initiated immediately because antibiotics improve survival
- Preferred regimen: Doxycycline 100 mg PO/IV bid for 7-14 days AND Ceftazidime 1-2 g IV/IM q8h
- Note: A single agent regimen with a fluoroquinolone such as Levofloxacin, Ciprofloxacin or Gatifloxacin, has been reported to be at least as effective in an animal model as combination drug regimens with Doxycycline and a Cephalosporin
- Pediatric regimen: Doxycycline AND Fluoroquinolones; trimethoprim-sulfamethoxazole AND an Aminoglycoside
### Bacteria – Atypical Organisms
# Chlamydophila pneumoniae
- Chlamydophila pneumoniae Return to Top
- 1. Atypical pneumonia
- 1.1 Adult
- Preferred regimen (1): Doxycycline 100 mg PO bid for 14-21 days
- Preferred regimen (2): Tetracycline 250 mg PO qid for 14-21 days
- Preferred regimen (3): Azithromycin 500 mg PO as a single dose, followed by 250 mg PO qd for 4 days
- Preferred regimen (4): Clarithromycin 500 mg PO bid for 10 days
- Preferred regimen (5): Levofloxacin 500 mg IV OR PO qd for 7 to 14 days
- Preferred regimen (6): Moxifloxacin 400 mg PO qd for 10 days.
- 1.2 Pediatric
- Preferred regimen (1): Erythromycin suspension PO 50 mg/kg/day for 10 to 14 days
- Preferred regimen (2): Clarithromycin suspension PO 15 mg/kg/day for 10 days
- Preferred regimen (3): Azithromycin suspension PO 10 mg/kg once on the first day, followed by 5 mg/kg qd daily for 4 days
- 2. Upper respiratory tract infection
- 2.1 Bronchitis
- Antibiotic therapy for C. pneumoniae is not required.
- 2.2 Pharyngitis
- Antibiotic therapy for C. pneumoniae is not required.
- 2.3 Sinusitis
- Antibiotic therapy is advisable if symptoms remain beyond 7-10 days.
# Chlamydia trachomatis
- Chlamydia trachomatis Return to Top
- 1 Chlaymydial infections
- 1.1 Chlamydial Infections in Adolescents and Adults
- Preferred regimen (1): Doxycycline 100 mg PO bid for 7 days
- Preferred regimen (2): Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
- Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days.
- Note: Patients should be instructed to refer their sex partners for evaluation, testing, and treatment if they had sexual contact with the patient during the 60 days preceding onset of the patient's symptoms or chlamydia diagnosis.
- 1.2 Chlamydial Infections in patients with HIV Infection
- Preferred regimen (1): Doxycycline 100 mg PO bid for 7 days
- Preferred regimen (2): Azithromycin 1 g PO in a single dose
- Preferred regimen (3): Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
- Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days.
- 1.3 Pregancy
- Preferred regimen: Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Amoxicillin 500 mg PO tid for 7 days
- Alternative regimen (2): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (3): Erythromycin base 250 mg PO qid for 14 days
- Alternative regimen (4): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (5): Erythromycin ethylsuccinate 400 mg PO qid for 14 days
- Note:Doxycycline, Ofloxacin, and Levofloxacin are contraindicated in pregnant women
- 1.4 Management of sex partners
- Preferred regimen (1): Doxycycline 100 mg PO bid for 7 days
- Preferred regimen (2): Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
- Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days.
- Note (1): Recent sex partners (i.e., persons having sexual contact with the infected patient within the 60 days preceding onset of symptoms or Chlamydia diagnosis) should be referred for evaluation, testing, and presumptive dual treatment.
- Note (2): If the patient’s last potential sexual exposure was >60 days before onset of symptoms or diagnosis, the most recent sex partner should be treated.
- Note (3): To avoid reinfection, sex partners should be instructed to abstain from unprotected sexual intercourse for 7 days after they and their sexual partner(s) have completed treatment and after resolution of symptoms, if present
- 2. Chlamydial infection among neonates
- 2.1 Ophthalmia Neonatorumcaused by C. trachomatis
- Preferred regimen: Erythromycin base or ethylsuccinate 50 mg/kg/ day PO qid for 14 days
- Alternative regimen: Azithromycin suspension 20 mg/kg /day PO qd for 3 days
- Note: The mothers of infants who have chlamydial infection and the sex partners of these women should be evaluated and treated.
- 2.2 Infant Pneumonia
- Preferred regimen: Erythromycin base or ethylsuccinate 50 mg/kg/ day PO qid for 14 days
- Alternative regimen: Azithromycin suspension 20 mg/kg /day PO qd for 3 days
- 3.Chlamydial infection among infants and childern
- 3.1 Infants and childern who weigh < 45 kg
- Preferred regimen: Erythromycin base or ethylsuccinate 50 mg/kg/ day PO qid for 14 days
- 3.2 Infants and childern who weigh ≥45 kg but who are aged <8 years
- Preferred regimen: Azithromycin 1 g PO in a single dose
- 3.3 Infants and childern aged ≥8 years
- Preferred regimen (1): Azithromycin 1 g PO in a single dose
- Preferred regimen (2): Doxycycline 100 mg PO bid for 7 days
- 4. Lymphogranuloma venereum (LGV)
- Preferred regimen: Doxycycline 100 mg PO bid for 21 days
- Alternative regimen: Erythromycin base 500 mg PO qid for 21 days
- Note (1): Azithromycin 1 g PO once weekly for 3 weeks is probably effective based on its chlamydial antimicrobial activity. Fluoroquinolone-based treatments might also be effective, but extended treatment intervals are likely required.
- Note (2): Pregnant and lactating women should be treated with Erythromycin. Azithromycin might prove useful for treatment of LGV in pregnancy, but no published data are available regarding its safety and efficacy. Doxycycline is contraindicated in pregnant women.
- Note (3): Persons with both LGV and HIV infection should receive the same regimens as those who are HIV negative. Prolonged therapy might be required, and delay in resolution of symptoms might occur.
- Note (4): Persons who have had sexual contact with a patient who has LGV within the 60 days before onset of the patient’s symptoms should be examined and tested for urethral, cervical, or rectal chlamydial infection depending on anatomic site of exposure. They should be presumptively treated with a chlamydia regimen ( Azithromycin 1 g PO single dose OR Doxycycline 100 mg PO bid for 7 days).
# Chlamydophila psittaci
- Chlamydophila psittaci Return to Top
- 1. ' Psittacosis
- 1.1 Adult
- Preferred regimen (1): Doxycycline 100 mg PO bid for 10-21 days
- Preferred regimen (2): Tetracycline 500 mg PO qid for 10-21 days
- Alternative regimen: Minocycline
- 1.2 Pediatric
- 1.2.1 Mild infection, Infants >3 months
- Preferred regimen: Azithromycin 10 mg/kg PO qd on day 1 THEN 5 mg/kg PO q24h for 4 days; (Maximum, 500 mg for 1st dose, 250 mg for subsequent doses)
- 1.2.2 Moderate-severe infection, Infants >3 months
- Preferred regimen: Azithromycin 10 mg/kg IV q24h for 2 days THEN 5 mg/kg PO qd for 3 days; (Maximum, 500 mg/dose IV; 250 mg/dose PO)
- 1.3 Pregnant Patients
- Preferred regimen: Azithromycin 500 mg PO on day 1 THEN by 250 mg qd on days 2-5 OR 500 mg IV as a single dose for at least 2 days, followed by 500 mg PO qd for 7- 10 days
# Coxiella burnetii
- Coxiella burnetii Return to Top
- 1. Acute Q fever
- 1.1 Adults
- Preferred Regimen: Doxycycline 100 mg PO bid for 14 days
- 1.2 Pediatric
- 1.2.1 ≥ 8 years old
- Preferred regimen:Doxycycline 2.2 mg/kg PO bid for 14 days (Maximum, 100 mg per dose)
- 1.2.2 < 8 years old with high risk criteria
- Preferred regimen:Doxycycline 2.2 mg/kg PO bid for 14 days (Maximum, 100 mg per dose)
- 1.2.3 < 8 years old with mild or uncomplicated illness
- Preferred regimen:Doxycycline 2.2 mg/kg PO bid for 5 days (Maximum, 100 mg per dose)
- Alternative regimen: (If patient remains febrile past 5 days of treatment) Trimethoprim/Sulfamethoxazole 4-20 mg/kg PO bid for 14 days (Maximum, 800 mg per dose)
- 1.3 Pregnant women
- Preferred regimen: Trimethoprim/sulfamethoxazole 160 mg/800 mg PO bid
- Note: Should be given throughout pregnancy
- 2. Chronic Q fever
- 2.1 Endocarditis or vascular infection
- Preferred regimen: Doxycycline 100 mg PO bid AND hydroxychloroquine 200 mg PO tid for ≥18 months
- Note: Childern and pregnant women consultation recommended
- 2.2 Non-cardiac organ disease
- Preferred regimen: Doxycycline 100 mg PO bid AND hydroxychloroquine 200 mg PO tid
- Note: childern and pregnant women consultation recommended
- 2.3 Postpartumwith serologic profile for chronic Q fever
- Preferred regimen: Doxycycline 100 mg PO bid AND hydroxychloroquine 200 mg PO tid for 12 months
- Note (1): Women should only be treated postpartum if serologic titers remain elevated >12 months after delivery (immunoglobulin G phase I titer ≥1:1024); Women treated during pregnancy for acute Q fever should be monitored similarly to other patients who are at high risk for progression to chronic disease (e.g., serologic monitoring at 3, 6, 12, 18, and 24 months after delivery)
- Note (2): Post-Q fever fatigue syndrome- no current recommendation
# Mycoplasma pneumoniae
- Mycoplasma pneumoniae Return to Top
- 1. Atypical pneumonia
- Preferred regimen (1): Azithromycin 500 mg PO qd on day 1 and 250 mg PO qd on days 2 to 5
- Preferred regimen (2): Clarithromycin 500 mg PO qd for 14 days
- Preferred regimen (3): Moxifloxacin 400 mg PO qd for 14 days
- Preferred regimen (4): Levofloxacin 750 mg PO qd for 14 days
- Alternative regimen : Doxycycline 100 mg PO bid for 14 days
# Mycoplasma genitalium
- Mycoplasma genitalium Return to Top
- 1. Urethritis and cervicitis
- Preferred regimen (macrolide-susceptible strains) (1): Azithromycin 1 g PO as a single dose
- Preferred regimen (macrolide-susceptible strains) (2): Azithromycin 500 mg PO as a dose followed by 250 mg PO qd for 4 days
- Preferred regimen (for patients with previous treatment failures): Moxifloxacin 400 mg PO qd for 7–14 days
- 2. Pelvic inflammatory disease (PID)
- Preferred regimen: Moxifloxacin 400 mg PO qd for 14 days
- 3. Specific considerations
- 3.1 Management of sex partners
- Sex partners should be managed according to guidelines for patients with nongonococcal urethritis, cervicitis, and pelvic inflammatory disease.
- 3.2 HIV infection
- Persons who have an M. genitalium infection and HIV infection should receive the same treatment regimen as those who are HIV negative.
### Bacteria – Miscellaneous
- Gardnerella vaginalis Return to Top
- 1.Bacterial Vaginosis
- Gardnerella vaginalis is one of the anaerobic bacteria causing Bacterial Vaginosis,which is a polymicrobial clinical syndrome
- Preferred regimen (1): Metronidazole 500 mg PO bid for 7 days
- Preferred regimen (2): Metronidazole gel 0.75%, one full applicator (5 g) intravaginally, qd for 5 days
- Preferred regimen (3): Clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7 days
- Alternative regimen (1): Tinidazole 2 g PO qd for 2 days
- Alternative regimen (2): Tinidazole 1 g PO qd for 5 days
- Alternative regimen (3): Clindamycin 300 mg PO bid for 7 days
- Alternative regimen (4): Clindamycin ovules 100 mg intravaginally once at bedtime for 3 days
- Note: Clindamycin ovules use an oleaginous base that might weaken latex or rubber products (e.g., condoms and vaginal contraceptive diaphragms). Use of such products within 72 hours following treatment with clindamycin ovules is not recommended.
- 2. Management of Sex Partners
- Routine treatment of sex partners is not recommended.
- 3. Special Considerations
- 3.1 Allergy, Intolerance, or Adverse Reactions
- Intravaginal Clindamycin cream is preferred in case of allergy or intolerance to Metronidazole or Tinidazole. Intravaginal Metronidazole gel can be considered for women who are not allergic to Metronidazole but do not tolerate oral metronidazole. It is advised to avoid consuming alcohol during treatment with nitroimidazoles. To reduce the possibility of a disulfiram-like reaction, abstinence from alcohol use should continue for 24 hours after completion of metronidazole or 72 hours after completion of tinidazole.
- 3.2 Pregnancy
- Preferred regimen (1): Metronidazole 500 mg PO bid for 7 days
- Preferred regimen (2): Metronidazole gel 0.75%, one full applicator (5 g) intravaginally, qd for 5 days
- Note: Tinidazole should be avoided during pregnancy
- 3.3 HIV Infection
- Women with HIV who have BV should receive the same treatment regimen as those who do not have HIV infection.
- Eikenella corrodens Return to Top
- Bordetella pertussis Return to Top
- Bartonella Return to Top
- Stenotrophomonas maltophilia Return to Top
- Acinetobacter baumannii Return to Top
- Yersinia enterocolitica Return to Top
- Yersinia enterocolitica infection (yersiniosis)
- 1. Enterocolitis and mesenteric adenitis
- Preferred regimen: Enterocolitis and adenitis usually self-limited. No antibiotic therapy is required unless clinically indicated.
- 2. Septicemia
- Preferred regimen (1): Doxycycline 100 mg IV q12h AND Tobramycin 5 mg/kg IV q24h
- Preferred regimen (2): Doxycycline 100 mg IV q12h AND Gentamicin 5 mg/kg IV q24h
- Alternative regimen (1): Ciprofloxacin 500 mg IV q12h
- Alternative regimen (2): TMP-SMX TMP 8 mg/kg/day and SMX 40 mg/kg/day IV q12h
- 3. Peritonitis
- Preferred regimen: Fluoroquinolones
- Yersinia pestis Return to Top
- Yersinia pseudotuberculosis Return to Top
### Bacteria – Anaerobic Gram-Negative Bacilli
- Bacteroides fragilis Return to Top
- Bacteroides fragilis
- 1. Monotherapy
- Preferred regimen (1): Imipenem
- Preferred regimen (2): Ertapenem
- Preferred regimen (3): Meropenem
- Preferred regimen (4): Doripenem 0.5-1.0 g IV q6h
- Preferred regimen (5): Piperacillin-tazobactam 3.375 g IV q6h
- Preferred regimen (6): Ampicillin-sulbactam 1-2 g IV q6h
- Preferred regimen (7): Tigecycline 100 mg IV THEN 50 mg IV q12h
- 2. Combination therapy
- Preferred regimen: Metronidazole 0.75-1.0 g IV q12h AND Cefotaxime 1.5-2 g IV q6h OR Aztreonam 1-2 g IV q8h OR Ceftriaxone 1 g IV q12h
- Fusobacterium necrophorum Return to Top
### Fungi
- Aspergillosis Return to Top
- 1. Invasive pulmonary aspergillosis
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- 2. Invasive sinus aspergillosis
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- 3. Tracheobronchial aspergillosis
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- 4. Chronic necrotizing pulmonary aspergillosis
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- 5. Aspergillosis of the CNS
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- Note: There are drug interactions with anticonvulsant therapy.
- 6. Aspergillus infections of the heart (endocarditis, pericarditis, and myocarditis)
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- Note: endocardial lesions generally require surgical treatment. Aspergillus pericarditis usually requires pericardiectomy.
- 7. Aspergillus osteomyelitis and septic arthritis
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- Note: Surgical resection of devitalized bone and cartilage is important for curative intent.
- 8. Aspergillus infections of the eye (endophthalmitis and keratitis)
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- Note: Topical therapy is indicated for keratitis, ophthalmologic intervention and management is recommended for all forms of ocular infection. Systemic therapy may be beneficial when treating aspergillus endophthalmitis.
- 9. Cutaneous aspergillosis
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- Note: Surgical resection is indicated when feasible.
- 10. Aspergillus peritonitis
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- 11. Prophylaxis against invasive aspergillosis
- Preferred regimen: Posaconazole PO 200 mg tid
- Alternative regimen: (1) Itraconazole 200 mg IV bid for 2 days then 200 mg IV qd OR Itraconazole PO 200mg bid
- Alternative regimen: (2) Micafungin 50 mg/day PO qd
- 12. Aspergilloma
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen: Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- 13. Chronic cavitary pulmonary aspergillosis
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- Note: long-term therapy might be needed.
- 14. Allergic bronchopulmonary Itraconazole aspergillosis
- Preferred regimen: Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (1): Voriconazole PO 200 mg bid
- Alternative regimen (2): Posaconazole PO 400 mg bid
- Note: Corticosteroids are a cornerstone of the therapy.
- 15. Allergic aspergillus sinusitis
- Preferred regimen: None or Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Note: Few data available for other agents.
- 16. Relative indications for surgical treatment of invasive aspergillosis
- Pulmonary lesion in proximity to great vessels or pericardium;
- Pericardial infection;
- Invasion of chest wall from contiguous pulmonary lesion;
- Aspergillus empyema;
- Persistent hemoptysis from a single cavitary lesion;
- Infection of skin and soft tissues;
- Infected vascular catheters and prosthetic devices;
- Endocarditis;
- Osteomyelitis;
- Sinusitis;
- Cerebral lesions.
- Blastomycosis Return to Top
- Blastomycosis
- 1. Mild to moderate pulmonary blastomycosis
- Preferred regimen: Itraconazole 200 mg PO qd or bid for 6–12 months
- Note: Oral Itraconazole, 200 mg tid PO for 3 days and THEN 200 mg PO qd or bid for 6–12 months
- 2. Moderately severe to severe pulmonary blastomycosis
- Preferred regimen (1): Lipid Amphotericin B 3–5 mg/kg IV qd for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
- Preferred regimen (2): Amphotericin B deoxycholate 0.7–1 mg/kg IV qd for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
- Note: Oral Itraconazole, 200 mg tid PO for 3 days THEN 200 mg PO bid, for a total of 6–12 months
- 3. Mild to moderate disseminated blastomycosis
- Preferred regimen: Itraconazole 200 mg PO qd or bid for 6–12 months
- Note (1): Treat osteoarticular disease for 12 months
- Note (2): Oral Itraconazole, 200 mg PO tid for 3 days THEN 200 mg PO bid, for 6–12 months
- 4. Moderately severe to severe disseminated blastomycosis
- Preferred regimen (1): Lipid Amphotericin B 3–5 mg/kg IV qd, for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
- Preferred regimen (2): Amphotericin B deoxycholate 0.7–1 mg/kg IV qd, for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
- Note: oral Itraconazole, 200 mg PO tid for 3 days THEN 200 mg PO bid, for 6–12 months
- 5. CNS disease
- Preferred regimen: Lipid Amphotericin B 5 mg/kg IV qd for 4–6 weeks AND an oral azole for at least 1 year
- Note (1): Step-down therapy can be with Fluconazole, 800 mg/day PO qd or bid OR Itraconazole, 200 mg bid or tid OR voriconazole, 200–400 mg bid.
- Note (2): Longer treatment may be required for immunosuppressed patients.
- 6. Immunosuppressed patients
- Preferred regimen (1): Lipid Amphotericin B 3–5 mg/kg IV qd, for 1–2 weeks, AND Itraconazole, 200 mg PO bid for 12 months
- Preferred regimen (2): Amphotericin B deoxycholate, 0.7–1 mg/kg IV qd, for 1–2 weeks, AND Itraconazole, 200 mg PO bid for 12 months
- Note (1): Oral Itraconazole, 200 mg PO tid for 3 days THEN 200 mg PO bid, for 12 months
- Note (2): Life-long suppressive treatment may be required if immunosuppression cannot be reversed.
- 7. Pregnant women
- Preferred regimen: Lipid Amphotericin B 3–5 mg/kg IV qd
- Note (1): Azoles should be avoided because of possible teratogenicity
- Note (2): If the newborn shows evidence of infection, treatment is recommended with Amphotericin B deoxycholate, 1.0 mg/kg IV qd
- 8. Children with mild to moderate disease
- Preferred regimen: Itraconazole 10 mg/kg PO qd for 6–12 months
- Note: Maximum dose 400 mg/day
- 9. Children with moderately severe to severe disease
- Preferred regimen (1): Amphotericin B deoxycholate 0.7–1 mg/kg IV qd for 1–2 weeks AND Itraconazole 10 mg/kg PO qd to a maximum of 400 mg/day for 6–12 months
- Preferred regimen (2): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg IV qd for 1–2 weeks AND Itraconazole 10 mg/kg PO qd to a maximum of 400 mg/day for 6–12 months
- Note: Children tolerate Amphotericin B deoxycholate better than adults do.
- Paracoccidioidomycosis Return to Top
- Preferred regimen (1):
- Adults: Itraconazole 200 mg/day PO
- Children: Itraconazole (5 yr) 5-10 mg/kg/day PO
- Note: Treatment duration based on organ involvement:
- Mild involvement: 6-9 months
- Moderate involvement: 12-18 months
- Preferred regimen (2):
- Adults Trimethoprim/sulfamethoxazole (TMP/SMX) TMP: 160-240 mg/day PO/IV, SMX: 800-1200 mg/day PO/IV bid
- Children Trimethoprim/sulfamethoxazole (TMP/SMX) TMP: 8-10 mg/kg PO/IV, SMX: 40-50 mg/kg PO/IV, bid
- Note (1): Treatment duration based on organ involvement:
- Minor involvement: 12 months
- Moderate involvement: 18-24 months
- Note (2): Preferred treatment in children due to larger experience.
- Note (3): Preferred in IV formulation in severe forms of the disease - 2 ampules IV tid until patient condition improves so that oral medication can be given.
- Preferred regimen (3): Amphotericin B deoxycholate 1 mg/kg/day IV until patient improves and can be treated by the oral route.
- Note: Preferred in severe forms of the disease.
- Alternative regimen (4): Ketoconazole 200-400 mg/day PO for 9-12 months
- Alternative regimen (5): Voriconazole initial dose 400 mg PO/IV q12h for one day, then 200 mg q12h for 6 months
- Note: Diminish the dose to 50% if weight is <40 kg.
- Candidiasis Return to Top
- 1. Candidemia
- 1.1. Nonneutropenic adults
- Preferred regimen (1): Fluconazole 800 mg (12 mg/kg) loading dose, THEN 400 mg (6 mg/kg) qd
- Preferred regimen (2): Caspofungin 70 mg loading dose, THEN 50 mg qd
- Preferred regimen (3): Micafungin 100 mg qd
- Preferred regimen (4): Anidulafungin 200 mg loading dose, THEN 100 mg qd
- Alternative regimen (1): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg qd
- Alternative regimen (2): Amphotericin B deoxycholate(AmB-d) 0.5–1.0 mg/kg qd
- Alternative regimen (3): Voriconazole 400 mg (6 mg/kg) PO/IV bid for 2 doses, THEN 200 mg (3 mg/kg) bid
- Note (1): Echinocandin includes Anidulafungin, Micafungin and Caspofungin.
- Note (2): Choose an echinocandin for moderately severe to severe illness and for patients with recent azole exposure.
- Note (3): Treat for 14 days after first negative blood culture result and resolution of signs and symptoms associated with candidemia.
- Note (4): Ophthalmological examination recommended for all patients.
- 1.2. Neutropenic patients
- Preferred regimen (1): Caspofungin 70 mg loading dose, THEN 50 mg qd
- Preferred regimen (2): Micafungin 100 mg qd
- Preferred regimen (3): Anidulafungin 200 mg loading dose, THEN 100 mg qd
- Preferred regimen (4): Lipid formulation of Amphotericin B (LFAmB) 3–5 mg/kg qd
- Alternative regimen (1): Fluconazole 800 mg (12 mg/kg) loading dose, THEN 400 mg (6 mg/kg) qd
- Alternative regimen (2): Voriconazole 400 mg (6 mg/kg) bid for 2 doses, THEN 200 mg (3 mg/kg) bid
- Note: Fluconazole is recommended for patients without recent azole exposure and who are not critically ill.
- 2. Suspected candidiasis treated with empiric antifungal therapy
- 2.1. Nonneutropenic patients
- Preferred regimen (1): Fluconazole 800 mg (12 mg/kg) loading dose, THEN 400 mg (6 mg/kg) daily
- Preferred regimen (2): Caspofungin 70 mg loading dose, THEN 50 mg daily
- Preferred regimen (3): Micafungin 100 mg daily
- Preferred regimen (4): Anidulafungin 200 mg loading dose, THEN 100 mg daily
- Alternative regimen (1): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily
- Alternative regimen (2): Amphotericin B deoxycholate(AmB-d) 0.5–1.0 mg/kg daily
- Note (1): Duration of therapy is uncertain, but should be discontinued if cultures and/or serodiagnostic tests have negative results.
- Note (2): Echinocandin includes Anidulafungin, Micafungin and Caspofungin.
- Note (3): Echinocandin is preferred for patients with recent azole exposure, patients with moderately severe to severe illness, or patients who are at high risk of infection due to C. glabrata or C. krusei.
- Note (4): Empirical antifungal therapy should be considered in critically ill patients with risk factors for invasive candidiasis and no other known cause of fever and should be based on clinical assessment of risk factors, serologic markers for invasive candidiasis, and/or culture data from nonsterile sites
- 2.2. Neutropenic patients
- Preferred regimen (1): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily
- Preferred regimen (2): Caspofungin 70 mg loading dose, THEN 50 mg daily
- Preferred regimen (3): Voriconazole 400 mg (6 mg/kg) bid for 2 doses, THEN 200 mg (3 mg/kg) bid
- Alternative regimen (1): Fluconazole 800 mg (12 mg/kg) loading dose, THEN 400 mg (6 mg/kg) daily
- Alternative regimen (2): Itraconazole 200 mg (3 mg/ kg) bid
- Note (1): In most neutropenic patients, it is appropriate to initiate empiric antifungal therapy after 4 days of persistent fever despite antibiotics.
- Note (2): Do not use an azole in patients with prior azole prophylaxis.
- 3. Urinary tract infection
- 3.1. Asymptomatic cystitis
- Preferred regimen: Therapy not usually indicated, unless patients are at high risk (e.g., neonates and neutropenic adults) or undergoing urologic procedures.
- Note (1): Elimination of predisposing factors recommended
- Note (2): For high-risk patients, treat as for disseminated candidiasis
- Note (3): For patients undergoing urologic procedures, fluconazole, 200–400 mg (3–6 mg/kg) daily or Amphotericin B deoxycholate (AmB-d) 0.3–0.6 mg/kg daily for several days before and after the procedure.
- 3.2. Symptomatic cystitis
- Preferred regimen: Fluconazole 200 mg (3 mg/kg) daily for 2 weeks
- Alternative regimen (1): Amphotericin B deoxycholate(AmB-d) 0.3–0.6 mg/kg for 1–7 days
- Alternative regimen (2): Flucytosine 25 mg/kg qid for 7–10 days
- Note: Amphotericin B deoxycholate (AmB-d) bladder irrigation is recommended only for patients with refractory fluconazole -resistant organisms (e.g., Candida krusei and Candida glabrata).
- 3.3 Pyelonephritis
- Preferred regimen (1): Fluconazole 200–400 mg (3–6 mg/kg) daily for 2 weeks
- Alternative regimen (1): Amphotericin B deoxycholate(AmB-d) 0.5–0.7 mg/kg daily ± Flucytosine (5-FC) 25 mg/kg qid
- Alternative regimen (2): Flucytosine (5-FC) 25 mg/kg qid for 2 weeks
- Note: For patients with pyelonephritis and suspected disseminated candidiasis, treat as for candidemia.
- 4. Urinary fungus balls
- Preferred regimen (1): Surgical removal strongly recommended
- Preferred regimen (2): Fluconazole 200–400 mg (3–6 mg/kg) daily
- Preferred regimen (3): Amphotericin B deoxycholate(AmB-d) 0.5–0.7 mg/kg daily ± Flucytosine (5-FC) 25 mg/kg qid
- Note (1): Local irrigation with Amphotericin B deoxycholate(AmB-d) may be a useful adjunct to systemic antifungal therapy.
- Note (2): Treatment duration should be until symptoms have resolved and urine cultures no longer yield Candida species.
- 5. Vulvovaginal candidiasis
- Preferred regimen (1): Butoconazole 2% cream 5 g intravaginally for 3 days
- Preferred regimen (2): Butoconazole 2% cream 5 g (butoconazole1-sustained release), single intravaginal application
- Preferred regimen (3): Clotrimazole 1% cream 5 g intravaginally for 7–14 days
- Preferred regimen (4): Clotrimazole 100-mg vaginal tablet for 7 days
- Preferred regimen (5): Clotrimazole 100-mg vaginal tablet, 2 tablets for 3 days
- Preferred regimen (6): Miconazole 2% cream 5 g intravaginally for 7 days
- Preferred regimen (7): Miconazole 100-mg vaginal suppository, 1 suppository for 7 days
- Preferred regimen (8): Miconazole 200-mg vaginal suppository, 1 suppository for 3 days
- Preferred regimen (9): Miconazole 1200-mg vaginal suppository, 1 suppository for 1 day
- Preferred regimen (10): Nystatin 100,000-unit vaginal tablet, 1 tablet for 14 days
- Preferred regimen (11): Tioconazole 6.5% ointment 5 g intravaginally in a single application
- Preferred regimen (12): Terconazole 0.4% cream 5 g intravaginally for 7 days
- Preferred regimen (13): Terconazole 0.4% cream 5 g intravaginally for 3 days
- Preferred regimen (14): Terconazole 80-mg vaginal suppository, 1 suppository for 3 days
- Preferred regimen (15): Fluconazole 150 mg single dose for uncomplicated vaginitis
- Note: For recurring Candida Vulvovaginal candidiasis (VVC), 10–14 days of induction therapy with a topical or oral azole, followed by fluconazole at a dosage of 150 mg once per week for 6 months, is recommended
- 6. Chronic disseminated candidiasis
- Preferred regimen (1): Fluconazole 400 mg (6 mg/kg) daily for stable patients
- Preferred regimen (2): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily for severely ill patients
- Preferred regimen (3): Amphotericin B deoxycholate(AmB-d) 0.5–0.7 mg/kg daily for severely ill patients
- Alternative regimen (1): Caspofungin 70 mg loading dose, THEN 50 mg daily, followed by oral Fluconazole when clinically appropriate
- Alternative regimen (2): Micafungin 100 mg daily, followed by oral Fluconazole when clinically appropriate
- Alternative regimen (3): Anidulafungin 200 mg loading dose, THEN 100 mg daily, followed by oral Fluconazole when clinically appropriate
- Note (1): Transition from Lipid formulation of amphotericin B(LFAmB) or Amphotericin B deoxycholate(AmB-d) to fluconazole is favored after several weeks in stable patients.
- Note (2): Duration of therapy is until lesions have resolved (usually months) and should continue through periods of immunosuppression (e.g., chemotherapy and transplantation).
- Note (3): Therapy should be continued for weeks to months, until calcification occurs or lesions resolve.
- 7. Candida osteoarticular infection
- 7.1. Osteomyelitis
- Preferred regimen (1): Fluconazole 400 mg (6 mg/kg) daily for 6–12 months
- Preferred regimen (2): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily for at least 2 weeks, then Fluconazole 400 mg daily for 6–12 months
- Alternative regimen (1): Caspofungin 70 mg loading dose, THEN 50 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily for 6–12 months
- Alternative regimen (2): Micafungin 100 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily for 6–12 months
- Alternative regimen (3): Anidulafungin 200 mg loading dose, THEN 100 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily for 6–12 months
- Alternative regimen (4): Amphotericin B deoxycholate(AmB-d) 0.5–1.0 mg/kg daily followed by Fluconazole at a dosage of 400 mg daily for 6–12 months
- Note (1): Duration of therapy usually is prolonged (6–12 months)
- Note (2): Surgical debridement is frequently necessary
- 7.2. Septic arthritis
- Preferred regimen (1): Fluconazole 400 mg (6 mg/kg) for at least 6 weeks
- Preferred regimen (2): Lipid formulation of amphotericin B (LFAmB) 3–5 mg/kg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily
- Alternative regimen (1): Caspofungin 70 mg loading dose, THEN 50 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily
- Alternative regimen (2): Micafungin 100 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily
- Alternative regimen (3): Anidulafungin 200 mg loading dose, THEN 100 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily
- Note (1): Duration of therapy usually is for at least 6 weeks, but few data are available.
- Note (2): Surgical debridement is recommended for all cases.
- Note (3): For infected prosthetic joints, removal is recommended for most cases.
- 8. CNS candidiasis
- Preferred regimen (1): Lipid formulation of amphotericin B(LFAmB) at a dosage of 3–5 mg/kg daily ± Flucytosine at a dosage of 25 mg/kg qid for several weeks followed by Fluconazole 400–800 mg (6–12 mg/kg) daily
- Alternative regimen (1): Fluconazole 400–800 mg (6–12 mg/ kg) daily for patients unable to tolerate Lipid formulation of amphotericin B (LFAmB)
- Note (1): Treat until all signs and symptoms, CSF abnormalities, and radiologic abnormalities have resolved.
- Note (2): Removal of intraventricular devices is recommended.
- 9. Candida endophthalmitis
- Preferred regimen (1): Amphotericin B deoxycholate(AmB-d) 0.7–1 mg/kg AND Flucytosine 25 mg/ kg qid
- Preferred regimen (2): Fluconazole 400–800 mg daily (loading dose of 12 mg/kg then 6–12 mg/kg daily) is an acceptable alternative for less severe endophthalmitis
- Alternative regimen (1): Lipid formulation of amphotericin B(LFAmB) at a dosage of 3–5 mg/kg daily
- Alternative regimen (2): Voriconazole 6 mg/kg q12h for 2 doses, then 3–4 mg/kg q12h
- Alternative regimen (3): Caspofungin 70 mg loading dose, THEN 50 mg daily
- Alternative regimen (4): Micafungin 100 mg daily
- Alternative regimen (5): Anidulafungin 200 mg loading dose, THEN 100 mg daily
- Note (1): Alternative therapy is recommended for patients intolerant of or experiencing failure of Amphotericin B and Flucytosine therapy
- Note (2): Duration of therapy is at least 4–6 weeks as determined by repeated examinations to verify resolution.
- Note (3): Diagnostic vitreal aspiration should be done if etiology unknown.
- Note (4): Fluconazole at a dosage of 400–800 mg daily (loading dose of 12 mg/kg then 6–12 mg/kg daily) is an acceptable alternative for less severe endophthalmitis
- Note (5): Surgical intervention for patients with severe endophthalmitis or vitreitis
- 10. Candida infection of the cardiovascular system
- 10.1. Endocarditis
- Preferred regimen (1): Lipid formulation of amphotericin B(LFAmB) at a dosage of 3–5 mg/kg daily ± Flucytosine at a dosage of 25 mg/kg qid
- Preferred regimen (2): Amphotericin B deoxycholate AmB-d 0.6–1 mg/kg daily ± Flucytosine 25 mg/kg qid
- Preferred regimen (3): Caspofungin 50–150 mg daily
- Preferred regimen (4): Micafungin 100–150 mg daily
- Preferred regimen (5): Anidulafungin 100–200 mg daily
- Alternative regimen (1): Step-down therapy to Fluconazole 400–800 mg (6–12 mg/kg) daily for susceptible organism in stable patient with negative blood culture results
- Note (1): Valve replacement is strongly recommended.
- Note (2): For those who are unable to undergo surgical removal of the valve, chronic suppression with fluconazole 400–800 mg (6–12 mg/kg) daily is recommended.
- Note (3): Lifelong suppressive therapy for prosthetic valve endocarditis if valve cannot be replaced is recommended.
- 10.2. Pericarditis or myocarditis
- Preferred regimen (1): Lipid formulation of amphotericin B (LFAmB) at a dosage of 3–5 mg/kg daily
- Preferred regimen (2): Fluconazole 400–800 mg (6–12 mg/kg) daily
- Preferred regimen (3): Caspofungin 50–150 mg daily
- Preferred regimen (4): Micafungin 100–150 mg daily
- Preferred regimen (5): Anidulafungin 100–200 mg daily
- Alternative regimen (1): After stable, step-down therapy to Fluconazole 400–800 mg (6–12 mg/kg) daily
- Note(1): Therapy is often for several months, but few data are available
- Note(2): A pericardial window or pericardiectomy is recommended.
- 10.3. Suppurative thrombophlebitis
- Preferred regimen (1): Lipid formulation of amphotericin B (LFAmB) at a dosage of 3–5 mg/kg daily
- Preferred regimen (2): Fluconazole 400–800 mg (6–12 mg/kg) daily
- Preferred regimen (3): Caspofungin 50–150 mg daily
- Preferred regimen (4): Micafungin 100–150 mg daily
- Preferred regimen (5): Anidulafungin 100–200 mg daily
- Alternative regimen (1): After stable, step-down therapy to Fluconazole 400–800 mg (6–12 mg/kg) daily
- Note(1): Surgical incision and drainage or resection of the vein is recommended if feasible.
- Note(2): Treat for at least 2 weeks after candidemia has cleared.
- 10.4. Infected pacemaker, ICD, or VAD
- Preferred regimen (1): Lipid formulation of amphotericin B(LFAmB) at a dosage of 3–5 mg/kg daily ± Flucytosine at a dosage of 25 mg/kg qid
- Preferred regimen (2): Amphotericin B deoxycholate (AmB-d) 0.6–1 mg/kg daily ± Flucytosine 25 mg/kg qid
- Preferred regimen (3): Caspofungin 50–150 mg daily
- Preferred regimen (4): Micafungin 100–150 mg daily
- Preferred regimen (5): Anidulafungin 100–200 mg daily
- Alternative regimen (1): Step-down therapy to Fluconazole 400–800 mg (6–12 mg/kg) daily for susceptible organism in stable patient with negative blood culture results
- Note(1): Removal of pacemakers and ICDs strongly recommended.
- Note(2): Treat for 4–6 weeks after the device removed.
- Note(3): For VAD that cannot be removed, chronic suppressive therapy with fluconazole is recommended.
- 11. Neonatal candidiasis
- Preferred regimen (1): Amphotericin B deoxycholate (AmB-d) 1 mg/kg daily for 3 weeks
- Preferred regimen (2): Fluconazole 12 mg/kg daily for 3 weeks
- Alternative regimen (1): Lipid formulation of amphotericin B (LFAmB) 3–5 mg/kg daily for 3 weeks
- Note (1): A lumbar puncture and dilated retinal examination should be performed on all neonates with suspected invasive candidiasis.
- Note (2): Intravascular catheter removal is strongly recommended.
- Note (3): Duration of therapy is at least 3 weeks.
- Note (4): Lipid formulation of amphotericin B (LFAmB) used only if there is no renal involvement.
- Note (5): Echinocandins should be used with caution when other agents cannot be used.
- 12. Candida isolated from respiratory secretions
- Preferred regimen (1): Therapy not recommended
- Note (1): Candida lower respiratory tract infection is rare and requires histopathologic evidence to confirm a diagnosis.
- 13. Nongenital mucocutaneous candidiasis
- 13.1. Oropharyngeal
- Preferred regimen (1): Clotrimazole troches 10 mg 5 times daily
- Preferred regimen (2): Nystatin suspension at a concentration of 100,000 U/mL and a dosage of 4–6 mL qid OR 1–2 Nystatin pastilles (200,000 U each) administered qid for 7–14 days
- Preferred regimen (3): Fluconazole 100–200 mg PO (3 mg/kg) daily for 7–14 days
- Alternative regimen (1): Itraconazole solution 200 mg daily
- Alternative regimen (2): Posaconazole suspension at a dosage of 400 mg twice daily for 3 days, THEN 400 mg daily for up to 28 days
- Alternative regimen (3): Voriconazole 200 mg bid
- Alternative regimen (4): Amphotericin B deoxycholate (AmB-d) 1-mL oral suspension administered at a dosage of 100 mg/mL qid
- Alternative regimen (5): Caspofungin 70 mg IV loading dose, THEN 50 mg daily
- Alternative regimen (6): Micafungin 100 mg IV daily
- Alternative regimen (7): Anidulafungin 200 mg IV loading dose, THEN 100 mg daily
- Alternative regimen (8): Amphotericin B deoxycholate (AmB-d) 0.3 mg/kg daily
- Note(1): Fluconazole is recommended for moderate-to-severe disease, and topical therapy with clotrimazole or nystatin is recommended for mild disease.
- Note(2): Treat uncomplicated disease for 7–14 days.
- Note(3): For refractory disease, itraconazole, voriconazole, posaconazole, or AmB suspension is recommended.
- 13.2. Esophageal
- Preferred regimen (1): Fluconazole 200–400 mg (3–6 mg/kg) PO daily
- Preferred regimen (2): Caspofungin 70 mg IV loading dose, THEN 50 mg daily
- Preferred regimen (3): Micafungin 100 mg IV daily
- Preferred regimen (4): Anidulafungin 200 mg IV loading dose, THEN 100 mg daily
- Preferred regimen (4): AmB-d 0.3–0.7 mg/kg daily
- Alternative regimen (1): Itraconazole oral solution 200 mg daily
- Alternative regimen (2): Posaconazole 400 mg bid
- Alternative regimen (3): Voriconazole 200 mg bid
- Note(1): Oral fluconazole is preferred.
- Note(2): For patients unable to tolerate an oral agent,Fluconazole IV, an echinocandin, or AmB-d is appropriate.
- Note(3): Treat for 14–21 days.
- Note(4): For patients with refractory disease, the alternative therapy as listed or AmB-d or an echinocandin is recommended.
- Chromoblastomycosis Return to Top
- Preferred regimen: Itraconazole 200-400 mg PO q24h OR 400 mg pulse therapy once daily for 1 week monthly for 6-12 months
- Note: Pulse therapy reduces cost but it is questionable if it produces resistance to the drug.
- Alternative regimen (1): Terbinafine 500-1000 mg PO qd for 6-12 months
- Alternative regimen (2): Posaconazole 800 mg PO qd for 6-12 months
- Alternative regimen (3): 5-fluorocytosine 100-150 mg/kg/day PO qd for 6-12 months
- Note: This disease has a low cure ratio and high relapse ratio. Physical treatment is needed to achieve better results:
- Cryosurgery with liquid nitrogen - most used physical therapy, it's used in localized lesions and it has a very good treatment response, probably achieved by immune mechanisms since fungi are eliminated from lesions as late as 1-2 weeks after the therapy.
- Thermotherapy - used in conjunction with systemic therapy, was developed by Japanese authors and consists in placing "pocket warmers" in the lesions for 24h/day for some months, as the fungi is sensible to heat.
- Laser vaporization - studied in Germany as an alternative therapy, reported to successfully treat relapsing lesions.
- Coccidioidomycosis Return to Top
- 1. Primary pulmonary infection
- 1.1 Indications for antifungal therapy
- Immunosupression (AIDS, therapy with high dose corticosteroids, receiptients of TNF-alpha, receiptients of an organ transplant)
- Diabetes
- Preexisting cardiomyopathy
- Pregnancy (third trimester)
- Filipino or African
- Weight loss of > 10%
- Intense night sweats persisting longer than 3 weeks
- Infiltrates involving more than one-half of one lung or portions of both lungs
- Prominent or persistent hilar adenopathy
- Anticoccidiodial complement-fixing antibody concentrations in excess of 1:16
- 1.2 Patients with low risk of complications or dissemination
- For many (if not most) patients, management may rely on periodic reassessment of symptoms and radiographic findings to assure resolution without antifungal treatment.
- 1.3 Patients with high risk of complications or dissemination
- 1.3.1 Mild to moderate pneumonia
- Preferred regimen (1): Itraconazole solution 200 mg PO bid or IV q12h
- Preferred regimen (2): Fluconazole 400 mg PO q24h for 3–12 months
- 1.3.2 Locally severe or disseminated pneumonia
- Preferred regimen: (Amphotericin B 0.6–1 mg/kg PO qd every 7 days THEN 0.8 mg/kg PO every other day OR Liposomal Amphotericin B 3-5 mg/kg IV q24 hrs OR Amphotericin B lipid complex 5 mg/kg IV q24 hrs until clinical improvement) followed by Itraconazole OR Fluconazole for at least 1 year.
- Note (1): Some use combination of Amphotericin B and Fluconazole for progressive severe disease; controlled series lacking.
- Note (2): Consultation with specialist recommendation, surgery may be required.
- 2. Meningitis
- 2.1 Adult
- Preferred regimen: Fluconazole 400–1,000 mg PO q24h indefinitely.
- Alternative regimen: Amphotericin B 3-5 mg/kg IV q24 hrs PLUS 0.1–0.3 mg qd intrathecal (intraventricular) via reservoir device OR Itraconazole 400–800 mg q24h OR Voriconazole
- Note: Some use combination of Amphotericin B and Fluconazole for progressive severe disease; controlled series lacking.
- 2.2 Child
- Preferred regimen: Fluconazole PO (Pediatric dose not established, 6 mg per kg q24h used)
- Alternative regimen: Amphotericin B 3-5 mg/kg IV q24 hrs PLUS 0.1–0.3 mg daily intrathecal (intraventricular) via reservoir device OR itra 400–800 mg q24h OR Voriconazole
- 3. Special considerations for HIV/AIDS patients
- 3.1 Clinically mild infections (e.g., focal pneumonia)
- Preferred regimen: Fluconazole 400 mg PO daily OR Itraconazole 200 mg PO bid
- Alternative regimen (unresponsive to Fluconazole or Itraconazole): Posaconazole 200 mg PO bid OR Voriconazole 200 mg PO bid
- Note: Itraconazole, posaconazole, and voriconazole may have significant interactions with certain antiretro viral agents. These interactions are complex and can be bi-directional
- 3.2 Severe, non-meningeal infection (diffuse pulmonary infection or severely ill patients with extrathoracic, disseminated disease)
- Preferred regimen: Amphotericin B deoxycholate 0.7–1.0 mg/kg IV q12hrs OR Lipid formulation Amphotericin B 4–6 mg/kg IV q24hrs. Duration of therapy: continue until clinical improvement, then switch to an azole.
- Alternative regimen: Some specialists will add a triazole (Fluconazole or Itraconazole, with Itraconazole (preferred for bone disease) 400 mg per day to Amphotericin B therapy and continue triazole once Amphotericin B is stopped
- Note (1): Therapeutic drug monitoring and dosage adjustment may be necessary to ensure triazole antifungal and antiretroviral efficacy and reduce concentration-related toxicities.
- Note (2): Therapy should be continued indefinitely in patients with diffuse pulmonary or disseminated diseases because relapse can occur in 25%–33% of HIV-negative patients. It can also occur in HIV-infected patients with CD4 counts >250 cells/μL
- 3.3 Meningeal Infections
- Preferred regimen: Fluconazole 400–800 mg IV or PO daily
- Alternative regimen: Itraconazole 200 mg PO tid for 3 days THEN 200 mg PO bid OR Posaconazole 200 mg PO bid OR Voriconazole 200–400 mg PO bid OR Intrathecal Amphotericin B deoxycholate when triazole antifungals are ineffective.
- Note (1): Intrathecal amphotericin B should only be given in consultation with a specialist and administered by an individual with experience with the technique.
- Note (2): Some patients with meningitis may develop hydrocephalus and require CSF shunting
- Note (3): Therapy should be lifelong in patients with meningeal infections because relapse occurs in 80% of HIV-infected patients after discontinuation of triazole therapy
- 3.4 Chronic Suppressive Therapy
- Preferred regimen (1): Fluconazole 400 mg PO qd
- Preferred regimen (2): Itraconazole 200 mg PO bid
- Alternative regimen (1): Posaconazole 200 mg PO bid
- Alternative regimen (2): Voriconazole 200 mg PO bid
- Cryptococcosis Return to Top
- Cryptococcus Return to Top
- 1. Cryptococcus neoformans
- 1.1 Cryptococcus neoformans meningitis in HIV infected patients
- Preferred regimen for induction and consolidation: (Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd (consider using lipid formulations for patients with renal dysfunction) OR Liposomal AmB 3-4mg/kg IV qd OR Amphotericin B lipid complex (ABLC) 5mg/kg IV qd) PLUS Flucytosine 100mg/kg/day PO or IV qid for at least 2 weeks followed by Fluconazole 400mg (6mg/kg) PO qd for at least 8 weeks.
- Alternative regimen for induction and consolidation (1): Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd OR Liposomal AmB 3-4 mg/kg IV qd OR AmB lipid complex 5mg/kg IV qd for 4-6 weeks
- Alternative regimen for induction and consolidation (2): Amphotericin B deoxycholate 0.7 mg/kg IV qd PLUS Fluconazole 800mg PO qd for 2 weeks, followed by Fluconazole 800mg PO qd for at least 8 weeks
- Alternative regimen for induction and consolidation (3): Fluconazole (>800 mg PO qd, 1200mg PO qd is favored) PLUS Flucytosine (100mg/kg/day PO qid) for 6 weeks
- Alternative regimen for induction and consolidation (4): Fluconazole PO 800-2000mg qd for 10-12 weeks
- Preferred regimen for maintenance and prophylactic therapy: Initiate HAART 2-10 weeks after commencing initial antifungal therapy AND Fluconazole 200mg PO qd
- Alternative regimen for maintenance and prophylactic therapy: Itraconazole 200mg PO bid - monitor drug-level OR Amphotericin B deoxycholate (1 mg/kg) per week IV (should be used in azole-intolerant patients).
- Note (1): Consider discontinuing supressive therapy if CD4 count is higher than 100 cells/uL AND undetectable OR very low HIV RNA level for more than 3 months. Consider reinstitution of maintenance therapy if CD4 count <100 cels/uL.
- Note (2): Do not use acetazolamide OR mannitol OR corticosteroids to treat increased intracranial pressure, instead it should be used lombar puncture in the absence of focal neurologic signs or impaired mentation (which, if present, patient must be submitted to CT or MRI scan first).
- Preferred regimen for induction and consolidation: (Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd (consider using lipid formulations for patients with renal dysfunction) OR Liposomal AmB 3-4mg/kg IV qd OR Amphotericin B lipid complex (ABLC) 5mg/kg IV qd) PLUS Flucytosine 100mg/kg/day PO or IV qid for at least 2 weeks followed by Fluconazole 400mg (6mg/kg) PO qd for at least 8 weeks
- Note: Consider surgery if lesions are larger than 3cm, accessible lesions with mass effect or lesions that are enlarging and not explained by IRIS.
- Preferred regimen: Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd PLUS Flucytosine 100mg/kg/day PO or IV qid for at least 4 weeks (which may be extended to 6 weeks if there is any neurological complication) followed by Fluconazole 400mg PO qd for 8 weeks. If there's toxicity to AmBd, consider changing to LFAmB in the second 2 weeks.
- Note (1): After induction and consolidation therapy, start Fluconazole 200mg (3mg/kg) PO qd for 6-12 months.
- Note (2): If Flucytosine is not given, consider lengthening the induction therapy for at least 2 weeks.
- Mild-moderate symptoms, without severe immunosupression and absence of diffuse pulmonary infiltrates:
- Preferred regimen: Fluconazole 400mg PO qd for 6-12 months
- Severe pneumonia or disseminated disease or CNS infection:
- Preferred regimen: treat like CNS cryptococcosis.
- Note (1): In HIV- infected patients, treatment should be stopped after 1 year if CD4 count is >100 and a cryptococcal antigen titer is <1:512 and not increasing.
- Note (2): Consider corticosteroid if ARDS is present in a context which it might be attributed to IRIS.
- Mild-moderate symptoms, without severe immunosupression and absence of diffuse pulmonary infiltrates:
- Preferred regimen: Fluconazole 400mg PO qd for 6-12 months
- Alternative regimen: if Fluconazole is unavailable or contraindicated, Itraconazole 200mg PO bid, Voriconazole 200 mg PO bid, and Posaconazole 400mg PO bid
- If there's severe pneumonia, disseminated disease or CNS infection:
- Preferred regimen: treat like CNS cryptococcosis for 6-12 months.
- Cryptococcemia or disseminated cryptococcic disease (involvement of at least 2 noncontiguous sites or cryptococcal antigen titer >1:512):
- Preferred regimen: treat like CNS infection.
- If infection occurs at a single site and no immunosupressive risk factors
- Preferred regimen: Fluconazole 400mg PO qd for 6-12 months
- Preferred regimen for induction and consolidation: Amphotericin B deoxycholate 1.0 mg/kg qd IV PLUS Flucytosine 100mg/kg PO or IV qid for 2 weeks followed by Fluconazole 10-12mg/kg PO qd for 8 weeks
- Alternative regimen: patients with renal dysfunction: change Amphotericin B deoxycholate by Liposomal AmB 5mg/kg IV qd or Amphotericin B lipid complex (ABLC) 5mg/kg IV qd
- Preferred regimen for maintenance: Fluconazole 6mg/kg PO qd. Discontinuation of maintenance therapy is poorly studied and should be individualized.
- Cryptococcal pneumonia:
- Preferred regimen Fluconazole 6-12mg/kg PO qd for 6-12 months
- Preferred regimen for induction and consolidation: Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd (consider using lipid formulations for patients with renal dysfunction - Liposomal AmB 3-4mg/kg IV qd OR Amphotericin B lipid complex (ABLC) 5mg/kg IV qd. Consider using Flucytosine in relationship to benefit risk basis, since it is a Category C drug for pregnancy. Start Fluconazole after delivery. Avoid use during first trimester and consider use in the last 2 trimesters with the need for continuous antifungal therapy during pregnancy.
- Note: If pulmonary cryptococcosis: perform close follow-up and administer fluconazole after delivery.
- Disseminated cryptococcosis or CNS disease:
- Preferred regimen: treatment is the same as C. neoformans.
- Pulmonary disease: single and small cryptococcoma:
- Preferred regimen: Fluconazole 400mg per day PO for 6-18months
- Pulmonary disease: Very large or multiple cryptococcomas:
- Preferred regimen: administer Flucytosine AND AmB deocycholate for 4-6 weeks, followed by fluconazole for 6-18 months.
- Note: Surgery should be considered if there is compression of vital structures OR failure to reduce the size of the cryptococcoma after 4 weeks of therapy
- Tinea cruris Return to Top
- Tinea Cruris
- 1. Topical cream/ointment
- Preferred regimen (1): Butenafine cream applied qd for 14 days
- Preferred regimen (2): Terbinafine cream applied bid for 14 days
- 2. Oral antifungal
- Preferred regimen: Fluconazole 200 mg qd for 10 days AND Terbinafine 250 mg qd for 30 days
- Note: Oral antifungal therapy is generally reserved for cases unresponsive to topical agents or can be used along with topical agents in severe cases.
- Tinea corporis Return to Top
- Tinea corporis
- Small, well-defined lesions
- Preferred regimen: Topical cream/ointment like Terbinafine OR Miconazole OR Econazole OR Clotrimazole
- Larger lesionss
- Preferred regimen: Terbinafine 250 mg/day PO for 2 weeks OR Itraconazole 200 mg/day PO for 1 wk OR Fluconazole 250 mg PO weekly for 2-4 weeks
- Tinea pedis Return to Top
- 1. Tinea pedis
- 1.1 Athlete's foot
- 1.1.1 Interdigital
- Preferred regimen: Topical cream/ointment Terbinafine OR Miconazole OR Econazole OR Clotrimazole
- 1.1.2 Dry type
- Preferred regimen (1): Terbinafine 250 mg/day PO for 2-4 weeks
- Preferred regimen (2): Itraconazole 400 mg/day PO for 1 week per month (repeated if necessary)
- Preferred regimen (3): Fluconazole 200 mg PO weekly for 4-8 weeks
- Tinea capitis Return to Top
- Tinea capitis
- Preferred regimen (1): Griseofulvin 10-20 mg/kg/day for minimum 6 weeks
- Preferred regimen (2): Itraconazole 4-6 mg/kg pulsed dose weekly
- Preferred regimen (3): Terbinafine if 40 kg: 250 mg/day
- Tinea barbae Return to Top
- Tinea Barbae
- Preferred regimen: Terbinafine PO 250mg/day for 4 weeks.
- Alternative regimen: Itraconazole PO 200mg/day for 2 weeks.
- Tinea incognito Return to Top
- Tinea Incognito
- Preferred regimen: Stop topical steroids and treat with topical 1% terbinafine cream for 6 weeks.
- Tinea manuum Return to Top
- Tinea Manuum
- Preferred regimen: topical or systemic terbinafine PO 250 mg/day por 2-4 weeks.
- Tinea versicolor Return to Top
- Tinea versicolor
- Preferred regimen: Ketoconazole 400 mg PO single dose OR 200 mg q24h for 7 days OR 2% cream once q24h for 2 weeks
- Alternative regimen: Fluconazole 400 mg PO single dose OR Itraconazole 400 mg PO q24h for 3–7 days
- Majocchi's granuloma Return to Top
- Majocchi's Granuloma
- Preferred regimen: Terbinafine PO 250mg/day for 2-4 weeks.
- Alternative regimen: Itraconazole 200mg PO bid for 1 week, per month for 2 months.
- Onychomycosis Return to Top
- Onychomycosis
- 10.1 Fingernails
- Preferred regimen: Terbinafine PO 250mg/day for 6 weeks OR Itraconazole PO 200mg twice a day for a week a month for 2 months (European guidelines).
- 10.2 Toenails
- Preferred regimen: Toenails Terbinafine PO 250mg/day for 12 weeks OR Itraconazole PO 200mg/day for 12 weeks (U.S. guidelines) OR Itraconazole PO 200mg twice a day for a week a month for 3 months (European guidelines).
- Note (1): There is no evidence that combining systemic and topic treatments has any benefit to the patient.
- Histoplasmosis Return to Top
- 1. Adult treatment:
- 1.1 Pulmonary
- 1.1.1 Acute pulmonary histoplasmosis
- 1.1.1.1 Moderate severe or severe
- Preferred regimen (1): Lipid formulation of Amphotericin B (3.0–5.0 mg/kg IV q12h for 1–2 weeks) THEN Itraconazole (200 mg tid for 3 days THEN 200 mg bid for a total of 12 weeks).
- Preferred regimen (2): Methylprednisolone (0.5–1.0 mg/kg IV q24h) during the first 1–2 weeks of antifungal therapy is recommended for patients who develop respiratory complications, including hypoxemia or significant respiratory distress
- Alternative regimen: The deoxycholate formulation of Amphotericin B (0.7–1.0 mg/kg q24h IV) is an alternative to a lipid formulation in patients who are at a low risk for nephrotoxicity.
- Note (1): In severe cases, cases accompanied by respiratory insufficiency, or hypoxemia, anecdotal reports suggest that corticosteroid therapy may hasten recovery
- Note (2): The pulmonary infiltrates should be resolved on the chest radiograph before antifungal therapy is stopped.
- 1.1.1.2 Mild to moderate:
- Treatment is usually unnecessary
- Preferred regimen for patients who continue to have symptoms for >1 month: Itraconazole (200 mg tid for 3 days {{then} 200 mg qd OR bid for 6–12 weeks)
- Note (1): Antifungal treatment is unnecessary in patients with mild symptoms caused by acute pulmonary histoplasmosis
- 1.1.2 Chronic cavitary pulmonary histoplasmosis:
- Preferred regimen: Itraconazole (200 mg tid for 3 days and THEN qd or bid for at least 1 year) is recommended
- Note (1): Blood levels of itraconazole should be obtained after the patient has been receiving this agent for at least 2 weeks to ensure adequate drug exposure
- Note (2): Patients with underlying emphysema often develop progressive pulmonary disease, which is characterized by cavities with surrounding inflammation after infection with hysotplasma capsulatum
- 1.1.3 Broncholithiasis
- Antifungal treatment is not recommended
- Note: Bronchoscopic or surgical removal of the broncholith is recommended
- 1.1.4 Pulmonary nodules (Histoplasmomas)
- Antifungal treatment is not recommended
- Note: There is no evidence that antifungal agents have any effect on histoplasmomas or that histoplasmomas contain viable organisms.
- 1.2 Mediastinitis
- 1.2.1 Mediastinal lymphadenitis
- 1.2.1.1 Asymptomatic cases
- Treatment is usually unnecessary
- 1.2.1.2 Patients who have symptoms that warrant treatment with corticosteroids and in those who continue to have symptoms for > 1 month
- Itraconazole (200 mg 3 tid for 3 days and THEN 200 mg qd or bid for 6–12 weeks)
- 1.2.1.2 Severe cases with obstruction or compression of contiguous structures
- Preferred regimen: Prednisone (0.5–1.0 mg/kg qd in tapering doses over 1–2 weeks)
- Note (1): Antifungal treatment is unnecessary in most patients with symptoms due to mediastinal lymphadenitis
- Note (2): Itraconazole is recommended for 6–12 weeks to reduce the risk of progressive disseminated disease caused by corticosteroid-induced immunosuppression in patients who are given corticosteroids and in patients whose symptoms last longer than 1 month.
- 1.2.2 Mediastinal granuloma
- 1.2.2.1 Asymptomatic cases
- Treatment is usually unnecessary
- 1.2.2.2 Symptomatic cases
- Preferred regimen: Itraconazole (200 mg 3 times qd for 3 days and THEN qd or bid for 6–12 weeks)
- Note (1): Itraconazole is appropriate for symptomatic cases but there are no controlled trials to prove its efficacy.
- Note (2): There is no evidence that mediastinal granuloma evolves into mediastinal fibrosis. Thus treatment with either surgery or itraconazole should not be used to prevent the development of mediastinal fibrosis
- 1.2.3 Mediastinal fibrosis
- Antifungal treatment is not recommended
- 1.2.3.1 If clinical findings cannot differentiate mediastinal fibrosis from mediastinal granuloma
- Preferred regimen: Itraconazole (200 mg qd or bid for 12 weeks)
- Note: The placement of intravascular stents is recommended for selected patients with pulmonary vessel obstruction
- Note (2): Mediastinal fibrosis is characterized by invasive fibrosis that encases mediastinal or hilar nodes and that is defined by occlusion of central vessels and airways
- 1.3 Pericarditis:
- 1.3.1 Mild cases
- Preferred regimen: Nonsteroidal anti-inflammatory therapy
- 1.3.2 Patients with evidence of hemodynamic compromise or unremitting symptoms after several days of therapy with nonsteroidal anti-inflammatory therapy
- Prednisone (0.5–1.0 mg/kg qd in tapering doses over 1–2 weeks)
- 1.3.3 If corticosteroids are administered
- Preferred regimen: Itraconazole (200 mg tid for 3 days and THEN qd or bid for 6–12 weeks)
- Note (1): Pericardial fluid removal is indicated for patients with hemodynamic compromise.
- Note (2): Pericarditis occurs as a complication of inflammation in adjacent mediastinal lymph nodes in patients with acute pulmonary histoplasmosis.
- 1.4 Central nervous system histoplasmosis
- Preferred regimen: Liposomal Amphotericin B (5.0 mg/kg qd for a total of 175 mg/kg given over 4–6 weeks) followed by Itraconazole (200 mg 2 or 3 times qd) for at least 1 year and until resolution of cerebro spinal fluid abnormalities including Histoplasma antigen levels.
- Note: Blood levels of Itraconazole should be obtained to ensure adequate drug exposure
- 1.5 Rheumatologic syndromes
- 1.5.1 Mild cases
- Preferred regimen: Nonsteroidal anti-inflammatory therapy
- 1.5.2 Severe cases
- Preferred regimen: Prednisone (0.5–1.0 mg/kg qd in tapering doses over 1–2 weeks)
- 1.5.3 Corticosteroids administration
- Itraconazole (200 mg 3 times tid for 3 days and THEN qd or bid for 6–12 weeks)
- Note (1): If corticosteroids are used, concurrent itraconazole treatment is recommended to reduce the risk of progressive infection
- Note (2): Bone or joint involvement is very rare in progressive disseminated histoplasmosis but it should not be overlooked.
- 1.6 Progressive disseminated histoplasmosis
- 1.6.1 Moderately severe to severe disease
- Preferred regimen: Liposomal Amphotericin B (3.0 mg/kg qd) is recommended for 1–2 weeks followed by oral Itraconazole (200 mg 3 times qd for 3 days and THEN 200 mg bid for a total of at least 12 months)
- Note (1): Substitution of another lipid formulation at a dosage of 5.0 mg/kg qd may be preferred in some patients because of cost or tolerability
- Note (2): The deoxycholate formulation of Amphotericin B (0.7–1.0 mg/kg qd) is an alternative to a lipid formulation in patients who are at a low risk for nephrotoxicity
- 1.6.2 Immunosupressed patients
- Lifelong suppressive therapy with Itraconazole (200 mg qd)
- 1.6.3 Mild to moderate disease
- Itraconazole (200 mg tid for 3 days and then bid qid for at least 12 months)
- Note (1): Lifelong suppressive therapy with itraconazole (200 mg daily) may be required in immunosuppressed patients if immunosuppression cannot be reversed and in patients who relapse despite receipt of appropriate therapy
- Note (2): Blood levels of itraconazole should be obtained to ensure adequate drug exposure
- Note (3): Antigen levels should be measured during therapy and for 12 months after therapy is ended to monitor for relapse. Persistent low-level antigenuria may not be a reason to prolong treatment in patients who have completed appropriate therapy and have no evidence of active infection.
- Note (4): Progressive disseminated histoplasmosis is fatal without therapy and treatment with either Amphotericin B or Itraconazole is highly effective. Among patients with AIDS and moderately severe to severe disseminated histoplasmosis, the rate of response was higher (88% vs. 64%) and the mortality rate was lower (2% vs. 13%) among recipients of liposomal amphotericin B (3 mg/kg qd for 1–2 weeks) than among recipients of the deoxycholate formulation.
- 1.7 Prophylaxis recommended for immunosuppressed patients
- Preferred regimen: Itraconazole (200 mg qd) in patients with HIV infection with CD4 cell counts 10 cases per 100 patient-years
- Note: Prophylaxis with Itraconazole (200 mg qd) may be appropriate in specific circumstances in other immunosuppressed patients
- 1.8 Performance Measures
- Preferred regimen: Itraconazole is the preferred azole for initial therapy for patients with mild-to-moderate histoplasmosis and as step-down therapy after receipt of Amphotericin B
- Note: When other azole agents are used, the medical record should document the specific reasons that Itraconazole was not used and why other azoles were used.
- 14.1 Severe or moderately severe histoplasmosis
- Preferred regimen: Amphotericin B
- Note: When Amphotericin B is used the patient's electrolyte level renal function and blood cell count should be monitored several times per week and documented in the medical record.
- Note (2): Itraconazole drug levels should be measured during the first month in patients with disseminated or chronic pulmonary histoplasmosis and these levels should be documented in the medical record as well as the physician's response to levels that are too low.
- Note (3): Itraconazole should not be given to patients receiving contraindicated medications (i.e., pimozide, quinidine, dofetilide, lovastatin, simvastatin, midazolam, and triazolam). Reasons for deviation from this practice should be documented in the medical record.
- 2. Pregnancy treatment
- Preferred regimen: Lipid formulation Amphotericin B (3.0–5.0 mg/kg qd for 4–6 weeks) is recommended
- Prefered regimen low risk for nephrotoxicity: The deoxycholate formulation of Amphotericin B (0.7–1.0 mg/kg qd) is an alternative to a lipid formulation
- Note (1): If the newborn shows evidence for infection, treatment is recommended with Amphotericin B deoxycholate (1.0 mg/kg daily for 4 weeks)
- Note (2): Unique issues in pregnancy include the risk of teratogenic complications of azole therapy and of transplacental transmission of Histoplasma capsulatum to the fetus
- 3. Children treatment
- 3.1 Acute pulmonary histoplasmosis
- Treatment indications and regimens are similar to those for adults, except that Amphotericin B deoxycholate (1.0 mg/kg daily) is usually well tolerated and the lipid preparations are not preferred
- Note: Itraconazole dosage: 5.0–10.0 mg/kg daily in 2 divided doses (not to exceed 400 mg daily), generally using the solution formulation
- Progressive disseminated histoplasmosis
- Prefered regimen: Amphotericin B deoxycholate (1.0 mg/kg qd for 4–6 weeks)
- Alternative regimen: Amphotericin B deoxycholate (1.0 mg/kg qd for 2–4 weeks) followed by itraconazole (5.0–10.0 mg/kg qd in 2 divided doses) to complete 3 months of therapy.
- Immunosuppressed patients if immunosuppression cannot be reversed and patients in relapse despite appropiate therapy
- Note (1): Longer therapy may be needed for patients with severe disease, immunosuppression, or primary immunodeficiency syndromes
- Note (2): Blood levels of itraconazole should be obtained to ensure adequate drug exposure
- Note (3): Antigen levels should be monitored during therapy and for 12 months after therapy is ended to monitor for relapse. Persistent low-level antigenuria may not be a reason to prolong treatment in patients who have completed appropriate therapy and have no evidence of active infection.
- Mucormycosis Return to Top
- Mucormycosis
- Treatment include surgical debridement of involved tissues, antifungal therapy, use of growth factors to accelerate recovery from neutropenia, provision of granulocyte transfusions with sustained circulating neutrophils until the patient recovers from neutropenia, and discontinuation or reduction in the dose of glucocorticoids, correction of metabolic acidosis and hyperglycemia.
- Preferred regimen (1): Amphotericin B Deoxycholate 1.0-1.5 mg/kg/day IV q24h
- Preferred regimen (2): Lipid Amphotericin B 5-10 mg/kg/day IV q24h
- Preferred regimen (3): Amphotericin B lipid complex 5-7.5 mg/kg/day IV q24h
- Alternative regimen (1):Caspofungin 70 mg IV load dose, 50 mg/day for >2 weeks PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h
- Pediatric dose: Caspofungin 50 mg/m² IV q24h PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h
- Alternative regimen (2): Micafungin OR Anidulafungin 100 mg/day for 2 weeks PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h
- Pediatric dose: Micafungin 4 mg/kg/day; Micafungin 10mg/kg/day for low-birth weight infants; Anidulafungin 1.5 mg/kg/day
- Alternative regimen (3): Deferasirox 20 mg/kg PO qd for 2–4 weeks PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h
- Alternative regimen (4): Posaconazole 800 mg/day PO qid or bid
- Alternative regimen (5): Initial: Isavuconazole 200 mg PO/IV q8h for 6 doses; maintenance: 200 mg PO/IV qd
- Note (1): start maintenance dose 12 to 24 hours after the last loading dose.
- Note (2): For salvage therapy: (Posaconazole 800 mg/day PO qid or bid ± Lipid Amphotericin B 5-10 mg/kg/day IV q24h) OR (Deferasirox 20 mg/kg PO qd for 2–4 weeks PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h) OR Granulocyte transfusions (for persistently neutropenic patients) ∼10ˆ9 cells/kg OR Recombinant cytokines G-CSF 5 μg/kg/day, GM-CSF 100–250 μg/m², or IFN-g at 50 μg/m² for those with body surface area ≥ 0.5 m² and 1.5 μg/kg for those with body surface area <0.5 m²
- Penicilliosis Return to Top
- Penicilliosis treatment
- 1. Mild disease
- Preferred regimen: Itraconazole 200 mg PO bid for 8 to 12 weeks without amphotericin B induction therapy
- Alternative regimen: Voriconazole 400 mg PO bid on day 1 THEN 200 mg PO bid for 12 weeks
- 2. Moderate-severe disease
- Preferred regimen: Liposomal Amphotericin B 3-5 mg/kg/day IV qd OR Amphotericin B lipid complex 5 mg/kg/day IV qd for 2 weeks THEN Itraconazole 200 mg PO bid for 10 weeks
- Alternative regimen: Voriconazole 6 mg/kg IV q12h on day 1 THEN 4 mg/kg q12h for at least 3 days THEN Voriconazole 200 mg PO bid for a total of 12 weeks
- 3. Maintenance therapy
- Preferred regimen Itraconazole 200 mg PO qd
- Alternative regimen: Voriconazole 200 mg PO bid
- Note: Voriconazole and Itraconazole use require serum levels to be monitored to ensure adequate absorption.
- Sporotrichosis Return to Top
- Lymphocutaneous/cutaneous
- Preferred regimen: Itraconazole 200mg PO qd
- Alternative regimen: Itraconazole 200 mg PO bid OR Terbinafine 500 mg PO bid OR Saturated solution potassium iodide with increasing doses OR Fluconazole 400–800 mg PO qd OR local hyperthermia
- Note (1): Treat for 2–4 weeks after lesions resolved
- Note (2): SSKI initiated at a dosage of 5 drops (using a standard eyedropper) q8h, increasing as tolerated to 40–50 drops q8h
- Osteoarticular
- Preferred regimen: Itraconazole 200mg PO bid for 12 months
- Alternative regimen: Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day IV OR Amphotericin B deoxycholate 0.7–1 mg/kg/day IV
- Note (1): Switch to Itraconazole after favorable response if AmB used
- Note (2): Treat for a total of at least 12 months
- Pulmonary
- Preferred regimen(1): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day IV for severe or life-threatening pulmonary sporotrichosis, then Itraconazole 200 mg PO bid
- Preferred regimen(2): Itraconazole 200 mg PO bid for 12 months for less severe disease
- Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/d IV THEN Itraconazole 200 mg PO bid OR surgical removal
- Note (1): Treat severe disease with an AmB formulation followed by Itraconazole
- Note (2): Treat less severe disease with Itraconazole
- Note (3): Treat for a total of at least 12 monthsSurgery combined with amphotericin B therapy is rec- ommended for localized pulmonary disease
- Meningitis
- Preferred regimen: Lipid amphotericin B (Lipid AmB) 5 mg/kg daily for 4–6 weeks, then Itraconazole 200 mg PO bid
- Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/d, then Itraconazole 200 mg PO bid
- Note (1): Length of therapy with AmB not established, but therapy for at least 4–6 weeks is recommended.
- Note (2): Treat for a total of at least 12 months.
- Note (3): May require long-term suppression with Itraconazole.
- Disseminated
- Preferred regimen: Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day, then Itraconazole 200 mg PO bid
- Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/day, then Itraconazole 200 mg PO bid
- Note(1): Therapy with AmB should be continued until the patient shows objective evidence of improvement.
- Note(2): Treat for a total of at least 12 months.
- Note(3): May require long-term suppression with Itraconazole.
- Pregnant women
- Preferred regimen(1): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day IV OR Amphotericin B deoxycholate 0.7–1 mg/kg/day IV for severe sporotrichosis
- Preferred regimen(2): Local hyperthermia for cutaneous disease.
- Note (1): It is preferable to wait until after delivery to treat non–life-threatening forms of sporotrichosis.
- Note (2): Azoles should be avoided.
- Children
- Preferred regimen:
- Mild disease: Itraconazole 6–10 mg/kg/day PO (400 mg/day maximum)
- Severe disease: Amphotericin B deoxycholate 0.7 mg/kg/day IV followed by Itraconazole 6–10 mg/kg PO up to a maximum of 400 mg PO daily, as step-down therapy
- Alternative regimen: Saturated solution potassium iodide with increasing doses for mild disease initiated at a dosage of 1 drop (using a standard eyedropper) q8h and increased as tolerated up to a maximum of 1 drop/kg or 40–50 drops q8h, whichever is lowest
- Pneumocystis jiroveci Return to Top
- 1. Preventing First Episode of PCP (Primary Prophylaxis)
- Preferred regimen: TMP-SMX 1 Double-Strength(DS) PO daily OR TMP-SMX 1 Single-Strength(SS) PO daily
- Alternative regimen (1): TMP-SMX 1 Double-Strength(DS) tid weekly OR Dapsone 100 mg PO daily or 50 mg PO bid
- Alternative regimen (2): Dapsone 50 mg PO AND (Pyrimethamine 50 mg PO AND Leucovorin 25 mg) PO weekly
- Alternative regimen (3): Dapsone 200 mg PO AND Pyrimethamine 75 mg PO AND Leucovorin 25 mg PO weekly
- Alternative regimen (4): Aerosolized Pentamidinec 300 mg via Respigard II™ nebulizer every month
- Alternative regimen (5): Atovaquone 1500 mg PO qd with food
- Alternative regimen (6): Atovaquone 1500 mg PO AND Pyrimethamine 25 mg PO AND Leucovorin 10 mg PO daily with food
- 2. Treatment of Pneumocystis Pneumonia
- 2.1. Moderate to Severe PCP
- Preferred regimen: TMP-SMX (TMP 15–20 mg and SMX 75–100 mg)/kg/day IV given q6h or q8h
- Note: May switch to PO after clinical improvement
- Alternative regimen (1): Pentamidine 4 mg/kg IV once daily infused over at least 60 minutes
- Note: May reduce the dose to 3 mg/kg IV once daily because of toxicities.
- Alternative regimen (2): Primaquine 30 mg (base) PO once daily AND (Clindamycin or )
- Note (1): Duration of PCP treatment is 21 days
- Note (2): Adjunctive corticosteroid may be indicated in some moderate to severe cases.Prednisone doses (beginning as early as possible and within 72 hours of PCP therapy) (AI):
- Note (3): Prednisone doses (beginning as early as possible and within 72 hours of PCP therapy)
- Days 1–5 40 mg PO BID
- Days 6–10 40 mg PO daily
- Days 11–21 20 mg PO daily
- 2.2. Mild to Moderate PCP
- Preferred regimen: TMP-SMX (TMP 15–20 mg/kg/day and SMX 75–100 mg/kg/day), given PO in 3 divided doses OR TMP-SMX Double-Strength(DS) - 2 tablets tid
- Alternative regimen (1): Dapsone 100 mg PO daily AND TMP 15 mg/kg/day PO (3 divided doses)
- Alternative regimen (2): Primaquine 30 mg (base) PO daily AND Clindamycin PO (450 mg q6h or 600 mg q8h)
- Alternative regimen (3): Atovaquone 750 mg PO BID with food
- Note: Duration of PCP treatment is 21 days
- 3. Preventing Subsequent Episode of PCP (Secondary Prophylaxis)
- Preferred regimen: TMP-SMX 1 Double-Strength(DS) PO daily OR TMP-SMX 1 Single-Strength(SS) PO daily
- Alternative regimen (1): TMP-SMX 1 Double-Strength(DS) tid weekly OR Dapsone 100 mg PO daily or 50 mg PO BID
- Alternative regimen (2): Dapsone 50 mg PO daily AND (Pyrimethamine 50 mg + Leucovorin 25 mg) PO weekly
- Alternative regimen (3): Dapsone 200 mg AND Pyrimethamine 75 mg AND Leucovorin 25 mg PO weekly
- Alternative regimen (4): Aerosolized Pentamidinec 300 mg via Respigard II™ nebulizer every month
- Alternative regimen (5): Atovaquone 1500 mg PO daily with food
- Alternative regimen (6): Atovaquone 1500 mg AND Pyrimethamine 25 mg AND Leucovorin 10 mg PO daily with food
### Mycobacteria
- Mycobacterium tuberculosis Return to Top
- 1. Standard Regimens for new patients
- 1.1 Adult
- 1.1.1 Initial phase
- Preferred regimen: Isoniazid 300 mg PO (5 mg/kg/day) qd for 8 weeks AND Rifampicin 600 mg PO (10 mg/kg/day) qd for 8 weeks AND Pyrazinamide 2 g PO (25 mg/kg/day) qd for 8 weeks AND Ethambutol 1.6 g PO (15 mg/kg/day) qd for 8 weeks
- Alternative regimen (1): Isoniazid 300 mg/day PO for 2 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO for 2 weeks (10 mg/kg/day) AND Pyrazinamide 2 g/day PO for 2 weeks (25 mg/kg/day) AND Ethambutol 1.6 g PO for 2 weeks (15 mg/kg/day), followed by Isoniazid 300 mg/day PO twice weekly for 6 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO twice weekly for 6 weeks (10 mg/kg/day) AND Pyrazinamide 2 g/day PO twice weekly for 6 weeks AND Ethambutol 1.6 g PO for 2 weeks (15 mg/kg/day)
- Alternative regimen (2): Isoniazid 300 mg/day PO thrice weekly for 8 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO thrice weekly for 8 weeks (10 mg/kg/day) AND Pyrazinamide 2g/day PO thrice weekly for 8 week (25 mg/kg/day) AND Ethambutol 1.6 g PO thrice weekly for 8 weeks (15 mg/kg/day)
- 1.1.2 Continuation phase
- Preferred regimen (1): Isoniazid 300 mg PO (5 mg/kg/day) qd AND Rifampicin 600 mg PO (10 mg/kg/day) qd for 18 weeks
- Preferred regimen (2): Isoniazid 300 mg PO twice weekly (5 mg/kg/day) AND Rifampicin 600 mg/day PO twice weekly (10 mg/kg/day) for 18 weeks
- Alternative regimen (1): Isoniazid 300 mg/day PO biweekly for 18 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO biweekly for 18 weeks (10 mg/kg/day)
- Alternative regimen (2): Isoniazid 300 mg/day PO thrice weekly for 18 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO thrice weekly for 18 weeks (10 mg/kg/day)
- 1.2 Pediatric
- 1.2.1 Initial phase
- Preferred regimen: Isoniazid 10 mg/kg PO (Maximum, 300 mg/day) AND Rifampicin 15 mg/kg PO (Maximum, 600 mg/day) AND Pyrazinamide 35 mg/kg PO (Maximum, 2 g/day) AND Ethambutol 20 mg/kg PO (Maximum, 1.6 g/day), each for 8 weeks
- 1.2.2 Continuation phase
- Preferred regimen: Isoniazid 10 mg/kg PO (Maximum, 300 mg/day) AND Rifampicin 15 mg/kg PO (Maximum, 600 mg/day), each drug daily for 18 weeks
- 2. MDR Tuberculosis
- 2.1 Adult
- Preferred regimen: 4 agents combination
- Agent 1: Pyrazinamide 20–30 mg/kg OR Ethambutol 15–25 mg/kg OR Rifabutin 5 mg/kg
- Agent 2: Capreomycin 15 mg/kg OR Kanamycin 15 mg/kg OR Amikacin 7.5-10 mg/kg OR Streptomycin 12–18 mg/kg
- Agent 3: Levofloxacin 500-1000 mg OR Moxifloxacin 400 mg OR Ofloxacin 400 mg
- Agent 4: Ethionamide 15-20 mg/kg OR Protionamide 15-20 mg/kg OR Cycloserine 10-15 mg/kg OR Terizidone 10-20 mg/kg OR Para-aminosalicylic acid 8-12 g/day IV q8-12h
- 2.2 Pediatric
- Preferred regimen: 4 agents combination
- Agent 1: Pyrazinamide 20-30 mg/kg (Maximum: 600 mg) OR Ethambutol 15-20 mg/kg OR Rifabutin 5 mg/kg
- Agent 2: Capreomycin 15-30 mg/kg (Maximum: 1000 mg) OR Kanamycin 15-30 mg/kg (Maximum: 1000 mg) OR Amikacin 15-22.5 mg/kg (Maximum: 1000 mg) OR Streptomycin 12-18 mg/kg AND
- Agent 3: Levofloxacin 7.5-10 mg/kg OR Moxifloxacin 7.5-10 mg/kg OR Ofloxacin 15-20 mg/kg/day q12h (Maximum: 800 mg)
- Agent 4: Ethionamide 15-20 mg/kg/day q12h (Maximum: 1000 mg) OR Protionamide 15-20 mg/kg/day q12h (Maximum: 1000 mg) OR Cycloserine 10-20 mg/kg (Maximum: 1000 mg) OR Terizidone 10-20 mg/kg (Maximum: 1000 mg) OR Para-aminosalicylic acid 150 mg/kg/day q8-12h(Maximum: 12,000 mg)
- 3. XDR Tuberculosis
- 3.1 Adult
- Preferred regimen: 3 agents combination
- Agent 1: Pyrazinamide 20–30 mg/kg OR Ethambutol 15–25 mg/kg OR Rifabutin 5 mg/kg
- Agent 2: Ethionamide 15-20 mg/kg OR Protionamide 15-20 mg/kg OR Cycloserine 10-15 mg/kg OR Terizidone 10-20 kg/mg OR Para-aminosalicylic acid 8-12 g/day q8-12h
- Agent 3: Clofazimine 50 mg/d AND 300 mg once a month OR Amoxicillin/clavulanate 500 mg/125 mg q12h OR Linezolid 300-600 mg OR Imipenem 500mg q6h OR Clarithromycin 500-1000 mg q12h OR Thioacetazone 2.5 mg/kg OR Isoniazid (high-dose) 16–20 mg/kg
- 3.2 Pediatric
- Preferred regimen: 3 agents combination
- Agent 1: Pyrazinamide 20-30 mg/kg (Maximum: 600 mg) OR Ethambutol 15 mg/kg OR Rifabutin 5 mg/kg
- Agent 2: Ethionamide 15-20 mg/kg (Maximum: 1000 mg) OR Protionamide 15-20 mg/kg (Maximum: 1000 mg) OR Cycloserine 10-20 mg/kg (Maximum: 1000 mg) OR Terizidone 10-20 mg/kg (Maximum: 1000 mg) OR Para-aminosalicylic acid 150 mg/kg/day q8-12h
- Agent 3: Clofazimine 50 mg/d AND 300 mg once a month OR Amoxicillin/clavulanate OR Linezolid 300-600 mg OR Imipenem 500mg q6h OR Clarithromycin 500-1000 mg q12h OR Thioacetazone 2.5 mg/kg OR Isoniazid (high-dose) 16–20 mg/kg
- Mycobacterium abscessus Return to Top
- 1.Limited, localized extrapulmonary disease
- Preferred regimen: Clarithromycin 500 mg PO bid ± Amikacin 10-15 mg/kg/day IV or 25 mg/kg three times weekly for 4 months
- Alternative regimen (1): Amikacin AND Cefoxitin 12 g/day PO for two weeks
- Note: until clinical improvement in severe cases
- Alternative regimen (2): Amikacin AND Imipenem 500 mg IV q6-8h for two weeks
- Note(1): Until clinical improvement in severe cases
- Note(2): Osteomyelitis should be treated for as least 6 months; Infected foreign bodies should be removed
- 2.Pulmonary or serious extrapulmonary disease
- Preferred regimen: Clarithromycin 500 mg PO bid AND Amikacin 15 mg/kg/day IV AND Cefoxitin 2g IV q4h OR Imipenem 1g IV q6h for at least 2-4 months
- Note: If limited by adverse effects THEN Clarithromycin 500 mg PO bid or 1000 mg XR qd OR Azithromycin 250 mg PO qd
- Alternative regimen(1): Tigecycline 100 mg IV loading dose THEN 50 mg IV q12h
- Note: could be substituted as one of the injectables
- Alternative regimen(2): Linezolid 600 mg PO bid or 600 mg PO qd AND Clarithromycin
- Note: Could replace parental tx if not tolerated or feasible
- Mycobacterium bovis Return to Top
- Mycobacterium bovis
- Note: Is intrinsically resistant to Pyrazinamide (PZA). The treatment of M. bovis is extrapolated from experience with the treatment of PZA-resistant M. tuberculosis
- 1. Pulmonary and most extrapulmonary disease
- Preferred regimen: Isoniazid AND Rifampin AND Ethambutol for 2 months, followed by Isoniazid AND Rifampin for 7 months
- 2. Meningitis
- Preferred regimen: Isoniazid AND Rifampin AND Ethambutol for 2 months, followed by Isoniazid AND Rifampin for 10 months
- Mycobacterium avium-intracellulare Return to Top
- 1. Treatment of MAC pulmonary disease
- 1.1 Patients with nodular/bronchiectatic disease
- Preferreday regimen: Clarithromycin 1,000 mg three times weekly OR Azithromycin 500–600 mg three times weekly AND Ethambutol 25 mg/kg three times weekly AND Rifampin 600 mg three times weekly
- Note: Patients should be treated until culture negative on therapy for 1 year
- 1.2 Patients with fibrocavitary or severe nodular/bronchiectatic disease
- Preferreday regimen: Clarithromycin 500–1,000 mg/day OR Azithromycin 250–300 mg/day OR Rifampin 600 mg/day OR Rifabutin 150–300 mg/day AND Ethambutol 15 mg/kg/day
- Note(1): Amikacin OR Streptomycin threetimes-weekly can be used early in therapy
- Note(2): Patients should be treated until culture negative on therapy for 1 year
- 2. Disseminateday MAC disease
- Preferreday regimen: Clarithromycin 1,000 mg/day OR Azithromycin 250 mg/day AND Ethambutol 15 mg/kg/day ± Rifabutin 150–350 mg/day
- Mycobacterium celatum Return to Top
- Mycobacterium celatum
- Preferred regimen: Clarithromycin AND Ethambutol AND Ciprofloxacin ± Rifabutin
- Mycobacterium chelonae Return to Top
- Mycobacterium chelonae
- 1. Localized infections
- Preferred regimen: Clarithromycin 500 mg PO bid
- Alternative regimen: Azithromycin
- 2. Disseminated or extensive disease
- 2.1 monotherapy
- Preferred regimen: Clarithromycin 500 mg PO bid for 6 months
- 2.2 multidrug therapy
- preferred regimen: Clarithromycin 500 mg PO bid AND Tobramycin 5 mg/kg IV q24h OR Imipenem 0.5-1 g IV q6h OR Linezolid 600 mg IV/PO q12h/bid for 4-8 weeks
- Alternative regimen: Moxifloxacin 400 mg PO qd AND Linezolid 600 mg PO bid
- Note(1): During initial treatment, multidrug therapy may prevent development of acquired resistance
- Note(2): Total treatment duration is 6 months
- 3. Keratitis (LASIK-related)
- Preferred regimen: Clarithromycin 500 mg PO bid AND Tobramycin 0.3% 2 gtts q4h AND Gatifloxacin 0.3% 1 gtt q4h OR Moxifloxacin 0.5% 1 gtt q4h
- Mycobacterium foruitum Return to Top
- Mycobacterium foruitum
- 1. In vitro isolates
- Susceptible agents: Amikacin (100%), Ciprofloxacin and Ofloxacin (100%), Sulfonamides (100%), Cefoxitin (50%), Imipenem (100%), Clarithromycin (80%), and Doxycycline (50%)
- 2. Disease
- 2.1 M. fortuitum lung disease
- At least two agents with in vitro activity against the clinical isolate should be given for at least 12 months of negative sputum cultures
- 2.2 Serious skin, bone, and soft tissue M fortuitum disease
- At least two agents with in vitro activity against the clinical isolate should be given for a minimum of 4 months; For bone infections, 6 months of therapy is recommended
- Mycobacterium haemophilum Return to Top
- Mycobacterium haemophilum
- 1. In vitro
- Susceptible: Amikacin, Clarithromycin, Ciprofloxacin, Rifampin, and Rifabutin
- Less susceptible: Doxycycline and Sulfonamides
- 2. Infection
- 2.1 Disseminated disease
- Preferred regimen: Clarithromycin AND Rifampin AND Rifabutin AND Ciprofloxacin
- Mycobacterium genavense Return to Top
- Mycobacterium genavense
- Susceptibility: Amikacin, Rifamycin, Fluoroquinolones, Streptomycin, and Macrolides
- Note(1): Ethambutol has limited activity
- Note(2): Optimal therapy is not determined, but multidrug therapies including Clarithromycin appear to be more effective than those without Clarithromycin
- Mycobacterium gordonae Return to Top
- Mycobacterium gordonae
- Preferred regimen: Ethambutol OR Rifabutin OR Clarithromycin OR Linezolid OR Fluoroquinolones
- Mycobacterium kansasii Return to Top
- Mycobacterium kansasii
- 1. pulmonary disease
- Preferred regimen: Rifampin 10 mg/kg/day (Maximum, 600 mg) PO AND Ethambutol 15 mg/kg/ day PO AND Isoniazid 5 mg/kg/day (Maximum 300 mg) PO AND Pyridoxine 50 mg/day PO
- Note: Treatment duration for M. kansasii lung disease should include 12 months of negative sputum cultures
- 2. Rifampin-resistant M. kansasii disease
- Preferred regimen: Clarithromycin OR Azithromycin OR Moxifloxacin OR Ethambutol OR Sulfamethoxazole OR Streptomycin
- Note(1): Use three-drug regimen
- Note(2): Patients undergoing therapy for M. kansasii lung disease should have close clinical monitoring with frequent sputum examinations for mycobacterial culture throughout therapy
- 3. Disseminated M. kansasii disease
- Note: The treatment regimen for disseminated disease should be the same as for pulmonary disease
- Mycobacterium marinum Return to Top
- Mycobacterium marinum
- 1. In vitro M. marinum isolates
- Susceptible: Rifampin, Rifabutin, Ethambutol, Clarithromycin, Sulfonamides, and Trimethoprim sulfamethoxazole
- Intermediately susceptible: Streptomycin, Doxycycline, and Minocycline
- Resistant: Isoniazid and Pyrazinamide
- Note: Two active agents for 1 to 2 months after resolution of symptoms, typically 3 to 4 months in total
- 2. Infection
- 2.1 skin and soft tissue infections
- Preferred regimen (1): Clarithromycin AND Ethambutol
- Preferred regimen (2): Ethambutol AND Rifampin
- Note: Azithromycin can replace Clarithromycin
- 2.2 osteomyelitis or deep structure infection
- Preferred regimen: Clarithromycin AND Ethambutol AND Rifampin
- Mycobacterium scrofulaceum Return to Top
- Mycobacterium scrofulaceum
- Susceptibility data are lacking and standard treatment regimens for M. scrofulaceum are controversial, emphasizing the need to perform susceptibility testing on confirmed disease-producing isolates of M. scrofulaceum
- Mycobacterium simiae Return to Top
- Mycobacterium simiae
- Preferred regimen: Clarithromycin AND Moxifloxacin AND Trimethoprim/sulfamethoxazole
- Mycobacterium ulcerans Return to Top
- Mycobacterium ulcerans
- 1. Preulcerative lesions
- Excision and primary closure, Rifampin monotherapy, or heat therapy
- 2. Established ulcers
- Most antimycobacterial agents are ineffective for the treatment of the ulcer; Surgical debridement combined with skin grafting is the usual treatment of choice
- 3. Control complications of the ulcer
- Preferred regimen: Clarithromycin AND Rifampin
- Mycobacterium xenopi Return to Top
- Mycobacterium xenopi
- 1. The cornerstone of therapy for M. xenopi
- Preferred regimen: Clarithromycin AND Rifampin AND Ethambutol
- Note: Therapy should be continued until the patient has maintained negative sputum cultures while on therapy for 12 months
- 2. Pulmonary disease
- Preferred regimen: INH AND Rifabutin OR Rifampin AND Ethambutol AND Clarithromycin ± Streptomycin
- Note: A quinolone, preferably Moxifloxacin, could be substituted for one of the antituberculous drugs
- 3. Extrapulmonary disease
- Note: Therapy for extrapulmonary disease would include the same agents as for pulmonary disease
- Mycobacterium leprae Return to Top
- Mycobacterium leprae
- 1. Multibacillary Leprosy (Skin smear positive)
- 1.1 Adult
- Preferred regimen: Dapsone 100 mg/day PO AND Rifampin 600 mg PO 4 times per week AND Clofazimine 50 mg PO qd for 12-24 months
- Note: Clofazimine should be supplemented by loading dose 300 mg PO monthly
- 1.2 Pediatric
- 1.2.1 < 35 kg
- Preferred regimen: Dapsone 1-2 mg/kg/day PO AND Rifampin 450 mg PO for 12-24 months
- 1.2.2 < 20 kg
- Preferred regimen: Dapsone 1-2 mg/kg/day PO AND Rifampin 300 mg PO for 12-24 months
- 1.2.3 < 12 kg
- Preferred regimen: Dapsone 1-2 mg/kg/day PO AND Rifampin 150 mg PO for 12-24 months
- 2. Paucibacillary Leprosy (Skin Smear negative)
- Preferred regimen: Rifampin 600 mg PO once a month for 6 months AND Dapsone 100 mg PO qd for 6 months
- 3. Erythema Nodosum Leprosum (ENL)
- 3.1 Mild
- Preferred regimen: Rest affect limb, analgesics, follow-up twice a week, check for iridocyclitis; Chloroquine OR Aspirin may be useful
- 3.2 Severe (numerous nodules + fever, ulcerating/pustular ENL, visceral involvement, nodules + neuritis, recurrent ENL)
- Preferred regimen: Prednisolone 30-40 mg/day PO for 1-2 weeks THEN taper over 12 weeks
- Alternative regimen (1): (If unresponsive to corticosteroids or if risk of corticosteroids prevent administration) Clofazimine 100 mg PO tid for maximum of 12 weeks THEN taper the dose to 100 mg PO bid for 12 weeks THEN 100 mg qd for 12-24 weeks
- Alternative regimen (2): (if not contraindicated) Thalidomide 200-400 mg/day PO THEN 50-100 mg/day after 1-2 weeks
- 4. Reversal Reaction
- Preferred regimen: Prednisolone start with 40 mg/day PO THEN taper by 10 mg twice a week for 12 weeks
- Mycobacterium smegmatis Return to Top
- Mycobacterium smegmatis
- 1. Mild disease
- Preferred regimen: Doxycycline PO AND Trimethoprim sulfamethoxazole PO
- 2. Severe disease
- Preferred regimen: Amikacin IV OR Imipenem IV
- Mycobacterium immunogenum Return to Top
- Mycobacterium immunogenum
- In vitro
- Susceptible: Amikacin and Clarithromycin
- Resistant: Ciprofloxacin, Doxycycline, Cefoxitin, Tobramycin, and Sulfamethoxazole
- Note: The optimal therapy for this organism is unknown; however, successful therapy is likely difficult due to the extensive antibiotic resistance of the organism
- Mycobacterium malmoense Return to Top
- Mycobacterium malmoense
- 1. In vitro
- Susceptible: Ethambutol, Ethionamide, Kanamycin, and Cycloserine
- Resistant: INH, Streptomycin, Rifampin, and Capreomycin
- 2. Pulmonary M. malmoense infection
- Preferred regimen: INH AND Rifampin AND Ethambutol ± Quinolones AND Macrolides
- Mycobacterium mucogenicum Return to Top
- Mycobacterium mucogenicum
- In vitro susceptible agents: Aminoglycosides, Cefoxitin, Clarithromycin, Minocycline, Doxycycline, Quinolones, Trimethoprim/sulfamethoxazole, and Imipenem
- Mycobacterium szulgai Return to Top
- Mycobacterium szulgai
- 1. in vitro susceptibility
- M. szulgai is susceptible in vitro to most antituberculous drugs including Quinolones and newer Macrolides
- 2. Infection
- 2.1 Pulmonary infection
- Three- or four-drug regimen based on susceptibility that includes 12 months of negative sputum cultures while on therapy
- 2.2 Extrapulmonary infection
- Combination anti-tuberculous medications based on in vitro susceptibilities for 4-6 months
- Mycobacterium terrae Return to Top
- Mycobacterium terrae
- 1. In vitro susceptibility
- All six of the isolates from a single center and 90% or more of an additional 22 isolates of M. terrae complex were susceptible to Ciprofloxacin and Sulfonamides. Recently, 11 isolates of M. terrae complex were also shown to be susceptible to Linezolid
- 2. Antimicrobial therapy
- Based on in vitro susceptibility results
### Parasites – Intestinal Protozoa
- Balantidium coli treatment
- Adult dosage:
- Preferred regimen: Metronidazole 750 mg PO tid for 5 days, Tetracycline 500 mg PO qid for 10 days
- Alternative regimen: Iodoquinol 650 mg PO tid for a 20-days
- Pediatric dosage:
- Preferred regimen: Metronidazole 35-50 mg/kg/day PO in three doses (maximum dosage: 2 g) for 5 days, Tetracycline 40 mg/kg/dose PO in four doses for 10 days.
- Alternative regimen: Iodoquinol 40 mg/kg/dose PO in three doses for 20 days AND Doxycycline.
- Note: Nitazoxanide, a broad-spectrum antiparasitic and antihelminthic drug, may be another treatment for balantidiosis.
- Blastocystis hominis Return to Top
- Blastocystis
- Preferred regimen (1): Metronidazole 750 mg PO tid or 1.5 g qd for 10 days
- Preferred regimen (2): Trimethoprim-sulfamethoxazole 1 DS PO bid or 2 DS PO qd for 7 days
- Preferred regimen (3): Iodoquinol 650 mg PO tid for 20 days
- Preferred regimen (4): Nitazoxanide 500 mg PO bid for 3 days
- Preferred regimen (5): Paromomycin 25-35 mg/kg/day PO tid for 7 days
- Note (1): Treatment of asymptomatic infections is unnecessary
- Note (2): One double strength tablet contains 160 mg trimethoprim/800 mg sulfamethoxazole
- Cryptosporidium parvum Return to Top
- 1. Immunocompetent
- Preferred regimen: No specific therapy recommended since healthy patients usually recover within a few weeks, but if needed: Nitazoxanide 500 mg PO bid for 3 days.
- 2. HIV
- Preferred regimen: Nitazoxanide 500 mg PO bid for 3 days
- 3. HIV and Immunodeficiency
- Preferred regimen: Effective antiretroviral therapy
- Note: Nitazoxanide is not licensed for immunodeficient patients
- Cryptosporidium hominis Return to Top
- 1. Immunocompetent
- Preferred regimen: No specific therapy recommended since healthy patients usually recover within a few weeks, but if needed: Nitazoxanide 500 mg PO bid for 3 days.
- 2. HIV
- Preferred regimen: Nitazoxanide 500 mg PO bid for 3 days
- 3. HIV and Immunodeficiency
- Preferred regimen: Effective antiretroviral therapy
- Note: Nitazoxanide is not licensed for immunodeficient patients
- Cyclospora cayetanensis Return to Top
- Cyclospora cayetanensis
- Preferred regimen: Trimethoprim-sulfamethoxazole one double-strength tablet PO bid for 7-10 days
- Alternative regimen(1): Ciprofloxacin 500 mg PO bid for 7 days
- Alternative regimen(2): Nitazoxanide 500 mg PO bid for 7 days
- Note(1): One double-strength tablet (160 mg TMP/800 mg SMX) .
- Note(2): Treatment is continued for 7 days in immunocompetent hosts and for 7 to 10 days in patients with HIV infection.
- Dientamoeba fragilis Return to Top
- Dientamoebiasis
- Preferred regimen: Iodoquinol 650 mg PO tid for 20 days
- Alternative regimen (1): Paromomycin 25–35 mg/kg/day PO in three divided doses for 7 days
- Alternative regimen (2): Metronidazole 500–750 mg PO tid for 10 days
- Alternative regimen (3): Tetracycline 500 mg PO qid for 10 days
- 1.1 Treatment in pregnancy
- The use of Iodoquinol in pregnancy is limited, and risk to the embryo-fetus is unknown, should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- Oral dose of Paromomycin generally is poorly absorbed from the gastrointestinal tract, with minimal, if any, systemic availability.
- Metronidazole is in pregnancy category B. Data on the use of this drug in pregnant women are conflicting. The available evidence suggests use during pregnancy has a low risk of congenital anomalies. May be used during pregnancy in those patients who will clearly benefit from the drug, although its use in the first trimester is generally not advised.
- 1.2 Treatment during lactation
- Iodoquinol should be used with caution in breastfeeding women.
- Oral dose of Paromomycin is unlikely to be excreted in breast milk, and the drug generally is poorly absorbed from the gastrointestinal tract.
- Metronidazole should be used during lactation only if the potential benefit of therapy to the mother justifies the potential risk to the infant.
- 1.3 Treatment in pediatric patients
- Iodoquinol 30–40 mg/kg/day (maximum 2 g) PO in 3 doses for 20 days. The safety of iodoquinol in children has not been established.
- Paromomycin 25–35 mg/kg/day PO in 3 doses for 7 days. The safety of oral dose in children has not been formally evaluated. However, the safety profiles likely are comparable in children and adults.
- Metronidazole 35–50 mg/kg/day PO in 3 doses for 10 days. The safety in children has not been established, is listed as an antiamebic and antigiardiasis medicine on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.
- Tetracycline 40 mg/kg/day (maximum 2 g) PO in 4 doses for 10 days
- Entamoeba histolytica Return to Top
- 1. Amebic Liver Abscess
- Preferred regimen: (Metronidazole 750 mg PO tid for 10 days OR Tinidazole 2 g PO qd for 5 days) AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
- Alternative regimen (1): Nitazoxanide 500 mg bid for 10 days AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
- Alternative regimen (2): Tinidazole 2 g PO qd for 5 days AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
- Alternative regimen (2): Tinidazole 2 g PO qd for 5 days
- 2. Amebic Colitis
- Preferred regimen: Metronidazole 500-750 mg PO tid for 7-10 days. Pediatric dose: 35-50 mg/kg per day tid AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
- Alternative regimen: Tinidazole 2 g PO qd for 5 days AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
- 3. Asymptomatic Intestinal Colonization
- Preferred regimen: Paromomycin 30 mg/kg/day PO tid for 5-10 days
- Alternative regimen (1): Diloxanide furoate 500 mg PO tid for 10 days
- Alternative regimen (2): Diiodohydroxyquin 650 mg PO tid for 20 days for adults and 30 to 40 mg/kg per day tid for 20 days for children
- Giardia lamblia Return to Top
- 1. Giardiasis
- 1.1 Adult
- Preferred regimen (1): Metronidazole 250 mg tid 5–7 days
- Preferred regimen (2): Tinidazole 2 g single dose
- Preferred regimen (3): Nitazoxanide 500 mg PO bid (with food)
- Alternative regimen (1): Paromomycin 500 mg tid 3 5–10 days
- Alternative regimen (2): Quinacrine 100 mg tid 3 5–7 days
- Alternative regimen (3): Furazolidone 100 mg qid 3 7–10 days
- 1.2 Pediatric
- Preferred regimen (1): Metronidazole 5 mg/kg tid 3 5–7 days
- Preferred regimen (2): Tinidazole 50 mg/kg single dose (max, 2 g)
- Preferred regimen (3): Nitazoxanide 100 mg PO bid for age 1-3 years or 200 mg PO bid for age 4-11 years (with food)
- Alternative regimen (1): Paromomycin 30 mg/kg/day in 3 doses 3 5–10 days
- Alternative regimen (2): Quinacrine 2 mg/kg tid 3 7 days
- Alternative regimen (3): Furazolidone 2 mg/kg qid 3 10 days
- Cystoisospora belli Return to Top
- 1. Cystoisospora belli treatment
- 1.1 Immunocompetent hosts
- In the immunocompetent hosts, symptoms of Cystoisospora infection are usually self-limited.
- Antimicrobial therapy to immunocompetent patients may be considered if symptoms do not start to resolve spontaneously after 5 to 7 days (depending upon severity)
- Prefered regimen: Trimethoprim-sulfamethoxazole 160 mg/800 mg PO bid for 7-10 days
- Alternative regimen (1) (for patients who are allergic to or intolerant of TMP-SMX): Pyrimethamine 50-75 mg/day PO qd or divided in 2 equal doses AND Leucovorin 10–25 mg PO qd
- Alternative regimen (2): Ciprofloxacin 500 mg PO bid for 7 days (second-line alternative)
- 1.1.1 In pregnancy
- TMP-SMX should be avoided near-term because of the potential for hyperbilirubinemia and kernicterus in the newborn.
- Ciprofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- 1.1.2 During lactation
- TMP-SMX generally should be avoided by women when nursing infants who are premature, jaundiced, ill, or stressed, or who have glucose-6-phosphate dehydrogenase deficiency.
- The American Academy of Pediatrics classifies Ciprofloxacin as usually compatible with breastfeeding, whereas the World Health Organization recommends avoiding Ciprofloxacin while breastfeeding and CDC recommends Ciprofloxacin should be used during lactation only if the potential benefit justifies the potential risk to the fetus.
- 1.1.3 In pediatric patients
- The use of TMP-SMX in children less than 2 months of age generally is not recommended.
- Available evidence is conflicting regarding the potential for growth defects and arthropathies in exposed children. Use of Ciprofloxacin in children requires assessment of potential risks and benefits.
- 1.2 Immunocompromised hosts
- Preferred regimen (1): Trimethoprim-sulfamethoxazole 160 mg/800 mg PO/IV qid for 10 days
- Preferred regimen (2): Trimethoprim-sulfamethoxazole 160 mg/800 mg PO/IV bid for 7-10 days
- Note (1): One approach is to start with TMP-SMX (160 mg/800 mg) bid regimen first, and increase daily dose and/or duration (up to 3–4 weeks) if symptoms worsen or persist.
- Note (2): IV therapy is recommended for patients with potential or documented malabsorption.
- Alternative regimen (1): Pyrimethamine 50–75 mg PO qd AND Leucovorin 10–25 mg PO qd
- Alternative regimen (2): Ciprofloxacin 500 mg PO bid for 7 days
- 2. Cystoisospora belli prophylaxis
- 2.1 Primary prophylaxis
- Insufficient evidence is available to support a general recommendation for primary prophylaxis for Cystoisosporiasis per se, especially for U.S. travelers in isoporiasis-endemic areas.
- 2.2 Secondary prophylaxis (preventing recurrence in patients with CD4 count < 200 cells/mm3)
- Prefered regimen: Trimethoprim-sulfamethoxazole 160 mg/800 mg PO 3 times weekly
- Alternative regimen (1): Trimethoprim-sulfamethoxazole 160 mg/800 mg PO qd
- Alternative regimen (2): Trimethoprim-sulfamethoxazole 320 mg/1600 mg PO 3 times weekly
- Alternative regimen (3): Pyrimethamine 25 mg PO qd AND Leucovorin 5–10 mg PO qd
- Alternative regimen (4): Ciprofloxacin 500 mg PO 3 times weekly (second-line alternative)
- Note (1): Criteria for discontinuation of chronic maintenance therapy: sustained increase in CD4 count > 200 cells/mm3 for > 6 months in response to ART and without evidence of active Cystoisospora belli infection
- Note (2): Because of concerns about possible teratogenicity associated with first-trimester drug exposure, clinicians may withhold secondary prophylaxis during the first trimester and treat only symptomatic infection.
- Microsporidiosis Return to Top
- 1. Ocular
- Preferred regimen: Albendazole 400 mg PO bid for 3 weeks AND Fumagillin eye drops.
- 2. Intestinal (diarrhea)
- Preferred regimen:
- Adult: Albendazole 400 mg PO bid for 3 weeks for E. intestinalis.
- Pediatric: Albendazole 15 mg/kg per day divided into 2 daily doses for 7 days for E. intestinalis.
- Note: Fumagillin 20 mg PO tid is the only reported effective treatment for E. bieneusi.
- 3. Disseminated
- Preferred regimen: Albendazole 400 mg po bid for 3 weeks.
### Parasites – Extraintestinal Protozoa
# Acanthamoeba
- Acanthamoeba Return to Top
- 1. Granulomatous amoebic encephalitis, meningitis, and disseminated Acanthamoeba disease
- Preferred regimen (1): Pentamidine AND Itraconazole AND Sulfadiazine AND Flucytosine
- Preferred regimen (2): Sulfadiazine AND Fluconazole AND Pyrimethamine
- Preferred regimen (3): Sulfadiazine AND Flucytosine AND TMP-SMX
- Preferred regimen (4): TMP-SMX AND Rifampin AND Ketoconazole
- Preferred regimen (5): Miltefosine AND Amikacin
- Preferred regimen (6): Miltefosine AND Voriconazole
- Preferred regimen (7): Pentamidine AND Itraconazole AND Flucytosine AND Levofloxacin AND Amphotericin B AND Rifampin
- Preferred regimen (8): Pentamidine AND Fluconazole AND Miltefosine
- Note: The mainstay of successful treatment includes early diagnosis and combination therapy with pentamidine, azole, sulfonamide, miltefosine, and possibly flucytosine.
- 2. Cutaneous acanthamoebiasis
- Preferred regimen: Pentamidine AND Sulfadiazine AND Flucytosine AND (Itraconazole OR Fluconazole) AND Chlorhexidine topical AND Ketoconazole topical
- 3. Acanthamoeba keratitis
- Preferred regimen: (Polyhexamethylene biguanide topical OR Chlorhexidine topical) ± (Propamidine topical OR Hexamidine topical)
- Note (1): Azole antifungal drugs (Ketoconazole, Itraconazole, Voriconazole) may be considered as oral or topical adjuncts.
- Note (2): The duration of therapy for Acanthamoeba keratitis may last six months to a year.
- Note (3): Pain control can be helped by topical cyclopegic solutions and oral nonsteroidal medications.
- Note (4): The use of corticosteroids to control inflammation is controversial.
- Note (5): Penetrating keratoplasty may help restore visual acuity.
# Balamuthia mandrillaris
- Balamuthia mandrillaris Return to Top
- 1. Granulomatous Amebic Encephalitis
- Preferred regimen (1): Pentamidine AND Flucytosine AND Fluconazole AND Sulfadiazine AND (Azithromycin OR Clarithromycin)
- Preferred regimen (2): Pentamidine AND Albendazole AND (Itraconazole OR Fluconazole) AND Miltefosine
# Naegleria fowleri
- Naegleria fowleri Return to Top
- Primary amoebic meningoencephalitis
- Preferred regimen: Amphotericin B 1.5 mg/kg/day bid for 3 days; then 1 mg/kg/day for 6 days AND 1.5 mg/day intrathecal for 2 days; then 1 mg/day intrathecal qd for 8 days.
- Note: Investigational drug called miltefosine also available for treatment.
# Babesia microti
- Babesia microti Return to Top
- Babesiosis
- 1. Mild/moderate disease
- Preferred regimen: Atovaquone 750 mg PO bid AND Azithromycin 600 mg PO qd for 7-10 days
- 2. Severe disease:
- Preferred regimen: Clindamycin 600 mg PO tid AND Quinine 650 mg PO tid for 7–10 days
- Preferred regimen: Clindamycin 1.2 g IV q12h
- Note (1): For overwhelming infection in asplenic patients and immunocompromised patients, treat for 6 or more weeks.
- Note (2): Consider transfusion if 10% parasitemia.
# Leishmania
- Leishmania Return to Top
- Leishmaniasis
- 1. Cutaneous Leishmaniasis
- Different Leishmania species cause Old World versus New World (American) cutaneous leishmaniasis. In the Old World (the Eastern Hemisphere), the etiologic agents include Leishmania tropica, L. major, and L. aethiopica, as well as L. infantum and L. donovani. The main species in the New World (the Western Hemisphere) are either in the L. mexicana species complex (L. mexicana, L. amazonensis, and L. venezuelensis) or the subgenus Viannia (L. braziliensis, L. guyanensis, L. panamensis, and L. peruviana). The Viannia subgenus is also referred to as the L. (V.) braziliensis species complex.
- 1.1 Systemic Therapy (Parenteral)
- Preferred Regimen (1): Sodium stibogluconate 20 mg/kg IV/IM q24h for 10-20 days
- Preferred Regimen (2): Meglumine antimoniate 20 mg/kg IV/IM q24h for 10-20 days
- Alternative Regimen (1): Liposomal amphotericin B 3 mg/kg/day IV infusion for 6-10 days
- Alternative Regimen (2): Pentamidine 2-3 mg/kg/day IV/IM for 4-7 days
- Note: Data supporting the use of amphotericin B for treatment of cutaneous and mucosal leishmaniasis are anecdotal; standard dosage regimens have not been established. In the United States, pentamidine isethionate is uncommonly used for treatment of cutaneous leishmaniasis. Its limitations include the potential for irreversible toxicity and variable effectiveness.
- 1.2 Systemic Therapy (Oral)
- 1.2.1 Adults and adolescents at least 12 years of age, who weigh from 33-44 kg
- Preferred Regimen:Miltefosine 50 mg PO q12h for 28 days
- 1.2.2 Adults and adolescents at least 12 years of age, who weigh >45 kg
- Preferred Regimen:Miltefosine 50 mg PO q8h for 28 days
- Alternative Regimen (1): Ketoconazole 600 mg qd for 28 days OR qd for 6 weeks
- Alternative Regimen (2): Fluconazole 200 mg qd for 6 weeks
- Note:The FDA-approved indications are limited to infection caused by three particular species, all three of which are New World species in the Viannia subgenus—namely, Leishmania (V.) braziliensis, L. (V.) panamensis, and L. (V.) guyanensis. The "azoles" showed modest activity against some Leishmania species in some cases, but are not FDA approved
- 1.3 Local Therapy
- List of possible local therapies
- Cryotherapy (with liquid nitrogen OR Thermotherapy (use of localized current field radiofrequency heat) OR Intralesional administration of SbV OR Topical application of Paromomycin (such as an ointment containing 15% Paromomycin/12% methylbenzethonium chloride in soft white paraffin)
- 2. Visceral Leishmaniasis
- Visceral leishmaniasis usually is caused by the species L. donovani and L. infantum (L. chagasi generally is considered synonymous with L. infantum)
- 2.1 Systemic Therapy (Parenteral)
- Preferred Regimen (1): Liposomal amphotericin B 3 mg/kg/day IV for 5 days, then once on day 14 and once on day 21 (Total dose: 21 mg/kg)
- Preferred Regimen (2): Sodium stibogluconate 20 mg/kg IV/IM q24h for 28 days
- Preferred Regimen (3): Meglumine antimoniate 20 mg/kg IV/IM q24h for 28 days
- Alternative Regimen: Amphotericin B deoxycholate 0.5-1 mg/kg IV q24h (Total dose: 15-20 mg/kg)
- Note: In immunosuppressed patients, dose is 4 mg/kg/day for 5 days, then once on day 10, 17, 24, 31, and 38 (Total dose: 40 mg/kg)
- 2.2 Systemic Therapy (Oral)
- 2.2.1 Adults and adolescents at least 12 years of age, who weigh from 33-44 kg
- Preferred Regimen: Miltefosine 50 mg PO q12h for 28 days
- 2.2.2 Adults and adolescents at least 12 years of age, who weigh >45 kg
- Preferred Regimen: Miltefosine 50 mg PO q8h for 28 days
# Plasmodium
- Plasmodium Return to Top
- 1. Plasmodium falciparum
- 1.1 Treatment of uncomplicated P. falciparum malaria
- 1.1.1 Treat children and adults with uncomplicated P. falciparum malaria (except pregnant women in their first trimester) with one of the following recommended ACT (artemisinin-based combination therapy)
- Preferred regimen (1): Artemether 5–24 mg/kg/day PO bid AND Lumefantrine 29–144 mg/kg/day PO bid for 3 days.
- Note: The first two doses should, ideally, be given 8 h apart.
- Dosage regimen based on Body weight (kg)
- Body weight (kg)-5 to < 15- Artemether 20 mg PO bid AND Lumefantrine 120 mg PO bid for 3 days
- Body weight (kg)-15 to < 25- Artemether 40 mg PO bid AND Lumefantrine 240 mg PO bid for 3 days
- Body weight (kg)-25 to < 35- Artemether 60 mg PO bid AND Lumefantrine 360 mg PO bid for 3 days
- Body weight (kg) ≥ 35- Artemether 80 mg PO bid AND Lumefantrine 480 mg PO bid for 3 days
- Preferred regimen (2): Artesunate 2–10 mg/kg/day PO qd AND Amodiaquine 7.5–15 mg/kg/day PO qd for 3 days
- Note: A total therapeutic dose range of 6–30 mg/kg/day artesunate and 22.5–45 mg/kg/day per dose amodiaquine is recommended.
- Dosage regimen based on Body weight (kg)
- Body weight (kg)-4.5 to < 9- Artesunate 25 mg PO qd AND Amodiaquine 67.5 mg PO qd for 3 days
- Body weight (kg)-9 to < 18 - Artesunate 50 mg PO qd AND Amodiaquine 135 mg PO qd for 3 days
- Body weight (kg)-18 to < 36- Artesunate 100 mg PO qd AND Amodiaquine 270 mg PO qd for 3 days
- Body weight (kg) ≥ 36 - Artesunate 200 mg PO qd AND Amodiaquine 540 mg PO qd for 3 days
- Preferred regimen (3): Artesunate 2–10 mg/kg/day PO qd AND Mefloquine 2–10 mg/kg/day PO qd for 3 days
- Dosage regimen based on Body weight (kg)
- Body weight (kg)-5 to < 9- Artesunate 25 mg PO qd AND Mefloquine 55 mg PO qd for 3 days
- Body weight (kg)-9to < 18- Artesunate 50 mg PO qd AND Mefloquine 110 mg PO qd for 3 days
- Body weight (kg)-18 to < 36- Artesunate 100 mg PO qd AND Mefloquine 220 mg PO qd for 3 days
- Body weight (kg)- ≥ 36 - Artesunate 200 mg PO qd AND Mefloquine 440 mg PO qd for 3 days
- Preferred regimen (4): Artesunate 2–10 mg/kg/day PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1.25 (25–70 / 1.25–3.5) mg/kg/day PO given as a single dose on day 1
- Dosage regimen based on Body weight (kg)
- Body weight (kg)-5 to < 10- Artesunate 25 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 250/12 mg PO given as a single dose on day 1
- Body weight (kg)-10 to < 25- Artesunate 50 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 500/25 mg PO given as a single dose on day 1
- Body weight (kg)-25 to < 50- Artesunate 100 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1000/50 mg PO given as a single dose on day 1
- Body weight (kg)- ≥50- Artesunate 200 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1500/75 mg PO given as a single dose on day 1
- Preferred regimen (5): Dihydroartemisinin 2–10 mg/kg/day PO qd AND Piperaquine16–27 mg/kg/day PO qd for 3 days
- Dosage regimen based on Body weight (kg)
- Body weight (kg)-5 to < 8- Dihydroartemisinin 20 mg PO qd AND Piperaquine 160 mg PO qd for 3 days
- Body weight (kg)-8 to < 11- Dihydroartemisinin 30 mg PO qd AND Piperaquine 240 mg PO qd for 3 days
- Body weight (kg)-11 to < 17 - Dihydroartemisinin 40 mg PO qd AND Piperaquine 320 mg PO qd for 3 days
- Body weight (kg)-17 to < 25- Dihydroartemisinin 60 mg PO qd AND Piperaquine 480 mg PO qd for 3 days
- Body weight (kg)-25 to < 36- Dihydroartemisinin 80 mg PO qd AND Piperaquine 640 mg PO qd for 3 days
- Body weight (kg)-36 to < 60- Dihydroartemisinin 120 mg PO qd AND Piperaquine 960 mg PO qd for 3 days
- Body weight (kg)-60 < 80 - Dihydroartemisinin 160 mg PO qd AND Piperaquine 1280 mg PO qd for 3 days
- Body weight (kg)- >80- Dose of Dihydroartemisinin 200 mg PO qd AND Piperaquine 1600 mg PO qd for 3 days
- 1.1.2 Reducing the transmissibility of treated P. falciparum infections In low-transmission areas in patients with P. falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months)
- Preferred regimen: Single dose of 0.25 mg/kg Primaquine with ACT
- 1.2 Recurrent Falciparum Malaria
- 1.2.1 Failure within 28 days
- Note:The recommended second-line treatment is an alternative ACT known to be effective in the region. Adherence to 7-day treatment regimens (with artesunate or quinine both of which should be co-administered with + tetracycline, or doxycycline or clindamycin) is likely to be poor if treatment is not directly observed; these regimens are no longer generally recommended.
- 1.2.2 Failure after 28 days
- Note: all presumed treatment failures after 4 weeks of initial treatment should, from an operational standpoint, be considered new infections and be treated with the first-line ACT. However, reuse of mefloquine within 60 days of first treatment is associated with an increased risk for neuropsychiatric reactions, and an alternative ACT should be used.
- 1.3 Reducing the transmissibility of treated P. falciparum infections In low-transmission areas in patients with P. falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months)
- Note: Single dose of 0.25 mg/kg bw Primaquine with ACT
- 1.4 Treating uncomplicated P. falciparum malaria in special risk groups
- 1.4.1 Pregnancy
- First trimester of pregnancy : Quinine AND Clindamycin 10mg/kg/day PO bid for 7 days
- Second and third trimesters : Mefloquine is considered safe for the treatment of malaria during the second and third trimesters; however, it should be given only in combination with an artemisinin derivative.
- Note (1): Quinine is associated with an increased risk for hypoglycaemia in late pregnancy, and it should be used (with clindamycin) only if effective alternatives are not available.
- Note (2): Primaquine and tetracyclines should not be used in pregnancy.
- 1.4.2 Infants less than 5kg body weight : with an ACT at the same mg/kg bw target dose as for children weighing 5 kg.
- 1.4.3 Patients co-infected with HIV: should avoid Artesunate + SP if they are also receiving Co-trimoxazole, and avoid Artesunate AND Amodiaquine if they are also receiving efavirenz or zidovudine.
- 1.4.4 Large and Obese adults: For obese patients, less drug is often distributed to fat than to other tissues; therefore, they should be dosed on the basis of an estimate of lean body weight, ideal body weight. Patients who are heavy but not obese require the same mg/kg bw doses as lighter patients.
- 1.4.5 Patients co-infected with TB: Rifamycins, in particular rifampicin, are potent CYP3A4 inducers with weak antimalarial activity. Concomitant administration of rifampicin during quinine treatment of adults with malaria was associated with a significant decrease in exposure to quinine and a five-fold higher recrudescence rate
- 1.4.6 Non-immune travellers : Treat travellers with uncomplicated P. falciparum malaria returning to nonendemic settings with an ACT.
- 1.4.7 Uncomplicated hyperparasitaemia: People with P. falciparum hyperparasitaemia are at increased risk of treatment failure, severe malaria and death so should be closely monitored, in addition to receiving an ACT.
- 2. Treatment of uncomplicated malaria caused by P. vivax, P. ovale, P. malariae or P. knowlesi
- 2.1 Blood Stage infection
- 2.1.1. Uncomplicated malaria caused by P. vivax
- 2.1.1.1 In areas with chloroquine-sensitive P. vivax
- Preferred regimen: Chloroquine total dose of 25 mg/kg PO. Chloroquine is given at an initial dose of 10 mg/kg, followed by 10 mg/kg on the second day and 5 mg/kg on the third day.
- 2.1.1.2 In areas with chloroquine-resistant P. vivax
- Note: ACTs containing Piperaquine, Mefloquine OR Lumefantrine are the recommended treatment, although Artesunate + Amodiaquine may also be effective in some areas. In the systematic review of ACTs for treating P. vivax malaria, Dihydroartemisinin + Piperaquine provided a longer prophylactic effect than ACTs with shorter half-lives (Artemether + Lumefantrine, Artesunate + Amodiaquine), with significantly fewer recurrent parasitaemias during 9 weeks of follow-up.
- 2.1.2 Uncomplicated malaria caused by P. ovale, P. malariae or P. knowlesi malaria
- Note: Resistance of P. ovale, P. malariae and P. knowlesi to antimalarial drugs is not well characterized, and infections caused by these three species are generally considered to be sensitive to chloroquine. In only one study, conducted in Indonesia, was resistance to chloroquine reported in P. malariae. The blood stages of P. ovale, P. malariae and P. knowlesi should therefore be treated with the standard regimen of ACT or Chloroquine, as for vivax malaria.
- 2.1.3 Mixed malaria infections
- Note: ACTs are effective against all malaria species and so are the treatment of choice for mixed infections.
- 2.2 Liver stages (hypnozoites) of P. vivax and P. ovale
- Note: To prevent relapse, treat P. vivax or P. ovale malaria in children and adults (except pregnant women, infants aged < 6 months, women breastfeeding infants < 6 months, women breastfeeding older infants unless they are known not to be G6PD deficient and people with G6PD deficiency) with a 14-day course of primaquine in all transmission settings. Strong recommendation, high-quality evidence In people with G6PD deficiency, consider preventing relapse by giving primaquine base at 0.75 mg base/kg bw once a week for 8 weeks, with close medical supervision for potential primaquine-induced adverse haematological effects.]
- 2.2.1 Primaquine for preventive relapse
- Preferred regimen: Primaquine 0.25–0.5 mg/kg/day PO qd for 14 days
- 2.2.2 Primaquine and glucose-6-phosphate dehydrogenase deficiency
- Preferred regimen: Primaquine 0.75 mg base/kg/day PO once a week for 8 weeks.
- Note: The decision to give or withhold Primaquine should depend on the possibility of giving the treatment under close medical supervision, with ready access to health facilities with blood transfusion services.
- 2.2.3 Prevention of relapse in pregnant or lacating women and infants
- Note: Primaquine is contraindicated in pregnant women, infants < 6 months of age and in lactating women (unless the infant is known not to be G6PD deficient).
- 3. Treatment of severe malaria
- 3.1 Treatment of severe falciparum infection with Artesunate
- 3.1.1 Adults and children with severe malaria (including infants, pregnant women in all trimesters and lactating women):-
- Preferred regimen: Artesunate IV/IM for at least 24 h and until they can tolerate oral medication. Once a patient has received at least 24 h of parenteral therapy and can tolerate oral therapy, complete treatment with 3 days of an ACT (add single dose Primaquine in areas of low transmission).
- 3.1.2 Young children weighing < 20 kg
- Preferred regimen:Artesunate 3 mg/kg per dose IV/IM q24h
- Alternatives regimen: use Artemether in preference to quinine for treating children and adults with severe malaria
- 3.2.Treating cases of suspected severe malaria pending transfer to a higher-level facility (pre-referral treatment)
- 3.2.1 Adults and children
- Preferred regimen: Artesunate IM q24h
- Alternative regimen: Artemether IM OR Quinine IM
- 3.2.2 Children < 6 years
- Preferred regimen: Where intramuscular injections of artesunate are not available, treat with a single rectal dose (10 mg/kg) of Artesunate, and refer immediately to an appropriate facility for further care.
- Note: Do not use rectal artesunate in older children and adults.
- 3.3 Pregancy
- Note: Parenteral artesunate is the treatment of choice in all trimesters. Treatment must not be delayed.
- 3.4 Treatment of severe P. Vivax infection
- Note: parenteral artesunate, treatment can be completed with a full treatment course of oral ACT or chloroquine (in countries where chloroquine is the treatment of choice). A full course of radical treatment with primaquine should be given after recovery.
- 3.5 Additional aspects of management in severe malaria
- Fluid therapy: It is not possible to give general recommendations on fluid replacement; each patient must be assessed individually and fluid resuscitation based on the estimated deficit.
- Blood Transfusion :In high-transmission settings, blood transfusion is generally recommended for children with a haemoglobin level of < 5 g/100 mL(haematocrit < 15%). In low-transmission settings, a threshold of 20% (haemoglobin,7 g/100 mL) is recommended.
- Exchange blood transfusion: Exchange blood transfusion requires intensive nursing care and a relatively large volume of blood, and it carries significant risks. There is no consensus on the indications, benefits and dangers involved or on practical details such as the volume of blood that should be exchanged. It is, therefore, not possible to make any recommendation regarding the use of exchange blood transfusion.
# Toxoplasma gondii
- Toxoplasma gondii Return to Top
- Toxoplasma gondii (treatment)
- 1. Lymphadenopathic toxoplasmosis
- Preferred regimen: Treatment of immunocompetent adults with lymphadenopathic toxoplasmosis is rarely indicated; this form of the disease is usually self-limited.
- 2. Ocular disease
- 2.1 Adults
- Preferred regimen: Pyrimethamine 100 mg PO for 1 day as a loading dose, then 25 to 50 mg/day AND Sulfadiazine 1 g PO qid AND folinic acid (Leucovorin 5-25 mg PO with each dose of Pyrimethamine
- 2.2 Pediatric
- Preferred regimen: Pyrimethamine 2 mg/kg PO first day then 1 mg/kg each day AND Sulfadiazine 50 mg/kg PO bid AND folinic acid (Leucovorin 7.5 mg/day PO ) for 4 to 6 weeks followed by reevaluation of the patient's condition
- Alternative regimen: The fixed combination of Trimethoprim with Sulfamethoxazole has been used as an alternative.
- Note: If the patient has a hypersensitivity reaction to sulfa drugs, Pyrimethamine AND Clindamycin can be used instead.
- 3. Maternal and fetal infection
- 3.1 First and early second trimesters
- Preferred regimen: Spiramycin is recommended
- 3.2 Late second and third trimesters
- Preferred regimen: Pyrimethamine/Sulfadiazine AND Leucovorin for women with acute T. gondii infection diagnosed at a reference laboratory during gestation.
- 3.3 Infant
- Note: If the infant is likely to be infected, then treatment with drugs such as Pyrimethamine, Atovaquone, Sulfadiazine, Leucovorin is typical. Congenitally infected newborns are generally treated with pyrimethamine, a sulfonamide, and leucovorin for 1 year.
- 4. Toxoplasma gondii Encephalitis in AIDS
- 4.1 Treatment for acute infection
- 4.1.1 Patients with weight <60 kg
- Preferred regimen: Pyrimethamine 200 mg PO 1 time, followed by Pyrimethamine 50 mg PO qd AND Atovaquone AND Sulfadiazine 1000 mg PO q6h AND Leucovorin 10–25 mg PO qd,
- 4.1.2 Patients with weight ≥60 kg
- Preferred regimen: Pyrimethamine 200 mg PO 1 time, followed by Pyrimethamine 75 mg PO qd AND Sulfadiazine 1500 mg PO q6h AND Leucovorin 10–25 mg PO qd and Leucovorin dose can be increased to 50 mg qd or bid
- Alternative regimen (1): Pyrimethamine AND Leucovorin AND Clindamycin 600 mg IV/ PO q6h
- Alternative regimen (2): TMP-SMX (TMP 5 mg/kg and SMX 25 mg/kg ) IV/PO bid
- Alternative regimen (3): Atovaquone 1500 mg PO bid AND Pyrimethamine AND Leucovorin
- Alternative regimen (4): Atovaquone1500 mg PO bid AND sulfadiazine 1000–1500 mg PO q6h (weight-based dosing, as in preferred therapy)
- Alternative regimen (5): Atovaquone 1500 mg PO bid
- Alternative regimen (6): Pyrimethamine AND Leucovorin AND Azithromycin 900–1200 mg PO qd
- Note: Treatment for at least 6 weeks; longer duration if clinical or radiologic disease is extensive or response is incomplete at 6 weeks.
- 4.2 Chronic maintenance therapy
- Preferred regimen: Pyrimethamine 25–50 mg PO qd AND sulfadiazine 2000–4000 mg PO qd (in 2–4 divided doses) AND Leucovorin 10–25 mg PO qd
- Alternative regimen (1): Clindamycin 600 mg PO q8h AND (Pyrimethamine 25–50 mg AND Leucovorin 10–25 mg) PO qd
- Alternative regimen (2): TMP-SMX DS 1 tablet bid
- Alternative regimen (3): Atovaquone 750–1500 mg PO bid AND (Pyrimethamine 25 mg AND Leucovorin 10 mg) PO qd
- Alternative regimen (4): Atovaquone 750–1500 mg PO bid
- Alternative regimen (5): Sulfadiazine 2000–4000 mg PO bid/qid
- Alternative regimen (6): Atovaquone 750–1500 mg PO bid Pyrimethamine and Leucovorin doses are the same as for preferred therapy
- Note: Adjunctive corticosteroids (e.g., Dexamethasone) should only be administered when clinically indicated to treat mass effect associated with focal lesions or associated edema; discontinue as soon as clinically feasible. Anticonvulsants should be administered to patients with a history of seizures and continued through acute treatment, but should not be used as seizure prophylaxis . If Clindamycin is used in place of Sulfadiazine, additional therapy must be added to prevent PCP.
- Toxoplasma gondii (prophylaxis)
- 1. Prophylaxis to prevent first episode of encephalitis in AIDS
- 1.1 Indications
- Toxoplasma IgG-positive patients with CD4 count <100 cells/µL
- Seronegative patients receiving PCP prophylaxis not active against toxoplasmosis should have toxoplasma serology retested if CD4 count decline to <100 cells/µL. Prophylaxis should be initiated if seroconversion occurred.
- 1.2 Prophylactic therapy
- Preferred regimen: TMP-SMX 1 DS PO daily
- Alternative regimen (1): TMP-SMX 1 DS PO three times weekly
- Alternative regimen (2): TMP-SMX 1 SS PO qd
- Alternative regimen (3): Dapsone 50 mg PO qd AND (Pyrimethamine 50 mg PO AND Leucovorin 25 mg) PO weekly
- Alternative regimen (4): Dapsone 200 mg PO AND Pyrimethamine 75 mg PO AND Leucovorin 25 mg PO weekly
- Alternative regimen (5): Atovaquone 1500 mg PO qd
- Alternative regimen (6): Atovaquone 1500 mg PO AND Pyrimethamine 25 mg PO AND Leucovorin 10 mg PO qd
# Trichomonas vaginalis
- Trichomonas vaginalis Return to Top
- 1. T. vaginalis infection in adults
- Preferred regimen (1): Metronidazole 2 g PO in a single dose
- Preferred regimen (2): Tinidazole 2 g PO in a single dose
- Alternative regimen: Metronidazole 500 mg PO bid for 7 days
- 2. T. vaginalis infection in pregnant and lactating Women
- 2.1 Pregnant women
- Preferred regimen: Metronidazole 2 g PO in a single dose.
- 2.2 Post-partum and Breastfeeding
- Preferred regimen (1): Metronidazole 2 g PO in a single dose.
- Preferred regimen (2): Tinidazole 2 g PO in a single dose
- Note (1): Do not breastfeed for 12-24 hrs following Metronidazole and 72 hrs following Tinidazole
- Note (2): Symptomatic pregnant women, regardless of pregnancy stage, should be tested and considered for treatment. Pregnant women should be advised of the risk and benefits to treatment as infection (definitely) and treatment (possibly)
- Note (3): Pregnant women with HIV who are treated for T. vaginalis infection should be retested 3 months after treatment.
- 3. T. vaginalis infection in patients with HIV
- Preferred regimen: Metronidazole 500 mg PO bid for 7 days
- 4. Persistent or recurrent trichomoniasis
- 4.1 Treatment failure
- Preferred regimen: Metronidazole 500 mg PO bid for 7 days
- 4.2 Treatment failure again
- Preferred regimen (1): Metronidazole 2 g PO for 7 days
- Preferred regimen (2): Tinidazole 2 g PO for 7 days
- 4.3 Nitroimidazole-resistant cases
- Preferred regimen: Tinidazole 2-3 g PO for 14 days
# African trypanosomiasis
- African trypanosomiasis Return to Top
- Sleeping sickness
- 1. East african trypanosomiasis
- 1.1 T. b. rhodesiense, hemolymphatic stage
- 1.1.1 Adult
- Preferred regimen: Suramin 1 gm IV on days 1,3,5,14, and 21
- 1.1.2 Pediatric
- Preferred regimen: Suramin 20 mg/kg IV on days 1, 3, 5, 14, and 21
- 1.2 T. b. rhodesiense, CNS involvement
- 1.2.1 Adult
- Preferred regimen: Melarsoprol 2-3.6 mg/kg/day IV for 3 days. After 7 days, 3.6 mg/kg/day for 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days.
- 1.2.2 Pediatric
- Preferred regimen: Melarsoprol 2-3.6 mg/kg/day IV for 3 days. After 7 days, 3.6 mg/kg/day for 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days
- 2. West african trypanosomiasis
- 2.1 T. b. gambiense, hemolymphatic stage
- 2.1.1 Adult
- Preferred regimen: Pentamidine 4 mg/kg/day IM/ IV for 7-10 days
- 2.1.2 Pediatric
- Preferred regimen: Pentamidine 4 mg/kg/day IM/IV for 7-10 days
- Note (1): Pentamidine should be used during pregnancy and lacation only if the potential benefit justifies the potential risk
- Note (2): IM/IV Pentamidine have a similar safety profile in children age 4 months and older as in adults. Pentamidine is listed as a medicine for the treatment of 1st stage African trypanosomiasis infection (Trypanosoma brucei gambiense) on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.
- 2.2 T. b. gambiense, CNS involvement
- 2.2.1 Adult
- Preferred regimen: Eflornithine 400 mg/kg/day IV qid for 14 days
- 2.2.2 Pediatric
- Preferred regimen: Eflornithine 400 mg/kg/day IV qid for 14 days
- Note (1): Eflornithine should be used during pregnancy and lactation, only if the potential benefit justifies the potential risk
- Note (2): The safety of Eflornithine in children has not been established. Eflornithine is not approved by the Food and Drug Administration (FDA) for use in pediatric patients. Eflornithine is listed for the treatment of 1st stage African trypanosomiasis inTrypanosoma brucei gambiense infection on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.
# American trypanosomiasis
- American trypanosomiasis Return to Top
- Chagas disease
- 1. Preferred regimen(1):
- Patients of age < 12 years- Benznidazole 5-7.5 mg/kg/ day PO bid for 60 days
- Patients of age 12 years or older- Benznidazole 5-7 mg/kg/day PO bid for 60 days
- 2. Preferred regimen(2):
- Patients of age ≤ 10 years- Nifurtimox 15-20 mg/kg/day PO tid/ qid for 90 days
- Patients of age 11-16 years- Nifurtimox 12.5-15 mg/kg/day PO tid/ qid for 90 days
- Patients of age 17 years or older- Nifurtimox 8-10 mg/kg/day PO tid/ qid for 90 days
- Note: In the United States, Nifurtimox and Benznidazole are not FDA approved and are available only from CDC under investigational protocols.
### Parasites – Intestinal Nematodes (Roundworms)
- Gnathostoma spinigerum Return to Top
- Eosinophilic Meningitis
Preferred regimen: Supportive measures. Anthelminthic therapy might be deleterious by augmenting the inflammation due to the death of the larvae. The use of corticosteroids is generally favored for suppression of the inflammation but there are no clinical trials that prove its efficacy.
- Preferred regimen: Supportive measures. Anthelminthic therapy might be deleterious by augmenting the inflammation due to the death of the larvae. The use of corticosteroids is generally favored for suppression of the inflammation but there are no clinical trials that prove its efficacy.
- Cutaneous disease:
- Preferred regimen: Albendazole 400 mg bid for 21 days OR Ivermectin 200 mcg/kg qd for 2 days
- Alternative regimen: Albendazole 400 mg qd for 21 days OR Ivermectin 200 mcg/kg qd single dose
- Ancylostoma braziliense Return to Top
- Cutaneous larva migrans treatment
- 1.1 In adults
- Preferred regimen: Albendazole 400 mg PO qd for 3-7 days
- Alternative regimen: Ivermectin 200 mcg/kg PO qd for 1-2 days
- 1.2 In children
- Preferred regimen: Albendazole > 2 years then 400 mg PO qd for 3 days
- Alternative regimen: Ivermectin > 15 kg give 200 mcg/kg single dose
- Note: Albendazole is contraindicated in children younger than 2 years age
- Angiostrongylus cantonensis Return to Top
- Preferred: Symptomatic therapy, serial lumber puncture, corticosteroids (prednisone 60 mg qd for 2 weeks) and analgesics.
- Note: Albendazole and Mebendazole are generally not recommended due to the risk of exacerbation of neurological symptoms following anthelminthic therapy.
- Ascaris lumbricoides Return to Top
- Preferred regimen: Albendazole 400 mg PO qd OR Mebendazole 500 mg PO qd or 100 mg bid for 3 days
- Note: Albendazole dose for children of 1-2 years is 200 mg instead of 400 mg.
- Alternative regimen (1): Ivermectin 150 to 200 µg/kg PO single dose
- Alternative regimen (2): Nitazoxanide 500 mg bid for 3 days
- Alternative regimen (3): Levamisole 120 mg PO single dose
- Note: Pediatric dose: 2.5 mg/kg
- Alternative regimen (4): Pyrantel Pamoate 11 mg/kg single dose PO - maximum 1.0 g
- Alternative regimen (5): Piperazine citrate 75 mg/kg qd for 2 days - maximum 3.5 g
- Capillaria philippinensis Return to Top
- 1. Intestinal capillariasis
- Preferred regimen: Albendazole 400 mg/day PO for 10-30 days
- Alternative regimen: Mebendazole 200 mg PO bid for 20-30 days
- Enterobius vermicularis Return to Top
- 1. Enterobius vermicularis
- Preferred regimen (1): Albendazole 400 mg PO single dose
- Preferred regimen (2): Mebendazole 100 mg PO single dose
- Preferred regimen (3): Ivermectin 200 µg/kg PO single dose
- Preferred regimen (4): Pyrantel pamoate 11 mg/kg up to 1.0 g PO single dose
- Note: A second dose is given 2 weeks later because of the frequency of reinfection and autoinfection.
- Necator americanus Return to Top
- Preferred regimen: Albendazole 400 mg PO single dose
- Alternative regimen (1): Mebendazole 100 mg PO bid or 500 mg daily for 3 days
- Alternative regimen (2): Pyrantel pamoate 11 mg/kg PO qd (maximum 1 g/day) for 3 days
- Ancylostoma duodenale Return to Top
- Preferred regimen: Albendazole 400 mg PO single dose
- Alternative regimen (1): Mebendazole 100 mg PO bid or 500 mg daily for 3 days
- Alternative regimen (2): Pyrantel pamoate 11 mg/kg PO qd (maximum 1 g/day) for 3 days
- Strongyloides stercoralis Return to Top
- Preferred regimen: Ivermectin 200 mcg/kg/day PO qd for 2 days or two doses 2 weeks apart from each other
- Alternative regimen: Albendazole 400 mg PO bid for 3-7 days
- Trichuris trichiura Return to Top
- Preferred regimen: Albendazole 400 mg PO qd for 3 days
- Alternatie regimen (1): Mebendazole 100 mg PO bid for 3 days
- Alternative regimen (2): Ivermectin 200 mcg/kg/day PO qd for 3 days
### Parasites – Extraintestinal Nematodes (Roundworms)
- Ancylostoma braziliense Return to Top
- Preferred regimen
- Adult: Albendazole 400mg PO qd for 3-7 days.
- Pediatric: Albendazole > 2 years 400mg PO qd for 3 days
- Note: This drug is contraindicated in children younger than 2 years.
- Alternative regimen
- Adult: Ivermectin 200 mcg/kg PO qd for one or two days.
- Pediatric: Ivermectin >15 kg give 200mcg/kg single dose.
- Angiostrongylus cantonensis Return to Top
- Preferred: Symptomatic therapy, serial lumber puncture, corticosteroids (prednisone 60mg qd for 2 weeks) and analgesics
- Note: Albendazole and Mebendazole are generally not recommended due to the risk of exacerbation of neurological symptoms following anthelminthic therapy.
- Filariasis Return to Top
- Filariasis
- 1. Lymphatic filariasis caused by Wuchereria bancrofti, Brugia malayi, Brugia timori
- Preferred regimen: Diethylcarbamazine 6 mg/kd/day PO tid for 12 days (single dose if patient will continue to live in endemic area or is younger than 9 years old)
- 2. Loa loa filariasis
- 2.1 Symptomatic loiasis with < 8,000 microfilariae/mL
- Preferred regimen: Diethylcarbamazine 8–10 mg/kd/day PO tid for 21 days
- 2.2 Symptomatic loiasis, with < 8,000 microfilariae/mL and failed 2 rounds DEC
- Preferred regimen: Albendazole 200 mg PO bid for 21 days
- 2.3 Symptomatic loiasis, with ≥ 8,000 microfilariae/ml to suppress microfilaremia prior to treatment with DEC
- Preferred regimen: Albendazole 200 mg PO bid for 21 days
- 2.4 Symptomatic loiasis, with ≥ 8,000 microfilariae/mL
- Preferred regimen: Apheresis followed by Diethylcarbamazine
- Note: Apheresis should be performed at an institution with experience in using this therapeutic modality for loiasis.
- 3. River blindness (onchocerciasis) caused by Onchocerca volvulus
- Preferred regimen: Ivermectin 150 μg/kg PO single dose, repeated every 6-12 mos until asymptomatic
- Alternative regimen: Doxycycline 100 mg PO qd for 6 weeks, alone or followed by Ivermectin 150 μg/kg PO single dose
- Note: Do NOT administer Diethylcarbamazine where onchocerciasis is endemic due to increased risk for severe local inflammation in patients with ocular microfilariae.
- 4. Mansonella ozzardi
- Preferred regimen: Ivermectin 200 μg/kg PO single dose
- Note: Endosymbiotic Wolbachia are essential to filarial growth, development, embryogenesis and survival and represent an additional target for therapy. Doxycycline 100–200 mg PO qd for 6–8 weeks results in loss of Wolbachia and decrease in both micro- and macrofilariae.
- 5. Mansonella perstans
- Preferred regimen: Doxycycline 100–200 mg PO qd for 6–8 weeks
- 6. Mansonella streptocerca
- Preferred regimen (1): Diethylcarbamazine 6 mg/kd/day PO tid for 12 days
- Preferred regimen (2): Ivermectin 150 μg/kg PO single dose
- 7. Tropical pulmonary eosinophilia caused by Wuchereria bancrofti
- Preferred regimen: Diethylcarbamazine 6 mg/kd/day PO tid for 12–21 days
- Gnathostoma spinigerum Return to Top
- 1. Eosinophilic Meningitis
Preferred regimen: Supportive measures. Anthelminthic therapy might be deleterious by augmenting the inflammation due to the death of the larvae. The use of corticosteroids is generally favored for suppression of the inflammation but there are no clinical trials that prove its efficacy.
- Preferred regimen: Supportive measures. Anthelminthic therapy might be deleterious by augmenting the inflammation due to the death of the larvae. The use of corticosteroids is generally favored for suppression of the inflammation but there are no clinical trials that prove its efficacy.
- 2. Cutaneous disease:
- Preferred regimen (1): Albendazole 400 mg bid for 21 days
- Preferred regimen (2): Ivermectin 200 mcg/kg once daily for 2 days
- Alternative regimen (1): Albendazole 400 mg daily for 21 days
- Alternative regimen (2): Ivermectin 200 mcg/kg once daily for 1 day
- Toxocariasis Return to Top
- 1.1 Visceral toxocariasis
- Preferred regimen: Albendazole 400 mg PO bid for five days (both adult and pediatric dosage)
- Alternative regimen: Mebendazole 100-200 mg PO bid for five days (both adult and pediatric dosage)
- Note: Treatment is indicated for moderate-severe cases. Patients with mild symptoms of toxocariasis may not require anthelminthic therapy as symptoms are limited.
- 1.2 Ocular toxocariasis
- Preferred regimen: Prednisone 0.5-1mg/kg/day PO q24h AND Albendazole 400mg PO bid for 2 to 4 weeks (pediatric dose: 400mg PO qd)
- Note: Surgical therapy might be neeeded.
- Trichinella spiralis Return to Top
- Trichinella spiralis
- Preferred regimen (1): Albendazole 400 mg PO bid for 8-14 days
- Preferred regimen (2): Mebendazole 200-400 mg PO tid for 3 days THEN 400-500 mg PO tid for 10 days
- Note (1): Both treatment schemes are suitable for adult and pediatric dosages
- Note (1): Albendazole and Mebendazole are contraindicated during pregnancy and not recommended in children aged 2 years.
- Alternative regimen (1): (severe symptoms) Prednisone 30 mg/day-60 mg/day for 10-15 days
- Alternative regimen (2): Pyrantel 10-20 mg/kg single dose for 2-3 days
### Parasites – Trematodes (Flukes)
- Clonorchis sinensis Return to Top
- Preferred regimen: Praziquantel 75mg/kg/day PO tid for 2 days
- Alternative regimen (1): Albendazole 10mg/kg/day PO qd for 7 days
- Alternative regimen (2): Tribendimidine 400mg PO single dose
- This regimen is still under investigation, but it appears to be as effective as Praziquantel.
- Note: Urgent biliary decompression might be required for patients with acute cholangitis.
- Dicrocoelium dendriticum Return to Top
- Preferred regimen: Praziquantel 25 mg/kg PO tid for 2 days
- Note: Praziquantel is not approved for treatment of children less than 4 years old.
- Alternative regimen (1): Myrrh (commiphora molmol) 12 mg/kg/day PO for 6 days
- Alternative regimen (2): Triclabendazole 10 mg/kg PO single dose
- Fasciola hepatica Return to Top
- Preferred regimen: Triclabendazole 10 mg/kg PO one dose
- Note: Two-dose (double-dose) triclabendazole therapy can be given to patients who have severe or heavy Fasciola infections (many parasites) or who did not respond to single-dose therapy.
- Alternative regimen: Nitazoxanide 500mg PO bid for 7 days
- Paragonimus westermani Return to Top
- Preferred regimen (1): Praziquantel 25 mg/kg PO tid for 3 days
- Preferred regimen (2): Triclabendazole 10 mg/kg PO qd or bid
- Alternative regimen (1): Bithinol 30-50mg/kg PO on alternate days for 10-15 doses
- Alternative regimen (2): Niclosamide 2mg/kg PO single dose
- Schistosomiasis Return to Top
- 1. Schistosoma mansoni, S. haematobium, S. intercalatum
- Preferred regimen: Praziquantel 40 mg/kg per day PO in qd or bid for one day
- Alternative regimen (1): Oxamniquine 20 mg/kg PO single dose
- Alternative regimen (2): Artemisinin no dose is established yet
- Alternative regimen (3): Mefloquine 250 mg PO single dose
- Note: There is no benefit in associating the alternative therapies to Praziquantel.
- Note: Praziquantel is not effective against larval/egg stages of the disease.
- 2. S. japonicum, S. mekongi
- Preferred regimen: Praziquantel 60 mg/kg per day PO bid for one day
- Alternative regimen (1): Artemisinin no dose is established yet
- Alternative regimen (2): Mefloquine 250 mg PO single dose
- Note: There is no benefit in associating the alternative therapies to Praziquantel.
- 3. Katayama Fever
- Preferred regimen: Prednisone 20-40 mg/day PO for 5 days, THEN Praziquantel
- Note: Praziquantel should be used after 4-6 weeks of exposure, because it cannot kill the larvae stages of the Schistosoma. Praziquantel should be used after acute schistosomiasis syndrome symptoms have resolved always together with corticosteroids, only when ova are detected in stool or urine samples.
- 4. Neuroschistosomiasis
- Preferred regimen: prednisone 1-2 mg/kg
- Note: Praziquantel should only be introduced after a few days of the initiation of corticosteroid therapy, due to the risk of increasing the inflammatory response.
### Parasites – Cestodes (Tapeworms)
- Echinococcus Return to Top
- Echinococcus treatment
- 1.1 Echinococcus granulosus (hydatid disease) treatment
- Preferred regimen: Albendazole ≥ 60 kg 400 mg PO bid or < 60 kg 10-15 mg/kg/day PO bid with meals for 3-6 months
- Alternative regimen: Mebendazole 40-50mg/kg/day PO tid for 3-6 months
- Note: Percutaneous aspiration-injection-reaspiration (PAIR). Puncture & needle aspirate cyst content. Instill hypertonic saline (15–30%) or absolute alcohol, wait 20–30 min, then re-aspirate with final irrigation. Administer Albendazole at least 4 hours before PAIR.
- Note: If surgery is needed, make sure to administer Albendazole for at least a week before the surgery, and to keep the medication for at least 4 weeks after the procedure.
- 1.2 Echinococcus multilocularis (alveolar cyst disease) treatment
- Preferred regimen: Albendazole ≥ 60 kg 400 mg PO bid or < 60 kg 15 mg/kg/day PO bid with meals for at least 2 years. Long-term follow up needed to evaluate progression of the lesions.
# Neurocysticercosis
- Neurocysticercosis Return to Top
- Neurocysticercosis treatment
- 1. Parenchymal neurocysticercosis
- 1.1 Single lesions
- Preferred regimen: Albendazole 15 mg/kg/day PO bid for 3-8 days AND Prednisone 1 mg/kg/day PO qid for 8-10 days followed by a taper
- 1.2 Multiple cysts
- Preferred regimen: Albendazole 15 mg/kg/day PO bid for 8-15 days and high-dose steroids
- Preferred regimen: Praziquantel 50 mg/kg/day PO tid AND Albendazole 15 mg/kg/day PO bid
- 1.3 Cysticercal encephalitis
- Cysticercal encephalitis (diffuse cerebral edema associated with multiple inflamed cysticerci) is a contraindication for antiparasitic therapy, since enhanced parasite killing can exacerbate host inflammatory response and lead to diffuse cerebral edema and potential transtentorial herniation. Most cases of cysticercal encephalitis improve with corticosteroid therapy
- 1.4 Calcified cysts
- Radiographic evidence of parenchymal calcifications is a significant risk factor for recurrent seizure activity; these lesions are present in about 10 percent of individuals in regions where neurocysticercosis is endemic. Seizures in these patients should be treated with antiepileptic therapy.
- 2. Extraparenchymal NCC
- 2.1 Subarachnoid cysts
- Preferred regimen: Albendazole 15 mg/kg/day PO bid for 28 days AND (Prednisone up to 60 mg/day PO OR Dexamethasone (up to 24 mg/day)) along with the antiparasitic therapy. The dose can often be tapered after a few weeks. However, in cases for which more prolonged steroid therapy is required, methotrexate can be used as a steroid-sparing agent
- 2.2 Giant cysts
- Giant cysticerci are usually accompanied by cerebral edema and mass effect, which should be managed with high-dose corticosteroids (with or without mannitol).
- 2.3 Intraventricular cysts
- Emergent management with CSF diversion via a ventriculostomy or placement of a ventriculo-peritoneal shunt
- Treatment of residual hydrocephalus may be managed with endoscopic foraminotomy and endoscopic third ventriculostomy; this approach may also allow debulking of cisternal cysticerci
- 2.4 Ocular cysticercosis
- Surgical excision is warranted in the setting of intraocular cysts
- Cysticercal involvement of the extraocular muscles should be managed with albendazole and corticosteroids.
- 2.5 Spinal cysticercosis
- Medical therapy with corticosteroids and antiparasitic drugs
- Sparganosis Return to Top
- Sparganosis (Spirometra mansonoides) treatment
- Preferred treatment: Surgical resection or ethanol injection of subcutaneous masses
- Note: Praziquantel 75 mg/kg/day PO qd for 3 days is controversial. It's been innefective in some cases, but has had some results in patients when surgical therapy wasn't an option.
### Parasites – Ectoparasites
- Body lice Return to Top
- Pediculus humanus, corporis treatment
- A body lice infestation is treated by improving the personal hygiene of the infested person, including assuring a regular (at least weekly) change of clean clothes.
- Clothing, bedding, and towels used by the infested person should be laundered using hot water (at least 130°F) and machine dried using the hot cycle.
- Sometimes the infested person also is treated with a pediculicide Ivermectin Lotion; however, a pediculicide Ivermectin generally is not necessary if hygiene is maintained and items are laundered appropriately at least once a week. A pediculicide Ivermectin should be applied exactly as directed on the bottle or by your physician.
- Head lice Return to Top
- Pediculus humanus, capitis treatment
- Preferred regimen (1): Permethrin 1% lotion apply to shampooed dried hair for 10 min.; repeat in 9-10 days
- Preferred regimen (2): Malathion 0.5% lotion (Ovide) apply to dry hair for 8–12hrs, then shampoo (2 doses 7-9 days apart)
- Alternative regimen: Ivermectin 200 μg/kg PO once; 3 doses at 7 day intervals reported effective.
- Pubic lice Return to Top
- Phthirus pubis treatment
- Preferred regimen (1): Permethrin 1% cream rinse applied to affected areas and washed off after 10 minutes
- Preferred regimen (2): Pyrethrins with piperonyl butoxide applied to the affected area and washed off after 10 minutes
- Alternative regimen (1): Malathion 0.5% lotion applied to affected areas and washed off after 8–12 hours
- Alternative regimen (2): Ivermectin 250 ug/kg PO, repeated in 2 weeks
- Myiasis Return to Top
- Preferred regimen: No medications approved by the FDA are available for treatment
- Note: Fly larvae need to be surgically removed.
- Fly larvae treatment
- Preferred treatment (1): Occlude punctum to prevent gas exchange with petrolatum, fingernail polish, makeup cream or bacon.
- Preferred treatment (2): When larva migrates, manually remove.
- Note (1): Myiasis is due to larvae of flies.
- Note (2): Usually cutaneous/subcutaneous nodule with central punctum.
- Scabies Return to Top
- Sarcoptes scabiei treatment
- 1. Adult
- Preferred regimen (1): Permethrin 5% cream applied to all areas of the body from the neck down and washed off after 8–14 hours
- Preferred regimen (2): Ivermectin 200 ug/kg PO qd and repeated in 2 weeks
- Alternative regimen: Lindane (1%) 1 oz of lotion or 30 g of cream applied in a thin layer to all areas of the body from the neck down and thoroughly washed off after 8 hours
- 2. Infants and young children
- Preferred regimen: Permethrin 5% cream applied to all areas of the body from the neck down and washed off after 8–14 hours
- Note: Infants and young children aged< 10 years should not be treated with lindane.
- 3. Crusted Scabies
- Crusted scabies (i.e., Norwegian scabies) is an aggressive infestation that usually occurs in immunodeficient, debilitated, or malnourished persons, including persons receiving systemic or potent topical glucocorticoids, organ transplant recipients, persons with HIV infection or human T-lymphotrophic virus-1-infection, and persons with hematologic malignancies.
- Preferred regimen: (Topical scabicide 5% topical Benzyl benzoate 5% OR topical Permethrin 5% cream (full-body application to be repeated daily for 7 days then twice weekly until discharge or cure) AND treatment with Ivermectin 200 ug/kg PO on days 1,2,8,9, and 15. Additional Ivermectin treatment on days 22 and 29 might be required for severe cases
- 4.Pregnant or Lactating Women
- Preferred regimen: Permethrin 5% cream applied to all areas of the body from the neck down and washed off after 8–14 hours
### Viruses
- Adenovirus Return to Top
- Adenovirus
- 1. In severe cases of pneumonia or post hematopoietic stem cell transplantation
- Preferred regimen (1): Cidofovir 5 mg/kg/week IV for 2 weeks, then every 2 weeks AND Probenecid 1.25 g/M2 PO given 3 hours before Cidofovir and 3 & 9 hours after each infusion
- Preferred regimen (2): Cidofovir 1 mg/kg IV 3 times per week
- Note: Ganciclovir, Foscarnet and Ribavirin are not recommended for use on adenovirus infection.
- 2. For hemorrhagic cystitis
- Preferred regimen: Cidofovir (5 mg/kg in 100 mL saline instilled into bladder) intravesical
- 3. Pink eye (viral conjunctivitis)
- Preferred regimen: No specific treatment available. If symptomatic, cold artificial tears may help.
- 4.Bronchitis
- Preferred regimen: No specific therapy recommended, treatment is symptomatic.
- SARS Return to Top
- Severe acute respiratory distress syndrome- coronavirus infection treatment
- Preferred regimen: supportive therapy
- Note: New therapies were studied for SARS during the last outbreaks which concluded:
- Ribavirin ineffective and probably harmful due to haemolytic anaemia
- Lopinavir AND Ritonavir is still controversial and need further investigation
- Interferon has no benefit and its studies are inconclusive
- Corticosteroids increases risk of fungal infections, some studies showed a higher incidence of psychosis, diabetes, avascular necrosis and osteoporosis
- Inhaled Nitric oxide potent mediator of airway inflammation, its has improved oxygenation in some studies
- Cytomegalovirus Return to Top
- Cytomegalovirus treatment
- 1. Immunocompetent patients
- 1.1 Mononucleosis syndrome
- Preferred regimen: supportive therapy
- 1.2 CMV in pregnancy
- Preferred regimen: Hyperimmune 200 IU/kg of maternal weight as single-dose during pregnancy
- 2. Immunocompromised patients
- 2.1 Retinitis
- Preferred regimen (1): Ganciclovir intraocular implant PLUS Valganciclovir 900 mg PO bid for 14-21 days THEN Valganciclovir 900mg PO qq for maintenance therapy - for immediate sight-threatening lesions
- Preferred regimen (2): Valganciclovir 900 mg PO bid for 14-21 days THEN Valganciclovir 900 mg PO qq for maintenance therapy - for peripheral lesions
- Alternative regimen (1): Foscarnet 60 mg/kg IV q8h OR Foscarnet 90 mg/kg IV q12h for 14-21 days THEN Foscarnet 90-120 mg/kg IV q24h
- Alternative regimen (2): Cidofovir 5 mg/kg IV for 2 weeks THEN Cidofovir 5 mg/kg IV every other week - each dose should be admnistered with IV saline hydration and probenecid
- Alternative regimen (3): Ganciclovir 5 mg/kg IV q12h for 14-21 days THEN Valganciclovir 900 mg PO bid
- Alternative regimen (4): Fomivirsen intravitreal injection - for relapses
- Note: keep a maintenance dose of Valganciclovir 900 mg PO qd until CD4 >100/mm³
- 2.2 Transplant patients
- Preferred regimen: Valganciclovir 900 mg PO bid OR Ganciclovir 5 mg/kg IV q12h for at least 2-3 weeek
- Note: Use Valganciclovir 900 mg PO qd for 1-3 months if high dose of immunosuppression.
- 2.3 Colitis, esophagitis, gastritis
- Preferred regimen: Ganciclovir 5 mg/kg/dose IV q12h for 3-6 weeks weeks for induction. There is no agreement on the use of maintenance.
- Alternative regimen: Cidofovir 5 mg/kg IV for 2 weeks, then 5 mg/kg every other week; each dose should be administered with IV saline hydration and oral probenecid 2 g PO 3h before each dose and further 1 g doses after 2h and 8h.
- Note: Switch to oral Valganciclovir when PO tolerated & when symptoms not severe enough to interfere with absorption.
- 2.4 Pneumonia
- Preferred regimen: Valganciclovir 900 mg PO bid for 14–21 days, then 900 mg PO qd for maintenance therapy
- Alternative regimen for retinitis: Ganciclovir 5 mg/kg IV q12h for 14–21 days, then Valganciclovir 900 mg PO qd
- Note: In bone marrow transplant patients, combine therapy with CMV immune globulin.
- 2.5 Encephalitis, ventriculitis
- Note: Treatment not defined, but should be considered the same as retinitis. Disease may develop while taking Ganciclovir as suppressive therapy.
- 2.6 Lumbosacral polyradiculopathy
- Preferred regimen: Ganciclovir, as with retinitis
- Alternative regimen: Foscarnet 40 mg/kg IV q12h another option
- Alternative regimen: Cidofovir 5 mg/kg IV for 2 weeks, then 5 mg/kg every other week; each dose should be administered with IV saline hydration and oral probenecid 2 g PO 3h before each dose and further 1 g doses after 2h and 8h.
- Note (1): Switch to Valganciclovir when possible.
- Note (2): Suppression continued until CD4 remains >100/mm³ for 6 months.
- 2.7 Peri/postnatal severe CMV infection in very low birth weight infants
- Preferred regimen: Ganciclovir 6 mg/kg/dose IV q12h for 3 weeks
- Enterovirus D68 Return to Top
- Enterovirus treatment
- Preferred regimen: supportive therapy
- Note: A new drug Pleconaril designed to affect Rhinovirus is being suggested to be effective against Enterovirus D68 but further investigation is required
- Ebola virus Return to Top
- Ebola virus treatment
- Preferred regimen: supportive therapy. There is no specific antiviral drug available for Ebola thus far. For information of investigational therapies including Favipiravir, Brincidofovir, ZMapp, TKM-Ebola, AVI-6002, and BCX4430, see here.
- Isolate patient
- Provide intravenous fluids (IV) (patients need large volumes in some cases) and maintain electrolytes at normal levels
- Maintain oxygen saturation and blood pressure
- Administer blood products if coagulopathy or bleeding, antiemetics if vomiting , antipyretics if fever, analgesics, anti-motility if severe diarrhea, total parenteral nutrition if patient has poor oral intake and dialysis if there's renal failure
- Treat other infections if they occur. Provide adequate Gram-negative coverage and gram-positive if the patient has any catheter or hospital-acquired pneumonia.
- If there's respiratory failure, invasive mechanical ventilation may be the best option to offer respiratory support
- Note (1): Recovery from Ebola depends on good supportive care and the patient’s immune response.
- Note (2): While there is no proven treatment available for Ebola virus disease, human convalescent whole blood has been used as an empirical treatment with promising results in a small group of EVD cases.
- Note (3): People who recover from Ebola infection develop antibodies that last for at least 10 years, possibly longer. It is not known if people who recover are immune for life or if they can become infected with a different species of Ebola.
- Note (4): Some people who have recovered from Ebola have developed long-term complications, such as joint and vision problems.
- Marburg virus Return to Top
- Marburg virus treatment
- Preferred regimen: supportive therapy including maintenance of blood volume and electrolyte balance, as well as analgesics and standard nursing care
- Hantavirus Return to Top
- Hantavirus cardiopulmonary syndrome treatment
- Preferred regimen: Supportive therapy, there is no specific treatment for hantavirus cardiopulmonary syndrome
- Note (1): ICU management should include careful assessment, monitoring and adjustment of volume status and cardiac function, including inotropic and vasopressor support if needed
- Note (2): Fluids should be administered carefully due to the potential for capillary leakage
- Note (3): Supplemental oxygen should be administered if patients become hypoxic
- Note (4): Equipment and materials for intubation and mechanical ventilation should be readily available since onset of respiratory failure may be precipitous
- Note (5): Extracorporeal membrane oxygenation was used with survival rates of 50% in some studies in patients with cardiac index output <2.5L/min/m²
- Dengue virus Return to Top
- Dengue virus
- 1. Patients who may be sent home
- These are patients who are able to tolerate adequate volumes of oral fluids and pass urine at least once every six hours, and do not have any of the warning signs, particularly when fever subsides
- Patients who are sent home should be monitored daily by health care providers for temperature pattern, volume of fluid intake and losses, urine output (volume and frequency), warning signs, signs of plasma leakage and bleeding, haematocrit, and white blood cell and platelet counts
- 2. Ambulatory patients with stable haematocrit can be sent home
- Encourage oral intake of oral rehydration solution (ORS), fruit juice and other fluids containing electrolytes and sugar to replace losses from fever and vomiting
- Give Paracetamol for high fever if the patient is uncomfortable. The interval of paracetamol dosing should not be less than six hours. Tepid sponge if the patient still has high fever
- Should be brought to hospital immediately if any of the following occur: no clinical improvement, deterioration around the time of defervescence, severe abdominal pain, persistent vomiting, cold and clammy extremities, lethargy or irritability/restlessness, bleeding (e.g. black stools or coffee-ground vomiting), not passing urine for more than 4–6 hours
- 3. Patients who should be referred for in-hospital management
- Patients may need to be admitted to a secondary health care centre for close observation, particularly as they approach the critical phase. These include patients with warning signs (Abdominal pain or tenderness, Persistent vomiting, Clinical fluid accumulation, Mucosal bleed, Lethargy, restlessness, Liver enlargment >2cm, Laboratory:increase in HCT concurrent with rapid decrease in platelet count), those with co-existing conditions that may make dengue or its management more complicated (such as pregnancy, infancy, old age, obesity, diabetes mellitus, renal failure, chronic haemolytic diseases), and those with certain social circumstances (such as living alone, or living far from a health facility without reliable means of transport)
- 3.1 With warning signs
- Obtain a reference haematocrit before fluid therapy. Give only isotonic solutions such as 0.9% saline, Ringer’s lactate, or Hartmann’s solution. Start with 5–7 ml/ kg/hour for 1–2 hours, then reduce to 3–5 ml/kg/hr for 2–4 hours, and then reduce to 2–3 ml/kg/hr or less according to the clinical response
- Reassess the clinical status and repeat the haematocrit. If the haematocrit remains the same or rises only minimally, continue with the same rate (2–3 ml/kg/hr) for another 2–4 hours. If the vital signs are worsening and haematocrit is rising rapidly, increase the rate to 5–10 ml/kg/hour for 1–2 hours. Reassess the clinical status, repeat the haematocrit and review fluid infusion rates accordingly
- Give the minimum intravenous fluid volume required to maintain good perfusion and urine output of about 0.5 ml/kg/hr. Intravenous fluids are usually needed for only 24–48 hours. Reduce intravenous fluids gradually when the rate of plasma leakage decreases towards the end of the critical phase. This is indicated by urine output and/or oral fluid intake that is/are adequate, or haematocrit decreasing below the baseline value in a stable patient
- Patients with warning signs should be monitored by health care providers until the period of risk is over. A detailed fluid balance should be maintained. Parameters that should be monitored include vital signs and peripheral perfusion (1–4 hourly until the patient is out of the critical phase), urine output (4–6 hourly), haematocrit (before and after fluid replacement, then 6–12 hourly), blood glucose, and other organ functions (such as renal profile, liver profile, coagulation profile, as indicated)
- 3.2 Without warning signs
- Encourage oral fluids. If not tolerated, start intravenous fluid therapy of 0.9% saline or Ringer’s lactate with or without dextrose at maintenance rate. For obese and overweight patients, use the ideal body weight for calculation of fluid infusion. Patients may be able to take oral fluids after a few hours of intravenous fluid therapy. Thus, it is necessary to revise the fluid infusion frequently. Give the minimum volume required to maintain good perfusion and urine output. Intravenous fluids are usually needed only for 24–48 hours
- Patients should be monitored by health care providers for temperature pattern, volume of fluid intake and losses, urine output (volume and frequency), warning signs, haematocrit, and white blood cell and platelet counts. Other laboratory tests (such as liver and renal functions tests) can be done, depending on the clinical picture and the facilities of the hospital or health centre
- 4. Severe dengue
- Severe dengue: Severe plasma leakage leading to dengue shock and/or fluid accumulation with respiratory distress; severe haemorrhages; severe organ impairment (hepatic damage, renal impairment, cardiomyopathy, encephalopathy or encephalitis)
- 4.1 Treatment of shock
- 4.1.1 Compensated shock
- Start intravenous fluid resuscitation with isotonic crystalloid solutions at 5–10 ml/kg/hour over one hour. Then reassess the patient’s condition (vital signs, capillary refill time, haematocrit, urine output). The next steps depend on the situation
- If the patient’s condition improves, intravenous fluids should be gradually reduced to 5–7 ml/kg/hr for 1–2 hours, then to 3–5 ml/kg/hr for 2–4 hours, then to 2–3 ml/kg/hr, and then further depending on haemodynamic status, which can be maintained for up to 24–48 hours
- If vital signs are still unstable (i.e. shock persists), check the haematocrit after the first bolus. If the haematocrit increases or is still high (>50%), repeat a second bolus of crystalloid solution at 10–20 ml/kg/hr for one hour. After this second bolus, if there is improvement, reduce the rate to 7–10 ml/ kg/hr for 1–2 hours, and then continue to reduce as above. If haematocrit decreases compared to the initial reference haematocrit (<40% in children and adult females, <45% in adult males), this indicates bleeding and the need to cross-match and transfuse blood as soon as possible
- Further boluses of crystalloid or colloidal solutions may need to be given during the next 24–48 hours
- 4.1.2 Hypotensive shock
- Initiate intravenous fluid resuscitation with crystalloid or colloid solution (if available) at 20 ml/kg as a bolus given over 15 minutes to bring the patient out of shock as quickly as possible
- If the patient’s condition improves, give a crystalloid/colloid infusion of 10 ml/kg/hr for one hour. Then continue with crystalloid infusion and gradually reduce to 5–7 ml/kg/hr for 1–2 hours, then to 3–5 ml/kg/hr for 2–4 hours, and then to 2–3 ml/kg/hr or less, which can be maintained for up to 24–48 hours
- If vital signs are still unstable (i.e. shock persists), review the haematocrit obtained before the first bolus. If the haematocrit was low (<40% in children and adult females, <45% in adult males), this indicates bleeding and the need to cross- match and transfuse blood as soon as possible (see treatment for haemorrhagic complications)
- If the haematocrit was high compared to the baseline value (if not available, use population baseline), change intravenous fluids to colloid solutions at 10–20 ml/kg as a second bolus over 30 minutes to one hour. After the second bolus, reassess the patient. If the condition improves, reduce the rate to 7–10 ml/kg/hr for 1–2 hours, then change back to crystalloid solution and reduce the rate of infusion as mentioned above. If the condition is still unstable, repeat the haematocrit after the second bolus
- If the haematocrit decreases compared to the previous value (<40% in children and adult females, less than 45% in adult males), this indicates bleeding and the need to cross-match and transfuse blood as soon as possible (see treatment for haemorrhagic complications). If the haematocrit increases compared to the previous value or remains very high ( more than 50%), continue colloid solutions at 10–20 ml/kg as a third bolus over one hour. After this dose, reduce the rate to 7–10 ml/kg/hr for 1–2 hours, then change back to crystalloid solution and reduce the rate of infusion as mentioned above when the patient’s condition improves
- Further boluses of fluids may need to be given during the next 24 hours. The rate and volume of each bolus infusion should be titrated to the clinical response. Patients with severe dengue should be admitted to the high-dependency or intensive care area
- 4.2 Treatment of haemorrhagic complications
- Blood transfusion required
- Give 5–10ml/kg of fresh-packed red cells or 10–20 ml/kg of fresh whole blood at an appropriate rate and observe the clinical response. It is important that fresh whole blood or fresh red cells are given. Oxygen delivery at tissue level is optimal with high levels of 2,3 di-phosphoglycerate (2,3 DPG). Stored blood loses 2,3 DPG, low levels of which impede the oxygen-releasing capacity of haemoglobin, resulting in functional tissue hypoxia. A good clinical response includes improving haemodynamic status and acid-base balance
- Consider repeating the blood transfusion if there is further blood loss or no appropriate rise in haematocrit after blood transfusion. There is little evidence to support the practice of transfusing platelet concentrates and/or fresh-frozen plasma for severe bleeding. It is being practised when massive bleeding can not be managed with just fresh whole blood/fresh-packed cells, but it may exacerbate the fluid overload
- Great care should be taken when inserting a naso-gastric tube which may cause severe haemorrhage and may block the airway. A lubricated oro-gastric tube may minimize the trauma during insertion. Insertion of central venous catheters should be done with ultra-sound guidance or by a very experienced person
- 5. Treatment of complications and other areas of treatment
- 5.1 Fluid overload
- Oxygen therapy should be given immediately
- When the following signs are present, intravenous fluids should be discontinued or reduced to the minimum rate necessary to maintain euglycaemia
- signs of cessation of plasma leakage; stable blood pressure, pulse and peripheral perfusion; haematocrit decreases in the presence of a good pulse volume; afebrile for more than 24–48 days (without the use of antipyretics); resolving bowel/abdominal symptoms; improving urine output
- The management of fluid overload varies according to the phase of the disease and the patient’s haemodynamic status. If the patient has stable haemodynamic status and is out of the critical phase (more than 24–48 hours of defervescence), stop intravenous fluids but continue close monitoring. If necessary, give oral or intravenous furosemide 0.1–0.5 mg/kg/dose once or twice daily, or a continuous infusion of furosemide 0.1 mg/kg/hour. Monitor serum potassium and correct the ensuing hypokalaemia
- If the patient has stable haemodynamic status but is still within the critical phase, reduce the intravenous fluid accordingly. Avoid diuretics during the plasma leakage phase because they may lead to intravascular volume depletion
- Patients who remain in shock with low or normal haematocrit levels but show signs of fluid overload may have occult haemorrhage. Further infusion of large volumes of intravenous fluids will lead only to a poor outcome. Careful fresh whole blood transfusion should be initiated as soon as possible. If the patient remains in shock and the haematocrit is elevated, repeated small boluses of a colloid solution may help
- 5.2 Other complications of dengue
- Both hyperglycaemia and hypoglycaemia may occur, even in the absence of diabetes mellitus and/or hypoglycaemic agents. Electrolyte and acid-base imbalances are also common observations in severe dengue and are probably related to gastrointestinal losses through vomiting and diarrhoea or to the use of hypotonic solutions for resuscitation and correction of dehydration. Hyponatraemia, hypokalaemia, hyperkalaemia, serum calcium imbalances and metabolic acidosis (sodium bicarbonate for metabolic acidosis is not recommended for pH ≥ 7.15) can occur. One should also be alert for co-infections and nosocomial infections.
- 5.3 Supportive care and adjuvant therapy
- renal replacement therapy, with a preference to continuous veno-venous haemodialysis (CWH), since peritoneal dialysis has a risk of bleeding;
- vasopressor and inotropic therapies as temporary measures to prevent life- threatening hypotension in dengue shock and during induction for intubation, while correction of intravascular volume is being vigorously carried out;
- further treatment of organ impairment, such as severe hepatic involvement or encephalopathy or encephalitis;
- further treatment of cardiac abnormalities, such as conduction abnormalities, may occur (the latter usually not requiring interventions)
- West Nile virus Return to Top
- West nile virus
- 1.1. Prevention
- No WNV vaccines are licensed for use in humans. In the absence of a vaccine, prevention of WNV disease depends on community-level mosquito control programs to reduce vector densities, personal protective measures to decrease exposure to infected mosquitoes, and screening of blood and organ donors.
- Personal protective measures include use of mosquito repellents, wearing long-sleeved shirts and long pants, and limiting outdoor exposure from dusk to dawn. Using air conditioning, installing window and door screens, and reducing peridomestic mosquito breeding sites, can further decrease the risk for WNV exposure.
- Blood and some organ donations in the United States are screened for WNV infection; health care professionals should remain vigilant for the possible transmission of WNV through blood transfusion or organ transplantation. Any suspected WNV infections temporally associated with blood transfusion or organ transplantation should be reported promptly to the appropriate state health department.
- 1.2. Treatment
- There is no specific treatment for WNV disease; clinical management is supportive. Patients with severe meningeal symptoms often require pain control for headaches and antiemetic therapy and rehydration for associated nausea and vomiting. Patients with encephalitis require close monitoring for the development of elevated intracranial pressure and seizures. Patients with encephalitis or poliomyelitis should be monitored for inability to protect their airway. Acute neuromuscular respiratory failure may develop rapidly and prolonged ventilatory support may be required.
- Yellow Fever Return to Top
- Yellow fever
- Preferred regimen: No specific treatment is available for yellow fever. In the toxic phase, supportive treatment includes therapies for treating dehydration and fever. Ribavirin has failed in several studies in the monkey model.
- Note: An international seminar held by WHO in 1984 recommended maintenance of nutrition, prevention of hypoglycemia, maintenance of the blood pressure with fluids and vasoactive drugs, prevention of bleeding with fresh-frozen plasma, dialysis if renal failure, correction of metabolic acidosis, administration of cimetidine IV to avoid gastric bleeding and oxygen if needed.
- Chikungunya virus Return to Top
- Preferred regimen: no specific therapeutics agents are available and there are no licensed vaccines to prevent Chikungunya Fever.
- Note: Anti inflammatory drugs can be used to control joint swelling and arthritis.
- Hepatitis A virus Return to Top
- Preferred regimen: No therapy recommended. If within 2 wks of exposure, IVIG 0.02 mL per kg IM times 1 protective.
- Hepatitis B virus Return to Top
- Acute Hepatitis B
- Chronic Hepatitis B
- 1. Patients with HBeAg-positive chronic hepatitis B
- 1.1. HBV DNA >20,000, ALT <2 times upper limit normal (ULN)
- Observe; consider treatment when ALT becomes elevated.
- Consider biopsy in persons 40 years, ALT persistently high normal >2 times upper limit normal (ULN), or with family history of HCC.
- Consider treatment if HBV DNA >20,000 IU/mL and biopsy shows moderate/severe inflammation or significant fibrosis.
- 1.2. HBV DNA >20,000, ALT >2 times upper limit normal (ULN)
- Preferred regimen (1): Pegylated IFN-alpha 180 mcg weekly SC for 48 weeks
- Preferred regimen (2): Tenofovir (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
- If creatinine clearance 30–49 give 300 mg q48 hrs
- If creatinine clearance 10–29 give 300 mg q72-96 hrs
- If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
- If creatinine clearance <10 without dialysis there is no recommendation
- Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
- Preferred regimen (3): Entecavir (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior Lamivudine treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
- If creatinine clearance 30–49 give 0.25 mg PO qd OR 0.5 mg PO q48 hr for patients with no prior Lamivudine treatment, and 0.5 mg PO qd OR 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
- If creatinine clearance 10–29 give 0.15 mg PO qd OR 0.5 mg PO q 72 hr for patients with no prior Lamivudine treatment, and 0.3 mg PO qd OR 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
- If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd OR 0.5 mg PO q7 days for patients with no prior Lamivudine treatment, and 0.1 mg PO qd OR 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
- Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
- Alternative regimen (1): Interferon alpha (IFNα) 5 MU daily or 10 MU thrice weekly SC for 16 weeks
- Alternative regimen (2): Lamivudine (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 100 mg PO qd
- If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
- If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
- If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
- If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
- The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.
- Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
- Alternative regimen (3): Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 10 mg PO daily
- If creatinine clearance 30–49 give 10 mg PO every other day
- If creatinine clearance 10–19 10 mg PO every third day
- If hemodialysis patients give 10 mg PO every week following dialysis
- Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
- Alternative regimen (4): Telbivudine (LdT) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 600 mg PO once daily
- If creatinine clearance 30–49 600 give mg PO once every 48 hours
- If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
- If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis
- Note (1): duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
- Note (2): Observe for 3-6 months and treat if no spontaneous HBeAg loss.
- Note (3): Consider liver biopsy prior to treatment if compensated.
- Note (4): Immediate treatment if icteric or clinical decompensation.
- Note (5): Interferon alpha (IFNα)/ pegylated interferon-alpha (peg-IFNα), Lamivudine (LAM), Adefovir (ADV), Entecavir (ETV), tenofovir disoproxil fumarate (TDF) or telbivudine (LdT) may be used as initial therapy.
- Note (6): Adefovir (ADV) not preferred due to weak antiviral activity and high rate of resistance after 1st year.
- Note (7): Lamivudine (LAM) and Telbivudine (LdT) not preferred due to high rate of drug resistance.
- Note (8): End-point of treatment – Seroconversion from HBeAg to anti-HBe.
- Note (9): Interferon alpha (IFNα) non-responders / contraindications to IFNα change to Tenofovir (TDF)/Entecavir (ETV).
- 1.3. Children with elevated ALT greater than 2 times normal
- Preferred regimen(1): Interferon alpha (IFNα) 6 MU/m2 SC thrice weekly with a maximum of 10 MU
- Preferred regimen(2): Lamivudine (LAM) 3 mg/kg/d PO with a maximum of 100 mg/d.
- 2. Patients with HBeAg-negative chronic hepatitis B
- 2.1. HBV DNA >2,000 IU/mL and elevated ALT >2 times normal
- Preferred regimen (1): Pegylated IFN-alpha 180 mcg weekly SC for 1 year
- Preferred regimen (2): Tenofovir (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
- If creatinine clearance 30–49 give 300 mg q48 hrs
- If creatinine clearance 10–29 give 300 mg q72-96 hrs
- If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
- If creatinine clearance <10 without dialysis there is no recommendation
- Note: duration of treatment is more than 1 year
- Preferred regimen (3): Entecavir (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior Lamivudine treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine
- If creatinine clearance 30–49 give 0.25 mg PO qd OR 0.5 mg PO q48 hr for patients with no prior Lamivudine treatment, and 0.5 mg PO qd OR 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine
- If creatinine clearance 10–29 give 0.15 mg PO qd OR 0.5 mg PO q 72 hr for patients with no prior Lamivudine treatment, and 0.3 mg PO qd OR 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine
- If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd OR 0.5 mg PO q7 days for patients with no prior Lamivudine treatment, and 0.1 mg PO qd OR 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine.
- Note: duration of treatment is more than 1 year
- Alternative regimen (1): Interferon alpha (IFNα) 5 MU daily or 10 MU thrice weekly SC for 1 year
- Alternative regimen (2): Lamivudine (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 100 mg PO qd
- If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
- If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
- If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
- If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
- The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.
- Note: duration of treatment is more than 1 year
- Alternative regimen (3): Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 10 mg PO daily
- If creatinine clearance 30–49 give 10 mg PO every other day
- If creatinine clearance 10–19 10 mg PO every third day
- If hemodialysis patients give 10 mg PO every week following dialysis
- Note: duration of treatment is more than 1 year
- Alternative regimen (4): Telbivudine (LdT)Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 600 mg PO once daily
- If creatinine clearance 30–49 600 give mg PO once every 48 hours
- If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
- If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis
- Note (1): duration of treatment is more than 1 year
- Note (2): Interferon alpha (IFNα)/ pegylated interferon-alpha (peg-IFNα), Lamivudine (LAM), Adefovir (ADV), Entecavir (ETV), tenofovir disoproxil fumarate (TDF) or telbivudine (LdT) may be used as initial therapy.
- Note (3): Adefovir (ADV) not preferred due to weak antiviral activity and high rate of resistance after 1st year.
- Note (4): Lamivudine (LAM) and Telbivudine (LdT) not preferred due to high rate of drug resistance.
- Note (5): End-point of treatment – not defined
- Note (6): Interferon alpha (IFNα) non-responders / contraindications to IFNα change to Tenofovir (TDF)/Entecavir (ETV).
- 3. HBV DNA >2,000 IU/mL and elevated ALT 1->2 times normal
- Consider liver biopsy and treat if liver biopsy shows moderate/severe necroinflammation or significant fibrosis.
- 4. HBV DNA <2,000 IU/mL and ALT < upper limit normal (ULN)
- Observe, treat if HBV DNA or ALT becomes higher.
- 5. +/- HBeAg and detectable HBV DNA with Cirrhosis
- 5.1. Compensated Cirrhosis and HBV DNA >2,000
- Preferred regimen (1): Entecavir (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior Lamivudine treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine.
- If creatinine clearance 30–49 give 0.25 mg PO qd OR 0.5 mg PO q48 hr for patients with no prior Lamivudine treatment, and 0.5 mg PO qd OR 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine.
- If creatinine clearance 10–29 give 0.15 mg PO qd OR 0.5 mg PO q 72 hr for patients with no prior Lamivudine treatment, and 0.3 mg PO qd OR 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine.
- If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd OR 0.5 mg PO q7 days for patients with no prior Lamivudine treatment, and 0.1 mg PO qd OR 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine.
- Preferred regimen (2): Tenofovir (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
- If creatinine clearance 30–49 give 300 mg q48 hrs
- If creatinine clearance 10–29 give 300 mg q72-96 hrs
- If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
- If creatinine clearance <10 without dialysis there is no recommendation
- Alternative regimen (1): Lamivudine (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 100 mg PO qd
- If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
- If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
- If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
- If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
- The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.
- Alternative regimen (2): Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 10 mg PO daily
- If creatinine clearance 30–49 give 10 mg PO every other day
- If creatinine clearance 10–19 give 10 mg PO every third day
- If hemodialysis patients give 10 mg PO every week following dialysis
- Alternative regimen (3): Telbivudine (LdT) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 600 mg PO once daily
- If creatinine clearance 30–49 600 give mg PO once every 48 hours
- If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
- If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis
- Note (1): LAM and LdT not preferred due to high rate of drug resistance.
- Note (2): ADV not preferred due to weak antiviral activity and high risk of resistance after 1st year.
- Note (3): These patients should receive long-term treatment. However, treatment may be stopped in HBeAg-positive patients if they have confirmed HBeAg seroconversion and have completed at least 6 months of consolidation therapy and in HBeAg-negative patients if they have confirmed HBsAg clearance.
- 5.2. Compensated Cirrhosis and HBV DNA <2,000
- Consider treatment if ALT elevated.
- 5.3. Decompensated Cirrhosis
- Preferred regimen (1): Tenofovir (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
- If creatinine clearance 30–49 give 300 mg q48 hrs
- If creatinine clearance 10–29 give 300 mg q72-96 hrs
- If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
- If creatinine clearance <10 without dialysis there is no recommendation
- Preferred regimen (2): Entecavir (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior Lamivudine treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine.
- If creatinine clearance 30–49 give 0.25 mg PO qd OR 0.5 mg PO q48 hr for patients with no prior Lamivudine treatment, and 0.5 mg PO qd OR 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine.
- If creatinine clearance 10–29 give 0.15 mg PO qd OR 0.5 mg PO q 72 hr for patients with no prior Lamivudine treatment, and 0.3 mg PO qd OR 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine.
- If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd OR 0.5 mg PO q7 days for patients with no prior Lamivudine treatment, and 0.1 mg PO qd OR 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine.
- Preferred regimen (3): Lamivudine (LAM) AND Adefovir (ADV)
- Lamivudine (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 100 mg PO qd
- If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
- If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
- If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
- If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
- The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.
- Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 10 mg PO daily
- If creatinine clearance 30–49 give 10 mg PO every other day
- If creatinine clearance 10–19 give 10 mg PO every third day
- If hemodialysis patients give 10 mg PO every week following dialysis
- Preferred regimen (4): Telbivudine (LdT) AND Adefovir (ADV)
- Telbivudine (LdT) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 600 mg PO once daily
- If creatinine clearance 30–49 600 give mg PO once every 48 hours
- If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
- If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis
- Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 10 mg PO daily
- If creatinine clearance 30–49 give 10 mg PO every other day
- If creatinine clearance 10–19 give 10 mg PO every third day
- If hemodialysis patients give 10 mg PO every week following dialysis
- Note: coordinate treatment with transplant center and refer for liver transplant.
- Life-long treatment is recommended.
- 6. +/- HBeAg and undetectable HBV DNA with Cirrhosis
- Compensated Cirrhosis: Observe
- Uncompensated Cirrhosis: Refer for liver transplant
- Hepatitis C virus Return to Top
Chronic Hepatitis C
- 1. Treatment regimens for chronic hepatitis C virus genotype 1
- 1.1. Treatment regimens for genotype 1a:
- Preferred regimen (1): Ledipasvir 90 mg PO qd AND Sofosbuvir 400 mg PO qd for 12 weeks
- Preferred regimen (2): Paritaprevir 150 mg PO qd AND Ritonavir 100 mg PO qd AND Ombitasvir 25 mg PO qd AND Dasabuvir 250 mg PO bid AND weight-based Ribavirin PO qd () for 12 weeks (no cirrhosis) OR 24 weeks (cirrhosis)
- Preferred regimen (3): Sofosbuvir 400 mg PO qd AND Simeprevir 150 mg PO qd ± weight-based Ribavirin PO qd () for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis)
- Note: these regimens are recommended for treatment-naive patients with HCV genotype 1a infection.
- 1.2. Treatment regimens for genotype 1b:
- Preferred regimen (1): Ledipasvir 90 mg PO qd AND Sofosbuvir 400 mg PO qd for 12 weeks
- Preferred regimen (2): Paritaprevir PO 150 mg qd AND Ritonavir 100 mg PO qd AND Ombitasvir 25 mg PO qd AND Dasabuvir 250 mg PO bid for 12 weeks. The addition of weight-based Ribavirin PO qd (1000 mg ) is recommended in patients with cirrhosis
- Preferred regimen (3): Sofosbuvir 400 mg PO qd AND Simeprevir 150 mg PO qd for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis)
- Note: these regimens are recommended for treatment-naive patients with HCV genotype 1b infection.
- 2. Treatment regimens for chronic hepatitis C virus genotype 2
- Preferred regimen: Sofosbuvir 400 mg PO qd AND weight-based RBV (1000 mg ) for 12 weeks
- Note (1): This regimen are recommended for treatment-naive patients with HCV genotype 2 infection.
- Note (2): Extending treatment to 16 weeks is recommended in patients with cirrhosis.
- 3. Treatment regimens for chronic hepatitis C virus genotype 3
- Preferred regimen: Sofosbuvir 400 mg PO qd and weight-based Ribavirin PO qd (1000 mg ) PO qd for 24 weeks
- Alternative regimen: Sofosbuvir 400 mg and weight-based Ribavirin PO qd (1000 mg ) PO qd AND weekly PEG-IFN for 12 weeks is an acceptable regimen for IFN-eligible, treatment-naive patients with HCV genotype 3 infection.
- Note: These regimens are recommended for treatment-naive patients with HCV genotype 3 infection.
- 4. Treatment regimens for chronic hepatitis C virus genotype 4
- Preferred regimen (1): Ledipasvir 90 mg PO qd AND Sofosbuvir 400 mg PO qd for 12 weeks
- Preferred regimen (2): Paritaprevir 150 mg PO qd AND Ritonavir 100 mg PO qd AND Ombitasvir 25 mg PO qd AND weight-based Ribavirin PO qd (1000 mg ) for 12 weeks
- Preferred regimen (3): Sofosbuvir 400 mg PO qd AND weight-based Ribavirin PO qd (1000 mg ) for 24 weeks
- Alternative regimen (1): Sofosbuvir 400 mg PO qd AND weight-based Ribavirin PO qd (1000 mg ) AND weekly PEG-IFN for 12 weeks
- Alternative regimen (2): Sofosbuvir 400 mg PO qd AND Simeprevir 150 mg PO qd ± weight-based Ribavirin PO qd (1000 mg ) for 12 weeks
- Note: These regimens are accpetable for treatment-naive patients with HCV genotype 3 infection.
- 5. Treatment regimens for chronic hepatitis C virus genotype 5
- Preferred regimen: Sofosbuvir 400 mg PO qd AND weight-based Ribavirin PO qd(1000 mg ) AND weekly PEG-IFN for 12 weeks is recommended for treatment-naive patients with HCV genotype 5 infection.
- Alternative regimen: Weekly PEG-IFN AND weight-based Ribavirin PO qd (1000 mg ) for 48 weeks is an alternative regimen for IFN-eligible, treatment-naive patients with HCV genotype 5 infection.
- 6. Treatment regimens for chronic hepatitis C virus genotype 6
- Preferred regimen: Ledipasvir 90 mg PO qd AND Sofosbuvir PO qd 400 mg for 12 weeks is recommended for treatment-naive patients with HCV genotype 6 infection.
- Alternative regimen: Sofosbuvir 400 mg PO qd AND weight-based Ribavirin PO qd (1000 mg ) AND weekly PEG-IFN for 12 weeks is an alternative regimen for IFN-eligible, treatment-naive patients with HCV genotype 6 infection.
- Hepatitis D virus Return to Top
- Preferred regimen: Interferon alpha(IFNα) 5 MU daily OR 9 MU three times a week for 6–12 months
- Hepatitis E virus Return to Top
- Hepatitis E treatment
- Preferred regimen: supportive therapy. There is no specific treatment available.
- Note (1): Hepatitis E is usually self-limiting, hospitalization is generally not required.
- Note (2): Hospitalization is required for people with fulminant hepatitis and should also be considered for symptomatic pregnant women.
- Epstein-Barr virus Return to Top
- Epstein-Barr Virus (EBV)
- There is no vaccine to protect against EBV infection. You can help protect yourself by not kissing or sharing drinks, food, or personal items, like toothbrushes, with people who have EBV infection.
- There is no specific treatment for EBV. However, some things can be done to help relieve symptoms, including
- drinking fluids to stay hydrated
- getting plenty of rest
- taking over-the-counter medications for pain and fever
- Human herpesvirus 6 Return to Top
- Human herpesvirus 6 treatment
- Preferred regimen: supportive therapy
- Note: If patient is immunocompromised, there are no antiviral regimens stablished as there are no clinical trials to validate their use on these cases. Consider administering Ganciclovir, Acyclovir, Foscarnet OR Cidofovir.
- Roseola Return to Top
- Human herpesvirus 7 (roseola virus) treatment
- Preferred regimen: Supportive therapy
- Note (1): Immunocompetent hosts with uncomplicated skin manifestations associated with HHV-7, particularly roseola infantum and pityriasis rosea, need only symptomatic management
- Note (2): For HIV-positive patients, antiretroviral therapy may be advisable
- Note (3): The most active antiviral compounds against HHV-7 are Cidofovir and Foscarnet
- Human herpesvirus 8 (KSHV) Return to Top
- 1. Mild to moderate Kaposi sarcoma
- Preferred regimen: initiate or optimize ART
- 2. Advanced Kaposi sarcoma (ACTG Stage T1, including disseminated cutaneous or visceral Kaposi sarcoma)
- Preferred regimen: chemotherapy (per oncology consult) AND ART
- 3. Primary effusion lymphoma
- Preferred regimen: chemotherapy (per oncology consult) AND ART
- Note: Valganciclovir PO or Ganciclovir IV can be used as adjunctive therapy.
- 4. Multicentric Castleman's disease
- Preferred regimen (1): Valganciclovir 900 mg PO bid for 3 weeks
- Preferred regimen (2): Ganciclovir 5 mg/kg IV q12h for 3 weeks
- Preferred regimen (3): Valganciclovir 900 mg PO BID AND Zidovudine 600 mg PO q6h for 7–21 days
- Alternative regimen: Rituximab 375 mg/m2 given weekly for 4–8 weeks (may be an alternative to or used adjunctively with antiviral therapy)
- Herpes simplex virus Return to Top
- Genital Herpes
- 1.First Clinical Episode of Genital Herpes
- Preferred Regimen (1): Acyclovir 400 mg PO tid for 7–10 days
- Preferred Regimen (2): Acyclovir 200 mg PO five times a day for 7–10 days
- Preferred Regimen (3): Valacyclovir 1 g PO bid for 7–10 days
- Preferred Regimen (4): Famciclovir 250 mg PO tid for 7–10 days
- Note:Treatment can be extended if healing is incomplete after 10 days of therapy.
- 2.Established HSV-2 Infection
- 2.1 Suppressive Therapy for Recurrent Genital Herpes
- Preferred Regimen (1): Acyclovir 400 mg PO bid
- Preferred Regimen (2): Valacyclovir 500 mg PO qd
- Preferred Regimen (3): Valacyclovir 1 g PO qd
- Preferred Regimen (4): Famciclovir 250 mg PO bid
- Note(1):Daily therapy with Acyclovir for as long as 6 years and with Valacyclovir OR Famciclovir for 1 year
- Note(2):Valacyclovir 500 mg qd might be less effective than other Valacyclovir OR Acyclovir dosing regimens in persons who have very frequent recurrences (i.e., ≥10 episodes per year).
- 2.2 Episodic Therapy for Recurrent Genital Herpes
- Preferred Regimen (1): Acyclovir 400 mg PO tid for 5 days
- Preferred Regimen (2): Acyclovir 800 mg PO bid for 5 days
- Preferred Regimen (3): Acyclovir 800 mg PO tid for 2 days
- Preferred Regimen (4): Valacyclovir 500 mg PO bid for 3 days
- Preferred Regimen (5): Valacyclovir 1 g PO qd for 5 days
- Preferred Regimen (6): Famciclovir 125 mg PO bid for 5 days
- Preferred Regimen (7): Famciclovir 1 g PO bid for 1 day
- Preferred Regimen (8): Famciclovir 500 mg once, followed by 250 mg PO bid for 2 days
- 3. Severe Disease (disseminated infection, pneumonitis, or hepatitis) or CNS complications (e.g., meningoencephalitis).
- Preferred Regimen: Acyclovir 5–10 mg/kg IV q8h for 2–7 days or until clinical improvement is observed, followed by oral antiviral therapy to complete at least 10 days of total therapy. HSV encephalitis requires 21 days of intravenous therapy. Impaired renal function warrants an adjustment in acyclovir dosage.
- 4. Special Considerations
- 4.1 HIV Infection
- 4.1.1 Daily Suppressive Therapy in Persons with HIV
- Preferred Regimen (1): Acyclovir 400–800 mg PO bid /tid
- Preferred Regimen (2): Valacyclovir 500 mg PO bid
- Preferred Regimen (3): Famciclovir 500 mg PO bid
- 4.1.2 Episodic Infection in Persons with HIV
- Preferred Regimen (1): Acyclovir 400 mg PO tid for 5–10 days
- Preferred Regimen (2): Valacyclovir 1 g PO bid for 5–10 days
- Preferred Regimen (3): Famciclovir 500 mg PO bid for 5–10 days
- Note: For severe HSV disease, initiating therapy with Acyclovir 5–10 mg/kg IV q8 h might be necessary.
- 4.2 Genital Herpes in Pregnancy
- Suppressive therapy of pregnant women with recurrent genital herpes
- Preferred Regimen (1): Acyclovir 400–800 mg PO bid /tid
- Preferred Regimen (2): Valacyclovir 500 mg PO bid
- Note:Treatment recommended starting at 36 weeks of gestation.
- 4.3 Neonatal Herpes
- Known or suspected neonatal herpes
- Preferred Regimen: Acyclovir 20 mg/kg IV q 8 h
- Note (1): Treatment for 14 days if disease is limited to the skin and mucous membranes, or
- Note (2): Treatment for 21 days for disseminated disease and that involving the central nervous system.
- 4.4 Acyclovir-resistant genital herpes
- Preferred Regimens: Foscarnet 40–80 mg/kg IV q8 h until clinical resolution is attained
- Alternative Regimen (1): Cidofovir 5 mg/kg IV once weekly might also be effective.
- Alternative Regimen (2): Imiquimod topical preparations should be applied to the lesions qd for 5 consecutive days.
- 4.5 Management of Sex Partners
- Preferred Regimen (1): Acyclovir 400 mg PO tid for 7–10 days
- Preferred Regimen (2): Acyclovir 200 mg PO five times a day for 7–10 days
- Preferred Regimen (3): Valacyclovir 1 g PO bid for 7–10 days
- Preferred Regimen (4): Famciclovir 250 mg PO tid for 7–10 days
- Note:The sex partners of persons who have genital herpes can benefit from evaluation and counseling. Symptomatic sex partners should be evaluated and treated
- 4.6 Allergy, Intolerance, and Adverse Reactions
- Allergic and other adverse reactions to oral Acyclovir, Valacyclovir, and Famciclovir are rare. Desensitization to acyclovir has been described.
# vzv
- Varicella-zoster virus Return to Top
- 1. Varicella zoster treatment
- 1.1 Non Immunocompromised person
- Preferred regimen (1): Acyclovir 500 mg PO five times a dayfor 7-10 days
- Preferred regimen (2): Famciclovir 500 mg PO tid for 7 days
- Preferred regimen (3): Valacyclovir 1 g PO tid for 7 days
- Preferred regimen (4): Brivudin 125 mg PO qd for 7 days
- 1.2 Immunocompromised person requiring hospitalization or persons with sever neurologic complications
- Preferred regimen (1): Acyclovir 10 mg/ kg IV q8h for 7-10 days
- Preferred regimen (2): Foscarnet 40 mg/ kg IV q8h until lesions are healed
- Note: Brivudin is not available in USA and has not been approved by FDA. Foscarnet is not approve by FDA
- 2. Treatment of VZV complications
- 2.1 VZV ophthalmicus
- Treatment includes the following
- (1) Famciclovir OR Valacyclovir for 7–10 days, preferably started within 72 h of rash onset (with Acyclovir IV given as needed for retinitis), to resolve acute disease and inhibit late inflammatory recurrences, AND Prednisone 20 mg PO tid for 4 days or bid for 6 days, and then qd for 4 day
- (2) Bacitracin-Polymyxin ophthalmic ointment administered bid ,to protect the ocular surface;
- (3) Topical Prednisolone 0.125%–1% 2–6 times daily prescribed and managed only by an ophthalmologist for corneal immune disease, episcleritis, scleritis, or iritis;
- (4) Homatropine 5% bid as needed for iritis
- (5) Latanaprost qd and/or Timolol maleate ophthalmic gel forming solution every morning)ocular pressure–lowering drugs given as needed for glaucoma
- Note (1): Systemic steroids are indicated in the presence of moderate to severe pain or rash, particularly if there is significant edema, which may cause orbital apex syndrome through pressure on the nerves entering the orbit.
- Note (2): pain medications and cool to tepid wet compresses (if tolerated) and no topical antivirals, because they are ineffective
- 2.2 VZV retinitis
- Preferred regimen: Acyclovir IV 10–15 mg/kg q8h for 10–14 days followed by Valacyclovir PO 1 g tid daily for 4–6 weeks
- 3 Recommendations for treating varicella zoster virus (VZV) Infections in HIV-Infected adults and adolescents
- 3.1 Primary Varicella Infection (Chickenpox)
- 3.1.1 Uncomplicated Cases
- Preferred regimen (1):Valacyclovir 1 g PO tid for 5–7 days
- Preferred regimen (2): Famciclovir 500 mg PO tid for 5–7 days
- Alternative regimen: Acyclovir 800 mg PO 5 times daily for 5–7 days
- 3.1.2 Severe or Complicated Cases
- Preferred regimen: Acyclovir 10–15 mg/kg IV q8h for 7–10 days
- Note: May switch to oral Famciclovir, Valacyclovir, or Acyclovir after defervescence if no evidence of visceral involvement is evident
- 3.2 Herpes Zoster (Shingles)
- 3.2.1 Acute Localized Dermatomal
- Preferred regimen (1): Valacyclovir 1000 mg PO tid for 7–10 days
- Preferred regimen (2): Famciclovir 500 mg PO tid for 7–10 days
- Alternative Therapy: Acyclovir 800 mg PO 5 times daily for 7–10 days
- Note: Longer duration should be considered if lesions resolve slowly
- 3.2.2 Extensive Cutaneous Lesion or Visceral Involvement
- Preferred regimen: Acyclovir 10–15 mg/kg IV q8h until clinical improvement is evident, then switch to (Valacyclovir 1 g PO tid, Famciclovir 500 mg PO tid, or Acyclovir 800 mg PO 5 times daily)—to complete a 10–14 day course, when formation of new lesions has ceased and signs and symptoms of visceral VZV infection are improving
- 3.3 PORN (Progressive outer retinal necrosis)
- Preferred regimen: Ganciclovir 5 mg/kg and/or Foscarnet 90 mg/kg IV q12h AND Ganciclovir 2 mg/0.05mL and/or foscarnet 1.2 mg/0.05mL intravitreal twice weekly.
- Note: Duration of therapy is not well defined and should be determined based on clinical, virologic, and immunologic response in consultation with experienced ophthalmologist and optimize ART regimen.
- Note: Ganciclovir ocular implants are no longer commercially available
- 3.4 ARN (Acute retinal necrosis)
- Preferred regimen: Acyclovir 10-15 mg/kg IV q8h for 10–14 days, followed by Valacyclovir 1 g PO tid for 6 weeks AND Ganciclovir 2 mg/0.05mL intravitreal qd/bid twice weekly
- Note: Duration of therapy is not well defined and should be determined based on clinical, virologic, and immunologic response in consultation with experienced ophthalmologist
- 4 Prevention of varicella zoster virus (VZV) Infections in HIV-Infected Adults and Adolescents
- 4.1 Pre-Exposure Prevention of VZV Primary Infection
- Indications
- Adult and adolescent patients with CD4 count ≥200 cells/mm3 without documentation of vaccination, health-care provider diagnosis or verification of a history of varicella or herpes zoster, laboratory confirmation of disease, or persons who are seronegative for VZV. Routine VZV serologic testing in HIV-infected adults and adolescents is not recommended.
- Vaccination
- Primary varicella vaccination (Varivax™), 2 doses (0.5 mL SQ) administered 3 months apart
- If vaccination results in disease because of vaccine virus, treatment with acyclovir is recommended.
- VZV-susceptible household contacts of susceptible HIV-infected persons should be vaccinated to prevent potential transmission of VZV to their HIV-infected contacts.
- If post-exposure VariZIG has been administered, wait at least 5 months before varicella vaccination.
- If post-exposure acyclovir has been administered, wait at least 3 days before varicella vaccine.
- 4.2 Post-Exposure Prophylaxis
- Indication
- Close contact with a person who has active varicella or herpes zoster, and
- Is susceptible to VZV (i.e., has no history of vaccination or of either condition, or is known to be VZV seronegative)
- Preferred regimen: VariZIG 125 IU /10 kg (maximum of 625 IU) IM, administered as soon as possible and within 10 days after exposure to a person with active varicella or herpes zoster
- Alternative regimen (Begin 7–10 Days After Exposure): Acyclovir 800 mg PO 5 times/day for 5–7 days OR Valacyclovir 1 g PO tid for 5–7 days
- If post-exposure VariZIG has been administered, wait at least 5 months before varicella vaccination.
- Note: Patients receiving monthly high dose IVIG (i.e., >400 mg/kg) are likely to be protected against VZV and probably do not require VariZIG if the last dose of IVIG was administered <3 weeks before VZV exposure.
- Note: Neither these pre-emptive interventions nor post-exposure varicella vaccination have been studied in HIV-infected adults and adolescents.
- If acyclovir or valacyclovir is used, varicella vaccines should not be given until at least 72 hours after the last dose of the antiviral drug.
# hpv
- Human papillomavirus Return to Top
- Anogenital Warts
- 1.Preferred regimen for External Anogenital Warts(i.e., penis, groin, scrotum, vulva, perineum, external anus, and perianus)
- 1.1 Patient-Applied: Imiquimod 3.75% or 5% cream OR Podofilox 0.5% solution or gel OR Sinecatechins 15% ointment
- 1.2 Provider-Administered: Cryotherapy with liquid nitrogen or cryoprobe OR Surgical removal either by tangential scissor excision, tangential shave excision, curettage, laser,or electrosurgery OR Trichloroacetic acid (TCA) OR Bichloroacetic acid (BCA) 80%-90% solution
- Note (1): Many persons with external anal warts also have intra-anal warts. Thus, persons with external anal warts might benefit from an inspection of the anal canal by digital examination, standard anoscopy, or high-resolution anoscopy.
- Note (2): Might weaken condoms and vaginal diaphragms.
- 2.Alternative Regimens for External Genital Warts
- 2.1 Urethral Meatus Warts
- Preferred regimen: Cryotherapy with liquid nitrogen OR Surgical removal
- 2.2 Vaginal Warts
- Preferred regimen: Cryotherapy with liquid nitrogen OR Surgical removal OR (TCA OR BCA 80%–90% solution)
- Note: The use of a cryoprobe in the vagina is not recommended because of the risk for vaginal perforation and fistula formation
- 2.3 Cervical Warts
- Preferred regimen: Cryotherapy with liquid nitrogen OR Surgical removal OR (TCA OR BCA 80%–90% solution)
- Note: Management of cervical warts should include consultation with a specialist.For women who have exophytic cervical warts, a biopsy evaluation to exclude high-grade SIL must be performed before treatment is initiated.
- 2.4 Intra-anal Warts
- Preferred regimen: Cryotherapy with liquid nitrogen OR Surgical removal OR (TCA OR BCA 80%–90% solution)
- Note: Management of intra-anal warts should include consultation with a specialist.
- 3. Specific considerations
- 3.1 Follow-up
- Most anogenital warts respond within 3 months of therapy. Factors that might affect response to therapy include immunosuppression and treatment compliance. In general, warts located on moist surfaces or in intertriginous areas respond best to topical treatment. A new treatment modality should be selected when no substantial improvement is observed after a complete course of treatment or in the event of severe side effects; treatment response and therapy-associated side effects should be evaluated throughout the course of therapy.
- 3.2 Management of sex partners
- Persons should inform current partner(s) about having genital warts because the types of HPV that cause warts can be passed on to partners. Partners should receive counseling messages that partners might already have HPV despite no visible signs of warts, so HPV testing of sex partners of persons with genital warts is not recommended.
- 3.3 Pregnancy
- Podofilox (podophyllotoxin), Podophyllin, and Sinecatechins should not be used during pregnancy. Imiquimod appears to pose low risk but should be avoided until more data are available.
- Cesarean delivery is indicated for women with anogenital warts if the pelvic outlet is obstructed or if vaginal delivery would result in excessive bleeding.
- Pregnant women with anogenital warts should be counseled concerning the low risk for warts on the larynx of their infants or children (recurrent respiratory papillomatosis).
- 3.4 HIV infection
- Data do not support altered approaches to treatment for persons with HIV infection.
- Squamous cell carcinomas arising in or resembling anogenital warts might occur more frequently among immunosuppressed persons, therefore requiring biopsy for confirmation of diagnosis for suspicious cases
- 3.5 High-grade squamous intraepithelial lesions
- Biopsy of an atypical wart might reveal HSIL or cancer of the anogenital tract. In this instance, referral to a specialist for treatment is recommended.
# influenza A& B
- Influenza A & B Return to Top
- Antiviral Medications Recommended for Treatment of Influenza
- 1. Adults
- Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg PO bid for 5 days
- Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) bid for 5 days
- Preferred regimen (3): Peramivir (Rapivab®) 600 mg IV for 15-30 minutes (single dose)
- Note: FDA approved and recommended Peramivir (Rapivab®) for use in adults ≥18 yrs
- 2. Children
- 2.1 Children < 1 yr
- Preferred regimen: Oseltamivir (Tamiflu®) 3 mg/kg/dose PO bid for 5 days
- 2.2 Children > 1 yr
- 2.2.1 Children ≤ 15 kg
- Preferred regimen: Oseltamivir (Tamiflu®) 30 mg PO bid for 5 days
- 2.2.2 Children > 15 to 23 kg
- Preferred regimen: Oseltamivir (Tamiflu®) 45 mg PO bid for 5 days
- 2.2.3 Children > 23 to 40 kg
- Preferred regimen: Oseltamivir (Tamiflu®) 60 mg PO bid for 5 days
- 2.2.4 Children > 40 kg
- Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg PO bid for 5 days
- Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) bid for 5 days, may be considered for children > 7 yrs old
- 3. Adult Patients with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis
- 3.1 Oseltamivir
- Creatinine clearance 61 to 90 mL/min-75 mg PO bid for 5 days
- Creatinine clearance 31 to 60 mL/min-30 mg PO bid for 5 days
- Creatinine clearance 10 to 30 mL/min-30 mg PO qd for 5 days
- ESRD Patients on Hemodialysis
- Creatinine clearance ≤10 mL/min-30 mg after every hemodialysis cycle. Treatment duration not to exceed 5 days
- ESRD Patients on Continuous Ambulatory Peritoneal Dialysis-A single 30 mg dose administered immediately after a dialysis exchange
- 3.2 Peramivir
- Creatinine clearance >50 mL/min-600mg IV single dose
- Creatinine clearance 30 to 49 mL/min-200mg IV single dose
- Creatinine clearance 10 to 29 mL/min-100mg IV single dose
- ESRD Patients on Hemodialysis-Dose administered after dialysis at a dose adjusted based on creatinine clearance
- Note: No dose adjustment is recommended for inhaled zanamivir for a 5-day course of treatment for patients with renal impairment.
- 4. Antiviral Medications Recommended for Chemoprophylaxis of Influenza
- 4.1. Adults
- Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg PO qd for 7days
- Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) qd for 7 days
- 4.2. Children
- 4.2.1 Children < 1 yr
- Preferred regimen: Oseltamivir (Tamiflu®) 3 mg/kg/dose PO qd for 7 days
- 4.2.2 Children > 1 yr
- 4.2.2.1 Children ≤ 15 kg
- Preferred regimen: Oseltamivir (Tamiflu®) 30 mg PO qd for 7 days
- 4.2.2.2 Children > 15 to 23 kg
- Preferred regimen: Oseltamivir (Tamiflu®) 45 mg PO qd for 7 days
- 4.2.2.3 Children > 23 to 40 kg
- Preferred regimen: Oseltamivir (Tamiflu®) 60 mg PO qd for 7 days
- 4.2.2.4 Children > 40 kg
- Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg PO qd for 7 days
- Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) qd for 7 days, may be considered for children > 7 yrs older
- Note: If child is < 3 months old, use of Oseltamivir for chemoprophylaxis is not recommended unless situation is judged critical due to limited data in this age group.
# Avian influenza
- Avian influenza Return to Top
- 1. Preferred regimen:Oseltamivir 75 mg PO qd for a minimum 10 days
- Note:Patients with severe disease may have diarrhea and may not absorb oseltamivir efficiently
- 2. Patients with Avian Influenza who have diarrhea and malabsorption
- Preferred regimen (1): Zanamivir 10 mg inhaled bid for minimum 5 days
- Preferred regimen (2): Peramivir 600 mg IV as a single dose for 1 day
- Note(1): Preliminary evidence demonstrates that Neuraminidase inhibitor can reduce the duration of viral replication and improve survival among patients with avian influenza. In cases of suspected avian influenza, one of the following 3 neuraminidase inhibitors should be administered as soon possible, preferably within 48 hours of symptom onset.
- Note(2): The use of Corticosteroids is not recommended.
- Note(3): Physicians may consider increasing either the recommended daily dose and/or the duration of treatment in cases of severe disease.
- Note(4): The use of Amantadine is not recommended as most H5N1 and H7N9 avian influenza viruses are resistant to it.
- Note(5): Supportive care is also an important cornerstone of the care of patients with avian influenza. Considering the severity of the illness and the possible complications, patients may require fluid resuscitation, vasopressors, intubation and ventilation, paracentesis, hemodialysis or hemofiltration, and parentral nutrition.
- Swine influenza Return to Top
- Swine influenza
- 1. Condition1: Patients who have severe or progressive clinical illness
- Preferred regimen: Oseltamivir 150 mg PO bid
- Note (1): Treatment duration depends on clinical response
- Note (2): Where the clinical course remains severe or progressive, despite 5 or more days of antiviral treatment, monitoring of virus replication and shedding, and antiviral drug susceptibility testing is desirable
- Note (3): Antiviral treatment should be maintained without a break until virus infection is resolved or there is satisfactory clinical improvement
- Note (4): Patients who have severe or progressive clinical illness, but who are unable to take oral medication may be treated with oseltamivir administered by nasogastric or orogastric tube
- 2. Condition2: In situations where oseltamivir is not available, or not possible to use, patients who have severe or progressive clinical illness
- Preferred regimen: Zanamivir inhaled
- Note: Zanamivir IV should be considered where available and is recommended for those with serious or progressive illness. If not available, Peramivir IV may be considered
- 3. Condition3: Severely immunosuppressed patients
- Preferred regimen: Antiviral chemoprophylaxis by using Oseltamivir OR Zanamivir
- Measles Return to Top
- Measles
- 1.1. Prevention
- 1.1.1. Vaccines
- Note (1): Measles can be prevented with measles-containing vaccine, which is primarily administered as the combination measles-mumps-rubella (MMR) vaccine. The combination measles-mumps-rubella-varicella (MMRV) vaccine can be used for children aged 12 months through 12 years for protection against measles, mumps, rubella and varicella. Single-antigen measles vaccine is not available.
- Note (2): Vaccination recommendations
- Children: CDC recommends routine childhood immunization for MMR vaccine starting with the first dose at 12 through 15 months of age, and the second dose at 4 through 6 years of age or at least 28 days following the first dose.
- Students at post-high school educational institutions: Students at post-high school educational institutions without evidence of measles immunity need two doses of MMR vaccine, with the second dose administered no earlier than 28 days after the first dose.
- Adults: People who are born during or after 1957 who do not have evidence of immunity against measles should get at least one dose of MMR vaccine.
- International travelers: People 6 months of age or older who will be traveling internationally should be protected against measles. Before travelling internationally,
- Infants 6 through 11 months of age should receive one dose of MMR vaccine
- Children 12 months of age or older should have documentation of two doses of MMR vaccine (the first dose of MMR vaccine should be administered at age 12 months or older; the second dose no earlier than 28 days after the first dose)
- Teenagers and adults born during or after 1957 without evidence of immunity against measles should have documentation of two doses of MMR vaccine, with the second dose administered no earlier than 28 days after the first dose
- 1.1.2. Post-exposure Prophylaxis
- 1.1.2.1. Indication
- People exposed to measles who cannot readily show that they have evidence of immunity against measles should be offered post-exposure prophylaxis (PEP) or be excluded from the setting (school, hospital, childcare). MMR vaccine, if administered within 72 hours of initial measles exposure, or immunoglobulin (IG), if administered within six days of exposure, may provide some protection or modify the clinical course of disease.
- Note (1): If MMR vaccine is not administered within 72 hours of exposure as PEP, MMR vaccine should still be offered at any interval following exposure to the disease in order to offer protection from future exposures. People who receive MMR vaccine or IG as PEP should be monitored for signs and symptoms consistent with measles for at least one incubation period.
- Note (2): If many measles cases are occurring among infants younger than 12 months of age, measles vaccination of infants as young as 6 months of age may be used as an outbreak control measure. Note that children vaccinated before their first birthday should be revaccinated when they are 12 through 15 months old and again when they are 4 through 6 years of age.
- Note (3): People who are at risk for severe illness and complications from measles, such as infants younger than 12 months of age, pregnant women without evidence of measles immunity, and people with severely compromised immune systems, should receive IG. Intramuscular IG (IGIM) should be given to all infants younger than 12 months of age who have been exposed to measles.
- Note (4): For infants aged 6 through 11 months, MMR vaccine can be given in place of IG, if administered within 72 hours of exposure. Because pregnant women might be at higher risk for severe measles and complications, intravenous IG (IGIV) should be administered to pregnant women without evidence of measles immunity who have been exposed to measles. People with severely compromised immune systems who are exposed to measles should receive IGIV regardless of immunologic or vaccination status because they might not be protected by MMR vaccine.
- Preferred regimen: The recommended dose of IGIM is 0.5 mL/kg of body weight (maximum dose = 15 mL) and the recommended dose of IGIV is 400 mg/kg.
- Note (5): If a healthcare provider without evidence of immunity is exposed to measles, MMR vaccine should be given within 72 hours, or IG should be given within 6 days when available. Exclude healthcare personnel without evidence of immunity from duty from day 5 after first exposure to day 21 after last exposure, regardless of post-exposure vaccine.
- 1.2. Treatment
- Note (1): There is no specific antiviral therapy for measles. Medical care is supportive and to help relieve symptoms and address complications such as bacterial infections.
- Note (2): Severe measles cases among children, such as those who are hospitalized, should be treated with vitamin A. Vitamin A should be administered immediately on diagnosis and repeated the next day. The recommended age-specific daily doses are
- 50,000 IU for infants younger than 6 months of age
- 100,000 IU for infants 6–11 months of age
- 200,000 IU for children 12 months of age and older
- Middle East respiratory syndrome Return to Top
- Middle East Respiratory Syndrome treatment
- Preferred regimen: supportive care. There is no antiviral recommended for this infection at this moment, even though experimental therapies are at research (IFNs, Ribavirin, Lopinavir, Mycophenolic acid, Cyclosporine, Chloroquine, Chlorpromazine, Loperamide, 6-mercaptopurine and 6-thioguanine). Supportive care include: administer oxygen to patients with severe acute pulmonary infection with signs of respiratory distress, hypoxaemia or shock; use conservative fluids management, avoid administering high-dose systemic glucocorticoids, use non-invasive ventilation, but, if its nor effective, do not delay endotracheal intubation; use lung-protective strategy for intubated patients, recognize sepsis as early as possible and treat it accordingly.
# Parainfluenza virus
- Parainfluenza virus Return to Top
- Parainfluenza virus
- 1. Adults
- Preferred regimen: Ribavirin PO/IV 10 mg/kg q8h
- Day 1: Start with 600 mg loading dose,then 200 mg q8h
- Day 2: 400 mg q8h
- Day 3: Increase the dose to a maximum of 10 mg/kg q8h
- 1.1 In case of adverse events
- Preferred regimen: Decrease dose or discontinue Ribavirin
- 1.2 Creatinine clearance
- 30–50 mL/min: Ribavirin PO/IV maximal 200 mg q8h
- 10–30 mL/ min: No recommendation can be given
- Parvovirus B19 Return to Top
- Parvovirus B19
- 1. Erythema infectiosum
- Supportive therapy: Symptomatic treatment only
- 2. Arthritis/arthalgia
- Preferred regimen: Nonsteroidal anti-inflammatory drugs (NSAID)
- 3.Transient aplastic crisis
- Supportive therapy: Transfusions and oxygen
- 4. Fetal hydrops
- Supportive therapy: Intrauterine blood transfusion
- 5. Chronic infection with anemia
- Preferred regimen: IVIG and transfusion
- 6.Chronic infection without anemia
- Preferred regimen: IVIG
- BK virus Return to Top
- Human polyomavirus (BK virus) treatment
- Maintenance regimen consisting of triple immunosuppression therapy: Calcineurin inhibitor (Cyclosporine or Tacrolimus) AND an antimetabolite (Azathioprine, Mycophenolate mofetil, or Mycophenolate sodium), AND Prednisone is to discontinue completely the antimetabolite (usually Mycophenolate) and decrease the dose of the Calcineurin inhibitor.
- Alternative regimen (1): Decrease the Mycophenolate dose by 50 percent, followed by a 50 percent decrease in the Calcineurin inhibitor at three months if decoy cells persist. If using this approach, the target serum Tacrolimus trough level is 4 to 6, and the target serum Cyclosporine trough level is 60 to 100 ng/mL. Mycophenolate may be discontinued completely if viral activation persists. Maintenance immunosuppression then consists of Tacrolimus and low-dose Prednisone.
- Alternative regimen (2): Reduce both the Calcineurin inhibitor and the Mycophenolate, which allows both the targeting of two pathways and lower total immunosuppression.
- Note (1): For those who are hypogammaglobulinemic, we administer intravenous immunoglobulins (IV IG) in replacement doses of 500 mg/kg. Quantitative immunoglobulins should be checked two to three months later to determine whether hypogammaglobulinemia has recurred. Intravenous immunoglobulins (IV IG) is also an option in certain settings, based upon polymerase chain reaction (PCR) and kidney biopsy results. IVIG may contain antibodies against BK and JC virus since these viruses are ubiquitous in the general population.
- Note (2): The goals of decreased immunosuppressive therapy are to restrain viral replication without triggering rejection.
- Note (3): Reduced immunosuppression (defined as lowering mean doses of Mycophenolate and Tacrolimus) resulted in the successful elimination of viremia (mean period of six months) and allograft survival.
- Note (4): Alternative approaches to reducing immunosuppression have also been effective
- 4.1 Changing from Tacrolimus to low-dose Cyclosporine not only reduces the effect of the Calcineurin inhibitor, but also reduces Mycophenolate concentrations.
- 4.2 Replacing the Calcineurin inhibitor with Sirolimus, with or without discontinuation of the antimetabolite, has the advantage of avoiding the long-term Calcineurin inhibitor-related nephrotoxic effects.
- 4.3 Lowering the dose of Calcineurin inhibitors may slow the loss of renal function.
- Primary Regimens
- Decrease immunosuppression if possible. (Cornerstone of Treatment)
- Suggested antiviral therapy is based on anecdotal data. If progressive renal dysfunction:
- Fluoroquinolone AND IVIG 500 mg/kg IV AND Leflunomide 100 mg for daily for 3 days, then 10-20 mg PO daily
- If refractory to all of the above, add Cidofovir 5 mg/kg once per week for 2 weeks, then once every other week if refractory to all of the above
- Ancillary Therapies in BK Virus Nephropathy
- Cidofovir 0.25-1.0 mg/kg IV biweekly for 8 wk without Probenecid, prehydration recommended
- Leflunomide 100 mg loading dose for 3 days, 20-60 mg/day, goal Leflunomide trough 50-100 ng/mL (consider lower trough goals of 20-40 ng/mL given hemolysis risk)
- IV Ig 1-2 g/kg IV for 1-2 doses or 150 mg/kg IV biweekly for 8 wk
- Fluoroquinolones-Ciproflaxacin 500 mg/day, duration dependent on virological response.
- JC virus Return to Top
- Progressive Multifocal Leukoencephalopathy (PML) caused by JC Virus ( John Cunningham virus) infections
- There is no specific antiviral therapy for JC virus infection.
- The main treatment approach is to reverse the immunosuppression caused by HIV.
- Initiate anti retroviral therapy (ART) immediately in ART-naive patients .
- Optimize ART in patients who develop Progressive Multifocal Leukoencephalopathy in phase of HIV viremia on ART .
- Corticosteroids may be used for Progressive Multifocal Leukoencephalopathy- immune reconstitution inflammatory syndrome (IRIS) characterized by contrast enhancement, edema or mass effect, and with clinical deterioration
- Rabies Return to Top
- Rabies treatment
- Preferred regimen: no specific therapetics agents are available once the disease is established.
- Note: There are vaccines and immunoglobulins available for postexposure prophylaxis
- Postexposure prophylaxis
- 1. For non immunized individuals
- 2. For immunized individuals
- Respiratory Syncytial Virus Return to Top
- Respiratory syncytial virus treatment
- Supportive therapy
- Hydration and supplemental oxygen.
- Routine use of Ribavirin not recommended. Ribavirin therapy associated with small increases in O2 saturation.
- No consistent decrease in need for mechanical ventilation or ICU stays. High cost, aerosol administration and potential toxicity
- Note (1): In adults, Respiratory syncytial virus accounted for 10.6% of hospitalizations for pneumonia, 11.4% for COPD, 7.2% for asthma & 5.4% for CHF in pts >65 yrs of age . Respiratory syncytial virus caused 11% of clinically important respiratory illnesses in military recruits
- Note (2): Respiratory Syncytial Virus major cause of morbidity in neonates/infants.
- Note (3): Nucleic acid test now approved to detect 12 respiratory viruses (xTAG Respiratory Viral Panel, Luminex Molecular Diagnostics).
- Prevention of Respiratory syncytial virus
- 1. In children <24 months old with chronic lung disease of prematurity (formerly broncho-pulmonary dysplasia) requiring supplemental oxygen or
- 2. In premature infants (<32 wks gestation) and <6 months old at start of Respiratory syncytial virus season or
- 3. In children with selected congenital heart diseases.
- Preferred regimen for prevention of Respiratory syncytial virus: Palivizumab (Synagis) 15 mg per kg IM q month Nov.-April
- Rhinovirus Return to Top
- Rhinovirus treatment (commom cold)
- Supportive therapy
- 1. Symptomatic treatment-Ipratropium bromide intranasal (2 sprays tid) AND Clemastine 1.34 mg 1–2 tab PO bid–tid (over the counter)
- 2. Symptomatic relief by Ipratropium nasal spray decreases rhinorrhea and sneezing vs placebo. AND Clemastine (an antihistamine) decreases sneezing, rhinorrhea but associated with dry nose, mouth & throat in 6–19%.OR Oral pleconaril given within 24 hrs of onset reduced duration (1 day) & severity of “cold symptoms” in DBPCT (p < .001).
- Note (1): No antiviral treatment indicated .
- Note (2): Found in half of children with community-acquired pneumonia; role in pathogenesis unclear (CID 39:681, 2004).
- Note (3): High rate of rhinovirus identified in children with significant lower resp tract infections
- Rotavirus Return to Top
- Rotavirus treatment,
- Treatment of diarrhoea caused by rotavirus
- Rehydration with oral rehydration salts (ORS) solution. oral rehydration salts (ORS) solution is a mixture of clean water, salt and sugar. It costs a few cents per treatment. oral rehydration salts (ORS) solution is absorbed in the small intestine and replaces the water and electrolytes lost in the faeces.
- Zinc supplements-with zinc supplements reduce the duration of a diarrhoea episode by 25% and are associated with a 30% reduction in stool volume.
- Rehydration with intravenous fluids in case of severe dehydration or shock.
- Nutrient-rich foods the vicious circle of malnutrition and diarrhoea can be broken by continuing to give nutrient-rich foods including breast milk during an episode, and by giving a nutritious diet including exclusive breastfeeding for the first six months of life to children when they are well.
- Consulting a health professional , in particular for management of persistent diarrhoea or when there is blood in stool or if there are signs of dehydration.
- Prevention
- Access to safe drinking-water
- Use of improved sanitation
- Hand washing with soap
- Exclusive breastfeeding for the first six months of life
- Good personal and food hygiene
- Health education about how infections spread; and Rotavirus vaccination.
# Smallpox
- Smallpox Return to Top
- Smallpox
- Supportive care is the mainstay of therapy.
- Currently, there are no anti-viral drugs of proven efficacy.
- Recently, animal studies suggest that cidofovir and its cyclic analogues, given at the time of or immediately after exposure, have promise for the prevention of cowpox, vaccinia, and monkeypox.
- Patients need adequate hydration and nutrition, because substantial amounts of fluid and protein can be lost by febrile persons with dense, often weeping lesions.
- 1. Secondary bacterial infection
- Penicillinase-resistant antimicrobial agents should be used
- If smallpox lesions are secondarily infected,
- If bacterial infection endangers the eyes
- Daily eye rinsing is required in severe cases.
- Topical idoxuridine should be considered for the treatment of corneal lesions, although its efficacy is unproved for smallpox.
- If the eruption is very dense and widespread.
# HIV/AIDS
- HIV/AIDS Return to Top
]- 1. Antiretroviral regimen options for treatment-naive patients
- 1.1. Integrase strand transfer inhibitor-based regimens
- Preferred regimen (1): Dolutegravir 50 mg PO qd AND Abacavir 600 mg-Lamivudine 300 mg PO qd in patients who are HLA-B*5701-negative
- Preferred regimen (2): Dolutegravir 50 mg PO qd AND Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Preferred regimen (3): Elvitegravir 150 mg-Cobicistat 150 mg-Tenofovir 300 mg-Emtricitabine 200 mg PO qd in patients with estimated CrCl ≥ 70 mL/min/1.73
- Preferred regimen (4): Raltegravir 400 mg PO bid AND Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Alternative regimen (1): Efavirenz 600 mg PO qd OR Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Alternative regimen (2): Rilpivirine 25 mg PO qd AND (Tenofovir 300 mg PO qd OR Emtricitabine 200 mg PO qd) for patients with CD4 count >200 cells/microL
- Alternative regimen (3): Raltegravir 400 mg PO bid AND (Abacavir 600 mg PO qd OR Lamivudine 300 mg PO qd) in patients who are HLA-B*5701-negative
- 1.2. Protease inhibitor-based regimen
- Preferred regimen: Darunavir 800 mg-Ritonavir 100 mg PO qd AND Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Alternative regimen (1): Atazanavir 300 mg-Cobicistat 150 mg PO qd AND Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd only for patients with pre-treatment estimated CrCl ≥70 mL/min
- Alternative regimen (2): Atazanavir 300 mg-Ritonavir 100 mg PO qd AND Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Alternative regimen (3): (Darunavir 800 mg-Cobicistat 150 mg PO qd OR Darunavir 800 mg-Ritonavir 100 mg PO qd) AND Abacavir 600 mg-Lamivudine 300 mg PO qd only for patients who are HLA-B*5701 negative
- Alternative regimen (4): Darunavir 800 mg-Cobicistat 150 mg PO qd AND Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd only for patients with pre-treatment estimated CrCl ≥70 mL/min
- Alternative regimen (5): Atazanavir 300 mg-Ritonavir 100 mg PO qd AND Abacavir 600 mg-Lamivudine 300 mg PO qd in patients who are HLA-B*5701-negative and with pre-treatment HIV RNA <100,000 copies/mL
- Alternative regimen (6): Lopinavir 400 mg-Ritonavir 100 mg PO qd or bid AND Abacavir 600 mg-Lamivudine 300 mg PO qd only for patients who are HLA-B*5701 negative
- Alternative regimen (7): Lopinavir 400 mg-Ritonavir 100 mg PO qd or bid AND Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd
- 1.3. A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen
- Alternative regimen (1): Efavirenz 600 mg-Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Alternative regimen (2): Rilpivirine 25 mg-Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- 1.4. Other regimen options
- 1.4.1. A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen
- Preferred regimen (1): Efavirenz 600 mg PO qd AND Abacavir 600 mg-Lamivudine 300 mg PO qd only for patients who are HLA-B*5701 negative and with pre-treatment HIV RNA <100,000 copies/mL.
- 1.4.2. Other regimens when tenofovir or abacavir cannot be used
- Preferred regimen (1): Darunavir 800 mg-Ritonavir 100 mg PO qd AND Raltegravir 400 mg PO qd only for patients with pre-treatment HIV RNA 200 cells/mm3.
- Preferred regimen (2): Lopinavir 400 mg-Ritonavir 100 mg PO bid AND Lamivudine 300 mg PO bid
- 1.5. Pediatric doses
- Abacavir 300 mg PO bid
- Lamivudine 4 mg/kg/dose PO bid; maximum 150 mg PO bid
- Stavudine 1 mg/kg/dose PO bid
- Tenofovir 8 mg/kg/dose PO bid
- Zidovudine 180-240 mg/m2/dose PO bid or 160 mg/m2/dose PO tid (range 90 mg/m2/dose-180 mg/m2/dose)
- Lopinavir 400 mg PO bid
- Nelfinavir 50 mg/kg/dose PO bid
- Raltegravir 300 mg PO bid
- Didanosine
- 20 to < 25 kg: 200 mg PO qd
- 25 to < 60 kg: 250 mg PO qd
- ≥60 kg: 400 mg PO qd
- Efavirenz
- 10 to < 15 kg: 200 mg PO qd
- 15 to <20 kg: 250 mg PO qd
- 20 to < 25 kg: 300 mg PO qd
- 25 to < 32.5 kg: 350 mg PO qd
- 32.5 to <40 kg: 400 mg PO qd
- ≥ 40 kg: 600 mg PO qd
- Nevirapine maximum 200 mg per dose
- Between 1 day and 8 years: 200 mg/m2/dose PO qd for 14 days, then 200 mg/m2/dose PO bid
- 8 years and above: 120-150 mg/m2/dose PO qd for 14 days, then 120-150 mg/m2/dose PO bid
- Note (1): Anti retroviral therapy for treatment naive patients is a life long therapy.
- Note (2): Tenofovir disoproxil fumarate should be avoided in patients with a creatinine clearance <50 mL/min.
- Note (3): Rilpivirine should be used in patients with a CD4 cell count >200 copies/mL and should not be used with proton pump inhibitors.
- Note (4): Efavirenz should not be used in pregnant women.
- 2. Pre-exposure prophylaxis (PrEP)
- Preferred regimen: Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd for ≤90-days
- Note (1): People with high risk behavior such as men who have sex with men, intravenous drug abusers, HIV-positive sexual partner, recent bacterial STI, high number of sex partners, history of inconsistent or no condom use, commercial sex work, people in high-prevalence area or network are advised to take pre-exposure prophylaxis of drugs.
- Note (2): Follow-up visits at least every 3 months to provide the following: HIV test, medication adherence counseling, behavioral risk reduction support, side effect assessment, STI symptom assessment, pregnancy testing.
- Note (3): At 3 months and every 6 months thereafter, assess renal function.
- Note (4): Every 6 months, test for bacterial STIs.
- 3. Post- exposure prophylaxis
- Preferred regimen: Raltegravir 400 mg PO bid AND Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd
- Preferred basic regimen for low-risk exposures (Eg: mucus membrane):
Zidovudine 100 mg PO qd AND Lamivudine 300 mg PO qd
Zidovudine 100 mg PO qd AND Emtricitabine 200 mg PO qd
Tenofovir 300 mg PO qd AND Lamivudine 300 mg PO qd
Tenofovir 300 mg PO qd AND Emtricitabine 200 mg PO qd
- Zidovudine 100 mg PO qd AND Lamivudine 300 mg PO qd
- Zidovudine 100 mg PO qd AND Emtricitabine 200 mg PO qd
- Tenofovir 300 mg PO qd AND Lamivudine 300 mg PO qd
- Tenofovir 300 mg PO qd AND Emtricitabine 200 mg PO qd
- Preferred expanded regimen for high-risk exposure (Eg: percutaneous needle stick)
Zidovudine 100 mg PO qd AND Lamivudine 300 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
Zidovudine 100 mg PO qd AND Emtricitabine 200 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
Tenofovir 300 mg PO qd AND Lamivudine 300 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
Tenofovir 300 mg PO qd AND Emtricitabine 200 mg PO qdAND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Zidovudine 100 mg PO qd AND Lamivudine 300 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Zidovudine 100 mg PO qd AND Emtricitabine 200 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Tenofovir 300 mg PO qd AND Lamivudine 300 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Tenofovir 300 mg PO qd AND Emtricitabine 200 mg PO qdAND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Note: Ideally therapy should be started within hours of exposure and continued for 28 days.
- 4. Perinatal antiretroviral regimen
- 4.1. Antepartum
- 4.1.1. Protease inhibitor-based regimen
- Preferred regimen: (Tenofovir 300 mg-Emtricitabine 200 mg PO qd (fixed dose combination) OR Tenofovir 300 mg-Lamivudine 300 mg PO qd OR Abacavir 600 mg-Lamivudine 300 mg PO qd OR Zidovudine 100 mg-Lamivudine 300 mg PO qd) AND (Atazanavir 300 mg-Ritonavir 100 mg PO qd OR Lopinavir 400 mg-Ritonavir 100 mg PO qd)
- 4.1.2. A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen:
- Preferred regimen (1): Efavirenz 600 mg-Tenofovir 300 mg-Emtricitabine 200 mg (fixed dose combination) PO qd
- Preferred regimen (2): Efavirenz 600 mg-Tenofovir 300 mg-Lamivudine 300 mg PO qd
- Alternative regimen: (Abacavir 600 mg-Lamivudine 300 mg PO qd OR Zidovudine 100 mg-Lamivudine 300 mg PO qd) AND Efavirenz 600 mg PO qd
- 4.2. Intrapartum
- Note (1): HIV RNA <1000 copies/mL and good adherance-Continue the regimen during delivery or cessarean section.
- Note (2): HIV RNA >1000 copies/mL near delivery, possible poor adherence, or unknown HIV RNA levels- Intravenous Zidovudine 2 mg/kg IV over 1 hr should be given three hours before cesarean section or delivery and then 1 mg/kg/hr IV continuous infusion until umbilical cord clamping.
- 4.3. Postpartum
- Note: Initiate anti retroviral therapy (ART) and continue after delivery and cessation of breastfeeding.
- 5. Infant antiretroviral prophylaxis for prevention of mother-to-child transmission of HIV
- 5.1 Prophylaxis for HIV-exposed infants of women who received antepartum antiretroviral prophylaxis
- Preferred regimen: Zidovudine (ZDV) 100 mg PO given at birth and continued till six weeks
- Note (1): Dose based on gestational age at birth and weight, initiated as soon after birth as possible and preferably within 6 to 12 hours of delivery.
- Note (2): ≥35 weeks gestation at birth: 4 mg/kg/dose orally (or, if unable to tolerate oral agents, 3 mg/kg/dose IV) every 12 hours.
- Note (3): ≥30 to <35 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours at age 15 days.
- Note (4): <30 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours after age four weeks.
- 5.2. Prophylaxis for HIV-exposed infants of women who received no antepartum antiretroviral prophylaxis
- Dose based on birth weight, initiated as soon after birth as possible.
- Birth weight 1.5 to 2 kg: 8 mg/dose orally.
- Birth weight >2 kg: 12 mg/dose orally.
- Dose based on gestational age at birth and weight, initiated as soon after birth as possible and preferably within 6 to 12 hours of delivery.
- ≥35 weeks gestation at birth: 4 mg/kg/dose orally (or, if unable to tolerate oral agents, 3 mg/kg/dose IV) every 12 hours.
- ≥30 to <35 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours at age 15 days.
- <30 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours after age four weeks.
- Note (1): Three doses in the first week of life.
- Note (2): First dose within 48 hours of birth (birth to 48 hrs).
- Note (3): Second dose 48 hours after first.
- Note (4): Third dose 96 hours after second.
- 6. Treatment and prevention of opportunistic infections
- 6.1. Pneumocystis pneumonia (PCP)
- 6.1.1. Prevention
- Indication
- CD4 count <200 cells/mm3
- Oropharyngeal candidiasis
- CD4 <14%
- History of AIDS-defining illness
- CD4 count >200 but <250 cells/mm3 if monitoring CD4 cell count every 3 months is not possible.
- Preferred regimen: Trimethoprim/sulfamethoxazole 160 mg/800 mg PO qd or 80 mg/400 mg PO qd
- Alternative regimen (1): Trimethoprim/sulfamethoxazole 160 mg/800 mg PO three times weekly
- Alternative regimen (2): Dapsone 100 mg PO qd or 50 mg PO bid
- Alternative regimen (3): Dapsone 50 mg PO qd AND (Pyrimethamine 50 mg-Leucovorin 25 mg) PO weekly
- Alternative regimen (4): Dapsone 200 mg PO qd AND (Pyrimethamine 75 mg-Leucovorin 25 mg) PO weekly
- Alternative regimen (5): Aerosolized Pentamidine 300 mg via Respigard nebulizer every month
- Alternative regimen (6): Atovaquone 1500 mg PO qd
- Alternative regimen (7): Atovaquone 1500 mg AND (Pyrimethamine 25 mg AND Leucovorin 10 mg) PO qd
- 6.1.2. Treatment
- 6.1.2.1. For Moderate-to-Severe PCP'
- Preferred regimen: Trimethoprim 15–20 mg AND Sulfamethoxazole 75–100 mg/kg/day IV given q6h or q8h, may switch to PO after clinical improvement
- Alternative regimen (1): Pentamidine 4 mg/kg IV daily infused over ≥60 minutes
- Note: Reduce dose to 3 mg/kg IV daily if toxic.
- Alternative regimen (2): Primaquine 30 mg (base) PO qd AND (Clindamycin 600 mg q6h IV OR 900 mg IV q8h OR Clindamycin 450 mg PO qid or 600 mg PO tid)
- 6.1.2.2. For Mild-to-Moderate PCP
- Preferred regimen: Trimethoprim 15–20 mg AND Sulfamethoxazole 75–100 mg/kg/day PO in TID OR Trimethoprim/sulfamethoxazole 160 mg/800 mg 2 tablets PO tid
- Alternative regimen (1): Dapsone 100 mg PO qd AND TMP 5 mg/kg PO tid
- Alternative regimen (2): Primaquine 30 mg (base) PO qd AND (Clindamycin 450 mg PO qid or 600 mg PO tid OR Atovaquone 750 mg PO bid with food)
- 6.1.3. Secondary prophylaxis, after completion of PCP treatment
- Preferred regimen (1): Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO qd OR Trimethoprim/Sulfamethoxazole 80 mg/400 mg PO qd
- Alternative regimen (1): Trimethoprim/sulfamethoxazole 160 mg/800 mg PO three times weekly
- Alternative regimen (2): Dapsone 100 mg PO qd
- Alternative regimen (3): Dapsone 50 mg PO qd AND Pyrimethamine 50 mg PO AND Leucovorin 25 mg PO weekly
- Alternative regimen (4): Dapsone 200 mg PO AND Pyrimethamine 75 mg PO AND Leucovorin 25 mg PO weekly
- Alternative regimen (5): Dapsone 100 mg PO qd
- Alternative regimen (6): Dapsone 50 mg PO qd AND Pyrimethamine 50 mg PO AND Leucovorin 25 mg PO weekly
- Alternative regimen (7): Dapsone 200 mg PO AND Pyrimethamine 75 mg PO AND Leucovorin 25 mg PO weekly
- Alternative regimen (8): Aerosolized Pentamidine 300 mg monthly via Respirgard nebulizer
- Alternative regimen (9): Atovaquone 1500 mg PO qd
- Alternative regimen (10): Atovaquone 1500 mg PO AND Pyrimethamine 25 mg PO AND Leucovorin 10 mg PO qd
- 6.1.4. Adjunctive corticosteroids
- Indications- PaO2 35 mmHg.
- Preferred regimen:
- Days 1–5: 40 mg PO bid
- Days 6–10: 40 mg PO qd
- Days 11–21: 20 mg PO qd
- Note (1): Trimethoprim/sulfamethoxazole should be permanently discontinued in patients with possible or definite stevens johnson syndrome or toxic epidermal necrosis.
- Note (2): Whenever possible, patients should be tested for G6PD before use of Dapsone or Primaquine. Alternative regimen should be used in patients found to have G6PD deficiency.
- 6.2. Toxoplasma gondii encephalitis
- 6.2.1. Prevention
- 6.2.1.1. Indication
- Toxoplasma IgG-positive patients with CD4 count <100 cells/µL.
- Seronegative patients receiving PCP prophylaxis not active against toxoplasmosis should have toxoplasma serology retested if CD4 count decline to <100 cellsµL.
- Prophylaxis should be initiated if seroconversion occurred.
- Preferred regimen: Trimethoprim/sulfamethoxazole 160 mg/800 mg PO qd
- Alternative regimen (1): Trimethoprim/sulfamethoxazole 160 mg/800 mg PO three times weekly
- Alternative regimen (2): Trimethoprim/sulfamethoxazole 80 mg/400 mg PO qd
- Alternative regimen (3): Dapsone 50 mg PO qd AND Pyrimethamine 50 mg PO weekly AND Leucovorin 25 mg PO weekly
- Alternative regimen (4): Dapsone 200 mg PO weekly AND Pyrimethamine 75 mg PO weekly AND Leucovorin 25 mg PO weekly
- Alternative regimen (5): Atovaquone 1500 mg PO qd
- Alternative regimen (6): Atovaquone 1500 mg PO qd AND Pyrimethamine 25 mg PO qd AND Leucovorin 10 mg PO qd
- 6.2.2. Treatment
- 6.2.2.1. Treatment of acute infection
- Preferred regimen: Pyrimethamine 200 mg PO single dose, followed by weight-based therapy:
- If <60 kg, Pyrimethamine 50 mg PO qd AND Sulfadiazine 1000 mg PO qid AND Leucovorin 10–25 mg PO qd
- If ≥60 kg, Pyrimethamine 75 mg PO qd AND Sulfadiazine 1500 mg PO qid AND Leucovorin 10–25 mg PO qd
- Note: At least 6 weeks; longer duration if clinical or radiologic disease is extensive or response is incomplete at 6 weeks.
- Alternative regimen (1): Pyrimethamine 50 mg PO qdAND Leucovorin 10–25 mg PO qd AND Clindamycin 600 mg IV or PO q6h
- Alternative regimen (2): Trimethoprim 5 mg/kg-Sulfamethoxazole 25 mg/kg IV or PO bid
- Alternative regimen (3): Atovaquone 1500 mg PO bid with food AND Pyrimethamine 50 mg PO qd AND Leucovorin 10–25 mg PO qd
- Alternative regimen (4): Atovaquone 1500 mg PO bid with food AND Sulfadiazine 1000–1500 mg PO qid (weight-based dosing, as in preferred therapy)
- Alternative regimen (5): Atovaquone 1500 mg PO bid with food
- Alternative regimen (6): Pyrimethamine 50 mg-Leucovorin 10–25 mg PO qd AND Azithromycin 900–1200 mg PO qd
- 6.2.2.2. Chronic maintenance therapy
- Preferred regimen: Pyrimethamine 25–50 mg PO qd AND Sulfadiazine 2000–4000 mg PO qd (in 2–4 divided doses) AND Leucovorin 10–25 mg PO qd
- Alternative regimen (1): Clindamycin 600 mg PO tid AND Pyrimethamine 25–50 mg-Leucovorin 10–25 mg PO qd
- Alternative regimen (2): Trimethoprim/sulfamethoxazole 160 mg/800 mg bid
- Alternative regimen (3): Atovaquone 750–1500 mg PO bid AND Pyrimethamine 25 mg-Leucovorin 10 mg PO qd
- Alternative regimen (4): Atovaquone 750–1500 mg PO bid AND Sulfadiazine 2000–4000 mg PO qd in 2–4 divided doses
- Alternative regimen (5): Atovaquone 750–1500 mg PO bid with food
- 6.3. Mycobacterium tuberculosis infection
- 6.3.1. Prevention
- 6.3.1.1. Indication
- Positive screening test for latent tuberculosis infection, with no evidence of active tuberculosis, and no prior treatment for active tuberculosis or latent tuberculosis infection.
- Close contact with a person with infectious tuberculosis, with no evidence of active tuberculosis, regardless of screening test results.
- Preferred regimen: (Isoniazid 300 mg PO qd AND Pyridoxine 25 mg PO qd for 9 months) OR (Isoniazid 900 mg PO two times a week (by DOT) AND Pyridoxine 25 mg PO qd for 9 months)
- Alternative regimen (1): Rifampin 600 mg PO qd for 4 months
- Alternative regimen (2): Rifabutin (dose adjusted based on concomitant ART) PO qd for 4 months
- 6.3.2. Treatment
- Preferred regimen
- Initiation phase: Isoniazid 300 mg PO qd AND (Rifampin 600 mg PO qd OR Rifabutin 300 mg PO qd) AND Pyrazinamide (upto 2000 mg) PO qd AND Ethambutol (upto 1600 mg) PO qd for initial phase for 2 months.
- Continuation phase: Isoniazid 300 mg PO qd AND (Rifampin 600 mg PO qd OR Rifabutin 300 mg PO qd) (5–7 times/week) or three times a week.
- Duration of therapy:
- Pulmonary tuberculosis: 6 months
- Pulmonary tuberculosis and culture positive after 2 months of tuberculosis treatment: 9 months
- Extra-pulmonary tuberculosis w/CNS infection: 9–12 months
- Extra-pulmonary tuberculosis with bone or joint involvement: 6 to 9 months
- Extra-pulmonary tuberculosis in other sites: 6 months
- Total duration of therapy should be based on number of doses received, not on calendar time
- 6.3.1.3. Treatment for drug-resistant tuberculosis
- Resistant to Isoniazid:
- Preferred regimen (1): (Rifampin 600 mg PO qd OR Rifabutin 300mg PO qd) AND Ethambutol (upto 1600 mg) PO qd AND Pyrazinamide (upto 2000 mg) PO qd AND (Moxifloxacin 400 mg PO or IV qd OR Levofloxacin 500-1000 mg PO or IV qd) for 2 months; followed by Rifampin 600 mg PO qd for 7 months.
- Preferred regimen (2): Rifabutin 300mg PO qd AND Ethambutol (upto 1600 mg) PO qd AND (Moxifloxacin 400 mg PO or IV qdOR Levofloxacin 500-1000 mg PO or IV qd) for 7 months
- 6.4. Disseminated mycobacterium avium complex (MAC) disease
- 6.4.1. Prevention
- 6.4.1.1. Indication-CD4 count <50 cells/µL—after ruling out active disseminated MAC disease based on clinical assessment
- Preferred regimen (1): Azithromycin 1200 mg PO once weekly
- Preferred regimen (2): Clarithromycin 500 mg PO bid
- Preferred regimen (3): Azithromycin 600 mg PO twice weekly.
- 6.4.2. Treatment
- Preferred regimen: Clarithromycin 500 mg PO bid AND Ethambutol 15 mg/kg PO qd OR Azithromycin 500–600 mg PO qd for at least 12 months of therapy
- Note (1): Treatment can be discontinued if no signs and symptoms of MAC disease and sustained (>6 months) CD4 count >100 cells/µL in response to anti retroviral therapy.
- Note (2): Addition of a third or fourth drug should be considered for patients with advanced immunosuppression (CD4 counts 2 log CFU/mL of blood), or in the absence of effective anti retroviral therapy which include Amikacin 10–15 mg/kg IV qd, Streptomycin 1 g IV or IM qd, Moxifloxacin 400 mg PO qd, Levofloxacin 500 mg PO qd.
- 6.5. Streptococcus pneumoniae infection
- 6.5.1. Prevention
- 6.5.1.1. Indication
- 6.5.1.1.1. For individuals who have not received any pneumococcal vaccine, regardless of CD4 count
- Preferred regimen: PCV13 0.5ml IM single dose
- Alternative regimen: PPV23 0.5 mL IM or SQ single dose
- Note (1): If CD4 count ≥200 cells/µL, administer PPV23 0.5 mL IM or SQ at least 8 weeks after the PCV13 vaccine.
- Note (2): If CD4 count <200 cells/µL, PPV23 can be offered at least 8 weeks after receiving PCV13 or can wait until CD4 count increased to ≥200 cells/µL.
- 6.5.1.1.2. For individuals who have previously received PPV23
- Note: One dose of PCV13 should be given atleast 1 year after the last receipt of PPV23
- 6.5.1.1.3. Re-vaccination
- If age 19–64 years and ≥5 years since the first PPV23 dose PPV23 0.5 mL IM or SQ
- If age ≥65 years, and if ≥5 years since the previous PPV23 dose PPV23 0.5 mL IM or SQ
- If age ≥65 years, and if ≥5 years since the previous PPV23 dose PPV23 0.5 mL IM or SQ
- 6.6. Influenza A and B virus infection
- 6.6.1. Prevention
- 6.6.1.1. Indication
- All HIV-infected patients
- Note (1): Inactivated influenza vaccine annually (per recommendation for the season).
- Note (2): Live-attenuated influenza vaccine is contraindicated in HIV-infected patients.
- 6.7. Syphilis
- 6.7.1. Prevention
- 6.7.1.1. Indication
- For individuals exposed to a sex partner with a diagnosis of primary, secondary, or early latent syphilis within past 90 days.
- For individuals exposed to a sex partner >90 days before syphilis diagnosis in the partner, if serologic test results are not available immediately and the opportunity for follow-up is uncertain.
- Preferred regimen: Benzathine penicillin G 2.4 million units IM single dose
- Alternative regimen (1): Doxycycline 100 mg PO bid for 14 days
- Alternative regimen (2): Ceftriaxone 1 g IM or IV q24h for 8– 10 days
- Alternative regimen (3): Azithromycin 2 g PO single dose
- Note: Azithromycin is not recommended for MSM or pregnant women.
- 6.7.2. Treatment
- 6.7.2.1. Early stage (primary, secondary, and early-latent syphilis)
- Preferred regimen: Benzathine penicillin G 2.4 million units IM single dose
- Alternative regimen (1): Doxycycline 100 mg PO bid for 14 days
- Alternative regimen (2): Ceftriaxone 1 g IM or IV q24h for 10–14 days
- Alternative regimen (3): Azithromycin 2 g PO single dose
- 6.7.2.2. Late-stage (tertiary–cardiovascular or gummatous disease)
- Preferred regimen: Benzathine penicillin G 2.4 million units IM weekly for 3 doses
- Alternative regimen: Doxycycline 100 mg PO bid for 28 days
- 6.7.2.3. Neurosyphilis (including otic or ocular disease)
- Preferred regimen: Aqueous crystalline Penicillin G 18– 24 million units per day (administered as 3–4 million units IV q4h or by continuous IV infusion) for 10–14 days with or without Benzathine penicillin G 2.4 million units IM weekly for 3 doses after completion of IV therapy
- Alternative regimen: Procaine penicillin 2.4 million units IM q24h AND Probenecid 500 mg PO qid for 10–14 days with or without Benzathine penicillin G 2.4 million units IM weekly for 3 doses after completion
- Note (1): The Jarisch-Herxheimer reaction is an acute febrile reaction accompanied by headache and myalgia that can occur within the first 24 hours after therapy for syphilis.
- Note (2): This reaction occurs most frequently in patients with early syphilis, high nontreponemal titers and prior penicillin treatment.
- 6.8. Histoplasma capsulatum infection
- 6.8.1. Prevention
- 6.8.1.1. Indication
- CD4 count ≤150 cells/µL and at high risk because of occupational exposure or live in a community with a hyperendemic rate of histoplasmosis (>10 cases/100 patient-years).
- Preferred regimen: Itraconazole 200 mg PO qd
- 6.8.2. Treatment
- 6.8.2.1. Moderately severe to severe disseminated disease
- Induction therapy (for at least 2 weeks or until clinically improved)
- Preferred regimen: Liposomal Amphotericin B 3 mg/kg IV q24h
- Maintenance therapy:
- Preferred regimen: Itraconazole 200 mg PO tid for 3 days, then 200 mg PO bid
- 6.8.2.2. Less severe disseminated disease
- Induction therapy:
- Preferred regimen: Liposomal Amphotericin B 3 mg/kg IV q24h
- Alternative regimen: Amphotericin B lipid complex 3 mg/kg IV q24h OR Amphotericin B cholesteryl sulfate complete 3 mg/kg IV q24h
- Note: Induction therapy should be for at least 2 weeks or until clinically improved.
- Maintenance therapy:
- Preferred regimen: Itraconazole 200 mg PO tid for 3 days and then Itraconazole 200 mg PO bid for 12 months
- Alternative regimen (1): Voriconazole 400 mg PO bid for 1 day, then 200 mg bid
- Alternative regimen (2): Posaconazole 400 mg PO bid
- Alternative regimen (3): Fluconazole 800 mg PO qd
- 6.8.2.3. Meningitis
- Induction therapy:
- Preferred regimen: Liposomal amphotericin B 5 mg/kg/day for 4–6 weeks
- Maintenance therapy:
- Preferred regimen: Itraconazole 200 mg PO bid to tid for ≥1 year
- Note: Treatment continued until resolution of abnormal CSF findings.
- Long-Term Suppression Therapy
- Preferred regimen: Itraconazole 200 mg PO qd
- Alternative regimen: Fluconazole 400 mg PO qd
- Note: Therapeutic drug monitoring and dosage adjustment may be necessary to ensure Triazole antifungal and ARV efficacy and reduce concentration-related toxicities.
- 6.9. Coccidioidomycosis
- 6.9.1. Prevention
- 6.9.1.1. Indication
- A new positive IgM or IgG serologic test in patients who live in a disease-endemic area and with CD4 count <250 cells/µL.
- Preferred regimen: Fluconazole 400 mg PO qd
- 6.9.2. Treatment
- 6.9.2.1. Clinically mild infections (e.g., focal pneumonia)
- Preferred regimen: Fluconazole 400 mg PO qd OR Itraconazole 200 mg PO bid
- Alternative regimen: Posaconazole 200 mg PO bid OR Voriconazole 200 mg PO bid
- 6.9.2.2. Severe, non-meningeal infection (diffuse pulmonary infection or severely ill patients with extrathoracic, disseminated disease)
- Preferred regimen: Amphotericin B deoxycholate 0.7–1.0 mg/kg IV qd OR Lipid formulation Amphotericin B 4–6 mg/kg IV qd
- Alternative regimen: Fluconazole or Itraconazole, with Itraconazole preferred for bone disease 400 mg per day to Amphotericin B therapy and continue triazole once Amphotericin B is stopped.
- 6.9.2.3. Meningeal infections
- Preferred regimen: Fluconazole 400–800 mg IV or PO qd
- Alternative regimen: Itraconazole 200 mg PO tid for 3 days, then 200 mg PO bid OR Posaconazole 200 mg PO bid OR Voriconazole 200–400 mg PO bid
- 6.9.2.4. Chronic suppressive therapy
- Preferred regimen: Fluconazole 400 mg PO qd OR Itraconazole 200 mg PO bid
- Alternative regimen: Posaconazole 200 mg PO bid OR Voriconazole 200 mg PO bid
- Note (1): Therapy should be continued indefinitely in patients with diffuse pulmonary or disseminated diseases because relapse can occur in 25%–33% of HIV-negative patients. It can also occur in HIV-infected patients with CD4 counts >250 cells/µL.
- Note (2): Therapy should be lifelong in patients with meningeal infections because relapse occurs in 80% of HIV-infected patients after discontinuation of triazole therapy.
- 6.10. Herpes simplex virus (HSV) Disease
- 6.10.1. Orolabial lesions (For 5–10 Days)
- Preferred regimen (1): Valacyclovir 1 g PO bid
- Preferred regimen (2): Famciclovir 500 mg PO bid
- Preferred regimen (3): Acyclovir 400 mg PO tid
- 6.10.2. Initial or recurrent genital HSV (For 5–14 Days)
- Preferred regimen (1): Valacyclovir 1 g PO bid
- Preferred regimen (2): Famciclovir 500 mg PO bid
- Preferred regimen (3): Acyclovir 400 mg PO tid
- 6.10.3. Severe mucocutaneous HSV
- Preferred regimen: Initial therapy Acyclovir 5 mg/kg IV q8h.
- Note: After lesions begin to regress, change to PO therapy as above. Continue until lesions are completely healed.
- 6.10.4. Chronic suppressive therapy
- Preferred regimen (1): Valacyclovir 500 mg PO bid
- Preferred regimen (2): Famciclovir 500 mg PO bid
- Preferred regimen (3): Acyclovir 400 mg PO bid
- 6.10.4. For acyclovir-resistant HSV
- Preferred therapy: Foscarnet 80–120 mg/kg/day IV q12h-q8h
- Alternative regimen: Cidofovir IV OR Topical Trifluridine OR Topical Imiquimod for 21-28 days
- Note: Continue indefinitely regardless of CD4 cell count.
- 6.11. Varicella-zoster virus (VZV) infection
- 6.11.1. Varicella-zoster virus (VZV) infection
- 6.11.1.2 Prevention
- 6.11.1.1. Pre-exposure prevention
- Indication: Patients with CD4 counts ≥200 cells/µL who have not been vaccinated, have no history of varicella or herpes zoster, or who are seronegative for VZV.
- Preferred regimen: Primary varicella vaccination, 2 doses (0.5 mL SQ each) administered 3 months apart
- Alternative regimen: VZV-susceptible household contacts of susceptible HIV-infected persons should be vaccinated to prevent potential transmission of VZV to their HIV-infected contacts
- Note (1): Routine VZV serologic testing in HIV-infected adults and adolescents is not recommended.
- Note (2): If vaccination results in disease because of vaccine virus, treatment with Acyclovir is recommended.
- 6.11.1.2. Post-exposure prevention
- Indication: Close contact with a person with chickenpox or herpes zoster; and is susceptible (i.e., no history of vaccination or of either condition, or known to be VZV seronegative).
- Preferred regimen: Varicella-zoster immune globulin (VariZIG™) 125 international units per 10 kg (maximum 625 international units) IM, administered as soon as possible and within 10 days after exposure.
- Alternative regimen (1): Acyclovir 800 mg PO qd for 5– 7 days
- Alternative regimen (2): Valacyclovir 1 g PO tid for 5–7 days
- Note (1): Individuals receiving monthly high-dose IVIG (>400 mg/kg) are likely to be protected if the last dose of IVIG was administered <3 weeks before exposure.
- Note (2): If antiviral therapy is used, varicella vaccines should not be given until at least 72 hours after the last dose of the antiviral drug.
- 6.11.1.2. Treatment
- 6.11.1.2.1 Primary varicella infection (chickenpox)
- 6.11.1.2.1. Uncomplicated cases (For 5–7 Days)
- Preferred regimen (1): Valacyclovir 1 g PO tid
- Preferred regimen (2): Famciclovir 500 mg PO tid
- 6.11.1.2.1. Severe or complicated Cases
- Preferred regimen: Acyclovir 10–15 mg/kg IV q8h for 7–10 days.
- Alternative regimen: Acyclovir 800 mg PO 5 times/day for 5-7 days.
- 6.11.1.2.2. Herpes zoster (Shingles)
- 6.11.1.2.2.1. Acute localized dermatomal
- Preferred regimen (1): Valacyclovir 1 g PO tid for 7–10 days; consider longer duration if lesions are slow to resolve
- Preferred regimen (2): Famciclovir 500 mg tid for 7–10 days; consider longer duration if lesions are slow to resolve
- 6.11.1.2.2.2. Extensive cutaneous lesion or visceral involvement
- Preferred regimen: Acyclovir 10–15 mg/kg IV q8h until clinical improvement is evident.
- Note: Treatment may switch to PO therapy (Valacyclovir, Famciclovir, or Acyclovir) after clinical improvement (i.e., when no new vesicle formation or improvement of signs and symptoms of visceral VZV), to complete a 10–14 day course.
- Alternative regimen: Acyclovir 800 mg PO 5 times/day for 7–10 days; consider longer duration if lesions are slow to resolve.
- 6.11.1.2.2.3. Progressive outer retinal necrosis (PORN)
- Preferred regimen: (Ganciclovir 5 mg/kg with or without Foscarnet 90 mg/kg) IV q12h AND (Ganciclovir 2 mg/0.05mL with or without Foscarnet 1.2 mg/0.05 ml) intravitreal injection biweekly.
- 6.11.1.2.2.4. Acute retinal necrosis (ARN)
- Preferred regimen: Acyclovir 10-15 mg/kg IV q8h AND (Ganciclovir 2 mg/0.05mL intravitreal injection 1-2 doses biweekly for 10-14 days, followed by Valacyclovir 1g PO tid for 6 weeks
- 6.12. Cytomegalovirus (CMV) Disease
- 6.12.1. Treatment
- 6.12.1.1. CMV retinitis
- Induction therapy
- Preferred regimen (1): Ganciclovir 2mg OR Foscarnet 2.4mg intravitreal injections for 1-4 doses over a period of 7-10 days to achieve high intraocular concentration faster
- Preferred regimen (2): Valganciclovir 900 mg PO bid for 14–21 days
- Alternative regimen (1): Ganciclovir 5 mg/kg IV q12h for 14–21 days
- Alternative regimen (2): Foscarnet 90 mg/kg IV q12h or 60 mg/kg q8h for 14–21 days
- Alternative regimen (3): Cidofovir 5 mg/kg/week IV for 2 weeks
- Note: Saline hydration before and after therapy should be given and Probenecid, 2 g PO 3 hours before dose, followed by 1 g PO 2 hours and 8 hours after the dose (total of 4 g) is recommended.
- Chronic maintenance (secondary prophylaxis):
- Preferred regimen: Valganciclovir 900 mg PO qd
- Alternative regimen (1): Ganciclovir 5 mg/kg IV 5–7 times weekly
- Alternative regimen (2): Foscarnet 90–120 mg/kg IV once daily
- Alternative regimen (3): Cidofovir 5 mg/kg/week IV for 2 weeks; saline hydration before and after therapy AND Probenecid, 2 g PO 3 hours before dose, followed by 1 g PO 2 hours and 8 hours after the dose (total of 4 g)
- 6.12.1.2. CMV esophagitis or colitis
- 6.12.1.2.1. Severe condition
- Preferred regimen: Ganciclovir 5 mg/kg IV q12h; may switch to Valganciclovir 900 mg PO bid once the patient can tolerate oral therapy for 21-42 days or till the symptoms are resolved
- Alternative regimen: Foscarnet 90 mg/kg IV q12h or 60 mg/kg q8h for 21-42 days
- Note: For patients with treatment-limiting toxicities to Ganciclovir or with Ganciclovir resistance, above regimen is recommended.
- 6.12.1.2.2. Mild disease and able to tolerate oral therapy
- Preferred regimen: Valganciclovir 900 mg PO bid 21-42 days
- 6.12.1.3. CMV neurological disease
- Preferred regimen: Ganciclovir 5 mg/kg IV q12h AND (Foscarnet 90 mg/kg IV q12h or 60 mg/kg IV q8h) to stabilize disease
- 6.13. HHV-8 Diseases (kaposi sarcoma , primary effusion lymphoma , multicentric castleman’s disease )
- 6.13.1. Treatment
- Mild to moderate KS (ACTG Stage T0)
- Note: Initiate or optimize anti retroviral therapy.
- Advanced KS
- Note: Chemotherapy (per oncology consult) AND anti retroviral therapy.
- Primary effusion lymphoma
- Preferred regimen (1): Valganciclovir 900 mg PO bid for 3 weeks
- Preferred regimen (2): Ganciclovir 5 mg/kg IV q12h for 3 weeks
- Preferred regimen (3): Valganciclovir 900 mg PO bid AND Zidovudine 600 mg PO qid for 7– 21 days
- Alternative regimen: Rituximab (375 mg/m2 given weekly for 4–8 weeks) may be an alternative to or used adjunctively with antiviral therapy
- Note: Valganciclovir PO OR Ganciclovir IV can be used as adjunctive therapy
- 6.14. Human papillomavirus (HPV) infection
- 6.14.1. Prevention
- For females aged 13–26 years
- Preferred regimen (1): HPV quadrivalent vaccine 0.5 mL IM at months 0, 1–2, and 6 OR HPV bivalent vaccine 0.5 mL IM at months 0, 1–2, and 6
- Males aged 13–26 years
- Preferred regimen (1): HPV quadrivalent vaccine 0.5 mL IM at months 0, 1–2, and 6
- 6.14.2. Treatment
- 6.14.2.1. Patient-applied therapy for uncomplicated external warts that can be easily identified by patients
- Preferred regimen (1): Podophyllotoxin (e.g., podofilox 0.5% solution or 0.5% gel)
- Note: Apply to all lesions bid for 3 consecutive days, followed by 4 days of no therapy, repeat weekly for up to 4 cycles, until lesions are no longer visible)
- Preferred regimen (2): Imiquimod 5% cream
- Note: Apply to lesion at bedtime and remove in the morning on 3 nonconsecutive nights weekly for up to 16 weeks, until lesions are no longer visible. Each treatment should be washed with soap and water 6–10 hours after application.
- Preferred regimen (3): Sinecatechins 15% ointment
- Note: Apply to affected areas tid for up to 16 weeks, until warts are completely cleared and not visible
- 6.14.2.2. Provider-applied therapy for complex or multicentric lesions, or lesions inaccessible to patient
- Note (1): Cryotherapy (liquid nitrogen or cryoprobe): Apply until each lesion is thoroughly frozen. Repeat every 1–2 weeks for up to 4 weeks, until lesions are no longer visible. Some providers allow the lesion to thaw, then freeze a second time in each session.
- Note (2): Trichloroacetic acid or bichloroacetic acid cauterization: 80%–90% aqueous solution, apply to wart only, allow to dry until a white frost develops. Repeat weekly for up to 6 weeks, until lesions are no longer visible.
- Note (3): Surgical excision or laser surgery to external or anal warts.
- Note (4): Podophyllin resin 10%–25% in tincture of benzoin: Apply to all lesions (up to 10 cm2 ), then wash off a few hours later, repeat weekly for up to 6 weeks until lesions are no longer visible.
- 6.15. Hepatitis A virus (HAV) infection
- 6.15.1. Prevention
- Indication: HAV-susceptible patients with chronic liver disease, or who are injection-drug users or homosexuals
- Preferred regimen: Hepatitis A vaccine 1 mL IM 2 doses at 0 and 6–12 months.
- Alternative regimen: Combined HAV and HBV vaccine 1 mL IM as a 3-dose (0, 1, and 6 months) or 4-dose series (days 0, 7, 21 to 30, and 12 months).
- Note (1): For patients susceptible to both HAV and hepatitis B virus (HBV) infection, alternative regimen is recommended.
- Note (2): IgG antibody response should be assessed 1 month after vaccination; nonresponders should be revaccinated when CD4 count >200 cells/µL.
- 6.16. Hepatitis B virus (HBV) infection
- 6.16.1. Prevention
- 6.16.1.1. Indication
- Patients without chronic HBV or without immunity to HBV (i.e., anti-HBs <10 international units/mL).
- Patients with isolated anti-HBc and negative HBV DNA.
- Early vaccination is recommended before CD4 count falls below 350 cells/µL.
- However, in patients with low CD4 cell counts, vaccination should not be deferred until CD4 count reaches >350 cells/µL, because some patients with CD4 counts <200 cells/µL do respond to vaccination.
- Preferred regimen (1): HBV vaccine IM (Engerix-B 20 µg/mL or Recombivax HB 10 µg/mL), 0, 1, and 6 months
- Preferred regimen (2): HBV vaccine IM (Engerix-B 40 µg/mL or Recombivax HB 20 µg/mL) 0, 1, 2 and 6 months
- Preferred regimen (3): Combined HAV and HBV vaccine, 1 mL IM as a 3-dose (0, 1, and 6 months) or 4-dose series (days 0, 7, 21 to 30, and 12 months)
- Alternative regimen: Some experts recommend vaccinating with 40-µg doses of either HBV vaccine
- Note: Anti-HBs should be obtained 1 month after completion of the vaccine series. Patients with anti-HBs <10 international units/mL at 1 month are considered nonresponders.
- Vaccine Non-Responders:
- Preferred regimen (1): HBV vaccine IM (Engerix-B 40 µg/mL or Recombivax HB 20 µg/mL), 0, 1, 2 and 6 months.
- Note (1): Vaccination non-responders have anti-HBs <10 international units/mL 1 month after vaccination series.
- Note (2): For patients with low CD4 counts at time of first vaccine series, some experts might delay revaccination until after a sustained increase in CD4 count with anti retroviral therapy.
- 6.16.2. Treatment
- Preferred regimen: Tenofovir 300 mg PO qdAND Emtricitabine 200 mg PO qd OR Lamivudine 300 mg PO qd AND additional drug(s) for HIV
- Note: Anti retroviral therapy regimen should include 2 drugs that are active against both HBV and HIV.
- Alternative regimen: Peginterferon alfa-2a 180 μg SQ once weekly for 48 weeks OR Peginterferon alfa 2b 1.5 μg/kg SQ once weekly for 48 weeks.
- Note: For HBV treatment is indicated for patients with elevated ALT and HBV DNA >2,000 IU/mL significant liver fibrosis, advanced liver disease or cirrhosis, above regimen is indicated.
- 6.17. Penicilliosis marneffei
- 6.17.1. Prevention
- 6.17.1.1. Indication
- Patients with CD4 cell counts <100 cells/µL who live or stay for a long period in rural areas in northern Thailand, Vietnam, or Southern China.
- Preferred regimen: Itraconazole 200 mg PO qd
- Alternative regimen: Fluconazole 400 mg PO once weekly
- 6.17.2. Treatment
- 6.17.2.1. For acute infection in severely ill patients
- Preferred regimen: Liposomal amphotericin B 3–5 mg/kg/day IV for 2 weeks, followed by Itraconazole 200 mg PO bid for 10 weeks, followed by chronic maintenance therapy
- Alternative regimen: Voriconazole 6 mg/kg IV q12h for 1 day, then 4 mg/kg IV q12h for at least 3 days, followed by 200 mg PO bid for a maximum of 12 weeks, followed by maintenance therapy
- 6.17.2.2. For mild disease
- Preferred regimen: Itraconazole 200 mg PO bid for 8 weeks; followed by chronic maintenance therapy
- Alternative regimen: Voriconazole 400 mg PO bid for 1 day, then 200 mg bid for a maximum of 12 weeks, followed by chronic maintenance therapy
- 6.17.2.3. Chronic Maintenance Therapy (Secondary Prophylaxis)
- Preferred regimen: Itraconazole 200 mg PO qd
- Note (1): Anti retroviral therapy should be initiated simultaneously with treatment for penicilliosis to improve treatment outcome.
- Note (2): Itraconazole and Voriconazole may have significant interactions with certain ARV agents. These interactions are complex and can be bi-directional.
- Note (3): Therapeutic drug monitoring and dosage adjustment may be necessary to ensure triazole antifungal and ARV efficacy and reduce concentration-related toxicities.
- 6.18. Isosporiasis
- 6.18.1. Treatment
- For Acute Infection:
- Preferred regimen (1): Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO (or IV) qid for 10 days
- Preferred regimen (2): Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO (or IV) bid for 7–10 days
- Alternative regimen (1): Pyrimethamine 50–75 mg PO daily AND Leucovorin 10–25 mg PO qd
- Alternative regimen (2): Ciprofloxacin 500 mg PO bid for 7 days as a second line alternative
- Chronic Maintenance Therapy (Secondary Prophylaxis):
- Preferred regimen (1): In patients with CD4 count <200/µL, Trimethoprim/sulfamethoxazole 160 mg/800 mg PO three times a week
- Alternative regimen (1): Trimethoprim/sulfamethoxazole 160 mg/800 mg PO qd or (320 mg/1600 mg) three times a week
- Alternative regimen (2): Pyrimethamine 25 mg PO qd AND Leucovorin 5–10 mg PO qd
- Alternative regimen (3): Ciprofloxacin 500 mg three times a week as a second-line alternative
- Note (1): Fluid and electrolyte management in patients with dehydration.
- Note (2): Immune reconstitution with anti retroviral therapy may result in fewer relapses.
- Note (3): IV therapy may be used for patients with potential or documented mal-absorption.
- 6.19. Chagas disease (American trypanosomiasis)
- 6.19.1. Treatment
- For acute, earlychronic, and reactivated Disease:
- Preferred regimen: Benznidazole 5–8 mg/kg/day PO in 2 divided doses for 30–60 days
- Alternative regimen: Nifurtimox 8–10 mg/kg/day PO for 90–120 days.
- 6.20. Leishmaniasis, visceral
- 6.20.1. Leishmaniasis, visceral
- 6.20.1.1. Treatment
- For initial infection:
- Preferred regimen (1): Liposomal amphotericin B 2–4 mg/kg IV qd
- Preferred regimen (2): Liposomal amphotericin B interrupted schedule (e.g., 4 mg/kg on days 1–5, 10, 17, 24, 31, 38)
- Alternative regimen (1): Amphotericin B deoxycholate 0.5–1.0 mg/kg IV q24h for total dose of 1.5–2.0 g
- Alternative regimen (2): Sodium stibogluconate (pentavalent antimony) 20 mg/kg IV or IM q24h for 28 days
- Alternative regimen (3): Miltefosine 100 mg PO qd for 4 weeks
- Chronic maintenance therapy (secondary prophylaxis); Especially in Patients with CD4 Count <200 cells/µL:
- Preferred regimen (1): Liposomal amphotericin B 4 mg/kg every 2–4 weeks
- Preferred regimen (2): Amphotericin B lipid complex 3 mg/kg every 21 days
- Alternative regimen: Sodium stibogluconate 20 mg/kg IV or IM every 4 weeks
- 6.20.2. Leishmaniasis, cutaneous
- Preferred regimen (1): Liposomal amphotericin B 2–4 mg/kg IV daily for 10 days
- Preferred regimen (2): Liposomal amphotericin B interrupted schedule (e.g., 4 mg/kg on days 1–5, 10, 17, 24, 31, 38) to achieve total dose of 20–60 mg/kg
- Preferred regimen (3): Sodium stibogluconate 20 mg/kg IV or IM daily for 3–4 weeks
- 6.21. Aspergillosis, invasive
- 6.21.1. Treatment
- Preferred regimen: Voriconazole 6 mg/kg IV q12h for 1 day, then 4 mg/kg IV q12h, followed by Voriconazole 200 mg PO q12h after clinical improvement until CD4 cell count >200 cells/µL and the infection appears to be resolved.
- Alternative regimen (1): Lipid formulation of Amphotericin B 5 mg/kg IV q24h
- Alternative regimen (2): Amphotericin B deoxycholate 1mg/kg IV q24h
- Alternative regimen (3): Caspofungin 70 mg IV single dose, then 50 mg IV q24h
- Alternative regimen (4): Micafungin 100–150 mg IV q24h
- Alternative regimen (5): Anidulafungin 200 mg IV single dose, then 100 mg IV q24h
- Alternative regimen (6): Posaconazole 200 mg PO qid, then, after condition improved, 400 mg PO bid
- 6.22. Malaria
- 6.22.1. Prevetion
- 6.22.1.1. Prophylaxis in all areas
- Preferred regimen (1): Atovaquone 250 mg and Proguanil hydrochloride 100 mg PO qd
- Pediatric doses: Pediatric tablets contain 62.5 mg atovaquone and 25 mg proguanil hydrochloride
- 5–8 kg: 1/2 pediatric tablet daily
- >8–10 kg: 3/4 pediatric tablet daily
- >10–20 kg: 1 pediatric tablet daily
- >20–30 kg: 2 pediatric tablets daily
- >30–40 kg: 3 pediatric tablets daily
- Note (1): Begin 1–2 days before travel to malarious areas. Take daily at the same time each day while in the malarious area and for 7 days after leaving such areas. Contraindicated in people with severe renal impairment (creatinine clearance <30 mL/min).
- Note (2): Atovaquone-proguanil should be taken with food or a milky drink. Not recommended for prophylaxis for children weighing <5 kg, pregnant women, and women breastfeeding infants weighing <5 kg. Partial tablet doses may need to be prepared by a pharmacist and dispensed in individual capsules.
- Preferred regimen (2): Doxycycline 100 mg PO qd
- Pediatric dose: ≥8 years of age: 2.2 mg/kg up to adult dose of 100 mg/day
- Note: Begin 1–2 days before travel to malarious areas. Take daily at the same time each day while in the malarious area and for 4 weeks after leaving such areas. Contraindicated in children <8 years of age and pregnant women.
- 6.22.1.2. Prophylaxis only in areas with chloroquine-sensitive malaria
- Preferred regimen: Chloroquine phosphate 300 mg base (500 mg salt) PO once a week
- Note: Begin 1–2 weeks before travel to malarious areas. Take weekly on the same day of the week while in the malarious area and for 4 weeks after leaving such areas. May exacerbate psoriasis.
- Alternative regimen: Hydroxychloroquine sulfate 400 mg salt PO once a week
- Note: Begin 1–2 weeks before travel to malarious areas. Take weekly on the same day of the week while in the malarious area and for 4 weeks after leaving such areas.
- Pediatric doses: Chloroquine phosphate 5 mg/kg base (8.3 mg/kg salt) orally, once/week, up to maximum adult dose of 300 mg base; Hydroxychloroquine sulfate 5 mg/kg base (6.5 mg/kg salt) orally, once/week, up to a maximum adult dose of 310 mg base
- 6.22.1.3. Prophylaxis in areas with mefloquine-sensitive malaria
- Preferred regimen: Mefloquine 250 mg PO once a week
- Note (1): Begin ≥2 weeks before travel to malarious areas. Take weekly on the same day of the week while in the malarious area and for 4 weeks after leaving such areas. Contraindicated in people allergic to mefloquine or related compounds (quinine, quinidine) and in people with active depression, a recent history of depression, generalized anxiety disorder, psychosis, schizophrenia, other major psychiatric disorders, or seizures.
- Note (2): Use with caution in persons with psychiatric disturbances or a previous history of depression. Not recommended for persons with cardiac conduction abnormalities.
- Pediatric dose: Mefloquine ≤9 kg: 4.6 mg/kg base (5 mg/kg salt) orally, once/week
- >9–19 kg: 1/4 tablet once/week
- >19–30 kg: 1/2 tablet once/week
- >30–45 kg: 3/4 tablet once/week
- >30–45 kg: 3/4 tablet once/week
- 6.22.1.4. Prophylaxis for short-duration travel to areas with principally Plasmodium vivax
- Preferred regimen: Primaquine 52.6 mg PO qd
- Note: Begin 1–2 days before travel to malarious areas. Take daily at the same time each day while in the malarious area and for 7 days after leaving such areas. Contraindicated in people with G6PD deficiency. Also contraindicated during pregnancy and lactation, unless the infant being breastfed has a documented normal G6PD level.
- Pediatric dose: Primaquine 0.5 mg/kg base (0.8 mg/kg salt) up to adult dose orally, daily
- 6.22.1.5. Terminal prophylaxis to decrease the risk for relapses of Plasmodium vivax and Plasmodium ovale
- Preferred regimen: Primaquine 52.6 mg PO qd for 14 days after departure from the malarious area
- Note: Indicated for people who have had prolonged exposure to P. vivax, P. ovale, or both. Contraindicated in people with G6PD deficiency. Also contraindicated during pregnancy and lactation, unless the infant being breastfed has a documented normal G6PD level.
- Pediatric dose: Primaquine 0.5 mg/kg base (0.8 mg/kg salt) up to adult dose orally, daily for 14 days after departure from the malarious area
- 6.22.2. Treatment
- Note (1): Patients coinfected with HIV should avoid Artesunate AND Sulfadoxine-Pyrimethamine if they are also receiving Co-trimoxazole, and avoid Artesunate AND Amodiaquine if they are also receiving Efavirenz OR Zidovudine.
- Note (2): Because Plasmodium falciparum malaria can progress within hours from mild symptoms or low-grade fever to severe disease or death, all HIV-infected patients with confirmed or suspected P. falciparum infection should be hospitalized for evaluation, initiation of treatment, and observation.
- 6.22.2.1. Plasmodium falciparum
- 6.22.2.1.1. Treatment of uncomplicated Plasmodium falciparum malaria
- 6.22.2.1.1.1. Treat children and adults with uncomplicated Plasmodium falciparum malaria (except pregnant women in their first trimester) with one of the following recommended ACT (artemisinin-based combination therapy)
- Preferred regimen (1): Artemether 5–24 mg/kg/day PO bid AND Lumefantrine 29–144 mg/kg/day PO bid for 3 days
- Note: The first two doses should, ideally, be given 8 hours apart.
- Dosage regimen based on Body weight (kg)
- Body weight (kg)-5 to < 15- Artemether 20 mg PO bid AND Lumefantrine 120 mg PO bid for 3 days
- Body weight (kg)-15 to < 25- Artemether 40 mg PO bid AND Lumefantrine 240 mg PO bid for 3 days
- Body weight (kg)-25 to < 35- Artemether 60 mg PO bid AND Lumefantrine 360 mg PO bid for 3 days
- Body weight (kg) ≥ 35- Artemether 80 mg PO bid AND Lumefantrine 480 mg PO bid for 3 days
- Preferred regimen (2): Artesunate 2–10 mg/kg/day PO qd AND Amodiaquine 7.5–15 mg/kg/day PO qd for 3 days
- Note: A total therapeutic dose range of 6–30 mg/kg/day Artesunate and 22.5–45 mg/kg/day per dose Amodiaquine is recommended.
- Dosage regimen based on body weight (kg)
- Body weight (kg)-4.5 to < 9- Artesunate 25 mg PO qd AND Amodiaquine 67.5 mg PO qd for 3 days
- Body weight (kg)-9 to < 18 - Artesunate 50 mg PO qd AND Amodiaquine 135 mg PO qd for 3 days
- Body weight (kg)-18 to < 36- Artesunate 100 mg PO qd AND Amodiaquine 270 mg PO qd for 3 days
- Body weight (kg) ≥ 36 - Artesunate 200 mg PO qd AND Amodiaquine 540 mg PO qd for 3 days
- Preferred regimen (3): Artesunate 2–10 mg/kg/day PO qd AND Mefloquine 2–10 mg/kg/day PO qd for 3 days
- Dosage regimen based on body weight (kg)
- Body weight (kg)-5 to < 9- Artesunate 25 mg PO qd AND Mefloquine 55 mg PO qd for 3 days
- Body weight (kg)-9to < 18- Artesunate 50 mg PO qd AND Mefloquine 110 mg PO qd for 3 days
- Body weight (kg)-18 to < 36- Artesunate 100 mg PO qd AND Mefloquine 220 mg PO qd for 3 days
- Body weight (kg)- ≥ 36 - Artesunate 200 mg PO qd AND Mefloquine 440 mg PO qd for 3 days
- Preferred regimen (4): Artesunate 2–10 mg/kg/day PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1.25 (25–70 / 1.25–3.5) mg/kg/day PO given as a single dose on day 1
- Dosage regimen based on body weight (kg)
- Body weight (kg)- 5 to < 10- Artesunate 25 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 250/12 mg PO given as a single dose on day 1
- Body weight (kg)- 10 to < 25- Artesunate 50 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 500/25 mg PO given as a single dose on day 1
- Body weight (kg)- 25 to < 50- Artesunate 100 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1000/50 mg PO given as a single dose on day 1
- Body weight (kg)- ≥50- Artesunate 200 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1500/75 mg PO given as a single dose on day 1
- Preferred regimen (5): Dihydroartemisinin 2–10 mg/kg/day PO qd AND Piperaquine16–27 mg/kg/day PO qd for 3 days
- Dosage regimen based on Body weight (kg)
- Body weight (kg)-5 to < 8: Dihydroartemisinin 20 mg PO qd AND Piperaquine 160 mg PO qd for 3 days
- Body weight (kg)-8 to < 11: Dihydroartemisinin 30 mg PO qd AND Piperaquine 240 mg PO qd for 3 days
- Body weight (kg)-11 to < 17: Dihydroartemisinin 40 mg PO qd AND Piperaquine 320 mg PO qd for 3 days
- Body weight (kg)-17 to < 25: Dihydroartemisinin 60 mg PO qd AND Piperaquine 480 mg PO qd for 3 days
- Body weight (kg)-25 to < 36: Dihydroartemisinin 80 mg PO qd AND Piperaquine 640 mg PO qd for 3 days
- Body weight (kg)-36 to < 60: Dihydroartemisinin 120 mg PO qd AND Piperaquine 960 mg PO qd for 3 days
- Body weight (kg)-60 < 80: Dihydroartemisinin 160 mg PO qd AND Piperaquine 1280 mg PO qd for 3 days
- Body weight (kg)- >80: Dose of Dihydroartemisinin 200 mg PO qd AND Piperaquine 1600 mg PO qd for 3 days
- 6.22.2.1.1.2 Reducing the transmissibility of treated Plasmodium falciparum infections In low-transmission areas in patients with Plasmodium falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months)
- Preferred regimen: Primaquine 0.25 mg/kg PO single dose with ACT
- 6.22.2.1.2. Recurrent falciparum malaria
- 6.22.2.1.2.1. Failure within 28 days
- Note: The recommended second-line treatment is an alternative ACT known to be effective in the region. Adherence to 7-day treatment regimens with Artesunate or Quinine both of which should be co-administered with Tetracycline, or Doxycycline or Clindamycin) is likely to be poor if treatment is not directly observed; these regimens are no longer generally recommended.
- 6.22.2.1.2.2. Failure after 28 days
- Note: All presumed treatment failures after 4 weeks of initial treatment should, from an operational standpoint, be considered new infections and be treated with the first-line ACT. However, reuse of Mefloquine within 60 days of first treatment is associated with an increased risk for neuropsychiatric reactions, and an alternative ACT should be used.
- 6.22.2.1.3. Reducing the transmissibility of treated Plasmodium falciparum infections in low-transmission areas in patients with Plasmodium falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months)
- Note: Single dose of 0.25 mg/kg biweekly Primaquine with ACT
- 6.22.2.1.4. Treating uncomplicated Plasmodium falciparum malaria in special risk groups
- 6.22.2.1.4.1. Pregnancy
- First trimester of pregnancy : Quinine AND Clindamycin 10 mg/kg/day PO bid for 7 days
- Second and third trimesters : Mefloquine is considered safe for the treatment of malaria during the second and third trimesters; however, it should be given only in combination with an artemisinin derivative.
- Note (1): Quinine is associated with an increased risk for hypoglycaemia in late pregnancy, and it should be used (with clindamycin) only if effective alternatives are not available.
- Note (2): Primaquine and Tetracyclines should not be used in pregnancy.
- 6.22.2.1.4.2. Infants less than 5kg body weight
- Note: They should be treated with an ACT at the same mg/kg bw target dose as for children weighing 5 kg.
- 6.22.2.1.4.4. Large and obese adults
- Note: For obese patients, less drug is often distributed to fat than to other tissues; therefore, they should be dosed on the basis of an estimate of lean body weight, ideal body weight. Patients who are heavy but not obese require the same mg/kg bw doses as lighter patients.
- 6.22.2.1.4.5. Non-immune travellers
- Note: Treat travellers with uncomplicated P. falciparum malaria returning to nonendemic settings with an ACT.
- 6.22.2.1.4.6. Uncomplicated hyperparasitaemia
- Note: People with P. falciparum hyperparasitaemia are at increased risk of treatment failure, severe malaria and death so should be closely monitored, in addition to receiving an ACT.
- 6.22.2.2. Treatment of uncomplicated malaria caused by Plasmodium vivax, Plasmodium ovale, Plasmodium malariae or Plasmodium knowlesi
- 6.22.2.2.1. Blood Stage infection
- 6.22.2.2.1.1. Uncomplicated malaria caused by Plasmodium vivax
- 6.22.2.2.1.1.1. In areas with chloroquine-sensitive Plasmodium vivax
- Preferred regimen: Chloroquine total dose of 25 mg/kg PO. Chloroquine is given at an initial dose of 10 mg/kg, followed by 10 mg/kg on the second day and 5 mg/kg on the third day PO
- 6.22.2.2.1.1.2. In areas with chloroquine-resistant Plasmodium vivax
- Note: ACTs containing Piperaquine, Mefloquine OR Lumefantrine are the recommended treatment, although Artesunate AND Amodiaquine may also be effective in some areas. In the systematic review of ACTs for treating P. vivax malaria, Dihydroartemisinin AND Piperaquine provided a longer prophylactic effect than ACTs with shorter half-lives (Artemether ANDLumefantrine) OR (Artesunate AND Amodiaquine), with significantly fewer recurrent parasitaemias during 9 weeks of follow-up.
- 6.22.2.2.1.2. Uncomplicated malaria caused by Plasmodium ovale, Plasmodium malariae or Plasmodium knowlesi malaria
- Note: Resistance of P. ovale, P. malariae and P. knowlesi to antimalarial drugs is not well characterized, and infections caused by these three species are generally considered to be sensitive to Chloroquine. In only one study, conducted in Indonesia, was resistance to Chloroquine reported in P. malariae. The blood stages of P. ovale, P. malariae and P. knowlesi should therefore be treated with the standard regimen of ACT or Chloroquine, as for vivax malaria.
- 6.22.2.2.1.3. Mixed malaria infections
- Note: ACTs are effective against all malaria species and so are the treatment of choice for mixed infections.
- 6.22.2.2.2. Liver stages (hypnozoites) of Plasmodium vivax and Plasmodium ovale
- Note: To prevent relapse, treat P. vivax or P. ovale malaria in children and adults (except pregnant women, infants aged < 6 months, women breastfeeding infants < 6 months, women breastfeeding older infants unless they are known not to be G6PD deficient and people with G6PD deficiency) with a 14-day course of Primaquine in all transmission settings. Strong recommendation, high-quality evidence In people with G6PD deficiency, consider preventing relapse by giving primaquine base at 0.75 mg base/kg bw once a week for 8 weeks, with close medical supervision for potential primaquine-induced adverse haematological effects.
- 6.22.2.2.2.1. Primaquine for preventive relapse
- Preferred regimen: Primaquine 0.25–0.5 mg/kg/day PO qd for 14 days
- 6.22.2.2.2.2. Primaquine and glucose-6-phosphate dehydrogenase deficiency
- Preferred regimen: Primaquine 0.75 mg base/kg/day PO once a week for 8 weeks
- Note: The decision to give or withhold Primaquine should depend on the possibility of giving the treatment under close medical supervision, with ready access to health facilities with blood transfusion services.
- 6.22.2.2.2.3. Prevention of relapse in pregnant or lacating women and infants
- Note: Primaquine is contraindicated in pregnant women, infants < 6 months of age and in lactating women (unless the infant is known not to be G6PD deficient)
- 6.22.2.3. Treatment of severe malaria
- 6.22.2.3.1. Treatment of severe falciparum infection with Artesunate
- 6.22.2.3.1.1. Adults and children with severe malaria (including infants, pregnant women in all trimesters and lactating women)
- Preferred regimen: Artesunate IV/IM for at least 24 h and until they can tolerate oral medication. Once a patient has received at least 24 h of parenteral therapy and can tolerate oral therapy, complete treatment with 3 days of an ACT (add single dose Primaquine in areas of low transmission).
- 6.22.2.3.1.2. Young children weighing < 20 kg
- Preferred regimen:Artesunate 3 mg/kg per dose IV/IM q24h
- Alternative regimen: use Artemether in preference to quinine for treating children and adults with severe malaria
- 6.22.2.3.2.Treating cases of suspected severe malaria pending transfer to a higher-level facility (pre-referral treatment)
- 6.22.2.3.2.1. Adults and children
- Preferred regimen: Artesunate IM q24h
- Alternative regimen: Artemether IM OR Quinine IM
- 6.22.2.3.2.2. Children < 6 years
- Preferred regimen: Where intramuscular injections of artesunate are not available, treat with a single rectal dose (10 mg/kg) of Artesunate, and refer immediately to an appropriate facility for further care.
- Note: Do not use rectal artesunate in older children and adults.
- 6.22.2.3.3. Pregancy
- Note: Parenteral artesunate is the treatment of choice in all trimesters. Treatment must not be delayed.
- 6.22.2.3.4. Treatment of severe Plasmodium Vivax infection
- Note: Parenteral Artesunate, treatment can be completed with a full treatment course of oral ACT or Chloroquine (in countries where Chloroquine is the treatment of choice). A full course of radical treatment with Primaquine should be given after recovery.
- 6.22.2.3.5. Additional aspects of management in severe malaria
- Fluid therapy: It is not possible to give general recommendations on fluid replacement; each patient must be assessed individually and fluid resuscitation based on the estimated deficit.
- Blood Transfusion: In high-transmission settings, blood transfusion is generally recommended for children with a haemoglobin level of < 5 g/100 mL(haematocrit < 15%). In low-transmission settings, a threshold of 20% (haemoglobin,7 g/100 mL) is recommended.
- Exchange blood transfusion: Exchange blood transfusion requires intensive nursing care and a relatively large volume of blood, and it carries significant risks. There is no consensus on the indications, benefits and dangers involved or on practical details such as the volume of blood that should be exchanged. It is, therefore, not possible to make any recommendation regarding the use of exchange blood transfusion.
- 6.23. Cryptococcosis
- 6.23.1. Treatment
- 6.23.1.1. Cryptococcal meningitis
- 6.23.1.1.1. Induction therapy
- Preferred regimen: Liposomal amphotericin B 3–4 mg/kg IV q24h AND Flucytosine 25 mg/kg PO qid for at least 2 weeks, followed by consolidation therapy
- Alternative regimen (1): Amphotericin B deoxycholate 0.7 mg/kg IV q24h AND Flucytosine 25 mg/kg PO qid
- Alternative regimen (2): Amphotericin B lipid complex 5 mg/kg IV q24h AND Flucytosine 25 mg/kg PO qid
- Alternative regimen (3): Liposomal Amphotericin B 3-4 mg/kg IV q24h AND Fluconazole 800 mg PO or IV q24h
- Alternative regimen (4): Amphotericin B deoxycholate 0.7 mg/kg IV q24h AND Fluconazole 800 mg PO or IV q24h
- Alternative regimen (5): Fluconazole 400–800 mg PO or IV qd AND Flucytosine 25 mg/kg PO qid
- Alternative regimen (6): Fluconazole 1200 mg PO or IV qd
- 6.23.1.1.2. Consolidation therapy
- Preferred regimen: Fluconazole 400 mg PO (or IV) qd for atleast 8 weeks
- Note: Preferred therapy followed by maintenance therapy.
- Maintenance therapy: Fluconazole 200 mg PO qd for at least 12 months
- Alternative regimen: Itraconazole 200 mg PO bid for 8 weeks
- 6.23.1.2. Non-CNS cryptococcosis with mild-to-moderate symptoms and focal pulmonary infiltrates
- Preferred regimen: Fluconazole, 400 mg PO qd for 12 months
- Note: Patients receiving Flucytosine should have either blood levels monitored (peak level 2 hours after dose should be 30–80 mcg/mL) or close monitoring of blood counts for development of cytopenia. Dosage should be adjusted in patients with renal insufficiency.
- 6.24. Mucocutaneous candidiasis
- 6.24.1. Treatment
- 6.24.1.1. For oropharyngeal candidiasis
- Oral Therapy
- Preferred regimen: Fluconazole 100 mg PO qd for 7-14 days.
- Alternative regimen: Itraconazole oral solution 200 mg PO qd for 7-14 days OR Posaconazole oral suspension 400 mg PO bid for 1 day, then 400 mg qd 7-14 days
- Topical therapy
- Preferred regimen: Clotrimazole troches, 10 mg PO 5 times daily OR Miconazole mucoadhesive buccal 50-mg tablet
- Note: Apply to mucosal surface over the canine fossa once daily (do not swallow, chew, or crush).
- Alternative regimen: Nystatin suspension 4–6 mL qid or 1–2 flavored pastilles 4– 5 times daily
- 6.24.1.2. For esophageal candidiasis
- Preferred regimen: Fluconazole 100 mg (up to 400 mg) PO or IV qd for 14-21 days OR Itraconazole oral solution 200 mg PO qd for 14-21 days
- Alternative regimen (1): Voriconazole 200 mg PO or IV bid for 14-21 days
- Alternative regimen (2): Anidulafungin 100 mg IV single dose, then 50 mg IV qd for 14-21 days
- Alternative regimen (3): Caspofungin 50 mg IV qd for 14-21 days
- Alternative regimen (4): Micafungin 150 mg IV qd for 14-21 days
- Alternative regimen (5): Amphotericin B deoxycholate 0.6 mg/kg IV qd for 14-21 days
- Alternative regimen (6): Lipid formulation of amphotericin B 3–4 mg/kg IV qd for 14-21 days
- 6.24.1.3. For uncomplicated vulvo-vaginal candidiasis
- Preferred regimen: Oral Fluconazole 150 mg for 1 dose OR Topical azoles (Clotrimazole, Butoconazole, Miconazole, Tioconazole, or Terconazole) for 3– 7 days
- Alternative regimen: Itraconazole oral solution 200 mg PO qd for 3–7 days
- 6.24.1.4. For severe or recurrent vulvovaginal candidiasis
- Preferred regimen: Fluconazole 100–200 mg PO qd for ≥7 days OR Topical antifungal ≥7 days
- 6.25. Bartonellosis
- 6.25.1. Treatment
- 6.25.1.1. For bacillary angiomatosis, peliosis hepatis, bacteremia, and osteomyelitis
- Preferred regimen (1): Doxycycline 100 mg PO or IV q12h for 3 months
- Preferred regimen (2): Erythromycin 500 mg PO or IV q6h for 3 months
- Alternative regimen (1): Azithromycin 500 mg PO qd
- Alternative regimen (2):} Clarithromycin 500 mg PO bid
- 6.25.1.2. Confirmed bartonella endocarditis
- Preferred regimen: Doxycycline 100 mg IV q12h AND Gentamicin 1 mg/kg IV q8h) for 2 weeks, then continue with Doxycycline 100 mg IV or PO q12h
- Altered regimen: Doxycycline 100 mg IV AND Rifabutin 300 mg PO or IV q12h for 2 weeks, then continue with Doxycycline 100 mg IV or PI q12h
- 6.25.1.3. CNS infections
- Preferred regimen: (Doxycycline 100 mg with or without Rifabutin 300 mg PO or IV q12h
- 6.25.1.4. Other severe infections
- Preferred regimen (1): Doxycycline 100 mg PO or IV with or without Rifabutin 300 mg PO or IV) q12h for 3 months
- Preferred regimen (2): Erythromycin 500 mg PO or IV q6h) with or without Rifabutin) 300 mg PO or IV q12h for 3 months.
- Note: If relapse occurs after initial (>3 month) course of therapy, longterm suppression with Doxycycline or a macrolide is recommended as long as CD4 count <200 cells/µL.
- 6.26. Campylobacteriosis
- 6.26.1. Treatment
- 6.26.1.1. For mild-to-moderate disease (If Susceptible)
- Preferred regimen: Ciprofloxacin 500–750 mg PO or 400 mg IV q12h OR Azithromycin 500 mg PO qd
- Alternative regimen: Levofloxacin 750 mg PO or IV q24h OR Moxifloxacin 400 mg (PO or IV) q24h
- 6.26.1.2. For campylobacter bacteremia
- Preferred regimen: Ciprofloxacin 500–750 mg PO or 400 mg IV q12h AND an aminoglycoside.
- Duration of Therapy:
- Gastroenteritis: 7–10 days (5 days with Azithromycin)
- Bacteremia: ≥14 days
- Recurrent bacteremia: 2–6 weeks.
- 6.27. Shigellosis
- 6.27.1. Treatment
- Preferred regimen: Ciprofloxacin 500–750 mg PO or 400 mg IV q12h
- Duration of Therapy:
- Gastroenteritis: 7–10 days
- Bacteremia: ≥14 days
- Recurrent Infections: 2–6 weeks
- Alternative regimen (1): Levofloxacin 750 mg PO or IV q24h for 5 days
- Alternative regimen (2): Moxifloxacin 400 mg PO or IV q24h for 5 days
- Alternative regimen (3): Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO or IV q12h for 5 days
- Alternative regimen (4): Azithromycin 500 mg PO qd for 5 days
- Note: Antimotility agents should be avoided.
- 6.28. Salmonellosis
- 6.28.1. Treatment
- Preferred regimen: Ciprofloxacin 500–750 mg PO or 400 mg IV q12h
- Alternative regimen (1): Levofloxacin 750 mg PO or IV q24h
- Alternative regimen (2): Moxifloxacin 400 mg PO or IV q24h
- Alternative regimen (3): Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO or IV q12h
- Alternative regimen (4): Cefotaxime 1 g IV q8h
- Alternative regimen (5): Ceftriaxone 1 g IV q24h
- Duration of therapy:
- For gastroenteritis without bacteremia:
- If CD4 count ≥200 cells/µL: 7–14 days.
- If CD4 count <200 cells/µL: 2–6 weeks.
- For gastroenteritis with bacteremia:
- If CD4 count ≥200/µL: 14 days; longer duration if bacteremia persists or if the infection is complicated (e.g., if metastatic foci of infection are present)
- If CD4 count <200 cells/µL: 2–6 weeks
- Note (1): The role of long-term secondary prophylaxis in patients with recurrent Salmonella bacteremia is not well established. Must weigh benefit against risks of long-term antibiotic exposure.
- Note (2): Secondary Prophylaxis Should Be Considered For:
- Patients with recurrent Salmonella gastroenteritis +/- bacteremia.
- Patients with CD4 <200 cells/µL with severe diarrhea.
- 6.29. Bacterial enteric infections
- 6.29.1. Empiric therapy
- Preferred regimen: Ciprofloxacin 500–750 mg PO or 400 mg IV q12h
- Alternative regimen: Ceftriaxone 1 g IV q24h OR Cefotaxime 1 g IV q8h
- Note: Antimotility agents should be avoided if there is concern about inflammatory diarrhea, including Clostridium-difficile-associated diarrhea.
- 6.30.Bacterial respiratory diseases
- 6.30.1. Treatment
- 6.30.1.1. Empiric outpatient therapy
- Preferred regimen: Amoxicillin 500 mg PO AND (Azithromycin 500 mg PO OR Clarithromycin 500 mg PO) qd for 7-10 days
- Alternative regimen: Amoxicillin 500 mg PO AND Doxycycline 100mg PO qd
- Note: Therapy should be adjusted based on the results of diagnostic workup.
- 6.30.1.2. For penicillin-allergic patients
- Preferred regimen: Ceftriaxone 1 g IV q24h AND (Azithromycin 500 mg PO OR Clarithromycin 500 mg PO) qd for 7-10 days
- Alternative regimen: Aztreonam 1 g IV q24h AND Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h
- 6.30.1.3. Empiric therapy for non-ICU hospitalized patients
- Preferred regimen: Ceftriaxone 1 g IV q24h AND (Azithromycin 500 mg PO OR Clarithromycin 500 mg PO) qd
- 6.30.1.3. Empiric therapy for patients at risk of pseudomonas pneumonia
- Preferred regimen: : Piperacillin-Tazobactam 2 g-0.25 g IV q24h AND (Ciprofloxacin 400 mg IV q8–12h OR Levofloxacin 750 mg IV) q24h
- 6.30.1.4. Empiric therapy for patients at risk for methicillin-resistant staphylococcus aureus pneumonia
- Preferred regimen: Amoxicillin 500 mg PO AND (Azithromycin 500 mg PO OR Clarithromycin 500 mg) PO AND Linezolid 600 mg (IV or PO).
- Note (1): Empiric therapy with a macrolide alone is not routinely recommended, because of increasing pneumococcal resistance.
- Note (2): Chemoprophylaxis can be considered for patients with frequent recurrences of serious bacterial pneumonia.
- 6.31. Cryptosporidiosis
- 6.31.1. Treatment
- Note (1): Initiate or optimize ART for immune restoration to CD4 count >100 cells/µL. Aggressive oral or IV rehydration and replacement of electrolyte loss and symptomatic treatment of diarrhea with anti-motility agents.
- Preferred regimen (1): Nitazoxanide 500–1000 mg PO bid for 14 days
- Preferred regimen (2): Paromomycin 500 mg PO qid for 14–21 days
- Note (2): With optimized anti retroviral therapy, symptomatic treatment and rehydration and electrolyte replacement is recommended. Tincture of opium may be more effective than Loperamide in management of diarrhea.
- 6.32. Microsporidiosis
- 6.32.1. Treatment
- 6.32.1.1. For GI infections caused by enterocytozoon bienuesi
- Note: Initiate or optimize anti retroviral therapy as immune restoration to CD4 count >100 cells/µL AND manage severe dehydration, malnutrition, and wasting by fluid support.
- Preferred therapy (1): Fumagillin 60 mg/day PO bid
- Preferred therapy (2): TNP-470 PO bid
- Preferred therapy (3): Nitazoxanide 1000 mg PO bid
- 6.32.1.2. For intestinal and disseminated (not ocular) infections caused by microsporidia other than E. bienuesi and vittaforma corneae
- Preferred regimen: Albendazole 400 mg PO bid, continue until CD4 count >200 cells/µL for >6 months after initiation of anti retroviral therapy
- Alternative regimen: Itraconazole 400 mg PO qd AND Albendazole 400 mg PO bid
- 6.32.1.3. For ocular infection
- Preferred regimen: Topical fumagillin bicylohexylammonium (Fumidil B) eye drops: 3 mg/mL in saline (fumagillin 70 µg/mL)—2 drops q2h for 4 days, then 2 drops qid AND Albendazole 400 mg PO bid, for management of systemic infection
- Note: Therapy should be continued until resolution of ocular symptoms and CD4 count increase to >200 cells/µL for >6 months in response to anti retroviral therapy.
- 6.33. Progressive Multifocal Leukoencephalopathy (PML)
- Note (1): There is no specific antiviral therapy for JC virus infection. The main treatment approach is to reverse the immunosuppression caused by HIV.
- Note (2): Initiate anti retroviral therapy immediately in anti retroviral therapy naive patients.
- Note (3): Optimize anti retroviral therapy in patients who develop PML in phase of HIV viremia on anti retroviral therapy.
- Note (4): Corticosteroids may be used for PML-IRIS characterized by contrast enhancement, edema or mass effect, and with clinical deterioration. | Sandbox ID3
# WikiDoc Infectious Disease Project — Pathogen-Based Infections
## Pathogens of Public Health Significance
## Pathogens of Clinical Significance
### Bacteria – Gram-Positive Cocci
# Enterococcus faecalis
- Enterococcus faecalis Return to Top
- 1. Bacteremia[1]
- 1.1 Ampicillin or penicillin susceptible
- Preferred regimen (1): Ampicillin 2 g IV q4-6h
- Preferred regimen (2): Ampicillin 2 g IV q4-6h AND Gentamicin 1 mg/kg IV/IM q8h
- 1.2 Ampicillin resistant and vancomycin susceptible or penicillin allergy
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h AND Gentamicin 1 mg/kg IV/IM q8h
- Preferred regimen (2): Linezolid 600 mg IV q12h
- Preferred regimen (3): Daptomycin 6 mg/kg IV q24h
- 1.3 Ampicillin and vancomycin resistant
- Preferred regimen (1): Linezolid 600 mg IV q12h
- Preferred regimen (2): Daptomycin 6 mg/kg IV q24h
- 2. Endocarditis[2][3]
- 2.1 Endocarditis in adults
- 2.1.1 Strains susceptible to penicillin, gentamicin, and vancomycin
- Preferred regimen: (Ampicillin 12 g IV q24h for 4–6 weeks OR Aqueous crystalline penicillin G sodium 18–30 MU IV q24h for 4–6 weeks) AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 4–6 weeks
- Alternative regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
- Note (1): In case of native valve endocarditis with symptoms ≤ 3 months, a 4-week course of therapy is recommended.
- Note (2): In case of native valve endocarditis with symptoms > 3 months, a 6-week course of therapy is recommended.
- Note (3): In case of prosthetic valve or other prosthetic cardiac material, a minimum of 6-week course of therapy is recommended.
- 2.1.2 Strains susceptible to penicillin, streptomycin, and vancomycin and resistant to gentamicin
- Preferred regimen: (Ampicillin 12 g IV q24h for 4–6 weeks OR Aqueous crystalline penicillin G sodium 24 MU IV q24h for 4–6 weeks) AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 4–6 weeks
- Alternate regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 6 weeks
- 2.1.3 Strains resistant to penicillin and susceptible to aminoglycoside and vancomycin
- 2.1.3.1 β Lactamase–producing strain
- Preferred regimen: Ampicillin-sulbactam 12 g IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h 6 weeks
- Alternate regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
- 2.1.3.2 Intrinsic penicillin resistance
- Preferred regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
- 2.1.4 Strains resistant to penicillin, aminoglycoside, and vancomycin
- Preferred regimen (1): (Imipenem OR Cilastatin 2 g/day IV for ≥ 8weeks) AND Ampicillin 12 g/day IV for ≥ 8 weeks
- Preferred regimen (2): Ceftriaxone sodium 4 g IV/IM q24h for ≥ 8weeks AND Ampicillin 12 g IV q24h for ≥ 8 weeks
- 2.2 Endocarditis in pediatrics
- 2.2.1 Strains susceptible to penicillin, gentamicin, and vancomycin
- Preferred regimen: (Ampicillin 300 mg/kg IV q24h for 4–6 weeks OR Penicillin 0.3 MU/kg IV q24h for 4–6 weeks) AND Gentamicin 3 mg/kg IV/IM q24h 4–6 weeks
- Note (1): In case of native valve endocarditis with symptoms ≤ 3 months, a 4-week course of therapy is recommended.
- Note (2): In case of native valve endocarditis with symptoms > 3 months, a 6-week course of therapy is recommended.
- Note (3): In case of prosthetic valve or other prosthetic cardiac material, a minimum of 6-week course of therapy is recommended.
- Alternate regimen : Vancomycin 40 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
- 2.2.2 Strains susceptible to penicillin, streptomycin, and vancomycin and resistant to gentamicin
- Preferred regimen: (Ampicillin 300 mg/kg IV q24h for 4–6 weeks OR Penicillin 0.3 MU/kg IV q24h for 4–6 weeks) AND Streptomycin 20–30 mg/kg IV/IM q24h for 4–6 weeks
- Alternate regimen: Vancomycin hydrochloride 40 mg/kg IV q24h for 6 weeks AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 6 weeks
- 2.2.3 Strains resistant to penicillin and susceptible to aminoglycoside and vancomycin
- 2.2.3.1 β Lactamase–producing strain
- Preferred regimen: Ampicillin-sulbactam 300 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
- Alternate regimen: Vancomycin 40 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
- 2.2.3.2 Intrinsic penicillin resistance
- Preferred regimen: Vancomycin 40 mg/kg IV q24h AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
- 2.2.4 Strains resistant to penicillin, aminoglycoside, and vancomycin
- Preferred regimen: Imipenem/Cilastatin 60–100 mg/kg IV q24h for ≥ 8 weeks AND Ampicillin 300 mg/kg IV q24h for ≥ 8 weeks
- Alternate regimen: Ceftriaxone 100 mg/kg IV/IM q24h AND Ampicillin 300 mg/kg IV q24h for ≥ 8 weeks
- 3. Meningitis[4]
- 3.1 Ampicillin susceptible
- Preferred regimen: Ampicillin 12 g/day IV q4h AND Gentamicin 5 mg/kg/day IV q8h
- 3.2 Ampicillin resistant
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Gentamicin 5 mg/kg/day IV q8h
- 3.3 Ampicillin and vancomycin resistant
- Preferred regimen: Linezolid 600 mg IV q12h
- 4. Urinary tract infections [5]
- Preferred regimen (1): Nitrofurantoin 100 mg PO q6h for 5 days
- Preferred regimen (2): Fosfomycin 3 g PO single dose
- Preferred regimen (3): Amoxicillin 875 mg to 1 g PO q12h for 5 days
- 5. Intra abdominal or wound infections [6]
- Preferred regimen (1): Penicillin
- Preferred regimen (2): Ampicillin
- Alternative regimen (Penicillin allergy or high-level Penicillin resistance): Vancomycin
- Alternative regimen (For complicated skin-skin structure and intra-abdominal infection): Tigecycline 100 mg IV single dose and 50 mg IV q12h
- Enterococcus faecium Return to Top
- 1. Bacteremia[7]
- 1.1 Ampicillin or penicillin susceptible
- Preferred regimen (1): Ampicillin 2 g IV q4-6h
- Preferred regimen (2): Ampicillin 2 g IV q4-6h AND Gentamicin 1 mg/kg IV/IM q8h
- 1.2 Ampicillin resistant and vancomycin susceptible or penicillin allergy
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h AND Gentamicin 1 mg/kg IV/IM q8h
- Preferred regimen (2): Linezolid 600 mg IV q12h
- Preferred regimen (3): Daptomycin 6 mg/kg IV q24h.
- 1.3 Ampicillin and vancomycin resistant
- Preferred regimen (1): Linezolid 600 mg IV q12h
- Preferred regimen (2): Daptomycin 6 mg/kg IV q24h
- 2. Endocarditis[2][8]
- 2.1 Endocarditis in adults
- 2.1.1 Strains susceptible to penicillin, gentamicin, and vancomycin
- Preferred regimen: (Ampicillin 12 g IV q24h for 4–6 weeks OR Aqueous crystalline penicillin G sodium 18–30 MU IV q24h for 4–6 weeks) AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 4–6 weeks
- Alternative regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
- Alternate regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
- Note (1): In case of native valve endocarditis with symptoms ≤ 3 months, a 4-week course of therapy is recommended.
- Note (2): In case of native valve endocarditis with symptoms > 3 months, a 6-week course of therapy is recommended.
- Note (3): In case of prosthetic valve or other prosthetic cardiac material, a minimum of 6-week course of therapy is recommended.
- 2.1.2 Strains susceptible to penicillin, streptomycin, and vancomycin and resistant to gentamicin
- Preferred regimen: (Ampicillin 12 g IV q24h for 4–6 weeks OR Aqueous crystalline penicillin G sodium 24 MU/day IV q24h for 4–6 weeks) AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 4–6 weeks
- Alternate regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 6 weeks
- 2.1.3 Strains resistant to penicillin and susceptible to aminoglycoside and vancomycin
- 2.1.3.1 β Lactamase–producing strain
- Preferred regimen: Ampicillin-sulbactam 12 g IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
- Alternate regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
- 2.1.3.2 Intrinsic penicillin resistance
- Preferred regimen: Vancomycin hydrochloride 30 mg/kg IV q24h for 6 weeks AND Gentamicin sulfate 3 mg/kg IV/IM q24h for 6 weeks
- 2.1.4 Strains resistant to penicillin, aminoglycoside, and vancomycin
- Preferred regimen (1): Linezolid 1200 mg IV/PO q24h ≥ 8 weeks
- Preferred regimen (2): Quinupristin-Dalfopristin 22.5 mg/kg IV q24h ≥ 8 weeks
- 2.2 Endocarditis in pediatrics
- 2.2.1 Strains susceptible to penicillin, gentamicin, and vancomycin
- Preferred regimen: (Ampicillin 300 mg/kg IV q24h for 4–6 weeks OR Penicillin 0.3MU/kg IV q24h for 4–6 weeks) AND Gentamicin 3 mg/kg IV/IM q24h 4–6 weeks
- Alternate regimen: Vancomycin 40 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
- Note (1): In case of native valve endocarditis with symptoms ≤ 3 months, a 4-week course of therapy is recommended.
- Note (2): In case of native valve endocarditis with symptoms > 3 months, a 6-week course of therapy is recommended.
- Note (3): In case of prosthetic valve or other prosthetic cardiac material, a minimum of 6-week course of therapy is recommended.
- 2.2.2 Strains Susceptible to penicillin, streptomycin, and vancomycin and resistant to gentamicin
- Preferred regimen: (Ampicillin 300 mg/kg IV q24h for 4–6 weeks OR Penicillin 0.3MU/kg IV q24h for 4–6 weeks) AND Streptomycin 20–30 mg/kg IV/IM q24h for 4–6 weeks
- Alternate regimen: Vancomycin hydrochloride 40 mg/kg IV q24h for 6 weeks AND Streptomycin sulfate 15 mg/kg IV/IM q24h for 6 weeks
- 2.2.3 Strains resistant to penicillin and susceptible to aminoglycoside and vancomycin
- 2.2.3.1 β Lactamase–producing strain
- Preferred regimen: Ampicillin-sulbactam 300 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
- Alternate regimen: Vancomycin 40 mg/kg IV q24h for 6 weeks AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
- 2.2.3.2 Intrinsic penicillin resistance
- Preferred regimen: Vancomycin 40 mg/kg IV q24h AND Gentamicin 3 mg/kg IV/IM q24h for 6 weeks
- 2.2.4 Strains resistant to penicillin, aminoglycoside, and vancomycin
- Preferred regimen (1): Linezolid 30 mg/kg IV/PO q24h ≥ 8 weeks
- Preferred regimen (2): Quinupristin-Dalfopristin 22.5 mg/kg IV q24h ≥ 8 weeks
- 3. Meningitis[4]
- 3.1 Ampicillin susceptible
- Preferred regimen: Ampicillin 12 g/day IV q4h AND Gentamicin 5 mg/kg/day IV q8h
- 3.2 Ampicillin resistant
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Gentamicin 5 mg/kg/day IV q8h
- 3.3 Ampicillin and vancomycin resistant
- Preferred regimen: Linezolid 600 mg IV q12h
- 4. Urinary tract infections[9]
- Preferred regimen (1): Nitrofurantoin 100 mg PO q6h for 5 days
- Preferred regimen (2): Fosfomycin 3 g PO single dose
- Preferred regimen (3): Amoxicillin 875 mg to 1 g PO q12h for 5 days
- 5. Intra abdominal or wound infections [10]
- Preferred regimen (1): Penicillin
- Preferred regimen (2): Ampicillin
- Alternative regimen (penicillin allergy or high-level penicillin resistance): Vancomycin
- Alternative regimen (for complicated skin-skin structure and intra-abdominal infection): Tigecycline 100 mg IV single dose and 50 mg IV q12h
- Staphylococcus aureus Return to Top
- Staphylococcus aureus treatment
- 1. Infectious endocarditis[11]
- 1.1 In adults
- Preferred regimen (1): Vancomycin 15-20 mg/kg IV q8-12h
- Preferred regimen (2): Daptomycin 6mg/kg/dose IV qd
- 2. Intravascular catheter-related infections[12]
- 2.1 Methicillin susceptible Staphylococcus aureus (MSSA)
- Preferred regimen (1): Nafcillin 2 g IV q6h
- Preferred regimen (2): Oxacillin 2 g IV q6h
- Alternative regimen (1): Cefazolin 2 g IV q8h
- Alternative regimen (2): Vancomycin 15 mg/kg IV q12h
- 2.1.1 Pediatric dose of Nafcillin
- 2.1.1.1 Neonates (< 4 weeks)
- For < 1200 g: Nafcillin 50 mg/kg/day q12h
- For ≤ 7 days of age and 1200–2000 g: Nafcillin 50 mg/kg/day q12h
- For ≤ 7 days of age and > 2000 g: Nafcillin 75 mg/kg/day q8h
- For > 7 days of age and 1200–2000 g: Nafcillin 75 mg/kg/day q8h
- For > 7 days of age and > 2000 g: Nafcillin 100 mg/kg/day q6h
- 2.1.1.2 Infants and children (> 4 weeks)
- Nafcillin 100–200 mg/kg/day q4–6h
- 2.1.2 Pediatric dose of Oxacillin
- 2.1.2.1 Neonates (< 4 weeks)
- For < 1200 g: Oxacillin 50 mg/kg/day q12h
- For Postnatal age < 7 days and 1200–2000 g: Oxacillin 50–100 mg/kg/day q12h
- For Postnatal age < 7 days and > 2000 g: Oxacillin 75–150 mg/kg/day q8h
- For Postnatal age ≥ 7 days and 1200–2000 g: Oxacillin 75–150 mg/kg/day q8h
- For Postnatal age ≥ 7 days and > 2000 g: Oxacillin 100–200 mg/kg/day q6h
- 2.1.2.2 Infants and children(> 4weeks)
- Oxacillin 150–200 mg/kg/day q4–6h
- 2.1.3 Pediatric dose of Cefazolin
- 2.1.3.1 Neonates (< 4 weeks)
- Postnatal age ≤ 7 days: Cefazolin 40 mg/kg/day q12h
- Postnatal age > 7 days and ≤ 2000 g: Cefazolin 40 mg/kg/day q12h
- Postnatal age > 7 days and > 2000 g: Cefazolin 60 mg/kg/day q8h
- 2.1.3.2 Infants and children (> 4 weeks)
- Cefazolin 50 mg/kg/day q8h.
- 2.1.4 Pediatric dose of Vancomycin
- 2.1.4.1 Neonates (< 4 weeks)
- Postnatal age ≤ 7 days and < 1200 g: Vancomycin 15 mg/kg/day q24h.
- Postnatal age ≤ 7 days and 1200–2000 g: Vancomycin 10–15 mg/kg q12–18h.
- Postnatal age ≤ 7 days and > 2000 g: Vancomycin 10–15 mg/kg q8–12h.
- Postnatal age > 7 days and < 1200 g: Vancomycin 15 mg/kg/day q24h.
- Postnatal age > 7 days and 1200–2000 g: Vancomycin 10–15 mg/kg q8–12h.
- Postnatal age > 7 days and > 2000 g: Vancomycin 15–20 mg/kg q8h.
- 2.1.4.2 Infants and children (> 4 weeks)
- Vancomycin 40 mg/kg/day q6–8h.
- 2.2 Methicillin resistant Staphylococcus aureus (MRSA)
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h
- Preferred regimen (2): Daptomycin 6–8 mg/kg/day IV
- Preferred regimen (3): Linezolid 10 mg/kg IV/PO q12h
- Preferred regimen (4): Vancomycin 15 mg/kg IV q12h AND (Rifampicin IV or Gentamycin IV)
- Preferred regimen (5): Trimethoprim-Sulfamethoxazole 6–12 mg TMP/kg/day q12h alone (if susceptible)
- 2.2.1 Pediatric dose of Linezolid
- 2.2.1.1 Neonates (< 4 weeks)
- For < 1200 g: Linezolid 10 mg/kg q8–12h (note: q12h in patients < 34 weeks gestation and < 1 week of age).
- For < 7 days of age and ≥ 1200 g: Linezolid 10 mg/kg q8–12h (note: q12h in patients < 34 weeks gestation and < 1 week of age).
- For ≥ 7 days and ≥ 1200 g: Linezolid 10 mg/kg q8h
- 2.2.1.2 Infants and children < 12 years (> 4 weeks)
- Linezolid 10 mg/kg q8h
- 2.2.1.3 Children ≥ 12 years and adolescents
- Linezolid 10 mg/kg q12h
- 2.2.2 Pediatric dose of Gentamycin
- 2.2.2.1 Neonates (< 4 weeks)
- Premature neonates and < 1000 g: Gentamycin 3.5 mg/kg q24h
- < 1200 g: Gentamycin 2.5 mg/kg q18-24h.
- Postnatal age ≤ 7 days: Gentamycin 2.5 mg/kg q12h.
- Postnatal age > 7 days and 1200–2000 g: Gentamycin 2.5 mg/kg q8-12h.
- Postnatal age > 7 days and > 1200 g: Gentamycin 2.5 mg/kg q8h.
- Premature neonates with normal renal function: Gentamycin 3.5–4 mg/kg q24h.
- Term neonates with normal renal function: Gentamycin 3.5–5 mg/kg q24h.
- 2.2.2.2 Infants and children < 5 years (> 4 weeks)
- Gentamycin 2.5 mg/kg q8h; qd dosing in patients with normal renal function, Gentamycin 5–7.5 mg/kg q24h.
- 2.2.2.3 Children ≥ 5 years
- Gentamycin 2–2.5 mg/kg q8h; qd with normal renal function, Gentamycin 5–7.5 mg/kg q24h.
- 2.2.3 Pediatric dose of Trimethoprim-Sulfamethoxazole
- 2.2.3.1 Infants > 2 months of age and children of mild-to-moderate infections
- Trimethoprim-Sulfamethoxazole 6–12 mg TMP/kg/day q12h; serious infection- Trimethoprim-Sulfamethoxazole 15–20 mg TMP/kg/day q6-8h.
- 3. Cellulitis[13]
- 3.1.1 In adults
- Preferred regimen (1): Clindamycin 300–450 mg PO tid
- Preferred regimen (2): Trimethoprim-Sulfamethoxazole 1–2 DS (double strength) tab PO bid
- Preferred regimen (3): Doxycycline 100 mg PO bid
- Preferred regimen (4): Minocycline 200 mg as a single dose THEN 100 mg PO bid
- Preferred regimen (5): Linezolid 600 mg PO bid
- 3.1.2 In children
- Preferred regimen (1): Clindamycin 10–13 mg/kg PO q6–8h, not to exceed 40 mg/kg/day
- Preferred regimen (2): Trimethoprim 4–6 mg/kg, Sulfamethoxazole 20–30 mg/kg PO q12h
- Preferred regimen (3)
- 3.1 If patient body weight < 45kg then Doxycycline 2 mg/kg PO q12h
- 3.2 If patient body weight 45kg then Doxycycline adult dose
- Preferred regimen (4): Minocycline 4 mg/kg PO 200 mg as a single dose, THEN Minocycline 2 mg/kg PO q12h
- Preferred regimen (5): Linezolid 10 mg/kg PO q8h, (max: 600 mg)
- 3.2 Nonpurulent cellulitis (defined as cellulitis with no purulent drainage or exudate and no associated abscess)
- 3.2.1 In adults
- Preferred regimen (1): Beta-lactam (eg, Cephalexin and Dicloxacillin) 500 mg PO qid
- Preferred regimen (2): Clindamycin 300–450 mg PO tid
- Preferred regimen (3): Amoxicillin 500 PO mg tid
- Preferred regimen (4): Linezolid 600 mg PO bid
- Note (1): Empirical therapy for beta-hemolytic streptococci is recommended. Empirical coverage for CA-MRSA is recommended in patients who do not respond to beta-lactam therapy and may be considered in those with systemic toxicity.
- Note (2): Provide coverage for both beta-hemolytic streptococci and CA-MRSA beta-lactam (eg, Amoxicillin) with or without Trimethoprim-Sulfamethoxazole or a Tetracycline
- 3.2.2 In children
- Preferred regimen (1): Clindamycin 10–13 mg/kg PO q6–8h, not to exceed 40 mg/kg/day
- Preferred regimen (2): Trimethoprim 4–6 mg/kg, Sulfamethoxazole 20–30 mg/kg PO q12h
- Preferred regimen (3): Linezolid 10 mg/kg PO q8h, not to exceed 600 mg
- Note (1): Clindamycin causes Clostridium difficile–associated disease may occur more frequently, compared with other oral agents.
- Note (2): Trimethoprim-Sulfamethoxazole not recommended for women in the third trimester of pregnancy and for children ,2 months of age.
- Note (3): Tetracyclines are not recommended for children under 8 years of age and are pregnancy category D.
- 4. Brain abscess[14][15][16]
- 4.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- 4.1.1 In adults
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 4–6 weeks
- Alternative regimen (1): Linezolid 600 mg PO/IV q12h for 4–6 weeks
- Alternative regimen (2): Trimethoprim-Sulfamethoxazole 5 mg/kg PO/IV q8–12h for 4–6 weeks
- 4.1.2 In children
- Preferred regimen (1): Vancomycin15 mg/kg/dose IV q6h
- Preferred regimen (2): Linezolid 10 mg/kg/dose PO/IV q8h
- Note: Consider the addition of Rifampin 600 mg qd OR 300–450 mg bid to Vancomycin.
- 4.2 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen (1): Nafcillin 2 g IV q4h
- Preferred regimen (2): Oxacillin 2 g IV q4h
- Alternative regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
- 5. Cerebrospinal fluid shunt infection[17][18]
- 5.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h with or without Rifampin 600 mg IV or PO q24h
- Note: Shunt removal is recommended, and it should not be replaced until cerebrospinal fluid cultures are repeatedly negative.
- 5.2 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen (1): Nafcillin 2 g IV q4h with or without Rifampin 600 mg IV/PO q24h
- Preferred regimen (2): Oxacillin 2 g IV q4h
- 6. Spinal epidural abscess[19][20][21][22]
- 6.1 Penicillin-susceptible Staphylococcus aureus or Streptococcus
- Preferred regimen: Penicillin G 4 MU IV q4h for 2–4 weeks, THEN PO to complete 6–8 weeks
- 6.2 Methicillin-susceptible Staphylococcus aureus or Streptococcus
- Preferred regimen (1): Cefazolin 2 g IV q8h for 2–4 weeks, THEN PO to complete 6–8 weeks
- Preferred regimen (2): Nafcillin 2 g IV q4h for 2–4 weeks, THEN PO to complete 6–8 weeks
- Preferred regimen (3): Oxacillin 2 g IV q4h for 2–4 weeks, THEN PO to complete 6–8 weeks
- Alternative regimen: Clindamycin 600 mg IV q6h for 2–4 weeks, THEN PO to complete 6–8 weeks
- 6.3 Methicillin-resistant Staphylococcus aureus (MRSA)
- 6.3.1 In adults
- Preferred regimen: Vancomycin loading dose 25–30 mg/kg IV THEN Vancomycin 15–20 mg/kg IV q8–12h for 2–4 weeks, THEN PO to complete 6–8 weeks
- Alternative regimen (1): Linezolid 600 mg PO/IV q12h for 4–6 weeks
- Alternative regimen (2): Trimethoprim-Sulfamethoxazole 5 mg/kg PO/IV q8–12h for 4–6 weeks
- 6.3.2 Pediatric dose
- Preferred regimen (1): Vancomycin 15 mg/kg IV q6h
- Preferred regimen (2): Linezolid 10 mg/kg PO/IV q8h
- Note: Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to Vancomycin in adult patients.
- 7. Bacterial meningitis
- 7.1 Methicillin susceptible Staphylococcus aureus (MSSA)
- Preferred regimen (1): Nafcillin 9–12 g/day IV q4h
- Preferred regimen (2): Oxacillin 9–12 g/day IV q4h
- Alternative regimen (1): Vancomycin 30–45 mg/kg/day IV q8–12h
- Alternative regimen (2): Meropenem 6 g/day IV q8h
- 7.2 Methicillin resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
- Alternative regimen (1): Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h
- Alternative regimen (2): Linezolid 600 mg IV q12h
- Note: Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to Vancomycin in adult patients.
- 8. Septic thrombosis of cavernous or dural venous sinus[23]
- 8.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- 8.1.1 In adults
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h for 4–6 weeks
- Alternative regimen (1): Linezolid 600 mg PO/IV q12h for 4–6 weeks
- Alternative regimen (2): Trimethoprim-Sulfamethoxazole 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks
- 8.1.2 Pediatric dose
- Preferred regimen (1): Vancomycin 15 mg/kg IV q6h
- Preferred regimen (2): Linezolid 10 mg/kg PO/IV q8h
- Note (1): Surgical evaluation for incision and drainage of contiguous sites of infection or abscess is recommended whenever possible.
- Note (2): Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to Vancomycin.
- 9. Subdural empyema
- 9.1 Methicillin-resistant Staphylococcus aureus (MRSA)[24]
- 9.1.1 In adults
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 4–6 weeks
- Alternative regimen (1): Linezolid 600 mg PO/IV q12h for 4–6 weeks
- Alternative regimen (2): Trimethoprim-Sulfamethoxazole 5 mg/kg PO/IV q8–12h for 4–6 weeks
- 9.1.2 In children
- Preferred regimen (1): Vancomycin 15 mg/kg IV q6h
- Preferred regimen (2): Linezolid 10 mg/kg PO/IV q8h
- Note: Consider the addition of Rifampin 600 mg qd or 300–450 mg bid to Vancomycin.
- 10. Acute conjunctivitis[25]
- 10.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin ointment 1% qid
- 11. Appendicitis
- 11.1 Health care–associated complicated intra-abdominal infection[26]
- 11.1.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h
- 12. Diverticulitis
- 12.1 Health care–associated complicated intra-abdominal infection[26]
- 12.1.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h.
- 13. Peritonitis secondary to bowel perforation, peritonitis secondary to ruptured appendix, peritonitis secondary to ruptured appendix, typhlitis
- 13.1 Health care–associated complicated intra-abdominal infection[26]
- 13.1.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h
- 14. Cystic fibrosis[27]
- 14.1 Adults
- 14.1.1 If methicillin sensitive staphylococcus aureus
- Preferred Regimen (1): Nafcillin 2 gm IV q4h
- Preferred Regimen (2): Oxacillin 2 gm IV q4h
- 14.1.2 If methicillin resistant staphylococcus aureus
- Preferred Regimen (1): Vancomycin 15-20 mg/kg IV q8-12h
- Preferred Regimen (2): Linezolid 600 mg PO/IV q12h
- 14.2 Pediatric
- 14.2.1 If methicillin sensitive staphylococcus aureus
- Preferred Regimen (1): Nafcillin 5 mg/kg q6h (Age >28 days)
- Preferred Regimen (2): Oxacillin 75 mg/kg q6h (Age >28 days)
- 14.2.2 If methicillin resistant staphylococcus aureus
- Preferred Regimen (1): Vancomycin 40 mg/kg q6-8h (Age >28 days)
- Preferred Regimen (2): Linezolid 10 mg/kg PO/IV q8h (up to age 12)
- 15. Bronchiectasis[28]
- 15.1 In adults
- 15.1.1 Recommended first-line treatment and length of treatment
- 15.1.1.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Flucloxacillin 500 mg PO qds for 14 days
- 15.1.1.2 Methicillin-resistant Staphylococcus aureus (MRSA)
- Patient's body weight is < 50 kg
- Preferred regimen: Rifampicin 450 mg PO qd AND Trimethoprim 200 mg PO bd for 14 days
- Patient's body weight is > 50 kg
- Preferred regimen: Rifampicin 600 mg PO qd AND Trimethoprim 200 mg PO bd for 14 days
- 15.1.1.3 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen (1): Vancomycin 1 g IV bd (monitor serum levels and adjust dose accordingly)
- Preferred regimen (2): Teicoplanin 400 mg qd for 14 days
- 15.1.2 Recommended second-line treatment and length of treatment
- 15.1.2.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Clarithromycin 500 mg PO bd 14 days
- 15.1.2.2 Methicillin-resistant Staphylococcus aureus (MRSA)
- Patient's body weight is < 50 kg
- Preferred regimen: Rifampicin 450 mg PO qd AND Doxycycline 200 mg PO qd for 14 days
- Patient's body weight is > 50 kg
- Preferred regimen: Rifampicin 600 mg PO qd AND Doxycycline 200 mg PO qd for 14 days
- Third-line: Linezolid 600 mg bd for 14 days
- 15.1.2.3 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Linezolid 600 mg IV bd for 14 days
- 15.2 In children
- 15.2.1 Recommended first-line treatment and length of treatment
- 15.2.1.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Flucloxacillin
- 15.2.1.2 Methicillin-resistant Staphylococcus aureus (MRSA)
- 15.2.1.2.1 Children (< 12 yr)
- Preferred regimen: Trimethoprim 4-6 mg/kg/day PO q12h
- 15.2.1.2.2 Children (> 12 yr)
- Preferred regimen (1): Trimethoprim 100-200 mg PO q12h
- Preferred regimen (2): Rifampicin 450 mg PO od (or Rifampicin 600 mg PO od)
- 15.2.1.3 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen (1): Vancomycin 45-60 mg/kg/day IV q8-12h
- Preferred regimen (2): Teicoplanin 400 mg qd for 14 days
- 15.2.2 Recommended second-line treatment and length of treatment
- 15.2.2.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Clarithromycin 15 mg/kg/day PO q12h
- 15.2.2.2 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen (1): Rifampicin AND Doxycycline 2-5 mg/kg/day PO/IV q12-24h (max dose: 200 mg/24 hr)
- Preferred regimen (2): Rifampicin AND Doxycycline 2-5 mg/kg/day PO/IV q12-24h (max dose: 200 mg/24 hr)
- Third-line: Linezolid 10 mg/kg PO/IV q12h
- 15.2.2.3 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Linezolid 10 mg/kg PO/IV q12h
- 15.3 Long-term oral antibiotic treatment
- 15.3.1 In adults
- 15.3.1.1 Recommended first-line treatment and length of treatment
- 15.3.1.1.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Flucloxacillin 500 mg PO bd
- 15.3.1.2 Recommended second-line treatment and length of treatment
- 15.3.1.2.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen: Clarithromycin 250 mg PO bd
- 16. Empyema[29]
- Preferred regimen (1): Nafcillin 2 gm IV q4h
- Preferred regimen (2): oxacillin 2 gm IV q4h (if MSSA)
- Alternative regimen (1): Vancomycin 1 gm IV q12h
- Alternative regimen (2): Linezolid 600 mg PO bid (if MRSA)
- 17. Community-acquired pneumonia[30]
- 17.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred Regimen (1): Nafcillin 1000-2000 mg q4h
- Preferred Regimen (2): Oxacillin 2 g IV q4h
- Preferred Regimen (3): Flucloxacillin 250 mg IM/IV q6h
- Alternative Regimen (1): Cefazolin 500 mg IV q12h
- Alternative Regimen (2): Clindamycin 150-450 mg PO q6-8h
- 17.2 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred Regimen (1): Vancomycin 45-60 mg/kg/day q8-12h (max: 2000 mg/dose) for 7-21 days
- Preferred Regimen (2): Linezolid 600 mg PO/IV q12h for 10-14 days
- Alternative Regimen: Trimethoprim-Sulfamethoxazole 1-2 double-strength tablets (800/160 mg) q12-24h
- 18. Olecranon bursitis or prepatellar bursitis
- 18.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen (1): Nafcillin 2 g IV q4h
- Preferred regimen (2): Oxacillin 2 g IV q4h
- Preferred regimen (3): Dicloxacillin 500 mg PO qid
- 18.2 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen (1): Vancomycin 1 g IV q12h
- Preferred regimen (2): Linezolid 600 mg PO qd
- Note: Initially aspirate q24h and treat for a minimum of 2–3 weeks.
- 19. Septic arthritis
- 19.1 In adults
- 19.1.1 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h
- Alternative regimen (1): Daptomycin 6 mg/kg IV q24h in adults
- Alternative regimen (2): Linezolid 600 mg PO/IV q12h
- Alternative regimen (3): Clindamycin 600 mg PO/IV q8h
- Alternative regimen (4): TMP-SMX 3.5–4.0 mg/kg PO/IV q8–12h
- 19.2.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen (1): Nafcillin 2 g IV q6h
- Preferred regimen (2): Clindamycin 900 mg IV q8h
- Alternative regimen (1): Cefazolin 0.25–1 g IV/IM q6–8h
- Alternative regimen (2): Vancomycin 500 mg IV q6h or 1 g IV q12h
- 19.2 In childern
- Preferred regimen (1): Vancomycin 15 mg/kg IV q6h
- Preferred regimen (2): Daptomycin 6–10 mg/kg IV q24h
- Preferred regimen (3): Linezolid 10 mg/kg PO/IV q8h
- Preferred regimen (4): Clindamycin 10–13 mg/kg PO/IV q6–8h
- 20. Septic arthritis, prosthetic joint infection (device-related osteoarticular infections)
- 20.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen (1): Nafcillin 2 g IV q4–6h
- Preferred regimen (2): Oxacillin 2 g IV q4–6h
- Alternative regimen (1): Cefazolin 1–2 g IV q8h
- Alternative regimen (2): Ceftriaxone 2 g IV q24h
- Alternative regimen (if allergic to penicillins) (3): Clindamycin 900 mg IV q8h
- Alternative regimen (if allergic to penicillins) (4): Vancomycin 15–20 mg/kg IV q8–12h, (max: 2 g per dose)
- 20.2 Methicillin-resistant Staphylococcus aureus (MRSA)
- Early-onset (2 months after surgery) or acute hematogenous prosthetic joint infections involving a stable implant with short duration (< 3 weeks) of symptoms and debridement (but device retention)
- Preferred regimen: Vancomycin AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks
- Alternative regimen (1): Daptomycin 6 mg/kg IV q24h AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks
- Alternative regimen (2): Linezolid 600 IV q8h AND Rifampin 600 mg PO qd or 300–450 mg PO bid for 2 weeks
- Note: The above regimen should be followed by Rifampin and a Fluoroquinolone, TMP/SMX, a Tetracycline or Clindamycin for 3-6 months for hips and knees, respectively.
- 21. Hematogenous osteomyelitis
- 21.1 Adult (> 21 yrs)
- 21.1.1 Methicillin-resistant Staphylococcus aureus (MRSA) possible
- Preferred regimen: Vancomycin 1 gm IV q12h (if over 100 kg, 1.5 gm IV q12h)
- 21.1.2 Methicillin-resistant Staphylococcus aureus (MRSA) unlikely
- Preferred regimen (1): Nafcillin
- Preferred regimen (2): Oxacillin 2 gm IV q4h
- 21.2 Children (> 4 months)-Adult
- 21.2.1 Methicillin-resistant Staphylococcus aureus (MRSA) possible
- Preferred regimen: Vancomycin 40 mg IV q6–8h
- 21.2.2 Methicillin-resistant Staphylococcus aureus (MRSA) unlikely
- Preferred regimen (1): Nafcillin
- Preferred regimen (2): Oxacillin q6h (max. 8–12 gm per day)
- Note: Add Ceftazidime 50 mg q8h or Cefepime 150 mg q8h if Gram negative bacilli on Gram stain
- 21.3 Newborn (< 4 months.)
- 21.3.1 Methicillin-resistant Staphylococcus aureus (MRSA) possible
- Preferred regimen (1): Vancomycin AND Ceftazidime 2 gm IV q8h
- Preferred regimen (2): Vancomycin AND Cefepime 2 gm IV q12h
- 21.3.2 Methicillin-resistant Staphylococcus aureus (MRSA) unlikely
- Preferred regimen (1): Nafcillin AND Ceftazidime
- Preferred regimen (2): Oxacillin AND Cefepime
- 21.4 Specific therapy
- 21.4.1 Methicillin-susceptible Staphylococcus aureus (MSSA)
- Preferred regimen (1): Nafcillin
- Preferred regimen (2): Oxacillin 2 gm IV q4h
- Preferred regimen (3): Cefazolin 2 gm IV q8h
- Alternative regimen: Vancomycin 1 gm IV q12h (if over 100 kg, 1.5 gm IV q12h)
- 21.4.2 Methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 1 gm IV q12h
- Alternative regimen: Linezolid 600 mg q12h PO/IV with or without Rifampin 300 mg PO/IV bid
- 22. Diabetic foot osteomyelitis
- High risk for MRSA
- Preferred regimen (1): Linezolid 600 mg IV or PO q12h
- Preferred regimen (2): Daptomycin 4 mg/kg IV q24h
- Preferred regimen (3): Vancomycin 15–20 mg/kg IV q8–12h (trough: 10–20 mg/L)
- 23. Necrotizing fasciitis[31]
- 23.1 In adult
- Preferred regimen (1): Nafcillin 1–2 g IV q4h (severe Pencillin allergy: Vancomycin, linezolid, quinupristin/dalfopristin, daptomycin)
- Preferred regimen (2): Oxacillin 1–2 g IV q4h
- Preferred regimen (3): Cefazolin 1 g IV q8h
- Preferred regimen (4): Vancomycin 15 mg/kg IV bid
- Preferred regimen (5): Clindamycin 600–900 mg IV q8h
- 23.2 In childern
- Preferred regimen (1): Nafcillin 50 mg/kg/dose IV q6h (severe Pencillin allergy: Vancomycin, linezolid, quinupristin/dalfopristin, daptomycin)
- Preferred regimen (2): Oxacillin 50 mg/kg/dose IV q6h
- Preferred regimen (3): Cefazolin 33 mg/kg/dose IV q8h
- Preferred regimen (4): Vancomycin 15 mg/kg/dose IV q6h
- Preferred regimen (5): Clindamycin 10–13 mg/kg/dose IV q8h (Bacteriostatic; potential cross-resistance and emergence of resistance in erythromycin-resistant strains; inducible resistance in methicillin resistent staphylococcus aureus)
- 24. Staphylococcal toxic shock syndrome[32]
- 24.1 Methicillin sensitive Staphylococcus aureus
- Preferred regimen (1): Cloxacillin 250-500 mg PO q6h (max dose: 4 g/24 hr)
- Preferred regimen (2): Nafcillin 4-12 g/24 hr IV q4-6hr (max dose: 12 g/24 hr)
- Preferred regimen (3): Cefazolin 0.5-2g IV/IM q8h (max dose: 12 g/24 hr) AND Clindamycin 150-600 mg IV, IM/PO q6-8h (max dose: 5 g/24 hr IV or IM or 2 g/24 hr PO)
- Alternative regimen (1): Clarithromycin 250-500 mg PO q12h (max dose: 1 g/24 hr) AND Clindamycin 150-600 mg IV, IM/PO q6-8h (max dose: 5 g/24 hr IV/IM or 2 g/24h PO)
- Alternative regimen (2): Rifampicin AND Linezolid 600 mg IV/PO q12h
- Alternative regimen (3): Daptomycin
- Alternative regimen (4): Tigecycline 100 mg loading dose THEN 50 mg IV q12h
- 24.2 Methicillin resistant Staphylococcus aureus
- Preferred regimen (1): Clindamycin 150-600 mg IV, IM/PO q6-8h (max dose: 5 g/24h IV/IM or 2 g/24h PO)
- Preferred regimen (2): Linezolid 600 mg IV/PO q12h AND Vancomycin 15-20 mg/kg IV q8-12h, (max: 2 g per dose)
- Preferred regimen (3): Teicoplanin
- Alternative regimen (1): Rifampicin AND Linezolid 600 mg IV/PO q12h
- Alternative regimen (2): Daptomycin
- Alternative regimen (3): Tigecycline 100 mg loading dose THEN 50 mg IV q12h
- 24.3 Glycopeptide resistant or intermediate Staphylococcus aureus
- Preferred regimen: Linezolid 600 mg IV/PO q12h AND Clindamycin 150-600 mg IV, IM/PO q6-8h (max dose: 5 g/24 hr IV/IM or 2 g/24h PO) (if sensitive)
- Alternative regimen (1): Daptomycin
- Alternative regimen (2): Tigecycline 100 mg loading dose THEN 50 mg IV q12h
- Staphylococcus aureus ,prophylaxis
- 1. Prophylaxis for coronary artery bypass graft-associated acute mediastinitis[33]
- 1.1 Methicillin susceptible staphylococcus aureus (MSSA)
- Preferred regimen: A first- or second-generation Cephalosporin is recommended for prophylaxis in patients without MRSA colonization.
- 1.2 Methicillin resistant staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin alone or in combination with other antibiotics to achieve broader coverage is recommended for prophylaxis in patients with proven or suspected MRSA colonization
- Note (1): Preoperative antibiotics should be administered to all patients to reduce the risk of mediastinitis in cardiac surgery.
- Note (2): The use of intranasal Mupirocin is reasonable in nasal carriers of Staphylococcus aureus.
- Staphylococcus haemolyticus Return to Top
- 1. Methicillin-susceptible strain[34][35]
- Preferred regimen (1): Nafcillin 1–2 g IV q4-6h (maximum 12 g/day)
- Preferred regimen (2): Oxacillin 1–2 g IVq4-6h (maximum 12 g/day)
- Preferred regimen (3): Cefazolin 0.5–2 g IV q6-8h
- Alternative regimen (1): TMP-SMX 4–5 mg/kg IV q6–12h
- Alternative regimen (2): Doxycycline 100–200 mg IV q12-24h
- 2. Methicillin-resistant, Glycopeptide-susceptible strain
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h
- 3. Methicillin-resistant, Glycopeptide-resistant strain
- Preferred regimen (1): Daptomycin 4–6 mg/kg IV q24h
- Preferred regimen (2): Linezolid 600 mg PO/IV q12h
- Staphylococcus epidermidis Return to Top
- Staphylococcus epidermidis[36]
- 1. Methicillin-sensitive Staphylococcus epidermidis
- Preferred regimen (1): Oxacillin 1-2 g IV q4h
- Preferred regimen (2): Nafcillin 1-2 g IV q4h
- Preferred regimen (3): Cephalothin
- Alternative regimen: Rifampin 600 mg/day PO qd AND Sulfamethoxazole and Trimethoprim ((or) Fluoroquinolones) AND Daptomycin 600 mg PO or IV q12h[37]
- Note: 75% of the S. epidermidis are methicillin-resistant.
- 2. Methicillin-resistant Staphylococcus epidermidis
- Preferred regimen: Vancomycin 1 g IV q12h with or without Rifampin 600 mg/day PO qd
- Note: For deep-seated infections consider adding Gentamicin with or without Rifampin 600 mg/day PO qd to the regimen[11]
- 3. Prosthetic device infections
- Preferred regimen: Oxacillin 1-2 g IV q4h ((or) Vancomycin 1 g IV q12h) AND Rifampin 600 mg/day PO qd AND Gentamicin 3 mg/kg/day IV/IM q8-24h is appropriate[11]
- Note: Duration depends on site of infection and severity.
- Staphylococcus lugdunensis Return to Top
- Staphylococcus lugdunensis treatment
- 1. Skin and soft tissue infections[38]
- Preferred regimen: Oxacillin 1-2 g IV q4h for 1-2 weeks
- Note: Abscesses should be drained if possible.
- 2. Endocarditis[39]
- 2.1 Native valve infectious endocarditis
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h (target trough concentration, 10 to 15 mcg/mL)
- Preferred regimen (for most patients with normal renal function) (2): Vancomycin 15 to 20 mg/kg (actual body weight) IV q8-12h -for trough concentration of 15 to 20 mcg/mL (minimum inhibitory concentration, 1 mcg/mL or less)
- Note: should consist of 6 weeks of parenteral beta-lactam therapy or Vancomycin (depending on susceptibility testing and beta-lactam hypersensitivity).
- 2.2 Prosthetic valve infective endocarditis
- Preferred regimen: Combination therapy including a beta-lactam (or Vancomycin) with an Aminoglycoside- Gentamicin 3 mg/kg/day in 1-3 divided doses and Rifampin 300 mg PO/IV q8h for at least 6 weeks
- Note (1): Combine with Vancomycin for the entire duration of therapy and Gentamicin for the first 2 weeks.
- Note (2): The Gentamicin should be administered for the first 2 weeks of therapy; the beta-lactam (or Vancomycin) and Rifampin should be continued for 6 weeks.
- Note (3): Surgery must be considered given the frequency of valvular compromise in the setting of Staphylococcus lugdunensis infective endocarditis.
- Note (4): The treatment of Staphylococcus lugdunensis pacemaker endocarditis includes antibiotic therapy as well as removal of the pacer system
- 3. Bacteremia[12]
- Preferred regimen: Oxacillin 1-2 g IV q4h for 1-2 weeks
- Note (1): Bacteremia without endocarditis (often related to an intravascular catheter) appears to have a good prognosis.
- Note (2): For intravascular catheter-related Staphylococcus lugdunensis bacteremia, the catheter should be removed, followed by 14 days of antibiotics, provided that all of the following are applicable
- 2.1 The patient is not diabetic or immunosuppressed.
- 2.2 There is no prosthetic material, thrombophlebitis, infective endocarditis, evidence of metastatic infection.
- 2.3 The patient’s fever and bacteremia resolve within 72 hours after initiation of appropriate antibiotic therapy.
- 4. Prosthetic devices[40],[12]
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h (target trough concentration, 10 to 15 mcg/mL)
- Preferred regimen (for most patients with normal renal function) (2): Vancomycin 15 to 20 mg/kg (actual body weight) IV q8-12h -for trough concentration of 15 to 20 mcg/mL (minimum inhibitory concentration, 1 mcg/mL or less)
- Preferred regimen (3): Daptomycin 6 mg/kg IV qd for 3 to 4 weeks
- Preferred regimen (4): Linezolid 600 mg IV q12h
- 5. Vertebral osteomyelitis, discitis
- Preferred regimen: Vancomycin 15 to 20 mg/kg IV q8-12h, not to exceed 2 g per dose
- 6. Septic arthritis in adults
- Preferred regimen: Vancomycin 15 mg/kg IV bd, not to exceed 2 g per 24 hours (unless cncentrations in serum are inappropriately low) for 4 weeks.
- Staphylococcus lugdunensis treatment
- 1. Skin and soft tissue infections[38]
- Preferred regimen: Oxacillin 1-2 g IV q4h for 1-2 weeks
- Note: Abscesses should be drained if possible.
- 2. Endocarditis[39]
- 2.1 Native valve infectious endocarditis
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h (target trough concentration, 10 to 15 mcg/mL)
- Preferred regimen (for most patients with normal renal function) (2): Vancomycin 15 to 20 mg/kg (actual body weight) IV q8-12h -for trough concentration of 15 to 20 mcg/mL (minimum inhibitory concentration, 1 mcg/mL or less)
- Note: should consist of 6 weeks of parenteral beta-lactam therapy or Vancomycin (depending on susceptibility testing and beta-lactam hypersensitivity).
- 2.2 Prosthetic valve infective endocarditis
- Preferred regimen: Combination therapy including a beta-lactam (or Vancomycin) with an Aminoglycoside- Gentamicin 3 mg/kg/day in 1-3 divided doses and Rifampin 300 mg PO/IV q8h for at least 6 weeks
- Note (1): Combine with Vancomycin for the entire duration of therapy and Gentamicin for the first 2 weeks.
- Note (2): The Gentamicin should be administered for the first 2 weeks of therapy; the beta-lactam (or Vancomycin) and Rifampin should be continued for 6 weeks.
- Note (3): Surgery must be considered given the frequency of valvular compromise in the setting of Staphylococcus lugdunensis infective endocarditis.
- Note (4): The treatment of Staphylococcus lugdunensis pacemaker endocarditis includes antibiotic therapy as well as removal of the pacer system
- 3. Bacteremia[12]
- Preferred regimen: Oxacillin 1-2 g IV q4h for 1-2 weeks
- Note (1): Bacteremia without endocarditis (often related to an intravascular catheter) appears to have a good prognosis.
- Note (2): For intravascular catheter-related Staphylococcus lugdunensis bacteremia, the catheter should be removed, followed by 14 days of antibiotics, provided that all of the following are applicable
- 2.1 The patient is not diabetic or immunosuppressed.
- 2.2 There is no prosthetic material, thrombophlebitis, infective endocarditis, evidence of metastatic infection.
- 2.3 The patient’s fever and bacteremia resolve within 72 hours after initiation of appropriate antibiotic therapy.
- 4. Prosthetic devices[40],[12]
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h (target trough concentration, 10 to 15 mcg/mL)
- Preferred regimen (for most patients with normal renal function) (2): Vancomycin 15 to 20 mg/kg (actual body weight) IV q8-12h -for trough concentration of 15 to 20 mcg/mL (minimum inhibitory concentration, 1 mcg/mL or less)
- Preferred regimen (3): Daptomycin 6 mg/kg IV qd for 3 to 4 weeks
- Preferred regimen (4): Linezolid 600 mg IV q12h
- 5. Vertebral osteomyelitis, discitis
- Preferred regimen: Vancomycin 15 to 20 mg/kg IV q8-12h, not to exceed 2 g per dose
- 6. Septic arthritis in adults
- Preferred regimen: Vancomycin 15 mg/kg IV bd, not to exceed 2 g per 24 hours (unless cncentrations in serum are inappropriately low) for 4 weeks.
- Staphylococcus lugdunensis treatment
- 1. Skin and soft tissue infections[38]
- Preferred regimen: Oxacillin 1-2 g IV q4h for 1-2 weeks
- Note: Abscesses should be drained if possible.
- 2. Endocarditis[39]
- 2.1 Native valve infectious endocarditis
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h (target trough concentration, 10 to 15 mcg/mL)
- Preferred regimen (for most patients with normal renal function) (2): Vancomycin 15 to 20 mg/kg (actual body weight) IV q8-12h -for trough concentration of 15 to 20 mcg/mL (minimum inhibitory concentration, 1 mcg/mL or less)
- Note: should consist of 6 weeks of parenteral beta-lactam therapy or Vancomycin (depending on susceptibility testing and beta-lactam hypersensitivity).
- 2.2 Prosthetic valve infective endocarditis
- Preferred regimen: Combination therapy including a beta-lactam (or Vancomycin) with an Aminoglycoside- Gentamicin 3 mg/kg/day in 1-3 divided doses and Rifampin 300 mg PO/IV q8h for at least 6 weeks
- Note (1): Combine with Vancomycin for the entire duration of therapy and Gentamicin for the first 2 weeks.
- Note (2): The Gentamicin should be administered for the first 2 weeks of therapy; the beta-lactam (or Vancomycin) and Rifampin should be continued for 6 weeks.
- Note (3): Surgery must be considered given the frequency of valvular compromise in the setting of Staphylococcus lugdunensis infective endocarditis.
- Note (4): The treatment of Staphylococcus lugdunensis pacemaker endocarditis includes antibiotic therapy as well as removal of the pacer system
- 3. Bacteremia[12]
- Preferred regimen: Oxacillin 1-2 g IV q4h for 1-2 weeks
- Note (1): Bacteremia without endocarditis (often related to an intravascular catheter) appears to have a good prognosis.
- Note (2): For intravascular catheter-related Staphylococcus lugdunensis bacteremia, the catheter should be removed, followed by 14 days of antibiotics, provided that all of the following are applicable
- 2.1 The patient is not diabetic or immunosuppressed.
- 2.2 There is no prosthetic material, thrombophlebitis, infective endocarditis, evidence of metastatic infection.
- 2.3 The patient’s fever and bacteremia resolve within 72 hours after initiation of appropriate antibiotic therapy.
- 4. Prosthetic devices[40],[12]
- Preferred regimen (1): Vancomycin 15 mg/kg IV q12h (target trough concentration, 10 to 15 mcg/mL)
- Preferred regimen (for most patients with normal renal function) (2): Vancomycin 15 to 20 mg/kg (actual body weight) IV q8-12h -for trough concentration of 15 to 20 mcg/mL (minimum inhibitory concentration, 1 mcg/mL or less)
- Preferred regimen (3): Daptomycin 6 mg/kg IV qd for 3 to 4 weeks
- Preferred regimen (4): Linezolid 600 mg IV q12h
- 5. Vertebral osteomyelitis, discitis
- Preferred regimen: Vancomycin 15 to 20 mg/kg IV q8-12h, not to exceed 2 g per dose
- 6. Septic arthritis in adults
- Preferred regimen: Vancomycin 15 mg/kg IV bd, not to exceed 2 g per 24 hours (unless cncentrations in serum are inappropriately low) for 4 weeks.
eeks
- Staphylococcus saprophyticus Return to Top
- Urinary tract infections[41]
- Preferred regimen (1): Cephalexin 500 mg PO qid
- Preferred regimen (2): Amoxicillin-Clavulanate 875/125 mg PO bid
- Preferred regimen (3): TMP-SMX 160–800 mg PO bid
- Alternative regimen: Levofloxacin 500 mg PO qd
- Streptobacillus moniliformis Return to Top
- Streptobacillus moniliformis treatment[42]
- 1. Migratory arthropathy and arthritis
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 2. Diarrhea, (especially kids) liver or spleen abscess
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 3. Undifferentiated fever
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 4. Endocarditis, myocarditis, pericarditis (cardiac)
- Preferred regimen: Penicillin 20 MU/day IV divided q4h. Optimal duration recommendation for infective endocarditis is 4 weeks.
- Alternative regimen: Cephalosporins-Ceftriaxone OR Clindamycin OR Erythromycin OR Chloramphenicol AND Streptomycin.
- 5. Meningitis, brain abscess
- Preferred regimen: Penicillin 20 MU/day IV divided q4h.
- Alternative regimen: Cephalosporins-Ceftriaxone OR Clindamycin OR Erythromycin OR Chloramphenicol AND Streptomycin.
- 6. Anemia
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 7. Pneumonia
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 8. Amnionitis (pregnancy)
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- 9. Renal abscess
- Preferred regimen (uncomplicated disease): Penicillin G 2.4-4.8 MU/day IV divided q6h. If better after 1 wk, switch to oral Amoxicillin OR Penicillin Vk complete 14 days.
- Streptococcus anginosus Return to Top
- 1. Dental abscess[43]
- Preferred regimen: Penicillin V 500 mg PO qid
- Alternative regimen: Vancomycin 15–20 mg/kg IV q8–12h
- 2. Brain abscess
- Preferred regimen (1): Penicillin G 18–24 MU/day IV q4–6h
- Preferred regimen (2): Ceftriaxone 2 g IV q12h
- Alternative regimen: Vancomycin 15–20 mg/kg IV q8–12h
- Streptococcus pneumoniae Return to Top
- Streptococcus pneumonia treatment
- 1. Lung (Community-acquired pneumonia)[30]
- 1.1 Penicillin sensitive (minimum inhibitory concentration < 2 mcg/ml)
- Preferred regimen: Penicillin G 5 to 24 MU IV in equally divided doses q4-6h, Amoxicillin 1 g PO tid (+/- macrolide)
- Alternative regimen: Macrolides (Azithromycin (IV) 500 mg IV qd for at least 2 days followed by 500 mg PO qd 7 to 10 days or Clarithromycin extended-release tablets 1000 mg PO qd for 7 days) and Oral Cephalosporins-Cefpodoxime 200 mg PO bd, (Cefprozil 500 mg PO bd, Cefditoren 400 mg PO bd, Cefdinir 300 mg PO bd), OR parenteral Cephalosporins-Ceftriaxone 2 g IV q24h (or Cefotaxime 1-2 g IV q6-8h), Clindamycin 600 to 1200 mg IV or IM q6-12h, do not give single IM doses >600 mg; IV infusion rates should not exceed 30 mg/min , Doxycycline 100 mg PO bd, respiratory flouroquniolones.
- 1.2 Penicillin-resistant (Penicillin minimum inhibitory concentration ≥2)
- Preferred regimen: Ceftriaxone 2 g IV q24h (or Cefotaxime 1-2 g IV q6-8h), respiratory Flouroquniolones Levofloxacin (Levaquin) 500 mg IV/PO q24h for 7 to 14 days or 750 mg IV/PO q24h for 5 days (or Moxifloxacin (Avelox) 400 mg PO/IV over 60 minutes q24h for 7 to 14 days)
- Alternative regimen: Vancomycin 2 g/day IV q6-12h over at least 60 minutes, Linezolid 600 mg IV/PO q12h for 7 to 21 days , high-dose Amoxicillin (3 g qd with Penicillin minimum concentration of inhibitory <4 mcg/mL).
- 2.Endocarditis[11]
- Preferred regimen (1): Aqueous crystalline Penicillin-G 6 MU q4-6h IV for 4 weeks
- Preferred regimen (2) (who are unable to tolerate beta lactams therapy): Vancomycin 15 mg/kg IV every 12 hours (target trough concentration, 10 to 15 mcg/mL) [9]; for troughs of 15 to 20 mcg/mL (MIC, 1 mcg/mL or less), dose 15 to 20 mg/kg (actual body weight) IV every 8 to 12 hours for most patients with normal renal function
- Preferred regimen (3) (If the isolate is resistant (MIC 2 g/mL) to cefotaxime): Cefotaxime 1-2 g q8-12h IV or IM (max dose: 12 g/24 hr) AND Vancomycin 15 mg/kg/day IV q12h AND Rifampin 300 mg IV/PO q8h for 6 weeks, in combination with appropriate antimicrobial therapy
- Alternative regimen (1): Cefazolin 0.5-2 g q8h IV or IM (max dose: 12 g/24 hr)
- Alternative regimen (2): Ceftriaxone 2 g IV q12h
- Note : Streptococcus pneumoniae with intermediate doses minimum inhibitory concentration (MIC) 0.12 g/mL–0.5 g/mL Penicillin resistance (MIC 0.1 to 1.0 g/mL) or high Penicillin resistance (MIC 2.0 g/mL) is being recovered from patients with bacteremia.
- 3. Sinuses (sinusitis)[44]
- Empiric therapy
- 3.1 For initial empiric treatment of acute bacterial rhinosinusitis in adults
- Preferred regimen: Amoxicillin 500 mg/Clavulanate 125 mg PO tid or Amoxicillin 875 mg/Clavulanate 125 mg PO bid for 5 to 7 days recommended by the Infectious Disease Society of America (IDSA)
- Alternative regimen (1): Doxycycline 100 mg PO q12h
- Note: Doxycycline can be used in patients with Penicillin allergy.
- Alternative regimen (2): A respiratory Fluoroquinolone (Levofloxacin or Moxifloxacin) is another recommended drug for Penicillin-allergic patients.
- 3.2 For second-line high-dose therapy for acute bacterial rhinosinusitis in adults
- Preferred regimen: Amoxicillin 2 g/Clavulanate 125 mg PO bid recommended by the Infectious Disease Society of America (IDSA).
- Note: The second line high dose therapy is recommended in adults who have failed initial therapy, in regions of high endemic rates (10% or greater) of invasive Penicillin-nonsusceptible Streptococcus pneumoniae, severe infection.
- 4. Bronchi (acute exacerbation of chronic bronchitis)[45]
- Preferred regimen (1): Amoxicillin 875 mg PO q12h or 500 mg PO q8h
- Preferred regimen (2): Doxycycline 100 mg PO q12h
- 5. CNS (meningitis)[4]
- Empiric therapy
- Preferred regimen: Vancomycin 15 mg/kg/day IV q12h AND a third-generation cephalosporin (Ceftriaxone 2 g IV q12h OR Cefotaxime 2 g IV q4h or 3 g q6h) AND Rifampin 600 mg IV qd in combination with Vancomycin
- Alternative regimen: Meropenem, fluoroquinolones
- Prevention
- 1. Pneumovax (23-valent) prevents bacteremia; impact on rates of CAP are modest or nil.
- 2. Prevnar vaccine for children <2 yrs age prevents invasive pneumococcal infection in adults by herd effect. Impact is impressive with rates of invasive pneumococcal infection down 80% in peds and 20-40% in adults.
- 3. Risk for bacteremia in splenectomy, HIV, smokers, black race, multiple myeloma, asthma.
- Streptococcus pyogenes Return to Top
- 1. Streptococcus pyogenes tonsilitis[46]
- Preferred regimen (1): Penicillin V 250 mg PO bid or tid (for children) 250 mg PO qid or 500 mg PO bid (for adults) for 10 days[47]
- Preferred regimen (2): Benzathine penicillin G if <27kg: 600,000 U, if >27kg 1,200,000 U IM single-dose[48]
- Alternative regimen (1): Amoxicillin 50 mg/kg/day PO qd for 10 days OR 25 mg/kg/day PO bid for 10 days. Its oral suspension is more tolerable to children and it is better absorbed by the GI tract[49]
- Alternative regimen (2): first generation Cephalosporins are acceptable for treating recurrent group A streptococcus infection but not as first-line therapy[50][48]
- Alternative regimen (3): Clarithromycin 250 mg PO bid for 10 days OR Azithromycin 12 mg/kg maximum 500 mg PO on day 1 THEN 6 mg/kg maximum 250 mg PO qd on days 2 through 5 OR Erythromycin 20 mg/kg/day PO or 40 mg/kg/day (ethylsuccinate) PO bid for 10 days.
- Alternative regimen (4): Clindamycin for penicillin-intolerant patients with erythromycin-resistant strains.
- Note: Intramuscular penicillin is the only therapy that has been shown to prevent initial attacks of rheumatic fever in controlled studies[51]
- 2. Recurrent Streptococcus pyogenes tonsilitis[52]
- Preferred regimen (1): Clindamycin 20-30 mg/kg/day PO tid (for children), 600 mg/day bid, tid or qid (for adults) for 10 days
- Preferred regimen (2): Amoxicillin-clavulanic acid 40 mg/kg/day PO tid (for children), 500 mg bid (for adults) for 10 days
- Alternative regimen: Benzathine penicillin G if <27kg: 600,000 U, if >27kg 1,200,000 U IM single-dose ± Rifampin 20 mg/kg/day PO bid for 4 days
- 3. Secondary prophylaxis for rheumatic fever[48]
- Preferred regimen (1): Benzathine penicillin G if <27kg: 600,000 U, if >27kg 1,200,000 U IM every 4 weeks
- Alternative regimen (1): Penicillin V potassium 250 mg PO bid
- Alternative regimen (2): Sulfadiazine if <27kg 0.5 g PO qd, if >27kg 1 g PO qd
- Duration of treatment: if residual cardiac disease, keep treatment until 40 patient is 40 years old or for 10 years (whichever is longer); if there's no residual cardiac disease keep treatment for 10 years or until age 21 years (whichever is longer); if there's rheumatic fever without carditis keep it for 5 years or until age 21 years (whichever is longer).
- Note: For patients allergic to penicillin and sulfadiazine, consider a macrolide or azalide antibiotic
- 4. Streptococcus pyogenes bacteremia[53]
- Preferred regimen: Penicillin G 4 million units IV q4h AND Clindamycin 900 mg IV q8h for at least 14 days
- Penicillin is added to the regimen to cover any other group A streptococcus which might be resistant to Clindamycin.
- Alternative regimen (1): Erythromycin
- Alternative regimen (2): Azithromycin
- Alternative regimen (3): Clarithromycin
- Alternative regimen (4): any other β-lactam[54]
- Note (1): Macrolide resistance is increasing.
- Note (2): Consider using intravenous immune globulin in patients with invasive infection and signs of shock. Immunoglobulin-G IV 1 g/kg day 1, then 0.5 g/kg days 2 & 3.
- Note (3): If shock, administer massive IV fluids (10-20 L/day), Albumin if <2 g/dL, debridement of necrotic tissue.
- 5. Streptococcus pyogenes celulitis
- Preferred regimen: treat as Streptococcus pyogenes bacteremia
- 6 Epiglottitis in childern[55]
- Preferred regimen (1): Cefotaxime 50 mg/kg IV q8h
- Preferred regimen (2): Ceftriaxone 50 mg/kg IV q24h
- Alternative regimen (1): Amoxicillin-SB 100–200 mg/kg qd q6h
- Alternative regimen (2): Trimethoprim-Sulfamethoxazole 8–12 mg/kg bid
- Note: Have tracheostomy set “at bedside.” Chloro is effective, but potentially less toxic alternative agents available.
- 7 Burn wound sepsis[56]
- Preferred regimen: Vancomycin 1 gm IV q12h AND (Amikacin 10 mg/kg IV loading dose then 7.5 mg/kg IV q12h) AND [ Piperacillin 4 g IV q4h (give ½ q24h dose of Piperacillin into subeschar tissues with surgical eschar removal within 12 hours]. Can use Piperacillin-Tazobactam if Piperacillin not available.
- 8. Soft tissue[57]
- Note: For necrotizing fasciitis, surgical consultation for emergent fasciotomy and debridement; repeat debridements usually necessary.
- 9. Muscle[58]
- Note: For myositis-debirdement is recommended.
- 10. Eye[59]
- 10.1 Keratitis
- 10.1.1 Acute bacterial keratitis
- Preferred regimen: Moxifloxacin eye gtts. 1 gtt tid for 7 days
- Alternative therapy: Gatifloxacin eye gtts. 1-2 gtts q2h while awake for 2 days, then q4h for 3-7 days.
- Note: Prefer Moxifloxacin due to enhanced lipophilicity and penetration into aqueous humor (1 gtt = 1 drop).
- 10.1.2 Keratitis due to dry cornea, diabetes, immunosuppression
- Preferred regimen: Cefazolin (50 mg/mL) AND (Gentamicin OR Tobramycin (14 mg/mL) q15–60 min around clock for 24–72 hrs, then slow reduction)
- Alternative therapy: Vancomycin (50 mg/mL) AND Ceftazidime (50 mg/mL) q15–60 min around clock for 24–72 hrs, then slow reduction.
- Note: Specific therapy guided by results of alginate swab culture and sensitivity. Ciprofloxacin 0.3% found clinically equivalent to CefazolinAND Tobramycin; only concern was efficacy of Ciprofloxacin vs S. pneumoniae
- 10.2 Dacryocystitis (lacrimal sac)
- Preferred regimen: Moxifloxacin 1 gtt tid for 7 days OR Cefazolin (50 mg/mL) (1 gtt = 1 drop)
- 11. Suppurative phlebitis[60]
- Preferred regimen: Vancomycin 15 mg/kg IV q12h (normal weight)
- Alternative regimen: Daptomycin 6 mg/kg IV q12h
- Note: Retrospective study for suppurative phlebitis recommends 2-3 weeks IV therapy and 2 weeks PO therapy.
- 12. Infected prosthetic joint[61]
- Preferred regimen: Penicillin G 2 million units IV q4h OR Ceftriaxone 2 g IV q24h for 4 weeks
- Note: Debridement & prosthesis retention with intravenous antibiotics.
- 13. “Hot” tender parotid swelling[62]
- Preferred regimen: Nafcillin OR Oxacillin 2 g IV q4h
- Note: Predisposing factors are stone(s) in Stensen’s duct, dehydration. Therapy depends on ID of specific etiologic organism.
- 14. Diabetic foot ulcer (ulcer with <2 cm of superficial inflammation)[63]
- Preferred regimen: (Trimethoprim-Sulfamethoxazole 800/160 mg 1-2 tabs PO bid OR Minocycline 100 mg PO bid) AND (Penicillin VK 500 mg PO qid OR selected Cephalosporins 2nd, 3rd generation - cefprozil 500 mg PO bid OR cefuroxime axetil 500 mg PO bid OR cefdinir 300 mg PO bid or 600 mg PO qd OR cefpodoxime 200 mg PO bid OR Fluoroquinolones Levofloxacin 750 mg PO qd).
- 15. Recurrent cellulitis, chronic lymphedema prophylaxis[64]
- Preferred regimen: Clindamycin 150 mg PO qd OR Trimethoprim-Sulfamethoxazole 800/160 mg 1 tablet PO qd OR “stand-by therapy” immediate treatment with Penicillin V OR Amoxicillin 500-750 mg PO bd at onset of symptoms.
- Streptococcus agalactiae Return to Top
- Streptococcus agalactiae treatment (GBS-group B Streptococcus)
- 1. Early onset group B streptococcal infections[65]
- 1.1 Bacteremia or sepsis or pneumonia
- 1.1.1 Empiric therapy
- Preferred regimen: Ampicillin 150 mg/kg IV q12h for 10 days AND Gentamicin 4 mg/kg IV q12h for 10 days-for infants born at ≥ 35 weeks gestation; Gentamicin 3 mg/kg IV q24h for 10 days-for infants born at < 35 weeks gestation
- 1.1.2 Definitive therapy
- Preferred regimen: Penicillin G 50,000-100,000 units/kg per day IV divided q12h for 10 days
- 1.2 Meningitis
- 1.2.1 Empiric therapy
- Preferred regimen: Ampicillin 100-150 mg/kg IV q8h for 14-21 days AND Gentamicin 4 mg/kg IV q24h for 14-21 days-for infants born at ≥ 35 weeks gestation; Gentamicin 3 mg/kg IV q24h for 14-21 days-for infants born at < 35 weeks gestation
- 1.2.2 Definitive therapy
- Preferred regimen: Penicillin G 250,000-450,000 units/kg per day IV divided q8h for 14-21 days
- Note: Cellulitis is the most frequent clinical manifestation of GBS-associated skin and soft tissue infections.
- 2. Late onset group b streptococcus infections in neonates and young infants (age > 1 week and body weight ≥ 1 kg with normal renal function)[66]
- 2.1 Bacteremia without a focus
- 2.1.1 Empiric therapy
- Preferred regimen: Ampicillin IV for 10 days, Nafcillin IV for 10 days, (OR Vancomycin IV for 10 days) AND Gentamicin IV for 10 days (OR Cefotaxime IV for 10 days)
- 2.1.2 Definitive therapy
- Preferred regimen: Penicillin G 75,000-150,000 units/kg per day IV divided q8h for 10 days
- 2.2 Meningitis
- 2.2.1 Empiric therapy
- Preferred regimen: Ampicillin IV for 14-21 days with or without Vancomycin IV for 14-21 day AND Gentamicin IV for 14-21 days OR Cefotaxime IV for 14-21 day
- 2.2.2 Definitive therapy
- Preferred regimen: Penicillin G 450,000-500,000 units/kg per day IV divided q6h for 14-21 days
- 2.3 Cellulitis or adenitis
- 2.3.1 Empiric therapy
- Preferred regimen: Nafcillin IV for 10-14 days (OR [[Vancomycin IV for 10-14 days) AND Gentamicin IV for 10-14 days (OR Cefotaxime IV for 10-14 days)
- 2.3.2 Definitive therapy
- Preferred regimen: Penicillin-G 75,000-150,000 units/kg per day IV divided q8h for 10-14 days
- 2.4 Septic arthritis
- 2.4.1 Empiric therapy
- Preferred regimen: Nafcillin IV for 14-21 days OR Vancomycin IV for 14-21 days AND Cefotaxime IV for 14-21 days
- 2.4.2 Definitive therapy
- Preferred regimen: Penicillin-G 75,000-150,000 units/kg per day IV divided q8h for 14-21 days
- 2.5 Osteomyelitis
- 2.5.1 Empiric therapy
- Preferred regimen: Nafcillin IV for 21-28 days OR Vancomycin IV for 21-28 days AND Cefotaxime IV for 21-28 days
- 2.5.2 Definitive therapy
- Preferred regimen: Penicillin-G 75,000-150,000 units/kg per day IV divided q8h for 21-28 days
- 2.6 Urinary tract infection
- 2.6.1 Empiric therapy
- Preferred regimen: Ampicillin IV for 10 days, Nafcillin IV for 10 days, (OR Vancomycin IV for 10 days) AND Gentamicin IV for 10 days (OR Cefotaxime IV for 10 days)
- 2.6.2 Definitive therapy
- Preferred regimen: Penicillin-G 75,000-150,000 units/kg per day IV divided q8h for 10 days
- Neonatal prophylaxis[67]
- Group B streptococcus infection (maternal dose for neonatal prophylaxis)
- Preferred regimen: Penicillin-G, Ampicillin 2 g IV initial dose, THEN 1 g q4h until delivery, Cefazolin ≥ 4h prior to delivery
### Bacteria – Gram-Positive Bacilli
- Actinomycosis Return to Top
- Actinomyces species including A. israeli[68]
- Preferred regimen: Penicillin 3-4 million units IV q4h for 2-6 weeks THEN Penicillin V 2-4 g/day PO qid for 6-12 months
- Alternative regimen (1): Erythromycin 500-1000 mg IV q6h OR 500 mg PO qid
- Alternative regimen (2): Tetracyclin 500 mg PO qid
- Alternative regimen (3): Doxycycline 100 mg IV q12h OR 100 mg PO bid
- Alternative regimen (4): Clindamycin 900 mg IV q8h OR 300-450 mg PO qd
- Alternative regimen (5): Minocycline 100 mg IV q12h OR 100 mg PO bid
- Arcanobacterium haemolyticum Return to Top
- Arcanobacterium haemolyticum treatment
- Preferred regimen: Erythromycin Base: 333 mg PO q8h; estolate/stearate/base: 250-500 mg q6h PO
- Alternative regimen: Benzathine Penicillin G 1.2 MU IM q3-4 weeks
# Anthracis
- Bacillus anthracis Return to Top
- Bacillus anthracis treatment
- 1. Treatment for cutaneous anthrax, without systemic involvement[69]
- Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown) (1): Ciprofloxacin 500 mg PO bid for 7-10 days
- Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown) (2): Doxycycline 100 mg PO bid for 7-10 days
- Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown) (3): Levofloxacin 750 mg PO qd for 7-10 days
- Preferred regimen (regardless of penicillin susceptibility or if susceptibility is unknown) (4): Moxifloxacin 400 mg PO qd for 7-10 days
- Alternative regimen (1): Clindamycin 600 mg PO tid for 7-10 days
- Alternative regimen (2): Amoxicillin 1 g PO tid (for penicillin-susceptible strains) for 7-10 days
- Alternative regimen (3): Penicillin VK 500 mg PO qid (for penicillin-susceptible strains) for 7-10 days
- Note: Duration of treatment is 60 days for bioterrorism-related cases and 7-10 days for naturally acquired cases.
- 2. Treatment for systemic anthrax including anthrax meningitis, inhalational anthrax, injectional anthrax, and gastrointestinal anthrax; and cutaneous anthrax with systemic involvement, extensive edema, or lesions of the head or neck[69]
- 2.1 Systemic anthrax with possible/confirmed meningitis
- 2.1.1 Bactericidal agent (fluoroquinolone)
- Preferred regimen (1): Ciprofloxacin 400 mg IV q8h for 2-3 weeks
- Preferred regimen (2): Levofloxacin 750 mg IV q24h for 2-3 weeks
- Preferred regimen (3): Moxifloxacin 400 mg IV q24h for 2-3 weeks AND
- 2.1.2 Bactericidal agent (ß-lactam) for all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- Preferred regimen (1): Meropenem 2 g IV q8h for 2-3 weeks
- Preferred regimen (2): Imipenem 1 g IV q6h for 2-3 weeks
- Preferred regimen (3): Doripenem 500 mg IV q8h for 2-3 weeks
- Preferred regimen (4): Penicillin G 4 MU IV q4h (for penicillin-susceptible strains) for 2-3 weeks
- Preferred regimen (5): Ampicillin 3 g IV q6h (for penicillin-susceptible strains) for 2-3 weeks AND
- 2.1.3 Protein synthesis inhibitor
- Preferred regimen (1): Linezolid 600 mg IV q12h for 2-3 weeks
- Preferred regimen (2): Clindamycin 900 mg IV q8h for 2-3 weeks
- Preferred regimen (3): Rifampin 600 mg IV q12h for 2-3 weeks
- Preferred regimen (4): Chloramphenicol 1 g IV q6-8h for 2-3 weeks
- Note (1): Patients exposed to aerosolized spores will require prophylaxis to complete an antimicrobial drug course of 60 days from onset of illness.
- Note (2): Increased risk for seizures associated with Imipenem/Cilastatin treatment.
- Note (3): Linezolid should be used with caution in patients with thrombocytopenia because it might exacerbate it. Linezolid use for > 14 days has additional hematopoietic toxicity.
- Note (4): Rifampin is not a protein synthesis inhibitor. However, it may be used in combination with other antimicrobial drugs on the basis of its in vitro synergy.
- 2.2 Systemic anthrax when meningitis has been excluded
- 2.2.1 Bactericidal agent
- Preferred regimen (1): Ciprofloxacin 400 mg IV q8h for 2 weeks
- Preferred regimen (2): Levofloxacin 750 mg IV q24h for 2 weeks
- Preferred regimen (3): Moxifloxacin 400 mg q24h for 2 weeks
- Preferred regimen (4): Meropenem 2 g IV q8h for 2 weeks
- Preferred regimen (5): Imipenem 1 g IV q6h for 2 weeks
- Preferred regimen (6): Doripenem 500 mg IV q8h for 2 weeks
- Preferred regimen (7): Vancomycin 20 mg/kg IV q8h (maintain serum trough concentrations of 15-20 µg/mL) for 2 weeks
- Preferred regimen (8): Penicillin G 4 MU IV q4h (penicillin-susceptible strains) for 2 weeks
- Preferred regimen (9): Ampicillin 3 g IV q6h (penicillin-susceptible strains) for 2 weeks AND
- 2.2.2 Protein synthesis inhibitor
- Preferred regimen (1): Clindamycin 900 mg IV q8h for 2 weeks
- Preferred regimen (2): Linezolid 600 mg IV q12h for 2 weeks
- Preferred regimen (3): Doxycycline 200 mg IV initially, then 100 mg IV q12h for 2 weeks
- Preferred regimen (4): Rifampin 600 mg IV q12h for 2 weeks
- Note: Patients exposed to aerosolized spores will require prophylaxis to complete an antimicrobial drug course of 60 days from onset of illness.
- 3. Specific considerations
- 3.1 Treatment of anthrax for pregnant Women
- 3.1.1 Intravenous antimicrobial treatment for systemic anthrax with possible/confirmed meningitis [70]
- 3.1.1.1 A Bactericidal Agent (Fluoroquinolone)
- Preferred regimen (1): Ciprofloxacin 400 mg IV q8h for 2–3 weeks OR
- Preferred regimen (2): Levofloxacin 750 mg IV q24h for 2–3 weeksOR
- 3.1.1.2 A Bactericidal Agent (ß-lactam)
- 3.1.1.2.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- Preferred regimen: Meropenem 2 g q8h for 2–3 weeks
- 3.1.1.2.2 Alternatives for penicillin-susceptible strains
- Alternative regimen (1): Ampicillin 3 g IV q6h for 2–3 weeks
- Alternative regimen (2): Penicillin G 4 MU IV q4h for 2–3 weeks OR
- 3.1.1.3 A Protein Synthesis Inhibitor
- Preferred regimen (1): Clindamycin 900 IV mg q8h for 2–3 weeks
- Preferred regimen (2): Rifampin 600 IV mg q12h for 2–3 weeks
- Note: At least one antibiotic with transplacental passage is recommended.
- 3.1.2 Intravenous antimicrobial treatment for systemic anthrax when meningitis has been excluded
- 3.1.2.1 A Bactericidal Antimicrobial
- Preferred regimen (1): Ciprofloxacin 400 mg IV q8h for 2 weeks
- Preferred regimen (2): Levofloxacin 750 mg IV q24h for 2 weeks OR
- 3.1.2.2 A Bactericidal Agent (ß-lactam)
- 3.1.2.2.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- Preferred regimen: Meropenem 2 g q8h for 2 weeks OR
- 3.1.2.2.2 Alternatives for penicillin-susceptible strains
- Alternative regimen (1): Ampicillin 3 g IV q6h for 2 weeks
- Alternative regimen (2): Penicillin G 4 MU IV q4h for 2 weeks OR
- 3.1.2.3 A Protein Synthesis Inhibitor
- Preferred regimen (1): Clindamycin 900 IV mg q8h for 2 weeks
- Preferred regimen (2): Rifampin 600 IV mg q12h for 2 weeks
- 3.1.3 Oral antimicrobial treatment for cutaneous anthrax without systemic involvement
- 3.1.3.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- Preferred regimen: Ciprofloxacin 400 mg IV q8h
- Note: Duration of treatment is 60 days
- 3.2 Treatment for anthrax in childern [71]
- 3.2.1 Treatment of cutaneous anthrax without systemic involvement (for children 1 month of age and older)
- 3.2.1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day PO bid (not to exceed 500 mg/dose) for 7-10 days
- Preferred regimen (2):
- If patients body weight is < 45 kg: Doxycycline 4.4 mg/kg/day PO bid (not to exceed 100 mg/dose) for 7-10 days
- If patients body weight is = 45 kg: Doxycycline 100 mg/dose PO bid for 7-10 days
- Preferred regimen (3): Clindamycin 30 mg/kg/day PO tid (not to exceed 600 mg/dose) for 7-10 days
- Preferred regimen (4):
- If patients body weight is < 50 kg: Levofloxacin 16 mg/kg/day PO bid (not to exceed 250 mg/dose) for 7-10 days
- If patients body weight is > 50 kg: Levofloxacin 500 mg PO qd for 7-10 days
- 3.2.1.2 Alternatives for penicillin-susceptible strains
- Alternative regimen (1):Amoxicillin 75 mg/kg/day PO tid (not to exceed 1 g/dose) for 7-10 days
- Alternative regimen (2): Penicillin VK 50-75 mg/kg/day PO tid or qid for 7-10 days
- 3.2.2 Combination therapy for systemic anthrax when meningitis can be ruled out (for children 1 month of age and older)
- 3.2.2.1 A bactericidal antimicrobial
- 3.2.2.1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q8h (not to exceed 400 mg/dose) for 14 days
- Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h (not to exceed 2 g/dose) for 14 days
- Preferred regimen (3):
- If patients body weight is < 50 kg: Levofloxacin 20 mg/kg/day IV divided q12h (not to exceed 250 mg/dose) for 14 days
- If patients body weight is > 50 kg: Levofloxacin 500 mg IV q24h for 14 days
- Preferred regimen (4): Imipenem/Cilastatin 100 mg/kg/day IV divided q6h (not to exceed 1 g/dose) for 14 days
- Preferred regimen (5): Vancomycin 60 mg/kg/day IV divided q8h (follow serum concentrations) for 14 days
- 3.2.2.1.2 Alternatives for penicillin-susceptible strains
- Alternative regimen (1): Penicillin G 400 000 U/kg/day IV divided q4h (not to exceed 4 MU/dose) for 14 days
- Alternative regimen (2): Ampicillin 200 mg/kg/day IV divided q6h (not to exceed 3 g/dose) for 14 days AND
- 3.2.2.2 A Protein Synthesis Inhibitor
- Preferred regimen (1): Clindamycin, 40 mg/kg/day IV divided q8h (not to exceed 900 mg/dose) for 14 days
- Preferred regimen (2): (non-CNS infection dose)
- If patient is < 12 y old: Linezolid 30 mg/kg/day IV divided q8h for 14 days
- If patient is = 12 y old: Linezolid 30 mg/kg/day IV divided q12h (not to exceed 600 mg/dose) for 14 days
- Preferred regimen (3):
- If patients body weight is < 45 kg: Doxycycline 4.4 mg/kg/day IV loading dose (not to exceed 200 mg) THEN Doxycycline 4.4 mg/kg/day IV divided q12h (not to exceed 100 mg/dose) for 14 days
- If patients body weight is =45 kg: Doxycycline 200 mg IV loading dose THEN Doxycycline 100 mg IV given q12h for 14 days
- Preferred regimen (4): Rifampin 20 mg/kg/day IV divided q12h (not to exceed 300 mg/dose) for 14 days
- Note: Duration of therapy for 14 days or longer until clinical criteria for stability are met. Will require prophylaxis to complete an antimicrobial course of up to 60 days from onset of illness.
- 3.2.3 Triple therapy for systemic anthrax (anthrax meningitis or disseminated infection and meningitis cannot be ruled out) for Children 1 Month of Age and Older
- 3.2.3.1 A bactericidal antimicrobial (fluoroquinolone)
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q8h (not to exceed 400 mg/dose) for 2–3 wks
- Preferred regimen (2):
- If patients body weight is < 50 kg: Levofloxacin 16 mg/kg/day IV divided q12h (not to exceed 250 mg/dose) for 2–3 wks
- If patients body weight is > 50 kg: Levofloxacin 500 mg IV q24h for 2–3 wks
- Preferred regimen (3):
- If patients age is 3 months to < 2 years: Moxifloxacin 12 mg/kg/day IV, divided q12h (not to exceed 200 mg/dose) for 2–3 wks
- If patients age is 2-5 years: Moxifloxacin 10 mg/kg/day IV divided q1h (not to exceed 200 mg/dose) for 2–3 wks
- If patients age is 6–11 years: Moxifloxacin 8 mg/kg/day IV divided q12h (not to exceed 200 mg/dose) for 2–3 wks
- If patients age is 12–17 years, = 45 kg body weight: Moxifloxacin 400 mg IV q24h for 2–3 wks
- If patients age is 12–17 years, < 45 kg body weight: Moxifloxacin 8 mg/kg/day IV divided q12h (not to exceed 200 mg/dose) for 2–3 wks AND
- 3.2.3.2 A bactericidal antimicrobial (ß-lactam or glycopeptide)
- 3.2.3.2.1 For all strains, regardless of penicillin susceptibility testing or if susceptibility is unknown:
- Preferred regimen (1): Meropenem 120 mg/kg/day IV divided q8h (not to exceed 2 g/dose) for 2–3 wks
- Preferred regimen (2): Imipenem/Cilastatin 100 mg/kg/day IV divided q6h (not to exceed 1 g/dose) for 2–3 wks
- Preferred regimen (3): Doripenem 120 mg/kg/day IV divided q8h (not to exceed 1 g/dose) for 2–3 wks
- Preferred regimen (4): Vancomycin 60 mg/kg/day IV divided q8h for 2–3 wks
- 3.2.3.2.2 Alternatives for penicillin-susceptible strains
- Alternative regimen (1): Penicillin G 400 000 U/kg/day IV divided q4h (not to exceed 4 MU/dose) for 2–3 wks
- Alternative regimen (2): Ampicillin 400 mg/kg/day IV divided q6h (not to exceed 3 g/dose) for 2–3 wks AND
- 3.2.3.3 A Protein Synthesis Inhibitor
- Preferred regimen (1):
- If patients age is < 12 y old: Linezolid 30 mg/kg/day IV divided q8h for 2–3 wk
- If patients age is = 12 y old: Linezolid 30 mg/kg/day,IV divided q12h (not to exceed 600 mg/dose) for 2–3 wk
- Preferred regimen (2): Clindamycin 40 mg/kg/day IV divided q8h (not to exceed 900 mg/dose) for 2–3 wk
- Preferred regimen (3): Rifampin 20 mg/kg/day IV divided q12h (not to exceed 300 mg/dose) for 2–3 wk
- Preferred regimen (4): Chloramphenicol 100 mg/kg/day IV divided q6h for 2–3 wk
- 3.2.4 Oral follow-up combination therapy for severe anthrax (for Children 1 Month of Age and Older)
- 3.2.4.1 A bactericidal antimicrobial
- 3.2.4.1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day PO bid (not to exceed 500 mg/dose)
- Preferred regimen (2):
- If patients body weight is < 50 kg: Levofloxacin 16 mg/kg/day PO bid (not to exceed 250 mg/dose)
- If patients body weight is = 50 kg: Levofloxacin 500 mg PO qd
- 3.2.4.1.2 Alternatives for penicillin-susceptible strains
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid (not to exceed 1 g/dose)
- Alternative regimen (2): Penicillin VK 50–75 mg/kg/day PO tid or qds AND
- 3.2.4.2 A protein synthesis inhibitor:
- Preferred regimen (1):Clindamycin 30 mg/kg/day PO tid (not to exceed 600 mg/dose)
- Preferred regimen (2):
- If the patients body weight is < 45 kg: Doxycycline 4.4 mg/kg/day PO bid (not exceed 100 mg/dose)
- If the patients body weight is = 45 kg: Doxycycline 100 mg PO bid
- Preferred regimen (3): (non-CNS infection dose):
- If the patients age is < 12 yrs old: Linezolid 30 mg/kg/day PO tid
- If the patients age is = 12 yrs old: Linezolid 30 mg/kg/day PO bid (not to exceed 600 mg/dose)
- Note: Duration of therapy to complete a treatment course of 14 days or greater. May require prophylaxis to complete an antimicrobial course of up to 60 days from onset of illness.
- 3.2.5 Dosing in preterm and term neonates 32 to 44 Weeks postmenstrual Age (Gestational Age Plus Chronologic Age)
- 3.2.5.1 Triple therapy for severe anthrax(anthrax meningitis or disseminated infection and meningitis cannot be ruled out)
- 3.2.5.1.1 Bactericidal antimicrobial (fluoroquinolone) therapy
- 3.2.5.1.1.1 For 32–34 weeks gestational age
- For 0–1 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (2): Moxifloxacin 5 mg/kg/day IV q24h for 2–3 weeks
- For 1–4 weeks of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (2): Moxifloxacin 5 mg/kg/day IV q24h for 2–3 weeks
- 3.2.5.1.1.2 For 34–37 week gestational age
- For 0–1 wk of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (2):Moxifloxacin 5 mg/kg/day IV q24h for 2–3 weeks
- For 1–4 wk of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (2): Moxifloxacin 5 mg/kg/day IV q24h for 2–3 weeks
- 3.2.5.1.1.3 Term newborn infant
- For 0–1 week of age
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (2): Moxifloxacin 10 mg/kg/day IV q24h for 2–3 weeks
- For 1–4 weeks of age
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (2): Moxifloxacin 10 mg/kg/day IV q24h for 2–3 weeks AND
- 3.2.5.1.2 A bactericidal antimicrobial (ß-lactam)
- 3.2.5.1.2.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown:
- 3.2.5.1.2.1.1 For 32–34 weeks gestational age
- For 0–1 week of Age :
- Preferred regimen (1): Meropenem 60 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Imipenem 50 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (3): Doripenem 20 mg/kg/day IV divided q12h for 2–3 weeks
- For 1–4 wk of Age :
- Preferred regimen (1): Meropenem 90 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Imipenem 75 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (3): Doripenem 30 mg/kg/day IV divided q8h for 2–3 weeks
- 3.2.5.1.2.1.2 For 34–37 week gestational age
- For 0–1 week of Age :
- Preferred regimen (1): Meropenem 60 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Imipenem 50 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (3): Doripenem 20 mg/kg/day IV divided q12h for 2–3 weeks
- For 1–4 week of Age :
- Preferred regimen (1): Meropenem 90 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Imipenem 75 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (3): Doripenem 30 mg/kg/day IV divided q8h for 2–3 weeks
- 3.2.5.1.2.1.3 Term newborn infant
- For < 1 week of age
- Preferred regimen (1): Meropenem 60 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Imipenem 50 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (3): Doripenem 20 mg/kg/day IV divided q12h for 2–3 weeks
- For 1–4 week of age
- Preferred regimen (1): Meropenem 90 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Imipenem 75 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (3): Doripenem 30 mg/kg/day IV divided q8h for 2–3 weeks
- 3.2.5.1.2.2 Alternatives for penicillin-susceptible strains
- 3.2.5.1.2.2.1 For 32–34 weeks gestational age
- For 0–1 week of age
- Alternative regimen (1): Penicillin G 200000 Units/kg/day IV divided q12h for 2–3 weeks
- Alternative regimen (2): Ampicillin 100 mg/kg/day IV divided q12h for 2–3 weeks
- For 1–4 week of age :
- Alternative regimen (1): Penicillin G 300000 Units/kg/day IV divided q12h for 2–3 weeks
- Alternative regimen (2): Ampicillin 150 mg/kg/day divided IV q12h for 2–3 weeks
- 3.2.5.1.2.2.2 For 34–37 week gestational age
- For < 1 week of age
- Alternative regimen (1): Penicillin G 300000 Units/kg/day IV divided q12h for 2–3 weeks
- Alternative regimen (2): Ampicillin 150 mg/kg/day IV divided q12h for 2–3 weeks
- For 1–4 week of age
- Alternative regimen (1): Penicillin G 400000 Units/kg/day IV divided q12h for 2–3 weeks
- Alternative regimen (2): Ampicillin 200 mg/kg/day IV divided q12h for 2–3 weeks
- 3.2.5.1.2.2.3 Term newborn infant
- For 0–1 week of age
- Alternative regimen (1): Penicillin G 300000 Units/kg/day IV divided q12h for 2–3 weeks
- Alternative regimen (2): Ampicillin 150 mg/kg/day IV divided q12h for 2–3 weeks
- For 1–4 week of age
- Alternative regimen (1): Penicillin G 400000 Units/kg/day IV divided q12h for 2–3 weeks
- Alternative regimen (2): Ampicillin 200 mg/kg/day IV divided q12h for 2–3 weeks AND
- 3.2.5.1.3 A protein synthesis inhibitor
- 3.2.5.1.3.1 For 32–34 weeks gestational age
- For < 1 week of age
- Preferred regimen (1): Linezolid 20 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (2): Clindamycin 10 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (4): Chloramphenicol 25 mg/kg/day IV q24h for 2–3 weeks
- For 1–4 week of age
- Preferred regimen (1): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (4): Chloramphenicol 50 mg/kg/day IV q12h for 2–3 weeks
- 3.2.5.1.3.2 For 34–37 week gestational age
- For < 1 week of age
- Preferred regimen (1): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (4): Chloramphenicol 25 mg/kg/day IV q24h for 2–3 weeks
- For 1–4 week of age
- Preferred regimen (1): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Clindamycin 20 mg/kg/day IV divided q6h for 2–3 weeks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (4): Chloramphenicol 50 mg/kg/day IV q12h for 2–3 weeks
- 3.2.5.1.3.3 Term newborn infant
- For < 1 week of age
- Preferred regimen (1): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (4): Chloramphenicol 25 mg/kg/day IV q24h for 2–3 weeks
- For 1–4 week of age
- Preferred regimen (1): Linezolid 30 mg/kg/day IV divided q8h for 2–3 weeks
- Preferred regimen (2): Clindamycin 20 mg/kg/day IV divided q6h for 2–3 weeks
- Preferred regimen (3): Rifampin 20 mg/kg/day IV divided q12h for 2–3 weeks
- Preferred regimen (4): Chloramphenicol 50 mg/kg/day IV q12h for 2–3 weeks
- Note :Duration of therapy for 2–3 weeks, until clinical criteria for stability are met. Will require prophylaxis to complete an antibiotic course of upto 60 days from onset of illness.
- 3.2.5.2 Therapy for severe anthrax when meningitis can be ruled out
- 3.2.5.2.1 A bactericidal antimicrobial
- 3.2.5.2.1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- 3.2.5.2.1.1.1 For 32–34 weeks gestational age
- For < 1 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2-3 weeks
- Preferred regimen (2): Meropenem 40 mg/kg/day IV divided q8h for 2-3 weeks
- Preferred regimen (3): Imipenem 40 mg/kg/day IV divided q12h for 2-3 weeks
- For 1–4 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2-3 weeks
- Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h for 2-3 weeks
- Preferred regimen (3): Imipenem 50 mg/kg/day IV divided q12h for 2-3 weeks
- 3.2.5.2.1.1.2 For 34–37 week gestational age
- For < 1 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2-3 weeks
- Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h for 2-3 weeks
- Preferred regimen (3): Imipenem 50 mg/kg/day IV divided q12h for 2-3 weeks
- For 1–4 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day IV divided q12h for 2-3 weeks
- Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h for 2-3 weeks
- Preferred regimen (3): Imipenem 75 mg/kg/day IV divided q8h for 2-3 weeks
- 3.2.5.2.1.1.3 Term Newborn Infant
- For < 1 week of age
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q12h for 2-3 weeks
- Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h for 2-3 weeks
- Preferred regimen (3): Imipenem 50 mg/kg/day IV divided q12h for 2-3 weeks
- For 1–4 week of age
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day IV divided q12h for 2-3 weeks
- Preferred regimen (2): Meropenem 60 mg/kg/day IV divided q8h for 2-3 weeks
- Preferred regimen (3): Imipenem 75 mg/kg/day IV divided q8h for 2-3 weeks
- Vancomycin IV (dosing based on serum creatinine for infants of 32 wk gestational age). Follow vancomycin serum concentrations to modify dose.
- If Serum creatinine < 0.7 then Vancomycin 15 mg/kg/dose IV q12h for 2-3 weeks
- If Serum creatinine 0.7 -0.9 then Vancomycin 20 mg/kg/dose IV q24h for 2-3 weeks
- If Serum creatinine 1–1.2 then Vancomycin 15 mg/kg/dose IV q24h for 2-3 weeks
- If Serum creatinine 1.3–1.6 then Vancomycin 10 mg/kg/dose IV q24h for 2-3 weeks
- If Serum creatinine > 1.6 then Vancomycin mg/kg/dose IV q48h for 2-3 weeks
- Note: Begin treatment with a 20 mg/kg loading dose OR
- 3.2.5.2.1.2 Alternatives for penicillin-susceptible strains
- 3.2.5.2.1.2.1 For 32–34 weeks gestational age
- For < 1 week of age
- Alternative regimen (1): Penicillin G 200000 U/kg/day IV divided q12h for 2-3 weeks
- Alternative regimen (2): Ampicillin 100 mg/kg/day IV divided q12h for 2-3 weeks
- For 1–4 week of age
- Alternative regimen (1): Penicillin G 300000 U/kg/day IV divided q8h for 2-3 weeks
- Alternative regimen (2): Ampicillin 150 mg/kg/day IV divided q8h for 2-3 weeks
- 3.2.5.2.1.2.2 For 34–37 week gestational age
- For < 1 week of age
- Alternative regimen (1): Penicillin G 300000 U/kg/day IV divided q8h for 2-3 weeks
- Alternative regimen (2): Ampicillin 150 mg/kg/day IV divided q8h for 2-3 weeks
- For 1–4 week of age
- Alternative regimen (1): Penicillin G 400000 U/kg/day IV divided q6h for 2-3 weeks
- Alternative regimen (2): Ampicillin 200 mg/kg/day IV divided q6h for 2-3 weeks
- 3.2.5.2.1.2.3 Term newborn infant
- For < 1 week of age
- Alternative regimen (1): Penicillin G 300000 U/kg/day IV divided q8h for 2-3 weeks
- Alternative regimen (2): Ampicillin 150 mg/kg/day IV divided q8h for 2-3 weeks
- For 1–4 week of age
- Alternative regimen (1): Penicillin G 400000 U/kg/day IV divided q6h for 2-3 weeks
- Alternative regimen (2):Ampicillin 200 mg/kg/day IV divided q6h for 2-3 weeks
- 3.2.5.2.2 A protein synthesis inhibitor
- 3.2.5.2.2.1 For 32–34 weeks gestational age
- For < 1 week of age
- Preferred regimen (1): Clindamycin 10 mg/kg/day IV divided q12h for 2–3 wks
- Preferred regimen (2): Linezolid 20 mg/kg/day IV divided q12h for 2–3 wks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV q24h for 2–3 wks
- For 1–4 week of age
- Preferred regimen (1): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 wks
- Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 wks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV q24h for 2–3 wks
- 3.2.5.2.2.2 For 34–37 week gestational age
- For < 1 week of age
- Preferred regimen (1): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 wks
- Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 wks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV q24h for 2–3 wks
- For 1–4 week of age
- Preferred regimen (1): Clindamycin 20 mg/kg/day IV divided q6h for 2–3 wks
- Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 wks
- Preferred regimen (3): Rifampin 10 mg/kg/day IV q24h for 2–3 wks
- 3.2.5.2.2.3 Term newborn infant
- For 0–1 week of age :
- Preferred regimen (1): Clindamycin 15 mg/kg/day IV divided q8h for 2–3 wks
- Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 wks
- Preferred regimen (3): Doxycycline 4.4 mg/kg/day IV divided q12h, (loading dose 4.4 mg/kg) for 2–3 wks
- Preferred regimen (4): Rifampin 10 mg/kg/day IV q24h for 2–3 wks
- For 1–4 week of age :
- Preferred regimen (1): Clindamycin 20 mg/kg/day IV divided q6h for 2–3 wks
- Preferred regimen (2): Linezolid 30 mg/kg/day IV divided q8h for 2–3 wks
- Preferred regimen (3): Doxycycline 4.4 mg/kg/day IV divided q12h, (loading dose 4.4 mg/kg) for 2–3 wks
- Preferred regimen (4): Rifampin 10 mg/kg/day IV q24h for 2–3 wks
- Note: Duration of therapy for 2–3 wks, until clinical criteria for stability are met (see text). Will require prophylaxis to complete an antimicrobial course of upto 60 days from onset of illness
- 3.2.5.3 Oral follow-up combination therapy for severe anthrax
- 3.2.5.3.1 A bactericidal antimicrobial
- 3.2.5.3.1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- 3.2.5.3.1.1.1 For 32–34 weeks gestational age
- For < 1 week of age
- Preferred regimen: Ciprofloxacin 20 mg/kg/day PO bid
- For 1–4 week of age
- Preferred regimen: Ciprofloxacin 20 mg/kg/day PO bid
- 3.2.5.3.1.1.2 For 34–37 week gestational age
- For < 1 week of age
- Preferred regimen: Ciprofloxacin 20 mg/kg/day PO bid
- For 1–4 week of age
- Preferred regimen: Ciprofloxacin 20 mg/kg/day PO bid
- 3.2.5.3.1.1.3 Term newborn infant
- For < 1 week of age
- Preferred regimen: Ciprofloxacin 30 mg/kg/day PO bid
- For 1–4 week of age
- Preferred regimen: Ciprofloxacin 30 mg/kg/day PO bid OR
- 3.2.5.3.1.2 Alternatives for penicillin-susceptible strains
- 3.2.5.3.1.2.1 For 32–34 weeks gestational age
- For < 1 week of age
- Alternative regimen (1): Amoxicillin 50 mg/kg/day PO bid
- Alternative regimen (2): Penicillin VK 50 mg/kg/day PO bid
- For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO bid
- Alternative regimen (2): Penicillin VK 75 mg/kg/day PO bid
- 3.2.5.3.1.2.2 For 34–37 week gestational age
- For < 1 week of age
- Alternative regimen (1): Amoxicillin 50 mg/kg/day PO bid
- Alternative regimen (2): Penicillin VK 50 mg/kg/day PO bid
- For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO bid
- Alternative regimen (2): Penicillin VK 75 mg/kg/day PO tid
- 3.2.5.3.1.2.3 Term newborn infant
- For < 1 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid
- Alternative regimen (2): Penicillin VK 75 mg/kg/day PO tid
- For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid
- Alternative regimen (2): Penicillin VK 75 mg/kg/day PO tid or qid
- 3.2.5.3.2 A protein synthesis inhibitor
- 3.2.5.3.2.1 For 32–34 weeks gestational age
- For < 1 week of age
- Preferred regimen (1): Clindamycin 10 mg/kg/day PO bid
- Preferred regimen (2): Linezolid 20 mg/kg/day PO bid
- For 1–4 week of age
- Preferred regimen (1): Clindamycin 15 mg/kg/day PO bid
- Preferred regimen (2): Linezolid 30 mg/kg/day PO bid
- 3.2.5.3.2.2 For 34–37 week gestational age
- For < 1 week of age
- Preferred regimen (1): Clindamycin 15 mg/kg/day PO tid
- Preferred regimen (2): Linezolid 30 mg/kg/day PO tid
- For 1–4 week of age
- Preferred regimen (1): Clindamycin 20 mg/kg/day PO qid
- Preferred regimen (2): Linezolid 30 mg/kg/day PO tid
- 3.2.5.3.2.3 Term newborn infant
- For < 1 week of age
- Preferred regimen (1): Clindamycin 15 mg/kg/day PO tid
- Preferred regimen (2): Doxycycline 4.4 mg/kg/day PO bid (loading dose 4.4 mg/kg)
- Preferred regimen (3): Linezolid 30 mg/kg/day PO tid
- For 1–4 week of age
- Preferred regimen (1): Clindamycin 20 mg/kg/day PO qid
- Preferred regimen (2): Doxycycline 4.4 mg/kg/day PO bid (loading dose 4.4 mg/kg)
- Preferred regimen (3): Linezolid 30 mg/kg/day PO tid
- Note: Duration of therapy to complete a treatment course of 10–14 days or greater. May require prophylaxis to complete an antimicrobial course of upto 60 days from onset of illness.
- 3.2.5.4 Treatment of cutaneous anthrax without systemic involvement
- 3.2.5.4.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- 3.2.5.4.1.1 For 32–34 weeks gestational age
- For < 1 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day PO bid
- Preferred regimen (2): Clindamycin 10 mg/kg/day PO bid
- For 1–4 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day PO bid
- Preferred regimen (2): Clindamycin 15 mg/kg/day PO tid
- 3.2.5.4.1.2 For 34–37 week gestational age
- For < 1 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day PO bid
- Preferred regimen (2): Clindamycin 15 mg/kg/day PO tid
- For 1–4 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day PO bid
- Preferred regimen (2): Clindamycin 20 mg/kg/day PO qid
- 3.2.5.4.1.3 Term newborn infant
- For < 1 week of age
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day PO bid
- Preferred regimen (2): Doxycycline 4.4 mg/kg/day PO bid (Loading dose 4.4 mg/kg)
- Preferred regimen (3): Clindamycin 15 mg/kg/day PO tid
- For 1–4 week of age
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day PO bid
- Preferred regimen (2): Doxycycline 4.4 mg/kg/day PO bid (Loading dose 4.4 mg/kg)
- Preferred regimen (3): Clindamycin 20 mg/kg/day PO qid
- 3.2.5.4.2 Alternatives for penicillin-susceptible strains
- 3.2.5.4.2.1 For 32–34 weeks gestational age
- For < 1 week of age
- Alternative regimen (1): Amoxicillin 50 mg/kg/day PO bid
- Alternative regimen (2): Penicillin Vk 50 mg/kg/day PO bid
- For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid
- Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO tid
- 3.2.5.4.2.2 For 34–37 week gestational age
- For < 1 week of age
- Alternative regimen (1): Amoxicillin 50 mg/kg/day PO bid
- Alternative regimen (2): Penicillin Vk 50 mg/kg/day PO bid
- For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO bid
- Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO bid
- 3.2.5.4.2.3 Term newborn infant
- For < 1 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid
- Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO tid
- For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day PO tid
- Alternative regimen (2): Penicillin Vk 75 mg/kg/day PO tid or qid
- Note : Duration of therapy for naturally acquired infection is 7–10 days and for a biological weapon–related event,may require additional prophylaxis for inhaled spores to complete an antimicrobial course of up to 60 days from onset of illness.
- Bacillus anthracis, postexposure prophylaxis
- 1. For adults[69]
- 1.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- Preferred regimen (1): Ciprofloxacin 500 mg IV q12h
- Preferred regimen (2): Doxycycline 100 mg IV q12h
- Preferred regimen (3): Levofloxacin 750 mg IV q24h
- Preferred regimen (4): Moxifloxacin 400 mg IV q24h
- Preferred regimen (5): Clindamycin 600 mg IV q8h
- 1.2 Alternatives for penicillin-susceptible strain
- Preferred regimen (1): Amoxicillin 1 g IV q8h
- Preferred regimen (2): Penicillin VK 500 mg IV q6h
- 2. For children = 1 month[71]
- 2.1 For penicillin-resistant strains or prior to susceptibility testing
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day, PO, bid (not to exceed 500 mg/dose)
- Preferred regimen (2):
- If patients body weight < 45 kg: Doxycycline 4.4 mg/kg/day, PO, bid (not to exceed 100 mg/dose)
- If patients body weight > 45 kg: Doxycycline 100 mg/dose, PO, bid
- Preferred regimen (3): Clindamycin 30 mg/kg/day, PO, tid (not to exceed 900 mg/dose)
- Preferred regimen (4):
- If patients body weight < 50 kg: Levofloxacin 16 mg/kg/day, PO, bid (not to exceed 250 mg/dose)
- If patients body weight > 50 kg: Levofloxacin 500 mg, PO, qd
- 2.2 For penicillin-susceptible strains
- Preferred regimen (1): Amoxicillin 75 mg/kg/day, PO, tid (not to exceed 1 g/dose)
- Preferred regimen (2): Penicillin VK 50-75 mg/kg/day, PO, id or tid
- Note: Duration of Therapy is 60 days after exposure
- 3. For children < 1 month
- 3.1 For all strains, regardless of penicillin susceptibility or if susceptibility is unknown
- 3.1.1 For 32–34 weeks gestational age
- 3.1.1.1 For < 1 week of Age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day, PO, bid
- Preferred regimen (2): Clindamycin 10 mg/kg/day, PO, bid
- 3.1.1.2 For 1–4 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day, PO,bid
- Preferred regimen (2): Clindamycin 15 mg/kg/day, PO, tid
- 3.1.2 For 34–37 week gestational age
- 3.1.2.1 For < 1 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day, PO, bid
- Preferred regimen (2): Clindamycin 15 mg/kg/day, PO, tid
- 3.1.2.2 For 1–4 week of age
- Preferred regimen (1): Ciprofloxacin 20 mg/kg/day, PO, bid
- Preferred regimen (2): Clindamycin 20 mg/kg/day, PO, id
- 3.1.3 Term newborn infant
- 3.1.3.1 For < 1 week of age
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day, PO, bid
- Preferred regimen (2): Doxycycline 4.4 mg/kg/day, PO, bid (Loading dose 4.4 mg/kg)
- Preferred regimen (3): Clindamycin 15 mg/kg/day, PO, tid
- 3.1.3.2 For 1–4 week of Age
- Preferred regimen (1): Ciprofloxacin 30 mg/kg/day, PO, bid
- Preferred regimen (2): Doxycycline 4.4 mg/kg/day, PO, bid (Loading dose 4.4 mg/kg)
- Preferred regimen (3): Clindamycin 20 mg/kg/day, PO, qid
- 3.2 Alternatives for penicillin-susceptible strains
- 3.2.1 For 32–34 weeks gestational age
- 3.2.1.1 For < 1 week of age
- Alternative regimen (1): Amoxicillin 50 mg/kg/day, PO, bid
- Alternative regimen (2): Penicillin Vk 50 mg/kg/day, PO, bid
- 3.2.1.2 For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day, PO, tid
- Alternative regimen (2): Penicillin Vk 75 mg/kg/day, PO, tid
- 3.2.2 For 34–37 week gestational age
- 3.2.2.1 For < 1 week of age
- Alternative regimen (1): Amoxicillin 50 mg/kg/day, PO, bid
- Alternative regimen (2): Penicillin Vk 50 mg/kg/day, PO, bid
- 3.2.2.2 For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day, PO, tid
- Alternative regimen (2): Penicillin Vk 75 mg/kg/day, PO, tid
- 3.2.3 Term newborn infant
- 3.2.3.1 For < 1 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day, PO, tid
- Alternative regimen (2): Penicillin Vk 75 mg/kg/day, PO, tid
- 3.2.3.2 For 1–4 week of age
- Alternative regimen (1): Amoxicillin 75 mg/kg/day, PO, tid
- Alternative regimen (2): Penicillin Vk 75 mg/kg/day, PO, id or tid
- Note: Duration of therapy is 60 days from exposure
- Bacillus cereus Return to Top
- 1. Food poisoning[72]
- Preferred regimen: Food poisoning is usually self-limited and requires no antibiotic therapy.
- 2. Bacteremia
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- Note (1): Bacillus cereus is commonly resistant to beta-lactams.
- Note (2): Pseudobacteremia is transient and usually results from contaminated blood cultures, gloves, or syringes.
- 3. Meningitis or brain abscess
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- Note: Blood culture isolates are mostly contaminates until proven otherwise, especially in intravenous drug user population.
- 4. Endophthalmitis
- Preferred regimen: Clindamycin 450 μg intravitreal AND Gentamicin 400 μg intravitreal OR Dexamethasone intravitreal AND Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- Note: Ophthalmological consultation, culture ocular fluids, early vitrectomy, and intravitreal antibiotics are necessary.
- 5. Endocarditis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Note: Most blood cultures in intravenous drug users are contaminates or represent transient bacteremia.
- 6. Soft tissue infection
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- 7. Pneumonia
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- Bacillus subtilis Return to Top
- Bacillus subtilis infection treatment[73][74][75]
- 1. Food poisoning
- Preferred regimen: supportive treatment
- 2. Other infections
- Preferred regimen: Vancomycin OR Clindamycin
- Alternative regimen: Ciprofloxacin OR Imipenem
- Note: Distinguish clinically significant infection from contamination before administering antibiotics.
- Clostridium botulinum Return to Top
- Botulism
- 1.Foodborne botulism[76]
- 1.1 Adult
- Preferred regimen: Heptavalent botulism antitoxin IV starting infusion rate (first 30 minutes): 0.5 mL/min; incremental infusion rate if tolerated (every 30 minutes): double the rate; maximum infusion rate: 2 mL/min
- 1.2 Children
- 1.2.1 Children < 1 year
- Preferred regimen: Heptavalent botulism antitoxin IV starting infusion rate (first 30 minutes): 0.01 mL/kg/min; incremental infusion rate if tolerated (every 30 minutes): 0.01 mL/kg/min ; maximum infusion rate: 0.03 mL/kg/min (10% of adult dose regardless of body weight)
- 1.2.1 Children 1-17 years
- Preferred regimen: Heptavalent botulism antitoxin IV starting infusion rate (first 30 minutes): 0.01 mL/kg/min; incremental infusion rate if tolerated (every 30 minutes): 0.01 mL/kg/min ; maximum infusion rate: 0.03 mL/kg/min (20 – 100% of adult dose)
- Note:Physicians may try to remove contaminated food still in the gut by inducing vomiting or by using enemas. A patient with severe botulism may require a ventilator as well as intensive medical and nursing care for several months.
- 2. Infant botulism[77]
- Preferred regimen: BabyBIG, Botulism Immune Globulin Intravenous (Human) (BIG-IV) is for the treatment of patients below one year of age.The recommended total dosage is 1mL/kg (50mg/kg), given as a single IV infusion as soon as the clinical diagnosis of infant botulism is made
- Note: infant with botulism must receive supportive care during their recovery. This includes ensuring proper nutrition,keeping the airway clear,watching for respiratory failure and if it develops,ventilator may be needed.
- 3. Wound botulism
- 3.1 Adult
- Preferred regimen (adult): Heptavalent botulism antitoxin IV starting infusion rate (first 30 minutes): 0.5 mL/min; incremental infusion rate if tolerated (every 30 minutes): double the rate; maximum infusion rate: 2 mL/min
- 3.2 Children
- 3.2.1 Children < 1 year
- Preferred regimen: Heptavalent botulism antitoxin IV starting infusion rate (first 30 minutes): 0.01 mL/kg/min; incremental infusion rate if tolerated (every 30 minutes): 0.01 mL/kg/min ; maximum infusion rate: 0.03 mL/kg/min (10% of adult dose regardless of body weight)
- 3.2.2 Children 1-17 years
- Preferred regimen: Heptavalent botulism antitoxin IV starting infusion rate (first 30 minutes): 0.01 mL/kg/min; incremental infusion rate if tolerated (every 30 minutes): 0.01 mL/kg/min ; maximum infusion rate: 0.03 mL/kg/min (20 – 100% of adult dose)
- Note (1): Physicians may try to remove contaminated food still in the gut by inducing vomiting or by using enemas. A patient with severe botulism may require a ventilator as well as intensive medical and nursing care for several months.
- Note (2): For wound botulism, antibiotics are used in addition to appropriate debridement.
- Note (3): Antibiotic therapy is recommended for wound botulism after antitoxin has been administered. Penicillin G 3 MU IV q4h in adults is frequently used. Metronidazole 500 mg IV q8h may be used as an alternative for penicillin-allergic patients.
- Clostridium perfringens Return to Top
- Clostridium perfringens [78]
- Gas gangrene
- Preferred regimen: Penicillin G 3-4 million units IV q4h AND (Clindamycin 900 mg IV q8h OR Tetracycline 500 mg IV q6h)[79]
- Clostridium tetani Return to Top
- 1. General measures
- Preferred regimen: Patients should be placed in a quiet shaded area and protected from tactile and auditory stimulation as much as possible; All wounds should be cleaned and debrided as indicated
- 2. Immunotherapy
- Preferred regimen: Human TIG 500 units IV/IM as soon as possible AND Age-appropriate TT-containing vaccine, 0.5 cc IM at a separate site
- Note: patients without a history of primary TT vaccination should receive a second dose 1–2 months after the first dose and a third dose 6–12 months later
- 3. Antibiotic treatment[80]
- Preferred regimen: Metronidazole 500 mg IV/PO q6h OR Penicillin G 100,000–200,000 IU/kg/day IV, administered in 2–4 divided doses
- Alternative regimen: Tetracyclines OR Macrolides OR Clindamycin OR Cephalosporins OR Chloramphenicol
- 4. Muscle spasm control
- Preferred regimen: Diazepam 5 mg IV OR Lorazepam 2 mg IV titrating to achieve spasm control without excessive sedation and hypoventilation
- Alternative regimen (1): Magnesium sulphate 5 g (or 75mg/kg) IV loading dose, then 2–3 g per hour until spasm control is achieved ± Benzodiazepines
- Note: Monitor patellar reflex as areflexia (absence of patellar reflex) occurs at the upper end of the therapeutic range (4mmol/L). If areflexia develops, dose should be decreased
- Alternative regimen (2): Baclofen OR Dantrolene 1–2 mg/kg IV/PO q4h
- Alternative regimen (3): Barbiturates 100–150 mg q1-4h by any route
- Alternative regimen (4): Chlorpromazine 50–150 mg IM q4–8h
- Pediatric regimen: Lorazepam 0.1–0.2 mg/kg IV q2–6h, titrating upward as needed; Barbiturates 6–10 mg/kg in children by any route; Chlorpromazine 4–12 mg IM every q4–8h
- Note: As for Benzodiazepines, large amounts may be required (up to 600 mg/day); oral preparations could be used but must be accompanied by careful monitoring to avoid respiratory depression or arrest
- 5. Autonomic dysfunction control
- Preferred regimen: Magnesium sulphate OR Morphine OR Esmolol
- 6. Airway/respiratory control
- Note: Drugs used to control spasm and provide sedation can result in respiratory depression. If spasm, including laryngeal spasm, is impeding or threatening adequate ventilation, mechanical ventilation is recommended when possible. Early tracheostomy is preferred as endotracheal tubes can provoke spasm and exacerbate airway compromise.
- Clostridium difficile Return to Top
- 1. Pseudomembranous colitis - mild to moderate[81]
- Preferred regimen:Metronidazole 500 mg PO tid for 10-14 days
- Alternative regimen: Vancomycin 125 mg PO qid for 10-14 days
- Note: If significant risk of recurrence: Vancomycin 125 mg PO qid for 10-14 days OR Fidaxomicin 200 mg PO bid for 10 days
- 2. Pseudomembranous colitis - severe[81]
- Preferred regimen: Vancomycin 125 mg PO qid for 10-14 days
- Note: If significant risk of recurrence: Vancomycin 125 mg PO qid for 10-14 days OR Fidaxomicin 200 mg PO bid for 10 days
- 3. Pseudomembranous colitis - severe, complicated[81]
- Preferred regimen: Vancomycin 125-500 mg PO qid for 10-14 days AND Vancomycin 500 mg diluted in 500 ml of saline as enema per rectum q6h AND Metronidazole 500 mg IV q8h
- Note: Consider urgent surgical consult
- 4. Recurrent pseudomembranous colitis[81]
- First recurrence treatment
- Preferred regimen: same as first episode or [Fidaxomicin]] 200 mg PO bid for 10 days
- Second or more recurrence treatment
- Preferred regimen: Vancomycin 125 mg PO qid for 14 days THEN Vancomycin 125 mg PO tid for 7 days THEN Vancomycin 125 mg PO bid for 7 days THEN Vancomycin 125 mg PO qd for 7 days THEN Vancomycin 125 mg PO q48h for 7 days THEN Vancomycin 125 mg PO q72h for 7 days OR Fidaxomicin 200 mg PO bid for 10 days
- Note: Consider expert consult for fecal microbiota transplantation
# Corynebacterium
- Corynebacterium diphtheriae Return to Top
- Diphtheria treatment [82] [83]
- 1. Antitoxin
- 1.1 Pharyngeal disease <48 hrs
- Preferred regimen: 20,000-40,000 U IV/IM
- 1.2 Nasopharyngeal
- Preferred regimen: 40-60,000 U IV/IM
- 1.3 Extensive disease, or > 72 hrs
- Preferred regimen: 80-120,000 U IV/IM
- Note: IV administration for severe disease
- 2. Antibiotics
- Preferred regimen: Erythromycin 40 mg/kg/day (Maximum, 2 gm/day) PO/IV for 14 days
- Alternative regimen: Procaine penicillin G 600,000 U/day IM qd for 14 days
- Note: Procaine penicillin G 300,000 U/day for those weighing 10 kg or less
- 3. Preventive antibiotic use
- Note: For close contacts, especially household contacts, a diphtheria booster, appropriate for age, should be given
- Preferred regimen: Benzathine penicillin G
- younger than 6 years old: 600,000 U IM
- 6 years old and older: 1,200,000 U IM
- Alternative regimen: Erythromycin
- Adult: 1 g/day PO 7-10 days
- Pediatric: 40 mg/kg/day PO 7-10 days
- Note (1): If surveillance of contacts cannot be maintained, they should receive benzathine penicillin G
- Note (2): Maintain close surveillance and begin antitoxin at the first signs of illness
- Corynebacterium jeikeium Return to Top
- Corynebacterium jeikeium[84]
- Preferred regimen : Vancomycin 1 gm IV q12h
- Alternative regimen : Penicillin G AND Anti pseudomonal aminoglycosides like Tobramycin, Gentamicin, Amikacin
- Corynebacterium urealyticum Return to Top
- Corynebacterium urealyticum[85]
- 1. Post renal transplant obstructive uropathy
- Preferred regimen (1): Vancomycin 1 gm IV q12h
- Preferred regimen (2): Teicoplanin 6 mg/kg/day IV q24h
- Coxiella burnetii Return to Top
- Q fever[86]
- 1. Acute Q fever
- 1.1 Adults
- Preferred Regimen: Doxycycline 100 mg PO bid for 14 days
- 1.2 Children
- 1.2.1 Children with age ≥8 years
- Preferred regimen: Doxycycline 2.2 mg/kg PO bid for 14 days (maximum 100 mg per dose)
- 1.2.2 Children with age <8 years with high risk criteria
- Preferred regimen: Doxycycline 2.2 mg/kg PO bid for 14 days (maximum: 100 mg per dose)
- 1.2.3 Children with age <8 years with mild or uncomplicated illness
- Preferred regimen: Doxycycline 2.2 mg/kg PO bid for 5 days (maximum 100 mg per dose).
- 1.2.3 Children with age < 8 years with mild or uncomplicated illness,who remains febrile past 5 days of treatment
- Preferred regimen: Trimethoprim/Sulfamethoxazole 4-20 mg/kg PO bid for 14 days (maximum: 800 mg per dose)
- 1.3 Pregnant women
- Preferred regimen: Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO bid a day throughout pregnancy
- 2. Chronic Q fever
- 2.1 Endocarditis or vascular infection
- Preferred regimen: Doxycycline 100 mg PO bid AND Hydroxychloroquine 200 mg PO tid for ≥18 months
- Note: childern and pregnant women- consultation Recommended
- 2.2 Noncardiac organ disease
- Preferred regimen: Doxycycline 100 mg PO bid AND Hydroxychloroquine 200 mg PO tid
- Note: childern and pregnant women- consultation Recommended
- 2.3 Postpartum with serologic profile for chronic Q fever
- Preferred regimen: Doxycycline 100 mg PO bid AND Hydroxychloroquine 200 mg PO tid for 12 months
- Note (1): Women should only be treated postpartum if serologic titers remain elevated >12 months after delivery (immunoglobulin G phase I titer ≥1:1024). Women treated during pregnancy for acute Q fever should be monitored similarly to other patients who are at high risk for progression to chronic disease (e.g., serologic monitoring at 3, 6, 12, 18, and 24 months after delivery)
- Note (2): Post-Q fever fatigue syndrome- no current recommendation.
- Ehrlichia Return to Top
- 1. Human Monocytic Ehrlichiosis or Human Granulocytic Anaplasmosis (adult) [87]
- Preferred regimen: Doxycycline 100 mg PO/IV q12h for 7-14 days
- Note: Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement
- Alternative regimen (1): Chloramphenicol 500mg PO qid
- Alternative regimen (2): Rifampin 600 mg PO/IV qd for 7-10 days
- 2. Human Monocytic Ehrlichiosis or Human Granulocytic Anaplasmosis (pediatric)
- 2.1 ≥ 8 years old
- Preferred regimen: Doxycycline 2 mg/kg IV/PO q12h (Maximum, 200 mg/day) for 10 days
- 2.2 < 8 years old without Lyme disease
- Preferred regimen: Doxycycline 2 mg/kg IV/PO q12h (Maximum, 200 mg/day) for 4-5 days (or 3 days after resolution of fever)
- 2.3 co-infected with Lyme disease
- Preferred regimen: Doxycycline (see above) THEN Amoxicillin 50 mg/kg/day tid (Maximum, 500 mg/dose) OR Cefuroxime 30 mg/kg/day bid (Maximum, 500 mg/dose) for 14 days
- Erysipelothrix rhusiopathiae Return to Top
- Erysipelothrix rhusiopathiae [88]
- 1. Erysipeloid of Rosenbach (localized cutaneous infection)
- Preferred regimen (1): Penicillin G benzathine 1.2 MU IV single dose
- Preferred regimen (2): Penicillin VK 250 mg PO qid for 5-7 days
- Preferred regimen (3): Procaine penicillin 0.6-1.2 MU IM qd for 5-7 days
- Alternative regimen (1): Erythromycin 250 mg PO qid for 5-7 days
- Alternative regimen (2): Doxycycline 100 mg PO bid for 5-7 days
- 2. Diffuse cutaneous infection
- Preferred regimen: See localized infection
- 3. Bacteremia or endocarditis
- Preferred regimen: Penicillin G benzathine 2-4 MU IV q4h for 4-6 weeks
- Alternative regimen (1): Ceftriaxone 2 g IV q24h for 4-6 weeks
- Alternative regimen (2): Imipenem 500 mg IV q6h for 4-6 weeks
- Alternative regimen (3): Ciprofloxacin 400 mg IV q12h for 4-6 weeks
- Alternative regimen (4): Daptomycin 6 mg/kg IV q24h for 4-6 weeks
- Note: Recommended duration of therapy for endocarditis is 4 to 6 weeks, although shorter courses consisting of 2 weeks of intravenous therapy followed by 2 to 4 weeks of oral therapy have been successful
- Listeria monocytogenes Return to Top
- 1. Meningitis [89]
- Preferred regimen: Ampicillin 2g IV q4-6h ± Gentamicin 1.7 mg/kg IV q8h for more than 3 weeks
- Alternative regimen: TMP-SMX 3-5 mg/kg (trimethoprim) IV q6h for more than 3 weeks
- 2. Bacteremia
- Preferred regimen: Ampicillin 2g IV q4-6h ± Gentamicin 1.7 mg/kg IV q8h for 2 weeks
- Alternative regimen: TMP-SMX 3-5 mg/kg (trimethoprim) q6h IV for 2 weeks
- 3. Brain abscess or rhomboencephalitis
- Preferred regimen: Ampicillin 2g IV q4-6h ± Gentamicin 1.7 mg/kg IV q8h for 4-6 weeks
- Alternative regimen: TMP-SMX 3-5 mg/kg (trimethoprim) q6h IV for 4-6 weeks
- 4. Gastroenteritis
- Preferred regimen (1): Amoxicillin 2g IV q4-6h
- Preferred regimen (2): TMP-SMX 3-5 mg/kg (trimethoprim) q6h IV for 7 days
- Lactobacillus Return to Top
- 1. Endovascular Infection [90]
- Preferred regiemn (1): Penicillin G 20 MU/day for 6 weeks
- Preferred regiemn (2): Gentamicin 1.3 mg/kg IV q8h (trough <1.5 mg/L) AND Polychlorinated naphthalene
- 2. Odontogenic Infection
- Preferred regiemn: Clindamycin 450 mg PO qid
- 3. Intrabdominal Abscess
- Preferred regiemn: Clindamycin 450 mg PO qid
- Leuconostoc Return to Top
- Leuconostoc [91]
- Preferred regimen (1): Penicillin G
- Preferred regimen (2): Ampicillin
- Alternative regimen (1): Clindamycin
- Alternative regimen (2): Erythromycin
- Alternative regimen (3): Minocycline
- Nocardia Return to Top
- 1. Sulfonamide-based therapies [92]
- 1.1 Pulmonary
- Preferred regimen: TMP-SMX 10 mg/kg/day (TMP) IV q6-12h for 3-6 weeks THEN 2 DS PO bid for at least 5 months
- 1.2 Pulmonary alternatives
- Preferred regimen: Sulfisoxazole OR Sulfadiazine OR Trisulfapyrimidine 3-6 g/day PO bid-qid OR TMP-SMX 2 DS bid up to 2 DS tid
- 1.3 CNS (AIDS, severe or disseminated disease)
- Preferred regimen: TMP-SMX 15 mg/kg/day (TMP) IV for 3-6 weeks THEN 3 DS PO bid for 6-12 months
- 1.4 CNS alternatives
- Preferred regimen: Imipenem 1000 mg IV q8h OR Ceftriaxone 2 g IV q12h OR Cefotaxime 2-3 g IV q6h AND Amikacin
- 1.5 Severe disease, compromised host, multiple sites
- Preferred regimen: TMP-SMX 15 mg/kg/day (TMP) IV AND Amikacin 7.5 mg/kg q12h OR Sulfonamide 6-12 mg/day PO
- 1.6 Sporotrichoid (cutaneous)
- Preferred regimen: TMP-SMX 1 DS bid for 4-6 months
- Note (1): Immunocompetent medicine use for 6 months; Immunosuppressed medicine for 12 months
- Note (2): Treat based on host, site of disease and in vitro activity; Sulfonamide usually preferred, must treat for 6-12 months; Preferred drugs for resistant strains are Amikacin and/or Imipenem
- Note (3): Seriously ill usually treated with IV Imipenem or Sulfonamide or Cefotaxime all potentially combined with Amikacin; less seriously ill treated with oral agents— especially TMP-SMX or Minocycline
- 2. Sulfonamide alternatives
- 2.1 Severe
- Preferred regimen (1): (For AIDS) (Imipenem 1000 mg IV q8h OR Meropenem 2 g q8h AND Amikacin 7.5 mg/kg q12h IV
- Preferred regimen (2): Cefotaxime 2-3 g q6-8h OR Ceftriaxone 2 g/day IV ± Amikacin
- 2.2 Mild
- Preferred regimen: Minocycline 100 mg bid for at least 6 months (initial treatment of local disease or maintenance)
- Alternative regimen: Amoxicillin clavulanate 875/125 mg bid OR Doxycycline OR Erythromycin OR Clarithromycin OR Linezolid OR Fluoroquinolone OR combinations for at least 6 months
- Propionibacterium acnes Return to Top
- Propiobacterium acnes [93]
- 1. Systemic infection
- Preferred regimen: Penicillin G 2 MU IV q4h for 2-4 weeks
- Alternative regimen (1): Clindamycin 600 mg IV q8h for 2-4 weeks
- Alternative regimen (2): Vancomycin 15 mg/kg IV q12h for 2-4 weeks
- 2. Shoulder prosthesis infection
- Preferred regimen: Amoxicillin AND Rifampin for 3-6 months
- 3. Acne vulgaris
- Topical antibiotics: Erythromycin OR Clindamycin
- Systemic antibiotics: Minocycline OR Doxycycline OR Trimethoprim-Sulfamethoxazole
- Rhodococcus equi Return to Top
- Rhodococcus equi [94]
- First line:
- Preferred regimen: Vancomycin 1 g IV q12h (15 mg/kg q12 for >70 kg) OR Imipenem 500 mg IV q6h AND Rifampin 600 mg PO qd OR Ciprofloxacin 750 mg PO bid OR Erythromycin 500 mg PO qid for at least 4 weeks or until infiltrate disappears
- Note: Should be administrated at least 8 weeks in immunocompromised patients
- Oral/maintenance therapy (after infiltrate clears):
- Preferred regimen (1): Ciprofloxacin 750 mg PO bid
- Preferred regimen (2): Erythromycin 500 mg PO qid
- Alternative regimen: Azithromycin OR TMP-SMX OR Chloramphenicol OR Clindamycin
- Note: Avoid Penicillins/Cephalosporins due to development of resistance; Linezolid effective in vitro, but no clinical reports of use
- Rickettsia prowazekii Return to Top
- Rickettsia rickettsii Return to Top
- 1. Adult [95] [96]
- Preferred regimen: Doxycycline 100 mg q12h
- Note: Patients should be treated for at least 3 days after the fever subsides and until there is evidence of clinical improvement. Standard duration of treatment is 7-14 days
- Alternative regimen: Chloramphenicol 500 mg PO qid for 7 days or stop 3 days after defervescence
- 2. Pediatric (under 45 kg (100 lbs))
- Preferred regimen: Doxycycline 2.2 mg/kg bid
- Note: The recommended dose and duration of medication needed to treat RMSF has not been shown to cause staining of permanent teeth, even when five courses are given before the age of eight. Healthcare providers should use doxycycline as the first-line treatment for suspected Rocky Mountain spotted fever in patients of all ages
- Rickettsia typhi Return to Top
### Bacteria – Gram-Negative Cocci and Coccobacilli
- Aggregatibacter aphrophilus Return to Top
- 1. Endocarditis[97]
- 1.1 Adults
- Preferred regimen (1): Ceftriaxone 2 g/day TV/IM q24h for 4 weeks
- Preferred regimen (2): Ampicillin-sulbactam 12 g/day TV q6h for 4 weeks
- Preferred regimen (3): Ciprofloxacin 1000 mg PO q24h OR 800 mg/day IV q12h for 4 weeks
- 1.2 Pediatrics
- Preferred regimen (1): Ceftriaxone 100 mg/kg/day TV/IM q24h for 4 weeks
- Preferred regimen (2): Ampicillin-sulbactam 300 mg/kg/day TV q6h/q4h for 4 weeks
- Preferred regimen (3): Ciprofloxacin 20-30 mg/kg/day IV/PO bid for 4 weeks
- Note (1): Floroquinolone therapy recommended for patients unable to tolerate Cephalosporin and ampicillin thearpy
- Note (2): For patients < 18 years, Flourouinolones are generally not recommended
- Note (3): For patients with endocarditis involving the prosthetic cardiac valve or other prosthetic cardiac material should be treated for 6 weeks
- 2. Abscess [98]
- Note: The small number of patients reported and the variety of antibiotics used, do not permit identification of the optimal therapeutic regimen for this organism.
# Bordetella pertusis
- Bordetella pertussis Return to Top
- Bordetella pertussis[99]
- 1. Whooping cough
- 1.1. Adults
- Preferred regimen (1): Azithromycin 500 mg PO single dose on day 1 THEN 250 mg PO qd on 2-5 days
- Preferred regimen (2): Erythromycin 2 g/day PO qid for 14 days
- Preferred regimen (3): Clarithromycin 1 g PO bid for 7 days.
- Alternative regimen (intolerant of macrolides): Trimethoprim 320 mg/day AND Sulfamethoxazole 1600 mg/day PO bid for 14 days
- 1.2. Infants <6 months of age
- 1.2.1. Infants <1 month
- Preferred regimen (1): Azithromycin 10 mg/kg PO qd for 5 days
- Preferred regimen (2) (if azithromycin unavailable): Erythromycin 40-50 mg/kg/day PO q6h for 14 days
- Note: TMP-SMX contraindicated for infants aged < 2 months
- 1.2.2. Infants of 1-5 months of age
- Preferred regimen (1): Azithromycin 10 mg/kg PO qd for 5 days
- Preferred regimen (2): Erythromycin 40-50 mg/kg/day PO qid for 14 days
- Preferred regimen (3): Clarithromycin 15 mg/kg PO bid for 7 days
- Alternative regimen: For infants aged ≥ 2 months TMP 8 mg/kg q24h AND SMX 40 mg/kg/day PO bid for 14 days
- 1.3. Infants ≥6 months of age-children
- Preferred regimen (1): Azithromycin 10 mg/kg single dose THEN 5 mg/kg (500 mg Maximum) qd for 2-5 days
- Preferred regimen (2): Erythromycin 40-50 mg/kg PO (2 g daily Maximum) qid for 14 days
- Preferred regimen (3): Clarithromycin 15 mg/kg PO (1 g daily Maximum) bid for 7 days
- Preferred regimen (4): TMP 8 mg/kg/day AND SMX 40 mg/kg/day bid for 14 days
- 2. Post exposure prophylaxis[100]
- Preferred regimen: The antibiotic regimens for post exposure prophylaxis are similar to the regimens used for the treatment of pertussis
- Note (1): Post exposure prophylaxis to an asymptomatic contacts within 21 days of onset of cough in the index patient can potentially prevent symptomatic infection
- Note (2): Close contacts include persons who have direct contact with respiratory, oral or nasal secretions from a symptomatic patient (eg: cough, sneeze, sharing food, eating utensils, mouth to mouth resuscitation, or performing a medical examination of the mouth, nose, throat.
- Note (3): Some close contacts are at high risk for acquiring severe disease following exposure to pertussis. These contacts include infants aged < 1 year , persons with some immunodeficiency conditions, or other underlying medical conditions such as chronic lung disease, respiratory insufficiency and cystic fibrosis.
# Brucella
- Brucella Return to Top
- Brucellosis [101],[102]
- 1.Uncomplicated brucellosis in adults and children ≥8yrs of age
- Preferred regimen: Doxycycline 100 mg PO bid for 6 weeks AND Streptomycin 1 g/day IM for 2-3 weeks
- Alternative regimen (1): Doxycycline 100 mg/day PO for six weeks AND Gentamicin 5mg/kg IM for 7-days
- Alternative regimen (2): Gentamicin 5mg/kg/day IV/ IM for 7-10 days AND Rifampicin 600–900 mg/day PO for six weeks
- 2. Complications of brucellosis
- 2.1 Spondylitis
- Preferred regimen:Doxycycline for 3 months AND Streptomycin for 2 to 3 weeks.
- 2.2 Neurobrucellosis
- Preferred regimen: Ceftriaxone 2 mg IV q12h for 1 month AND Doxycycline 100 mg PO bid for 4-5 month AND Rifampicin 600–900 mg/day PO for 4-5 month
- 2.3 Brucella endocarditis
- Preferred regimen: Doxycycline AND an Aminoglycoside for at least 8 weeks, and therapy should be continued for several weeks after surgery when valve replacement is necessary
- Note: Rifampicin OR Trimethoprim/sulfamethoxazole are used for their ability to penetrate cell membranes
- 3. Pregnancy
- Preferred regimen: Rifampin 900 mg PO qd for 6 weeks
- Note: Adding Trimethoprim-sulfamethoxazole can be considered, but this option should probably be avoided preceding the 13th week and after the 36th week of gestation because of concern about teratogenicity and kernicterus.
- 4.For children < 8 yrs of age
- Preferred regimen (1): TMP/SMZ 8/40 mg/ kg/day PO bid for 6 weeks AND Streptomycin 30 mg/kg/day IM q24h for 3 weeks
- Preferred regimen (2): Gentamicin 5 mg/kg/day IM/ IV q24h for 7-10 days
- Alternative regimen (1): TMP/SMZ AND Rifampicin 15 mg/kg/day PO for 6 weeks
- Alternative regimen (2): Rifampicin AND an Aminoglycoside
- Eikenella corrodens Return to Top
- 1. Human bite/soft tissue infections [103]
- 1.1 Severe
- Preferred regimen: Ampicillin sulbactam 1.5-3 g IV q6h
- Alternative regimen (1): Doxycycline 100 mg IV bid
- Alternative regimen (2): Moxifloxacin 400 mg IV q24h
- Alternative regimen (3): Levofloxacin 500 mg IV q24h
- 1.2 Mild
- Preferred regimen: Amoxicillin clavulanate 250-500 mg tid or 875/125 mg PO bid
- Alternative regimen (1): Doxycycline 100 mg PO bid
- Alternative regimen (2): Moxifloxacin 400 mg PO qd
- Alternative regimen (3): Levofloxacin 500 mg PO qd
- 2. Head and neck infections
- 2.1 Severe
- Preferred regimen: Ampicillin sulbactam 1.5-3 g IV q6h
- Alternative regimen (1): Doxycycline 100 mg IV bid
- Alternative regimen (2): Moxifloxacin 400 mg IV q24h
- Alternative regimen (3): Levofloxacin 500 mg IV q24h
- 2.2 Mild
- Preferred regimen: Amoxicillin clavulanate 250-500 mg tid or 875/125 mg PO bid
- Alternative regimen (1): Doxycycline 100 mg PO bid
- Alternative regimen (2): Moxifloxacin 400 mg PO qd
- Alternative regimen (3): Levofloxacin 500 mg PO qd
- 3. Endocarditis
- Preferred regimen (1): Ceftriaxone 1 g IV q12h
- Preferred regimen (1): Cefotaxime 1-2 g IV q8h
- Preferred regimen (1): Cefepime 1-2g IV q8h
# Haemophilus ducreyi
- Haemophilus ducreyi Return to Top
- 1. Chancroid[104]
- Preferred Regimen (1): Azithromycin 1 g PO in a single dose
- Preferred Regimen (2): Ceftriaxone 250 mg IM in a single dose
- Preferred Regimen (3): Ciprofloxacin 500 mg PO bid for 3 days
- Preferred Regimen (4): Erythromycin base 500 mg PO tid for 7 days
- Note: Patients should be tested for HIV infection at the time chancroid is diagnosed. If the initial test results were negative, a serologic test for syphilis and HIV infection should be performed 3 months after the diagnosis of chancroid.
- 1.1 Follow-up
- Patients should be re-examined 3–7 days after initiation of therapy. If treatment is successful, ulcers usually improve symptomatically within 3 days and objectively within 7 days after therapy. If no clinical improvement is evident, the clinician must consider whether 1) the diagnosis is correct, 2) the patient is coinfected with another STD, 3) the patient is infected with HIV, 4) the treatment was not used as instructed, or 5) the H. ducreyi strain causing the infection is resistant to the prescribed antimicrobial.
- Clinical resolution of fluctuant lymphadenopathy is slower than that of ulcers and might require needle aspiration or incision and drainage, despite otherwise successful therapy. Although needle aspiration of buboes is a simpler procedure, incision and drainage might be preferred because of reduced need for subsequent drainage procedures.
- 1.2 Management of sex partners
- Regardless of whether symptoms of the disease are present, sex partners of patients who have chancroid should be examined and treated if they had sexual contact with the patient during the 10 days preceding the patient’s onset of symptoms.
- 1.3 Pregnancy
- Ciprofloxacin presents a low risk to the fetus during pregnancy, with a potential for toxicity during breastfeeding. Alternative drugs should be used during pregnancy and lactation
- 1.4 HIV Infection
- Persons with HIV infection who have chancroid should be monitored closely because they are more likely to experience treatment failure and to have ulcers that heal slowly. Persons with HIV infection might require repeated or longer courses of therapy, and treatment failures can occur with any regimen.
# Haemophilus influenzae
- Haemophilus influenzae Return to Top
- Haemophilus influenzae[105]
- 1. Non- life threatening infections[106]
- 1.1 Adults
- Preferred regimen (1): Amoxicillin-clavulanate 500 mg PO tid or 875 mg PO bid
- Preferred regimen (2): Amoxicillin 500 mg PO tid
- Preferred regimen (3): TMP-SMX DS PO bid
- Preferred regimen (4): Cefuroxime 250-500 mg PO bid
- Preferred regimen (5): Moxifloxacin 400 mg PO qd
- Preferred regimen (6): Levofloxacin 500 mg PO qd
- Preferred regimen (7): Azithromycin 500 mg PO single dose then 250 mg for 4 days
- Preferred regimen (8): Clarithromycin 500 mg PO bid or XL 500 mg PO q24h
- Note: Treatment duration of otitis media is 10-14 days, acute exacerbation of chronic bronchitis is 5 days (quinolone - 14 days), sinusitis is 10-14 days.
- 2. Meningitis[107]
- Dexamethasone 0.15 mg/kg 15-20 mins before first dose of antibiotic and then q6h for 4 days
- 2.1 Adults
- Preferred regimen (1): Ceftriaxone 2 g IV q12h (4 g maximum)
- Preferred regimen (2): Cefotaxime 2 g IV q4-6h (12 g maximum)
- Preferred regimen (3): Ampicillin 2 g IV q4h if sensitive
- Alternative regimen: Ciprofloxacin 400 mg IV q8h OR other Fluoroquinolones
- 2.2 Pediatric
- 2.2.1 Neonates < 7 days
- 2.2.1.1 Weight < 2 kg
- Preferred regimen: Cefotaxime 50 mg/kg IV q12h for 10-14 days
- 2.2.1.2 Weight > 2 kg
- Preferred regimen (1): Cefotaxime 50 mg/kg IV q8h
- Preferred regimen (2): Ceftriaxone 50 mg/kg IV q24h for 10-14 days
- 2.2.2 Neonates >7 days
- 2.2.2.1 Weight > 2 kg
- Preferred regimen (1): Cefotaxime 50 mg/kg IV q6-8h
- Preferred regimen (2): Ceftriaxone 75 mg/kg IV q24h for 10-14 days
- 2.2.3 Children
- Preferred regimen (1): Cefotaxime 200 mg/kg/day IV q6h
- Preferred regimen (2): Ceftriaxone 100 mg/kg IV q12-24h for 10-14 days
- 2.3 Post-meningitis exposure prophylaxis[108]
- Preferred regimen (1): Rifampin 600 mg PO qd for 4 days
- 3. Severe infections[109]
- 3.1 Adults
- Preferred regimen (1): Ceftriaxone 1-2 g IV q24 or q12h
- Preferred regimen (2): Cefotaxime 2 g IV q6h
- Alternative regimen (1): Ciprofloxacin 400 mg IV q8h or other Fluoroquinolones
- Alternative regimen (2): Ampicillin 2 g IV q6h if sensitive
# Neisseria gonorrhoeae
- Neisseria gonorrhoeae Return to Top
- Neisseria gonorrhoeae treatment[110]
- 1. Gonococcal infections in adolescents and adults
- 1.1 Uncomplicated gonococcal infections of the cervix, urethra, and rectum
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- Alternative regimen: Cefixime 400 mg PO in a single dose AND Azithromycin 1 g PO in a single dose (if ceftriaxone is not available)
- 1.2 Uncomplicated gonococcal infections of the pharynx
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.2.1 Management of sex partners
- Expedited partner therapy: Cefixime 400 mg PO in a single dose AND Azithromycin 1 g PO in a single dose
- Note (1): Recent sex partners (i.e., persons having sexual contact with the infected patient within the 60 days preceding onset of symptoms or gonorrhea diagnosis) should be referred for evaluation, testing, and presumptive dual treatment.
- Note (2): If the patient’s last potential sexual exposure was >60 days before onset of symptoms or diagnosis, the most recent sex partner should be treated.
- Note (3): To avoid reinfection, sex partners should be instructed to abstain from unprotected sexual intercourse for 7 days after they and their sexual partner(s) have completed treatment and after resolution of symptoms, if present.
- 1.2.2 Allergy, intolerance, and adverse reactions
- Preferred regimen (1): Gemifloxacin 320 mg PO in a single dose AND Azithromycin 2 g PO in a single dose
- Preferred regimen (2): Gentamicin 240 mg IM in a single dose AND Azithromycin 2 g PO in a single dose
- Note: Use of ceftriaxone or cefixime is contraindicated in persons with a history of an IgE-mediated penicillin allergy (e.g., anaphylaxis, Stevens Johnson syndrome, and toxic epidermal necrolysis).
- 1.2.3 Pregnancy
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.2.4 Suspected cephalosporin treatment failure
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Gemifloxacin 320 mg PO single dose AND Azithromycin 2 g PO single dose (when isolates have elevated cephalosporin MICs)
- Alternative regimen (2): Gentamicin 240 mg IM single dose AND Azithromycin 2 g PO single dose (when isolates have elevated cephalosporin MICs)
- Alternative regimen (3): Ceftriaxone 250 mg IM as a single dose AND Azithromycin 2 g PO as a single dose (failure after treatment with cefixime and azithromycin)
- Note: Treatment failure should be considered in: (1) persons whose symptoms do not resolve within 3–5 days after appropriate treatment and report no sexual contact during the post-treatment follow-up period; (2) persons with a positive test-of-cure (i.e., positive culture ≥ 72 hours or positive NAAT ≥ 7 days after receiving recommended treatment) when no sexual contact is reported during the post-treatment follow-up period; (3) persons who have a positive culture on test-of-cure (if obtained) if there is evidence of decreased susceptibility to cephalosporins on antimicrobial susceptibility testing, regardless of whether sexual contact is reported during the post-treatment follow-up period.
- 1.3 Gonococcal conjunctivitis
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.3.1 Management of sex partners
- Patients should be instructed to refer their sex partners for evaluation and treatment.
- 1.4 Disseminated gonococcal infection
- 1.4.1 Arthritis and arthritis-dermatitis syndrome
- Preferred regimen: Ceftriaxone 1 g IM/IV q24h for 7 days AND Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Cefotaxime 1 g IV q8h for 7 days
- Alternative regimen (2): Ceftizoxime 1 g IV q8h for 7 days AND Azithromycin 1 g PO in a single dose
- 1.4.2 Gonococcal meningitis and endocarditis
- Preferred regimen: Ceftriaxone 1-2 g IV q 12-24 h for 10-14 days AND Azithromycin 1 g PO in a single dose
- 2. Gonococcal infections among neonates
- 2.1 Ophthalmia neonatorum caused by N. gonorrhoeae
- Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg
- 2.1.1 Management of mothers and their sex partners
- Mothers of infants with ophthalmia neonatorum caused by N. gonorrhoeae should be evaluated, tested, and presumptively treated for gonorrhea, along with their sex partner(s).
- 2.2 Disseminated gonococcal infection and gonococcal scalp abscesses in neonates
- Preferred regimen (1): Ceftriaxone 25-50 mg/kg/day IM/IV q24h for 7 days
- Preferred regimen (2): Cefotaxime 25 mg/kg IM/IV q12h for 7 days.
- Note (1): The duration of treatment is 10-14 days if meningitis is documented.
- Note (2): Ceftriaxone should be administered cautiously to hyperbilirubinemic infants, especially those born prematurely.
- 2.2.1 Management of mothers and their sex partners
- Mothers of infants who have DGI or scalp abscesses caused by N. gonorrhoeae should be evaluated, tested, and presumptively treated for gonorrhea, along with their sex partner(s).
- 2.3 Neonates born to mothers who have gonococcal infection
- Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg
- 2.3.1 Management of mothers and their sex partners
- Mothers who have gonorrhea and their sex partners should be evaluated, tested, and presumptively treated for gonorrhea.
- 3. Gonococcal infections among infants and children
- 3.1 Infants and children who weigh ≤ 45 kg and who have uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis
- Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg
- 3.2 Children who weigh > 45 kg and who have uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1g PO in a single dose
- Alternative regimen: Cefixime 400 mg PO single dose AND Azithromycin 1 g PO single dose.(If ceftriaxone is not available)
- 3.3 Children who weigh ≤ 45 kg and who have bacteremia or arthritis
- Preferred regimen: Ceftriaxone 50 mg/kg (maximum dose: 1 g) IM/IV q24h for 7 days
- 3.4 Children who weigh > 45 kg and who have bacteremia or arthritis
- Preferred regimen: Ceftriaxone 1 g IM/IV q24h for 7 days
# Neisseria meningitidis
- Neisseria meningitidis Return to Top
- 1. Meningococcal meningitis or meningococcemia, treatment[4][111]
- 1.1 Adults
- 1.1.1 Penicillin MIC < 0.1 mcg/mL
- Preferred regimen (1): Penicillin G 4 MU IV q4h for 7 days
- Preferred regimen (2): Ampicillin 2 g IV q4h for 7 days
- Alternative regimen (1): Ceftriaxone 4 g/day IV q12-24h for 7 days
- Alternative regimen (2): Cefotaxime 8-12 g/day IV q4-6h for 7 days
- Alternative regimen (3): Chloramphenicol 4-6 g/day IV q6h for 7 days
- 1.1.2 Penicillin MIC 0.1-1.0 mcg/mL
- Preferred regimen (1): Ceftriaxone 4 g/day IV q12-24h for 7 days
- Preferred regimen (2): Cefotaxime 8-12 g/day IV q4-6h for 7 days
- Alternative regimen (1): Cefepime 2 g IV q8h for 7 days
- Alternative regimen (2): Chloramphenicol 4-6 g/day IV q6h for 7 days
- Alternative regimen (3): Moxifloxacin 400 mg IV q24h for 7 days
- Alternative regimen (4): Meropenem 2 g IV q8h for 7 days
- 1.2 Neonates (birth-7 days old)
- 1.2.1 Penicillin MIC < 0.1 mcg/mL
- Preferred regimen (1): Penicillin G 0.15 MU/kg/day IV q8-12h for 7 days
- Preferred regimen (2): Ampicillin 150 mg/kg/day IV q8h for 7 days
- Alternative regimen (1): Cefotaxime 100-150 mg/kg/day IV q8-12h for 7 days
- Alternative regimen (2): Chloramphenicol 25 mg/kg/day IV q24h for 7 days
- 1.2.2 Penicillin MIC 0.1-1.0 mcg/mL
- Preferred regimen: Cefotaxime 100-150 mg/kg/day IV q8-12h for 7 days
- Alternative regimen: Chloramphenicol 25 mg/kg/day IV q24h for 7 days
- 1.3 Neonates (8-28 days old)
- 1.3.1 Penicillin MIC < 0.1 mcg/mL
- Preferred regimen (1): Penicillin G 0.2 MU/kg/day IV q6-8h for 7 days
- Preferred regimen (2): Ampicillin 200 mg/kg/day IV q6-8h for 7 days
- Alternative regimen (1): Cefotaxime 150-200 mg/kg/day IV q6-8h for 7 days
- Alternative regimen (2): Chloramphenicol 50 mg/kg/day IV q12-24h for 7 days
- 1.3.2 Penicillin MIC 0.1-1.0 mcg/mL
- Preferred regimen : Cefotaxime 150-200 mg/kg/day IV q6-8h for 7 days
- Alternative regimen : Chloramphenicol 50 mg/kg/day IV q12-24h for 7 days
- 1.4 Infants and children
- 1.4.1 Penicillin MIC < 0.1 mcg/mL
- Preferred regimen (1): Penicillin G 0.3 MU/kg/day IV q4-6h for 7 days
- Preferred regimen (2): Ampicillin 300 mg/kg/day IV q6h for 7 days
- Alternative regimen (1): Ceftriaxone 80-100 mg/kg/day IV q12-24h for 7 days
- Alternative regimen (2): Cefotaxime 225-300 mg/kg/day IV q6-8h for 7 days
- Alternative regimen (3): Chloramphenicol 75-100 mg/kg/day IV q6h for 7 days
- 1.4.2 Penicillin MIC 0.1-1.0 mcg/mL
- Preferred regimen (1): Ceftriaxone 80-100 mg/kg/day IV q12-24h for 7 days
- Preferred regimen (2): Cefotaxime 225-300 mg/kg/day IV q6-8h for 7 days
- Alternative regimen (1): Cefepime 150 mg/kg/day IV q8h for 7 days
- Alternative regimen (2): Chloramphenicol 75-100 mg/kg/day q6h for 7 days
- Alternative regimen (3): Meropenem 120 mg/kg/day IV q8h for 7 days
- Note (1): Dexamethasone has not been shown to be beneficial in meningococcal meningitis and should be discontinued once this diagnosis is established.[112][113]
- Note (2): Clinical data are limited on the use of fluoroquinolones for therapy for meningococcal meningitis but may be considered in patients not responding to standard therapy or when disease is caused by resistant organisms.
- 2. Meningococcal meningitis, prophylaxis for household and close contacts[114]
- 2.1 Adults
- Preferred regimen (1): Rifampin 600 mg PO bid for 2 days
- Preferred regimen (2): Ciprofloxacin 500 mg PO single dose
- Preferred regimen (3): Ceftriaxone 250 mg IM single dose
- 2.2 Children < 15 years
- Preferred regimen: Ceftriaxone 12 mg IM single dose
- 2.3 Children ≥ 1 month
- Preferred regimen: Rifampin 10 mg /kg PO bid for 2 days
- 2.4 Children < 1 month
- Preferred regimen: Rifampin 5 mg/kg PO bid for 2 days
- Moraxella catarrhalis Return to Top
- Moraxella catarrhalis [115]
- Preferred regimen(1): TMP-SMX 1DS PO bid
- Preferred regimen(2): Erythromycin 500 mg PO qid
- Preferred regimen(3): Clarithromycin 500 mg PO bid or XL 1 g PO qd
- Preferred regimen(4): Azithromycin 500 mg PO single dose THEN 250 mg PO qd
- Preferred regimen(5): Doxycycline 100 mg PO/IV bid/q12h
- Preferred regimen(6): Cefprozil 200-500 mg PO bid
- Preferred regimen(7): Cefpodoxime 200-400 mg PO bid
- Preferred regimen(8): Cefuroxime 250-500 mg PO bid
- Preferred regimen(9): Cefdinir 300 mg PO bid
- Preferred regimen(10): Moxifloxacin 400 mg IV/PO qd
- Preferred regimen(11): Levofloxacin 500 mg IV/PO qd
- Preferred regimen(12): Amoxicillin clavulanate 875/125 mg PO bid or XL 2000/125 PO bid
- Pasteurella multocida Return to Top
- Pasteurella multocida [116]
- Preferred regimen (1): Amoxicillin clavulanate 500 mg PO tid or 875 mg PO bid with food
- Note: Its also a preferred empirical coverage of animal bite wounds
- Preferred regimen (2): Ampicillin sulbactam 3 g IV q6h
- Preferred regimen (3): Ciprofloxacin 500 mg PO bid or 400 mg IV q12h
- Preferred regimen (4): Levofloxacin 500 mg PO qd or IV q24h
- Alternative regimen (1): Doxycycline 100 mg PO bid
- Alternative regimen (2): TMP-SMX DS PO bid (for beta-lactam allergic patients )
- Alternative regimen (3): Penicillin 500 mg PO qid or 4 MU IV q4h (use only if isolate known to be susceptible)
### Bacteria – Spirochetes
- Borrelia burgdorferi Return to Top
- Lyme disease [117]
- 1. Early Lyme Disease
- 1.1 Erythema migrans
- 1.1.1 Adult
- Preferred regimen (1): Doxycycline 100 mg PO bid for 10-21 days
- Preferred regimen (2): Amoxicillin 500 mg PO tid for 14-21 days
- Preferred regimen (3): Cefuroxime axetil 500 mg bid for 14-21 days
- Alternatie regimen (1): Azithromycin 500 mg PO qd for 7–10 days
- Alternatie regimen (2): Clarithromycin 500 mg PO bid for 14–21 days (if the patient is not pregnant)
- Alternatie regimen (3): Erythromycin 500 mg PO qid for 14–21 days
- 1.1.2 Pediatric
- 1.1.2.1 children <8 years of age
- Preferred regimen (1): Amoxicillin 50 mg/kg/day PO q8h (Maximum of 500 mg per dose)
- Preferred regimen (2): Cefuroxime axetil 30 mg/kg/day PO q12h（Maximum, 500 mg per dose)
- 1.1.2.2 children ≥8 years of age
- Preferred regimen (1): Doxycycline 4 mg/kg/day PO q12h（Maximum, 100 mg per dose）
- Preferred regimen (2): Azithromycin 10 mg/kg PO qd (Maximum, 500 mg qd)
- Preferred regimen (3): Clarithromycin 7.5 mg/kg PO bid (Maximum, 500 mg per dose)
- Preferred regimen (4): Erythromycin 12.5 mg/kg PO qid (Maximum, 500 mg per dose)
- 1.2 When erythema migrans cannot be reliably distinguished from community-acquired bacterial cellulitis
- Preferred regimen: Amoxicillin-Clavulanate 500 mg PO tid
- Pediatric regimen: Amoxicillin-Clavulanate 50 mg/kg/day q8h (Maximum, 500 mg per dose)
- 1.3 Lyme meningitis and other manifestations of early neurologic Lyme disease
- 1.3.1 Adult
- Preferred regimen: Ceftriaxone 2 g IV q24h for 10–28 days
- Alternative regimen (1): Cefotaxime 2 g IV q8h
- Alternative regimen (2): Penicillin G 18–24 MU q4h (for patients with normal renal function)
- Alternative regimen (3): Doxycycline 200–400 mg/day PO bid for 10–28 days
- 1.3.2 Pediatric
- Preferred regimen (1): Ceftriaxone 50–75 mg/kg IV single dose (Maximum, 2 g)
- Preferred regimen (2): Cefotaxime 150–200 mg/kg/day IV q6-8h (Maximum, 6 g per day)
- Alternative regimen (1): Penicillin G 200,000–400,000 units/kg/day IV q4h (for normal renal function) (maximum, 18–24 MU per day)
- Alternative regimen (2): Doxycycline 4–8 mg/kg/day PO bid (maximum, 100–200 mg per dose) (≥8 years old)
- 1.4 Lyme carditis
- Preferred regimen: Ceftriaxone 2 g IV q24h for 10–28 days
- Note: patients with advanced heart block, a temporary pacemaker may be required; expert consultation with a cardiologist is recommended; Use of the pacemaker may be discontinued when the advanced heart block has resolved; An oral antibiotic treatment regimen should be used for completion of therapy and for outpatients, as is used for patients with erythema migrans without carditis (see above)
- 1.5 Borrelial lymphocytoma
- Preferred regimen: The same regimens used to treat patients with erythema migrans (see above)
- 2. Late Lyme Disease
- 2.1 Lyme arthritis
- Preferred regimen (1): Doxycycline 100 mg PO bid
- Preferred regimen (2): Amoxicillin 500 mg PO tid
- Alternative regimen: Cefuroxime axetil 500 mg PO bid for 28 days
- Pediatric regimen: Amoxicillin 50 mg/kg/day tid (Maximum, 500 mg per dose); Cefuroxime axetil 30 mg/kg/day bid (Maximum,500 mg per dose); (≥8 years of age) Doxycycline 4 mg/kg/day bid (Maximum, 100 mg per dose)
- Note: For patients who have persistent or recurrent joint swelling after a recommended course of oral antibiotic therapy, we recommend re-treatment with another 4-week course of oral antibiotics or with a 2–4 weeks course of Ceftriaxone IV
- 2.2 patients with arthritis and objective evidence of neurologic disease
- Preferred regimen: Ceftriaxone IV for 2–4 weeks
- Alternative regimen (1): Cefotaxime IV
- Alternative regimen (1): Penicillin G IV
- Pediatric regime: Ceftriaxone; Cefotaxime; Penicillin G IV
- 2.3 Late neurologic Lyme disease
- Preferred regimen: Ceftriaxone IV for 2 to 4 weeks
- Alternative regimen (1): Cefotaxime IV
- Alternative regimen (2): Penicillin G IV
- Pediatric regimen: Ceftriaxone; Cefotaxime; Penicillin G
- 2.4 Acrodermatitis chronica atrophicans
- Preferred regimen (1): Doxycycline 100 mg PO bid for 21 days
- Preferred regimen (2): Amoxicillin 500 mg PO tid for 21 days
- Preferred regimen (3): Cefuroxime axetil 500 mg PO bid for 21 days
- 3. Post–Lyme Disease Syndromes
- Preferred regimen: Further antibiotic therapy for Lyme disease should not be given unless there are objective findings of active disease (including physical findings, abnormalities on cerebrospinal or synovial fluid analysis, or changes on formal neuropsychologic testing)
- Borrelia recurrentis Return to Top
- 1. Tick-Borne Relapsing Fever [118]
- Preferred regimen: Doxycycline 100 mg PO bid for 5-10 days
- Alternative regimen: Erythromycin 500 mg PO qid for 5-10 days
- Note: If meningitis/encephalitis present, use Ceftriaxone 2 g IV q12h for 14 days
- 2. Louse-Borne Relapsing Fever
- Preferred regimen: Tetracycline 500 mg PO single dose
- Alternative regimen: Erythromycin 500 mg PO single dose
- Leptospira Return to Top
- 1. Severe [119] [120]
- Preferred regimen: Penicillin 1.5 MU IV q6h for 5-7 days
- 2. Less severe
- Preferred regimen (1): Amoxycillin
- Preferred regimen (2): Ampicillin
- Preferred regimen (3): Doxycycline 100 mg IV/PO q12h/bid for 5-7 days
- Preferred regimen (4): Erythromycin
- Preferred regimen (5): Ceftriaxone 1 g IV q24h for 5-7 days
- Preferred regimen (6): Cefotaxime
- Preferred regimen (7): Quinolone PO
- Treponema pallidum Return to Top
- 1. Syphilis Among non-HIV-Infected Persons [121]
- 1.1 Primary and Secondary Syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM single dose
- Pediatric regimen: Benzathine penicillin G 50,000 U/kg (Maximum, 2.4 MU) IM single dose
- 1.2 Latent Syphilis
- 1.2.1 Early Latent Syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM in a single dose
- Pediatric regimen: Benzathine penicillin G 50,000 U/kg (Maximum, 2.4 MU) IM single dose
- 1.2.2 Late Latent Syphilis or Latent Syphilis of Unknown Duration
- Preferred regimen: Benzathine penicillin G 7.2 MU total, administered as 3 doses of 2.4 MU IM each at 1 week intervals
- Pediatric regimen: Benzathine penicillin G 50,000 U/kg IM (Maximum, 2.4 MU), administered as 3 doses at 1 week intervals (total 150,000 U/kg up to the adult total dose of 7.2 MU)
- 1.3 Tertiary Syphilis
- Preferred regimen: Benzathine penicillin G 7.2 MU total, administered as 3 doses of 2.4 MU IM each at 1 week intervals
- 1.4 Neurosyphilis and ocular syphilis
- Preferred regimen: Aqueous crystalline penicillin G 18-24 MU per day, administered as 3-4 MU IV q4h or continuous infusion, for 10-14 days
- Alternative regimen: Procaine penicillin 2.4 MU IM q24h AND Probenecid 500 mg PO qid for 10-14 days
- 2. Syphilis Among HIV-Infected Persons
- 2.1 Primary and Secondary Syphilis Among HIV-Infected Persons
- Preferred regimen: Benzathine penicillin G 2.4 MU IM single dose
- 2.2 Latent Syphilis Among HIV-Infected Persons
- 2.2.1 early latent
- Preferred regimen: Benzathine penicillin G 2.4 MU IM single dose
- 2.2.2 late latent
- Preferred regimen: Benzathine penicillin G 2.4 MU once a week for 3 weeks
- 2.3 Neurosyphilis Among HIV-Infected Persons
- Preferred regimen: Aqueous crystalline penicillin G 18-24 MU per day, administered as 3-4 MU IV q4h or continuous infusion, for 10-14 days
- Alternative regimen: Procaine penicillin 2.4 MU IM q24h AND Probenecid 500 mg PO qid for 10-14 days
- 3. Syphilis During Pregnancy
- Pregnant women should be treated with the penicillin regimen appropriate for their stage of infection
- 4. Congenital Syphilis in neonates
- 4.1 condition1: Infants with proven or highly probable disease and (1) an abnormal physical examination that is consistent with congenital syphilis;（2）a serum quantitative nontreponemal serologic titer that is fourfold higher than the mother's titer; or（3）a positive darkfield test of body fluid(s).
- Preferred regimen (1): Aqueous crystalline penicillin G 100,000-150,000 U/kg/day, administered as 50,000 U/kg/dose IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days
- Preferred regimen (2): Procaine penicillin G 50,000 U/kg/dose IM q24h for 10 days
- Note: If more than 1 day of therapy is missed, the entire course should be restarted. Data are insufficient regarding the use of other antimicrobial agents (e.g., ampicillin). When possible, a full 10-day course of penicillin is preferred, even if ampicillin was initially provided for possible sepsis. The use of agents other than penicillin requires close serologic follow-up to assess adequacy of therapy. In all other situations, the maternal history of infection with T. pallidum and treatment for syphilis must be considered when evaluating and treating the infant.
- 4.2 condition2: Infants who have a normal physical examination and a serum quantitive nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1) mother was not treated, inadequately treated, or has no documentation of having received treatment; (2) mother was treated with erythromycin or another nonpenicillin regimen; or (3) mother received treatment <4 weeks before delivery.
- Preferred regimen (1): Aqueous crystalline penicillin G 100,000-150,000 U/kg/day, administered as 50,000 U/kg/dose IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days
- Preferred regimen (2): Procaine penicillin G 50,000 U/kg/dose IM q24h for 10 days
- Preferred regimen (3): Benzathine penicillin G 50,000 U/kg/dose IM single dose
- Note: If the mother has untreated early syphilis at delivery, 10 days of parenteral therapy can be considered
- 4.3 condition3: Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1) mother was treated during pregnancy, treatment was appropriate for the stage of infection, and treatment was administered >4 weeks before delivery and (2) mother has no evidence of reinfection or relapse.
- Preferred regimen: Benzathine penicillin G 50,000 U/kg/dose IM single dose
- 4.4 condition4: Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the (1) mother's treatment was adequate before pregnancy; and (2) mother's nontreponemal serologic titer remained low and stable before and during pregnancy and at delivery (VDRL <1:2; RPR <1:4).
- No treatment is required
- Benzathine penicillin G 50,000 U/kg IM single dose might be considered, particularly if follow-up is uncertain.
- 5. Congenital Syphilis in infants and children
- Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg q4–6h for 10 days
### Bacteria – Gram-Negative Bacilli
- Achromobacter xylosoxidans Return to Top
- Achromobacter xylosoxidans treatment[122],[123],[124],[125],[126],[127]
- Preferred regimen: most active agents are Piperacillin-Tazobactam, Meropenem AND Trimethoprim–Sulfamethoxazole whereas Ceftazidime is more active than Cefepime
- Alternative regimen: Colistin inhaled, could also be considered
- Note : Achromobacter (formerly Alcaligenes) xylosoxidans is a newly emerging microorganism isolated with increased frequency from the lungs of patients with cystic fibrosis. Combination therapy has been recommended for the treatment of Achromobacter xylosoxidans pulmonary exacerbations in cystic fibrosis
# Acinetobacter baumannii
- Acinetobacter baumannii Return to Top
- Acinetobacter baumannii[128]
- Preferred regimen (1): Imipenem 0.5-1 g IV q6h
- Preferred regimen (2): Ampicillin/sulbactam 3 g IV q4h
- Preferred regimen (3): Cefepime 1-2 g IV q8h
- Preferred regimen (4): Colistin 2.5 mg/kg IV q12h
- Preferred regimen (5): Tigecycline 100 mg IV single dose THEN 50 mg IV q12h
- Preferred regimen (6): Amikacin 7.5 mg/kg IV q12h or 15 mg/kg IV q24h
- Preferred regimen (7) (pan-resistant isolates): Colistin 5 mg/kg/day IV q12h ± Imipenem
- Preferred regimen (8) (pan-resistant isolates): Ampicillin-sulbactam 3 g IV q4h
- Alternative regimen (1): Ceftriaxone 1-2 g IV qd
- Alternative regimen (2): Cefotaxime 2-3 g IV q6-8h
- Alternative regimen (3): Ciprofloxacin 400 mg IV q8-12h or 750 mg PO bid
- Alternative regimen (4): TMP-SMX 15-20 mg (TMP)/kg/day IV q6-8h or 2 DS PO bid
# Aeromonas hydrophila
- Aeromonas hydrophila Return to Top
- Aeromonas hydrophila [129]
- 1. Diarrhea
- Preferred regimen (if not self-limiting, or if severe): Ciprofloxacin 500 mg PO bid.
- Alternate regimen: TMP-SMX 1 DS PO bid
- Note: High resistance to sulfa agents described in Taiwan and Spain
- 2. Skin and soft tissue infection
- 2.1 Mild infection
- Preferred regimen (1): Ciprofloxacin 500 mg PO bid
- Preferred regimen (2): Levofloxacin 500 mg qd
- 2.2 Severe infection or sepsis
- Preferred regimen (1): Ciprofloxacin 400 mg IV q8h
- Preferred regimen (2): Levofloxacin 750 mg IV q24h
- Note (1): For suspicion of water-based injury,empiric coverage for Vibrio doxycycline 100 mg bid, although flouroquinolones may also cover and vancomycin 15 mg/kg IV q12h with or without clindamycin or linezolid for inhibition of gram-positive toxin production
- Note (2): Alternatives to fluoroquinolones for Aeromonas coverage include carbapenems (ertapenem, doripenem, imipenem or meropenem), ceftriaxone, cefepime and aztreonam
- 3. Prevention
- Preferred regimen: Frequent recommendations include using a Cephalosporin (e.g.,cefuroxime,ceftriaxone or cefixime) OR a Fluoroquinolone (e.g.,ciprofloxacin or levofloxacin) during treatment with medicinal leeches
- Note (1): Duration of antibiotic use is 3-5 days, some recommend continuing until wound or eschar resolves
- Note (2): Aeromonas isolates from leeches have been described as uniformly susceptible to fluoroquinolones
# Bartonella
- Bartonella Return to Top
- Bartonella[130]
- 1. Bartonella quintana
- 1.1 Acute or chronic infections without endocarditis[131]
- Preferred regimen: Doxycycline 200 mg PO qd or 100 mg bid for 4 weeks AND Gentamicin 3 mg/kg IV qd for the first 2 weeks
- 1.2 Endocarditis[11]
- Preferred regimen: Gentamicin 3 mg/kg/day IV q8h for 14 days AND Ceftriaxone 2 g IV q24h for 6 weeks ± Doxycycline 100 mg PO bid for 6 weeks
- 2. Bartonella elizabethae
- 2.1 Endocarditis[11]
- Preferred regimen: Gentamicin 3 mg/kg/day IV q8h for 14 days AND Ceftriaxone 2 g IV q24h for 6 weeks ± Doxycycline 100 mg PO bid for 6 weeks
- 3. Bartonella bacilliformis
- 3.1 Oroya fever
- Preferred regimen: Ciprofloxacin 500 mg PO bid for 14 days
- Note: If severe disease, add Ceftriaxone 1 g IV qd for 14 days
- 3.2 Verruga peruana[132]
- Preferred regimen: Azithromycin 500 mg PO qd for 7 days
- Alternative regimen (1): Rifampin 600 mg PO qd for 14-21 days
- Alternative regimen (2): Ciprofloxacin 500 mg bid for 7-10 days
- 4. Bartonella henselae[133]
- 4.1 Cat scratch disease
- No treatment recommended for typical cat scratch disease, consider treatment if there is an extensive lymphadenopathy
- 4.1.1 If extensive lymphadenopathy
- Preferred regimen (1) (pediatrics): Azithromycin 500 mg PO on day 1 THEN 250 mg PO qd on days 2 to 5
- Preferred regimen (2) (adults): Azithromycin 1 g PO at day 1 THEN 500 mg PO for 4 days
- 4.2 Endocarditis
- Preferred regimen: Gentamicin 3 mg/kg/day IV q8h for 14 days AND Ceftriaxone 2 g/day IV for 6weeks ± Doxycycline 100 mg PO bid for 6 weeks
- 4.3 Retinitis
- Preferred regimen: Doxycycline 100 mg bid AND Rifampin 300 mg bid PO for 4-6 weeks
- 4.4 Bacillary angiomatosis[134]
- Preferred regimen (1): Erythromycin 500 mg PO qid for 2 months at least
- Preferred regimen (2): Doxycycline 100 mg PO bid for 2 months at least
- 4.5 Bacillary Pelliosis[134]
- Preferred regimen (1): Erythromycin 500 mg PO qid for 4 months at least
- Preferred regimen (2): Doxycycline 100 mg PO bid for 4 months at least
# Bordetella pertussis
- Bordetella pertussis Return to Top
- Bordetella pertussis[135]
- 1. Whooping cough
- 1.1 Adults
- Preferred regimen (1): Azithromycin 500 mg PO single dose on day 1 THEN 250 mg PO qd on 2-5 days
- Preferred regimen (2): Erythromycin 2 g/day PO qid for 14 days
- Preferred regimen (3): Clarithromycin 1 g PO bid for 7 days.
- Alternative regimen (intolerant of macrolides): Trimethoprim 320 mg/day AND Sulfamethoxazole 1600 mg/day PO bid for 14 days
- 1.2 Infants <6 months of age
- 1.2.1 Infants <1 month
- Preferred regimen (1): Azithromycin 10 mg/kg PO qd for 5 days
- Preferred regimen (2) (if azithromycin unavailable): Erythromycin 40-50 mg/kg/day PO q6h for 14 days
- Note: TMP-SMX contraindicated for infants aged < 2 months
- 1.2.2 Infants of 1-5 months of age
- Preferred regimen (1): Azithromycin 10 mg/kg PO qd for 5 days
- Preferred regimen (2): Erythromycin 40-50 mg/kg/day PO qid for 14 days
- Preferred regimen (3): Clarithromycin 15 mg/kg PO bid for 7 days
- Alternative regimen: For infants aged ≥ 2 months TMP 8 mg/kg q24h AND SMX 40 mg/kg/day PO bid for 14 days
- 1.3 Infants ≥6 months of age-children
- Preferred regimen(1): Azithromycin 10 mg/kg single dose THEN 5 mg/kg (500 mg Maximum) qd for 2-5 days
- Preferred regimen(2): Erythromycin 40-50 mg/kg PO (2 g daily Maximum) qid for 14 days
- Preferred regimen(3): Clarithromycin 15 mg/kg PO (1 g daily Maximum) bid for 7 days
- Preferred regimen(4): TMP 8 mg/kg/day AND SMX 40 mg/kg/day bid for 14 days
- 2. Post exposure prophylaxis[136]
- Preferred regimen: The antibiotic regimens for post exposure prophylaxis are similar to the regimens used for the treatment of pertussis
- Note (1): Post exposure prophylaxis to an asymptomatic contacts within 21 days of onset of cough in the index patient can potentially prevent symptomatic infection
- Note (2): Close contacts include persons who have direct contact with respiratory, oral or nasal secretions from a symptomatic patient (eg: cough, sneeze, sharing food, eating utensils, mouth to mouth resuscitation, or performing a medical examination of the mouth, nose, throat.
- Note (3): Some close contacts are at high risk for acquiring severe disease following exposure to pertussis. These contacts include infants aged < 1 year , persons with some immunodeficiency conditions, or other underlying medical conditions such as chronic lung disease, respiratory insufficiency and cystic fibrosis.
# Burkholderia cepacia
- Burkholderia cepacia Return to Top
- Burkholderia cepacia complex[137]
- Preferred regimen (1): Ceftazidime 2 g IV q8h
- Preferred regimen (2): Imipenem 1 g IV q6h
- Preferred regimen (3): Meropenem 1-2 g IV q8h
- Preferred regimen (4): Minocycline 100 mg IV/PO bid
# Burkholderia pseudomallei
- Burkholderia pseudomallei Return to Top
- Burkholderia pseudomallei
- 1. Melioidosis[138]
- 1.1 Intial intensive therapy (Minimum of 10-14 days)
- Preferred regimen (1): Ceftazidime 50 mg/kg upto 2 g q6h
- Preferred regimen (2): Meropenem 25 mg/kg upto 1 g q8h
- Preferred regimen (3): Imipenem 25 mg/kg upto 1 g q6h
- Note: Any one of the three may be combined with TMP-SMX 6/30 mg/kg upto 320/1600 mg/kg q12h (recommended for neurologic, bone, joint, cutaneous and prostatic melioidosis)
- 1.2 Eradication therapy (Minimum of 3 months)
- Preferred regimen: TMP-SMX 6/30 mg/kg upto 320/1600 mg/kg q12h
# Campylobacter fetus
- Campylobacter fetus Return to Top
- Campylobacter fetus[139]
- 1. Gastroenteritis
- Preferred regimen: Gentamicin 5 mg/kg IV q24h
- Alternative regimen (1): Ampicillin 100 mg/kg IV q6h
- Alternative regimen (2): Imipenem 500 mg IV q6h
- Campylobacter jejuni Return to Top
- Campylobacter jejuni
- 1. Gastroenteritis[140]
- Most patients donot require antibiotics and symptoms last < 1 week
- 1.1 Indications for the treatment
- Highfevers
- Bloodystools
- Prolonged illness > 1 week
- Pregnancy
- HIV and other immunosuppressed states
- 1.2 Treatment regimen [141]
- Preferred regimen (1):Erythromycin stearate 500 mg PO bid for 5 days
- Preferred regimen (2): Ciprofloxacin 500 mg PO bid for 3–5 days
- Alternative regimen (1): TMP-SMX DS PO bid for 3–5 days
- Note (1): Campylobacter resistance to TMP-SMX common in tropics
- Note (2): Extraintestinal infections should be treated for longer duration (e.g.,2-4 weeks)
# Capnocytophaga canimorsus
- Capnocytophaga canimorsus Return to Top
- Capnocytophaga canimorsus[142]
- 1. Severe cellulitis/sepsis or endocarditis
- Preferred regimen (1) (Beta-lactam/beta-lactamase inhibitor): Ampicillin/sulbactam 3 g IV q6h
- Preferred regimen (2) (Non-beta-lactamase producing): Penicillin G 2-4 MU IV q24h
- Alternative regimen (1): Ceftriaxone 1-2 g IV q24h
- Alternative regimen (2): Meropenem 1 g IV q8h
- Alternative regimen (3) (complicated infections or immunocompromise): Clindamycin 600 mg IV q8h may be combined with above agents
- Note (1): Resistance to aztreonam described, and variable susceptibility reported to TMP-SMX and aminoglycosides
- Note (2): For endocarditis, alternatives to penicillins not well established, treated for duration of 6 weeks
- Note (3): For non-endocarditis infections, duration not well established, but most authorities recommend at least 14-21 days of therapy
- 2. Mild cellulitis/dog or cat bites
- Preferred regimen (1): Amoxicillin/clavulanate 500 mg PO q8h or 875 mg PO bid
- Preferred regimen (2): Amoxicillin 500 mg PO q8h
- Alternative regimen (1): Clindamycin 300 mg PO q6h
- Alternative regimen (2): Doxycycline 100 mg PO bid
- Alternative regimen (3): Clarithromycin 500 mg PO bid
- Alternative regimen (4): Moxifloxacin 400 mg PO qd
- 3. Meningitis or brain abscess
- Preferred regimen (1): Ceftriaxone 2 g IV q12h AND Ampicillin 2 g IV q4h
- Preferred regimen (2) (if beta-lactamase producing or polymicrobial brain abscess): Imipenem/Cilastin 1000 mg q6-8h AND Clindamycin 600 mg IV q8h
- 4. Prevention
- Although no firm data supports this recommendation, many clinicians do give prophylaxis for dog and cat bites in asplenic patients with Amoxicillin/clavulanate for 7-10 days.
# Citrobacter freundii
- Citrobacter freundii Return to Top
- Citrobacter freundii[143]
- Preferred regimen (1): Meropenem 1-2 g IV q8h
- Preferred regimen (2): Imipenem 1 g IV q6h
- Preferred regimen (3): Doripenem 500 mg IV q8h
- Preferred regimen (4): Cefepime 1-2 g IV q8h
- Preferred regimen (5): Ciprofloxacin 400 mg IV q12h or 500 mg PO bid for UTI
- Preferred regimen (6): Gentamicin 5 mg/kg IV q24h
- Alternate regimen (1): Piperacillin-tazobactam 3.375 mg IV q6h
- Alternate regimen (2): Aztreonam 1-2 g IV q6h
- Alternate regimen (3): TMP-SMX 5 mg/kg q6h IV or DS PO bid for UTI
- Note: Usually carbenicillin sensitive, cephalothin resistant
# Citrobacter koseri
- Citrobacter koseri Return to Top
- Citrobacter koseri[144]
- Preferred regimen (1): Ceftriaxone 1-2 g IV q12-24h
- Preferred regimen (2): Cefotaxime 1-2 g IV q6h
- Preferred regimen (3): Cefepime 1-2 IV q8h
- Alternate regimen (1): Ciprofloxacin 400 mg IV q12h or 500 mg PO q12h for UTI
- Alternate regimen (2): Imipenem 1 g IV q6h
- Alternate regimen (3): Doripenem 500 mg IV q8h
- Alternate regimen (4): Meropenem 1-2 g IV q8h
- Alternate regimen (5): Aztreonam 1-2 g IV q6h
- Alternate regimen (6): TMP-SMX 5 mg/kg IV q6h or DS PO bid for UTI
- Note: Usually Ampicillin resistant, but may be sensitive to first generation cephalosporins
- Elizabethkingia meningoseptica Return to Top
- 1. Bacteremia[145][146]
- Preferred regimen (1): Levofloxacin 750 mg IV/PO q24h
- Preferred regimen (2): TMP-SMX 8–10 mg/kg/day IV divided q6–8h
- Alternative regimen (1): Ciprofloxacin 400 mg IV q12h
- Alternative regimen (2): TMP-SMX 8–10 mg/kg/day IV divided q6–8h
# Enterobacter
- Enterobacter Return to Top
- Enterobacter species including E. aerogenes and E. cloacae[147][148][149][150][151]
- 1. Empiric antimicrobial therapy pending in vitro susceptibility
- 1.1 Non–life-threatening infections or MDR-GNB prevalence < 20%
- Preferred regimen: Piperacillin-Tazobactam 3.375 g IV q6h ± Aminoglycosides
- Alternative regimen: Ciprofloxacin 400 mg IV q8–12h
- 1.2 Life-threatening infections or MDR-GNB prevalence > 20%
- Preferred regimen: Meropenem 0.5–1 g IV q8h
- Alternative regimen (1): Colistin AND Meropenem 0.5–1 g IV q8h
- Alternative regimen (2): Colistin AND Imipenem 500 mg IV q6h
- Alternative regimen (3): Colistin AND Doripenem 500 mg IV q8h
- Alternative regimen (4): Colistin AND Ertapenem 1 g IV q24h
- Alternative regimen (5): Colistin AND Fosfomycin 6 g IV q6h
- 2. In vitro susceptibility available
- 2.1 Susceptible to all tested agents
- Preferred regimen: Piperacillin-Tazobactam 3.375 g IV q6h
- Alternative regimen (1): Ciprofloxacin 400 mg IV q8–12h
- Alternative regimen (2): Cefepime 2 g IV q8h (if MIC ≤ 1 μg/mL)
- 2.2 Extended spectrum beta-lactamase (ESBL)-producing Enterobacter spp.
- Preferred regimen: Meropenem 0.5–1 g IV q8h
- Alternative regimen (1): Imipenem 500 mg IV q6h
- Alternative regimen (2): Doripenem 500 mg IV q8h
- Alternative regimen (3): Ertapenem 1 g IV q24h
- Alternative regimen (4): Cefepime 2 g IV q8h (if MIC ≤ 1 μg/mL)
- 2.3 Resistant to all tested agents
- Preferred regimen: Colistin AND Meropenem 0.5–1 g IV q8h
- Alternative regimen (1): Colistin AND Imipenem 500 mg IV q6h
- Alternative regimen (2): Colistin AND Doripenem 500 mg IV q8h
- Alternative regimen (3): Colistin AND Ertapenem 1 g IV q24h
- Alternative regimen (4): Colistin AND Minocycline 100 mg IV q12h
# Escherichia coli
- Escherichia coli Return to Top
- Escherichia coli[152]
- 1. Meningitits
- Preferred regimen (1): Ceftriaxone 4 g IV q12–24h
- Preferred regimen (2): Cefotaxime 8–12 g/day IV q4–6h
- Alternative regimen (1): Aztreonam 6–8 g/day IV q6–8h
- Alternative regimen (2): Gatifloxacin 400 mg/day IV q24h
- Alternative regimen (3): Moxifloxacin 400 mg/day IV q24h
- Alternative regimen (4): Meropenem 6 g/day IV q8h
- Alternative regimen (5): Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day IV q6–12h
- Alternative regimen (6): Ampicillin 12 g/day IV q4h
- 2. Uncomplicated urinary tract infection[153]
- Preferred agents (IDSA/AUA Guidelines): TMP-SMX DS PO bid for 3 days
- Alternative regimen (1): Ciprofloxacin 250 mg PO bid
- Alternative regimen (2): Ciprofloxacin 500 mg XR qd for 3 days
- Alternative regimen (3): Levofloxacin 250 mg PO qd for 3 days.
- Alternative regimen (4): Nitrofurantoin 100 mg PO q6h
- Alternative regimen (5): Nitrofurantoin macrocrystals 100 mg PO bid for 7 days
- Alternative regimen (6): Fosfomycin 3 g sachet PO single dose
- Note: For older patients, those with comorbidities (e.g., diabetes mellitus) use 7-10 days course.
- 3. Pyelonephritis
- 3.1 Acute uncomplicated pyelonephritis[154]
- Preferred regimen (1): Ciprofloxacin 500 mg bid PO for 5-7 days
- Preferred regimen (2): Ciprofloxacin-Erythromycin 1000 mg q24h
- Preferred regimen (3): Levofloxacin 750 mg q24h
- Preferred regimen (4): Ofloxacin 400 mg bid
- Preferred regimen (5): Moxifloxacin 400 mg q24h
- Alternative regimen (1): Amoxicillin-Clavulanic acid 875/125 mg PO q12h or 500/125 mg PO tid or 1000 /125 mg PO bid
- Alternative regimen (2): Oral Cephalosporins
- Alternative regimen (3): TMP-SMX 2 mg/kg IV q6h PO for 14 days
- 3.2 Acute pyelonephritis (Hospitalized)[155]
- Preferred regimen (1): Ciprofloxacin 400 mg IV q12h
- Preferred regimen (2): Ampicillin and Gentamicin
- Preferred regimen (3): Piperacillin-Tazobactam 3.375 g IV q4-6h for 14 days
- Alternative regimen (1): Ticarcillin-Clavulanate 3.1 g IV q6h
- Alternative regimen (2): Ampicillin-Sulbactam 3 g IV q6h
- Alternative regimen (3): Piperacillin-Tazobactam 3.375 g IV q4-6h
- Alternative regimen (4): Ertapenem 1 g IV q24h
- Alternative regimen (5): Doripenem 500 mg q8h for 14 days
- 4. Traveler’s diarrhea[156]
- 4.1 Prophylaxis
- Preferred regimen (1): Bismuth subsalicylate two chewable tablets qid
- Preferred regimen (2): Norfloxacin 400 mg PO qd
- Preferred regimen (3): Ciprofloxacin 500 mg PO qd
- Preferred regimen (4): Rifaximin 200 mg PO qd or bid
- 4.2 Symptomatic treatment
- Preferred regimen (1): Bismuth subsalicylate 1 oz PO every 30 min for 8 doses
- Preferred regimen (2): Loperamide 4 mg PO then 2 mg after each loose stool not to exceed 16 mg daily
- 4.3 Antibiotic treatment
- Preferred regimen (1): Fluoroquinolones, Norfloxacin 400 mg PO bid
- Preferred regimen (2): Ciprofloxacin 500 mg PO bid
- Preferred regimen (3): Ofloxacin 200 mg PO bid
- Preferred regimen (4): Levofloxacin 500 mg PO qd
- Preferred regimen (5): Azithromycin 1000 mg PO single dose
- Preferred regimen (6): Rifaximin 200 mg PO tid
- 5. Malacoplakia[157]
- Preferred regimen (1): Bethanechol chloride AND Ciprofloxacin 400 mg IV q12h
- Preferred regimen (2): Bethanechol chloride AND TMP-SMX 2 mg/kg (TMP component IV q6h)
- 6. Bacteremia/pneumonia[158]
- Preferred regimen (1): Ceftriaxone 1-2 g IV q24h
- Preferred regimen (2): Ciprofloxacin 400 mg IV q12h or 500 mg PO q12h
- Preferred regimen (3): Levofloxacin 500 mg PO/IV q24h
- Preferred regimen (4): Moxifloxacin 400 mg IV/PO q24h
- Preferred regimen (5): Ampicillin 2 g IV q6h (if sensitive)
- Preferred regimen (6): TMP-SMX 5-10 mg/kg/day for q6-8h IV (if sensitive)
- Alternative regimen (1): Imipenem, Meropenem, Ertapenem, Doripenem; Ceftazidime, Cefepime; Cefazolin or Cefuroxime (if sensitive); Aztreonam; Ticarcillin, Piperacillin; Piperacillin-Tazobactam
- Alternative regimen (2): Ampicillin-sulbactam 3 g IV q6h AND (Gentamicin 1.5 mg/kg IV q8h or 5-7 mg/kg/day IV OR Tobramycin 5 mg/kg/day IV)
- Note (1): A 7- to 14-day course of antibiotic therapy is usually recommended.
- Note (2): The choice of antimicrobial agents should be based on susceptibility results.
- Note (3): Monotherapy with aminoglycosides is generally not recommended for bacteremia or pneumonia.
# Francisella tularensis
- Francisella tularensis Return to Top
- Francisella tularensis[159]
- 1. Tularemia
- Preferred regimen (1): Streptomycin 1 g IM bid
- Preferred regimen (2): Gentamicin 5 mg/kg IV q24h for 10 days
- Preferred regimen (3) (pregnancy): Gentamicin 5 mg/kg IV q24h for 10 days
- Alternative regimen (1): Doxycycline 100 mg IV bid
- Alternative regimen (2): Chloramphenicol 1 g IV q6h
- Alternative regimen (3): Ciprofloxacin 400 mg IV bid until stable THEN PO for 14-21 days (total)
# Helicobacter pylori
- Helicobacter pylori Return to Top
- 1. Peptic ulcer disease[160]
- In patients aged 55 years or younger with no alarm features, two management options may be considered:
- 1.1 Indications for eradication therapy
- In moderate to high prevalence of H. pylori infection (≥ 10%): Test-and-treat strategy using a validated noninvasive test (urea breathing test or stool antigen test)
- In low prevalence situations: Treatment indicated after the empiric trial of acid suppression with a proton pump inhibitor for 4–8 weeks
- 1.2 Proton pump inhibitors (PPI)
- Preferred regimen (1): Lansoprazole 30 mg q12h
- Preferred regimen (2): Omeprazole 20 mg q12h
- Preferred regimen (3): Esomeprazole 40 mg q24h
- Preferred regimen (4): Rabeprazole 20 mg q12h
- 1.3 Regimens for Initial Treatment
- 1.3.1 Triple therapy
- Preferred regimen (1): Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid AND Clarithromycin 500 mg bid for 7-14 days
- Preferred regimen (2): Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid AND Metronidazole 500 mg bid for 7-14 days
- Preferred regimen (3) (Levofloxacin triple therapy): Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid AND Levofloxacin 500 mg bid for 10 days
- Preferred regimen (4) (Rifabutin triple therapy): Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid AND Rifabutin 150-300 mg/day for 10 days
- 1.3.2 Quadruple therapy
- Preferred regimen (1): Proton pump inhibitor standard dose bid AND Metronidazole 250 mg q6h AND Tetracycline 500 mg q6h AND Bismuth (dose depends on preparation) for 10-14 days
- Preferred regimen (2) non-bismuth quadruple therapy (concomitant therapy): Proton pump inhibitor (standard dose twice daily) for 7–14 days AND Clarithromycin 500 mg bid for 7–14 days AND Amoxicillin 1 g bid for 10 days AND Metronidazole 250 mg qid for 7–14 days
- 1.3.3 Sequential therapy
- Preferred regimen: Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid for 1-5 days followed by Proton pump inhibitor standard dose bid AND Clarithromycin 500 mg bid AND Tinidazole 500 mg bid for 6-10 days
- Note: Alternative triple therapies appropriate for patients with an allergy to Amoxicillin include (Proton pump inhibitor and Clarithromycin and Metronidazole) or (Proton pump inhibitor and Tetracycline and Metronidazole)
- 1.5 Clarithromycin resistance
- 1.5.1 Clarithromycin resistance ≥ 20%
- Preferred regimen (1) (bismuth quadruple therapy): Proton pump inhibitor standard dose bid AND Metronidazole 250 mg q6h AND Tetracycline 500 mg q6h AND Bismuth (dose depends on preparation) for 10-14 days
- Preferred regimen (2) (sequential therapy): Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid for 1-5 days followed by Proton pump inhibitor standard dose bid AND Clarithromycin 500 mg bid AND Tinidazole 500 mg bid for 6-10 days
- Preferred regimen (3) non-bismuth quadruple therapy (concomitant therapy): Proton pump inhibitor (standard dose twice daily) for 7–14 days AND Clarithromycin 500 mg bid for 7–14 days AND Amoxicillin 1 g bid for 10 days AND Metronidazole 250 mg qid for 7–14 days
- Alternative regimen: Proton pump inhibitor standard dose bid AND Amoxicillin 1 g bid AND Levofloxacin 500 mg bid for 10 days
- 1.5.2 Clarithromycin resistance < 20%
- Preferred regimen (1): Proton pump inhibitor standard dose bid for 7-14 days AND Clarithromycin 500 mg bid for 7–14 days AND Amoxicillin 1 g bid for 7–14 days OR Metronidazole 250 mg qid for 7–14 days
- Preferred regimen (2): Proton pump inhibitor standard dose bid AND Metronidazole 250 mg q6h AND Tetracycline 500 mg q6h AND Bismuth (dose depends on preparation) for 10-14 days
- Alternative regimen (1):Proton pump inhibitor standard dose bid AND Metronidazole 250 mg q6h AND Tetracycline 500 mg q6h AND Bismuth (dose depends on preparation) for 10-14 days
- Alternative regimen (2): Proton pump inhibitor standard dose bid for 10 days AND Levofloxacin 500 mg bid for 10 days AND Amoxicillin 1 g bid for 10 days
# Klebsiella granulomatis
- Klebsiella granulomatis Return to Top
- Klebsiella granulomatis (formly known as Calymmatobacterium granulomatis)
- 1. Granuloma inguinale (donovanosis)[161]
- Preferred regimen: Azithromycin 1 g PO once a week or 500 mg qd for 3 weeks THEN until all lesions have completely healed
- Alternative regimen (1): Doxycycline 100 mg PO bid for 3 weeks THEN until all lesions have completely healed
- Alternative regimen (2): Ciprofloxacin 750 mg PO bid for at least 3 weeks THEN until all lesions have completely healed
- Alternative regimen (3): Erythromycin base 500 mg PO qid for at least 3 weeks THEN until all lesions have completely healed
- Alternative regimen (4): Trimethoprim-sulfamethoxazole DS (160 mg/800 mg) tablet PO bid for at least 3 weeks THEN until all lesions have completely healed
# Klebsiella pneumoniae
- Klebsiella pneumoniae Return to Top
- Klebsiella pneumoniae[162]
- 1. Severe, nosocomial infections
- 1.1 Non-ESBLs in pneumonia, sepsis, complicated UTI, or intra-abdominal infections
- Preferred regimen (1): Cefepime 2 g IV q8h
- Preferred regimen (2): Ceftazidime 2 g IV q8h
- Preferred regimen (3): Imipenem 500 mg IV q6h
- Preferred regimen (4): Meropenem 1 g IV q8h
- Preferred regimen (5): Piperacillin-tazobactam 4.5 g IV q6h AND Aminoglycoside
- Alternative regimen (1): Ceftriaxone 1 g IV q24h AND Metronidazole 500 mg IV q6h or 1 g IV q12h
- Alternative regimen (2): Moxifloxacin 400 mg IV/PO q24h
- 1.2 ESBLs in pneumonia, sepsis, complicated UTI, or intra-abdominal infections
- Preferred regimen (1): Imipenem 500 mg IV q6h
- Preferred regimen (2): Meropenem 1 g IV q8h
- Preferred regimen (3): Ertapenem 1 g IV q24h
- Preferred regimen (4): Doripenem 500 mg IV q8h
- Note: In ESBLs, inconsistent activity is seen with aminoglycosides, fluoroquinolones, and piperacillin-tazobactam. Avoid cephalosporins.
# Klebsiella rhinoscleromatis
- Klebsiella rhinoscleromatis Return to Top
- 1. Rhinoscleroma[163][164][165]
- Preferred regimen (1): Ciprofloxacin 500–750 mg PO bid for 2–3 months
- Preferred regimen (2): Levofloxacin 750 mg PO qd for 2–3 months
- Preferred regimen (3): Trimethoprim-Sulfamethoxazole 1 DS tab PO bid for 3 months AND Rifampicin 300 mg PO bid for 3 months
- Alternative regimen: Tetracycline OR Streptomycin OR Doxycycline OR Ceftriaxone OR Ofloxacin
- Note (1): The optimal duration of antimicrobial therapy remains unclear. A 6-week to 6-month course of antibiotics until histology exams and cultures are negative may be required.
- Note (2): Use of topical antiseptics such as Acriflavinium and Rifampin ointment has been reported with resolution of symptoms.[166]
# Legionella pneumophila
- Legionella pneumophila Return to Top
- 1.Atypical pneumonia (Legionnaires' disease )[167]
- 1.1 Mild pneumonia inpatient or outpatient, non immunocompromised
- Preferred regimen (1): Azithromycin 500 mg PO qd for 3-5 days
- Preferred regimen (2): Levofloxacin 500 mg PO qd for 7-10 days
- Preferred regimen (3): Ciprofloxacin 500 mg PO bid for 7-10 days
- Preferred regimen (4): Moxifloxacin 400 mg PO qd for 7-10 days
- Preferred regimen (5): Clarithromycin 500 mg PO bid for 10-14 days
- Alternative regimen (1): Doxycycline 200 mg PO loading dose, then 100 mg PO bid for 10-14 days
- Alternative regimen (2): Erythromycin 500 mg PO qid for 10-14 days
- Note: Patients with mild disease may be treated entirely with oral therapy.
- 1.2 Moderate to severe pneumonia or immunocompromised
- Preferred regimen (1): Azithromycin 500 mg PO/IV q24h for 5-7 days
- Preferred regimen (2): Levofloxacin 500 mg PO/IV q24h for 7-10 days OR 750 mg PO/IV q24h for 5-7 days
- Alternative regimen (1): Ciprofloxacin 750 mg PO bid for 14 days
- Alternative regimen (2): Moxifloxacin 400 mg PO qd for 14 days
- Alternative regimen (3): Erythromycin 750-1000 mg IV q6h for 3-7 days, then 500 mg PO qid for a total course of 21 days
- Alternative regimen (4): Clarithromycin 500 mg IV q12h for 3-7 days, and then 500 mg PO bid for a total course of 21 days
- Note: Severely ill patients parenteral therapy is advised until improvement is seen and oral absorption is sufficient.
- 2 Pontiac fever
- Pontiac fever is febrile, self-limited form of Legionella infection which requires only symptomatic therapy, such as analgesics for headache. Antibiotics are not indicated.
# Moraxella catarrhalis
- Moraxella catarrhalis Return to Top
- Moraxella catarrhalis[168]
- Preferred regimen (1): TMP-SMX 1DS PO bid
- Preferred regimen (2): Erythromycin 500 mg PO q6h
- Preferred regimen (3): Clarithromycin 500 mg bid or XL 1 g PO qd
- Preferred regimen (4): Azithromycin 500 mg single dose THEN 250 mg PO qd
- Preferred regimen (5): Doxycycline 100 mg PO/IV bid
- Preferred regimen (6): Parenteral cephalosporins such as Cefuroxime OR Cefotaxime OR Ceftriaxone
- Preferred regimen (7): Cefprozil 200-500 mg PO bid
- Preferred regimen (8): Cefpodoxime 200-400 mg PO bid
- Preferred regimen (9): Cefuroxime 250-500 mg PO bid
- Preferred regimen (10): Cefdinir 300 mg bid
- Preferred regimen (11): Moxifloxacin 400 mg IV/PO qd
- Preferred regimen (12): Levofloxacin 500 mg IV/PO qd
- Preferred regimen (13): Amoxicillin-Clavulanate 875/125 mg PO bid or XL 2000/125 PO bid
# Morganella morganii
- Morganella morganii Return to Top
- Morganella morganii[169]
- Preferred regimen (1): Imipenem 500 mg IV q6h
- Preferred regimen (2): Meropenem 1.0 g IV q8h (adjust dose if necessary for renal function).
- Note (1): Carbapenems are considered first line therapy due to inducible cephalosporinases, and presence of extended-spectrum beta-lactamases in some isolates
- Note (2): Duration of treatment for UTI (generally complicated) is 7 days and duration of treatment for bacteremia is 14 days
- Note (3): Tigecycline is not reliably effective
- Alternative Regimen (1): Cefepime 2.0 g IV q8-12h
- Alternative Regimen (2): Ciprofloxacin 500 mg PO/400 mg IV q12h
- Alternative Regimen (3): Piperacillin 3 g IV q6h
- Alternative Regimen (4): Ticarcillin 3 g IV q4h
- Alternative Regimen (5): Gentamicin
- Alternative Regimen (6): Tobramycin 1 mg/kg IV q24h
- Alternative Regimen (7): Amikacin 3 mg/kg IV q24h
- Note: Aminoglycosides can be used alone for treatment of UTI
# Plesiomonas shigelloides
- Plesiomonas shigelloides Return to Top
- Plesiomonas shigelloides[170]
- 1. Immunocompetent hosts or severe Infection
- Preferred regimen: Ciprofloxacin 500 mg PO bid or 400 mg IV q12h
- Alternative regimen (1): Ofloxacin 300 mg PO bid
- Alternative regimen (2): Norfloxacin 400 mg PO bid
- Alternative regimen (3): TMP-SMX DS PO bid for 3 days
- Alternative regimen (4): Ceftriaxone 1-2 g IV qd in severe cases
- 2. Immunocompromised hosts
- Preferred regimen: Ciprofloxacin 500 mg PO bid for 3 days
- Alternative regimen (1): Ofloxacin 300 mg PO bid
- Alternative regimen (2): Norfloxacin 400 mg PO bid
- Alternative regimen (3): TMP-SMX DS PO bid for 3 days if susceptible
# Proteus mirabilis
- Proteus mirabilis Return to Top
- Proteus mirabilis[171]
- Preferred regimen (1): Ampicillin 500 mg PO q6h or 2 g IV q6h
- Preferred regimen (2): Cefuroxime 250 mg PO bid or 750 mg IV q8h
- Preferred regimen (3): Ciprofloxacin 250-500 mg PO bid or 400 mg IV q12h
- Preferred regimen (4): Levofloxacin 500 mg PO OD or 500 mg IV q24h
- Note: Duration of treatment for uncomplicated UTI 3 days, pyelonephritis 7-14 days, complicated UTI 10-21 days and bacteremia is 7-14 days
# Indole positive Proteus species
- Indole positive Proteus species[172]
- Preferred regimen (1): Ceftriaxone 1 g IV q24h
- Preferred regimen (2): Imipenem 500 mg IV q6h
- Preferred regimen (3): Ciprofloxacin 400 mg IV q12h or 250-500 mg PO bid
- Preferred regimen (4): Levofloxacin 500 mg IV/PO q24h
# Providencia
- Providencia Return to Top
- Providencia[173]
- 1. Complicated uti/bacteremia/acute prostatitis
- Preferred regimen (1): Ciprofloxacin 500-750 mg PO q12h or 400 mg IV q8-12h
- Preferred regimen (2): Levofloxacin 500 mg IV/PO q24h
- Preferred regimen (3): Piperacillin-Tazobactam 3.375 mg IV q6h
- Preferred regimen (4): Ceftriaxone 1-2 g IV q24h (donot use if ESBL suspected or critically ill)
- Preferred regimen (5): Meropenem 1 g IV q8h (consider if critically ill or ESBL suspected)
- Preferred regimen (6): Amikacin 7.5 mg/kg IV q12h
- Preferred regimen (7): Gentamicin
- Preferred regimen (8): Tobramycin acceptable if susceptible but many species are resistant
- Note (1): Duration of treatment for (UTI) is 7 days common or 3-5 days after defervescence or control/elimination of complicating factors (e.g.,removal of foreign material catheter).
- Note (2): Duration of treatment for (bacteremia) is 10-14 days or 3-5 days after defervescence or control/elimination of complicating factors
- Note (3): Duration for acute prostatitis (2 weeks), shorter than chronic prostatitis (4-6 weeks)
- Alternative regimen: TMP-SMX DS PO q12h for 10-14 days or TMP 5-10 mg/kg/day IV q6h
# Pseudomonas aeruginosa
- Pseudomonas aeruginosa Return to Top
- Pseudomonas aeruginosa[174]
- Preferred regimen (1): Cefepime 2 g IV q8h
- Preferred regimen (2): Ceftazidime 2 g IV q8h
- Preferred regimen (3): Piperacillin 3-4 g IV q4h in (no benefit for pseudomonas from beta-lactamase inhibitor)
- Preferred regimen (4): Ticarcillin 3-4 g IV q4h (no benefit for pseudomonas from beta-lactamase inhibitor)
- Preferred regimen (5): Imipenem 500 mg—1 g IV q6h
- Preferred regimen (6): Meropenem 1 g IV q8h
- Preferred regimen (7): Doripenem 500 mg IV q8h
- Preferred regimen (8): Ciprofloxacin 400 mg IV q8h or 750 mg PO q12h (for less serious infections)
- Preferred regimen (9): Aztreonam 2 g IV q6-8h
- Preferred regimen (10): Colistin 2.5 mg/kg IV q12h
- Preferred regimen (11): Polymyxin B 0.75-1.25 mg/kg IV q12h
- Preferred regimen (12): Gentamicin
- Preferred regimen (13): Tobramycin 1.7-2.0 mg/Kg IV q8h or 5-7 mg/kg IV
- Preferred regimen (14): Amikacin 2.5 mg/kg IV q12h
- Note: Amikacin > Tobramycin > Gentamicin with respect to P.aeruginosa susceptibility percentages at most institutions.
# Salmonella
- Salmonella Return to Top
- 1. Salmonellosis in immunocompetent hosts[175]
- 1.1 Gastroenteritis
- Antimicrobial therapy is usually not recommended for uncomplicated diarrheal illness.
- 1.1.1 Indications for antimicrobial therapy
- severedisease,
- Age > 50 yrs
- Prosthesis
- Presence of valvular heart disease
- Severe atherosclerosis
- Cancer
- Uremia
- Immunosuppression
- 1.1.2 Treatment regimens
- Preferred regimen (1): TMP-SMX DS PO bid for 5-7 days
- Preferred regimen (2): Ciprofloxacin 500 mg PO bid for 5-7 days
- Preferred regimen (3): Ceftriaxone 2 g IV q24h for 5-7 days
- 1.2 Typhoid fever[176]
- 1.2.1 Uncomplicated typhoid
- Preferred regimen (1) (fully susceptible): Fluoroquinolone (e.g., Ofloxacin 15 mg/kg PO qd for 5–7 days)
- Preferred regimen (2) (multi drug-resistant): Fluoroquinolone (Ofloxacin 15 mg/kg PO qd for 5–7 days)
- Preferred regimen (3) (quinolone-resistant): Azithromycin 8–10 mg/kg PO qd for 7 days
- Preferred regimen (4) (quinolone-resistant): Fluoroquinolone 20 mg/kg PO qd for 10-14 days
- Alternative regimen (1) (fully susceptible): Chloramphenicol 50–75 mg/kg PO qd for 14-21 days
- Alternative regimen (2) (fully susceptible): Amoxicillin 75–100 mg/kg PO qd for 14 days
- Alternative regimen (3) (fully susceptible): Trimethoprim–Sulfamethoxazole, 8 mg/kg (trimethoprim)– 40 mg/kg (sulfamethoxazole) PO qd for 14 days
- Alternative regimen (4) (multi drug-resistant): Azithromycin 8–10 mg/kg PO for 7 days
- Alternative regimen (5) (multi drug-resistant): Third-generation cephalosporin, e.g., Cefixime 20 mg/kg PO qd for 7-14 days
- Alternative regimen (6) (quinolone-resistant): Third-generation cephalosporin, e.g., Cefixime 20 mg/kg PO qd for 7-14 days
- 1.2.2 Severe typhoid
- Preferred regimen (1) (fully susceptible): Fluoroquinolone (e.g., Ofloxacin 15 mg/kg IV qd for 10-14 days)
- Preferred regimen (2) (multi drug-resistant): Fluoroquinolone (Ofloxacin 15 mg/kg IV qd for 10-14 days)
- Preferred regimen (3) (quinolone-resistant): Ceftriaxone 60 mg/kg IV qd for 10-14 days
- Preferred regimen (4) (quinolone-resistant): Cefotaxime 80 mg/kg IV qd for 10-14 days
- Alternative regimen (1) (fully susceptible): Chloramphenicol 100 mg/kg PO qd for 14-21 days
- Alternative regimen (2) (fully susceptible): Ampicillin 100 mg/kg PO qd for 14-21 days
- Alternative regimen (3) (fully susceptible): Trimethoprim–Sulfamethoxazole, 8 mg/kg (trimethoprim)– 40 mg/kg (sulfamethoxazole) IV qd for 10-14 days
- Alternative regimen (4) (multi drug-resistant): Ceftriaxone 60 mg/kg IV qd for 10-14 days
- Alternative regimen (5) (multi drug-resistant): Cefotaxime 80 mg/kg IV qd for 10-14 days
- Alternative regimen (6) (quinolone-resistant): Fluoroquinolone 20 mg/kg IV qd for 10-14 days
- 1.3 Non-typhoid (serious infection)[177]
- Preferred regimen (1): 3rd generation cephalosporin (Ceftriaxone/Cefotaxime)
- Preferred regimen (2): Fluoroquinolone (Ciprofloxacin, Levofloxacin)
- 1.4 Bacteremia[178]
- Preferred regimen (1): Ceftriaxone 2 g IV q24h
- Preferred regimen (2): Cefotaxime 2 g IV q6-8h for 7-14 days
- Preferred regimen (3): Ciprofloxacin 400 mg IV q12h for 7-14 days
- 1.5 Vascular prosthesis infection[179]
- Preferred regimen (1): Ceftriaxone
- Preferred regimen (2): Cefotaxime
- Preferred regimen (3): Ciprofloxacin 400 mg IV q12h for 6 weeks
- 1.6 Osteomyelitis[180]
- Preferred regimen (1): Ceftriaxone 2 g IV q24h
- Preferred regimen (2): Cefotaxime 2 g IV q6-8h
- Preferred regimen (3): Ciprofloxacin 750 mg PO bid for ≥ 4 weeks
- 1.7 Arthritis[181]
- Preferred regimen (1): Ceftriaxone 2 g IV q24h
- Preferred regimen (2): Cefotaxime 2 g IV q6-8h for 6 weeks
- 1.8 Endocarditis[182]
- Preferred regimen (1): Ceftriaxone 2 g IV q24h
- Preferred regimen (2): Cefotaxime 2 g IV q6-8h for 6 weeks
- 1.9 UTI[183]
- Preferred regimen (1): Ceftriaxone
- Preferred regimen (2): Cefotaxime
- Preferred regimen (3): Ciprofloxacin IV for 1-2 weeks THEN (oral Ciprofloxacin OR TMP-SMX for 6 weeks)
- 1.10 Carrier state[184]
- Preferred regimen (1): Ciprofloxacin 500 mg PO bid for 4-6 weeks
- Preferred regimen (2): TMP-SMX 1DS bid PO for 6 weeks
- Preferred regimen (3): Amoxicillin 500 mg PO for 6 weeks
- 2. Salmonellosis in immunocompromised hosts
- 2.1 HIV and salmonellosis[185]
- 2.1.1 Gastroenteritis
- Preferred regimen: Ciprofloxacin 500-750 mg PO bid or 400 mg IV q12h, if susceptible
- Alternative regimen (1): Levofloxacin 750 mg PO/IV q24h
- Alternative regimen (2): Moxifloxacin 400 mg PO/IV q24h
- Alternative regimen (3): TMP 160 mg AND SMX 800 mg PO/IV q12h
- Alternative regimen (4): Ceftriaxone 1 g IV q24h
- Alternative regimen (5): Cefotaxime 1 g IV q8h
- Duration of treatment for gastroenteritis without bacteremia
- If CD4 count ≥ 200 cells/μL: Duration of treatment is 7–14 days
- If CD4 count < 200 cells/μL: Duration of treatment is 2–6 weeks
- Duration of treatment for gastroenteritis with bacteremia
- If CD4 count ≥ 200/μL: Duration of treatment is 14 days; longer duration if bacteremia persists or if the infection is complicated (e.g., if metastatic foci of infection are present)
- If CD4 count < 200 cells/μL: Duration of treatment is 2–6 weeks
- Note: Secondary prophylaxis should be considered for
- Patients with recurrent Salmonella gastroenteritis with or without bacteremia
- Patients with CD4 < 200 cells/μL with severe diarrhea
# Serratia marcescens
- Serratia marcescens Return to Top
- Serratia marcescens[186]
- 1. Bacteremia, pneumonia or serious infections
- Preferred regimen (1): Cefepime 1-2 g IV q8h
- Preferred regimen (2): Imipenem 0.5-1.0 g IV q6h
- Preferred regimen (3): Ciprofloxacin 400 mg IV q8h
- Alternative regimen (1): Aztreonam
- Alternative regimen (2): Gentamicin
- Alternative regimen (3): Amikacin
- Alternative regimen (4): Piperacillin-tazobactam also often effective
- Note: Duration depends on clinical response, usually 7-14 days
- 2. Endocarditis
- Note: Choice dictated by sensitivities, 4 to 6 week duration of parenteral therapy.
- 3. Osteomyelitis
- Note (1): Choice dictated by sensitivity profile, treat for 6-12 weeks depending upon response.
- Note (2): Use IV treatment until stable/clinically improved (10-14 days Minimum) then may convert to oral therapy if appropriate.
- 4. UTI
- Preferred regimen (1): Ciprofloxacin 250 mg PO bid or 400 mg IV q12h
- Preferred regimen (2): Levofloxacin 250 mg PO qd or 500mg IV q24h
- Note: Fluoroquinolones often sensitive but in seriously ill patient consider empiric coverage with two drugs (e.g.,beta-lactam and aminoglycoside or fluoroquinolones and carbapenem) until susceptibilities known.
# Shigella
- Shigella Return to Top
- 1. Shigellosis [187]
- 1.1 Adults
- Preferred regimen (1): Ciprofloxacin 500 mg PO bid for 3 days
- Alternative regimen (1): Pivmecillinam 100 mg PO qid for 5 days
- Alternative regimen (2): Azithromycin 1-1.5 g PO qd for 1 to 5 days
- 1.2 Pediatrics
- Preferred regimen (1): Ciprofloxacin 15 mg/kg PO bid for 3 days
- Alternative regimen (1): Pivmecillinam 20 mg/kg PO qid for 5 days
- Alternative regimen (2): Ceftriaxone 50-100 mg/kg IM qd for 2 to 5 days
- Alternative regimen (3): Azithromycin 6-20 mg/kg PO qd for 1 to 5 days
# Stenotrophomonas maltophilia
- Stenotrophomonas maltophilia Return to Top
- Stenotrophomonas maltophilia[188]
- Preferred treatment: TMP-SMX 15-20 mg/kg/day (TMP component) IV/PO q8h
- Alternative treatment (1): Ceftazidime 2 g IV q8h
- Alternative treatment (2): Ticarcillin-clavulanate 3.1 g IV q4h
- Alternative treatment (3): Tigecycline 100 mg IV single dose THEN 50 mg IV q12h
- Alternative treatment (4): Ciprofloxacin 500-750 mg PO /400 mg IV q12h
- Alternative treatment (5): Moxifloxacin 400 mg PO/IV
- Alternative treatment (6): Levofloxacin 750 mg PO/IV .
- Alternative treatment (7) (Multiply-resistantance): Colistin 2.5 mg/kg q12h IV
- Note: Treatment duration uncertain, but usually ≥ 14 days
- Vibrio cholerae Return to Top
- 1. WHO [189] [190]
- Note: Antibiotic treatment for cholera patients with severe dehydration only
- Adults
- Preferred regimen: Doxycycline 300 mg po single dose
- Alternative regimen: Tetracycline 12.5 mg/kg PO qid for 3 days
- Pediatric
- Under 12 years old
- Preferred regimen: Erythromycin 12.5 mg/kg PO qid for 3 days
- Over 12 years old
- Preferred regimen: Doxycycline 300 mg po single dose
- Alternative regimen: Tetracycline 12.5 mg/kg PO qid for 3 days
- 2. Pan American Health Organization [191]
- Note: Antibiotic treatment for cholera patients with moderate or severe dehydration
- 2.1 Adult
- Preferred regimen: Doxycycline 300 mg po single dose
- Alternative regimen (1): Ciprofloxacin 1 g PO single dose
- Alternative regimen (2): Azithromycin 1 g PO single dose
- 2.2 Pediatric
- 2.2.1 Children over 3 year, who can swallow tablets
- Preferred regimen (1): Erythromycin 12.5 mg/kg/ PO qid for 3 days
- Preferred regimen (2): Azithromycin 20 mg/kg PO in a single dose
- Alternative regimen (1): Ciprofloxacin suspension or tablets 20 mg/kg PO single dose
- Alternative regimen (2): Doxycycline suspension or tablets 2-4 mg/kg PO single dose
- Note: Although doxycycline has been associated with a low risk of yellowing of the teeth in children, its benefits outweigh its risks
- 2.2.2 Children under 3 year, or infants who cannot swallow tablets
- Preferred regimen (1): Erythromycin suspension 12.5 mg/kg/ PO qid for 3 days
- Preferred regimen (2): Azithromycin suspension 20 mg/kg PO single dose
- Alternative regimen (1): Ciprofloxacin suspension 20 mg/kg PO single dose
- Alternative regimen (2): Doxycycline syrup 2-4 mg/kg PO single dose
- 2.3 Pregnancy
- Preferred regimen (!): Erythromycin 500 mg/ PO qid for 3 days
- Preferred regimen (2): Azithromycin 1 g PO single dose
- Vibrio parahaemolyticus Return to Top
- Vibrio parahaemolyticus [192]
- 1. Mild to Moderate
- Treatment is not necessary in most cases of V. parahaemolyticus infection
- There is no evidence that antibiotic treatment decreases the severity or the length of the illness
- Patients should drink plenty of liquids to replace fluids lost through diarrhea
- 2. Severe or prolonged illnesses
- Preferred regimen: Tetracycline OR Ciprofloxacin
- Vibrio vulnificus Return to Top
- Vibrio vulnificus [193]
- Note: If V. vulnificus is suspected, treatment should be initiated immediately because antibiotics improve survival
- Preferred regimen: Doxycycline 100 mg PO/IV bid for 7-14 days AND Ceftazidime 1-2 g IV/IM q8h
- Note: A single agent regimen with a fluoroquinolone such as Levofloxacin, Ciprofloxacin or Gatifloxacin, has been reported to be at least as effective in an animal model as combination drug regimens with Doxycycline and a Cephalosporin
- Pediatric regimen: Doxycycline AND Fluoroquinolones; trimethoprim-sulfamethoxazole AND an Aminoglycoside
### Bacteria – Atypical Organisms
# Chlamydophila pneumoniae
- Chlamydophila pneumoniae Return to Top
- 1. Atypical pneumonia [194]
- 1.1 Adult
- Preferred regimen (1): Doxycycline 100 mg PO bid for 14-21 days
- Preferred regimen (2): Tetracycline 250 mg PO qid for 14-21 days
- Preferred regimen (3): Azithromycin 500 mg PO as a single dose, followed by 250 mg PO qd for 4 days
- Preferred regimen (4): Clarithromycin 500 mg PO bid for 10 days
- Preferred regimen (5): Levofloxacin 500 mg IV OR PO qd for 7 to 14 days
- Preferred regimen (6): Moxifloxacin 400 mg PO qd for 10 days.
- 1.2 Pediatric
- Preferred regimen (1): Erythromycin suspension PO 50 mg/kg/day for 10 to 14 days
- Preferred regimen (2): Clarithromycin suspension PO 15 mg/kg/day for 10 days
- Preferred regimen (3): Azithromycin suspension PO 10 mg/kg once on the first day, followed by 5 mg/kg qd daily for 4 days
- 2. Upper respiratory tract infection[195]
- 2.1 Bronchitis
- Antibiotic therapy for C. pneumoniae is not required.
- 2.2 Pharyngitis
- Antibiotic therapy for C. pneumoniae is not required.
- 2.3 Sinusitis
- Antibiotic therapy is advisable if symptoms remain beyond 7-10 days.
# Chlamydia trachomatis
- Chlamydia trachomatis Return to Top
- 1 Chlaymydial infections [196]
- 1.1 Chlamydial Infections in Adolescents and Adults
- Preferred regimen (1): Doxycycline 100 mg PO bid for 7 days
- Preferred regimen (2): Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
- Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days.
- Note: Patients should be instructed to refer their sex partners for evaluation, testing, and treatment if they had sexual contact with the patient during the 60 days preceding onset of the patient's symptoms or chlamydia diagnosis.
- 1.2 Chlamydial Infections in patients with HIV Infection
- Preferred regimen (1): Doxycycline 100 mg PO bid for 7 days
- Preferred regimen (2): Azithromycin 1 g PO in a single dose
- Preferred regimen (3): Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
- Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days.
- 1.3 Pregancy
- Preferred regimen: Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Amoxicillin 500 mg PO tid for 7 days
- Alternative regimen (2): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (3): Erythromycin base 250 mg PO qid for 14 days
- Alternative regimen (4): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (5): Erythromycin ethylsuccinate 400 mg PO qid for 14 days
- Note:Doxycycline, Ofloxacin, and Levofloxacin are contraindicated in pregnant women
- 1.4 Management of sex partners
- Preferred regimen (1): Doxycycline 100 mg PO bid for 7 days
- Preferred regimen (2): Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
- Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days.
- Note (1): Recent sex partners (i.e., persons having sexual contact with the infected patient within the 60 days preceding onset of symptoms or Chlamydia diagnosis) should be referred for evaluation, testing, and presumptive dual treatment.
- Note (2): If the patient’s last potential sexual exposure was >60 days before onset of symptoms or diagnosis, the most recent sex partner should be treated.
- Note (3): To avoid reinfection, sex partners should be instructed to abstain from unprotected sexual intercourse for 7 days after they and their sexual partner(s) have completed treatment and after resolution of symptoms, if present
- 2. Chlamydial infection among neonates
- 2.1 Ophthalmia Neonatorumcaused by C. trachomatis
- Preferred regimen: Erythromycin base or ethylsuccinate 50 mg/kg/ day PO qid for 14 days
- Alternative regimen: Azithromycin suspension 20 mg/kg /day PO qd for 3 days
- Note: The mothers of infants who have chlamydial infection and the sex partners of these women should be evaluated and treated.
- 2.2 Infant Pneumonia
- Preferred regimen: Erythromycin base or ethylsuccinate 50 mg/kg/ day PO qid for 14 days
- Alternative regimen: Azithromycin suspension 20 mg/kg /day PO qd for 3 days
- 3.Chlamydial infection among infants and childern
- 3.1 Infants and childern who weigh < 45 kg
- Preferred regimen: Erythromycin base or ethylsuccinate 50 mg/kg/ day PO qid for 14 days
- 3.2 Infants and childern who weigh ≥45 kg but who are aged <8 years
- Preferred regimen: Azithromycin 1 g PO in a single dose
- 3.3 Infants and childern aged ≥8 years
- Preferred regimen (1): Azithromycin 1 g PO in a single dose
- Preferred regimen (2): Doxycycline 100 mg PO bid for 7 days
- 4. Lymphogranuloma venereum (LGV) [197]
- Preferred regimen: Doxycycline 100 mg PO bid for 21 days
- Alternative regimen: Erythromycin base 500 mg PO qid for 21 days
- Note (1): Azithromycin 1 g PO once weekly for 3 weeks is probably effective based on its chlamydial antimicrobial activity. Fluoroquinolone-based treatments might also be effective, but extended treatment intervals are likely required.
- Note (2): Pregnant and lactating women should be treated with Erythromycin. Azithromycin might prove useful for treatment of LGV in pregnancy, but no published data are available regarding its safety and efficacy. Doxycycline is contraindicated in pregnant women.
- Note (3): Persons with both LGV and HIV infection should receive the same regimens as those who are HIV negative. Prolonged therapy might be required, and delay in resolution of symptoms might occur.
- Note (4): Persons who have had sexual contact with a patient who has LGV within the 60 days before onset of the patient’s symptoms should be examined and tested for urethral, cervical, or rectal chlamydial infection depending on anatomic site of exposure. They should be presumptively treated with a chlamydia regimen ( Azithromycin 1 g PO single dose OR Doxycycline 100 mg PO bid for 7 days).
# Chlamydophila psittaci
- Chlamydophila psittaci Return to Top
- 1. ' Psittacosis [198]
- 1.1 Adult
- Preferred regimen (1): Doxycycline 100 mg PO bid for 10-21 days
- Preferred regimen (2): Tetracycline 500 mg PO qid for 10-21 days
- Alternative regimen: Minocycline
- 1.2 Pediatric
- 1.2.1 Mild infection, Infants >3 months
- Preferred regimen: Azithromycin 10 mg/kg PO qd on day 1 THEN 5 mg/kg PO q24h for 4 days; (Maximum, 500 mg for 1st dose, 250 mg for subsequent doses)
- 1.2.2 Moderate-severe infection, Infants >3 months
- Preferred regimen: Azithromycin 10 mg/kg IV q24h for 2 days THEN 5 mg/kg PO qd for 3 days; (Maximum, 500 mg/dose IV; 250 mg/dose PO)
- 1.3 Pregnant Patients
- Preferred regimen: Azithromycin 500 mg PO on day 1 THEN by 250 mg qd on days 2-5 OR 500 mg IV as a single dose for at least 2 days, followed by 500 mg PO qd for 7- 10 days
# Coxiella burnetii
- Coxiella burnetii Return to Top
- 1. Acute Q fever [199]
- 1.1 Adults
- Preferred Regimen: Doxycycline 100 mg PO bid for 14 days
- 1.2 Pediatric
- 1.2.1 ≥ 8 years old
- Preferred regimen:Doxycycline 2.2 mg/kg PO bid for 14 days (Maximum, 100 mg per dose)
- 1.2.2 < 8 years old with high risk criteria
- Preferred regimen:Doxycycline 2.2 mg/kg PO bid for 14 days (Maximum, 100 mg per dose)
- 1.2.3 < 8 years old with mild or uncomplicated illness
- Preferred regimen:Doxycycline 2.2 mg/kg PO bid for 5 days (Maximum, 100 mg per dose)
- Alternative regimen: (If patient remains febrile past 5 days of treatment) Trimethoprim/Sulfamethoxazole 4-20 mg/kg PO bid for 14 days (Maximum, 800 mg per dose)
- 1.3 Pregnant women
- Preferred regimen: Trimethoprim/sulfamethoxazole 160 mg/800 mg PO bid
- Note: Should be given throughout pregnancy
- 2. Chronic Q fever
- 2.1 Endocarditis or vascular infection
- Preferred regimen: Doxycycline 100 mg PO bid AND hydroxychloroquine 200 mg PO tid for ≥18 months
- Note: Childern and pregnant women consultation recommended
- 2.2 Non-cardiac organ disease
- Preferred regimen: Doxycycline 100 mg PO bid AND hydroxychloroquine 200 mg PO tid
- Note: childern and pregnant women consultation recommended
- 2.3 Postpartumwith serologic profile for chronic Q fever
- Preferred regimen: Doxycycline 100 mg PO bid AND hydroxychloroquine 200 mg PO tid for 12 months
- Note (1): Women should only be treated postpartum if serologic titers remain elevated >12 months after delivery (immunoglobulin G phase I titer ≥1:1024); Women treated during pregnancy for acute Q fever should be monitored similarly to other patients who are at high risk for progression to chronic disease (e.g., serologic monitoring at 3, 6, 12, 18, and 24 months after delivery)
- Note (2): Post-Q fever fatigue syndrome- no current recommendation
# Mycoplasma pneumoniae
- Mycoplasma pneumoniae Return to Top
- 1. Atypical pneumonia[200][201]
- Preferred regimen (1): Azithromycin 500 mg PO qd on day 1 and 250 mg PO qd on days 2 to 5
- Preferred regimen (2): Clarithromycin 500 mg PO qd for 14 days
- Preferred regimen (3): Moxifloxacin 400 mg PO qd for 14 days
- Preferred regimen (4): Levofloxacin 750 mg PO qd for 14 days
- Alternative regimen : Doxycycline 100 mg PO bid for 14 days
# Mycoplasma genitalium
- Mycoplasma genitalium Return to Top
- 1. Urethritis and cervicitis[202]
- Preferred regimen (macrolide-susceptible strains) (1): Azithromycin 1 g PO as a single dose
- Preferred regimen (macrolide-susceptible strains) (2): Azithromycin 500 mg PO as a dose followed by 250 mg PO qd for 4 days
- Preferred regimen (for patients with previous treatment failures): Moxifloxacin 400 mg PO qd for 7–14 days
- 2. Pelvic inflammatory disease (PID)[203]
- Preferred regimen: Moxifloxacin 400 mg PO qd for 14 days
- 3. Specific considerations[204]
- 3.1 Management of sex partners
- Sex partners should be managed according to guidelines for patients with nongonococcal urethritis, cervicitis, and pelvic inflammatory disease.
- 3.2 HIV infection
- Persons who have an M. genitalium infection and HIV infection should receive the same treatment regimen as those who are HIV negative.
### Bacteria – Miscellaneous
- Gardnerella vaginalis Return to Top
- 1.Bacterial Vaginosis[205]
- Gardnerella vaginalis is one of the anaerobic bacteria causing Bacterial Vaginosis,which is a polymicrobial clinical syndrome
- Preferred regimen (1): Metronidazole 500 mg PO bid for 7 days
- Preferred regimen (2): Metronidazole gel 0.75%, one full applicator (5 g) intravaginally, qd for 5 days
- Preferred regimen (3): Clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7 days
- Alternative regimen (1): Tinidazole 2 g PO qd for 2 days
- Alternative regimen (2): Tinidazole 1 g PO qd for 5 days
- Alternative regimen (3): Clindamycin 300 mg PO bid for 7 days
- Alternative regimen (4): Clindamycin ovules 100 mg intravaginally once at bedtime for 3 days
- Note: Clindamycin ovules use an oleaginous base that might weaken latex or rubber products (e.g., condoms and vaginal contraceptive diaphragms). Use of such products within 72 hours following treatment with clindamycin ovules is not recommended.
- 2. Management of Sex Partners
- Routine treatment of sex partners is not recommended.
- 3. Special Considerations
- 3.1 Allergy, Intolerance, or Adverse Reactions
- Intravaginal Clindamycin cream is preferred in case of allergy or intolerance to Metronidazole or Tinidazole. Intravaginal Metronidazole gel can be considered for women who are not allergic to Metronidazole but do not tolerate oral metronidazole. It is advised to avoid consuming alcohol during treatment with nitroimidazoles. To reduce the possibility of a disulfiram-like reaction, abstinence from alcohol use should continue for 24 hours after completion of metronidazole or 72 hours after completion of tinidazole.
- 3.2 Pregnancy
- Preferred regimen (1): Metronidazole 500 mg PO bid for 7 days
- Preferred regimen (2): Metronidazole gel 0.75%, one full applicator (5 g) intravaginally, qd for 5 days
- Note: Tinidazole should be avoided during pregnancy
- 3.3 HIV Infection
- Women with HIV who have BV should receive the same treatment regimen as those who do not have HIV infection.
- Eikenella corrodens Return to Top
- Bordetella pertussis Return to Top
- Bartonella Return to Top
- Stenotrophomonas maltophilia Return to Top
- Acinetobacter baumannii Return to Top
- Yersinia enterocolitica Return to Top
- Yersinia enterocolitica infection (yersiniosis)
- 1. Enterocolitis and mesenteric adenitis[206]
- Preferred regimen: Enterocolitis and adenitis usually self-limited. No antibiotic therapy is required unless clinically indicated.
- 2. Septicemia[207]
- Preferred regimen (1): Doxycycline 100 mg IV q12h AND Tobramycin 5 mg/kg IV q24h
- Preferred regimen (2): Doxycycline 100 mg IV q12h AND Gentamicin 5 mg/kg IV q24h
- Alternative regimen (1): Ciprofloxacin 500 mg IV q12h
- Alternative regimen (2): TMP-SMX TMP 8 mg/kg/day and SMX 40 mg/kg/day IV q12h
- 3. Peritonitis[208]
- Preferred regimen: Fluoroquinolones
- Yersinia pestis Return to Top
- Yersinia pseudotuberculosis Return to Top
### Bacteria – Anaerobic Gram-Negative Bacilli
- Bacteroides fragilis Return to Top
- Bacteroides fragilis [209]
- 1. Monotherapy
- Preferred regimen (1): Imipenem
- Preferred regimen (2): Ertapenem
- Preferred regimen (3): Meropenem
- Preferred regimen (4): Doripenem 0.5-1.0 g IV q6h
- Preferred regimen (5): Piperacillin-tazobactam 3.375 g IV q6h
- Preferred regimen (6): Ampicillin-sulbactam 1-2 g IV q6h
- Preferred regimen (7): Tigecycline 100 mg IV THEN 50 mg IV q12h
- 2. Combination therapy
- Preferred regimen: Metronidazole 0.75-1.0 g IV q12h AND Cefotaxime 1.5-2 g IV q6h OR Aztreonam 1-2 g IV q8h OR Ceftriaxone 1 g IV q12h
- Fusobacterium necrophorum Return to Top
### Fungi
- Aspergillosis Return to Top[210]
- 1. Invasive pulmonary aspergillosis
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd[211][210]
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- 2. Invasive sinus aspergillosis
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd[211][210]
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- 3. Tracheobronchial aspergillosis
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd[211][210]
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- 4. Chronic necrotizing pulmonary aspergillosis
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd[211][210]
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- 5. Aspergillosis of the CNS
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd[211][210]
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- Note: There are drug interactions with anticonvulsant therapy.
- 6. Aspergillus infections of the heart (endocarditis, pericarditis, and myocarditis)
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd[211][210]
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- Note: endocardial lesions generally require surgical treatment. Aspergillus pericarditis usually requires pericardiectomy.
- 7. Aspergillus osteomyelitis and septic arthritis
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd[211][210]
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- Note: Surgical resection of devitalized bone and cartilage is important for curative intent.
- 8. Aspergillus infections of the eye (endophthalmitis and keratitis)
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd[211][210]
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- Note: Topical therapy is indicated for keratitis, ophthalmologic intervention and management is recommended for all forms of ocular infection. Systemic therapy may be beneficial when treating aspergillus endophthalmitis.
- 9. Cutaneous aspergillosis
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd[211][210]
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- Note: Surgical resection is indicated when feasible.
- 10. Aspergillus peritonitis
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd[211][210]
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- 11. Prophylaxis against invasive aspergillosis
- Preferred regimen: Posaconazole PO 200 mg tid
- Alternative regimen: (1) Itraconazole 200 mg IV bid for 2 days then 200 mg IV qd OR Itraconazole PO 200mg bid
- Alternative regimen: (2) Micafungin 50 mg/day PO qd
- 12. Aspergilloma
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen: Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- 13. Chronic cavitary pulmonary aspergillosis
- Preferred regimen: Voriconazole 6 mg/kg IV q12h single dose, THEN 4 mg/kg IV q12h or PO 200 mg q12h
- Alternative regimen (1): Liposomal Amphotericin B (L-AMB) 3–5 mg/kg/day IV qd
- Alternative regimen (2): Amphotericin B lipid complex (ABLC) 5 mg/ kg/day IV qd
- Alternative regimen (3): Caspofungin 70 mg IV single dose THEN 50 mg/day IV qd
- Alternative regimen (4): Posaconazole 200 mg PO qid if patient is critical, then 400 mg PO bid after stabilization of the disease.
- Alternative regimen (5): Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (6): Micafungin 100–150 mg/day PO qd[211][210]
- Note: Micafungin has been evaluated as salvage therapy for invasive aspergillosis but remains investigational for this indication, and the dosage has not been established.
- Note: long-term therapy might be needed.
- 14. Allergic bronchopulmonary Itraconazole aspergillosis
- Preferred regimen: Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Alternative regimen (1): Voriconazole PO 200 mg bid
- Alternative regimen (2): Posaconazole PO 400 mg bid
- Note: Corticosteroids are a cornerstone of the therapy.
- 15. Allergic aspergillus sinusitis
- Preferred regimen: None or Itraconazole dosage depends upon formulation - 600 mg/day PO for 3 days, THEN 400 mg/day PO OR 200 mg q12h IV for 2 days, THEN 200 mg IV qd
- Note: Few data available for other agents.
- 16. Relative indications for surgical treatment of invasive aspergillosis
- Pulmonary lesion in proximity to great vessels or pericardium;
- Pericardial infection;
- Invasion of chest wall from contiguous pulmonary lesion;
- Aspergillus empyema;
- Persistent hemoptysis from a single cavitary lesion;
- Infection of skin and soft tissues;
- Infected vascular catheters and prosthetic devices;
- Endocarditis;
- Osteomyelitis;
- Sinusitis;
- Cerebral lesions.
- Blastomycosis Return to Top
- Blastomycosis[212]
- 1. Mild to moderate pulmonary blastomycosis
- Preferred regimen: Itraconazole 200 mg PO qd or bid for 6–12 months
- Note: Oral Itraconazole, 200 mg tid PO for 3 days and THEN 200 mg PO qd or bid for 6–12 months
- 2. Moderately severe to severe pulmonary blastomycosis
- Preferred regimen (1): Lipid Amphotericin B 3–5 mg/kg IV qd for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
- Preferred regimen (2): Amphotericin B deoxycholate 0.7–1 mg/kg IV qd for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
- Note: Oral Itraconazole, 200 mg tid PO for 3 days THEN 200 mg PO bid, for a total of 6–12 months
- 3. Mild to moderate disseminated blastomycosis
- Preferred regimen: Itraconazole 200 mg PO qd or bid for 6–12 months
- Note (1): Treat osteoarticular disease for 12 months
- Note (2): Oral Itraconazole, 200 mg PO tid for 3 days THEN 200 mg PO bid, for 6–12 months
- 4. Moderately severe to severe disseminated blastomycosis
- Preferred regimen (1): Lipid Amphotericin B 3–5 mg/kg IV qd, for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
- Preferred regimen (2): Amphotericin B deoxycholate 0.7–1 mg/kg IV qd, for 1–2 weeks AND Itraconazole 200 mg PO bid for 6–12 months
- Note: oral Itraconazole, 200 mg PO tid for 3 days THEN 200 mg PO bid, for 6–12 months
- 5. CNS disease
- Preferred regimen: Lipid Amphotericin B 5 mg/kg IV qd for 4–6 weeks AND an oral azole for at least 1 year
- Note (1): Step-down therapy can be with Fluconazole, 800 mg/day PO qd or bid OR Itraconazole, 200 mg bid or tid OR voriconazole, 200–400 mg bid.
- Note (2): Longer treatment may be required for immunosuppressed patients.
- 6. Immunosuppressed patients
- Preferred regimen (1): Lipid Amphotericin B 3–5 mg/kg IV qd, for 1–2 weeks, AND Itraconazole, 200 mg PO bid for 12 months
- Preferred regimen (2): Amphotericin B deoxycholate, 0.7–1 mg/kg IV qd, for 1–2 weeks, AND Itraconazole, 200 mg PO bid for 12 months
- Note (1): Oral Itraconazole, 200 mg PO tid for 3 days THEN 200 mg PO bid, for 12 months
- Note (2): Life-long suppressive treatment may be required if immunosuppression cannot be reversed.
- 7. Pregnant women
- Preferred regimen: Lipid Amphotericin B 3–5 mg/kg IV qd
- Note (1): Azoles should be avoided because of possible teratogenicity
- Note (2): If the newborn shows evidence of infection, treatment is recommended with Amphotericin B deoxycholate, 1.0 mg/kg IV qd
- 8. Children with mild to moderate disease
- Preferred regimen: Itraconazole 10 mg/kg PO qd for 6–12 months
- Note: Maximum dose 400 mg/day
- 9. Children with moderately severe to severe disease
- Preferred regimen (1): Amphotericin B deoxycholate 0.7–1 mg/kg IV qd for 1–2 weeks AND Itraconazole 10 mg/kg PO qd to a maximum of 400 mg/day for 6–12 months
- Preferred regimen (2): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg IV qd for 1–2 weeks AND Itraconazole 10 mg/kg PO qd to a maximum of 400 mg/day for 6–12 months
- Note: Children tolerate Amphotericin B deoxycholate better than adults do.
- Paracoccidioidomycosis Return to Top
- Preferred regimen (1): [213]
- Adults: Itraconazole 200 mg/day PO
- Children: Itraconazole (<30/kg and >5 yr) 5-10 mg/kg/day PO
- Note: Treatment duration based on organ involvement:
- Mild involvement: 6-9 months
- Moderate involvement: 12-18 months
- Preferred regimen (2): [213]
- Adults Trimethoprim/sulfamethoxazole (TMP/SMX) TMP: 160-240 mg/day PO/IV, SMX: 800-1200 mg/day PO/IV bid
- Children Trimethoprim/sulfamethoxazole (TMP/SMX) TMP: 8-10 mg/kg PO/IV, SMX: 40-50 mg/kg PO/IV, bid
- Note (1): Treatment duration based on organ involvement:
- Minor involvement: 12 months
- Moderate involvement: 18-24 months
- Note (2): Preferred treatment in children due to larger experience.
- Note (3): Preferred in IV formulation in severe forms of the disease - 2 ampules IV tid until patient condition improves so that oral medication can be given.
- Preferred regimen (3): Amphotericin B deoxycholate 1 mg/kg/day IV until patient improves and can be treated by the oral route.[213]
- Note: Preferred in severe forms of the disease.[213]
- Alternative regimen (4): Ketoconazole 200-400 mg/day PO for 9-12 months[214]
- Alternative regimen (5): Voriconazole initial dose 400 mg PO/IV q12h for one day, then 200 mg q12h for 6 months[215]
- Note: Diminish the dose to 50% if weight is <40 kg.
- Candidiasis Return to Top
- 1. Candidemia[216]
- 1.1. Nonneutropenic adults
- Preferred regimen (1): Fluconazole 800 mg (12 mg/kg) loading dose, THEN 400 mg (6 mg/kg) qd
- Preferred regimen (2): Caspofungin 70 mg loading dose, THEN 50 mg qd
- Preferred regimen (3): Micafungin 100 mg qd
- Preferred regimen (4): Anidulafungin 200 mg loading dose, THEN 100 mg qd
- Alternative regimen (1): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg qd
- Alternative regimen (2): Amphotericin B deoxycholate(AmB-d) 0.5–1.0 mg/kg qd
- Alternative regimen (3): Voriconazole 400 mg (6 mg/kg) PO/IV bid for 2 doses, THEN 200 mg (3 mg/kg) bid
- Note (1): Echinocandin includes Anidulafungin, Micafungin and Caspofungin.
- Note (2): Choose an echinocandin for moderately severe to severe illness and for patients with recent azole exposure.
- Note (3): Treat for 14 days after first negative blood culture result and resolution of signs and symptoms associated with candidemia.
- Note (4): Ophthalmological examination recommended for all patients.
- 1.2. Neutropenic patients
- Preferred regimen (1): Caspofungin 70 mg loading dose, THEN 50 mg qd
- Preferred regimen (2): Micafungin 100 mg qd
- Preferred regimen (3): Anidulafungin 200 mg loading dose, THEN 100 mg qd
- Preferred regimen (4): Lipid formulation of Amphotericin B (LFAmB) 3–5 mg/kg qd
- Alternative regimen (1): Fluconazole 800 mg (12 mg/kg) loading dose, THEN 400 mg (6 mg/kg) qd
- Alternative regimen (2): Voriconazole 400 mg (6 mg/kg) bid for 2 doses, THEN 200 mg (3 mg/kg) bid
- Note: Fluconazole is recommended for patients without recent azole exposure and who are not critically ill.
- 2. Suspected candidiasis treated with empiric antifungal therapy[216]
- 2.1. Nonneutropenic patients
- Preferred regimen (1): Fluconazole 800 mg (12 mg/kg) loading dose, THEN 400 mg (6 mg/kg) daily
- Preferred regimen (2): Caspofungin 70 mg loading dose, THEN 50 mg daily
- Preferred regimen (3): Micafungin 100 mg daily
- Preferred regimen (4): Anidulafungin 200 mg loading dose, THEN 100 mg daily
- Alternative regimen (1): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily
- Alternative regimen (2): Amphotericin B deoxycholate(AmB-d) 0.5–1.0 mg/kg daily
- Note (1): Duration of therapy is uncertain, but should be discontinued if cultures and/or serodiagnostic tests have negative results.
- Note (2): Echinocandin includes Anidulafungin, Micafungin and Caspofungin.
- Note (3): Echinocandin is preferred for patients with recent azole exposure, patients with moderately severe to severe illness, or patients who are at high risk of infection due to C. glabrata or C. krusei.
- Note (4): Empirical antifungal therapy should be considered in critically ill patients with risk factors for invasive candidiasis and no other known cause of fever and should be based on clinical assessment of risk factors, serologic markers for invasive candidiasis, and/or culture data from nonsterile sites
- 2.2. Neutropenic patients
- Preferred regimen (1): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily
- Preferred regimen (2): Caspofungin 70 mg loading dose, THEN 50 mg daily
- Preferred regimen (3): Voriconazole 400 mg (6 mg/kg) bid for 2 doses, THEN 200 mg (3 mg/kg) bid
- Alternative regimen (1): Fluconazole 800 mg (12 mg/kg) loading dose, THEN 400 mg (6 mg/kg) daily
- Alternative regimen (2): Itraconazole 200 mg (3 mg/ kg) bid
- Note (1): In most neutropenic patients, it is appropriate to initiate empiric antifungal therapy after 4 days of persistent fever despite antibiotics.
- Note (2): Do not use an azole in patients with prior azole prophylaxis.
- 3. Urinary tract infection[216]
- 3.1. Asymptomatic cystitis
- Preferred regimen: Therapy not usually indicated, unless patients are at high risk (e.g., neonates and neutropenic adults) or undergoing urologic procedures.
- Note (1): Elimination of predisposing factors recommended
- Note (2): For high-risk patients, treat as for disseminated candidiasis
- Note (3): For patients undergoing urologic procedures, fluconazole, 200–400 mg (3–6 mg/kg) daily or Amphotericin B deoxycholate (AmB-d) 0.3–0.6 mg/kg daily for several days before and after the procedure.
- 3.2. Symptomatic cystitis
- Preferred regimen: Fluconazole 200 mg (3 mg/kg) daily for 2 weeks
- Alternative regimen (1): Amphotericin B deoxycholate(AmB-d) 0.3–0.6 mg/kg for 1–7 days
- Alternative regimen (2): Flucytosine 25 mg/kg qid for 7–10 days
- Note: Amphotericin B deoxycholate (AmB-d) bladder irrigation is recommended only for patients with refractory fluconazole -resistant organisms (e.g., Candida krusei and Candida glabrata).
- 3.3 Pyelonephritis
- Preferred regimen (1): Fluconazole 200–400 mg (3–6 mg/kg) daily for 2 weeks
- Alternative regimen (1): Amphotericin B deoxycholate(AmB-d) 0.5–0.7 mg/kg daily ± Flucytosine (5-FC) 25 mg/kg qid
- Alternative regimen (2): Flucytosine (5-FC) 25 mg/kg qid for 2 weeks
- Note: For patients with pyelonephritis and suspected disseminated candidiasis, treat as for candidemia.
- 4. Urinary fungus balls[216]
- Preferred regimen (1): Surgical removal strongly recommended
- Preferred regimen (2): Fluconazole 200–400 mg (3–6 mg/kg) daily
- Preferred regimen (3): Amphotericin B deoxycholate(AmB-d) 0.5–0.7 mg/kg daily ± Flucytosine (5-FC) 25 mg/kg qid
- Note (1): Local irrigation with Amphotericin B deoxycholate(AmB-d) may be a useful adjunct to systemic antifungal therapy.
- Note (2): Treatment duration should be until symptoms have resolved and urine cultures no longer yield Candida species.
- 5. Vulvovaginal candidiasis[216]
- Preferred regimen (1): Butoconazole 2% cream 5 g intravaginally for 3 days
- Preferred regimen (2): Butoconazole 2% cream 5 g (butoconazole1-sustained release), single intravaginal application
- Preferred regimen (3): Clotrimazole 1% cream 5 g intravaginally for 7–14 days
- Preferred regimen (4): Clotrimazole 100-mg vaginal tablet for 7 days
- Preferred regimen (5): Clotrimazole 100-mg vaginal tablet, 2 tablets for 3 days
- Preferred regimen (6): Miconazole 2% cream 5 g intravaginally for 7 days
- Preferred regimen (7): Miconazole 100-mg vaginal suppository, 1 suppository for 7 days
- Preferred regimen (8): Miconazole 200-mg vaginal suppository, 1 suppository for 3 days
- Preferred regimen (9): Miconazole 1200-mg vaginal suppository, 1 suppository for 1 day
- Preferred regimen (10): Nystatin 100,000-unit vaginal tablet, 1 tablet for 14 days
- Preferred regimen (11): Tioconazole 6.5% ointment 5 g intravaginally in a single application
- Preferred regimen (12): Terconazole 0.4% cream 5 g intravaginally for 7 days
- Preferred regimen (13): Terconazole 0.4% cream 5 g intravaginally for 3 days
- Preferred regimen (14): Terconazole 80-mg vaginal suppository, 1 suppository for 3 days
- Preferred regimen (15): Fluconazole 150 mg single dose for uncomplicated vaginitis
- Note: For recurring Candida Vulvovaginal candidiasis (VVC), 10–14 days of induction therapy with a topical or oral azole, followed by fluconazole at a dosage of 150 mg once per week for 6 months, is recommended
- 6. Chronic disseminated candidiasis[216]
- Preferred regimen (1): Fluconazole 400 mg (6 mg/kg) daily for stable patients
- Preferred regimen (2): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily for severely ill patients
- Preferred regimen (3): Amphotericin B deoxycholate(AmB-d) 0.5–0.7 mg/kg daily for severely ill patients
- Alternative regimen (1): Caspofungin 70 mg loading dose, THEN 50 mg daily, followed by oral Fluconazole when clinically appropriate
- Alternative regimen (2): Micafungin 100 mg daily, followed by oral Fluconazole when clinically appropriate
- Alternative regimen (3): Anidulafungin 200 mg loading dose, THEN 100 mg daily, followed by oral Fluconazole when clinically appropriate
- Note (1): Transition from Lipid formulation of amphotericin B(LFAmB) or Amphotericin B deoxycholate(AmB-d) to fluconazole is favored after several weeks in stable patients.
- Note (2): Duration of therapy is until lesions have resolved (usually months) and should continue through periods of immunosuppression (e.g., chemotherapy and transplantation).
- Note (3): Therapy should be continued for weeks to months, until calcification occurs or lesions resolve.
- 7. Candida osteoarticular infection[216]
- 7.1. Osteomyelitis
- Preferred regimen (1): Fluconazole 400 mg (6 mg/kg) daily for 6–12 months
- Preferred regimen (2): Lipid formulation of amphotericin B(LFAmB) 3–5 mg/kg daily for at least 2 weeks, then Fluconazole 400 mg daily for 6–12 months
- Alternative regimen (1): Caspofungin 70 mg loading dose, THEN 50 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily for 6–12 months
- Alternative regimen (2): Micafungin 100 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily for 6–12 months
- Alternative regimen (3): Anidulafungin 200 mg loading dose, THEN 100 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily for 6–12 months
- Alternative regimen (4): Amphotericin B deoxycholate(AmB-d) 0.5–1.0 mg/kg daily followed by Fluconazole at a dosage of 400 mg daily for 6–12 months
- Note (1): Duration of therapy usually is prolonged (6–12 months)
- Note (2): Surgical debridement is frequently necessary
- 7.2. Septic arthritis
- Preferred regimen (1): Fluconazole 400 mg (6 mg/kg) for at least 6 weeks
- Preferred regimen (2): Lipid formulation of amphotericin B (LFAmB) 3–5 mg/kg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily
- Alternative regimen (1): Caspofungin 70 mg loading dose, THEN 50 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily
- Alternative regimen (2): Micafungin 100 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily
- Alternative regimen (3): Anidulafungin 200 mg loading dose, THEN 100 mg daily for at least 2 weeks followed by Fluconazole at a dosage of 400 mg daily
- Note (1): Duration of therapy usually is for at least 6 weeks, but few data are available.
- Note (2): Surgical debridement is recommended for all cases.
- Note (3): For infected prosthetic joints, removal is recommended for most cases.
- 8. CNS candidiasis[216]
- Preferred regimen (1): Lipid formulation of amphotericin B(LFAmB) at a dosage of 3–5 mg/kg daily ± Flucytosine at a dosage of 25 mg/kg qid for several weeks followed by Fluconazole 400–800 mg (6–12 mg/kg) daily
- Alternative regimen (1): Fluconazole 400–800 mg (6–12 mg/ kg) daily for patients unable to tolerate Lipid formulation of amphotericin B (LFAmB)
- Note (1): Treat until all signs and symptoms, CSF abnormalities, and radiologic abnormalities have resolved.
- Note (2): Removal of intraventricular devices is recommended.
- 9. Candida endophthalmitis[216]
- Preferred regimen (1): Amphotericin B deoxycholate(AmB-d) 0.7–1 mg/kg AND Flucytosine 25 mg/ kg qid
- Preferred regimen (2): Fluconazole 400–800 mg daily (loading dose of 12 mg/kg then 6–12 mg/kg daily) is an acceptable alternative for less severe endophthalmitis
- Alternative regimen (1): Lipid formulation of amphotericin B(LFAmB) at a dosage of 3–5 mg/kg daily
- Alternative regimen (2): Voriconazole 6 mg/kg q12h for 2 doses, then 3–4 mg/kg q12h
- Alternative regimen (3): Caspofungin 70 mg loading dose, THEN 50 mg daily
- Alternative regimen (4): Micafungin 100 mg daily
- Alternative regimen (5): Anidulafungin 200 mg loading dose, THEN 100 mg daily
- Note (1): Alternative therapy is recommended for patients intolerant of or experiencing failure of Amphotericin B and Flucytosine therapy
- Note (2): Duration of therapy is at least 4–6 weeks as determined by repeated examinations to verify resolution.
- Note (3): Diagnostic vitreal aspiration should be done if etiology unknown.
- Note (4): Fluconazole at a dosage of 400–800 mg daily (loading dose of 12 mg/kg then 6–12 mg/kg daily) is an acceptable alternative for less severe endophthalmitis
- Note (5): Surgical intervention for patients with severe endophthalmitis or vitreitis
- 10. Candida infection of the cardiovascular system[216]
- 10.1. Endocarditis
- Preferred regimen (1): Lipid formulation of amphotericin B(LFAmB) at a dosage of 3–5 mg/kg daily ± Flucytosine at a dosage of 25 mg/kg qid
- Preferred regimen (2): Amphotericin B deoxycholate AmB-d 0.6–1 mg/kg daily ± Flucytosine 25 mg/kg qid
- Preferred regimen (3): Caspofungin 50–150 mg daily
- Preferred regimen (4): Micafungin 100–150 mg daily
- Preferred regimen (5): Anidulafungin 100–200 mg daily
- Alternative regimen (1): Step-down therapy to Fluconazole 400–800 mg (6–12 mg/kg) daily for susceptible organism in stable patient with negative blood culture results
- Note (1): Valve replacement is strongly recommended.
- Note (2): For those who are unable to undergo surgical removal of the valve, chronic suppression with fluconazole 400–800 mg (6–12 mg/kg) daily is recommended.
- Note (3): Lifelong suppressive therapy for prosthetic valve endocarditis if valve cannot be replaced is recommended.
- 10.2. Pericarditis or myocarditis
- Preferred regimen (1): Lipid formulation of amphotericin B (LFAmB) at a dosage of 3–5 mg/kg daily
- Preferred regimen (2): Fluconazole 400–800 mg (6–12 mg/kg) daily
- Preferred regimen (3): Caspofungin 50–150 mg daily
- Preferred regimen (4): Micafungin 100–150 mg daily
- Preferred regimen (5): Anidulafungin 100–200 mg daily
- Alternative regimen (1): After stable, step-down therapy to Fluconazole 400–800 mg (6–12 mg/kg) daily
- Note(1): Therapy is often for several months, but few data are available
- Note(2): A pericardial window or pericardiectomy is recommended.
- 10.3. Suppurative thrombophlebitis
- Preferred regimen (1): Lipid formulation of amphotericin B (LFAmB) at a dosage of 3–5 mg/kg daily
- Preferred regimen (2): Fluconazole 400–800 mg (6–12 mg/kg) daily
- Preferred regimen (3): Caspofungin 50–150 mg daily
- Preferred regimen (4): Micafungin 100–150 mg daily
- Preferred regimen (5): Anidulafungin 100–200 mg daily
- Alternative regimen (1): After stable, step-down therapy to Fluconazole 400–800 mg (6–12 mg/kg) daily
- Note(1): Surgical incision and drainage or resection of the vein is recommended if feasible.
- Note(2): Treat for at least 2 weeks after candidemia has cleared.
- 10.4. Infected pacemaker, ICD, or VAD
- Preferred regimen (1): Lipid formulation of amphotericin B(LFAmB) at a dosage of 3–5 mg/kg daily ± Flucytosine at a dosage of 25 mg/kg qid
- Preferred regimen (2): Amphotericin B deoxycholate (AmB-d) 0.6–1 mg/kg daily ± Flucytosine 25 mg/kg qid
- Preferred regimen (3): Caspofungin 50–150 mg daily
- Preferred regimen (4): Micafungin 100–150 mg daily
- Preferred regimen (5): Anidulafungin 100–200 mg daily
- Alternative regimen (1): Step-down therapy to Fluconazole 400–800 mg (6–12 mg/kg) daily for susceptible organism in stable patient with negative blood culture results
- Note(1): Removal of pacemakers and ICDs strongly recommended.
- Note(2): Treat for 4–6 weeks after the device removed.
- Note(3): For VAD that cannot be removed, chronic suppressive therapy with fluconazole is recommended.
- 11. Neonatal candidiasis[216]
- Preferred regimen (1): Amphotericin B deoxycholate (AmB-d) 1 mg/kg daily for 3 weeks
- Preferred regimen (2): Fluconazole 12 mg/kg daily for 3 weeks
- Alternative regimen (1): Lipid formulation of amphotericin B (LFAmB) 3–5 mg/kg daily for 3 weeks
- Note (1): A lumbar puncture and dilated retinal examination should be performed on all neonates with suspected invasive candidiasis.
- Note (2): Intravascular catheter removal is strongly recommended.
- Note (3): Duration of therapy is at least 3 weeks.
- Note (4): Lipid formulation of amphotericin B (LFAmB) used only if there is no renal involvement.
- Note (5): Echinocandins should be used with caution when other agents cannot be used.
- 12. Candida isolated from respiratory secretions[216]
- Preferred regimen (1): Therapy not recommended
- Note (1): Candida lower respiratory tract infection is rare and requires histopathologic evidence to confirm a diagnosis.
- 13. Nongenital mucocutaneous candidiasis[216]
- 13.1. Oropharyngeal
- Preferred regimen (1): Clotrimazole troches 10 mg 5 times daily
- Preferred regimen (2): Nystatin suspension at a concentration of 100,000 U/mL and a dosage of 4–6 mL qid OR 1–2 Nystatin pastilles (200,000 U each) administered qid for 7–14 days
- Preferred regimen (3): Fluconazole 100–200 mg PO (3 mg/kg) daily for 7–14 days
- Alternative regimen (1): Itraconazole solution 200 mg daily
- Alternative regimen (2): Posaconazole suspension at a dosage of 400 mg twice daily for 3 days, THEN 400 mg daily for up to 28 days
- Alternative regimen (3): Voriconazole 200 mg bid
- Alternative regimen (4): Amphotericin B deoxycholate (AmB-d) 1-mL oral suspension administered at a dosage of 100 mg/mL qid
- Alternative regimen (5): Caspofungin 70 mg IV loading dose, THEN 50 mg daily
- Alternative regimen (6): Micafungin 100 mg IV daily
- Alternative regimen (7): Anidulafungin 200 mg IV loading dose, THEN 100 mg daily
- Alternative regimen (8): Amphotericin B deoxycholate (AmB-d) 0.3 mg/kg daily
- Note(1): Fluconazole is recommended for moderate-to-severe disease, and topical therapy with clotrimazole or nystatin is recommended for mild disease.
- Note(2): Treat uncomplicated disease for 7–14 days.
- Note(3): For refractory disease, itraconazole, voriconazole, posaconazole, or AmB suspension is recommended.
- 13.2. Esophageal
- Preferred regimen (1): Fluconazole 200–400 mg (3–6 mg/kg) PO daily
- Preferred regimen (2): Caspofungin 70 mg IV loading dose, THEN 50 mg daily
- Preferred regimen (3): Micafungin 100 mg IV daily
- Preferred regimen (4): Anidulafungin 200 mg IV loading dose, THEN 100 mg daily
- Preferred regimen (4): AmB-d 0.3–0.7 mg/kg daily
- Alternative regimen (1): Itraconazole oral solution 200 mg daily
- Alternative regimen (2): Posaconazole 400 mg bid
- Alternative regimen (3): Voriconazole 200 mg bid
- Note(1): Oral fluconazole is preferred.
- Note(2): For patients unable to tolerate an oral agent,Fluconazole IV, an echinocandin, or AmB-d is appropriate.
- Note(3): Treat for 14–21 days.
- Note(4): For patients with refractory disease, the alternative therapy as listed or AmB-d or an echinocandin is recommended.
- Chromoblastomycosis Return to Top[217]
- Preferred regimen: Itraconazole 200-400 mg PO q24h OR 400 mg pulse therapy once daily for 1 week monthly for 6-12 months
- Note: Pulse therapy reduces cost but it is questionable if it produces resistance to the drug.
- Alternative regimen (1): Terbinafine 500-1000 mg PO qd for 6-12 months
- Alternative regimen (2): Posaconazole 800 mg PO qd for 6-12 months
- Alternative regimen (3): 5-fluorocytosine 100-150 mg/kg/day PO qd for 6-12 months
- Note: This disease has a low cure ratio and high relapse ratio. Physical treatment is needed to achieve better results:
- Cryosurgery with liquid nitrogen - most used physical therapy, it's used in localized lesions and it has a very good treatment response, probably achieved by immune mechanisms since fungi are eliminated from lesions as late as 1-2 weeks after the therapy.
- Thermotherapy - used in conjunction with systemic therapy, was developed by Japanese authors and consists in placing "pocket warmers" in the lesions for 24h/day for some months, as the fungi is sensible to heat.
- Laser vaporization - studied in Germany as an alternative therapy, reported to successfully treat relapsing lesions.
- Coccidioidomycosis Return to Top
- 1. Primary pulmonary infection [218]
- 1.1 Indications for antifungal therapy
- Immunosupression (AIDS, therapy with high dose corticosteroids, receiptients of TNF-alpha, receiptients of an organ transplant)
- Diabetes
- Preexisting cardiomyopathy
- Pregnancy (third trimester)
- Filipino or African
- Weight loss of > 10%
- Intense night sweats persisting longer than 3 weeks
- Infiltrates involving more than one-half of one lung or portions of both lungs
- Prominent or persistent hilar adenopathy
- Anticoccidiodial complement-fixing antibody concentrations in excess of 1:16
- 1.2 Patients with low risk of complications or dissemination
- For many (if not most) patients, management may rely on periodic reassessment of symptoms and radiographic findings to assure resolution without antifungal treatment.
- 1.3 Patients with high risk of complications or dissemination
- 1.3.1 Mild to moderate pneumonia
- Preferred regimen (1): Itraconazole solution 200 mg PO bid or IV q12h
- Preferred regimen (2): Fluconazole 400 mg PO q24h for 3–12 months
- 1.3.2 Locally severe or disseminated pneumonia
- Preferred regimen: (Amphotericin B 0.6–1 mg/kg PO qd every 7 days THEN 0.8 mg/kg PO every other day OR Liposomal Amphotericin B 3-5 mg/kg IV q24 hrs OR Amphotericin B lipid complex 5 mg/kg IV q24 hrs until clinical improvement) followed by Itraconazole OR Fluconazole for at least 1 year.
- Note (1): Some use combination of Amphotericin B and Fluconazole for progressive severe disease; controlled series lacking.
- Note (2): Consultation with specialist recommendation, surgery may be required.
- 2. Meningitis
- 2.1 Adult
- Preferred regimen: Fluconazole 400–1,000 mg PO q24h indefinitely.
- Alternative regimen: Amphotericin B 3-5 mg/kg IV q24 hrs PLUS 0.1–0.3 mg qd intrathecal (intraventricular) via reservoir device OR Itraconazole 400–800 mg q24h OR Voriconazole
- Note: Some use combination of Amphotericin B and Fluconazole for progressive severe disease; controlled series lacking.
- 2.2 Child
- Preferred regimen: Fluconazole PO (Pediatric dose not established, 6 mg per kg q24h used)
- Alternative regimen: Amphotericin B 3-5 mg/kg IV q24 hrs PLUS 0.1–0.3 mg daily intrathecal (intraventricular) via reservoir device OR itra 400–800 mg q24h OR Voriconazole
- 3. Special considerations for HIV/AIDS patients[219]
- 3.1 Clinically mild infections (e.g., focal pneumonia)
- Preferred regimen: Fluconazole 400 mg PO daily OR Itraconazole 200 mg PO bid
- Alternative regimen (unresponsive to Fluconazole or Itraconazole): Posaconazole 200 mg PO bid OR Voriconazole 200 mg PO bid
- Note: Itraconazole, posaconazole, and voriconazole may have significant interactions with certain antiretro viral agents. These interactions are complex and can be bi-directional
- 3.2 Severe, non-meningeal infection (diffuse pulmonary infection or severely ill patients with extrathoracic, disseminated disease)
- Preferred regimen: Amphotericin B deoxycholate 0.7–1.0 mg/kg IV q12hrs OR Lipid formulation Amphotericin B 4–6 mg/kg IV q24hrs. Duration of therapy: continue until clinical improvement, then switch to an azole.
- Alternative regimen: Some specialists will add a triazole (Fluconazole or Itraconazole, with Itraconazole (preferred for bone disease) 400 mg per day to Amphotericin B therapy and continue triazole once Amphotericin B is stopped
- Note (1): Therapeutic drug monitoring and dosage adjustment may be necessary to ensure triazole antifungal and antiretroviral efficacy and reduce concentration-related toxicities.
- Note (2): Therapy should be continued indefinitely in patients with diffuse pulmonary or disseminated diseases because relapse can occur in 25%–33% of HIV-negative patients. It can also occur in HIV-infected patients with CD4 counts >250 cells/μL
- 3.3 Meningeal Infections
- Preferred regimen: Fluconazole 400–800 mg IV or PO daily
- Alternative regimen: Itraconazole 200 mg PO tid for 3 days THEN 200 mg PO bid OR Posaconazole 200 mg PO bid OR Voriconazole 200–400 mg PO bid OR Intrathecal Amphotericin B deoxycholate when triazole antifungals are ineffective.
- Note (1): Intrathecal amphotericin B should only be given in consultation with a specialist and administered by an individual with experience with the technique.
- Note (2): Some patients with meningitis may develop hydrocephalus and require CSF shunting
- Note (3): Therapy should be lifelong in patients with meningeal infections because relapse occurs in 80% of HIV-infected patients after discontinuation of triazole therapy
- 3.4 Chronic Suppressive Therapy
- Preferred regimen (1): Fluconazole 400 mg PO qd
- Preferred regimen (2): Itraconazole 200 mg PO bid
- Alternative regimen (1): Posaconazole 200 mg PO bid
- Alternative regimen (2): Voriconazole 200 mg PO bid
- Cryptococcosis Return to Top
- Cryptococcus Return to Top
- 1. Cryptococcus neoformans
- 1.1 Cryptococcus neoformans meningitis in HIV infected patients[220]
- Preferred regimen for induction and consolidation: (Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd (consider using lipid formulations for patients with renal dysfunction) OR Liposomal AmB 3-4mg/kg IV qd OR Amphotericin B lipid complex (ABLC) 5mg/kg IV qd) PLUS Flucytosine 100mg/kg/day PO or IV qid for at least 2 weeks followed by Fluconazole 400mg (6mg/kg) PO qd for at least 8 weeks.
- Alternative regimen for induction and consolidation (1): Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd OR Liposomal AmB 3-4 mg/kg IV qd OR AmB lipid complex 5mg/kg IV qd for 4-6 weeks
- Alternative regimen for induction and consolidation (2): Amphotericin B deoxycholate 0.7 mg/kg IV qd PLUS Fluconazole 800mg PO qd for 2 weeks, followed by Fluconazole 800mg PO qd for at least 8 weeks
- Alternative regimen for induction and consolidation (3): Fluconazole (>800 mg PO qd, 1200mg PO qd is favored) PLUS Flucytosine (100mg/kg/day PO qid) for 6 weeks
- Alternative regimen for induction and consolidation (4): Fluconazole PO 800-2000mg qd for 10-12 weeks
- Preferred regimen for maintenance and prophylactic therapy: Initiate HAART 2-10 weeks after commencing initial antifungal therapy AND Fluconazole 200mg PO qd
- Alternative regimen for maintenance and prophylactic therapy: Itraconazole 200mg PO bid - monitor drug-level OR Amphotericin B deoxycholate (1 mg/kg) per week IV (should be used in azole-intolerant patients).
- Note (1): Consider discontinuing supressive therapy if CD4 count is higher than 100 cells/uL AND undetectable OR very low HIV RNA level for more than 3 months. Consider reinstitution of maintenance therapy if CD4 count <100 cels/uL.
- Note (2): Do not use acetazolamide OR mannitol OR corticosteroids to treat increased intracranial pressure, instead it should be used lombar puncture in the absence of focal neurologic signs or impaired mentation (which, if present, patient must be submitted to CT or MRI scan first).
- Preferred regimen for induction and consolidation: (Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd (consider using lipid formulations for patients with renal dysfunction) OR Liposomal AmB 3-4mg/kg IV qd OR Amphotericin B lipid complex (ABLC) 5mg/kg IV qd) PLUS Flucytosine 100mg/kg/day PO or IV qid for at least 2 weeks followed by Fluconazole 400mg (6mg/kg) PO qd for at least 8 weeks
- Note: Consider surgery if lesions are larger than 3cm, accessible lesions with mass effect or lesions that are enlarging and not explained by IRIS.
- Preferred regimen: Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd PLUS Flucytosine 100mg/kg/day PO or IV qid for at least 4 weeks (which may be extended to 6 weeks if there is any neurological complication) followed by Fluconazole 400mg PO qd for 8 weeks. If there's toxicity to AmBd, consider changing to LFAmB in the second 2 weeks.
- Note (1): After induction and consolidation therapy, start Fluconazole 200mg (3mg/kg) PO qd for 6-12 months.
- Note (2): If Flucytosine is not given, consider lengthening the induction therapy for at least 2 weeks.
- Mild-moderate symptoms, without severe immunosupression and absence of diffuse pulmonary infiltrates:
- Preferred regimen: Fluconazole 400mg PO qd for 6-12 months
- Severe pneumonia or disseminated disease or CNS infection:
- Preferred regimen: treat like CNS cryptococcosis.
- Note (1): In HIV- infected patients, treatment should be stopped after 1 year if CD4 count is >100 and a cryptococcal antigen titer is <1:512 and not increasing.
- Note (2): Consider corticosteroid if ARDS is present in a context which it might be attributed to IRIS.
- Mild-moderate symptoms, without severe immunosupression and absence of diffuse pulmonary infiltrates:
- Preferred regimen: Fluconazole 400mg PO qd for 6-12 months
- Alternative regimen: if Fluconazole is unavailable or contraindicated, Itraconazole 200mg PO bid, Voriconazole 200 mg PO bid, and Posaconazole 400mg PO bid
- If there's severe pneumonia, disseminated disease or CNS infection:
- Preferred regimen: treat like CNS cryptococcosis for 6-12 months.
- Cryptococcemia or disseminated cryptococcic disease (involvement of at least 2 noncontiguous sites or cryptococcal antigen titer >1:512):
- Preferred regimen: treat like CNS infection.
- If infection occurs at a single site and no immunosupressive risk factors
- Preferred regimen: Fluconazole 400mg PO qd for 6-12 months
- Preferred regimen for induction and consolidation: Amphotericin B deoxycholate 1.0 mg/kg qd IV PLUS Flucytosine 100mg/kg PO or IV qid for 2 weeks followed by Fluconazole 10-12mg/kg PO qd for 8 weeks
- Alternative regimen: patients with renal dysfunction: change Amphotericin B deoxycholate by Liposomal AmB 5mg/kg IV qd or Amphotericin B lipid complex (ABLC) 5mg/kg IV qd
- Preferred regimen for maintenance: Fluconazole 6mg/kg PO qd. Discontinuation of maintenance therapy is poorly studied and should be individualized.
- Cryptococcal pneumonia:
- Preferred regimen Fluconazole 6-12mg/kg PO qd for 6-12 months
- Preferred regimen for induction and consolidation: Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd (consider using lipid formulations for patients with renal dysfunction - Liposomal AmB 3-4mg/kg IV qd OR Amphotericin B lipid complex (ABLC) 5mg/kg IV qd. Consider using Flucytosine in relationship to benefit risk basis, since it is a Category C drug for pregnancy. Start Fluconazole after delivery. Avoid use during first trimester and consider use in the last 2 trimesters with the need for continuous antifungal therapy during pregnancy.
- Note: If pulmonary cryptococcosis: perform close follow-up and administer fluconazole after delivery.
- Disseminated cryptococcosis or CNS disease:
- Preferred regimen: treatment is the same as C. neoformans.
- Pulmonary disease: single and small cryptococcoma:
- Preferred regimen: Fluconazole 400mg per day PO for 6-18months
- Pulmonary disease: Very large or multiple cryptococcomas:
- Preferred regimen: administer Flucytosine AND AmB deocycholate for 4-6 weeks, followed by fluconazole for 6-18 months.
- Note: Surgery should be considered if there is compression of vital structures OR failure to reduce the size of the cryptococcoma after 4 weeks of therapy
- Tinea cruris Return to Top
- Tinea Cruris[221]
- 1. Topical cream/ointment
- Preferred regimen (1): Butenafine cream applied qd for 14 days
- Preferred regimen (2): Terbinafine cream applied bid for 14 days
- 2. Oral antifungal
- Preferred regimen: Fluconazole 200 mg qd for 10 days AND Terbinafine 250 mg qd for 30 days
- Note: Oral antifungal therapy is generally reserved for cases unresponsive to topical agents or can be used along with topical agents in severe cases.
- Tinea corporis Return to Top
- Tinea corporis[222]
- Small, well-defined lesions
- Preferred regimen: Topical cream/ointment like Terbinafine OR Miconazole OR Econazole OR Clotrimazole
- Larger lesionss
- Preferred regimen: Terbinafine 250 mg/day PO for 2 weeks OR Itraconazole 200 mg/day PO for 1 wk OR Fluconazole 250 mg PO weekly for 2-4 weeks
- Tinea pedis Return to Top
- 1. Tinea pedis[223]
- 1.1 Athlete's foot
- 1.1.1 Interdigital
- Preferred regimen: Topical cream/ointment Terbinafine OR Miconazole OR Econazole OR Clotrimazole
- 1.1.2 Dry type
- Preferred regimen (1): Terbinafine 250 mg/day PO for 2-4 weeks
- Preferred regimen (2): Itraconazole 400 mg/day PO for 1 week per month (repeated if necessary)
- Preferred regimen (3): Fluconazole 200 mg PO weekly for 4-8 weeks
- Tinea capitis Return to Top
- Tinea capitis[224]
- Preferred regimen (1): Griseofulvin 10-20 mg/kg/day for minimum 6 weeks
- Preferred regimen (2): Itraconazole 4-6 mg/kg pulsed dose weekly
- Preferred regimen (3): Terbinafine if <20 kg: 62.5 mg/day, if 20-40 kg: 125 mg/day, if >40 kg: 250 mg/day
- Tinea barbae Return to Top
- Tinea Barbae
- Preferred regimen: Terbinafine PO 250mg/day for 4 weeks.
- Alternative regimen: Itraconazole PO 200mg/day for 2 weeks.
- Tinea incognito Return to Top
- Tinea Incognito
- Preferred regimen: Stop topical steroids and treat with topical 1% terbinafine cream for 6 weeks.
- Tinea manuum Return to Top
- Tinea Manuum
- Preferred regimen: topical or systemic terbinafine PO 250 mg/day por 2-4 weeks.
- Tinea versicolor Return to Top
- Tinea versicolor[225]
- Preferred regimen: Ketoconazole 400 mg PO single dose OR 200 mg q24h for 7 days OR 2% cream once q24h for 2 weeks
- Alternative regimen: Fluconazole 400 mg PO single dose OR Itraconazole 400 mg PO q24h for 3–7 days
- Majocchi's granuloma Return to Top
- Majocchi's Granuloma
- Preferred regimen: Terbinafine PO 250mg/day for 2-4 weeks.
- Alternative regimen: Itraconazole 200mg PO bid for 1 week, per month for 2 months.
- Onychomycosis Return to Top
- Onychomycosis[226]
- 10.1 Fingernails
- Preferred regimen: Terbinafine PO 250mg/day for 6 weeks OR Itraconazole PO 200mg twice a day for a week a month for 2 months (European guidelines).
- 10.2 Toenails
- Preferred regimen: Toenails Terbinafine PO 250mg/day for 12 weeks OR Itraconazole PO 200mg/day for 12 weeks (U.S. guidelines) OR Itraconazole PO 200mg twice a day for a week a month for 3 months (European guidelines).
- Note (1): There is no evidence that combining systemic and topic treatments has any benefit to the patient.
- Histoplasmosis Return to Top
- 1. Adult treatment: [227]
- 1.1 Pulmonary
- 1.1.1 Acute pulmonary histoplasmosis
- 1.1.1.1 Moderate severe or severe
- Preferred regimen (1): Lipid formulation of Amphotericin B (3.0–5.0 mg/kg IV q12h for 1–2 weeks) THEN Itraconazole (200 mg tid for 3 days THEN 200 mg bid for a total of 12 weeks).
- Preferred regimen (2): Methylprednisolone (0.5–1.0 mg/kg IV q24h) during the first 1–2 weeks of antifungal therapy is recommended for patients who develop respiratory complications, including hypoxemia or significant respiratory distress
- Alternative regimen: The deoxycholate formulation of Amphotericin B (0.7–1.0 mg/kg q24h IV) is an alternative to a lipid formulation in patients who are at a low risk for nephrotoxicity.
- Note (1): In severe cases, cases accompanied by respiratory insufficiency, or hypoxemia, anecdotal reports suggest that corticosteroid therapy may hasten recovery
- Note (2): The pulmonary infiltrates should be resolved on the chest radiograph before antifungal therapy is stopped.
- 1.1.1.2 Mild to moderate:
- Treatment is usually unnecessary
- Preferred regimen for patients who continue to have symptoms for >1 month: Itraconazole (200 mg tid for 3 days {{then} 200 mg qd OR bid for 6–12 weeks)
- Note (1): Antifungal treatment is unnecessary in patients with mild symptoms caused by acute pulmonary histoplasmosis
- 1.1.2 Chronic cavitary pulmonary histoplasmosis:
- Preferred regimen: Itraconazole (200 mg tid for 3 days and THEN qd or bid for at least 1 year) is recommended
- Note (1): Blood levels of itraconazole should be obtained after the patient has been receiving this agent for at least 2 weeks to ensure adequate drug exposure
- Note (2): Patients with underlying emphysema often develop progressive pulmonary disease, which is characterized by cavities with surrounding inflammation after infection with hysotplasma capsulatum
- 1.1.3 Broncholithiasis
- Antifungal treatment is not recommended
- Note: Bronchoscopic or surgical removal of the broncholith is recommended
- 1.1.4 Pulmonary nodules (Histoplasmomas)
- Antifungal treatment is not recommended**
- Note: There is no evidence that antifungal agents have any effect on histoplasmomas or that histoplasmomas contain viable organisms.
- 1.2 Mediastinitis
- 1.2.1 Mediastinal lymphadenitis
- 1.2.1.1 Asymptomatic cases
- Treatment is usually unnecessary
- 1.2.1.2 Patients who have symptoms that warrant treatment with corticosteroids and in those who continue to have symptoms for > 1 month
- Itraconazole (200 mg 3 tid for 3 days and THEN 200 mg qd or bid for 6–12 weeks)
- 1.2.1.2 Severe cases with obstruction or compression of contiguous structures
- Preferred regimen: Prednisone (0.5–1.0 mg/kg qd [maximum 80 mg qd] in tapering doses over 1–2 weeks)
- Note (1): Antifungal treatment is unnecessary in most patients with symptoms due to mediastinal lymphadenitis
- Note (2): Itraconazole is recommended for 6–12 weeks to reduce the risk of progressive disseminated disease caused by corticosteroid-induced immunosuppression in patients who are given corticosteroids and in patients whose symptoms last longer than 1 month.
- 1.2.2 Mediastinal granuloma
- 1.2.2.1 Asymptomatic cases
- Treatment is usually unnecessary
- 1.2.2.2 Symptomatic cases
- Preferred regimen: Itraconazole (200 mg 3 times qd for 3 days and THEN qd or bid for 6–12 weeks)
- Note (1): Itraconazole is appropriate for symptomatic cases but there are no controlled trials to prove its efficacy.
- Note (2): There is no evidence that mediastinal granuloma evolves into mediastinal fibrosis. Thus treatment with either surgery or itraconazole should not be used to prevent the development of mediastinal fibrosis
- 1.2.3 Mediastinal fibrosis
- Antifungal treatment is not recommended**
- 1.2.3.1 If clinical findings cannot differentiate mediastinal fibrosis from mediastinal granuloma
- Preferred regimen: Itraconazole (200 mg qd or bid for 12 weeks)
- Note: The placement of intravascular stents is recommended for selected patients with pulmonary vessel obstruction
- Note (2): Mediastinal fibrosis is characterized by invasive fibrosis that encases mediastinal or hilar nodes and that is defined by occlusion of central vessels and airways
- 1.3 Pericarditis:
- 1.3.1 Mild cases
- Preferred regimen: Nonsteroidal anti-inflammatory therapy
- 1.3.2 Patients with evidence of hemodynamic compromise or unremitting symptoms after several days of therapy with nonsteroidal anti-inflammatory therapy
- Prednisone (0.5–1.0 mg/kg qd [maximum, 80 mg qd] in tapering doses over 1–2 weeks)
- 1.3.3 If corticosteroids are administered
- Preferred regimen: Itraconazole (200 mg tid for 3 days and THEN qd or bid for 6–12 weeks)
- Note (1): Pericardial fluid removal is indicated for patients with hemodynamic compromise.
- Note (2): Pericarditis occurs as a complication of inflammation in adjacent mediastinal lymph nodes in patients with acute pulmonary histoplasmosis.
- 1.4 Central nervous system histoplasmosis
- Preferred regimen: Liposomal Amphotericin B (5.0 mg/kg qd for a total of 175 mg/kg given over 4–6 weeks) followed by Itraconazole (200 mg 2 or 3 times qd) for at least 1 year and until resolution of cerebro spinal fluid abnormalities including Histoplasma antigen levels.
- Note: Blood levels of Itraconazole should be obtained to ensure adequate drug exposure
- 1.5 Rheumatologic syndromes
- 1.5.1 Mild cases
- Preferred regimen: Nonsteroidal anti-inflammatory therapy
- 1.5.2 Severe cases
- Preferred regimen: Prednisone (0.5–1.0 mg/kg qd [maximum, 80 mg qd] in tapering doses over 1–2 weeks)
- 1.5.3 Corticosteroids administration
- Itraconazole (200 mg 3 times tid for 3 days and THEN qd or bid for 6–12 weeks)
- Note (1): If corticosteroids are used, concurrent itraconazole treatment is recommended to reduce the risk of progressive infection
- Note (2): Bone or joint involvement is very rare in progressive disseminated histoplasmosis but it should not be overlooked.
- 1.6 Progressive disseminated histoplasmosis
- 1.6.1 Moderately severe to severe disease
- Preferred regimen: Liposomal Amphotericin B (3.0 mg/kg qd) is recommended for 1–2 weeks followed by oral Itraconazole (200 mg 3 times qd for 3 days and THEN 200 mg bid for a total of at least 12 months)
- Note (1): Substitution of another lipid formulation at a dosage of 5.0 mg/kg qd may be preferred in some patients because of cost or tolerability
- Note (2): The deoxycholate formulation of Amphotericin B (0.7–1.0 mg/kg qd) is an alternative to a lipid formulation in patients who are at a low risk for nephrotoxicity
- 1.6.2 Immunosupressed patients
- Lifelong suppressive therapy with Itraconazole (200 mg qd)
- 1.6.3 Mild to moderate disease
- Itraconazole (200 mg tid for 3 days and then bid qid for at least 12 months)
- Note (1): Lifelong suppressive therapy with itraconazole (200 mg daily) may be required in immunosuppressed patients if immunosuppression cannot be reversed and in patients who relapse despite receipt of appropriate therapy
- Note (2): Blood levels of itraconazole should be obtained to ensure adequate drug exposure
- Note (3): Antigen levels should be measured during therapy and for 12 months after therapy is ended to monitor for relapse. Persistent low-level antigenuria may not be a reason to prolong treatment in patients who have completed appropriate therapy and have no evidence of active infection.
- Note (4): Progressive disseminated histoplasmosis is fatal without therapy and treatment with either Amphotericin B or Itraconazole is highly effective. Among patients with AIDS and moderately severe to severe disseminated histoplasmosis, the rate of response was higher (88% vs. 64%) and the mortality rate was lower (2% vs. 13%) among recipients of liposomal amphotericin B (3 mg/kg qd for 1–2 weeks) than among recipients of the deoxycholate formulation.
- 1.7 Prophylaxis recommended for immunosuppressed patients
- Preferred regimen: Itraconazole (200 mg qd) in patients with HIV infection with CD4 cell counts <150 cells/mm3 in specific areas of endemicity where the incidence of histoplasmosis is >10 cases per 100 patient-years
- Note: Prophylaxis with Itraconazole (200 mg qd) may be appropriate in specific circumstances in other immunosuppressed patients
- 1.8 Performance Measures
- Preferred regimen: Itraconazole is the preferred azole for initial therapy for patients with mild-to-moderate histoplasmosis and as step-down therapy after receipt of Amphotericin B
- Note: When other azole agents are used, the medical record should document the specific reasons that Itraconazole was not used and why other azoles were used.
- 14.1 Severe or moderately severe histoplasmosis
- Preferred regimen: Amphotericin B
- Note: When Amphotericin B is used the patient's electrolyte level renal function and blood cell count should be monitored several times per week and documented in the medical record.
- Note (2): Itraconazole drug levels should be measured during the first month in patients with disseminated or chronic pulmonary histoplasmosis and these levels should be documented in the medical record as well as the physician's response to levels that are too low.
- Note (3): Itraconazole should not be given to patients receiving contraindicated medications (i.e., pimozide, quinidine, dofetilide, lovastatin, simvastatin, midazolam, and triazolam). Reasons for deviation from this practice should be documented in the medical record.
- 2. Pregnancy treatment
- Preferred regimen: Lipid formulation Amphotericin B (3.0–5.0 mg/kg qd for 4–6 weeks) is recommended
- Prefered regimen low risk for nephrotoxicity: The deoxycholate formulation of Amphotericin B (0.7–1.0 mg/kg qd) is an alternative to a lipid formulation
- Note (1): If the newborn shows evidence for infection, treatment is recommended with Amphotericin B deoxycholate (1.0 mg/kg daily for 4 weeks)
- Note (2): Unique issues in pregnancy include the risk of teratogenic complications of azole therapy and of transplacental transmission of Histoplasma capsulatum to the fetus
- 3. Children treatment
- 3.1 Acute pulmonary histoplasmosis
- Treatment indications and regimens are similar to those for adults, except that Amphotericin B deoxycholate (1.0 mg/kg daily) is usually well tolerated and the lipid preparations are not preferred
- Note: Itraconazole dosage: 5.0–10.0 mg/kg daily in 2 divided doses (not to exceed 400 mg daily), generally using the solution formulation
- Progressive disseminated histoplasmosis
- Prefered regimen: Amphotericin B deoxycholate (1.0 mg/kg qd for 4–6 weeks)
- Alternative regimen: Amphotericin B deoxycholate (1.0 mg/kg qd for 2–4 weeks) followed by itraconazole (5.0–10.0 mg/kg qd in 2 divided doses) to complete 3 months of therapy.
- Immunosuppressed patients if immunosuppression cannot be reversed and patients in relapse despite appropiate therapy
- Note (1): Longer therapy may be needed for patients with severe disease, immunosuppression, or primary immunodeficiency syndromes
- Note (2): Blood levels of itraconazole should be obtained to ensure adequate drug exposure
- Note (3): Antigen levels should be monitored during therapy and for 12 months after therapy is ended to monitor for relapse. Persistent low-level antigenuria may not be a reason to prolong treatment in patients who have completed appropriate therapy and have no evidence of active infection.
- Mucormycosis Return to Top
- Mucormycosis[228]
- Treatment include surgical debridement of involved tissues, antifungal therapy, use of growth factors to accelerate recovery from neutropenia, provision of granulocyte transfusions with sustained circulating neutrophils until the patient recovers from neutropenia, and discontinuation or reduction in the dose of glucocorticoids, correction of metabolic acidosis and hyperglycemia.
- Preferred regimen (1): Amphotericin B Deoxycholate 1.0-1.5 mg/kg/day IV q24h
- Preferred regimen (2): Lipid Amphotericin B 5-10 mg/kg/day IV q24h
- Preferred regimen (3): Amphotericin B lipid complex 5-7.5 mg/kg/day IV q24h
- Alternative regimen (1):Caspofungin 70 mg IV load dose, 50 mg/day for >2 weeks PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h
- Pediatric dose: Caspofungin 50 mg/m² IV q24h PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h
- Alternative regimen (2): Micafungin OR Anidulafungin 100 mg/day for 2 weeks PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h
- Pediatric dose: Micafungin 4 mg/kg/day; Micafungin 10mg/kg/day for low-birth weight infants; Anidulafungin 1.5 mg/kg/day
- Alternative regimen (3): Deferasirox 20 mg/kg PO qd for 2–4 weeks PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h
- Alternative regimen (4): Posaconazole 800 mg/day PO qid or bid
- Alternative regimen (5): Initial: Isavuconazole 200 mg PO/IV q8h for 6 doses; maintenance: 200 mg PO/IV qd
- Note (1): start maintenance dose 12 to 24 hours after the last loading dose.
- Note (2): For salvage therapy: (Posaconazole 800 mg/day PO qid or bid ± Lipid Amphotericin B 5-10 mg/kg/day IV q24h) OR (Deferasirox 20 mg/kg PO qd for 2–4 weeks PLUS Lipid Amphotericin B 5-10 mg/kg/day IV q24h) OR Granulocyte transfusions (for persistently neutropenic patients) ∼10ˆ9 cells/kg OR Recombinant cytokines G-CSF 5 μg/kg/day, GM-CSF 100–250 μg/m², or IFN-g at 50 μg/m² for those with body surface area ≥ 0.5 m² and 1.5 μg/kg for those with body surface area <0.5 m²
- Penicilliosis Return to Top
- Penicilliosis treatment
- 1. Mild disease
- Preferred regimen: Itraconazole 200 mg PO bid for 8 to 12 weeks without amphotericin B induction therapy[229]
- Alternative regimen: Voriconazole 400 mg PO bid on day 1 THEN 200 mg PO bid for 12 weeks[230]
- 2. Moderate-severe disease
- Preferred regimen: Liposomal Amphotericin B 3-5 mg/kg/day IV qd OR Amphotericin B lipid complex 5 mg/kg/day IV qd for 2 weeks THEN Itraconazole 200 mg PO bid for 10 weeks[231]
- Alternative regimen: Voriconazole 6 mg/kg IV q12h on day 1 THEN 4 mg/kg q12h for at least 3 days THEN Voriconazole 200 mg PO bid for a total of 12 weeks[230]
- 3. Maintenance therapy[232]
- Preferred regimen Itraconazole 200 mg PO qd
- Alternative regimen: Voriconazole 200 mg PO bid
- Note: Voriconazole and Itraconazole use require serum levels to be monitored to ensure adequate absorption.
- Sporotrichosis Return to Top
[233]
- Lymphocutaneous/cutaneous
- Preferred regimen: Itraconazole 200mg PO qd
- Alternative regimen: Itraconazole 200 mg PO bid OR Terbinafine 500 mg PO bid OR Saturated solution potassium iodide with increasing doses OR Fluconazole 400–800 mg PO qd OR local hyperthermia
- Note (1): Treat for 2–4 weeks after lesions resolved
- Note (2): SSKI initiated at a dosage of 5 drops (using a standard eyedropper) q8h, increasing as tolerated to 40–50 drops q8h
- Osteoarticular
- Preferred regimen: Itraconazole 200mg PO bid for 12 months
- Alternative regimen: Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day IV OR Amphotericin B deoxycholate 0.7–1 mg/kg/day IV
- Note (1): Switch to Itraconazole after favorable response if AmB used
- Note (2): Treat for a total of at least 12 months
- Pulmonary
- Preferred regimen(1): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day IV for severe or life-threatening pulmonary sporotrichosis, then Itraconazole 200 mg PO bid
- Preferred regimen(2): Itraconazole 200 mg PO bid for 12 months for less severe disease
- Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/d IV THEN Itraconazole 200 mg PO bid OR surgical removal
- Note (1): Treat severe disease with an AmB formulation followed by Itraconazole
- Note (2): Treat less severe disease with Itraconazole
- Note (3): Treat for a total of at least 12 monthsSurgery combined with amphotericin B therapy is rec- ommended for localized pulmonary disease
- Meningitis
- Preferred regimen: Lipid amphotericin B (Lipid AmB) 5 mg/kg daily for 4–6 weeks, then Itraconazole 200 mg PO bid
- Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/d, then Itraconazole 200 mg PO bid
- Note (1): Length of therapy with AmB not established, but therapy for at least 4–6 weeks is recommended.
- Note (2): Treat for a total of at least 12 months.
- Note (3): May require long-term suppression with Itraconazole.
- Disseminated
- Preferred regimen: Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day, then Itraconazole 200 mg PO bid
- Alternative regimen: Amphotericin B deoxycholate 0.7–1 mg/kg/day, then Itraconazole 200 mg PO bid
- Note(1): Therapy with AmB should be continued until the patient shows objective evidence of improvement.
- Note(2): Treat for a total of at least 12 months.
- Note(3): May require long-term suppression with Itraconazole.
- Pregnant women
- Preferred regimen(1): Lipid amphotericin B (Lipid AmB) 3–5 mg/kg/day IV OR Amphotericin B deoxycholate 0.7–1 mg/kg/day IV for severe sporotrichosis
- Preferred regimen(2): Local hyperthermia for cutaneous disease.
- Note (1): It is preferable to wait until after delivery to treat non–life-threatening forms of sporotrichosis.
- Note (2): Azoles should be avoided.
- Children
- Preferred regimen:
- Mild disease: Itraconazole 6–10 mg/kg/day PO (400 mg/day maximum)
- Severe disease: Amphotericin B deoxycholate 0.7 mg/kg/day IV followed by Itraconazole 6–10 mg/kg PO up to a maximum of 400 mg PO daily, as step-down therapy
- Alternative regimen: Saturated solution potassium iodide with increasing doses for mild disease initiated at a dosage of 1 drop (using a standard eyedropper) q8h and increased as tolerated up to a maximum of 1 drop/kg or 40–50 drops q8h, whichever is lowest
- Pneumocystis jiroveci Return to Top
- 1. Preventing First Episode of PCP (Primary Prophylaxis)[234]
- Preferred regimen: TMP-SMX 1 Double-Strength(DS) PO daily OR TMP-SMX 1 Single-Strength(SS) PO daily
- Alternative regimen (1): TMP-SMX 1 Double-Strength(DS) tid weekly OR Dapsone 100 mg PO daily or 50 mg PO bid
- Alternative regimen (2): Dapsone 50 mg PO AND (Pyrimethamine 50 mg PO AND Leucovorin 25 mg) PO weekly
- Alternative regimen (3): Dapsone 200 mg PO AND Pyrimethamine 75 mg PO AND Leucovorin 25 mg PO weekly
- Alternative regimen (4): Aerosolized Pentamidinec 300 mg via Respigard II™ nebulizer every month
- Alternative regimen (5): Atovaquone 1500 mg PO qd with food
- Alternative regimen (6): Atovaquone 1500 mg PO AND Pyrimethamine 25 mg PO AND Leucovorin 10 mg PO daily with food
- 2. Treatment of Pneumocystis Pneumonia[235]
- 2.1. Moderate to Severe PCP
- Preferred regimen: TMP-SMX (TMP 15–20 mg and SMX 75–100 mg)/kg/day IV given q6h or q8h
- Note: May switch to PO after clinical improvement
- Alternative regimen (1): Pentamidine 4 mg/kg IV once daily infused over at least 60 minutes
- Note: May reduce the dose to 3 mg/kg IV once daily because of toxicities.
- Alternative regimen (2): Primaquine 30 mg (base) PO once daily AND (Clindamycin [IV 600 mg q6h or 900 mg q8h] or [PO 450 mg q6h or 600 mg q8h])
- Note (1): Duration of PCP treatment is 21 days
- Note (2): Adjunctive corticosteroid may be indicated in some moderate to severe cases.Prednisone doses (beginning as early as possible and within 72 hours of PCP therapy) (AI):
- Note (3): Prednisone doses (beginning as early as possible and within 72 hours of PCP therapy)
- Days 1–5 40 mg PO BID
- Days 6–10 40 mg PO daily
- Days 11–21 20 mg PO daily
- 2.2. Mild to Moderate PCP
- Preferred regimen: TMP-SMX (TMP 15–20 mg/kg/day and SMX 75–100 mg/kg/day), given PO in 3 divided doses OR TMP-SMX Double-Strength(DS) - 2 tablets tid
- Alternative regimen (1): Dapsone 100 mg PO daily AND TMP 15 mg/kg/day PO (3 divided doses)
- Alternative regimen (2): Primaquine 30 mg (base) PO daily AND Clindamycin PO (450 mg q6h or 600 mg q8h)
- Alternative regimen (3): Atovaquone 750 mg PO BID with food
- Note: Duration of PCP treatment is 21 days
- 3. Preventing Subsequent Episode of PCP (Secondary Prophylaxis)[236]
- Preferred regimen: TMP-SMX 1 Double-Strength(DS) PO daily OR TMP-SMX 1 Single-Strength(SS) PO daily
- Alternative regimen (1): TMP-SMX 1 Double-Strength(DS) tid weekly OR Dapsone 100 mg PO daily or 50 mg PO BID
- Alternative regimen (2): Dapsone 50 mg PO daily AND (Pyrimethamine 50 mg + Leucovorin 25 mg) PO weekly
- Alternative regimen (3): Dapsone 200 mg AND Pyrimethamine 75 mg AND Leucovorin 25 mg PO weekly
- Alternative regimen (4): Aerosolized Pentamidinec 300 mg via Respigard II™ nebulizer every month
- Alternative regimen (5): Atovaquone 1500 mg PO daily with food
- Alternative regimen (6): Atovaquone 1500 mg AND Pyrimethamine 25 mg AND Leucovorin 10 mg PO daily with food
### Mycobacteria
- Mycobacterium tuberculosis Return to Top
- 1. Standard Regimens for new patients [237]
- 1.1 Adult
- 1.1.1 Initial phase
- Preferred regimen: Isoniazid 300 mg PO (5 mg/kg/day) qd for 8 weeks AND Rifampicin 600 mg PO (10 mg/kg/day) qd for 8 weeks AND Pyrazinamide 2 g PO (25 mg/kg/day) qd for 8 weeks AND Ethambutol 1.6 g PO (15 mg/kg/day) qd for 8 weeks
- Alternative regimen (1): Isoniazid 300 mg/day PO for 2 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO for 2 weeks (10 mg/kg/day) AND Pyrazinamide 2 g/day PO for 2 weeks (25 mg/kg/day) AND Ethambutol 1.6 g PO for 2 weeks (15 mg/kg/day), followed by Isoniazid 300 mg/day PO twice weekly for 6 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO twice weekly for 6 weeks (10 mg/kg/day) AND Pyrazinamide 2 g/day PO twice weekly for 6 weeks AND Ethambutol 1.6 g PO for 2 weeks (15 mg/kg/day)
- Alternative regimen (2): Isoniazid 300 mg/day PO thrice weekly for 8 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO thrice weekly for 8 weeks (10 mg/kg/day) AND Pyrazinamide 2g/day PO thrice weekly for 8 week (25 mg/kg/day) AND Ethambutol 1.6 g PO thrice weekly for 8 weeks (15 mg/kg/day)
- 1.1.2 Continuation phase
- Preferred regimen (1): Isoniazid 300 mg PO (5 mg/kg/day) qd AND Rifampicin 600 mg PO (10 mg/kg/day) qd for 18 weeks
- Preferred regimen (2): Isoniazid 300 mg PO twice weekly (5 mg/kg/day) AND Rifampicin 600 mg/day PO twice weekly (10 mg/kg/day) for 18 weeks
- Alternative regimen (1): Isoniazid 300 mg/day PO biweekly for 18 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO biweekly for 18 weeks (10 mg/kg/day)
- Alternative regimen (2): Isoniazid 300 mg/day PO thrice weekly for 18 weeks (5 mg/kg/day) AND Rifampicin 600 mg/day PO thrice weekly for 18 weeks (10 mg/kg/day)
- 1.2 Pediatric
- 1.2.1 Initial phase
- Preferred regimen: Isoniazid 10 mg/kg PO (Maximum, 300 mg/day) AND Rifampicin 15 mg/kg PO (Maximum, 600 mg/day) AND Pyrazinamide 35 mg/kg PO (Maximum, 2 g/day) AND Ethambutol 20 mg/kg PO (Maximum, 1.6 g/day), each for 8 weeks
- 1.2.2 Continuation phase
- Preferred regimen: Isoniazid 10 mg/kg PO (Maximum, 300 mg/day) AND Rifampicin 15 mg/kg PO (Maximum, 600 mg/day), each drug daily for 18 weeks
- 2. MDR Tuberculosis [238]
- 2.1 Adult
- Preferred regimen: 4 agents combination
- Agent 1: Pyrazinamide 20–30 mg/kg OR Ethambutol 15–25 mg/kg OR Rifabutin 5 mg/kg
- Agent 2: Capreomycin 15 mg/kg OR Kanamycin 15 mg/kg OR Amikacin 7.5-10 mg/kg OR Streptomycin 12–18 mg/kg
- Agent 3: Levofloxacin 500-1000 mg OR Moxifloxacin 400 mg OR Ofloxacin 400 mg
- Agent 4: Ethionamide 15-20 mg/kg OR Protionamide 15-20 mg/kg OR Cycloserine 10-15 mg/kg OR Terizidone 10-20 mg/kg OR Para-aminosalicylic acid 8-12 g/day IV q8-12h
- 2.2 Pediatric
- Preferred regimen: 4 agents combination
- Agent 1: Pyrazinamide 20-30 mg/kg (Maximum: 600 mg) OR Ethambutol 15-20 mg/kg OR Rifabutin 5 mg/kg
- Agent 2: Capreomycin 15-30 mg/kg (Maximum: 1000 mg) OR Kanamycin 15-30 mg/kg (Maximum: 1000 mg) OR Amikacin 15-22.5 mg/kg (Maximum: 1000 mg) OR Streptomycin 12-18 mg/kg AND
- Agent 3: Levofloxacin 7.5-10 mg/kg OR Moxifloxacin 7.5-10 mg/kg OR Ofloxacin 15-20 mg/kg/day q12h (Maximum: 800 mg)
- Agent 4: Ethionamide 15-20 mg/kg/day q12h (Maximum: 1000 mg) OR Protionamide 15-20 mg/kg/day q12h (Maximum: 1000 mg) OR Cycloserine 10-20 mg/kg (Maximum: 1000 mg) OR Terizidone 10-20 mg/kg (Maximum: 1000 mg) OR Para-aminosalicylic acid 150 mg/kg/day q8-12h(Maximum: 12,000 mg)
- 3. XDR Tuberculosis [239]
- 3.1 Adult
- Preferred regimen: 3 agents combination
- Agent 1: Pyrazinamide 20–30 mg/kg OR Ethambutol 15–25 mg/kg OR Rifabutin 5 mg/kg
- Agent 2: Ethionamide 15-20 mg/kg OR Protionamide 15-20 mg/kg OR Cycloserine 10-15 mg/kg OR Terizidone 10-20 kg/mg OR Para-aminosalicylic acid 8-12 g/day q8-12h
- Agent 3: Clofazimine 50 mg/d AND 300 mg once a month OR Amoxicillin/clavulanate 500 mg/125 mg q12h OR Linezolid 300-600 mg OR Imipenem 500mg q6h OR Clarithromycin 500-1000 mg q12h OR Thioacetazone 2.5 mg/kg OR Isoniazid (high-dose) 16–20 mg/kg
- 3.2 Pediatric
- Preferred regimen: 3 agents combination
- Agent 1: Pyrazinamide 20-30 mg/kg (Maximum: 600 mg) OR Ethambutol 15 mg/kg OR Rifabutin 5 mg/kg
- Agent 2: Ethionamide 15-20 mg/kg (Maximum: 1000 mg) OR Protionamide 15-20 mg/kg (Maximum: 1000 mg) OR Cycloserine 10-20 mg/kg (Maximum: 1000 mg) OR Terizidone 10-20 mg/kg (Maximum: 1000 mg) OR Para-aminosalicylic acid 150 mg/kg/day q8-12h
- Agent 3: Clofazimine 50 mg/d AND 300 mg once a month OR Amoxicillin/clavulanate OR Linezolid 300-600 mg OR Imipenem 500mg q6h OR Clarithromycin 500-1000 mg q12h OR Thioacetazone 2.5 mg/kg OR Isoniazid (high-dose) 16–20 mg/kg
- Mycobacterium abscessus Return to Top
- 1.Limited, localized extrapulmonary disease [240]
- Preferred regimen: Clarithromycin 500 mg PO bid ± Amikacin 10-15 mg/kg/day IV or 25 mg/kg three times weekly for 4 months
- Alternative regimen (1): Amikacin AND Cefoxitin 12 g/day PO for two weeks
- Note: until clinical improvement in severe cases
- Alternative regimen (2): Amikacin AND Imipenem 500 mg IV q6-8h for two weeks
- Note(1): Until clinical improvement in severe cases
- Note(2): Osteomyelitis should be treated for as least 6 months; Infected foreign bodies should be removed
- 2.Pulmonary or serious extrapulmonary disease
- Preferred regimen: Clarithromycin 500 mg PO bid AND Amikacin 15 mg/kg/day IV AND Cefoxitin 2g IV q4h OR Imipenem 1g IV q6h for at least 2-4 months
- Note: If limited by adverse effects THEN Clarithromycin 500 mg PO bid or 1000 mg XR qd OR Azithromycin 250 mg PO qd
- Alternative regimen(1): Tigecycline 100 mg IV loading dose THEN 50 mg IV q12h
- Note: could be substituted as one of the injectables
- Alternative regimen(2): Linezolid 600 mg PO bid or 600 mg PO qd AND Clarithromycin
- Note: Could replace parental tx if not tolerated or feasible
- Mycobacterium bovis Return to Top
- Mycobacterium bovis [241]
- Note: Is intrinsically resistant to Pyrazinamide (PZA). The treatment of M. bovis is extrapolated from experience with the treatment of PZA-resistant M. tuberculosis
- 1. Pulmonary and most extrapulmonary disease
- Preferred regimen: Isoniazid AND Rifampin AND Ethambutol for 2 months, followed by Isoniazid AND Rifampin for 7 months
- 2. Meningitis
- Preferred regimen: Isoniazid AND Rifampin AND Ethambutol for 2 months, followed by Isoniazid AND Rifampin for 10 months
- Mycobacterium avium-intracellulare Return to Top
- 1. Treatment of MAC pulmonary disease [242]
- 1.1 Patients with nodular/bronchiectatic disease
- Preferreday regimen: Clarithromycin 1,000 mg three times weekly OR Azithromycin 500–600 mg three times weekly AND Ethambutol 25 mg/kg three times weekly AND Rifampin 600 mg three times weekly
- Note: Patients should be treated until culture negative on therapy for 1 year
- 1.2 Patients with fibrocavitary or severe nodular/bronchiectatic disease
- Preferreday regimen: Clarithromycin 500–1,000 mg/day OR Azithromycin 250–300 mg/day OR Rifampin 600 mg/day OR Rifabutin 150–300 mg/day AND Ethambutol 15 mg/kg/day
- Note(1): Amikacin OR Streptomycin threetimes-weekly can be used early in therapy
- Note(2): Patients should be treated until culture negative on therapy for 1 year
- 2. Disseminateday MAC disease
- Preferreday regimen: Clarithromycin 1,000 mg/day OR Azithromycin 250 mg/day AND Ethambutol 15 mg/kg/day ± Rifabutin 150–350 mg/day
- Mycobacterium celatum Return to Top
- Mycobacterium celatum [243]
- Preferred regimen: Clarithromycin AND Ethambutol AND Ciprofloxacin ± Rifabutin
- Mycobacterium chelonae Return to Top
- Mycobacterium chelonae [244]
- 1. Localized infections
- Preferred regimen: Clarithromycin 500 mg PO bid
- Alternative regimen: Azithromycin
- 2. Disseminated or extensive disease
- 2.1 monotherapy
- Preferred regimen: Clarithromycin 500 mg PO bid for 6 months
- 2.2 multidrug therapy
- preferred regimen: Clarithromycin 500 mg PO bid AND Tobramycin 5 mg/kg IV q24h OR Imipenem 0.5-1 g IV q6h OR Linezolid 600 mg IV/PO q12h/bid for 4-8 weeks
- Alternative regimen: Moxifloxacin 400 mg PO qd AND Linezolid 600 mg PO bid
- Note(1): During initial treatment, multidrug therapy may prevent development of acquired resistance
- Note(2): Total treatment duration is 6 months
- 3. Keratitis (LASIK-related)
- Preferred regimen: Clarithromycin 500 mg PO bid AND Tobramycin 0.3% 2 gtts q4h AND Gatifloxacin 0.3% 1 gtt q4h OR Moxifloxacin 0.5% 1 gtt q4h
- Mycobacterium foruitum Return to Top
- Mycobacterium foruitum [245]
- 1. In vitro isolates
- Susceptible agents: Amikacin (100%), Ciprofloxacin and Ofloxacin (100%), Sulfonamides (100%), Cefoxitin (50%), Imipenem (100%), Clarithromycin (80%), and Doxycycline (50%)
- 2. Disease
- 2.1 M. fortuitum lung disease
- At least two agents with in vitro activity against the clinical isolate should be given for at least 12 months of negative sputum cultures
- 2.2 Serious skin, bone, and soft tissue M fortuitum disease
- At least two agents with in vitro activity against the clinical isolate should be given for a minimum of 4 months; For bone infections, 6 months of therapy is recommended
- Mycobacterium haemophilum Return to Top
- Mycobacterium haemophilum [246]
- 1. In vitro
- Susceptible: Amikacin, Clarithromycin, Ciprofloxacin, Rifampin, and Rifabutin
- Less susceptible: Doxycycline and Sulfonamides
- 2. Infection
- 2.1 Disseminated disease
- Preferred regimen: Clarithromycin AND Rifampin AND Rifabutin AND Ciprofloxacin
- Mycobacterium genavense Return to Top
- Mycobacterium genavense [247]
- Susceptibility: Amikacin, Rifamycin, Fluoroquinolones, Streptomycin, and Macrolides
- Note(1): Ethambutol has limited activity
- Note(2): Optimal therapy is not determined, but multidrug therapies including Clarithromycin appear to be more effective than those without Clarithromycin
- Mycobacterium gordonae Return to Top
- Mycobacterium gordonae [248]
- Preferred regimen: Ethambutol OR Rifabutin OR Clarithromycin OR Linezolid OR Fluoroquinolones
- Mycobacterium kansasii Return to Top
- Mycobacterium kansasii [249]
- 1. pulmonary disease
- Preferred regimen: Rifampin 10 mg/kg/day (Maximum, 600 mg) PO AND Ethambutol 15 mg/kg/ day PO AND Isoniazid 5 mg/kg/day (Maximum 300 mg) PO AND Pyridoxine 50 mg/day PO
- Note: Treatment duration for M. kansasii lung disease should include 12 months of negative sputum cultures
- 2. Rifampin-resistant M. kansasii disease
- Preferred regimen: Clarithromycin OR Azithromycin OR Moxifloxacin OR Ethambutol OR Sulfamethoxazole OR Streptomycin
- Note(1): Use three-drug regimen
- Note(2): Patients undergoing therapy for M. kansasii lung disease should have close clinical monitoring with frequent sputum examinations for mycobacterial culture throughout therapy
- 3. Disseminated M. kansasii disease
- Note: The treatment regimen for disseminated disease should be the same as for pulmonary disease
- Mycobacterium marinum Return to Top
- Mycobacterium marinum [250]
- 1. In vitro M. marinum isolates
- Susceptible: Rifampin, Rifabutin, Ethambutol, Clarithromycin, Sulfonamides, and Trimethoprim sulfamethoxazole
- Intermediately susceptible: Streptomycin, Doxycycline, and Minocycline
- Resistant: Isoniazid and Pyrazinamide
- Note: Two active agents for 1 to 2 months after resolution of symptoms, typically 3 to 4 months in total
- 2. Infection
- 2.1 skin and soft tissue infections
- Preferred regimen (1): Clarithromycin AND Ethambutol
- Preferred regimen (2): Ethambutol AND Rifampin
- Note: Azithromycin can replace Clarithromycin
- 2.2 osteomyelitis or deep structure infection
- Preferred regimen: Clarithromycin AND Ethambutol AND Rifampin
- Mycobacterium scrofulaceum Return to Top
- Mycobacterium scrofulaceum [251]
- Susceptibility data are lacking and standard treatment regimens for M. scrofulaceum are controversial, emphasizing the need to perform susceptibility testing on confirmed disease-producing isolates of M. scrofulaceum
- Mycobacterium simiae Return to Top
- Mycobacterium simiae [252]
- Preferred regimen: Clarithromycin AND Moxifloxacin AND Trimethoprim/sulfamethoxazole
- Mycobacterium ulcerans Return to Top
- Mycobacterium ulcerans [253]
- 1. Preulcerative lesions
- Excision and primary closure, Rifampin monotherapy, or heat therapy
- 2. Established ulcers
- Most antimycobacterial agents are ineffective for the treatment of the ulcer; Surgical debridement combined with skin grafting is the usual treatment of choice
- 3. Control complications of the ulcer
- Preferred regimen: Clarithromycin AND Rifampin
- Mycobacterium xenopi Return to Top
- Mycobacterium xenopi [254]
- 1. The cornerstone of therapy for M. xenopi
- Preferred regimen: Clarithromycin AND Rifampin AND Ethambutol
- Note: Therapy should be continued until the patient has maintained negative sputum cultures while on therapy for 12 months
- 2. Pulmonary disease
- Preferred regimen: INH AND Rifabutin OR Rifampin AND Ethambutol AND Clarithromycin ± Streptomycin
- Note: A quinolone, preferably Moxifloxacin, could be substituted for one of the antituberculous drugs
- 3. Extrapulmonary disease
- Note: Therapy for extrapulmonary disease would include the same agents as for pulmonary disease
- Mycobacterium leprae Return to Top
- Mycobacterium leprae [255]
- 1. Multibacillary Leprosy (Skin smear positive)
- 1.1 Adult
- Preferred regimen: Dapsone 100 mg/day PO AND Rifampin 600 mg PO 4 times per week AND Clofazimine 50 mg PO qd for 12-24 months
- Note: Clofazimine should be supplemented by loading dose 300 mg PO monthly
- 1.2 Pediatric
- 1.2.1 < 35 kg
- Preferred regimen: Dapsone 1-2 mg/kg/day PO AND Rifampin 450 mg PO for 12-24 months
- 1.2.2 < 20 kg
- Preferred regimen: Dapsone 1-2 mg/kg/day PO AND Rifampin 300 mg PO for 12-24 months
- 1.2.3 < 12 kg
- Preferred regimen: Dapsone 1-2 mg/kg/day PO AND Rifampin 150 mg PO for 12-24 months
- 2. Paucibacillary Leprosy (Skin Smear negative)
- Preferred regimen: Rifampin 600 mg PO once a month for 6 months AND Dapsone 100 mg PO qd for 6 months
- 3. Erythema Nodosum Leprosum (ENL)
- 3.1 Mild
- Preferred regimen: Rest affect limb, analgesics, follow-up twice a week, check for iridocyclitis; Chloroquine OR Aspirin may be useful
- 3.2 Severe (numerous nodules + fever, ulcerating/pustular ENL, visceral involvement, nodules + neuritis, recurrent ENL)
- Preferred regimen: Prednisolone 30-40 mg/day PO for 1-2 weeks THEN taper over 12 weeks
- Alternative regimen (1): (If unresponsive to corticosteroids or if risk of corticosteroids prevent administration) Clofazimine 100 mg PO tid for maximum of 12 weeks THEN taper the dose to 100 mg PO bid for 12 weeks THEN 100 mg qd for 12-24 weeks
- Alternative regimen (2): (if not contraindicated) Thalidomide 200-400 mg/day PO THEN 50-100 mg/day after 1-2 weeks
- 4. Reversal Reaction
- Preferred regimen: Prednisolone start with 40 mg/day PO THEN taper by 10 mg twice a week for 12 weeks
- Mycobacterium smegmatis Return to Top
- Mycobacterium smegmatis [256]
- 1. Mild disease
- Preferred regimen: Doxycycline PO AND Trimethoprim sulfamethoxazole PO
- 2. Severe disease
- Preferred regimen: Amikacin IV OR Imipenem IV
- Mycobacterium immunogenum Return to Top
- Mycobacterium immunogenum [257]
- In vitro
- Susceptible: Amikacin and Clarithromycin
- Resistant: Ciprofloxacin, Doxycycline, Cefoxitin, Tobramycin, and Sulfamethoxazole
- Note: The optimal therapy for this organism is unknown; however, successful therapy is likely difficult due to the extensive antibiotic resistance of the organism
- Mycobacterium malmoense Return to Top
- Mycobacterium malmoense[258]
- 1. In vitro
- Susceptible: Ethambutol, Ethionamide, Kanamycin, and Cycloserine
- Resistant: INH, Streptomycin, Rifampin, and Capreomycin
- 2. Pulmonary M. malmoense infection
- Preferred regimen: INH AND Rifampin AND Ethambutol ± Quinolones AND Macrolides
- Mycobacterium mucogenicum Return to Top
- Mycobacterium mucogenicum [259]
- In vitro susceptible agents: Aminoglycosides, Cefoxitin, Clarithromycin, Minocycline, Doxycycline, Quinolones, Trimethoprim/sulfamethoxazole, and Imipenem
- Mycobacterium szulgai Return to Top
- Mycobacterium szulgai [260][261]
- 1. in vitro susceptibility
- M. szulgai is susceptible in vitro to most antituberculous drugs including Quinolones and newer Macrolides
- 2. Infection
- 2.1 Pulmonary infection
- Three- or four-drug regimen based on susceptibility that includes 12 months of negative sputum cultures while on therapy
- 2.2 Extrapulmonary infection
- Combination anti-tuberculous medications based on in vitro susceptibilities for 4-6 months
- Mycobacterium terrae Return to Top
- Mycobacterium terrae [262]
- 1. In vitro susceptibility
- All six of the isolates from a single center and 90% or more of an additional 22 isolates of M. terrae complex were susceptible to Ciprofloxacin and Sulfonamides. Recently, 11 isolates of M. terrae complex were also shown to be susceptible to Linezolid
- 2. Antimicrobial therapy
- Based on in vitro susceptibility results
### Parasites – Intestinal Protozoa
- Balantidium coli treatment[263]
- Adult dosage:
- Preferred regimen: Metronidazole 750 mg PO tid for 5 days, Tetracycline 500 mg PO qid for 10 days
- Alternative regimen: Iodoquinol 650 mg PO tid for a 20-days
- Pediatric dosage:
- Preferred regimen: Metronidazole 35-50 mg/kg/day PO in three doses (maximum dosage: 2 g) for 5 days, Tetracycline 40 mg/kg/dose PO in four doses for 10 days.
- Alternative regimen: Iodoquinol 40 mg/kg/dose PO in three doses for 20 days AND Doxycycline.
- Note: Nitazoxanide, a broad-spectrum antiparasitic and antihelminthic drug, may be another treatment for balantidiosis.
- Blastocystis hominis Return to Top
- Blastocystis[264]
- Preferred regimen (1): Metronidazole 750 mg PO tid or 1.5 g qd for 10 days
- Preferred regimen (2): Trimethoprim-sulfamethoxazole 1 DS PO bid or 2 DS PO qd for 7 days
- Preferred regimen (3): Iodoquinol 650 mg PO tid for 20 days
- Preferred regimen (4): Nitazoxanide 500 mg PO bid for 3 days
- Preferred regimen (5): Paromomycin 25-35 mg/kg/day PO tid for 7 days
- Note (1): Treatment of asymptomatic infections is unnecessary
- Note (2): One double strength tablet contains 160 mg trimethoprim/800 mg sulfamethoxazole
- Cryptosporidium parvum Return to Top
- 1. Immunocompetent[265]
- Preferred regimen: No specific therapy recommended since healthy patients usually recover within a few weeks, but if needed: Nitazoxanide 500 mg PO bid for 3 days.
- 2. HIV[266]
- Preferred regimen: Nitazoxanide 500 mg PO bid for 3 days
- 3. HIV and Immunodeficiency[267]
- Preferred regimen: Effective antiretroviral therapy
- Note: Nitazoxanide is not licensed for immunodeficient patients
- Cryptosporidium hominis Return to Top
- 1. Immunocompetent[268]
- Preferred regimen: No specific therapy recommended since healthy patients usually recover within a few weeks, but if needed: Nitazoxanide 500 mg PO bid for 3 days.[269]
- 2. HIV[270]
- Preferred regimen: Nitazoxanide 500 mg PO bid for 3 days
- 3. HIV and Immunodeficiency[271]
- Preferred regimen: Effective antiretroviral therapy
- Note: Nitazoxanide is not licensed for immunodeficient patients
- Cyclospora cayetanensis Return to Top
- Cyclospora cayetanensis[272]
- Preferred regimen: Trimethoprim-sulfamethoxazole one double-strength tablet PO bid for 7-10 days
- Alternative regimen(1): Ciprofloxacin 500 mg PO bid for 7 days
- Alternative regimen(2): Nitazoxanide 500 mg PO bid for 7 days
- Note(1): One double-strength tablet (160 mg TMP/800 mg SMX) .
- Note(2): Treatment is continued for 7 days in immunocompetent hosts and for 7 to 10 days in patients with HIV infection.
- Dientamoeba fragilis Return to Top
- Dientamoebiasis[273][274][275]
- Preferred regimen: Iodoquinol 650 mg PO tid for 20 days
- Alternative regimen (1): Paromomycin 25–35 mg/kg/day PO in three divided doses for 7 days
- Alternative regimen (2): Metronidazole 500–750 mg PO tid for 10 days
- Alternative regimen (3): Tetracycline 500 mg PO qid for 10 days
- 1.1 Treatment in pregnancy
- The use of Iodoquinol in pregnancy is limited, and risk to the embryo-fetus is unknown, should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- Oral dose of Paromomycin generally is poorly absorbed from the gastrointestinal tract, with minimal, if any, systemic availability.
- Metronidazole is in pregnancy category B. Data on the use of this drug in pregnant women are conflicting. The available evidence suggests use during pregnancy has a low risk of congenital anomalies. May be used during pregnancy in those patients who will clearly benefit from the drug, although its use in the first trimester is generally not advised.
- 1.2 Treatment during lactation
- Iodoquinol should be used with caution in breastfeeding women.
- Oral dose of Paromomycin is unlikely to be excreted in breast milk, and the drug generally is poorly absorbed from the gastrointestinal tract.
- Metronidazole should be used during lactation only if the potential benefit of therapy to the mother justifies the potential risk to the infant.
- 1.3 Treatment in pediatric patients
- Iodoquinol 30–40 mg/kg/day (maximum 2 g) PO in 3 doses for 20 days. The safety of iodoquinol in children has not been established.
- Paromomycin 25–35 mg/kg/day PO in 3 doses for 7 days. The safety of oral dose in children has not been formally evaluated. However, the safety profiles likely are comparable in children and adults.
- Metronidazole 35–50 mg/kg/day PO in 3 doses for 10 days. The safety in children has not been established, is listed as an antiamebic and antigiardiasis medicine on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.
- Tetracycline 40 mg/kg/day (maximum 2 g) PO in 4 doses for 10 days
- Entamoeba histolytica Return to Top
- 1. Amebic Liver Abscess[276]
- Preferred regimen: (Metronidazole 750 mg PO tid for 10 days OR Tinidazole 2 g PO qd for 5 days) AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
- Alternative regimen (1): Nitazoxanide 500 mg bid for 10 days AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
- Alternative regimen (2): Tinidazole 2 g PO qd for 5 days AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
- Alternative regimen (2): Tinidazole 2 g PO qd for 5 days
- 2. Amebic Colitis[277]
- Preferred regimen: Metronidazole 500-750 mg PO tid for 7-10 days. Pediatric dose: 35-50 mg/kg per day tid AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
- Alternative regimen: Tinidazole 2 g PO qd for 5 days AND (Paromomycin 30 mg/kg/day PO tid for 5-10 days OR Diloxanide furoate 500 mg PO tid for 10 days)
- 3. Asymptomatic Intestinal Colonization[278]
- Preferred regimen: Paromomycin 30 mg/kg/day PO tid for 5-10 days
- Alternative regimen (1): Diloxanide furoate 500 mg PO tid for 10 days
- Alternative regimen (2): Diiodohydroxyquin 650 mg PO tid for 20 days for adults and 30 to 40 mg/kg per day tid for 20 days for children
- Giardia lamblia Return to Top
- 1. Giardiasis[279][280]
- 1.1 Adult
- Preferred regimen (1): Metronidazole 250 mg tid 5–7 days
- Preferred regimen (2): Tinidazole 2 g single dose
- Preferred regimen (3): Nitazoxanide 500 mg PO bid (with food)
- Alternative regimen (1): Paromomycin 500 mg tid 3 5–10 days
- Alternative regimen (2): Quinacrine 100 mg tid 3 5–7 days
- Alternative regimen (3): Furazolidone 100 mg qid 3 7–10 days
- 1.2 Pediatric
- Preferred regimen (1): Metronidazole 5 mg/kg tid 3 5–7 days
- Preferred regimen (2): Tinidazole 50 mg/kg single dose (max, 2 g)
- Preferred regimen (3): Nitazoxanide 100 mg PO bid for age 1-3 years or 200 mg PO bid for age 4-11 years (with food)
- Alternative regimen (1): Paromomycin 30 mg/kg/day in 3 doses 3 5–10 days
- Alternative regimen (2): Quinacrine 2 mg/kg tid 3 7 days
- Alternative regimen (3): Furazolidone 2 mg/kg qid 3 10 days
- Cystoisospora belli Return to Top
- 1. Cystoisospora belli treatment[281]
- 1.1 Immunocompetent hosts
- In the immunocompetent hosts, symptoms of Cystoisospora infection are usually self-limited.
- Antimicrobial therapy to immunocompetent patients may be considered if symptoms do not start to resolve spontaneously after 5 to 7 days (depending upon severity)
- Prefered regimen: Trimethoprim-sulfamethoxazole 160 mg/800 mg PO bid for 7-10 days
- Alternative regimen (1) (for patients who are allergic to or intolerant of TMP-SMX): Pyrimethamine 50-75 mg/day PO qd or divided in 2 equal doses AND Leucovorin 10–25 mg PO qd
- Alternative regimen (2): Ciprofloxacin 500 mg PO bid for 7 days (second-line alternative)
- 1.1.1 In pregnancy
- TMP-SMX should be avoided near-term because of the potential for hyperbilirubinemia and kernicterus in the newborn.
- Ciprofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- 1.1.2 During lactation
- TMP-SMX generally should be avoided by women when nursing infants who are premature, jaundiced, ill, or stressed, or who have glucose-6-phosphate dehydrogenase deficiency.
- The American Academy of Pediatrics classifies Ciprofloxacin as usually compatible with breastfeeding, whereas the World Health Organization recommends avoiding Ciprofloxacin while breastfeeding and CDC recommends Ciprofloxacin should be used during lactation only if the potential benefit justifies the potential risk to the fetus.
- 1.1.3 In pediatric patients
- The use of TMP-SMX in children less than 2 months of age generally is not recommended.
- Available evidence is conflicting regarding the potential for growth defects and arthropathies in exposed children. Use of Ciprofloxacin in children requires assessment of potential risks and benefits.
- 1.2 Immunocompromised hosts
- Preferred regimen (1): Trimethoprim-sulfamethoxazole 160 mg/800 mg PO/IV qid for 10 days
- Preferred regimen (2): Trimethoprim-sulfamethoxazole 160 mg/800 mg PO/IV bid for 7-10 days
- Note (1): One approach is to start with TMP-SMX (160 mg/800 mg) bid regimen first, and increase daily dose and/or duration (up to 3–4 weeks) if symptoms worsen or persist.
- Note (2): IV therapy is recommended for patients with potential or documented malabsorption.
- Alternative regimen (1): Pyrimethamine 50–75 mg PO qd AND Leucovorin 10–25 mg PO qd
- Alternative regimen (2): Ciprofloxacin 500 mg PO bid for 7 days
- 2. Cystoisospora belli prophylaxis[282]
- 2.1 Primary prophylaxis
- Insufficient evidence is available to support a general recommendation for primary prophylaxis for Cystoisosporiasis per se, especially for U.S. travelers in isoporiasis-endemic areas.
- 2.2 Secondary prophylaxis (preventing recurrence in patients with CD4 count < 200 cells/mm3)
- Prefered regimen: Trimethoprim-sulfamethoxazole 160 mg/800 mg PO 3 times weekly
- Alternative regimen (1): Trimethoprim-sulfamethoxazole 160 mg/800 mg PO qd
- Alternative regimen (2): Trimethoprim-sulfamethoxazole 320 mg/1600 mg PO 3 times weekly
- Alternative regimen (3): Pyrimethamine 25 mg PO qd AND Leucovorin 5–10 mg PO qd
- Alternative regimen (4): Ciprofloxacin 500 mg PO 3 times weekly (second-line alternative)
- Note (1): Criteria for discontinuation of chronic maintenance therapy: sustained increase in CD4 count > 200 cells/mm3 for > 6 months in response to ART and without evidence of active Cystoisospora belli infection
- Note (2): Because of concerns about possible teratogenicity associated with first-trimester drug exposure, clinicians may withhold secondary prophylaxis during the first trimester and treat only symptomatic infection.
- Microsporidiosis Return to Top
- 1. Ocular[283]
- Preferred regimen: Albendazole 400 mg PO bid for 3 weeks AND Fumagillin eye drops.
- 2. Intestinal (diarrhea)[284]
- Preferred regimen:
- Adult: Albendazole 400 mg PO bid for 3 weeks for E. intestinalis.
- Pediatric: Albendazole 15 mg/kg per day divided into 2 daily doses for 7 days for E. intestinalis.
- Note: Fumagillin 20 mg PO tid is the only reported effective treatment for E. bieneusi.
- 3. Disseminated[285]
- Preferred regimen: Albendazole 400 mg po bid for 3 weeks.
### Parasites – Extraintestinal Protozoa
# Acanthamoeba
- Acanthamoeba Return to Top
- 1. Granulomatous amoebic encephalitis, meningitis, and disseminated Acanthamoeba disease[286][287]
- Preferred regimen (1): Pentamidine AND Itraconazole AND Sulfadiazine AND Flucytosine
- Preferred regimen (2): Sulfadiazine AND Fluconazole AND Pyrimethamine
- Preferred regimen (3): Sulfadiazine AND Flucytosine AND TMP-SMX
- Preferred regimen (4): TMP-SMX AND Rifampin AND Ketoconazole
- Preferred regimen (5): Miltefosine AND Amikacin
- Preferred regimen (6): Miltefosine AND Voriconazole
- Preferred regimen (7): Pentamidine AND Itraconazole AND Flucytosine AND Levofloxacin AND Amphotericin B AND Rifampin
- Preferred regimen (8): Pentamidine AND Fluconazole AND Miltefosine
- Note: The mainstay of successful treatment includes early diagnosis and combination therapy with pentamidine, azole, sulfonamide, miltefosine, and possibly flucytosine.
- 2. Cutaneous acanthamoebiasis[288][289][290]
- Preferred regimen: Pentamidine AND Sulfadiazine AND Flucytosine AND (Itraconazole OR Fluconazole) AND Chlorhexidine topical AND Ketoconazole topical
- 3. Acanthamoeba keratitis[291]
- Preferred regimen: (Polyhexamethylene biguanide topical OR Chlorhexidine topical) ± (Propamidine topical OR Hexamidine topical)
- Note (1): Azole antifungal drugs (Ketoconazole, Itraconazole, Voriconazole) may be considered as oral or topical adjuncts.
- Note (2): The duration of therapy for Acanthamoeba keratitis may last six months to a year.
- Note (3): Pain control can be helped by topical cyclopegic solutions and oral nonsteroidal medications.
- Note (4): The use of corticosteroids to control inflammation is controversial.
- Note (5): Penetrating keratoplasty may help restore visual acuity.
# Balamuthia mandrillaris
- Balamuthia mandrillaris Return to Top
- 1. Granulomatous Amebic Encephalitis[292][293]
- Preferred regimen (1): Pentamidine AND Flucytosine AND Fluconazole AND Sulfadiazine AND (Azithromycin OR Clarithromycin)
- Preferred regimen (2): Pentamidine AND Albendazole AND (Itraconazole OR Fluconazole) AND Miltefosine
# Naegleria fowleri
- Naegleria fowleri Return to Top
- Primary amoebic meningoencephalitis[294][295]
- Preferred regimen: Amphotericin B 1.5 mg/kg/day bid for 3 days; then 1 mg/kg/day for 6 days AND 1.5 mg/day intrathecal for 2 days; then 1 mg/day intrathecal qd for 8 days.
- Note: Investigational drug called miltefosine also available for treatment.
# Babesia microti
- Babesia microti Return to Top
- Babesiosis
- 1. Mild/moderate disease[296]
- Preferred regimen: Atovaquone 750 mg PO bid AND Azithromycin 600 mg PO qd for 7-10 days
- 2. Severe disease:
- Preferred regimen: Clindamycin 600 mg PO tid AND Quinine 650 mg PO tid for 7–10 days
- Preferred regimen: Clindamycin 1.2 g IV q12h
- Note (1): For overwhelming infection in asplenic patients and immunocompromised patients, treat for 6 or more weeks.
- Note (2): Consider transfusion if 10% parasitemia.
# Leishmania
- Leishmania Return to Top
- Leishmaniasis
- 1. Cutaneous Leishmaniasis[297]
- Different Leishmania species cause Old World versus New World (American) cutaneous leishmaniasis. In the Old World (the Eastern Hemisphere), the etiologic agents include Leishmania tropica, L. major, and L. aethiopica, as well as L. infantum and L. donovani. The main species in the New World (the Western Hemisphere) are either in the L. mexicana species complex (L. mexicana, L. amazonensis, and L. venezuelensis) or the subgenus Viannia (L. [V.] braziliensis, L. [V.] guyanensis, L. [V.] panamensis, and L. [V.] peruviana). The Viannia subgenus is also referred to as the L. (V.) braziliensis species complex.
- 1.1 Systemic Therapy (Parenteral)
- Preferred Regimen (1): Sodium stibogluconate 20 mg/kg IV/IM q24h for 10-20 days
- Preferred Regimen (2): Meglumine antimoniate 20 mg/kg IV/IM q24h for 10-20 days
- Alternative Regimen (1): Liposomal amphotericin B 3 mg/kg/day IV infusion for 6-10 days
- Alternative Regimen (2): Pentamidine 2-3 mg/kg/day IV/IM for 4-7 days
- Note: Data supporting the use of amphotericin B for treatment of cutaneous and mucosal leishmaniasis are anecdotal; standard dosage regimens have not been established. In the United States, pentamidine isethionate is uncommonly used for treatment of cutaneous leishmaniasis. Its limitations include the potential for irreversible toxicity and variable effectiveness.
- 1.2 Systemic Therapy (Oral)
- 1.2.1 Adults and adolescents at least 12 years of age, who weigh from 33-44 kg
- Preferred Regimen:Miltefosine 50 mg PO q12h for 28 days
- 1.2.2 Adults and adolescents at least 12 years of age, who weigh >45 kg
- Preferred Regimen:Miltefosine 50 mg PO q8h for 28 days
- Alternative Regimen (1): Ketoconazole 600 mg qd for 28 days OR qd for 6 weeks
- Alternative Regimen (2): Fluconazole 200 mg qd for 6 weeks
- Note:The FDA-approved indications are limited to infection caused by three particular species, all three of which are New World species in the Viannia subgenus—namely, Leishmania (V.) braziliensis, L. (V.) panamensis, and L. (V.) guyanensis. The "azoles" showed modest activity against some Leishmania species in some cases, but are not FDA approved
- 1.3 Local Therapy
- List of possible local therapies
- Cryotherapy (with liquid nitrogen OR Thermotherapy (use of localized current field radiofrequency heat) OR Intralesional administration of SbV OR Topical application of Paromomycin (such as an ointment containing 15% Paromomycin/12% methylbenzethonium chloride in soft white paraffin)
- 2. Visceral Leishmaniasis
- Visceral leishmaniasis usually is caused by the species L. donovani and L. infantum (L. chagasi generally is considered synonymous with L. infantum)
- 2.1 Systemic Therapy (Parenteral)
- Preferred Regimen (1): Liposomal amphotericin B 3 mg/kg/day IV for 5 days, then once on day 14 and once on day 21 (Total dose: 21 mg/kg)
- Preferred Regimen (2): Sodium stibogluconate 20 mg/kg IV/IM q24h for 28 days
- Preferred Regimen (3): Meglumine antimoniate 20 mg/kg IV/IM q24h for 28 days
- Alternative Regimen: Amphotericin B deoxycholate 0.5-1 mg/kg IV q24h (Total dose: 15-20 mg/kg)
- Note: In immunosuppressed patients, dose is 4 mg/kg/day for 5 days, then once on day 10, 17, 24, 31, and 38 (Total dose: 40 mg/kg)
- 2.2 Systemic Therapy (Oral)
- 2.2.1 Adults and adolescents at least 12 years of age, who weigh from 33-44 kg
- Preferred Regimen: Miltefosine 50 mg PO q12h for 28 days
- 2.2.2 Adults and adolescents at least 12 years of age, who weigh >45 kg
- Preferred Regimen: Miltefosine 50 mg PO q8h for 28 days
# Plasmodium
- Plasmodium Return to Top
- 1. Plasmodium falciparum[298]
- 1.1 Treatment of uncomplicated P. falciparum malaria
- 1.1.1 Treat children and adults with uncomplicated P. falciparum malaria (except pregnant women in their first trimester) with one of the following recommended ACT (artemisinin-based combination therapy)
- Preferred regimen (1): Artemether 5–24 mg/kg/day PO bid AND Lumefantrine 29–144 mg/kg/day PO bid for 3 days.
- Note: The first two doses should, ideally, be given 8 h apart.
- Dosage regimen based on Body weight (kg)
- Body weight (kg)-5 to < 15- Artemether 20 mg PO bid AND Lumefantrine 120 mg PO bid for 3 days
- Body weight (kg)-15 to < 25- Artemether 40 mg PO bid AND Lumefantrine 240 mg PO bid for 3 days
- Body weight (kg)-25 to < 35- Artemether 60 mg PO bid AND Lumefantrine 360 mg PO bid for 3 days
- Body weight (kg) ≥ 35- Artemether 80 mg PO bid AND Lumefantrine 480 mg PO bid for 3 days
- Preferred regimen (2): Artesunate 2–10 mg/kg/day PO qd AND Amodiaquine 7.5–15 mg/kg/day PO qd for 3 days
- Note: A total therapeutic dose range of 6–30 mg/kg/day artesunate and 22.5–45 mg/kg/day per dose amodiaquine is recommended.
- Dosage regimen based on Body weight (kg)
- Body weight (kg)-4.5 to < 9- Artesunate 25 mg PO qd AND Amodiaquine 67.5 mg PO qd for 3 days
- Body weight (kg)-9 to < 18 - Artesunate 50 mg PO qd AND Amodiaquine 135 mg PO qd for 3 days
- Body weight (kg)-18 to < 36- Artesunate 100 mg PO qd AND Amodiaquine 270 mg PO qd for 3 days
- Body weight (kg) ≥ 36 - Artesunate 200 mg PO qd AND Amodiaquine 540 mg PO qd for 3 days
- Preferred regimen (3): Artesunate 2–10 mg/kg/day PO qd AND Mefloquine 2–10 mg/kg/day PO qd for 3 days
- Dosage regimen based on Body weight (kg)
- Body weight (kg)-5 to < 9- Artesunate 25 mg PO qd AND Mefloquine 55 mg PO qd for 3 days
- Body weight (kg)-9to < 18- Artesunate 50 mg PO qd AND Mefloquine 110 mg PO qd for 3 days
- Body weight (kg)-18 to < 36- Artesunate 100 mg PO qd AND Mefloquine 220 mg PO qd for 3 days
- Body weight (kg)- ≥ 36 - Artesunate 200 mg PO qd AND Mefloquine 440 mg PO qd for 3 days
- Preferred regimen (4): Artesunate 2–10 mg/kg/day PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1.25 (25–70 / 1.25–3.5) mg/kg/day PO given as a single dose on day 1
- Dosage regimen based on Body weight (kg)
- Body weight (kg)-5 to < 10- Artesunate 25 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 250/12 mg PO given as a single dose on day 1
- Body weight (kg)-10 to < 25- Artesunate 50 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 500/25 mg PO given as a single dose on day 1
- Body weight (kg)-25 to < 50- Artesunate 100 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1000/50 mg PO given as a single dose on day 1
- Body weight (kg)- ≥50- Artesunate 200 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1500/75 mg PO given as a single dose on day 1
- Preferred regimen (5): Dihydroartemisinin 2–10 mg/kg/day PO qd AND Piperaquine16–27 mg/kg/day PO qd for 3 days
- Dosage regimen based on Body weight (kg)
- Body weight (kg)-5 to < 8- Dihydroartemisinin 20 mg PO qd AND Piperaquine 160 mg PO qd for 3 days
- Body weight (kg)-8 to < 11- Dihydroartemisinin 30 mg PO qd AND Piperaquine 240 mg PO qd for 3 days
- Body weight (kg)-11 to < 17 - Dihydroartemisinin 40 mg PO qd AND Piperaquine 320 mg PO qd for 3 days
- Body weight (kg)-17 to < 25- Dihydroartemisinin 60 mg PO qd AND Piperaquine 480 mg PO qd for 3 days
- Body weight (kg)-25 to < 36- Dihydroartemisinin 80 mg PO qd AND Piperaquine 640 mg PO qd for 3 days
- Body weight (kg)-36 to < 60- Dihydroartemisinin 120 mg PO qd AND Piperaquine 960 mg PO qd for 3 days
- Body weight (kg)-60 < 80 - Dihydroartemisinin 160 mg PO qd AND Piperaquine 1280 mg PO qd for 3 days
- Body weight (kg)- >80- Dose of Dihydroartemisinin 200 mg PO qd AND Piperaquine 1600 mg PO qd for 3 days
- 1.1.2 Reducing the transmissibility of treated P. falciparum infections In low-transmission areas in patients with P. falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months)
- Preferred regimen: Single dose of 0.25 mg/kg Primaquine with ACT
- 1.2 Recurrent Falciparum Malaria
- 1.2.1 Failure within 28 days
- Note:The recommended second-line treatment is an alternative ACT known to be effective in the region. Adherence to 7-day treatment regimens (with artesunate or quinine both of which should be co-administered with + tetracycline, or doxycycline or clindamycin) is likely to be poor if treatment is not directly observed; these regimens are no longer generally recommended.
- 1.2.2 Failure after 28 days
- Note: all presumed treatment failures after 4 weeks of initial treatment should, from an operational standpoint, be considered new infections and be treated with the first-line ACT. However, reuse of mefloquine within 60 days of first treatment is associated with an increased risk for neuropsychiatric reactions, and an alternative ACT should be used.
- 1.3 Reducing the transmissibility of treated P. falciparum infections In low-transmission areas in patients with P. falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months)
- Note: Single dose of 0.25 mg/kg bw Primaquine with ACT
- 1.4 Treating uncomplicated P. falciparum malaria in special risk groups
- 1.4.1 Pregnancy
- First trimester of pregnancy : Quinine AND Clindamycin 10mg/kg/day PO bid for 7 days
- Second and third trimesters : Mefloquine is considered safe for the treatment of malaria during the second and third trimesters; however, it should be given only in combination with an artemisinin derivative.
- Note (1): Quinine is associated with an increased risk for hypoglycaemia in late pregnancy, and it should be used (with clindamycin) only if effective alternatives are not available.
- Note (2): Primaquine and tetracyclines should not be used in pregnancy.
- 1.4.2 Infants less than 5kg body weight : with an ACT at the same mg/kg bw target dose as for children weighing 5 kg.
- 1.4.3 Patients co-infected with HIV: should avoid Artesunate + SP if they are also receiving Co-trimoxazole, and avoid Artesunate AND Amodiaquine if they are also receiving efavirenz or zidovudine.
- 1.4.4 Large and Obese adults: For obese patients, less drug is often distributed to fat than to other tissues; therefore, they should be dosed on the basis of an estimate of lean body weight, ideal body weight. Patients who are heavy but not obese require the same mg/kg bw doses as lighter patients.
- 1.4.5 Patients co-infected with TB: Rifamycins, in particular rifampicin, are potent CYP3A4 inducers with weak antimalarial activity. Concomitant administration of rifampicin during quinine treatment of adults with malaria was associated with a significant decrease in exposure to quinine and a five-fold higher recrudescence rate
- 1.4.6 Non-immune travellers : Treat travellers with uncomplicated P. falciparum malaria returning to nonendemic settings with an ACT.
- 1.4.7 Uncomplicated hyperparasitaemia: People with P. falciparum hyperparasitaemia are at increased risk of treatment failure, severe malaria and death so should be closely monitored, in addition to receiving an ACT.
- 2. Treatment of uncomplicated malaria caused by P. vivax, P. ovale, P. malariae or P. knowlesi
- 2.1 Blood Stage infection
- 2.1.1. Uncomplicated malaria caused by P. vivax
- 2.1.1.1 In areas with chloroquine-sensitive P. vivax
- Preferred regimen: Chloroquine total dose of 25 mg/kg PO. Chloroquine is given at an initial dose of 10 mg/kg, followed by 10 mg/kg on the second day and 5 mg/kg on the third day.
- 2.1.1.2 In areas with chloroquine-resistant P. vivax
- Note: ACTs containing Piperaquine, Mefloquine OR Lumefantrine are the recommended treatment, although Artesunate + Amodiaquine may also be effective in some areas. In the systematic review of ACTs for treating P. vivax malaria, Dihydroartemisinin + Piperaquine provided a longer prophylactic effect than ACTs with shorter half-lives (Artemether + Lumefantrine, Artesunate + Amodiaquine), with significantly fewer recurrent parasitaemias during 9 weeks of follow-up.
- 2.1.2 Uncomplicated malaria caused by P. ovale, P. malariae or P. knowlesi malaria
- Note: Resistance of P. ovale, P. malariae and P. knowlesi to antimalarial drugs is not well characterized, and infections caused by these three species are generally considered to be sensitive to chloroquine. In only one study, conducted in Indonesia, was resistance to chloroquine reported in P. malariae. The blood stages of P. ovale, P. malariae and P. knowlesi should therefore be treated with the standard regimen of ACT or Chloroquine, as for vivax malaria.
- 2.1.3 Mixed malaria infections
- Note: ACTs are effective against all malaria species and so are the treatment of choice for mixed infections.
- 2.2 Liver stages (hypnozoites) of P. vivax and P. ovale
- Note: To prevent relapse, treat P. vivax or P. ovale malaria in children and adults (except pregnant women, infants aged < 6 months, women breastfeeding infants < 6 months, women breastfeeding older infants unless they are known not to be G6PD deficient and people with G6PD deficiency) with a 14-day course of primaquine in all transmission settings. Strong recommendation, high-quality evidence In people with G6PD deficiency, consider preventing relapse by giving primaquine base at 0.75 mg base/kg bw once a week for 8 weeks, with close medical supervision for potential primaquine-induced adverse haematological effects.]
- 2.2.1 Primaquine for preventive relapse
- Preferred regimen: Primaquine 0.25–0.5 mg/kg/day PO qd for 14 days
- 2.2.2 Primaquine and glucose-6-phosphate dehydrogenase deficiency
- Preferred regimen: Primaquine 0.75 mg base/kg/day PO once a week for 8 weeks.
- Note: The decision to give or withhold Primaquine should depend on the possibility of giving the treatment under close medical supervision, with ready access to health facilities with blood transfusion services.
- 2.2.3 Prevention of relapse in pregnant or lacating women and infants
- Note: Primaquine is contraindicated in pregnant women, infants < 6 months of age and in lactating women (unless the infant is known not to be G6PD deficient).
- 3. Treatment of severe malaria
- 3.1 Treatment of severe falciparum infection with Artesunate
- 3.1.1 Adults and children with severe malaria (including infants, pregnant women in all trimesters and lactating women):-
- Preferred regimen: Artesunate IV/IM for at least 24 h and until they can tolerate oral medication. Once a patient has received at least 24 h of parenteral therapy and can tolerate oral therapy, complete treatment with 3 days of an ACT (add single dose Primaquine in areas of low transmission).
- 3.1.2 Young children weighing < 20 kg
- Preferred regimen:Artesunate 3 mg/kg per dose IV/IM q24h
- Alternatives regimen: use Artemether in preference to quinine for treating children and adults with severe malaria
- 3.2.Treating cases of suspected severe malaria pending transfer to a higher-level facility (pre-referral treatment)
- 3.2.1 Adults and children
- Preferred regimen: Artesunate IM q24h
- Alternative regimen: Artemether IM OR Quinine IM
- 3.2.2 Children < 6 years
- Preferred regimen: Where intramuscular injections of artesunate are not available, treat with a single rectal dose (10 mg/kg) of Artesunate, and refer immediately to an appropriate facility for further care.
- Note: Do not use rectal artesunate in older children and adults.
- 3.3 Pregancy
- Note: Parenteral artesunate is the treatment of choice in all trimesters. Treatment must not be delayed.
- 3.4 Treatment of severe P. Vivax infection
- Note: parenteral artesunate, treatment can be completed with a full treatment course of oral ACT or chloroquine (in countries where chloroquine is the treatment of choice). A full course of radical treatment with primaquine should be given after recovery.
- 3.5 Additional aspects of management in severe malaria
- Fluid therapy: It is not possible to give general recommendations on fluid replacement; each patient must be assessed individually and fluid resuscitation based on the estimated deficit.
- Blood Transfusion :In high-transmission settings, blood transfusion is generally recommended for children with a haemoglobin level of < 5 g/100 mL(haematocrit < 15%). In low-transmission settings, a threshold of 20% (haemoglobin,7 g/100 mL) is recommended.
- Exchange blood transfusion: Exchange blood transfusion requires intensive nursing care and a relatively large volume of blood, and it carries significant risks. There is no consensus on the indications, benefits and dangers involved or on practical details such as the volume of blood that should be exchanged. It is, therefore, not possible to make any recommendation regarding the use of exchange blood transfusion.
# Toxoplasma gondii
- Toxoplasma gondii Return to Top
- Toxoplasma gondii (treatment)
- 1. Lymphadenopathic toxoplasmosis[299]
- Preferred regimen: Treatment of immunocompetent adults with lymphadenopathic toxoplasmosis is rarely indicated; this form of the disease is usually self-limited.
- 2. Ocular disease[300]
- 2.1 Adults
- Preferred regimen: Pyrimethamine 100 mg PO for 1 day as a loading dose, then 25 to 50 mg/day AND Sulfadiazine 1 g PO qid AND folinic acid (Leucovorin 5-25 mg PO with each dose of Pyrimethamine
- 2.2 Pediatric
- Preferred regimen: Pyrimethamine 2 mg/kg PO first day then 1 mg/kg each day AND Sulfadiazine 50 mg/kg PO bid AND folinic acid (Leucovorin 7.5 mg/day PO ) for 4 to 6 weeks followed by reevaluation of the patient's condition
- Alternative regimen: The fixed combination of Trimethoprim with Sulfamethoxazole has been used as an alternative.
- Note: If the patient has a hypersensitivity reaction to sulfa drugs, Pyrimethamine AND Clindamycin can be used instead.
- 3. Maternal and fetal infection[301]
- 3.1 First and early second trimesters
- Preferred regimen: Spiramycin is recommended
- 3.2 Late second and third trimesters
- Preferred regimen: Pyrimethamine/Sulfadiazine AND Leucovorin for women with acute T. gondii infection diagnosed at a reference laboratory during gestation.
- 3.3 Infant
- Note: If the infant is likely to be infected, then treatment with drugs such as Pyrimethamine, Atovaquone, Sulfadiazine, Leucovorin is typical. Congenitally infected newborns are generally treated with pyrimethamine, a sulfonamide, and leucovorin for 1 year.
- 4. Toxoplasma gondii Encephalitis in AIDS[302]
- 4.1 Treatment for acute infection
- 4.1.1 Patients with weight <60 kg
- Preferred regimen: Pyrimethamine 200 mg PO 1 time, followed by Pyrimethamine 50 mg PO qd AND Atovaquone AND Sulfadiazine 1000 mg PO q6h AND Leucovorin 10–25 mg PO qd,
- 4.1.2 Patients with weight ≥60 kg
- Preferred regimen: Pyrimethamine 200 mg PO 1 time, followed by Pyrimethamine 75 mg PO qd AND Sulfadiazine 1500 mg PO q6h AND Leucovorin 10–25 mg PO qd and Leucovorin dose can be increased to 50 mg qd or bid
- Alternative regimen (1): Pyrimethamine AND Leucovorin AND Clindamycin 600 mg IV/ PO q6h
- Alternative regimen (2): TMP-SMX (TMP 5 mg/kg and SMX 25 mg/kg ) IV/PO bid
- Alternative regimen (3): Atovaquone 1500 mg PO bid AND Pyrimethamine AND Leucovorin
- Alternative regimen (4): Atovaquone1500 mg PO bid AND sulfadiazine 1000–1500 mg PO q6h (weight-based dosing, as in preferred therapy)
- Alternative regimen (5): Atovaquone 1500 mg PO bid
- Alternative regimen (6): Pyrimethamine AND Leucovorin AND Azithromycin 900–1200 mg PO qd
- Note: Treatment for at least 6 weeks; longer duration if clinical or radiologic disease is extensive or response is incomplete at 6 weeks.
- 4.2 Chronic maintenance therapy
- Preferred regimen: Pyrimethamine 25–50 mg PO qd AND sulfadiazine 2000–4000 mg PO qd (in 2–4 divided doses) AND Leucovorin 10–25 mg PO qd
- Alternative regimen (1): Clindamycin 600 mg PO q8h AND (Pyrimethamine 25–50 mg AND Leucovorin 10–25 mg) PO qd
- Alternative regimen (2): TMP-SMX DS 1 tablet bid
- Alternative regimen (3): Atovaquone 750–1500 mg PO bid AND (Pyrimethamine 25 mg AND Leucovorin 10 mg) PO qd
- Alternative regimen (4): Atovaquone 750–1500 mg PO bid
- Alternative regimen (5): Sulfadiazine 2000–4000 mg PO bid/qid
- Alternative regimen (6): Atovaquone 750–1500 mg PO bid Pyrimethamine and Leucovorin doses are the same as for preferred therapy
- Note: Adjunctive corticosteroids (e.g., Dexamethasone) should only be administered when clinically indicated to treat mass effect associated with focal lesions or associated edema; discontinue as soon as clinically feasible. Anticonvulsants should be administered to patients with a history of seizures and continued through acute treatment, but should not be used as seizure prophylaxis . If Clindamycin is used in place of Sulfadiazine, additional therapy must be added to prevent PCP.
- Toxoplasma gondii (prophylaxis)
- 1. Prophylaxis to prevent first episode of encephalitis in AIDS[303]
- 1.1 Indications
- Toxoplasma IgG-positive patients with CD4 count <100 cells/µL
- Seronegative patients receiving PCP prophylaxis not active against toxoplasmosis should have toxoplasma serology retested if CD4 count decline to <100 cells/µL. Prophylaxis should be initiated if seroconversion occurred.
- 1.2 Prophylactic therapy
- Preferred regimen: TMP-SMX 1 DS PO daily
- Alternative regimen (1): TMP-SMX 1 DS PO three times weekly
- Alternative regimen (2): TMP-SMX 1 SS PO qd
- Alternative regimen (3): Dapsone 50 mg PO qd AND (Pyrimethamine 50 mg PO AND Leucovorin 25 mg) PO weekly
- Alternative regimen (4): Dapsone 200 mg PO AND Pyrimethamine 75 mg PO AND Leucovorin 25 mg PO weekly
- Alternative regimen (5): Atovaquone 1500 mg PO qd
- Alternative regimen (6): Atovaquone 1500 mg PO AND Pyrimethamine 25 mg PO AND Leucovorin 10 mg PO qd
# Trichomonas vaginalis
- Trichomonas vaginalis Return to Top
- 1. T. vaginalis infection in adults [304]
- Preferred regimen (1): Metronidazole 2 g PO in a single dose
- Preferred regimen (2): Tinidazole 2 g PO in a single dose
- Alternative regimen: Metronidazole 500 mg PO bid for 7 days
- 2. T. vaginalis infection in pregnant and lactating Women
- 2.1 Pregnant women
- Preferred regimen: Metronidazole 2 g PO in a single dose.
- 2.2 Post-partum and Breastfeeding
- Preferred regimen (1): Metronidazole 2 g PO in a single dose.
- Preferred regimen (2): Tinidazole 2 g PO in a single dose
- Note (1): Do not breastfeed for 12-24 hrs following Metronidazole and 72 hrs following Tinidazole
- Note (2): Symptomatic pregnant women, regardless of pregnancy stage, should be tested and considered for treatment. Pregnant women should be advised of the risk and benefits to treatment as infection (definitely) and treatment (possibly)
- Note (3): Pregnant women with HIV who are treated for T. vaginalis infection should be retested 3 months after treatment.
- 3. T. vaginalis infection in patients with HIV
- Preferred regimen: Metronidazole 500 mg PO bid for 7 days
- 4. Persistent or recurrent trichomoniasis
- 4.1 Treatment failure
- Preferred regimen: Metronidazole 500 mg PO bid for 7 days
- 4.2 Treatment failure again
- Preferred regimen (1): Metronidazole 2 g PO for 7 days
- Preferred regimen (2): Tinidazole 2 g PO for 7 days
- 4.3 Nitroimidazole-resistant cases
- Preferred regimen: Tinidazole 2-3 g PO for 14 days
# African trypanosomiasis
- African trypanosomiasis Return to Top
- Sleeping sickness[305]
- 1. East african trypanosomiasis
- 1.1 T. b. rhodesiense, hemolymphatic stage
- 1.1.1 Adult
- Preferred regimen: Suramin 1 gm IV on days 1,3,5,14, and 21
- 1.1.2 Pediatric
- Preferred regimen: Suramin 20 mg/kg IV on days 1, 3, 5, 14, and 21
- 1.2 T. b. rhodesiense, CNS involvement
- 1.2.1 Adult
- Preferred regimen: Melarsoprol 2-3.6 mg/kg/day IV for 3 days. After 7 days, 3.6 mg/kg/day for 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days.
- 1.2.2 Pediatric
- Preferred regimen: Melarsoprol 2-3.6 mg/kg/day IV for 3 days. After 7 days, 3.6 mg/kg/day for 3 days. Give a 3rd series of 3.6 mg/kg/d after 7 days
- 2. West african trypanosomiasis
- 2.1 T. b. gambiense, hemolymphatic stage
- 2.1.1 Adult
- Preferred regimen: Pentamidine 4 mg/kg/day IM/ IV for 7-10 days
- 2.1.2 Pediatric
- Preferred regimen: Pentamidine 4 mg/kg/day IM/IV for 7-10 days
- Note (1): Pentamidine should be used during pregnancy and lacation only if the potential benefit justifies the potential risk
- Note (2): IM/IV Pentamidine have a similar safety profile in children age 4 months and older as in adults. Pentamidine is listed as a medicine for the treatment of 1st stage African trypanosomiasis infection (Trypanosoma brucei gambiense) on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.
- 2.2 T. b. gambiense, CNS involvement
- 2.2.1 Adult
- Preferred regimen: Eflornithine 400 mg/kg/day IV qid for 14 days
- 2.2.2 Pediatric
- Preferred regimen: Eflornithine 400 mg/kg/day IV qid for 14 days
- Note (1): Eflornithine should be used during pregnancy and lactation, only if the potential benefit justifies the potential risk
- Note (2): The safety of Eflornithine in children has not been established. Eflornithine is not approved by the Food and Drug Administration (FDA) for use in pediatric patients. Eflornithine is listed for the treatment of 1st stage African trypanosomiasis inTrypanosoma brucei gambiense infection on the WHO Model List of Essential Medicines for Children, intended for the use of children up to 12 years of age.
# American trypanosomiasis
- American trypanosomiasis Return to Top
- Chagas disease[306]
- 1. Preferred regimen(1):
- Patients of age < 12 years- Benznidazole 5-7.5 mg/kg/ day PO bid for 60 days
- Patients of age 12 years or older- Benznidazole 5-7 mg/kg/day PO bid for 60 days
- 2. Preferred regimen(2):
- Patients of age ≤ 10 years- Nifurtimox 15-20 mg/kg/day PO tid/ qid for 90 days
- Patients of age 11-16 years- Nifurtimox 12.5-15 mg/kg/day PO tid/ qid for 90 days
- Patients of age 17 years or older- Nifurtimox 8-10 mg/kg/day PO tid/ qid for 90 days
- Note: In the United States, Nifurtimox and Benznidazole are not FDA approved and are available only from CDC under investigational protocols.
### Parasites – Intestinal Nematodes (Roundworms)
- Gnathostoma spinigerum Return to Top
- Eosinophilic Meningitis
Preferred regimen: Supportive measures. Anthelminthic therapy might be deleterious by augmenting the inflammation due to the death of the larvae. The use of corticosteroids is generally favored for suppression of the inflammation but there are no clinical trials that prove its efficacy.[307]
- Preferred regimen: Supportive measures. Anthelminthic therapy might be deleterious by augmenting the inflammation due to the death of the larvae. The use of corticosteroids is generally favored for suppression of the inflammation but there are no clinical trials that prove its efficacy.[307]
- Cutaneous disease:
- Preferred regimen: Albendazole 400 mg bid for 21 days OR Ivermectin 200 mcg/kg qd for 2 days[308]
- Alternative regimen: Albendazole 400 mg qd for 21 days OR Ivermectin 200 mcg/kg qd single dose[309]
- Ancylostoma braziliense Return to Top
- Cutaneous larva migrans treatment[310]
- 1.1 In adults
- Preferred regimen: Albendazole 400 mg PO qd for 3-7 days
- Alternative regimen: Ivermectin 200 mcg/kg PO qd for 1-2 days
- 1.2 In children
- Preferred regimen: Albendazole > 2 years then 400 mg PO qd for 3 days
- Alternative regimen: Ivermectin > 15 kg give 200 mcg/kg single dose
- Note: Albendazole is contraindicated in children younger than 2 years age
- Angiostrongylus cantonensis Return to Top
- Preferred: Symptomatic therapy, serial lumber puncture, corticosteroids (prednisone 60 mg qd for 2 weeks) and analgesics.[311]
- Note: Albendazole and Mebendazole are generally not recommended due to the risk of exacerbation of neurological symptoms following anthelminthic therapy.[312]
- Ascaris lumbricoides Return to Top
- Preferred regimen: Albendazole 400 mg PO qd OR Mebendazole 500 mg PO qd or 100 mg bid for 3 days[313]
- Note: Albendazole dose for children of 1-2 years is 200 mg instead of 400 mg.
- Alternative regimen (1): Ivermectin 150 to 200 µg/kg PO single dose[314]
- Alternative regimen (2): Nitazoxanide 500 mg bid for 3 days [315]
- Alternative regimen (3): Levamisole 120 mg PO single dose
- Note: Pediatric dose: 2.5 mg/kg [316]
- Alternative regimen (4): Pyrantel Pamoate 11 mg/kg single dose PO - maximum 1.0 g[316]
- Alternative regimen (5): Piperazine citrate 75 mg/kg qd for 2 days - maximum 3.5 g[316]
- Capillaria philippinensis Return to Top
- 1. Intestinal capillariasis[317][318][319]
- Preferred regimen: Albendazole 400 mg/day PO for 10-30 days
- Alternative regimen: Mebendazole 200 mg PO bid for 20-30 days
- Enterobius vermicularis Return to Top
- 1. Enterobius vermicularis[320]
- Preferred regimen (1): Albendazole 400 mg PO single dose
- Preferred regimen (2): Mebendazole 100 mg PO single dose
- Preferred regimen (3): Ivermectin 200 µg/kg PO single dose
- Preferred regimen (4): Pyrantel pamoate 11 mg/kg up to 1.0 g PO single dose
- Note: A second dose is given 2 weeks later because of the frequency of reinfection and autoinfection.
- Necator americanus Return to Top
- Preferred regimen: Albendazole 400 mg PO single dose[321]
- Alternative regimen (1): Mebendazole 100 mg PO bid or 500 mg daily for 3 days
- Alternative regimen (2): Pyrantel pamoate 11 mg/kg PO qd (maximum 1 g/day) for 3 days[322]
- Ancylostoma duodenale Return to Top
- Preferred regimen: Albendazole 400 mg PO single dose[321]
- Alternative regimen (1): Mebendazole 100 mg PO bid or 500 mg daily for 3 days
- Alternative regimen (2): Pyrantel pamoate 11 mg/kg PO qd (maximum 1 g/day) for 3 days[323]
- Strongyloides stercoralis Return to Top
- Preferred regimen: Ivermectin 200 mcg/kg/day PO qd for 2 days or two doses 2 weeks apart from each other[324]
- Alternative regimen: Albendazole 400 mg PO bid for 3-7 days[325]
- Trichuris trichiura Return to Top
- Preferred regimen: Albendazole 400 mg PO qd for 3 days
- Alternatie regimen (1): Mebendazole 100 mg PO bid for 3 days
- Alternative regimen (2): Ivermectin 200 mcg/kg/day PO qd for 3 days[326]
### Parasites – Extraintestinal Nematodes (Roundworms)
- Ancylostoma braziliense Return to Top
- Preferred regimen[327]
- Adult: Albendazole 400mg PO qd for 3-7 days.
- Pediatric: Albendazole > 2 years 400mg PO qd for 3 days
- Note: This drug is contraindicated in children younger than 2 years.
- Alternative regimen[328]
- Adult: Ivermectin 200 mcg/kg PO qd for one or two days.
- Pediatric: Ivermectin >15 kg give 200mcg/kg single dose.
- Angiostrongylus cantonensis Return to Top
- Preferred: Symptomatic therapy, serial lumber puncture, corticosteroids (prednisone 60mg qd for 2 weeks) and analgesics[329]
- Note: Albendazole and Mebendazole are generally not recommended due to the risk of exacerbation of neurological symptoms following anthelminthic therapy.[312]
- Filariasis Return to Top
- Filariasis[330][331][332]
- 1. Lymphatic filariasis caused by Wuchereria bancrofti, Brugia malayi, Brugia timori
- Preferred regimen: Diethylcarbamazine 6 mg/kd/day PO tid for 12 days (single dose if patient will continue to live in endemic area or is younger than 9 years old)
- 2. Loa loa filariasis[333]
- 2.1 Symptomatic loiasis with < 8,000 microfilariae/mL
- Preferred regimen: Diethylcarbamazine 8–10 mg/kd/day PO tid for 21 days
- 2.2 Symptomatic loiasis, with < 8,000 microfilariae/mL and failed 2 rounds DEC
- Preferred regimen: Albendazole 200 mg PO bid for 21 days
- 2.3 Symptomatic loiasis, with ≥ 8,000 microfilariae/ml to suppress microfilaremia prior to treatment with DEC
- Preferred regimen: Albendazole 200 mg PO bid for 21 days
- 2.4 Symptomatic loiasis, with ≥ 8,000 microfilariae/mL
- Preferred regimen: Apheresis followed by Diethylcarbamazine
- Note: Apheresis should be performed at an institution with experience in using this therapeutic modality for loiasis.
- 3. River blindness (onchocerciasis) caused by Onchocerca volvulus
- Preferred regimen: Ivermectin 150 μg/kg PO single dose, repeated every 6-12 mos until asymptomatic
- Alternative regimen: Doxycycline 100 mg PO qd for 6 weeks, alone or followed by Ivermectin 150 μg/kg PO single dose
- Note: Do NOT administer Diethylcarbamazine where onchocerciasis is endemic due to increased risk for severe local inflammation in patients with ocular microfilariae.
- 4. Mansonella ozzardi
- Preferred regimen: Ivermectin 200 μg/kg PO single dose
- Note: Endosymbiotic Wolbachia are essential to filarial growth, development, embryogenesis and survival and represent an additional target for therapy. Doxycycline 100–200 mg PO qd for 6–8 weeks results in loss of Wolbachia and decrease in both micro- and macrofilariae.
- 5. Mansonella perstans
- Preferred regimen: Doxycycline 100–200 mg PO qd for 6–8 weeks
- 6. Mansonella streptocerca
- Preferred regimen (1): Diethylcarbamazine 6 mg/kd/day PO tid for 12 days
- Preferred regimen (2): Ivermectin 150 μg/kg PO single dose
- 7. Tropical pulmonary eosinophilia caused by Wuchereria bancrofti
- Preferred regimen: Diethylcarbamazine 6 mg/kd/day PO tid for 12–21 days
- Gnathostoma spinigerum Return to Top
- 1. Eosinophilic Meningitis
Preferred regimen: Supportive measures. Anthelminthic therapy might be deleterious by augmenting the inflammation due to the death of the larvae. The use of corticosteroids is generally favored for suppression of the inflammation but there are no clinical trials that prove its efficacy.[307]
- Preferred regimen: Supportive measures. Anthelminthic therapy might be deleterious by augmenting the inflammation due to the death of the larvae. The use of corticosteroids is generally favored for suppression of the inflammation but there are no clinical trials that prove its efficacy.[307]
- 2. Cutaneous disease:
- Preferred regimen (1): Albendazole 400 mg bid for 21 days[334]
- Preferred regimen (2): Ivermectin 200 mcg/kg once daily for 2 days[335]
- Alternative regimen (1): Albendazole 400 mg daily for 21 days[336]
- Alternative regimen (2): Ivermectin 200 mcg/kg once daily for 1 day[337]
- Toxocariasis Return to Top
- 1.1 Visceral toxocariasis
- Preferred regimen: Albendazole 400 mg PO bid for five days (both adult and pediatric dosage)[338]
- Alternative regimen: Mebendazole 100-200 mg PO bid for five days (both adult and pediatric dosage)[339]
- Note: Treatment is indicated for moderate-severe cases. Patients with mild symptoms of toxocariasis may not require anthelminthic therapy as symptoms are limited.[340]
- 1.2 Ocular toxocariasis
- Preferred regimen: Prednisone 0.5-1mg/kg/day PO q24h AND Albendazole 400mg PO bid for 2 to 4 weeks (pediatric dose: 400mg PO qd)[341]
- Note: Surgical therapy might be neeeded.
- Trichinella spiralis Return to Top
- Trichinella spiralis[342]
- Preferred regimen (1): Albendazole 400 mg PO bid for 8-14 days
- Preferred regimen (2): Mebendazole 200-400 mg PO tid for 3 days THEN 400-500 mg PO tid for 10 days
- Note (1): Both treatment schemes are suitable for adult and pediatric dosages
- Note (1): Albendazole and Mebendazole are contraindicated during pregnancy and not recommended in children aged 2 years.
- Alternative regimen (1): (severe symptoms) Prednisone 30 mg/day-60 mg/day for 10-15 days
- Alternative regimen (2): Pyrantel 10-20 mg/kg single dose for 2-3 days
### Parasites – Trematodes (Flukes)
- Clonorchis sinensis Return to Top
- Preferred regimen: Praziquantel 75mg/kg/day PO tid for 2 days[343]
- Alternative regimen (1): Albendazole 10mg/kg/day PO qd for 7 days[344]
- Alternative regimen (2): Tribendimidine 400mg PO single dose[345]
- This regimen is still under investigation, but it appears to be as effective as Praziquantel.
- Note: Urgent biliary decompression might be required for patients with acute cholangitis.
- Dicrocoelium dendriticum Return to Top
- Preferred regimen: Praziquantel 25 mg/kg PO tid for 2 days[346]
- Note: Praziquantel is not approved for treatment of children less than 4 years old.[347]
- Alternative regimen (1): Myrrh (commiphora molmol) 12 mg/kg/day PO for 6 days[348]
- Alternative regimen (2): Triclabendazole 10 mg/kg PO single dose[348]
- Fasciola hepatica Return to Top
- Preferred regimen: Triclabendazole 10 mg/kg PO one dose[349]
- Note: Two-dose (double-dose) triclabendazole therapy can be given to patients who have severe or heavy Fasciola infections (many parasites) or who did not respond to single-dose therapy.
- Alternative regimen: Nitazoxanide 500mg PO bid for 7 days
- Paragonimus westermani Return to Top
- Preferred regimen (1): Praziquantel 25 mg/kg PO tid for 3 days[350]
- Preferred regimen (2): Triclabendazole 10 mg/kg PO qd or bid
- Alternative regimen (1): Bithinol 30-50mg/kg PO on alternate days for 10-15 doses
- Alternative regimen (2): Niclosamide 2mg/kg PO single dose
- Schistosomiasis Return to Top
- 1. Schistosoma mansoni, S. haematobium, S. intercalatum[351]
- Preferred regimen: Praziquantel 40 mg/kg per day PO in qd or bid for one day
- Alternative regimen (1): Oxamniquine 20 mg/kg PO single dose[352][353]
- Alternative regimen (2): Artemisinin no dose is established yet[351]
- Alternative regimen (3): Mefloquine 250 mg PO single dose
- Note: There is no benefit in associating the alternative therapies to Praziquantel.
- Note: Praziquantel is not effective against larval/egg stages of the disease.[211]
- 2. S. japonicum, S. mekongi[351]
- Preferred regimen: Praziquantel 60 mg/kg per day PO bid for one day
- Alternative regimen (1): Artemisinin no dose is established yet
- Alternative regimen (2): Mefloquine 250 mg PO single dose
- Note: There is no benefit in associating the alternative therapies to Praziquantel.
- 3. Katayama Fever
- Preferred regimen: Prednisone 20-40 mg/day PO for 5 days, THEN Praziquantel[354]
- Note: Praziquantel should be used after 4-6 weeks of exposure, because it cannot kill the larvae stages of the Schistosoma. Praziquantel should be used after acute schistosomiasis syndrome symptoms have resolved always together with corticosteroids, only when ova are detected in stool or urine samples.[355]
- 4. Neuroschistosomiasis
- Preferred regimen: prednisone 1-2 mg/kg
- Note: Praziquantel should only be introduced after a few days of the initiation of corticosteroid therapy, due to the risk of increasing the inflammatory response.
### Parasites – Cestodes (Tapeworms)
- Echinococcus Return to Top
- Echinococcus treatment[356]
- 1.1 Echinococcus granulosus (hydatid disease) treatment[357]
- Preferred regimen: Albendazole ≥ 60 kg 400 mg PO bid or < 60 kg 10-15 mg/kg/day PO bid with meals for 3-6 months
- Alternative regimen: Mebendazole 40-50mg/kg/day PO tid for 3-6 months
- Note: Percutaneous aspiration-injection-reaspiration (PAIR). Puncture & needle aspirate cyst content. Instill hypertonic saline (15–30%) or absolute alcohol, wait 20–30 min, then re-aspirate with final irrigation. Administer Albendazole at least 4 hours before PAIR.
- Note: If surgery is needed, make sure to administer Albendazole for at least a week before the surgery, and to keep the medication for at least 4 weeks after the procedure.
- 1.2 Echinococcus multilocularis (alveolar cyst disease) treatment[358]
- Preferred regimen: Albendazole ≥ 60 kg 400 mg PO bid or < 60 kg 15 mg/kg/day PO bid with meals for at least 2 years. Long-term follow up needed to evaluate progression of the lesions.
# Neurocysticercosis
- Neurocysticercosis Return to Top
- Neurocysticercosis treatment
- 1. Parenchymal neurocysticercosis
- 1.1 Single lesions[359]
- Preferred regimen: Albendazole 15 mg/kg/day PO bid for 3-8 days AND Prednisone 1 mg/kg/day PO qid for 8-10 days followed by a taper
- 1.2 Multiple cysts
- Preferred regimen: Albendazole 15 mg/kg/day PO bid for 8-15 days and high-dose steroids
- Preferred regimen: Praziquantel 50 mg/kg/day PO tid AND Albendazole 15 mg/kg/day PO bid
- 1.3 Cysticercal encephalitis [359]
- Cysticercal encephalitis (diffuse cerebral edema associated with multiple inflamed cysticerci) is a contraindication for antiparasitic therapy, since enhanced parasite killing can exacerbate host inflammatory response and lead to diffuse cerebral edema and potential transtentorial herniation. Most cases of cysticercal encephalitis improve with corticosteroid therapy
- 1.4 Calcified cysts
- Radiographic evidence of parenchymal calcifications is a significant risk factor for recurrent seizure activity; these lesions are present in about 10 percent of individuals in regions where neurocysticercosis is endemic. Seizures in these patients should be treated with antiepileptic therapy.
- 2. Extraparenchymal NCC
- 2.1 Subarachnoid cysts
- Preferred regimen: Albendazole 15 mg/kg/day PO bid for 28 days AND (Prednisone up to 60 mg/day PO OR Dexamethasone (up to 24 mg/day)) along with the antiparasitic therapy. The dose can often be tapered after a few weeks. However, in cases for which more prolonged steroid therapy is required, methotrexate can be used as a steroid-sparing agent
- 2.2 Giant cysts
- Giant cysticerci are usually accompanied by cerebral edema and mass effect, which should be managed with high-dose corticosteroids (with or without mannitol).
- 2.3 Intraventricular cysts
- Emergent management with CSF diversion via a ventriculostomy or placement of a ventriculo-peritoneal shunt
- Treatment of residual hydrocephalus may be managed with endoscopic foraminotomy and endoscopic third ventriculostomy; this approach may also allow debulking of cisternal cysticerci
- 2.4 Ocular cysticercosis
- Surgical excision is warranted in the setting of intraocular cysts
- Cysticercal involvement of the extraocular muscles should be managed with albendazole and corticosteroids.
- 2.5 Spinal cysticercosis
- Medical therapy with corticosteroids and antiparasitic drugs
- Sparganosis Return to Top
- Sparganosis (Spirometra mansonoides) treatment [360]
- Preferred treatment: Surgical resection or ethanol injection of subcutaneous masses
- Note: Praziquantel 75 mg/kg/day PO qd for 3 days is controversial. It's been innefective in some cases, but has had some results in patients when surgical therapy wasn't an option.[361]
### Parasites – Ectoparasites
- Body lice Return to Top
- Pediculus humanus, corporis treatment[362]
- A body lice infestation is treated by improving the personal hygiene of the infested person, including assuring a regular (at least weekly) change of clean clothes.
- Clothing, bedding, and towels used by the infested person should be laundered using hot water (at least 130°F) and machine dried using the hot cycle.
- Sometimes the infested person also is treated with a pediculicide Ivermectin Lotion; however, a pediculicide Ivermectin generally is not necessary if hygiene is maintained and items are laundered appropriately at least once a week. A pediculicide Ivermectin should be applied exactly as directed on the bottle or by your physician.
- Head lice Return to Top
- Pediculus humanus, capitis treatment[363]
- Preferred regimen (1): Permethrin 1% lotion apply to shampooed dried hair for 10 min.; repeat in 9-10 days
- Preferred regimen (2): Malathion 0.5% lotion (Ovide) apply to dry hair for 8–12hrs, then shampoo (2 doses 7-9 days apart)
- Alternative regimen: Ivermectin 200 μg/kg PO once; 3 doses at 7 day intervals reported effective.
- Pubic lice Return to Top
- Phthirus pubis treatment[364]
- Preferred regimen (1): Permethrin 1% cream rinse applied to affected areas and washed off after 10 minutes
- Preferred regimen (2): Pyrethrins with piperonyl butoxide applied to the affected area and washed off after 10 minutes
- Alternative regimen (1): Malathion 0.5% lotion applied to affected areas and washed off after 8–12 hours
- Alternative regimen (2): Ivermectin 250 ug/kg PO, repeated in 2 weeks
- Myiasis Return to Top
- Preferred regimen: No medications approved by the FDA are available for treatment[365]
- Note: Fly larvae need to be surgically removed.
- Fly larvae treatment [366]
- Preferred treatment (1): Occlude punctum to prevent gas exchange with petrolatum, fingernail polish, makeup cream or bacon.
- Preferred treatment (2): When larva migrates, manually remove.
- Note (1): Myiasis is due to larvae of flies.
- Note (2): Usually cutaneous/subcutaneous nodule with central punctum.
- Scabies Return to Top
- Sarcoptes scabiei treatment[367]
- 1. Adult
- Preferred regimen (1): Permethrin 5% cream applied to all areas of the body from the neck down and washed off after 8–14 hours
- Preferred regimen (2): Ivermectin 200 ug/kg PO qd and repeated in 2 weeks
- Alternative regimen: Lindane (1%) 1 oz of lotion or 30 g of cream applied in a thin layer to all areas of the body from the neck down and thoroughly washed off after 8 hours
- 2. Infants and young children
- Preferred regimen: Permethrin 5% cream applied to all areas of the body from the neck down and washed off after 8–14 hours
- Note: Infants and young children aged< 10 years should not be treated with lindane.
- 3. Crusted Scabies
- Crusted scabies (i.e., Norwegian scabies) is an aggressive infestation that usually occurs in immunodeficient, debilitated, or malnourished persons, including persons receiving systemic or potent topical glucocorticoids, organ transplant recipients, persons with HIV infection or human T-lymphotrophic virus-1-infection, and persons with hematologic malignancies.
- Preferred regimen: (Topical scabicide 5% topical Benzyl benzoate 5% OR topical Permethrin 5% cream (full-body application to be repeated daily for 7 days then twice weekly until discharge or cure) AND treatment with Ivermectin 200 ug/kg PO on days 1,2,8,9, and 15. Additional Ivermectin treatment on days 22 and 29 might be required for severe cases
- 4.Pregnant or Lactating Women
- Preferred regimen: Permethrin 5% cream applied to all areas of the body from the neck down and washed off after 8–14 hours
### Viruses
- Adenovirus Return to Top
- Adenovirus[368]
- 1. In severe cases of pneumonia or post hematopoietic stem cell transplantation
- Preferred regimen (1): Cidofovir 5 mg/kg/week IV for 2 weeks, then every 2 weeks AND Probenecid 1.25 g/M2 PO given 3 hours before Cidofovir and 3 & 9 hours after each infusion
- Preferred regimen (2): Cidofovir 1 mg/kg IV 3 times per week
- Note: Ganciclovir, Foscarnet and Ribavirin are not recommended for use on adenovirus infection.[369]
- 2. For hemorrhagic cystitis
- Preferred regimen: Cidofovir (5 mg/kg in 100 mL saline instilled into bladder) intravesical[370]
- 3. Pink eye (viral conjunctivitis)
- Preferred regimen: No specific treatment available. If symptomatic, cold artificial tears may help.
- 4.Bronchitis
- Preferred regimen: No specific therapy recommended, treatment is symptomatic.
- SARS Return to Top
- Severe acute respiratory distress syndrome- coronavirus infection treatment[371][372][373]
- Preferred regimen: supportive therapy
- Note: New therapies were studied for SARS during the last outbreaks which concluded:
- Ribavirin ineffective and probably harmful due to haemolytic anaemia
- Lopinavir AND Ritonavir is still controversial and need further investigation
- Interferon has no benefit and its studies are inconclusive
- Corticosteroids increases risk of fungal infections, some studies showed a higher incidence of psychosis, diabetes, avascular necrosis and osteoporosis
- Inhaled Nitric oxide potent mediator of airway inflammation, its has improved oxygenation in some studies
- Cytomegalovirus Return to Top
- Cytomegalovirus treatment[374]
- 1. Immunocompetent patients
- 1.1 Mononucleosis syndrome
- Preferred regimen: supportive therapy
- 1.2 CMV in pregnancy
- Preferred regimen: Hyperimmune 200 IU/kg of maternal weight as single-dose during pregnancy
- 2. Immunocompromised patients
- 2.1 Retinitis
- Preferred regimen (1): Ganciclovir intraocular implant PLUS Valganciclovir 900 mg PO bid for 14-21 days THEN Valganciclovir 900mg PO qq for maintenance therapy - for immediate sight-threatening lesions
- Preferred regimen (2): Valganciclovir 900 mg PO bid for 14-21 days THEN Valganciclovir 900 mg PO qq for maintenance therapy - for peripheral lesions
- Alternative regimen (1): Foscarnet 60 mg/kg IV q8h OR Foscarnet 90 mg/kg IV q12h for 14-21 days THEN Foscarnet 90-120 mg/kg IV q24h
- Alternative regimen (2): Cidofovir 5 mg/kg IV for 2 weeks THEN Cidofovir 5 mg/kg IV every other week - each dose should be admnistered with IV saline hydration and probenecid
- Alternative regimen (3): Ganciclovir 5 mg/kg IV q12h for 14-21 days THEN Valganciclovir 900 mg PO bid
- Alternative regimen (4): Fomivirsen intravitreal injection - for relapses
- Note: keep a maintenance dose of Valganciclovir 900 mg PO qd until CD4 >100/mm³
- 2.2 Transplant patients
- Preferred regimen: Valganciclovir 900 mg PO bid OR Ganciclovir 5 mg/kg IV q12h for at least 2-3 weeek
- Note: Use Valganciclovir 900 mg PO qd for 1-3 months if high dose of immunosuppression.
- 2.3 Colitis, esophagitis, gastritis
- Preferred regimen: Ganciclovir 5 mg/kg/dose IV q12h for 3-6 weeks weeks for induction. There is no agreement on the use of maintenance.
- Alternative regimen: Cidofovir 5 mg/kg IV for 2 weeks, then 5 mg/kg every other week; each dose should be administered with IV saline hydration and oral probenecid 2 g PO 3h before each dose and further 1 g doses after 2h and 8h.
- Note: Switch to oral Valganciclovir when PO tolerated & when symptoms not severe enough to interfere with absorption.
- 2.4 Pneumonia
- Preferred regimen: Valganciclovir 900 mg PO bid for 14–21 days, then 900 mg PO qd for maintenance therapy
- Alternative regimen for retinitis: Ganciclovir 5 mg/kg IV q12h for 14–21 days, then Valganciclovir 900 mg PO qd
- Note: In bone marrow transplant patients, combine therapy with CMV immune globulin.
- 2.5 Encephalitis, ventriculitis
- Note: Treatment not defined, but should be considered the same as retinitis. Disease may develop while taking Ganciclovir as suppressive therapy.
- 2.6 Lumbosacral polyradiculopathy
- Preferred regimen: Ganciclovir, as with retinitis
- Alternative regimen: Foscarnet 40 mg/kg IV q12h another option
- Alternative regimen: Cidofovir 5 mg/kg IV for 2 weeks, then 5 mg/kg every other week; each dose should be administered with IV saline hydration and oral probenecid 2 g PO 3h before each dose and further 1 g doses after 2h and 8h.
- Note (1): Switch to Valganciclovir when possible.
- Note (2): Suppression continued until CD4 remains >100/mm³ for 6 months.
- 2.7 Peri/postnatal severe CMV infection in very low birth weight infants
- Preferred regimen: Ganciclovir 6 mg/kg/dose IV q12h for 3 weeks[375]
- Enterovirus D68 Return to Top
- Enterovirus treatment[376]
- Preferred regimen: supportive therapy
- Note: A new drug Pleconaril designed to affect Rhinovirus is being suggested to be effective against Enterovirus D68 but further investigation is required[377]
- Ebola virus Return to Top
- Ebola virus treatment[378][379]
- Preferred regimen: supportive therapy. There is no specific antiviral drug available for Ebola thus far. For information of investigational therapies including Favipiravir, Brincidofovir, ZMapp, TKM-Ebola, AVI-6002, and BCX4430, see here.
- Isolate patient
- Provide intravenous fluids (IV) (patients need large volumes in some cases) and maintain electrolytes at normal levels
- Maintain oxygen saturation and blood pressure
- Administer blood products if coagulopathy or bleeding, antiemetics if vomiting , antipyretics if fever, analgesics, anti-motility if severe diarrhea, total parenteral nutrition if patient has poor oral intake and dialysis if there's renal failure
- Treat other infections if they occur. Provide adequate Gram-negative coverage and gram-positive if the patient has any catheter or hospital-acquired pneumonia.
- If there's respiratory failure, invasive mechanical ventilation may be the best option to offer respiratory support
- Note (1): Recovery from Ebola depends on good supportive care and the patient’s immune response.
- Note (2): While there is no proven treatment available for Ebola virus disease, human convalescent whole blood has been used as an empirical treatment with promising results in a small group of EVD cases.[380][381]
- Note (3): People who recover from Ebola infection develop antibodies that last for at least 10 years, possibly longer. It is not known if people who recover are immune for life or if they can become infected with a different species of Ebola.
- Note (4): Some people who have recovered from Ebola have developed long-term complications, such as joint and vision problems.
- Marburg virus Return to Top
- Marburg virus treatment
- Preferred regimen: supportive therapy including maintenance of blood volume and electrolyte balance, as well as analgesics and standard nursing care[382][383]
- Hantavirus Return to Top
- Hantavirus cardiopulmonary syndrome treatment[384]
- Preferred regimen: Supportive therapy, there is no specific treatment for hantavirus cardiopulmonary syndrome
- Note (1): ICU management should include careful assessment, monitoring and adjustment of volume status and cardiac function, including inotropic and vasopressor support if needed
- Note (2): Fluids should be administered carefully due to the potential for capillary leakage
- Note (3): Supplemental oxygen should be administered if patients become hypoxic
- Note (4): Equipment and materials for intubation and mechanical ventilation should be readily available since onset of respiratory failure may be precipitous
- Note (5): Extracorporeal membrane oxygenation was used with survival rates of 50% in some studies in patients with cardiac index output <2.5L/min/m²[385]
- Dengue virus Return to Top
- Dengue virus [386]
- 1. Patients who may be sent home
- These are patients who are able to tolerate adequate volumes of oral fluids and pass urine at least once every six hours, and do not have any of the warning signs, particularly when fever subsides
- Patients who are sent home should be monitored daily by health care providers for temperature pattern, volume of fluid intake and losses, urine output (volume and frequency), warning signs, signs of plasma leakage and bleeding, haematocrit, and white blood cell and platelet counts
- 2. Ambulatory patients with stable haematocrit can be sent home
- Encourage oral intake of oral rehydration solution (ORS), fruit juice and other fluids containing electrolytes and sugar to replace losses from fever and vomiting
- Give Paracetamol for high fever if the patient is uncomfortable. The interval of paracetamol dosing should not be less than six hours. Tepid sponge if the patient still has high fever
- Should be brought to hospital immediately if any of the following occur: no clinical improvement, deterioration around the time of defervescence, severe abdominal pain, persistent vomiting, cold and clammy extremities, lethargy or irritability/restlessness, bleeding (e.g. black stools or coffee-ground vomiting), not passing urine for more than 4–6 hours
- 3. Patients who should be referred for in-hospital management
- Patients may need to be admitted to a secondary health care centre for close observation, particularly as they approach the critical phase. These include patients with warning signs (Abdominal pain or tenderness, Persistent vomiting, Clinical fluid accumulation, Mucosal bleed, Lethargy, restlessness, Liver enlargment >2cm, Laboratory:increase in HCT concurrent with rapid decrease in platelet count), those with co-existing conditions that may make dengue or its management more complicated (such as pregnancy, infancy, old age, obesity, diabetes mellitus, renal failure, chronic haemolytic diseases), and those with certain social circumstances (such as living alone, or living far from a health facility without reliable means of transport)
- 3.1 With warning signs
- Obtain a reference haematocrit before fluid therapy. Give only isotonic solutions such as 0.9% saline, Ringer’s lactate, or Hartmann’s solution. Start with 5–7 ml/ kg/hour for 1–2 hours, then reduce to 3–5 ml/kg/hr for 2–4 hours, and then reduce to 2–3 ml/kg/hr or less according to the clinical response
- Reassess the clinical status and repeat the haematocrit. If the haematocrit remains the same or rises only minimally, continue with the same rate (2–3 ml/kg/hr) for another 2–4 hours. If the vital signs are worsening and haematocrit is rising rapidly, increase the rate to 5–10 ml/kg/hour for 1–2 hours. Reassess the clinical status, repeat the haematocrit and review fluid infusion rates accordingly
- Give the minimum intravenous fluid volume required to maintain good perfusion and urine output of about 0.5 ml/kg/hr. Intravenous fluids are usually needed for only 24–48 hours. Reduce intravenous fluids gradually when the rate of plasma leakage decreases towards the end of the critical phase. This is indicated by urine output and/or oral fluid intake that is/are adequate, or haematocrit decreasing below the baseline value in a stable patient
- Patients with warning signs should be monitored by health care providers until the period of risk is over. A detailed fluid balance should be maintained. Parameters that should be monitored include vital signs and peripheral perfusion (1–4 hourly until the patient is out of the critical phase), urine output (4–6 hourly), haematocrit (before and after fluid replacement, then 6–12 hourly), blood glucose, and other organ functions (such as renal profile, liver profile, coagulation profile, as indicated)
- 3.2 Without warning signs
- Encourage oral fluids. If not tolerated, start intravenous fluid therapy of 0.9% saline or Ringer’s lactate with or without dextrose at maintenance rate. For obese and overweight patients, use the ideal body weight for calculation of fluid infusion. Patients may be able to take oral fluids after a few hours of intravenous fluid therapy. Thus, it is necessary to revise the fluid infusion frequently. Give the minimum volume required to maintain good perfusion and urine output. Intravenous fluids are usually needed only for 24–48 hours
- Patients should be monitored by health care providers for temperature pattern, volume of fluid intake and losses, urine output (volume and frequency), warning signs, haematocrit, and white blood cell and platelet counts. Other laboratory tests (such as liver and renal functions tests) can be done, depending on the clinical picture and the facilities of the hospital or health centre
- 4. Severe dengue
- Severe dengue: Severe plasma leakage leading to dengue shock and/or fluid accumulation with respiratory distress; severe haemorrhages; severe organ impairment (hepatic damage, renal impairment, cardiomyopathy, encephalopathy or encephalitis)
- 4.1 Treatment of shock
- 4.1.1 Compensated shock
- Start intravenous fluid resuscitation with isotonic crystalloid solutions at 5–10 ml/kg/hour over one hour. Then reassess the patient’s condition (vital signs, capillary refill time, haematocrit, urine output). The next steps depend on the situation
- If the patient’s condition improves, intravenous fluids should be gradually reduced to 5–7 ml/kg/hr for 1–2 hours, then to 3–5 ml/kg/hr for 2–4 hours, then to 2–3 ml/kg/hr, and then further depending on haemodynamic status, which can be maintained for up to 24–48 hours
- If vital signs are still unstable (i.e. shock persists), check the haematocrit after the first bolus. If the haematocrit increases or is still high (>50%), repeat a second bolus of crystalloid solution at 10–20 ml/kg/hr for one hour. After this second bolus, if there is improvement, reduce the rate to 7–10 ml/ kg/hr for 1–2 hours, and then continue to reduce as above. If haematocrit decreases compared to the initial reference haematocrit (<40% in children and adult females, <45% in adult males), this indicates bleeding and the need to cross-match and transfuse blood as soon as possible
- Further boluses of crystalloid or colloidal solutions may need to be given during the next 24–48 hours
- 4.1.2 Hypotensive shock
- Initiate intravenous fluid resuscitation with crystalloid or colloid solution (if available) at 20 ml/kg as a bolus given over 15 minutes to bring the patient out of shock as quickly as possible
- If the patient’s condition improves, give a crystalloid/colloid infusion of 10 ml/kg/hr for one hour. Then continue with crystalloid infusion and gradually reduce to 5–7 ml/kg/hr for 1–2 hours, then to 3–5 ml/kg/hr for 2–4 hours, and then to 2–3 ml/kg/hr or less, which can be maintained for up to 24–48 hours
- If vital signs are still unstable (i.e. shock persists), review the haematocrit obtained before the first bolus. If the haematocrit was low (<40% in children and adult females, <45% in adult males), this indicates bleeding and the need to cross- match and transfuse blood as soon as possible (see treatment for haemorrhagic complications)
- If the haematocrit was high compared to the baseline value (if not available, use population baseline), change intravenous fluids to colloid solutions at 10–20 ml/kg as a second bolus over 30 minutes to one hour. After the second bolus, reassess the patient. If the condition improves, reduce the rate to 7–10 ml/kg/hr for 1–2 hours, then change back to crystalloid solution and reduce the rate of infusion as mentioned above. If the condition is still unstable, repeat the haematocrit after the second bolus
- If the haematocrit decreases compared to the previous value (<40% in children and adult females, less than 45% in adult males), this indicates bleeding and the need to cross-match and transfuse blood as soon as possible (see treatment for haemorrhagic complications). If the haematocrit increases compared to the previous value or remains very high ( more than 50%), continue colloid solutions at 10–20 ml/kg as a third bolus over one hour. After this dose, reduce the rate to 7–10 ml/kg/hr for 1–2 hours, then change back to crystalloid solution and reduce the rate of infusion as mentioned above when the patient’s condition improves
- Further boluses of fluids may need to be given during the next 24 hours. The rate and volume of each bolus infusion should be titrated to the clinical response. Patients with severe dengue should be admitted to the high-dependency or intensive care area
- 4.2 Treatment of haemorrhagic complications
- Blood transfusion required
- Give 5–10ml/kg of fresh-packed red cells or 10–20 ml/kg of fresh whole blood at an appropriate rate and observe the clinical response. It is important that fresh whole blood or fresh red cells are given. Oxygen delivery at tissue level is optimal with high levels of 2,3 di-phosphoglycerate (2,3 DPG). Stored blood loses 2,3 DPG, low levels of which impede the oxygen-releasing capacity of haemoglobin, resulting in functional tissue hypoxia. A good clinical response includes improving haemodynamic status and acid-base balance
- Consider repeating the blood transfusion if there is further blood loss or no appropriate rise in haematocrit after blood transfusion. There is little evidence to support the practice of transfusing platelet concentrates and/or fresh-frozen plasma for severe bleeding. It is being practised when massive bleeding can not be managed with just fresh whole blood/fresh-packed cells, but it may exacerbate the fluid overload
- Great care should be taken when inserting a naso-gastric tube which may cause severe haemorrhage and may block the airway. A lubricated oro-gastric tube may minimize the trauma during insertion. Insertion of central venous catheters should be done with ultra-sound guidance or by a very experienced person
- 5. Treatment of complications and other areas of treatment
- 5.1 Fluid overload
- Oxygen therapy should be given immediately
- When the following signs are present, intravenous fluids should be discontinued or reduced to the minimum rate necessary to maintain euglycaemia
- signs of cessation of plasma leakage; stable blood pressure, pulse and peripheral perfusion; haematocrit decreases in the presence of a good pulse volume; afebrile for more than 24–48 days (without the use of antipyretics); resolving bowel/abdominal symptoms; improving urine output
- The management of fluid overload varies according to the phase of the disease and the patient’s haemodynamic status. If the patient has stable haemodynamic status and is out of the critical phase (more than 24–48 hours of defervescence), stop intravenous fluids but continue close monitoring. If necessary, give oral or intravenous furosemide 0.1–0.5 mg/kg/dose once or twice daily, or a continuous infusion of furosemide 0.1 mg/kg/hour. Monitor serum potassium and correct the ensuing hypokalaemia
- If the patient has stable haemodynamic status but is still within the critical phase, reduce the intravenous fluid accordingly. Avoid diuretics during the plasma leakage phase because they may lead to intravascular volume depletion
- Patients who remain in shock with low or normal haematocrit levels but show signs of fluid overload may have occult haemorrhage. Further infusion of large volumes of intravenous fluids will lead only to a poor outcome. Careful fresh whole blood transfusion should be initiated as soon as possible. If the patient remains in shock and the haematocrit is elevated, repeated small boluses of a colloid solution may help
- 5.2 Other complications of dengue
- Both hyperglycaemia and hypoglycaemia may occur, even in the absence of diabetes mellitus and/or hypoglycaemic agents. Electrolyte and acid-base imbalances are also common observations in severe dengue and are probably related to gastrointestinal losses through vomiting and diarrhoea or to the use of hypotonic solutions for resuscitation and correction of dehydration. Hyponatraemia, hypokalaemia, hyperkalaemia, serum calcium imbalances and metabolic acidosis (sodium bicarbonate for metabolic acidosis is not recommended for pH ≥ 7.15) can occur. One should also be alert for co-infections and nosocomial infections.
- 5.3 Supportive care and adjuvant therapy
- renal replacement therapy, with a preference to continuous veno-venous haemodialysis (CWH), since peritoneal dialysis has a risk of bleeding;
- vasopressor and inotropic therapies as temporary measures to prevent life- threatening hypotension in dengue shock and during induction for intubation, while correction of intravascular volume is being vigorously carried out;
- further treatment of organ impairment, such as severe hepatic involvement or encephalopathy or encephalitis;
- further treatment of cardiac abnormalities, such as conduction abnormalities, may occur (the latter usually not requiring interventions)
- West Nile virus Return to Top
- West nile virus
- 1.1. Prevention
- No WNV vaccines are licensed for use in humans. In the absence of a vaccine, prevention of WNV disease depends on community-level mosquito control programs to reduce vector densities, personal protective measures to decrease exposure to infected mosquitoes, and screening of blood and organ donors.
- Personal protective measures include use of mosquito repellents, wearing long-sleeved shirts and long pants, and limiting outdoor exposure from dusk to dawn. Using air conditioning, installing window and door screens, and reducing peridomestic mosquito breeding sites, can further decrease the risk for WNV exposure.
- Blood and some organ donations in the United States are screened for WNV infection; health care professionals should remain vigilant for the possible transmission of WNV through blood transfusion or organ transplantation. Any suspected WNV infections temporally associated with blood transfusion or organ transplantation should be reported promptly to the appropriate state health department.
- 1.2. Treatment
- There is no specific treatment for WNV disease; clinical management is supportive. Patients with severe meningeal symptoms often require pain control for headaches and antiemetic therapy and rehydration for associated nausea and vomiting. Patients with encephalitis require close monitoring for the development of elevated intracranial pressure and seizures. Patients with encephalitis or poliomyelitis should be monitored for inability to protect their airway. Acute neuromuscular respiratory failure may develop rapidly and prolonged ventilatory support may be required.
- Yellow Fever Return to Top
- Yellow fever[387][388]
- Preferred regimen: No specific treatment is available for yellow fever. In the toxic phase, supportive treatment includes therapies for treating dehydration and fever. Ribavirin has failed in several studies in the monkey model.
- Note: An international seminar held by WHO in 1984 recommended maintenance of nutrition, prevention of hypoglycemia, maintenance of the blood pressure with fluids and vasoactive drugs, prevention of bleeding with fresh-frozen plasma, dialysis if renal failure, correction of metabolic acidosis, administration of cimetidine IV to avoid gastric bleeding and oxygen if needed.
- Chikungunya virus Return to Top
- Preferred regimen: no specific therapeutics agents are available and there are no licensed vaccines to prevent Chikungunya Fever.
- Note: Anti inflammatory drugs can be used to control joint swelling and arthritis.
- Hepatitis A virus Return to Top
- Preferred regimen: No therapy recommended. If within 2 wks of exposure, IVIG 0.02 mL per kg IM times 1 protective.
- Hepatitis B virus Return to Top
- Acute Hepatitis B
- Chronic Hepatitis B
- 1. Patients with HBeAg-positive chronic hepatitis B[390]
- 1.1. HBV DNA >20,000, ALT <2 times upper limit normal (ULN)[390]
- Observe; consider treatment when ALT becomes elevated.
- Consider biopsy in persons 40 years, ALT persistently high normal >2 times upper limit normal (ULN), or with family history of HCC.
- Consider treatment if HBV DNA >20,000 IU/mL and biopsy shows moderate/severe inflammation or significant fibrosis.
- 1.2. HBV DNA >20,000, ALT >2 times upper limit normal (ULN)[390]
- Preferred regimen (1): Pegylated IFN-alpha 180 mcg weekly SC for 48 weeks
- Preferred regimen (2): Tenofovir (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
- If creatinine clearance 30–49 give 300 mg q48 hrs
- If creatinine clearance 10–29 give 300 mg q72-96 hrs
- If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
- If creatinine clearance <10 without dialysis there is no recommendation
- Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
- Preferred regimen (3): Entecavir (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior Lamivudine treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
- If creatinine clearance 30–49 give 0.25 mg PO qd OR 0.5 mg PO q48 hr for patients with no prior Lamivudine treatment, and 0.5 mg PO qd OR 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
- If creatinine clearance 10–29 give 0.15 mg PO qd OR 0.5 mg PO q 72 hr for patients with no prior Lamivudine treatment, and 0.3 mg PO qd OR 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
- If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd OR 0.5 mg PO q7 days for patients with no prior Lamivudine treatment, and 0.1 mg PO qd OR 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine for minimum 1 year, continue for at least 6 months after HBeAg seroconversion.
- Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
- Alternative regimen (1): Interferon alpha (IFNα) 5 MU daily or 10 MU thrice weekly SC for 16 weeks
- Alternative regimen (2): Lamivudine (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 100 mg PO qd
- If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
- If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
- If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
- If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
- The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.
- Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
- Alternative regimen (3): Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 10 mg PO daily
- If creatinine clearance 30–49 give 10 mg PO every other day
- If creatinine clearance 10–19 10 mg PO every third day
- If hemodialysis patients give 10 mg PO every week following dialysis
- Note: duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
- Alternative regimen (4): Telbivudine (LdT) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 600 mg PO once daily
- If creatinine clearance 30–49 600 give mg PO once every 48 hours
- If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
- If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis
- Note (1): duration of treatment is minimum 1 year, continue for at least 6 months after HBeAg seroconversion
- Note (2): Observe for 3-6 months and treat if no spontaneous HBeAg loss.
- Note (3): Consider liver biopsy prior to treatment if compensated.
- Note (4): Immediate treatment if icteric or clinical decompensation.
- Note (5): Interferon alpha (IFNα)/ pegylated interferon-alpha (peg-IFNα), Lamivudine (LAM), Adefovir (ADV), Entecavir (ETV), tenofovir disoproxil fumarate (TDF) or telbivudine (LdT) may be used as initial therapy.
- Note (6): Adefovir (ADV) not preferred due to weak antiviral activity and high rate of resistance after 1st year.
- Note (7): Lamivudine (LAM) and Telbivudine (LdT) not preferred due to high rate of drug resistance.
- Note (8): End-point of treatment – Seroconversion from HBeAg to anti-HBe.
- Note (9): Interferon alpha (IFNα) non-responders / contraindications to IFNα change to Tenofovir (TDF)/Entecavir (ETV).
- 1.3. Children with elevated ALT greater than 2 times normal[390]
- Preferred regimen(1): Interferon alpha (IFNα) 6 MU/m2 SC thrice weekly with a maximum of 10 MU
- Preferred regimen(2): Lamivudine (LAM) 3 mg/kg/d PO with a maximum of 100 mg/d.
- 2. Patients with HBeAg-negative chronic hepatitis B[390]
- 2.1. HBV DNA >2,000 IU/mL and elevated ALT >2 times normal
- Preferred regimen (1): Pegylated IFN-alpha 180 mcg weekly SC for 1 year
- Preferred regimen (2): Tenofovir (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
- If creatinine clearance 30–49 give 300 mg q48 hrs
- If creatinine clearance 10–29 give 300 mg q72-96 hrs
- If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
- If creatinine clearance <10 without dialysis there is no recommendation
- Note: duration of treatment is more than 1 year
- Preferred regimen (3): Entecavir (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior Lamivudine treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine
- If creatinine clearance 30–49 give 0.25 mg PO qd OR 0.5 mg PO q48 hr for patients with no prior Lamivudine treatment, and 0.5 mg PO qd OR 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine
- If creatinine clearance 10–29 give 0.15 mg PO qd OR 0.5 mg PO q 72 hr for patients with no prior Lamivudine treatment, and 0.3 mg PO qd OR 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine
- If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd OR 0.5 mg PO q7 days for patients with no prior Lamivudine treatment, and 0.1 mg PO qd OR 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine.
- Note: duration of treatment is more than 1 year
- Alternative regimen (1): Interferon alpha (IFNα) 5 MU daily or 10 MU thrice weekly SC for 1 year
- Alternative regimen (2): Lamivudine (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 100 mg PO qd
- If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
- If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
- If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
- If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
- The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.
- Note: duration of treatment is more than 1 year
- Alternative regimen (3): Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 10 mg PO daily
- If creatinine clearance 30–49 give 10 mg PO every other day
- If creatinine clearance 10–19 10 mg PO every third day
- If hemodialysis patients give 10 mg PO every week following dialysis
- Note: duration of treatment is more than 1 year
- Alternative regimen (4): Telbivudine (LdT)Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 600 mg PO once daily
- If creatinine clearance 30–49 600 give mg PO once every 48 hours
- If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
- If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis
- Note (1): duration of treatment is more than 1 year
- Note (2): Interferon alpha (IFNα)/ pegylated interferon-alpha (peg-IFNα), Lamivudine (LAM), Adefovir (ADV), Entecavir (ETV), tenofovir disoproxil fumarate (TDF) or telbivudine (LdT) may be used as initial therapy.
- Note (3): Adefovir (ADV) not preferred due to weak antiviral activity and high rate of resistance after 1st year.
- Note (4): Lamivudine (LAM) and Telbivudine (LdT) not preferred due to high rate of drug resistance.
- Note (5): End-point of treatment – not defined
- Note (6): Interferon alpha (IFNα) non-responders / contraindications to IFNα change to Tenofovir (TDF)/Entecavir (ETV).
- 3. HBV DNA >2,000 IU/mL and elevated ALT 1->2 times normal[390]
- Consider liver biopsy and treat if liver biopsy shows moderate/severe necroinflammation or significant fibrosis.
- 4. HBV DNA <2,000 IU/mL and ALT < upper limit normal (ULN)[390]
- Observe, treat if HBV DNA or ALT becomes higher.
- 5. +/- HBeAg and detectable HBV DNA with Cirrhosis[390]
- 5.1. Compensated Cirrhosis and HBV DNA >2,000
- Preferred regimen (1): Entecavir (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior Lamivudine treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine.
- If creatinine clearance 30–49 give 0.25 mg PO qd OR 0.5 mg PO q48 hr for patients with no prior Lamivudine treatment, and 0.5 mg PO qd OR 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine.
- If creatinine clearance 10–29 give 0.15 mg PO qd OR 0.5 mg PO q 72 hr for patients with no prior Lamivudine treatment, and 0.3 mg PO qd OR 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine.
- If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd OR 0.5 mg PO q7 days for patients with no prior Lamivudine treatment, and 0.1 mg PO qd OR 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine.
- Preferred regimen (2): Tenofovir (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
- If creatinine clearance 30–49 give 300 mg q48 hrs
- If creatinine clearance 10–29 give 300 mg q72-96 hrs
- If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
- If creatinine clearance <10 without dialysis there is no recommendation
- Alternative regimen (1): Lamivudine (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 100 mg PO qd
- If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
- If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
- If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
- If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
- The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.
- Alternative regimen (2): Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 10 mg PO daily
- If creatinine clearance 30–49 give 10 mg PO every other day
- If creatinine clearance 10–19 give 10 mg PO every third day
- If hemodialysis patients give 10 mg PO every week following dialysis
- Alternative regimen (3): Telbivudine (LdT) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 600 mg PO once daily
- If creatinine clearance 30–49 600 give mg PO once every 48 hours
- If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
- If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis
- Note (1): LAM and LdT not preferred due to high rate of drug resistance.
- Note (2): ADV not preferred due to weak antiviral activity and high risk of resistance after 1st year.
- Note (3): These patients should receive long-term treatment. However, treatment may be stopped in HBeAg-positive patients if they have confirmed HBeAg seroconversion and have completed at least 6 months of consolidation therapy and in HBeAg-negative patients if they have confirmed HBsAg clearance.
- 5.2. Compensated Cirrhosis and HBV DNA <2,000
- Consider treatment if ALT elevated.
- 5.3. Decompensated Cirrhosis
- Preferred regimen (1): Tenofovir (TDF) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 300 mg q24 hrs
- If creatinine clearance 30–49 give 300 mg q48 hrs
- If creatinine clearance 10–29 give 300 mg q72-96 hrs
- If creatinine clearance <10 with dialysis give 300 mg once a week or after a total of approximately 12 hours of dialysis
- If creatinine clearance <10 without dialysis there is no recommendation
- Preferred regimen (2): Entecavir (ETV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 give 0.5 mg PO daily for patients with no prior Lamivudine treatment, and 1 mg PO daily for patients who are refractory/resistant to lamivudine.
- If creatinine clearance 30–49 give 0.25 mg PO qd OR 0.5 mg PO q48 hr for patients with no prior Lamivudine treatment, and 0.5 mg PO qd OR 1 mg PO q 48 hr for patients who are refractory/resistant to lamivudine.
- If creatinine clearance 10–29 give 0.15 mg PO qd OR 0.5 mg PO q 72 hr for patients with no prior Lamivudine treatment, and 0.3 mg PO qd OR 1 mg PO q 72 hr for patients who are refractory/resistant to lamivudine.
- If creatinine clearance <10 or hemodialysis or continuous ambulatory peritoneal dialysis give 0.05 mg PO qd OR 0.5 mg PO q7 days for patients with no prior Lamivudine treatment, and 0.1 mg PO qd OR 1 mg PO q 7 days for patients who are refractory/resistant to lamivudine.
- Preferred regimen (3): Lamivudine (LAM) AND Adefovir (ADV)
- Lamivudine (LAM) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 100 mg PO qd
- If creatinine clearance 30–49 give 100 mg PO first dose, then 50 mg PO qd
- If creatinine clearance 15–29 give 100 mg PO first dose, then 25 mg PO qd
- If creatinine clearance 5-14 give 35 mg PO first dose, then 15 mg PO qd
- If creatinine clearance <5 give 35 mg PO first dose, then 10 mg PO qd
- The recommended dose of lamivudine for persons coinfected with HIV is 150mg PO twice daily.
- Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 10 mg PO daily
- If creatinine clearance 30–49 give 10 mg PO every other day
- If creatinine clearance 10–19 give 10 mg PO every third day
- If hemodialysis patients give 10 mg PO every week following dialysis
- Preferred regimen (4): Telbivudine (LdT) AND Adefovir (ADV)
- Telbivudine (LdT) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 600 mg PO once daily
- If creatinine clearance 30–49 600 give mg PO once every 48 hours
- If creatinine clearance <30 (not requiring dialysis) give 600 mg PO once every 72 hours
- If End-stage renal disease give 600 mg PO once every 96 hours after hemodialysis
- Adefovir (ADV) Adjustment of Adult Dosage in Accordance with Creatinine Clearance:
- If creatinine clearance >50 or normal renal function give 10 mg PO daily
- If creatinine clearance 30–49 give 10 mg PO every other day
- If creatinine clearance 10–19 give 10 mg PO every third day
- If hemodialysis patients give 10 mg PO every week following dialysis
- Note: coordinate treatment with transplant center and refer for liver transplant.
- Life-long treatment is recommended.
- 6. +/- HBeAg and undetectable HBV DNA with Cirrhosis[390]
- Compensated Cirrhosis: Observe
- Uncompensated Cirrhosis: Refer for liver transplant
- Hepatitis C virus Return to Top
Chronic Hepatitis C
- 1. Treatment regimens for chronic hepatitis C virus genotype 1[391]
- 1.1. Treatment regimens for genotype 1a:
- Preferred regimen (1): Ledipasvir 90 mg PO qd AND Sofosbuvir 400 mg PO qd for 12 weeks
- Preferred regimen (2): Paritaprevir 150 mg PO qd AND Ritonavir 100 mg PO qd AND Ombitasvir 25 mg PO qd AND Dasabuvir 250 mg PO bid AND weight-based Ribavirin PO qd ([1000 mg <75 kg] to [1200 mg >75 kg]) for 12 weeks (no cirrhosis) OR 24 weeks (cirrhosis)
- Preferred regimen (3): Sofosbuvir 400 mg PO qd AND Simeprevir 150 mg PO qd ± weight-based Ribavirin PO qd ([1000 mg <75 kg] to [1200 mg >75 kg]) for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis)
- Note: these regimens are recommended for treatment-naive patients with HCV genotype 1a infection.
- 1.2. Treatment regimens for genotype 1b:
- Preferred regimen (1): Ledipasvir 90 mg PO qd AND Sofosbuvir 400 mg PO qd for 12 weeks
- Preferred regimen (2): Paritaprevir PO 150 mg qd AND Ritonavir 100 mg PO qd AND Ombitasvir 25 mg PO qd AND Dasabuvir 250 mg PO bid for 12 weeks. The addition of weight-based Ribavirin PO qd (1000 mg [<75kg] to 1200 mg [>75 kg]) is recommended in patients with cirrhosis
- Preferred regimen (3): Sofosbuvir 400 mg PO qd AND Simeprevir 150 mg PO qd for 12 weeks (no cirrhosis) or 24 weeks (cirrhosis)
- Note: these regimens are recommended for treatment-naive patients with HCV genotype 1b infection.
- 2. Treatment regimens for chronic hepatitis C virus genotype 2[392]
- Preferred regimen: Sofosbuvir 400 mg PO qd AND weight-based RBV (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 12 weeks
- Note (1): This regimen are recommended for treatment-naive patients with HCV genotype 2 infection.
- Note (2): Extending treatment to 16 weeks is recommended in patients with cirrhosis.
- 3. Treatment regimens for chronic hepatitis C virus genotype 3[393]
- Preferred regimen: Sofosbuvir 400 mg PO qd and weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) PO qd for 24 weeks
- Alternative regimen: Sofosbuvir 400 mg and weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) PO qd AND weekly PEG-IFN for 12 weeks is an acceptable regimen for IFN-eligible, treatment-naive patients with HCV genotype 3 infection.
- Note: These regimens are recommended for treatment-naive patients with HCV genotype 3 infection.
- 4. Treatment regimens for chronic hepatitis C virus genotype 4
- Preferred regimen (1): Ledipasvir 90 mg PO qd AND Sofosbuvir 400 mg PO qd for 12 weeks
- Preferred regimen (2): Paritaprevir 150 mg PO qd AND Ritonavir 100 mg PO qd AND Ombitasvir 25 mg PO qd AND weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 12 weeks
- Preferred regimen (3): Sofosbuvir 400 mg PO qd AND weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 24 weeks
- Alternative regimen (1): Sofosbuvir 400 mg PO qd AND weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) AND weekly PEG-IFN for 12 weeks
- Alternative regimen (2): Sofosbuvir 400 mg PO qd AND Simeprevir 150 mg PO qd ± weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 12 weeks
- Note: These regimens are accpetable for treatment-naive patients with HCV genotype 3 infection.
- 5. Treatment regimens for chronic hepatitis C virus genotype 5[394]
- Preferred regimen: Sofosbuvir 400 mg PO qd AND weight-based Ribavirin PO qd(1000 mg [<75 kg] to 1200 mg [>75 kg]) AND weekly PEG-IFN for 12 weeks is recommended for treatment-naive patients with HCV genotype 5 infection.
- Alternative regimen: Weekly PEG-IFN AND weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) for 48 weeks is an alternative regimen for IFN-eligible, treatment-naive patients with HCV genotype 5 infection.
- 6. Treatment regimens for chronic hepatitis C virus genotype 6[395]
- Preferred regimen: Ledipasvir 90 mg PO qd AND Sofosbuvir PO qd 400 mg for 12 weeks is recommended for treatment-naive patients with HCV genotype 6 infection.
- Alternative regimen: Sofosbuvir 400 mg PO qd AND weight-based Ribavirin PO qd (1000 mg [<75 kg] to 1200 mg [>75 kg]) AND weekly PEG-IFN for 12 weeks is an alternative regimen for IFN-eligible, treatment-naive patients with HCV genotype 6 infection.
- Hepatitis D virus Return to Top
- Preferred regimen: Interferon alpha(IFNα) 5 MU daily OR 9 MU three times a week for 6–12 months [396]
- Hepatitis E virus Return to Top
- Hepatitis E treatment[397]
- Preferred regimen: supportive therapy. There is no specific treatment available.
- Note (1): Hepatitis E is usually self-limiting, hospitalization is generally not required.
- Note (2): Hospitalization is required for people with fulminant hepatitis and should also be considered for symptomatic pregnant women.
- Epstein-Barr virus Return to Top
- Epstein-Barr Virus (EBV) [398]
- There is no vaccine to protect against EBV infection. You can help protect yourself by not kissing or sharing drinks, food, or personal items, like toothbrushes, with people who have EBV infection.
- There is no specific treatment for EBV. However, some things can be done to help relieve symptoms, including
- drinking fluids to stay hydrated
- getting plenty of rest
- taking over-the-counter medications for pain and fever
- Human herpesvirus 6 Return to Top
- Human herpesvirus 6 treatment[399][400]
- Preferred regimen: supportive therapy
- Note: If patient is immunocompromised, there are no antiviral regimens stablished as there are no clinical trials to validate their use on these cases. Consider administering Ganciclovir, Acyclovir, Foscarnet OR Cidofovir.[401][400]
- Roseola Return to Top
- Human herpesvirus 7 (roseola virus) treatment
- Preferred regimen: Supportive therapy
- Note (1): Immunocompetent hosts with uncomplicated skin manifestations associated with HHV-7, particularly roseola infantum and pityriasis rosea, need only symptomatic management[401]
- Note (2): For HIV-positive patients, antiretroviral therapy may be advisable[402]
- Note (3): The most active antiviral compounds against HHV-7 are Cidofovir and Foscarnet[403][401]
- Human herpesvirus 8 (KSHV) Return to Top
- 1. Mild to moderate Kaposi sarcoma[404]
- Preferred regimen: initiate or optimize ART
- 2. Advanced Kaposi sarcoma (ACTG Stage T1, including disseminated cutaneous or visceral Kaposi sarcoma)
- Preferred regimen: chemotherapy (per oncology consult) AND ART
- 3. Primary effusion lymphoma
- Preferred regimen: chemotherapy (per oncology consult) AND ART
- Note: Valganciclovir PO or Ganciclovir IV can be used as adjunctive therapy.
- 4. Multicentric Castleman's disease
- Preferred regimen (1): Valganciclovir 900 mg PO bid for 3 weeks
- Preferred regimen (2): Ganciclovir 5 mg/kg IV q12h for 3 weeks
- Preferred regimen (3): Valganciclovir 900 mg PO BID AND Zidovudine 600 mg PO q6h for 7–21 days
- Alternative regimen: Rituximab 375 mg/m2 given weekly for 4–8 weeks (may be an alternative to or used adjunctively with antiviral therapy)
- Herpes simplex virus Return to Top
- Genital Herpes[405]
- 1.First Clinical Episode of Genital Herpes
- Preferred Regimen (1): Acyclovir 400 mg PO tid for 7–10 days
- Preferred Regimen (2): Acyclovir 200 mg PO five times a day for 7–10 days
- Preferred Regimen (3): Valacyclovir 1 g PO bid for 7–10 days
- Preferred Regimen (4): Famciclovir 250 mg PO tid for 7–10 days
- Note:Treatment can be extended if healing is incomplete after 10 days of therapy.
- 2.Established HSV-2 Infection
- 2.1 Suppressive Therapy for Recurrent Genital Herpes
- Preferred Regimen (1): Acyclovir 400 mg PO bid
- Preferred Regimen (2): Valacyclovir 500 mg PO qd
- Preferred Regimen (3): Valacyclovir 1 g PO qd
- Preferred Regimen (4): Famciclovir 250 mg PO bid
- Note(1):Daily therapy with Acyclovir for as long as 6 years and with Valacyclovir OR Famciclovir for 1 year
- Note(2):Valacyclovir 500 mg qd might be less effective than other Valacyclovir OR Acyclovir dosing regimens in persons who have very frequent recurrences (i.e., ≥10 episodes per year).
- 2.2 Episodic Therapy for Recurrent Genital Herpes
- Preferred Regimen (1): Acyclovir 400 mg PO tid for 5 days
- Preferred Regimen (2): Acyclovir 800 mg PO bid for 5 days
- Preferred Regimen (3): Acyclovir 800 mg PO tid for 2 days
- Preferred Regimen (4): Valacyclovir 500 mg PO bid for 3 days
- Preferred Regimen (5): Valacyclovir 1 g PO qd for 5 days
- Preferred Regimen (6): Famciclovir 125 mg PO bid for 5 days
- Preferred Regimen (7): Famciclovir 1 g PO bid for 1 day
- Preferred Regimen (8): Famciclovir 500 mg once, followed by 250 mg PO bid for 2 days
- 3. Severe Disease (disseminated infection, pneumonitis, or hepatitis) or CNS complications (e.g., meningoencephalitis).
- Preferred Regimen: Acyclovir 5–10 mg/kg IV q8h for 2–7 days or until clinical improvement is observed, followed by oral antiviral therapy to complete at least 10 days of total therapy. HSV encephalitis requires 21 days of intravenous therapy. Impaired renal function warrants an adjustment in acyclovir dosage.
- 4. Special Considerations
- 4.1 HIV Infection
- 4.1.1 Daily Suppressive Therapy in Persons with HIV
- Preferred Regimen (1): Acyclovir 400–800 mg PO bid /tid
- Preferred Regimen (2): Valacyclovir 500 mg PO bid
- Preferred Regimen (3): Famciclovir 500 mg PO bid
- 4.1.2 Episodic Infection in Persons with HIV
- Preferred Regimen (1): Acyclovir 400 mg PO tid for 5–10 days
- Preferred Regimen (2): Valacyclovir 1 g PO bid for 5–10 days
- Preferred Regimen (3): Famciclovir 500 mg PO bid for 5–10 days
- Note: For severe HSV disease, initiating therapy with Acyclovir 5–10 mg/kg IV q8 h might be necessary.
- 4.2 Genital Herpes in Pregnancy
- Suppressive therapy of pregnant women with recurrent genital herpes
- Preferred Regimen (1): Acyclovir 400–800 mg PO bid /tid
- Preferred Regimen (2): Valacyclovir 500 mg PO bid
- Note:Treatment recommended starting at 36 weeks of gestation.
- 4.3 Neonatal Herpes
- Known or suspected neonatal herpes
- Preferred Regimen: Acyclovir 20 mg/kg IV q 8 h
- Note (1): Treatment for 14 days if disease is limited to the skin and mucous membranes, or
- Note (2): Treatment for 21 days for disseminated disease and that involving the central nervous system.
- 4.4 Acyclovir-resistant genital herpes
- Preferred Regimens: Foscarnet 40–80 mg/kg IV q8 h until clinical resolution is attained
- Alternative Regimen (1): Cidofovir 5 mg/kg IV once weekly might also be effective.
- Alternative Regimen (2): Imiquimod topical preparations should be applied to the lesions qd for 5 consecutive days.
- 4.5 Management of Sex Partners
- Preferred Regimen (1): Acyclovir 400 mg PO tid for 7–10 days
- Preferred Regimen (2): Acyclovir 200 mg PO five times a day for 7–10 days
- Preferred Regimen (3): Valacyclovir 1 g PO bid for 7–10 days
- Preferred Regimen (4): Famciclovir 250 mg PO tid for 7–10 days
- Note:The sex partners of persons who have genital herpes can benefit from evaluation and counseling. Symptomatic sex partners should be evaluated and treated
- 4.6 Allergy, Intolerance, and Adverse Reactions
- Allergic and other adverse reactions to oral Acyclovir, Valacyclovir, and Famciclovir are rare. Desensitization to acyclovir has been described.
# vzv
- Varicella-zoster virus Return to Top
- 1. Varicella zoster treatment[406]
- 1.1 Non Immunocompromised person
- Preferred regimen (1): Acyclovir 500 mg PO five times a dayfor 7-10 days
- Preferred regimen (2): Famciclovir 500 mg PO tid for 7 days
- Preferred regimen (3): Valacyclovir 1 g PO tid for 7 days
- Preferred regimen (4): Brivudin 125 mg PO qd for 7 days
- 1.2 Immunocompromised person requiring hospitalization or persons with sever neurologic complications
- Preferred regimen (1): Acyclovir 10 mg/ kg IV q8h for 7-10 days
- Preferred regimen (2): Foscarnet 40 mg/ kg IV q8h until lesions are healed
- Note: Brivudin is not available in USA and has not been approved by FDA. Foscarnet is not approve by FDA
- 2. Treatment of VZV complications[407]
- 2.1 VZV ophthalmicus
- Treatment includes the following
- (1) Famciclovir OR Valacyclovir for 7–10 days, preferably started within 72 h of rash onset (with Acyclovir IV given as needed for retinitis), to resolve acute disease and inhibit late inflammatory recurrences, AND Prednisone 20 mg PO tid for 4 days or bid for 6 days, and then qd for 4 day
- (2) Bacitracin-Polymyxin ophthalmic ointment administered bid ,to protect the ocular surface;
- (3) Topical Prednisolone 0.125%–1% 2–6 times daily prescribed and managed only by an ophthalmologist for corneal immune disease, episcleritis, scleritis, or iritis;
- (4) Homatropine 5% bid as needed for iritis
- (5) Latanaprost qd and/or Timolol maleate ophthalmic gel forming solution every morning)ocular pressure–lowering drugs given as needed for glaucoma
- Note (1): Systemic steroids are indicated in the presence of moderate to severe pain or rash, particularly if there is significant edema, which may cause orbital apex syndrome through pressure on the nerves entering the orbit.
- Note (2): pain medications and cool to tepid wet compresses (if tolerated) and no topical antivirals, because they are ineffective
- 2.2 VZV retinitis
- Preferred regimen: Acyclovir IV 10–15 mg/kg q8h for 10–14 days followed by Valacyclovir PO 1 g tid daily for 4–6 weeks
- 3 Recommendations for treating varicella zoster virus (VZV) Infections in HIV-Infected adults and adolescents[408]
- 3.1 Primary Varicella Infection (Chickenpox)
- 3.1.1 Uncomplicated Cases
- Preferred regimen (1):Valacyclovir 1 g PO tid for 5–7 days
- Preferred regimen (2): Famciclovir 500 mg PO tid for 5–7 days
- Alternative regimen: Acyclovir 800 mg PO 5 times daily for 5–7 days
- 3.1.2 Severe or Complicated Cases
- Preferred regimen: Acyclovir 10–15 mg/kg IV q8h for 7–10 days
- Note: May switch to oral Famciclovir, Valacyclovir, or Acyclovir after defervescence if no evidence of visceral involvement is evident
- 3.2 Herpes Zoster (Shingles)
- 3.2.1 Acute Localized Dermatomal
- Preferred regimen (1): Valacyclovir 1000 mg PO tid for 7–10 days
- Preferred regimen (2): Famciclovir 500 mg PO tid for 7–10 days
- Alternative Therapy: Acyclovir 800 mg PO 5 times daily for 7–10 days
- Note: Longer duration should be considered if lesions resolve slowly
- 3.2.2 Extensive Cutaneous Lesion or Visceral Involvement
- Preferred regimen: Acyclovir 10–15 mg/kg IV q8h until clinical improvement is evident, then switch to (Valacyclovir 1 g PO tid, Famciclovir 500 mg PO tid, or Acyclovir 800 mg PO 5 times daily)—to complete a 10–14 day course, when formation of new lesions has ceased and signs and symptoms of visceral VZV infection are improving
- 3.3 PORN (Progressive outer retinal necrosis)
- Preferred regimen: Ganciclovir 5 mg/kg and/or Foscarnet 90 mg/kg IV q12h AND Ganciclovir 2 mg/0.05mL and/or foscarnet 1.2 mg/0.05mL intravitreal twice weekly.
- Note: Duration of therapy is not well defined and should be determined based on clinical, virologic, and immunologic response in consultation with experienced ophthalmologist and optimize ART regimen.
- Note: Ganciclovir ocular implants are no longer commercially available
- 3.4 ARN (Acute retinal necrosis)
- Preferred regimen: Acyclovir 10-15 mg/kg IV q8h for 10–14 days, followed by Valacyclovir 1 g PO tid for 6 weeks AND Ganciclovir 2 mg/0.05mL intravitreal qd/bid twice weekly
- Note: Duration of therapy is not well defined and should be determined based on clinical, virologic, and immunologic response in consultation with experienced ophthalmologist
- 4 Prevention of varicella zoster virus (VZV) Infections in HIV-Infected Adults and Adolescents
- 4.1 Pre-Exposure Prevention of VZV Primary Infection
- Indications
- Adult and adolescent patients with CD4 count ≥200 cells/mm3 without documentation of vaccination, health-care provider diagnosis or verification of a history of varicella or herpes zoster, laboratory confirmation of disease, or persons who are seronegative for VZV. Routine VZV serologic testing in HIV-infected adults and adolescents is not recommended.
- Vaccination
- Primary varicella vaccination (Varivax™), 2 doses (0.5 mL SQ) administered 3 months apart
- If vaccination results in disease because of vaccine virus, treatment with acyclovir is recommended.
- VZV-susceptible household contacts of susceptible HIV-infected persons should be vaccinated to prevent potential transmission of VZV to their HIV-infected contacts.
- If post-exposure VariZIG has been administered, wait at least 5 months before varicella vaccination.
- If post-exposure acyclovir has been administered, wait at least 3 days before varicella vaccine.
- 4.2 Post-Exposure Prophylaxis
- Indication
- Close contact with a person who has active varicella or herpes zoster, and
- Is susceptible to VZV (i.e., has no history of vaccination or of either condition, or is known to be VZV seronegative)
- Preferred regimen: VariZIG 125 IU /10 kg (maximum of 625 IU) IM, administered as soon as possible and within 10 days after exposure to a person with active varicella or herpes zoster
- Alternative regimen (Begin 7–10 Days After Exposure): Acyclovir 800 mg PO 5 times/day for 5–7 days OR Valacyclovir 1 g PO tid for 5–7 days
- If post-exposure VariZIG has been administered, wait at least 5 months before varicella vaccination.
- Note: Patients receiving monthly high dose IVIG (i.e., >400 mg/kg) are likely to be protected against VZV and probably do not require VariZIG if the last dose of IVIG was administered <3 weeks before VZV exposure.
- Note: Neither these pre-emptive interventions nor post-exposure varicella vaccination have been studied in HIV-infected adults and adolescents.
- If acyclovir or valacyclovir is used, varicella vaccines should not be given until at least 72 hours after the last dose of the antiviral drug.
# hpv
- Human papillomavirus Return to Top
- Anogenital Warts[409]
- 1.Preferred regimen for External Anogenital Warts(i.e., penis, groin, scrotum, vulva, perineum, external anus, and perianus)
- 1.1 Patient-Applied: Imiquimod 3.75% or 5% cream OR Podofilox 0.5% solution or gel OR Sinecatechins 15% ointment
- 1.2 Provider-Administered: Cryotherapy with liquid nitrogen or cryoprobe OR Surgical removal either by tangential scissor excision, tangential shave excision, curettage, laser,or electrosurgery OR Trichloroacetic acid (TCA) OR Bichloroacetic acid (BCA) 80%-90% solution
- Note (1): Many persons with external anal warts also have intra-anal warts. Thus, persons with external anal warts might benefit from an inspection of the anal canal by digital examination, standard anoscopy, or high-resolution anoscopy.
- Note (2): Might weaken condoms and vaginal diaphragms.
- 2.Alternative Regimens for External Genital Warts
- 2.1 Urethral Meatus Warts
- Preferred regimen: Cryotherapy with liquid nitrogen OR Surgical removal
- 2.2 Vaginal Warts
- Preferred regimen: Cryotherapy with liquid nitrogen OR Surgical removal OR (TCA OR BCA 80%–90% solution)
- Note: The use of a cryoprobe in the vagina is not recommended because of the risk for vaginal perforation and fistula formation
- 2.3 Cervical Warts
- Preferred regimen: Cryotherapy with liquid nitrogen OR Surgical removal OR (TCA OR BCA 80%–90% solution)
- Note: Management of cervical warts should include consultation with a specialist.For women who have exophytic cervical warts, a biopsy evaluation to exclude high-grade SIL must be performed before treatment is initiated.
- 2.4 Intra-anal Warts
- Preferred regimen: Cryotherapy with liquid nitrogen OR Surgical removal OR (TCA OR BCA 80%–90% solution)
- Note: Management of intra-anal warts should include consultation with a specialist.
- 3. Specific considerations
- 3.1 Follow-up
- Most anogenital warts respond within 3 months of therapy. Factors that might affect response to therapy include immunosuppression and treatment compliance. In general, warts located on moist surfaces or in intertriginous areas respond best to topical treatment. A new treatment modality should be selected when no substantial improvement is observed after a complete course of treatment or in the event of severe side effects; treatment response and therapy-associated side effects should be evaluated throughout the course of therapy.
- 3.2 Management of sex partners
- Persons should inform current partner(s) about having genital warts because the types of HPV that cause warts can be passed on to partners. Partners should receive counseling messages that partners might already have HPV despite no visible signs of warts, so HPV testing of sex partners of persons with genital warts is not recommended.
- 3.3 Pregnancy
- Podofilox (podophyllotoxin), Podophyllin, and Sinecatechins should not be used during pregnancy. Imiquimod appears to pose low risk but should be avoided until more data are available.
- Cesarean delivery is indicated for women with anogenital warts if the pelvic outlet is obstructed or if vaginal delivery would result in excessive bleeding.
- Pregnant women with anogenital warts should be counseled concerning the low risk for warts on the larynx of their infants or children (recurrent respiratory papillomatosis).
- 3.4 HIV infection
- Data do not support altered approaches to treatment for persons with HIV infection.
- Squamous cell carcinomas arising in or resembling anogenital warts might occur more frequently among immunosuppressed persons, therefore requiring biopsy for confirmation of diagnosis for suspicious cases
- 3.5 High-grade squamous intraepithelial lesions
- Biopsy of an atypical wart might reveal HSIL or cancer of the anogenital tract. In this instance, referral to a specialist for treatment is recommended.
# influenza A& B
- Influenza A & B Return to Top
- Antiviral Medications Recommended for Treatment of Influenza
- 1. Adults
- Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg PO bid for 5 days
- Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) bid for 5 days
- Preferred regimen (3): Peramivir (Rapivab®) 600 mg IV for 15-30 minutes (single dose)
- Note: FDA approved and recommended Peramivir (Rapivab®) for use in adults ≥18 yrs
- 2. Children
- 2.1 Children < 1 yr
- Preferred regimen: Oseltamivir (Tamiflu®) 3 mg/kg/dose PO bid for 5 days
- 2.2 Children > 1 yr
- 2.2.1 Children ≤ 15 kg
- Preferred regimen: Oseltamivir (Tamiflu®) 30 mg PO bid for 5 days
- 2.2.2 Children > 15 to 23 kg
- Preferred regimen: Oseltamivir (Tamiflu®) 45 mg PO bid for 5 days
- 2.2.3 Children > 23 to 40 kg
- Preferred regimen: Oseltamivir (Tamiflu®) 60 mg PO bid for 5 days
- 2.2.4 Children > 40 kg
- Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg PO bid for 5 days
- Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) bid for 5 days, may be considered for children > 7 yrs old
- 3. Adult Patients with Renal Impairment or End Stage Renal Disease (ESRD) on Dialysis
- 3.1 Oseltamivir
- Creatinine clearance 61 to 90 mL/min-75 mg PO bid for 5 days
- Creatinine clearance 31 to 60 mL/min-30 mg PO bid for 5 days
- Creatinine clearance 10 to 30 mL/min-30 mg PO qd for 5 days
- ESRD Patients on Hemodialysis
- Creatinine clearance ≤10 mL/min-30 mg after every hemodialysis cycle. Treatment duration not to exceed 5 days
- ESRD Patients on Continuous Ambulatory Peritoneal Dialysis-A single 30 mg dose administered immediately after a dialysis exchange
- 3.2 Peramivir
- Creatinine clearance >50 mL/min-600mg IV single dose
- Creatinine clearance 30 to 49 mL/min-200mg IV single dose
- Creatinine clearance 10 to 29 mL/min-100mg IV single dose
- ESRD Patients on Hemodialysis-Dose administered after dialysis at a dose adjusted based on creatinine clearance
- Note: No dose adjustment is recommended for inhaled zanamivir for a 5-day course of treatment for patients with renal impairment.
- 4. Antiviral Medications Recommended for Chemoprophylaxis of Influenza
- 4.1. Adults
- Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg PO qd for 7days
- Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) qd for 7 days
- 4.2. Children
- 4.2.1 Children < 1 yr
- Preferred regimen: Oseltamivir (Tamiflu®) 3 mg/kg/dose PO qd for 7 days
- 4.2.2 Children > 1 yr
- 4.2.2.1 Children ≤ 15 kg
- Preferred regimen: Oseltamivir (Tamiflu®) 30 mg PO qd for 7 days
- 4.2.2.2 Children > 15 to 23 kg
- Preferred regimen: Oseltamivir (Tamiflu®) 45 mg PO qd for 7 days
- 4.2.2.3 Children > 23 to 40 kg
- Preferred regimen: Oseltamivir (Tamiflu®) 60 mg PO qd for 7 days
- 4.2.2.4 Children > 40 kg
- Preferred regimen (1): Oseltamivir (Tamiflu®) 75 mg PO qd for 7 days
- Preferred regimen (2): Zanamivir (Relenza®) 10 mg (two 5-mg inhalations) qd for 7 days, may be considered for children > 7 yrs older
- Note: If child is < 3 months old, use of Oseltamivir for chemoprophylaxis is not recommended unless situation is judged critical due to limited data in this age group.
# Avian influenza
- Avian influenza Return to Top
- 1. Preferred regimen:Oseltamivir 75 mg PO qd for a minimum 10 days [410][411]
- Note:Patients with severe disease may have diarrhea and may not absorb oseltamivir efficiently
- 2. Patients with Avian Influenza who have diarrhea and malabsorption
- Preferred regimen (1): Zanamivir 10 mg inhaled bid for minimum 5 days
- Preferred regimen (2): Peramivir 600 mg IV as a single dose for 1 day
- Note(1): Preliminary evidence demonstrates that Neuraminidase inhibitor can reduce the duration of viral replication and improve survival among patients with avian influenza. In cases of suspected avian influenza, one of the following 3 neuraminidase inhibitors should be administered as soon possible, preferably within 48 hours of symptom onset.
- Note(2): The use of Corticosteroids is not recommended.
- Note(3): Physicians may consider increasing either the recommended daily dose and/or the duration of treatment in cases of severe disease.
- Note(4): The use of Amantadine is not recommended as most H5N1 and H7N9 avian influenza viruses are resistant to it.[412]
- Note(5): Supportive care is also an important cornerstone of the care of patients with avian influenza. Considering the severity of the illness and the possible complications, patients may require fluid resuscitation, vasopressors, intubation and ventilation, paracentesis, hemodialysis or hemofiltration, and parentral nutrition.
- Swine influenza Return to Top
- Swine influenza [413]
- 1. Condition1: Patients who have severe or progressive clinical illness
- Preferred regimen: Oseltamivir 150 mg PO bid
- Note (1): Treatment duration depends on clinical response
- Note (2): Where the clinical course remains severe or progressive, despite 5 or more days of antiviral treatment, monitoring of virus replication and shedding, and antiviral drug susceptibility testing is desirable
- Note (3): Antiviral treatment should be maintained without a break until virus infection is resolved or there is satisfactory clinical improvement
- Note (4): Patients who have severe or progressive clinical illness, but who are unable to take oral medication may be treated with oseltamivir administered by nasogastric or orogastric tube
- 2. Condition2: In situations where oseltamivir is not available, or not possible to use, patients who have severe or progressive clinical illness
- Preferred regimen: Zanamivir inhaled
- Note: Zanamivir IV should be considered where available and is recommended for those with serious or progressive illness. If not available, Peramivir IV may be considered
- 3. Condition3: Severely immunosuppressed patients
- Preferred regimen: Antiviral chemoprophylaxis by using Oseltamivir OR Zanamivir
- Measles Return to Top
- Measles
- 1.1. Prevention
- 1.1.1. Vaccines
- Note (1): Measles can be prevented with measles-containing vaccine, which is primarily administered as the combination measles-mumps-rubella (MMR) vaccine. The combination measles-mumps-rubella-varicella (MMRV) vaccine can be used for children aged 12 months through 12 years for protection against measles, mumps, rubella and varicella. Single-antigen measles vaccine is not available.
- Note (2): Vaccination recommendations
- Children: CDC recommends routine childhood immunization for MMR vaccine starting with the first dose at 12 through 15 months of age, and the second dose at 4 through 6 years of age or at least 28 days following the first dose.
- Students at post-high school educational institutions: Students at post-high school educational institutions without evidence of measles immunity need two doses of MMR vaccine, with the second dose administered no earlier than 28 days after the first dose.
- Adults: People who are born during or after 1957 who do not have evidence of immunity against measles should get at least one dose of MMR vaccine.
- International travelers: People 6 months of age or older who will be traveling internationally should be protected against measles. Before travelling internationally,
- Infants 6 through 11 months of age should receive one dose of MMR vaccine
- Children 12 months of age or older should have documentation of two doses of MMR vaccine (the first dose of MMR vaccine should be administered at age 12 months or older; the second dose no earlier than 28 days after the first dose)
- Teenagers and adults born during or after 1957 without evidence of immunity against measles should have documentation of two doses of MMR vaccine, with the second dose administered no earlier than 28 days after the first dose
- 1.1.2. Post-exposure Prophylaxis
- 1.1.2.1. Indication
- People exposed to measles who cannot readily show that they have evidence of immunity against measles should be offered post-exposure prophylaxis (PEP) or be excluded from the setting (school, hospital, childcare). MMR vaccine, if administered within 72 hours of initial measles exposure, or immunoglobulin (IG), if administered within six days of exposure, may provide some protection or modify the clinical course of disease.
- Note (1): If MMR vaccine is not administered within 72 hours of exposure as PEP, MMR vaccine should still be offered at any interval following exposure to the disease in order to offer protection from future exposures. People who receive MMR vaccine or IG as PEP should be monitored for signs and symptoms consistent with measles for at least one incubation period.
- Note (2): If many measles cases are occurring among infants younger than 12 months of age, measles vaccination of infants as young as 6 months of age may be used as an outbreak control measure. Note that children vaccinated before their first birthday should be revaccinated when they are 12 through 15 months old and again when they are 4 through 6 years of age.
- Note (3): People who are at risk for severe illness and complications from measles, such as infants younger than 12 months of age, pregnant women without evidence of measles immunity, and people with severely compromised immune systems, should receive IG. Intramuscular IG (IGIM) should be given to all infants younger than 12 months of age who have been exposed to measles.
- Note (4): For infants aged 6 through 11 months, MMR vaccine can be given in place of IG, if administered within 72 hours of exposure. Because pregnant women might be at higher risk for severe measles and complications, intravenous IG (IGIV) should be administered to pregnant women without evidence of measles immunity who have been exposed to measles. People with severely compromised immune systems who are exposed to measles should receive IGIV regardless of immunologic or vaccination status because they might not be protected by MMR vaccine.
- Preferred regimen: The recommended dose of IGIM is 0.5 mL/kg of body weight (maximum dose = 15 mL) and the recommended dose of IGIV is 400 mg/kg.
- Note (5): If a healthcare provider without evidence of immunity is exposed to measles, MMR vaccine should be given within 72 hours, or IG should be given within 6 days when available. Exclude healthcare personnel without evidence of immunity from duty from day 5 after first exposure to day 21 after last exposure, regardless of post-exposure vaccine.
- 1.2. Treatment
- Note (1): There is no specific antiviral therapy for measles. Medical care is supportive and to help relieve symptoms and address complications such as bacterial infections.
- Note (2): Severe measles cases among children, such as those who are hospitalized, should be treated with vitamin A. Vitamin A should be administered immediately on diagnosis and repeated the next day. The recommended age-specific daily doses are
- 50,000 IU for infants younger than 6 months of age
- 100,000 IU for infants 6–11 months of age
- 200,000 IU for children 12 months of age and older
- Middle East respiratory syndrome Return to Top
- Middle East Respiratory Syndrome treatment
- Preferred regimen: supportive care. There is no antiviral recommended for this infection at this moment, even though experimental therapies are at research (IFNs, Ribavirin, Lopinavir, Mycophenolic acid, Cyclosporine, Chloroquine, Chlorpromazine, Loperamide, 6-mercaptopurine and 6-thioguanine). Supportive care include: administer oxygen to patients with severe acute pulmonary infection with signs of respiratory distress, hypoxaemia or shock; use conservative fluids management, avoid administering high-dose systemic glucocorticoids, use non-invasive ventilation, but, if its nor effective, do not delay endotracheal intubation; use lung-protective strategy for intubated patients, recognize sepsis as early as possible and treat it accordingly.[414]
# Parainfluenza virus
- Parainfluenza virus Return to Top
- Parainfluenza virus[415]
- 1. Adults
- Preferred regimen: Ribavirin PO/IV 10 mg/kg q8h
- Day 1: Start with 600 mg loading dose,then 200 mg q8h
- Day 2: 400 mg q8h
- Day 3: Increase the dose to a maximum of 10 mg/kg q8h
- 1.1 In case of adverse events
- Preferred regimen: Decrease dose or discontinue Ribavirin
- 1.2 Creatinine clearance
- 30–50 mL/min: Ribavirin PO/IV maximal 200 mg q8h
- 10–30 mL/ min: No recommendation can be given
- Parvovirus B19 Return to Top
- Parvovirus B19[416]
- 1. Erythema infectiosum
- Supportive therapy: Symptomatic treatment only
- 2. Arthritis/arthalgia
- Preferred regimen: Nonsteroidal anti-inflammatory drugs (NSAID)
- 3.Transient aplastic crisis
- Supportive therapy: Transfusions and oxygen
- 4. Fetal hydrops
- Supportive therapy: Intrauterine blood transfusion
- 5. Chronic infection with anemia
- Preferred regimen: IVIG and transfusion
- 6.Chronic infection without anemia
- Preferred regimen: IVIG
- BK virus Return to Top
- Human polyomavirus (BK virus) treatment
- Maintenance regimen consisting of triple immunosuppression therapy: Calcineurin inhibitor (Cyclosporine or Tacrolimus) AND an antimetabolite (Azathioprine, Mycophenolate mofetil, or Mycophenolate sodium), AND Prednisone is to discontinue completely the antimetabolite (usually Mycophenolate) and decrease the dose of the Calcineurin inhibitor.
- Alternative regimen (1): Decrease the Mycophenolate dose by 50 percent, followed by a 50 percent decrease in the Calcineurin inhibitor at three months if decoy cells persist. If using this approach, the target serum Tacrolimus trough level is 4 to 6, and the target serum Cyclosporine trough level is 60 to 100 ng/mL. Mycophenolate may be discontinued completely if viral activation persists. Maintenance immunosuppression then consists of Tacrolimus and low-dose Prednisone.
- Alternative regimen (2): Reduce both the Calcineurin inhibitor and the Mycophenolate, which allows both the targeting of two pathways and lower total immunosuppression.
- Note (1): For those who are hypogammaglobulinemic, we administer intravenous immunoglobulins (IV IG) in replacement doses of 500 mg/kg. Quantitative immunoglobulins should be checked two to three months later to determine whether hypogammaglobulinemia has recurred. Intravenous immunoglobulins (IV IG) is also an option in certain settings, based upon polymerase chain reaction (PCR) and kidney biopsy results. IVIG may contain antibodies against BK and JC virus since these viruses are ubiquitous in the general population.
- Note (2): The goals of decreased immunosuppressive therapy are to restrain viral replication without triggering rejection.
- Note (3): Reduced immunosuppression (defined as lowering mean doses of Mycophenolate and Tacrolimus) resulted in the successful elimination of viremia (mean period of six months) and allograft survival.
- Note (4): Alternative approaches to reducing immunosuppression have also been effective
- 4.1 Changing from Tacrolimus to low-dose Cyclosporine not only reduces the effect of the Calcineurin inhibitor, but also reduces Mycophenolate concentrations.
- 4.2 Replacing the Calcineurin inhibitor with Sirolimus, with or without discontinuation of the antimetabolite, has the advantage of avoiding the long-term Calcineurin inhibitor-related nephrotoxic effects.
- 4.3 Lowering the dose of Calcineurin inhibitors may slow the loss of renal function.
- Primary Regimens
- Decrease immunosuppression if possible. (Cornerstone of Treatment)
- Suggested antiviral therapy is based on anecdotal data. If progressive renal dysfunction:
- Fluoroquinolone AND IVIG 500 mg/kg IV AND Leflunomide 100 mg for daily for 3 days, then 10-20 mg PO daily
- If refractory to all of the above, add Cidofovir 5 mg/kg once per week for 2 weeks, then once every other week if refractory to all of the above
- Ancillary Therapies in BK Virus Nephropathy
- Cidofovir 0.25-1.0 mg/kg IV biweekly for 8 wk without Probenecid, prehydration recommended
- Leflunomide 100 mg loading dose for 3 days, 20-60 mg/day, goal Leflunomide trough 50-100 ng/mL (consider lower trough goals of 20-40 ng/mL given hemolysis risk)
- IV Ig 1-2 g/kg IV for 1-2 doses or 150 mg/kg IV biweekly for 8 wk
- Fluoroquinolones-Ciproflaxacin 500 mg/day, duration dependent on virological response.
- JC virus Return to Top
- Progressive Multifocal Leukoencephalopathy (PML) caused by JC Virus ( John Cunningham virus) infections[417]
- There is no specific antiviral therapy for JC virus infection.
- The main treatment approach is to reverse the immunosuppression caused by HIV.
- Initiate anti retroviral therapy (ART) immediately in ART-naive patients .
- Optimize ART in patients who develop Progressive Multifocal Leukoencephalopathy in phase of HIV viremia on ART .
- Corticosteroids may be used for Progressive Multifocal Leukoencephalopathy- immune reconstitution inflammatory syndrome (IRIS) characterized by contrast enhancement, edema or mass effect, and with clinical deterioration
- Rabies Return to Top
- Rabies treatment
- Preferred regimen: no specific therapetics agents are available once the disease is established.
- Note: There are vaccines and immunoglobulins available for postexposure prophylaxis
- Postexposure prophylaxis
- 1. For non immunized individuals
- 2. For immunized individuals
- Respiratory Syncytial Virus Return to Top
- Respiratory syncytial virus treatment
- Supportive therapy
- Hydration and supplemental oxygen.
- Routine use of Ribavirin not recommended. Ribavirin therapy associated with small increases in O2 saturation.
- No consistent decrease in need for mechanical ventilation or ICU stays. High cost, aerosol administration and potential toxicity[418]
- Note (1): In adults, Respiratory syncytial virus accounted for 10.6% of hospitalizations for pneumonia, 11.4% for COPD, 7.2% for asthma & 5.4% for CHF in pts >65 yrs of age [419]. Respiratory syncytial virus caused 11% of clinically important respiratory illnesses in military recruits[420]
- Note (2): Respiratory Syncytial Virus major cause of morbidity in neonates/infants.
- Note (3): Nucleic acid test now approved to detect 12 respiratory viruses (xTAG Respiratory Viral Panel, Luminex Molecular Diagnostics).
- Prevention of Respiratory syncytial virus
- 1. In children <24 months old with chronic lung disease of prematurity (formerly broncho-pulmonary dysplasia) requiring supplemental oxygen or
- 2. In premature infants (<32 wks gestation) and <6 months old at start of Respiratory syncytial virus season or
- 3. In children with selected congenital heart diseases.
- Preferred regimen for prevention of Respiratory syncytial virus: Palivizumab (Synagis) 15 mg per kg IM q month Nov.-April[418]
- Rhinovirus Return to Top
- Rhinovirus treatment (commom cold)
- Supportive therapy
- 1. Symptomatic treatment-Ipratropium bromide intranasal (2 sprays tid) AND Clemastine 1.34 mg 1–2 tab PO bid–tid (over the counter)
- 2. Symptomatic relief by Ipratropium nasal spray decreases rhinorrhea and sneezing vs placebo.[422] AND Clemastine (an antihistamine) decreases sneezing, rhinorrhea but associated with dry nose, mouth & throat in 6–19%.[423]OR Oral pleconaril given within 24 hrs of onset reduced duration (1 day) & severity of “cold symptoms” in DBPCT (p < .001).[424]
- Note (1): No antiviral treatment indicated . [425]
- Note (2): Found in half of children with community-acquired pneumonia; role in pathogenesis unclear (CID 39:681, 2004). [426]
- Note (3): High rate of rhinovirus identified in children with significant lower resp tract infections [427]
- Rotavirus Return to Top
- Rotavirus treatment[428], [429]
- Treatment of diarrhoea caused by rotavirus
- Rehydration with oral rehydration salts (ORS) solution. oral rehydration salts (ORS) solution is a mixture of clean water, salt and sugar. It costs a few cents per treatment. oral rehydration salts (ORS) solution is absorbed in the small intestine and replaces the water and electrolytes lost in the faeces.
- Zinc supplements-with zinc supplements reduce the duration of a diarrhoea episode by 25% and are associated with a 30% reduction in stool volume.
- Rehydration with intravenous fluids in case of severe dehydration or shock.
- Nutrient-rich foods the vicious circle of malnutrition and diarrhoea can be broken by continuing to give nutrient-rich foods including breast milk during an episode, and by giving a nutritious diet including exclusive breastfeeding for the first six months of life to children when they are well.
- Consulting a health professional , in particular for management of persistent diarrhoea or when there is blood in stool or if there are signs of dehydration.
- Prevention
- Access to safe drinking-water
- Use of improved sanitation
- Hand washing with soap
- Exclusive breastfeeding for the first six months of life
- Good personal and food hygiene
- Health education about how infections spread; and Rotavirus vaccination.
# Smallpox
- Smallpox Return to Top
- Smallpox [430]
- Supportive care is the mainstay of therapy.
- Currently, there are no anti-viral drugs of proven efficacy.
- Recently, animal studies suggest that cidofovir and its cyclic analogues, given at the time of or immediately after exposure, have promise for the prevention of cowpox, vaccinia, and monkeypox.
- Patients need adequate hydration and nutrition, because substantial amounts of fluid and protein can be lost by febrile persons with dense, often weeping lesions.
- 1. Secondary bacterial infection
- Penicillinase-resistant antimicrobial agents should be used
- If smallpox lesions are secondarily infected,
- If bacterial infection endangers the eyes
- Daily eye rinsing is required in severe cases.
- Topical idoxuridine should be considered for the treatment of corneal lesions, although its efficacy is unproved for smallpox.
- If the eruption is very dense and widespread.
# HIV/AIDS
- HIV/AIDS Return to Top
]* 1. Antiretroviral regimen options for treatment-naive patients[431]
- 1.1. Integrase strand transfer inhibitor-based regimens
- Preferred regimen (1): Dolutegravir 50 mg PO qd AND Abacavir 600 mg-Lamivudine 300 mg PO qd in patients who are HLA-B*5701-negative
- Preferred regimen (2): Dolutegravir 50 mg PO qd AND Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Preferred regimen (3): Elvitegravir 150 mg-Cobicistat 150 mg-Tenofovir 300 mg-Emtricitabine 200 mg PO qd in patients with estimated CrCl ≥ 70 mL/min/1.73
- Preferred regimen (4): Raltegravir 400 mg PO bid AND Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Alternative regimen (1): Efavirenz 600 mg PO qd OR Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Alternative regimen (2): Rilpivirine 25 mg PO qd AND (Tenofovir 300 mg PO qd OR Emtricitabine 200 mg PO qd) for patients with CD4 count >200 cells/microL
- Alternative regimen (3): Raltegravir 400 mg PO bid AND (Abacavir 600 mg PO qd OR Lamivudine 300 mg PO qd) in patients who are HLA-B*5701-negative
- 1.2. Protease inhibitor-based regimen
- Preferred regimen: Darunavir 800 mg-Ritonavir 100 mg PO qd AND Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Alternative regimen (1): Atazanavir 300 mg-Cobicistat 150 mg PO qd AND Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd only for patients with pre-treatment estimated CrCl ≥70 mL/min
- Alternative regimen (2): Atazanavir 300 mg-Ritonavir 100 mg PO qd AND Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Alternative regimen (3): (Darunavir 800 mg-Cobicistat 150 mg PO qd OR Darunavir 800 mg-Ritonavir 100 mg PO qd) AND Abacavir 600 mg-Lamivudine 300 mg PO qd only for patients who are HLA-B*5701 negative
- Alternative regimen (4): Darunavir 800 mg-Cobicistat 150 mg PO qd AND Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd only for patients with pre-treatment estimated CrCl ≥70 mL/min
- Alternative regimen (5): Atazanavir 300 mg-Ritonavir 100 mg PO qd AND Abacavir 600 mg-Lamivudine 300 mg PO qd in patients who are HLA-B*5701-negative and with pre-treatment HIV RNA <100,000 copies/mL
- Alternative regimen (6): Lopinavir 400 mg-Ritonavir 100 mg PO qd or bid AND Abacavir 600 mg-Lamivudine 300 mg PO qd only for patients who are HLA-B*5701 negative
- Alternative regimen (7): Lopinavir 400 mg-Ritonavir 100 mg PO qd or bid AND Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd
- 1.3. A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen
- Alternative regimen (1): Efavirenz 600 mg-Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- Alternative regimen (2): Rilpivirine 25 mg-Tenofovir 300 mg-Emtricitabine 200 mg PO qd
- 1.4. Other regimen options
- 1.4.1. A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen
- Preferred regimen (1): Efavirenz 600 mg PO qd AND Abacavir 600 mg-Lamivudine 300 mg PO qd only for patients who are HLA-B*5701 negative and with pre-treatment HIV RNA <100,000 copies/mL.
- 1.4.2. Other regimens when tenofovir or abacavir cannot be used
- Preferred regimen (1): Darunavir 800 mg-Ritonavir 100 mg PO qd AND Raltegravir 400 mg PO qd only for patients with pre-treatment HIV RNA <100,000 copies/mL and CD4 cell count >200 cells/mm3.
- Preferred regimen (2): Lopinavir 400 mg-Ritonavir 100 mg PO bid AND Lamivudine 300 mg PO bid
- 1.5. Pediatric doses
- Abacavir 300 mg PO bid
- Lamivudine 4 mg/kg/dose PO bid; maximum 150 mg PO bid
- Stavudine 1 mg/kg/dose PO bid
- Tenofovir 8 mg/kg/dose PO bid
- Zidovudine 180-240 mg/m2/dose PO bid or 160 mg/m2/dose PO tid (range 90 mg/m2/dose-180 mg/m2/dose)
- Lopinavir 400 mg PO bid
- Nelfinavir 50 mg/kg/dose PO bid
- Raltegravir 300 mg PO bid
- Didanosine
- 20 to < 25 kg: 200 mg PO qd
- 25 to < 60 kg: 250 mg PO qd
- ≥60 kg: 400 mg PO qd
- Efavirenz
- 10 to < 15 kg: 200 mg PO qd
- 15 to <20 kg: 250 mg PO qd
- 20 to < 25 kg: 300 mg PO qd
- 25 to < 32.5 kg: 350 mg PO qd
- 32.5 to <40 kg: 400 mg PO qd
- ≥ 40 kg: 600 mg PO qd
- Nevirapine maximum 200 mg per dose
- Between 1 day and 8 years: 200 mg/m2/dose PO qd for 14 days, then 200 mg/m2/dose PO bid
- 8 years and above: 120-150 mg/m2/dose PO qd for 14 days, then 120-150 mg/m2/dose PO bid
- Note (1): Anti retroviral therapy for treatment naive patients is a life long therapy.
- Note (2): Tenofovir disoproxil fumarate should be avoided in patients with a creatinine clearance <50 mL/min.
- Note (3): Rilpivirine should be used in patients with a CD4 cell count >200 copies/mL and should not be used with proton pump inhibitors.
- Note (4): Efavirenz should not be used in pregnant women.
- 2. Pre-exposure prophylaxis (PrEP)
- Preferred regimen: Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd for ≤90-days
- Note (1): People with high risk behavior such as men who have sex with men, intravenous drug abusers, HIV-positive sexual partner, recent bacterial STI, high number of sex partners, history of inconsistent or no condom use, commercial sex work, people in high-prevalence area or network are advised to take pre-exposure prophylaxis of drugs.
- Note (2): Follow-up visits at least every 3 months to provide the following: HIV test, medication adherence counseling, behavioral risk reduction support, side effect assessment, STI symptom assessment, pregnancy testing.
- Note (3): At 3 months and every 6 months thereafter, assess renal function.
- Note (4): Every 6 months, test for bacterial STIs.
- 3. Post- exposure prophylaxis
- Preferred regimen: Raltegravir 400 mg PO bid AND Tenofovir disoproxil fumarate 300 mg-Emtricitabine 200 mg PO qd
- Preferred basic regimen for low-risk exposures (Eg: mucus membrane):
Zidovudine 100 mg PO qd AND Lamivudine 300 mg PO qd
Zidovudine 100 mg PO qd AND Emtricitabine 200 mg PO qd
Tenofovir 300 mg PO qd AND Lamivudine 300 mg PO qd
Tenofovir 300 mg PO qd AND Emtricitabine 200 mg PO qd
- Zidovudine 100 mg PO qd AND Lamivudine 300 mg PO qd
- Zidovudine 100 mg PO qd AND Emtricitabine 200 mg PO qd
- Tenofovir 300 mg PO qd AND Lamivudine 300 mg PO qd
- Tenofovir 300 mg PO qd AND Emtricitabine 200 mg PO qd
- Preferred expanded regimen for high-risk exposure (Eg: percutaneous needle stick)
Zidovudine 100 mg PO qd AND Lamivudine 300 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
Zidovudine 100 mg PO qd AND Emtricitabine 200 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
Tenofovir 300 mg PO qd AND Lamivudine 300 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
Tenofovir 300 mg PO qd AND Emtricitabine 200 mg PO qdAND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Zidovudine 100 mg PO qd AND Lamivudine 300 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Zidovudine 100 mg PO qd AND Emtricitabine 200 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Tenofovir 300 mg PO qd AND Lamivudine 300 mg PO qd AND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Tenofovir 300 mg PO qd AND Emtricitabine 200 mg PO qdAND Lopinavir 400 mg-Ritonavir 100 mg PO qd
- Note: Ideally therapy should be started within hours of exposure and continued for 28 days.
- 4. Perinatal antiretroviral regimen
- 4.1. Antepartum
- 4.1.1. Protease inhibitor-based regimen
- Preferred regimen: (Tenofovir 300 mg-Emtricitabine 200 mg PO qd (fixed dose combination) OR Tenofovir 300 mg-Lamivudine 300 mg PO qd OR Abacavir 600 mg-Lamivudine 300 mg PO qd OR Zidovudine 100 mg-Lamivudine 300 mg PO qd) AND (Atazanavir 300 mg-Ritonavir 100 mg PO qd OR Lopinavir 400 mg-Ritonavir 100 mg PO qd)
- 4.1.2. A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen:
- Preferred regimen (1): Efavirenz 600 mg-Tenofovir 300 mg-Emtricitabine 200 mg (fixed dose combination) PO qd
- Preferred regimen (2): Efavirenz 600 mg-Tenofovir 300 mg-Lamivudine 300 mg PO qd
- Alternative regimen: (Abacavir 600 mg-Lamivudine 300 mg PO qd OR Zidovudine 100 mg-Lamivudine 300 mg PO qd) AND Efavirenz 600 mg PO qd
- 4.2. Intrapartum
- Note (1): HIV RNA <1000 copies/mL and good adherance-Continue the regimen during delivery or cessarean section.
- Note (2): HIV RNA >1000 copies/mL near delivery, possible poor adherence, or unknown HIV RNA levels- Intravenous Zidovudine 2 mg/kg IV over 1 hr should be given three hours before cesarean section or delivery and then 1 mg/kg/hr IV continuous infusion until umbilical cord clamping.
- 4.3. Postpartum
- Note: Initiate anti retroviral therapy (ART) and continue after delivery and cessation of breastfeeding.
- 5. Infant antiretroviral prophylaxis for prevention of mother-to-child transmission of HIV
- 5.1 Prophylaxis for HIV-exposed infants of women who received antepartum antiretroviral prophylaxis
- Preferred regimen: Zidovudine (ZDV) 100 mg PO given at birth and continued till six weeks
- Note (1): Dose based on gestational age at birth and weight, initiated as soon after birth as possible and preferably within 6 to 12 hours of delivery.
- Note (2): ≥35 weeks gestation at birth: 4 mg/kg/dose orally (or, if unable to tolerate oral agents, 3 mg/kg/dose IV) every 12 hours.
- Note (3): ≥30 to <35 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours at age 15 days.
- Note (4): <30 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours after age four weeks.
- 5.2. Prophylaxis for HIV-exposed infants of women who received no antepartum antiretroviral prophylaxis
- Dose based on birth weight, initiated as soon after birth as possible.
- Birth weight 1.5 to 2 kg: 8 mg/dose orally.
- Birth weight >2 kg: 12 mg/dose orally.
- Dose based on gestational age at birth and weight, initiated as soon after birth as possible and preferably within 6 to 12 hours of delivery.
- ≥35 weeks gestation at birth: 4 mg/kg/dose orally (or, if unable to tolerate oral agents, 3 mg/kg/dose IV) every 12 hours.
- ≥30 to <35 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours at age 15 days.
- <30 weeks gestation at birth: 2 mg/kg/dose orally (or 1.5 mg/kg/dose IV) every 12 hours, advanced to 3 mg/kg/dose orally (or 2.3 mg/kg/dose IV) every 12 hours after age four weeks.
- Note (1): Three doses in the first week of life.
- Note (2): First dose within 48 hours of birth (birth to 48 hrs).
- Note (3): Second dose 48 hours after first.
- Note (4): Third dose 96 hours after second.
- 6. Treatment and prevention of opportunistic infections
- 6.1. Pneumocystis pneumonia (PCP)
- 6.1.1. Prevention
- Indication
- CD4 count <200 cells/mm3
- Oropharyngeal candidiasis
- CD4 <14%
- History of AIDS-defining illness
- CD4 count >200 but <250 cells/mm3 if monitoring CD4 cell count every 3 months is not possible.
- Preferred regimen: Trimethoprim/sulfamethoxazole 160 mg/800 mg PO qd or 80 mg/400 mg PO qd
- Alternative regimen (1): Trimethoprim/sulfamethoxazole 160 mg/800 mg PO three times weekly
- Alternative regimen (2): Dapsone 100 mg PO qd or 50 mg PO bid
- Alternative regimen (3): Dapsone 50 mg PO qd AND (Pyrimethamine 50 mg-Leucovorin 25 mg) PO weekly
- Alternative regimen (4): Dapsone 200 mg PO qd AND (Pyrimethamine 75 mg-Leucovorin 25 mg) PO weekly
- Alternative regimen (5): Aerosolized Pentamidine 300 mg via Respigard nebulizer every month
- Alternative regimen (6): Atovaquone 1500 mg PO qd
- Alternative regimen (7): Atovaquone 1500 mg AND (Pyrimethamine 25 mg AND Leucovorin 10 mg) PO qd
- 6.1.2. Treatment
- 6.1.2.1. For Moderate-to-Severe PCP'
- Preferred regimen: Trimethoprim 15–20 mg AND Sulfamethoxazole 75–100 mg/kg/day IV given q6h or q8h, may switch to PO after clinical improvement
- Alternative regimen (1): Pentamidine 4 mg/kg IV daily infused over ≥60 minutes
- Note: Reduce dose to 3 mg/kg IV daily if toxic.
- Alternative regimen (2): Primaquine 30 mg (base) PO qd AND (Clindamycin 600 mg q6h IV OR 900 mg IV q8h OR Clindamycin 450 mg PO qid or 600 mg PO tid)
- 6.1.2.2. For Mild-to-Moderate PCP
- Preferred regimen: Trimethoprim 15–20 mg AND Sulfamethoxazole 75–100 mg/kg/day PO in TID OR Trimethoprim/sulfamethoxazole 160 mg/800 mg 2 tablets PO tid
- Alternative regimen (1): Dapsone 100 mg PO qd AND TMP 5 mg/kg PO tid
- Alternative regimen (2): Primaquine 30 mg (base) PO qd AND (Clindamycin 450 mg PO qid or 600 mg PO tid OR Atovaquone 750 mg PO bid with food)
- 6.1.3. Secondary prophylaxis, after completion of PCP treatment
- Preferred regimen (1): Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO qd OR Trimethoprim/Sulfamethoxazole 80 mg/400 mg PO qd
- Alternative regimen (1): Trimethoprim/sulfamethoxazole 160 mg/800 mg PO three times weekly
- Alternative regimen (2): Dapsone 100 mg PO qd
- Alternative regimen (3): Dapsone 50 mg PO qd AND Pyrimethamine 50 mg PO AND Leucovorin 25 mg PO weekly
- Alternative regimen (4): Dapsone 200 mg PO AND Pyrimethamine 75 mg PO AND Leucovorin 25 mg PO weekly
- Alternative regimen (5): Dapsone 100 mg PO qd
- Alternative regimen (6): Dapsone 50 mg PO qd AND Pyrimethamine 50 mg PO AND Leucovorin 25 mg PO weekly
- Alternative regimen (7): Dapsone 200 mg PO AND Pyrimethamine 75 mg PO AND Leucovorin 25 mg PO weekly
- Alternative regimen (8): Aerosolized Pentamidine 300 mg monthly via Respirgard nebulizer
- Alternative regimen (9): Atovaquone 1500 mg PO qd
- Alternative regimen (10): Atovaquone 1500 mg PO AND Pyrimethamine 25 mg PO AND Leucovorin 10 mg PO qd
- 6.1.4. Adjunctive corticosteroids
- Indications- PaO2 <70 mmHg at room air OR Alveolar-arterial O2 gradient >35 mmHg.
- Preferred regimen:
- Days 1–5: 40 mg PO bid
- Days 6–10: 40 mg PO qd
- Days 11–21: 20 mg PO qd
- Note (1): Trimethoprim/sulfamethoxazole should be permanently discontinued in patients with possible or definite stevens johnson syndrome or toxic epidermal necrosis.
- Note (2): Whenever possible, patients should be tested for G6PD before use of Dapsone or Primaquine. Alternative regimen should be used in patients found to have G6PD deficiency.
- 6.2. Toxoplasma gondii encephalitis
- 6.2.1. Prevention
- 6.2.1.1. Indication
- Toxoplasma IgG-positive patients with CD4 count <100 cells/µL.
- Seronegative patients receiving PCP prophylaxis not active against toxoplasmosis should have toxoplasma serology retested if CD4 count decline to <100 cellsµL.
- Prophylaxis should be initiated if seroconversion occurred.
- Preferred regimen: Trimethoprim/sulfamethoxazole 160 mg/800 mg PO qd
- Alternative regimen (1): Trimethoprim/sulfamethoxazole 160 mg/800 mg PO three times weekly
- Alternative regimen (2): Trimethoprim/sulfamethoxazole 80 mg/400 mg PO qd
- Alternative regimen (3): Dapsone 50 mg PO qd AND Pyrimethamine 50 mg PO weekly AND Leucovorin 25 mg PO weekly
- Alternative regimen (4): Dapsone 200 mg PO weekly AND Pyrimethamine 75 mg PO weekly AND Leucovorin 25 mg PO weekly
- Alternative regimen (5): Atovaquone 1500 mg PO qd
- Alternative regimen (6): Atovaquone 1500 mg PO qd AND Pyrimethamine 25 mg PO qd AND Leucovorin 10 mg PO qd
- 6.2.2. Treatment
- 6.2.2.1. Treatment of acute infection
- Preferred regimen: Pyrimethamine 200 mg PO single dose, followed by weight-based therapy:
- If <60 kg, Pyrimethamine 50 mg PO qd AND Sulfadiazine 1000 mg PO qid AND Leucovorin 10–25 mg PO qd
- If ≥60 kg, Pyrimethamine 75 mg PO qd AND Sulfadiazine 1500 mg PO qid AND Leucovorin 10–25 mg PO qd
- Note: At least 6 weeks; longer duration if clinical or radiologic disease is extensive or response is incomplete at 6 weeks.
- Alternative regimen (1): Pyrimethamine 50 mg PO qdAND Leucovorin 10–25 mg PO qd AND Clindamycin 600 mg IV or PO q6h
- Alternative regimen (2): Trimethoprim 5 mg/kg-Sulfamethoxazole 25 mg/kg IV or PO bid
- Alternative regimen (3): Atovaquone 1500 mg PO bid with food AND Pyrimethamine 50 mg PO qd AND Leucovorin 10–25 mg PO qd
- Alternative regimen (4): Atovaquone 1500 mg PO bid with food AND Sulfadiazine 1000–1500 mg PO qid (weight-based dosing, as in preferred therapy)
- Alternative regimen (5): Atovaquone 1500 mg PO bid with food
- Alternative regimen (6): Pyrimethamine 50 mg-Leucovorin 10–25 mg PO qd AND Azithromycin 900–1200 mg PO qd
- 6.2.2.2. Chronic maintenance therapy
- Preferred regimen: Pyrimethamine 25–50 mg PO qd AND Sulfadiazine 2000–4000 mg PO qd (in 2–4 divided doses) AND Leucovorin 10–25 mg PO qd
- Alternative regimen (1): Clindamycin 600 mg PO tid AND Pyrimethamine 25–50 mg-Leucovorin 10–25 mg PO qd
- Alternative regimen (2): Trimethoprim/sulfamethoxazole 160 mg/800 mg bid
- Alternative regimen (3): Atovaquone 750–1500 mg PO bid AND Pyrimethamine 25 mg-Leucovorin 10 mg PO qd
- Alternative regimen (4): Atovaquone 750–1500 mg PO bid AND Sulfadiazine 2000–4000 mg PO qd in 2–4 divided doses
- Alternative regimen (5): Atovaquone 750–1500 mg PO bid with food
- 6.3. Mycobacterium tuberculosis infection
- 6.3.1. Prevention
- 6.3.1.1. Indication
- Positive screening test for latent tuberculosis infection, with no evidence of active tuberculosis, and no prior treatment for active tuberculosis or latent tuberculosis infection.
- Close contact with a person with infectious tuberculosis, with no evidence of active tuberculosis, regardless of screening test results.
- Preferred regimen: (Isoniazid 300 mg PO qd AND Pyridoxine 25 mg PO qd for 9 months) OR (Isoniazid 900 mg PO two times a week (by DOT) AND Pyridoxine 25 mg PO qd for 9 months)
- Alternative regimen (1): Rifampin 600 mg PO qd for 4 months
- Alternative regimen (2): Rifabutin (dose adjusted based on concomitant ART) PO qd for 4 months
- 6.3.2. Treatment
- Preferred regimen
- Initiation phase: Isoniazid 300 mg PO qd AND (Rifampin 600 mg PO qd OR Rifabutin 300 mg PO qd) AND Pyrazinamide (upto 2000 mg) PO qd AND Ethambutol (upto 1600 mg) PO qd for initial phase for 2 months.
- Continuation phase: Isoniazid 300 mg PO qd AND (Rifampin 600 mg PO qd OR Rifabutin 300 mg PO qd) (5–7 times/week) or three times a week.
- Duration of therapy:
- Pulmonary tuberculosis: 6 months
- Pulmonary tuberculosis and culture positive after 2 months of tuberculosis treatment: 9 months
- Extra-pulmonary tuberculosis w/CNS infection: 9–12 months
- Extra-pulmonary tuberculosis with bone or joint involvement: 6 to 9 months
- Extra-pulmonary tuberculosis in other sites: 6 months
- Total duration of therapy should be based on number of doses received, not on calendar time
- 6.3.1.3. Treatment for drug-resistant tuberculosis
- Resistant to Isoniazid:
- Preferred regimen (1): (Rifampin 600 mg PO qd OR Rifabutin 300mg PO qd) AND Ethambutol (upto 1600 mg) PO qd AND Pyrazinamide (upto 2000 mg) PO qd AND (Moxifloxacin 400 mg PO or IV qd OR Levofloxacin 500-1000 mg PO or IV qd) for 2 months; followed by Rifampin 600 mg PO qd for 7 months.
- Preferred regimen (2): Rifabutin 300mg PO qd AND Ethambutol (upto 1600 mg) PO qd AND (Moxifloxacin 400 mg PO or IV qdOR Levofloxacin 500-1000 mg PO or IV qd) for 7 months
- 6.4. Disseminated mycobacterium avium complex (MAC) disease
- 6.4.1. Prevention
- 6.4.1.1. Indication-CD4 count <50 cells/µL—after ruling out active disseminated MAC disease based on clinical assessment
- Preferred regimen (1): Azithromycin 1200 mg PO once weekly
- Preferred regimen (2): Clarithromycin 500 mg PO bid
- Preferred regimen (3): Azithromycin 600 mg PO twice weekly.
- 6.4.2. Treatment
- Preferred regimen: Clarithromycin 500 mg PO bid AND Ethambutol 15 mg/kg PO qd OR Azithromycin 500–600 mg PO qd for at least 12 months of therapy
- Note (1): Treatment can be discontinued if no signs and symptoms of MAC disease and sustained (>6 months) CD4 count >100 cells/µL in response to anti retroviral therapy.
- Note (2): Addition of a third or fourth drug should be considered for patients with advanced immunosuppression (CD4 counts <50 cells/µL), high mycobacterial loads (>2 log CFU/mL of blood), or in the absence of effective anti retroviral therapy which include Amikacin 10–15 mg/kg IV qd, Streptomycin 1 g IV or IM qd, Moxifloxacin 400 mg PO qd, Levofloxacin 500 mg PO qd.
- 6.5. Streptococcus pneumoniae infection
- 6.5.1. Prevention
- 6.5.1.1. Indication
- 6.5.1.1.1. For individuals who have not received any pneumococcal vaccine, regardless of CD4 count
- Preferred regimen: PCV13 0.5ml IM single dose
- Alternative regimen: PPV23 0.5 mL IM or SQ single dose
- Note (1): If CD4 count ≥200 cells/µL, administer PPV23 0.5 mL IM or SQ at least 8 weeks after the PCV13 vaccine.
- Note (2): If CD4 count <200 cells/µL, PPV23 can be offered at least 8 weeks after receiving PCV13 or can wait until CD4 count increased to ≥200 cells/µL.
- 6.5.1.1.2. For individuals who have previously received PPV23
- Note: One dose of PCV13 should be given atleast 1 year after the last receipt of PPV23
- 6.5.1.1.3. Re-vaccination
- If age 19–64 years and ≥5 years since the first PPV23 dose PPV23 0.5 mL IM or SQ
- If age ≥65 years, and if ≥5 years since the previous PPV23 dose PPV23 0.5 mL IM or SQ
- If age ≥65 years, and if ≥5 years since the previous PPV23 dose PPV23 0.5 mL IM or SQ
- 6.6. Influenza A and B virus infection
- 6.6.1. Prevention
- 6.6.1.1. Indication
- All HIV-infected patients
- Note (1): Inactivated influenza vaccine annually (per recommendation for the season).
- Note (2): Live-attenuated influenza vaccine is contraindicated in HIV-infected patients.
- 6.7. Syphilis
- 6.7.1. Prevention
- 6.7.1.1. Indication
- For individuals exposed to a sex partner with a diagnosis of primary, secondary, or early latent syphilis within past 90 days.
- For individuals exposed to a sex partner >90 days before syphilis diagnosis in the partner, if serologic test results are not available immediately and the opportunity for follow-up is uncertain.
- Preferred regimen: Benzathine penicillin G 2.4 million units IM single dose
- Alternative regimen (1): Doxycycline 100 mg PO bid for 14 days
- Alternative regimen (2): Ceftriaxone 1 g IM or IV q24h for 8– 10 days
- Alternative regimen (3): Azithromycin 2 g PO single dose
- Note: Azithromycin is not recommended for MSM or pregnant women.
- 6.7.2. Treatment
- 6.7.2.1. Early stage (primary, secondary, and early-latent syphilis)
- Preferred regimen: Benzathine penicillin G 2.4 million units IM single dose
- Alternative regimen (1): Doxycycline 100 mg PO bid for 14 days
- Alternative regimen (2): Ceftriaxone 1 g IM or IV q24h for 10–14 days
- Alternative regimen (3): Azithromycin 2 g PO single dose
- 6.7.2.2. Late-stage (tertiary–cardiovascular or gummatous disease)
- Preferred regimen: Benzathine penicillin G 2.4 million units IM weekly for 3 doses
- Alternative regimen: Doxycycline 100 mg PO bid for 28 days
- 6.7.2.3. Neurosyphilis (including otic or ocular disease)
- Preferred regimen: Aqueous crystalline Penicillin G 18– 24 million units per day (administered as 3–4 million units IV q4h or by continuous IV infusion) for 10–14 days with or without Benzathine penicillin G 2.4 million units IM weekly for 3 doses after completion of IV therapy
- Alternative regimen: Procaine penicillin 2.4 million units IM q24h AND Probenecid 500 mg PO qid for 10–14 days with or without Benzathine penicillin G 2.4 million units IM weekly for 3 doses after completion
- Note (1): The Jarisch-Herxheimer reaction is an acute febrile reaction accompanied by headache and myalgia that can occur within the first 24 hours after therapy for syphilis.
- Note (2): This reaction occurs most frequently in patients with early syphilis, high nontreponemal titers and prior penicillin treatment.
- 6.8. Histoplasma capsulatum infection
- 6.8.1. Prevention
- 6.8.1.1. Indication
- CD4 count ≤150 cells/µL and at high risk because of occupational exposure or live in a community with a hyperendemic rate of histoplasmosis (>10 cases/100 patient-years).
- Preferred regimen: Itraconazole 200 mg PO qd
- 6.8.2. Treatment
- 6.8.2.1. Moderately severe to severe disseminated disease
- Induction therapy (for at least 2 weeks or until clinically improved)
- Preferred regimen: Liposomal Amphotericin B 3 mg/kg IV q24h
- Maintenance therapy:
- Preferred regimen: Itraconazole 200 mg PO tid for 3 days, then 200 mg PO bid
- 6.8.2.2. Less severe disseminated disease
- Induction therapy:
- Preferred regimen: Liposomal Amphotericin B 3 mg/kg IV q24h
- Alternative regimen: Amphotericin B lipid complex 3 mg/kg IV q24h OR Amphotericin B cholesteryl sulfate complete 3 mg/kg IV q24h
- Note: Induction therapy should be for at least 2 weeks or until clinically improved.
- Maintenance therapy:
- Preferred regimen: Itraconazole 200 mg PO tid for 3 days and then Itraconazole 200 mg PO bid for 12 months
- Alternative regimen (1): Voriconazole 400 mg PO bid for 1 day, then 200 mg bid
- Alternative regimen (2): Posaconazole 400 mg PO bid
- Alternative regimen (3): Fluconazole 800 mg PO qd
- 6.8.2.3. Meningitis
- Induction therapy:
- Preferred regimen: Liposomal amphotericin B 5 mg/kg/day for 4–6 weeks
- Maintenance therapy:
- Preferred regimen: Itraconazole 200 mg PO bid to tid for ≥1 year
- Note: Treatment continued until resolution of abnormal CSF findings.
- Long-Term Suppression Therapy
- Preferred regimen: Itraconazole 200 mg PO qd
- Alternative regimen: Fluconazole 400 mg PO qd
- Note: Therapeutic drug monitoring and dosage adjustment may be necessary to ensure Triazole antifungal and ARV efficacy and reduce concentration-related toxicities.
- 6.9. Coccidioidomycosis
- 6.9.1. Prevention
- 6.9.1.1. Indication
- A new positive IgM or IgG serologic test in patients who live in a disease-endemic area and with CD4 count <250 cells/µL.
- Preferred regimen: Fluconazole 400 mg PO qd
- 6.9.2. Treatment
- 6.9.2.1. Clinically mild infections (e.g., focal pneumonia)
- Preferred regimen: Fluconazole 400 mg PO qd OR Itraconazole 200 mg PO bid
- Alternative regimen: Posaconazole 200 mg PO bid OR Voriconazole 200 mg PO bid
- 6.9.2.2. Severe, non-meningeal infection (diffuse pulmonary infection or severely ill patients with extrathoracic, disseminated disease)
- Preferred regimen: Amphotericin B deoxycholate 0.7–1.0 mg/kg IV qd OR Lipid formulation Amphotericin B 4–6 mg/kg IV qd
- Alternative regimen: Fluconazole or Itraconazole, with Itraconazole preferred for bone disease 400 mg per day to Amphotericin B therapy and continue triazole once Amphotericin B is stopped.
- 6.9.2.3. Meningeal infections
- Preferred regimen: Fluconazole 400–800 mg IV or PO qd
- Alternative regimen: Itraconazole 200 mg PO tid for 3 days, then 200 mg PO bid OR Posaconazole 200 mg PO bid OR Voriconazole 200–400 mg PO bid
- 6.9.2.4. Chronic suppressive therapy
- Preferred regimen: Fluconazole 400 mg PO qd OR Itraconazole 200 mg PO bid
- Alternative regimen: Posaconazole 200 mg PO bid OR Voriconazole 200 mg PO bid
- Note (1): Therapy should be continued indefinitely in patients with diffuse pulmonary or disseminated diseases because relapse can occur in 25%–33% of HIV-negative patients. It can also occur in HIV-infected patients with CD4 counts >250 cells/µL.
- Note (2): Therapy should be lifelong in patients with meningeal infections because relapse occurs in 80% of HIV-infected patients after discontinuation of triazole therapy.
- 6.10. Herpes simplex virus (HSV) Disease
- 6.10.1. Orolabial lesions (For 5–10 Days)
- Preferred regimen (1): Valacyclovir 1 g PO bid
- Preferred regimen (2): Famciclovir 500 mg PO bid
- Preferred regimen (3): Acyclovir 400 mg PO tid
- 6.10.2. Initial or recurrent genital HSV (For 5–14 Days)
- Preferred regimen (1): Valacyclovir 1 g PO bid
- Preferred regimen (2): Famciclovir 500 mg PO bid
- Preferred regimen (3): Acyclovir 400 mg PO tid
- 6.10.3. Severe mucocutaneous HSV
- Preferred regimen: Initial therapy Acyclovir 5 mg/kg IV q8h.
- Note: After lesions begin to regress, change to PO therapy as above. Continue until lesions are completely healed.
- 6.10.4. Chronic suppressive therapy
- Preferred regimen (1): Valacyclovir 500 mg PO bid
- Preferred regimen (2): Famciclovir 500 mg PO bid
- Preferred regimen (3): Acyclovir 400 mg PO bid
- 6.10.4. For acyclovir-resistant HSV
- Preferred therapy: Foscarnet 80–120 mg/kg/day IV q12h-q8h
- Alternative regimen: Cidofovir IV OR Topical Trifluridine OR Topical Imiquimod for 21-28 days
- Note: Continue indefinitely regardless of CD4 cell count.
- 6.11. Varicella-zoster virus (VZV) infection
- 6.11.1. Varicella-zoster virus (VZV) infection
- 6.11.1.2 Prevention
- 6.11.1.1. Pre-exposure prevention
- Indication: Patients with CD4 counts ≥200 cells/µL who have not been vaccinated, have no history of varicella or herpes zoster, or who are seronegative for VZV.
- Preferred regimen: Primary varicella vaccination, 2 doses (0.5 mL SQ each) administered 3 months apart
- Alternative regimen: VZV-susceptible household contacts of susceptible HIV-infected persons should be vaccinated to prevent potential transmission of VZV to their HIV-infected contacts
- Note (1): Routine VZV serologic testing in HIV-infected adults and adolescents is not recommended.
- Note (2): If vaccination results in disease because of vaccine virus, treatment with Acyclovir is recommended.
- 6.11.1.2. Post-exposure prevention
- Indication: Close contact with a person with chickenpox or herpes zoster; and is susceptible (i.e., no history of vaccination or of either condition, or known to be VZV seronegative).
- Preferred regimen: Varicella-zoster immune globulin (VariZIG™) 125 international units per 10 kg (maximum 625 international units) IM, administered as soon as possible and within 10 days after exposure.
- Alternative regimen (1): Acyclovir 800 mg PO qd for 5– 7 days
- Alternative regimen (2): Valacyclovir 1 g PO tid for 5–7 days
- Note (1): Individuals receiving monthly high-dose IVIG (>400 mg/kg) are likely to be protected if the last dose of IVIG was administered <3 weeks before exposure.
- Note (2): If antiviral therapy is used, varicella vaccines should not be given until at least 72 hours after the last dose of the antiviral drug.
- 6.11.1.2. Treatment
- 6.11.1.2.1 Primary varicella infection (chickenpox)
- 6.11.1.2.1. Uncomplicated cases (For 5–7 Days)
- Preferred regimen (1): Valacyclovir 1 g PO tid
- Preferred regimen (2): Famciclovir 500 mg PO tid
- 6.11.1.2.1. Severe or complicated Cases
- Preferred regimen: Acyclovir 10–15 mg/kg IV q8h for 7–10 days.
- Alternative regimen: Acyclovir 800 mg PO 5 times/day for 5-7 days.
- 6.11.1.2.2. Herpes zoster (Shingles)
- 6.11.1.2.2.1. Acute localized dermatomal
- Preferred regimen (1): Valacyclovir 1 g PO tid for 7–10 days; consider longer duration if lesions are slow to resolve
- Preferred regimen (2): Famciclovir 500 mg tid for 7–10 days; consider longer duration if lesions are slow to resolve
- 6.11.1.2.2.2. Extensive cutaneous lesion or visceral involvement
- Preferred regimen: Acyclovir 10–15 mg/kg IV q8h until clinical improvement is evident.
- Note: Treatment may switch to PO therapy (Valacyclovir, Famciclovir, or Acyclovir) after clinical improvement (i.e., when no new vesicle formation or improvement of signs and symptoms of visceral VZV), to complete a 10–14 day course.
- Alternative regimen: Acyclovir 800 mg PO 5 times/day for 7–10 days; consider longer duration if lesions are slow to resolve.
- 6.11.1.2.2.3. Progressive outer retinal necrosis (PORN)
- Preferred regimen: (Ganciclovir 5 mg/kg with or without Foscarnet 90 mg/kg) IV q12h AND (Ganciclovir 2 mg/0.05mL with or without Foscarnet 1.2 mg/0.05 ml) intravitreal injection biweekly.
- 6.11.1.2.2.4. Acute retinal necrosis (ARN)
- Preferred regimen: Acyclovir 10-15 mg/kg IV q8h AND (Ganciclovir 2 mg/0.05mL intravitreal injection 1-2 doses biweekly for 10-14 days, followed by Valacyclovir 1g PO tid for 6 weeks
- 6.12. Cytomegalovirus (CMV) Disease
- 6.12.1. Treatment
- 6.12.1.1. CMV retinitis
- Induction therapy
- Preferred regimen (1): Ganciclovir 2mg OR Foscarnet 2.4mg intravitreal injections for 1-4 doses over a period of 7-10 days to achieve high intraocular concentration faster
- Preferred regimen (2): Valganciclovir 900 mg PO bid for 14–21 days
- Alternative regimen (1): Ganciclovir 5 mg/kg IV q12h for 14–21 days
- Alternative regimen (2): Foscarnet 90 mg/kg IV q12h or 60 mg/kg q8h for 14–21 days
- Alternative regimen (3): Cidofovir 5 mg/kg/week IV for 2 weeks
- Note: Saline hydration before and after therapy should be given and Probenecid, 2 g PO 3 hours before dose, followed by 1 g PO 2 hours and 8 hours after the dose (total of 4 g) is recommended.
- Chronic maintenance (secondary prophylaxis):
- Preferred regimen: Valganciclovir 900 mg PO qd
- Alternative regimen (1): Ganciclovir 5 mg/kg IV 5–7 times weekly
- Alternative regimen (2): Foscarnet 90–120 mg/kg IV once daily
- Alternative regimen (3): Cidofovir 5 mg/kg/week IV for 2 weeks; saline hydration before and after therapy AND Probenecid, 2 g PO 3 hours before dose, followed by 1 g PO 2 hours and 8 hours after the dose (total of 4 g)
- 6.12.1.2. CMV esophagitis or colitis
- 6.12.1.2.1. Severe condition
- Preferred regimen: Ganciclovir 5 mg/kg IV q12h; may switch to Valganciclovir 900 mg PO bid once the patient can tolerate oral therapy for 21-42 days or till the symptoms are resolved
- Alternative regimen: Foscarnet 90 mg/kg IV q12h or 60 mg/kg q8h for 21-42 days
- Note: For patients with treatment-limiting toxicities to Ganciclovir or with Ganciclovir resistance, above regimen is recommended.
- 6.12.1.2.2. Mild disease and able to tolerate oral therapy
- Preferred regimen: Valganciclovir 900 mg PO bid 21-42 days
- 6.12.1.3. CMV neurological disease
- Preferred regimen: Ganciclovir 5 mg/kg IV q12h AND (Foscarnet 90 mg/kg IV q12h or 60 mg/kg IV q8h) to stabilize disease
- 6.13. HHV-8 Diseases (kaposi sarcoma [KS], primary effusion lymphoma [PEL], multicentric castleman’s disease [MCD])
- 6.13.1. Treatment
- Mild to moderate KS (ACTG Stage T0)
- Note: Initiate or optimize anti retroviral therapy.
- Advanced KS [ACTG Stage T1, Including Disseminated Cutaneous (AI) Or Visceral KS]
- Note: Chemotherapy (per oncology consult) AND anti retroviral therapy.
- Primary effusion lymphoma
- Preferred regimen (1): Valganciclovir 900 mg PO bid for 3 weeks
- Preferred regimen (2): Ganciclovir 5 mg/kg IV q12h for 3 weeks
- Preferred regimen (3): Valganciclovir 900 mg PO bid AND Zidovudine 600 mg PO qid for 7– 21 days
- Alternative regimen: Rituximab (375 mg/m2 given weekly for 4–8 weeks) may be an alternative to or used adjunctively with antiviral therapy
- Note: Valganciclovir PO OR Ganciclovir IV can be used as adjunctive therapy
- 6.14. Human papillomavirus (HPV) infection
- 6.14.1. Prevention
- For females aged 13–26 years
- Preferred regimen (1): HPV quadrivalent vaccine 0.5 mL IM at months 0, 1–2, and 6 OR HPV bivalent vaccine 0.5 mL IM at months 0, 1–2, and 6
- Males aged 13–26 years
- Preferred regimen (1): HPV quadrivalent vaccine 0.5 mL IM at months 0, 1–2, and 6
- 6.14.2. Treatment
- 6.14.2.1. Patient-applied therapy for uncomplicated external warts that can be easily identified by patients
- Preferred regimen (1): Podophyllotoxin (e.g., podofilox 0.5% solution or 0.5% gel)
- Note: Apply to all lesions bid for 3 consecutive days, followed by 4 days of no therapy, repeat weekly for up to 4 cycles, until lesions are no longer visible)
- Preferred regimen (2): Imiquimod 5% cream
- Note: Apply to lesion at bedtime and remove in the morning on 3 nonconsecutive nights weekly for up to 16 weeks, until lesions are no longer visible. Each treatment should be washed with soap and water 6–10 hours after application.
- Preferred regimen (3): Sinecatechins 15% ointment
- Note: Apply to affected areas tid for up to 16 weeks, until warts are completely cleared and not visible
- 6.14.2.2. Provider-applied therapy for complex or multicentric lesions, or lesions inaccessible to patient
- Note (1): Cryotherapy (liquid nitrogen or cryoprobe): Apply until each lesion is thoroughly frozen. Repeat every 1–2 weeks for up to 4 weeks, until lesions are no longer visible. Some providers allow the lesion to thaw, then freeze a second time in each session.
- Note (2): Trichloroacetic acid or bichloroacetic acid cauterization: 80%–90% aqueous solution, apply to wart only, allow to dry until a white frost develops. Repeat weekly for up to 6 weeks, until lesions are no longer visible.
- Note (3): Surgical excision or laser surgery to external or anal warts.
- Note (4): Podophyllin resin 10%–25% in tincture of benzoin: Apply to all lesions (up to 10 cm2 ), then wash off a few hours later, repeat weekly for up to 6 weeks until lesions are no longer visible.
- 6.15. Hepatitis A virus (HAV) infection
- 6.15.1. Prevention
- Indication: HAV-susceptible patients with chronic liver disease, or who are injection-drug users or homosexuals
- Preferred regimen: Hepatitis A vaccine 1 mL IM 2 doses at 0 and 6–12 months.
- Alternative regimen: Combined HAV and HBV vaccine 1 mL IM as a 3-dose (0, 1, and 6 months) or 4-dose series (days 0, 7, 21 to 30, and 12 months).
- Note (1): For patients susceptible to both HAV and hepatitis B virus (HBV) infection, alternative regimen is recommended.
- Note (2): IgG antibody response should be assessed 1 month after vaccination; nonresponders should be revaccinated when CD4 count >200 cells/µL.
- 6.16. Hepatitis B virus (HBV) infection
- 6.16.1. Prevention
- 6.16.1.1. Indication
- Patients without chronic HBV or without immunity to HBV (i.e., anti-HBs <10 international units/mL).
- Patients with isolated anti-HBc and negative HBV DNA.
- Early vaccination is recommended before CD4 count falls below 350 cells/µL.
- However, in patients with low CD4 cell counts, vaccination should not be deferred until CD4 count reaches >350 cells/µL, because some patients with CD4 counts <200 cells/µL do respond to vaccination.
- Preferred regimen (1): HBV vaccine IM (Engerix-B 20 µg/mL or Recombivax HB 10 µg/mL), 0, 1, and 6 months
- Preferred regimen (2): HBV vaccine IM (Engerix-B 40 µg/mL or Recombivax HB 20 µg/mL) 0, 1, 2 and 6 months
- Preferred regimen (3): Combined HAV and HBV vaccine, 1 mL IM as a 3-dose (0, 1, and 6 months) or 4-dose series (days 0, 7, 21 to 30, and 12 months)
- Alternative regimen: Some experts recommend vaccinating with 40-µg doses of either HBV vaccine
- Note: Anti-HBs should be obtained 1 month after completion of the vaccine series. Patients with anti-HBs <10 international units/mL at 1 month are considered nonresponders.
- Vaccine Non-Responders:
- Preferred regimen (1): HBV vaccine IM (Engerix-B 40 µg/mL or Recombivax HB 20 µg/mL), 0, 1, 2 and 6 months.
- Note (1): Vaccination non-responders have anti-HBs <10 international units/mL 1 month after vaccination series.
- Note (2): For patients with low CD4 counts at time of first vaccine series, some experts might delay revaccination until after a sustained increase in CD4 count with anti retroviral therapy.
- 6.16.2. Treatment
- Preferred regimen: Tenofovir 300 mg PO qdAND Emtricitabine 200 mg PO qd OR Lamivudine 300 mg PO qd AND additional drug(s) for HIV
- Note: Anti retroviral therapy regimen should include 2 drugs that are active against both HBV and HIV.
- Alternative regimen: Peginterferon alfa-2a 180 μg SQ once weekly for 48 weeks OR Peginterferon alfa 2b 1.5 μg/kg SQ once weekly for 48 weeks.
- Note: For HBV treatment is indicated for patients with elevated ALT and HBV DNA >2,000 IU/mL significant liver fibrosis, advanced liver disease or cirrhosis, above regimen is indicated.
- 6.17. Penicilliosis marneffei
- 6.17.1. Prevention
- 6.17.1.1. Indication
- Patients with CD4 cell counts <100 cells/µL who live or stay for a long period in rural areas in northern Thailand, Vietnam, or Southern China.
- Preferred regimen: Itraconazole 200 mg PO qd
- Alternative regimen: Fluconazole 400 mg PO once weekly
- 6.17.2. Treatment
- 6.17.2.1. For acute infection in severely ill patients
- Preferred regimen: Liposomal amphotericin B 3–5 mg/kg/day IV for 2 weeks, followed by Itraconazole 200 mg PO bid for 10 weeks, followed by chronic maintenance therapy
- Alternative regimen: Voriconazole 6 mg/kg IV q12h for 1 day, then 4 mg/kg IV q12h for at least 3 days, followed by 200 mg PO bid for a maximum of 12 weeks, followed by maintenance therapy
- 6.17.2.2. For mild disease
- Preferred regimen: Itraconazole 200 mg PO bid for 8 weeks; followed by chronic maintenance therapy
- Alternative regimen: Voriconazole 400 mg PO bid for 1 day, then 200 mg bid for a maximum of 12 weeks, followed by chronic maintenance therapy
- 6.17.2.3. Chronic Maintenance Therapy (Secondary Prophylaxis)
- Preferred regimen: Itraconazole 200 mg PO qd
- Note (1): Anti retroviral therapy should be initiated simultaneously with treatment for penicilliosis to improve treatment outcome.
- Note (2): Itraconazole and Voriconazole may have significant interactions with certain ARV agents. These interactions are complex and can be bi-directional.
- Note (3): Therapeutic drug monitoring and dosage adjustment may be necessary to ensure triazole antifungal and ARV efficacy and reduce concentration-related toxicities.
- 6.18. Isosporiasis
- 6.18.1. Treatment
- For Acute Infection:
- Preferred regimen (1): Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO (or IV) qid for 10 days
- Preferred regimen (2): Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO (or IV) bid for 7–10 days
- Alternative regimen (1): Pyrimethamine 50–75 mg PO daily AND Leucovorin 10–25 mg PO qd
- Alternative regimen (2): Ciprofloxacin 500 mg PO bid for 7 days as a second line alternative
- Chronic Maintenance Therapy (Secondary Prophylaxis):
- Preferred regimen (1): In patients with CD4 count <200/µL, Trimethoprim/sulfamethoxazole 160 mg/800 mg PO three times a week
- Alternative regimen (1): Trimethoprim/sulfamethoxazole 160 mg/800 mg PO qd or (320 mg/1600 mg) three times a week
- Alternative regimen (2): Pyrimethamine 25 mg PO qd AND Leucovorin 5–10 mg PO qd
- Alternative regimen (3): Ciprofloxacin 500 mg three times a week as a second-line alternative
- Note (1): Fluid and electrolyte management in patients with dehydration.
- Note (2): Immune reconstitution with anti retroviral therapy may result in fewer relapses.
- Note (3): IV therapy may be used for patients with potential or documented mal-absorption.
- 6.19. Chagas disease (American trypanosomiasis)
- 6.19.1. Treatment
- For acute, earlychronic, and reactivated Disease:
- Preferred regimen: Benznidazole 5–8 mg/kg/day PO in 2 divided doses for 30–60 days
- Alternative regimen: Nifurtimox 8–10 mg/kg/day PO for 90–120 days.
- 6.20. Leishmaniasis, visceral
- 6.20.1. Leishmaniasis, visceral
- 6.20.1.1. Treatment
- For initial infection:
- Preferred regimen (1): Liposomal amphotericin B 2–4 mg/kg IV qd
- Preferred regimen (2): Liposomal amphotericin B interrupted schedule (e.g., 4 mg/kg on days 1–5, 10, 17, 24, 31, 38)
- Alternative regimen (1): Amphotericin B deoxycholate 0.5–1.0 mg/kg IV q24h for total dose of 1.5–2.0 g
- Alternative regimen (2): Sodium stibogluconate (pentavalent antimony) 20 mg/kg IV or IM q24h for 28 days
- Alternative regimen (3): Miltefosine 100 mg PO qd for 4 weeks
- Chronic maintenance therapy (secondary prophylaxis); Especially in Patients with CD4 Count <200 cells/µL:
- Preferred regimen (1): Liposomal amphotericin B 4 mg/kg every 2–4 weeks
- Preferred regimen (2): Amphotericin B lipid complex 3 mg/kg every 21 days
- Alternative regimen: Sodium stibogluconate 20 mg/kg IV or IM every 4 weeks
- 6.20.2. Leishmaniasis, cutaneous
- Preferred regimen (1): Liposomal amphotericin B 2–4 mg/kg IV daily for 10 days
- Preferred regimen (2): Liposomal amphotericin B interrupted schedule (e.g., 4 mg/kg on days 1–5, 10, 17, 24, 31, 38) to achieve total dose of 20–60 mg/kg
- Preferred regimen (3): Sodium stibogluconate 20 mg/kg IV or IM daily for 3–4 weeks
- 6.21. Aspergillosis, invasive
- 6.21.1. Treatment
- Preferred regimen: Voriconazole 6 mg/kg IV q12h for 1 day, then 4 mg/kg IV q12h, followed by Voriconazole 200 mg PO q12h after clinical improvement until CD4 cell count >200 cells/µL and the infection appears to be resolved.
- Alternative regimen (1): Lipid formulation of Amphotericin B 5 mg/kg IV q24h
- Alternative regimen (2): Amphotericin B deoxycholate 1mg/kg IV q24h
- Alternative regimen (3): Caspofungin 70 mg IV single dose, then 50 mg IV q24h
- Alternative regimen (4): Micafungin 100–150 mg IV q24h
- Alternative regimen (5): Anidulafungin 200 mg IV single dose, then 100 mg IV q24h
- Alternative regimen (6): Posaconazole 200 mg PO qid, then, after condition improved, 400 mg PO bid
- 6.22. Malaria
- 6.22.1. Prevetion
- 6.22.1.1. Prophylaxis in all areas
- Preferred regimen (1): Atovaquone 250 mg and Proguanil hydrochloride 100 mg PO qd
- Pediatric doses: Pediatric tablets contain 62.5 mg atovaquone and 25 mg proguanil hydrochloride
- 5–8 kg: 1/2 pediatric tablet daily
- >8–10 kg: 3/4 pediatric tablet daily
- >10–20 kg: 1 pediatric tablet daily
- >20–30 kg: 2 pediatric tablets daily
- >30–40 kg: 3 pediatric tablets daily
- Note (1): Begin 1–2 days before travel to malarious areas. Take daily at the same time each day while in the malarious area and for 7 days after leaving such areas. Contraindicated in people with severe renal impairment (creatinine clearance <30 mL/min).
- Note (2): Atovaquone-proguanil should be taken with food or a milky drink. Not recommended for prophylaxis for children weighing <5 kg, pregnant women, and women breastfeeding infants weighing <5 kg. Partial tablet doses may need to be prepared by a pharmacist and dispensed in individual capsules.
- Preferred regimen (2): Doxycycline 100 mg PO qd
- Pediatric dose: ≥8 years of age: 2.2 mg/kg up to adult dose of 100 mg/day
- Note: Begin 1–2 days before travel to malarious areas. Take daily at the same time each day while in the malarious area and for 4 weeks after leaving such areas. Contraindicated in children <8 years of age and pregnant women.
- 6.22.1.2. Prophylaxis only in areas with chloroquine-sensitive malaria
- Preferred regimen: Chloroquine phosphate 300 mg base (500 mg salt) PO once a week
- Note: Begin 1–2 weeks before travel to malarious areas. Take weekly on the same day of the week while in the malarious area and for 4 weeks after leaving such areas. May exacerbate psoriasis.
- Alternative regimen: Hydroxychloroquine sulfate 400 mg salt PO once a week
- Note: Begin 1–2 weeks before travel to malarious areas. Take weekly on the same day of the week while in the malarious area and for 4 weeks after leaving such areas.
- Pediatric doses: Chloroquine phosphate 5 mg/kg base (8.3 mg/kg salt) orally, once/week, up to maximum adult dose of 300 mg base; Hydroxychloroquine sulfate 5 mg/kg base (6.5 mg/kg salt) orally, once/week, up to a maximum adult dose of 310 mg base
- 6.22.1.3. Prophylaxis in areas with mefloquine-sensitive malaria
- Preferred regimen: Mefloquine 250 mg PO once a week
- Note (1): Begin ≥2 weeks before travel to malarious areas. Take weekly on the same day of the week while in the malarious area and for 4 weeks after leaving such areas. Contraindicated in people allergic to mefloquine or related compounds (quinine, quinidine) and in people with active depression, a recent history of depression, generalized anxiety disorder, psychosis, schizophrenia, other major psychiatric disorders, or seizures.
- Note (2): Use with caution in persons with psychiatric disturbances or a previous history of depression. Not recommended for persons with cardiac conduction abnormalities.
- Pediatric dose: Mefloquine ≤9 kg: 4.6 mg/kg base (5 mg/kg salt) orally, once/week
- >9–19 kg: 1/4 tablet once/week
- >19–30 kg: 1/2 tablet once/week
- >30–45 kg: 3/4 tablet once/week
- >30–45 kg: 3/4 tablet once/week
- 6.22.1.4. Prophylaxis for short-duration travel to areas with principally Plasmodium vivax
- Preferred regimen: Primaquine 52.6 mg PO qd
- Note: Begin 1–2 days before travel to malarious areas. Take daily at the same time each day while in the malarious area and for 7 days after leaving such areas. Contraindicated in people with G6PD deficiency. Also contraindicated during pregnancy and lactation, unless the infant being breastfed has a documented normal G6PD level.
- Pediatric dose: Primaquine 0.5 mg/kg base (0.8 mg/kg salt) up to adult dose orally, daily
- 6.22.1.5. Terminal prophylaxis to decrease the risk for relapses of Plasmodium vivax and Plasmodium ovale
- Preferred regimen: Primaquine 52.6 mg PO qd for 14 days after departure from the malarious area
- Note: Indicated for people who have had prolonged exposure to P. vivax, P. ovale, or both. Contraindicated in people with G6PD deficiency. Also contraindicated during pregnancy and lactation, unless the infant being breastfed has a documented normal G6PD level.
- Pediatric dose: Primaquine 0.5 mg/kg base (0.8 mg/kg salt) up to adult dose orally, daily for 14 days after departure from the malarious area
- 6.22.2. Treatment
- Note (1): Patients coinfected with HIV should avoid Artesunate AND Sulfadoxine-Pyrimethamine if they are also receiving Co-trimoxazole, and avoid Artesunate AND Amodiaquine if they are also receiving Efavirenz OR Zidovudine.
- Note (2): Because Plasmodium falciparum malaria can progress within hours from mild symptoms or low-grade fever to severe disease or death, all HIV-infected patients with confirmed or suspected P. falciparum infection should be hospitalized for evaluation, initiation of treatment, and observation.
- 6.22.2.1. Plasmodium falciparum[432]
- 6.22.2.1.1. Treatment of uncomplicated Plasmodium falciparum malaria
- 6.22.2.1.1.1. Treat children and adults with uncomplicated Plasmodium falciparum malaria (except pregnant women in their first trimester) with one of the following recommended ACT (artemisinin-based combination therapy)
- Preferred regimen (1): Artemether 5–24 mg/kg/day PO bid AND Lumefantrine 29–144 mg/kg/day PO bid for 3 days
- Note: The first two doses should, ideally, be given 8 hours apart.
- Dosage regimen based on Body weight (kg)
- Body weight (kg)-5 to < 15- Artemether 20 mg PO bid AND Lumefantrine 120 mg PO bid for 3 days
- Body weight (kg)-15 to < 25- Artemether 40 mg PO bid AND Lumefantrine 240 mg PO bid for 3 days
- Body weight (kg)-25 to < 35- Artemether 60 mg PO bid AND Lumefantrine 360 mg PO bid for 3 days
- Body weight (kg) ≥ 35- Artemether 80 mg PO bid AND Lumefantrine 480 mg PO bid for 3 days
- Preferred regimen (2): Artesunate 2–10 mg/kg/day PO qd AND Amodiaquine 7.5–15 mg/kg/day PO qd for 3 days
- Note: A total therapeutic dose range of 6–30 mg/kg/day Artesunate and 22.5–45 mg/kg/day per dose Amodiaquine is recommended.
- Dosage regimen based on body weight (kg)
- Body weight (kg)-4.5 to < 9- Artesunate 25 mg PO qd AND Amodiaquine 67.5 mg PO qd for 3 days
- Body weight (kg)-9 to < 18 - Artesunate 50 mg PO qd AND Amodiaquine 135 mg PO qd for 3 days
- Body weight (kg)-18 to < 36- Artesunate 100 mg PO qd AND Amodiaquine 270 mg PO qd for 3 days
- Body weight (kg) ≥ 36 - Artesunate 200 mg PO qd AND Amodiaquine 540 mg PO qd for 3 days
- Preferred regimen (3): Artesunate 2–10 mg/kg/day PO qd AND Mefloquine 2–10 mg/kg/day PO qd for 3 days
- Dosage regimen based on body weight (kg)
- Body weight (kg)-5 to < 9- Artesunate 25 mg PO qd AND Mefloquine 55 mg PO qd for 3 days
- Body weight (kg)-9to < 18- Artesunate 50 mg PO qd AND Mefloquine 110 mg PO qd for 3 days
- Body weight (kg)-18 to < 36- Artesunate 100 mg PO qd AND Mefloquine 220 mg PO qd for 3 days
- Body weight (kg)- ≥ 36 - Artesunate 200 mg PO qd AND Mefloquine 440 mg PO qd for 3 days
- Preferred regimen (4): Artesunate 2–10 mg/kg/day PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1.25 (25–70 / 1.25–3.5) mg/kg/day PO given as a single dose on day 1
- Dosage regimen based on body weight (kg)
- Body weight (kg)- 5 to < 10- Artesunate 25 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 250/12 mg PO given as a single dose on day 1
- Body weight (kg)- 10 to < 25- Artesunate 50 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 500/25 mg PO given as a single dose on day 1
- Body weight (kg)- 25 to < 50- Artesunate 100 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1000/50 mg PO given as a single dose on day 1
- Body weight (kg)- ≥50- Artesunate 200 mg PO qd for 3 days AND Sulfadoxine-Pyrimethamine 1500/75 mg PO given as a single dose on day 1
- Preferred regimen (5): Dihydroartemisinin 2–10 mg/kg/day PO qd AND Piperaquine16–27 mg/kg/day PO qd for 3 days
- Dosage regimen based on Body weight (kg)
- Body weight (kg)-5 to < 8: Dihydroartemisinin 20 mg PO qd AND Piperaquine 160 mg PO qd for 3 days
- Body weight (kg)-8 to < 11: Dihydroartemisinin 30 mg PO qd AND Piperaquine 240 mg PO qd for 3 days
- Body weight (kg)-11 to < 17: Dihydroartemisinin 40 mg PO qd AND Piperaquine 320 mg PO qd for 3 days
- Body weight (kg)-17 to < 25: Dihydroartemisinin 60 mg PO qd AND Piperaquine 480 mg PO qd for 3 days
- Body weight (kg)-25 to < 36: Dihydroartemisinin 80 mg PO qd AND Piperaquine 640 mg PO qd for 3 days
- Body weight (kg)-36 to < 60: Dihydroartemisinin 120 mg PO qd AND Piperaquine 960 mg PO qd for 3 days
- Body weight (kg)-60 < 80: Dihydroartemisinin 160 mg PO qd AND Piperaquine 1280 mg PO qd for 3 days
- Body weight (kg)- >80: Dose of Dihydroartemisinin 200 mg PO qd AND Piperaquine 1600 mg PO qd for 3 days
- 6.22.2.1.1.2 Reducing the transmissibility of treated Plasmodium falciparum infections In low-transmission areas in patients with Plasmodium falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months)
- Preferred regimen: Primaquine 0.25 mg/kg PO single dose with ACT
- 6.22.2.1.2. Recurrent falciparum malaria
- 6.22.2.1.2.1. Failure within 28 days
- Note: The recommended second-line treatment is an alternative ACT known to be effective in the region. Adherence to 7-day treatment regimens with Artesunate or Quinine both of which should be co-administered with Tetracycline, or Doxycycline or Clindamycin) is likely to be poor if treatment is not directly observed; these regimens are no longer generally recommended.
- 6.22.2.1.2.2. Failure after 28 days
- Note: All presumed treatment failures after 4 weeks of initial treatment should, from an operational standpoint, be considered new infections and be treated with the first-line ACT. However, reuse of Mefloquine within 60 days of first treatment is associated with an increased risk for neuropsychiatric reactions, and an alternative ACT should be used.
- 6.22.2.1.3. Reducing the transmissibility of treated Plasmodium falciparum infections in low-transmission areas in patients with Plasmodium falciparum malaria (except pregnant women, infants aged < 6 months and women breastfeeding infants aged < 6 months)
- Note: Single dose of 0.25 mg/kg biweekly Primaquine with ACT
- 6.22.2.1.4. Treating uncomplicated Plasmodium falciparum malaria in special risk groups
- 6.22.2.1.4.1. Pregnancy
- First trimester of pregnancy : Quinine AND Clindamycin 10 mg/kg/day PO bid for 7 days
- Second and third trimesters : Mefloquine is considered safe for the treatment of malaria during the second and third trimesters; however, it should be given only in combination with an artemisinin derivative.
- Note (1): Quinine is associated with an increased risk for hypoglycaemia in late pregnancy, and it should be used (with clindamycin) only if effective alternatives are not available.
- Note (2): Primaquine and Tetracyclines should not be used in pregnancy.
- 6.22.2.1.4.2. Infants less than 5kg body weight
- Note: They should be treated with an ACT at the same mg/kg bw target dose as for children weighing 5 kg.
- 6.22.2.1.4.4. Large and obese adults
- Note: For obese patients, less drug is often distributed to fat than to other tissues; therefore, they should be dosed on the basis of an estimate of lean body weight, ideal body weight. Patients who are heavy but not obese require the same mg/kg bw doses as lighter patients.
- 6.22.2.1.4.5. Non-immune travellers
- Note: Treat travellers with uncomplicated P. falciparum malaria returning to nonendemic settings with an ACT.
- 6.22.2.1.4.6. Uncomplicated hyperparasitaemia
- Note: People with P. falciparum hyperparasitaemia are at increased risk of treatment failure, severe malaria and death so should be closely monitored, in addition to receiving an ACT.
- 6.22.2.2. Treatment of uncomplicated malaria caused by Plasmodium vivax, Plasmodium ovale, Plasmodium malariae or Plasmodium knowlesi
- 6.22.2.2.1. Blood Stage infection
- 6.22.2.2.1.1. Uncomplicated malaria caused by Plasmodium vivax
- 6.22.2.2.1.1.1. In areas with chloroquine-sensitive Plasmodium vivax
- Preferred regimen: Chloroquine total dose of 25 mg/kg PO. Chloroquine is given at an initial dose of 10 mg/kg, followed by 10 mg/kg on the second day and 5 mg/kg on the third day PO
- 6.22.2.2.1.1.2. In areas with chloroquine-resistant Plasmodium vivax
- Note: ACTs containing Piperaquine, Mefloquine OR Lumefantrine are the recommended treatment, although Artesunate AND Amodiaquine may also be effective in some areas. In the systematic review of ACTs for treating P. vivax malaria, Dihydroartemisinin AND Piperaquine provided a longer prophylactic effect than ACTs with shorter half-lives (Artemether ANDLumefantrine) OR (Artesunate AND Amodiaquine), with significantly fewer recurrent parasitaemias during 9 weeks of follow-up.
- 6.22.2.2.1.2. Uncomplicated malaria caused by Plasmodium ovale, Plasmodium malariae or Plasmodium knowlesi malaria
- Note: Resistance of P. ovale, P. malariae and P. knowlesi to antimalarial drugs is not well characterized, and infections caused by these three species are generally considered to be sensitive to Chloroquine. In only one study, conducted in Indonesia, was resistance to Chloroquine reported in P. malariae. The blood stages of P. ovale, P. malariae and P. knowlesi should therefore be treated with the standard regimen of ACT or Chloroquine, as for vivax malaria.
- 6.22.2.2.1.3. Mixed malaria infections
- Note: ACTs are effective against all malaria species and so are the treatment of choice for mixed infections.
- 6.22.2.2.2. Liver stages (hypnozoites) of Plasmodium vivax and Plasmodium ovale
- Note: To prevent relapse, treat P. vivax or P. ovale malaria in children and adults (except pregnant women, infants aged < 6 months, women breastfeeding infants < 6 months, women breastfeeding older infants unless they are known not to be G6PD deficient and people with G6PD deficiency) with a 14-day course of Primaquine in all transmission settings. Strong recommendation, high-quality evidence In people with G6PD deficiency, consider preventing relapse by giving primaquine base at 0.75 mg base/kg bw once a week for 8 weeks, with close medical supervision for potential primaquine-induced adverse haematological effects.
- 6.22.2.2.2.1. Primaquine for preventive relapse
- Preferred regimen: Primaquine 0.25–0.5 mg/kg/day PO qd for 14 days
- 6.22.2.2.2.2. Primaquine and glucose-6-phosphate dehydrogenase deficiency
- Preferred regimen: Primaquine 0.75 mg base/kg/day PO once a week for 8 weeks
- Note: The decision to give or withhold Primaquine should depend on the possibility of giving the treatment under close medical supervision, with ready access to health facilities with blood transfusion services.
- 6.22.2.2.2.3. Prevention of relapse in pregnant or lacating women and infants
- Note: Primaquine is contraindicated in pregnant women, infants < 6 months of age and in lactating women (unless the infant is known not to be G6PD deficient)
- 6.22.2.3. Treatment of severe malaria
- 6.22.2.3.1. Treatment of severe falciparum infection with Artesunate
- 6.22.2.3.1.1. Adults and children with severe malaria (including infants, pregnant women in all trimesters and lactating women)
- Preferred regimen: Artesunate IV/IM for at least 24 h and until they can tolerate oral medication. Once a patient has received at least 24 h of parenteral therapy and can tolerate oral therapy, complete treatment with 3 days of an ACT (add single dose Primaquine in areas of low transmission).
- 6.22.2.3.1.2. Young children weighing < 20 kg
- Preferred regimen:Artesunate 3 mg/kg per dose IV/IM q24h
- Alternative regimen: use Artemether in preference to quinine for treating children and adults with severe malaria
- 6.22.2.3.2.Treating cases of suspected severe malaria pending transfer to a higher-level facility (pre-referral treatment)
- 6.22.2.3.2.1. Adults and children
- Preferred regimen: Artesunate IM q24h
- Alternative regimen: Artemether IM OR Quinine IM
- 6.22.2.3.2.2. Children < 6 years
- Preferred regimen: Where intramuscular injections of artesunate are not available, treat with a single rectal dose (10 mg/kg) of Artesunate, and refer immediately to an appropriate facility for further care.
- Note: Do not use rectal artesunate in older children and adults.
- 6.22.2.3.3. Pregancy
- Note: Parenteral artesunate is the treatment of choice in all trimesters. Treatment must not be delayed.
- 6.22.2.3.4. Treatment of severe Plasmodium Vivax infection
- Note: Parenteral Artesunate, treatment can be completed with a full treatment course of oral ACT or Chloroquine (in countries where Chloroquine is the treatment of choice). A full course of radical treatment with Primaquine should be given after recovery.
- 6.22.2.3.5. Additional aspects of management in severe malaria
- Fluid therapy: It is not possible to give general recommendations on fluid replacement; each patient must be assessed individually and fluid resuscitation based on the estimated deficit.
- Blood Transfusion: In high-transmission settings, blood transfusion is generally recommended for children with a haemoglobin level of < 5 g/100 mL(haematocrit < 15%). In low-transmission settings, a threshold of 20% (haemoglobin,7 g/100 mL) is recommended.
- Exchange blood transfusion: Exchange blood transfusion requires intensive nursing care and a relatively large volume of blood, and it carries significant risks. There is no consensus on the indications, benefits and dangers involved or on practical details such as the volume of blood that should be exchanged. It is, therefore, not possible to make any recommendation regarding the use of exchange blood transfusion.
- 6.23. Cryptococcosis
- 6.23.1. Treatment
- 6.23.1.1. Cryptococcal meningitis
- 6.23.1.1.1. Induction therapy
- Preferred regimen: Liposomal amphotericin B 3–4 mg/kg IV q24h AND Flucytosine 25 mg/kg PO qid for at least 2 weeks, followed by consolidation therapy
- Alternative regimen (1): Amphotericin B deoxycholate 0.7 mg/kg IV q24h AND Flucytosine 25 mg/kg PO qid
- Alternative regimen (2): Amphotericin B lipid complex 5 mg/kg IV q24h AND Flucytosine 25 mg/kg PO qid
- Alternative regimen (3): Liposomal Amphotericin B 3-4 mg/kg IV q24h AND Fluconazole 800 mg PO or IV q24h
- Alternative regimen (4): Amphotericin B deoxycholate 0.7 mg/kg IV q24h AND Fluconazole 800 mg PO or IV q24h
- Alternative regimen (5): Fluconazole 400–800 mg PO or IV qd AND Flucytosine 25 mg/kg PO qid
- Alternative regimen (6): Fluconazole 1200 mg PO or IV qd
- 6.23.1.1.2. Consolidation therapy
- Preferred regimen: Fluconazole 400 mg PO (or IV) qd for atleast 8 weeks
- Note: Preferred therapy followed by maintenance therapy.
- Maintenance therapy: Fluconazole 200 mg PO qd for at least 12 months
- Alternative regimen: Itraconazole 200 mg PO bid for 8 weeks
- 6.23.1.2. Non-CNS cryptococcosis with mild-to-moderate symptoms and focal pulmonary infiltrates
- Preferred regimen: Fluconazole, 400 mg PO qd for 12 months
- Note: Patients receiving Flucytosine should have either blood levels monitored (peak level 2 hours after dose should be 30–80 mcg/mL) or close monitoring of blood counts for development of cytopenia. Dosage should be adjusted in patients with renal insufficiency.
- 6.24. Mucocutaneous candidiasis
- 6.24.1. Treatment
- 6.24.1.1. For oropharyngeal candidiasis
- Oral Therapy
- Preferred regimen: Fluconazole 100 mg PO qd for 7-14 days.
- Alternative regimen: Itraconazole oral solution 200 mg PO qd for 7-14 days OR Posaconazole oral suspension 400 mg PO bid for 1 day, then 400 mg qd 7-14 days
- Topical therapy
- Preferred regimen: Clotrimazole troches, 10 mg PO 5 times daily OR Miconazole mucoadhesive buccal 50-mg tablet
- Note: Apply to mucosal surface over the canine fossa once daily (do not swallow, chew, or crush).
- Alternative regimen: Nystatin suspension 4–6 mL qid or 1–2 flavored pastilles 4– 5 times daily
- 6.24.1.2. For esophageal candidiasis
- Preferred regimen: Fluconazole 100 mg (up to 400 mg) PO or IV qd for 14-21 days OR Itraconazole oral solution 200 mg PO qd for 14-21 days
- Alternative regimen (1): Voriconazole 200 mg PO or IV bid for 14-21 days
- Alternative regimen (2): Anidulafungin 100 mg IV single dose, then 50 mg IV qd for 14-21 days
- Alternative regimen (3): Caspofungin 50 mg IV qd for 14-21 days
- Alternative regimen (4): Micafungin 150 mg IV qd for 14-21 days
- Alternative regimen (5): Amphotericin B deoxycholate 0.6 mg/kg IV qd for 14-21 days
- Alternative regimen (6): Lipid formulation of amphotericin B 3–4 mg/kg IV qd for 14-21 days
- 6.24.1.3. For uncomplicated vulvo-vaginal candidiasis
- Preferred regimen: Oral Fluconazole 150 mg for 1 dose OR Topical azoles (Clotrimazole, Butoconazole, Miconazole, Tioconazole, or Terconazole) for 3– 7 days
- Alternative regimen: Itraconazole oral solution 200 mg PO qd for 3–7 days
- 6.24.1.4. For severe or recurrent vulvovaginal candidiasis
- Preferred regimen: Fluconazole 100–200 mg PO qd for ≥7 days OR Topical antifungal ≥7 days
- 6.25. Bartonellosis
- 6.25.1. Treatment
- 6.25.1.1. For bacillary angiomatosis, peliosis hepatis, bacteremia, and osteomyelitis
- Preferred regimen (1): Doxycycline 100 mg PO or IV q12h for 3 months
- Preferred regimen (2): Erythromycin 500 mg PO or IV q6h for 3 months
- Alternative regimen (1): Azithromycin 500 mg PO qd
- Alternative regimen (2):} Clarithromycin 500 mg PO bid
- 6.25.1.2. Confirmed bartonella endocarditis
- Preferred regimen: Doxycycline 100 mg IV q12h AND Gentamicin 1 mg/kg IV q8h) for 2 weeks, then continue with Doxycycline 100 mg IV or PO q12h
- Altered regimen: Doxycycline 100 mg IV AND Rifabutin 300 mg PO or IV q12h for 2 weeks, then continue with Doxycycline 100 mg IV or PI q12h
- 6.25.1.3. CNS infections
- Preferred regimen: (Doxycycline 100 mg with or without Rifabutin 300 mg PO or IV q12h
- 6.25.1.4. Other severe infections
- Preferred regimen (1): Doxycycline 100 mg PO or IV with or without Rifabutin 300 mg PO or IV) q12h for 3 months
- Preferred regimen (2): Erythromycin 500 mg PO or IV q6h) with or without Rifabutin) 300 mg PO or IV q12h for 3 months.
- Note: If relapse occurs after initial (>3 month) course of therapy, longterm suppression with Doxycycline or a macrolide is recommended as long as CD4 count <200 cells/µL.
- 6.26. Campylobacteriosis
- 6.26.1. Treatment
- 6.26.1.1. For mild-to-moderate disease (If Susceptible)
- Preferred regimen: Ciprofloxacin 500–750 mg PO or 400 mg IV q12h OR Azithromycin 500 mg PO qd
- Alternative regimen: Levofloxacin 750 mg PO or IV q24h OR Moxifloxacin 400 mg (PO or IV) q24h
- 6.26.1.2. For campylobacter bacteremia
- Preferred regimen: Ciprofloxacin 500–750 mg PO or 400 mg IV q12h AND an aminoglycoside.
- Duration of Therapy:
- Gastroenteritis: 7–10 days (5 days with Azithromycin)
- Bacteremia: ≥14 days
- Recurrent bacteremia: 2–6 weeks.
- 6.27. Shigellosis
- 6.27.1. Treatment
- Preferred regimen: Ciprofloxacin 500–750 mg PO or 400 mg IV q12h
- Duration of Therapy:
- Gastroenteritis: 7–10 days
- Bacteremia: ≥14 days
- Recurrent Infections: 2–6 weeks
- Alternative regimen (1): Levofloxacin 750 mg PO or IV q24h for 5 days
- Alternative regimen (2): Moxifloxacin 400 mg PO or IV q24h for 5 days
- Alternative regimen (3): Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO or IV q12h for 5 days
- Alternative regimen (4): Azithromycin 500 mg PO qd for 5 days
- Note: Antimotility agents should be avoided.
- 6.28. Salmonellosis
- 6.28.1. Treatment
- Preferred regimen: Ciprofloxacin 500–750 mg PO or 400 mg IV q12h
- Alternative regimen (1): Levofloxacin 750 mg PO or IV q24h
- Alternative regimen (2): Moxifloxacin 400 mg PO or IV q24h
- Alternative regimen (3): Trimethoprim/Sulfamethoxazole 160 mg/800 mg PO or IV q12h
- Alternative regimen (4): Cefotaxime 1 g IV q8h
- Alternative regimen (5): Ceftriaxone 1 g IV q24h
- Duration of therapy:
- For gastroenteritis without bacteremia:
- If CD4 count ≥200 cells/µL: 7–14 days.
- If CD4 count <200 cells/µL: 2–6 weeks.
- For gastroenteritis with bacteremia:
- If CD4 count ≥200/µL: 14 days; longer duration if bacteremia persists or if the infection is complicated (e.g., if metastatic foci of infection are present)
- If CD4 count <200 cells/µL: 2–6 weeks
- Note (1): The role of long-term secondary prophylaxis in patients with recurrent Salmonella bacteremia is not well established. Must weigh benefit against risks of long-term antibiotic exposure.
- Note (2): Secondary Prophylaxis Should Be Considered For:
- Patients with recurrent Salmonella gastroenteritis +/- bacteremia.
- Patients with CD4 <200 cells/µL with severe diarrhea.
- 6.29. Bacterial enteric infections
- 6.29.1. Empiric therapy
- Preferred regimen: Ciprofloxacin 500–750 mg PO or 400 mg IV q12h
- Alternative regimen: Ceftriaxone 1 g IV q24h OR Cefotaxime 1 g IV q8h
- Note: Antimotility agents should be avoided if there is concern about inflammatory diarrhea, including Clostridium-difficile-associated diarrhea.
- 6.30.Bacterial respiratory diseases
- 6.30.1. Treatment
- 6.30.1.1. Empiric outpatient therapy
- Preferred regimen: Amoxicillin 500 mg PO AND (Azithromycin 500 mg PO OR Clarithromycin 500 mg PO) qd for 7-10 days
- Alternative regimen: Amoxicillin 500 mg PO AND Doxycycline 100mg PO qd
- Note: Therapy should be adjusted based on the results of diagnostic workup.
- 6.30.1.2. For penicillin-allergic patients
- Preferred regimen: Ceftriaxone 1 g IV q24h AND (Azithromycin 500 mg PO OR Clarithromycin 500 mg PO) qd for 7-10 days
- Alternative regimen: Aztreonam 1 g IV q24h AND Levofloxacin 750 mg IV q24h OR Moxifloxacin 400 mg IV q24h
- 6.30.1.3. Empiric therapy for non-ICU hospitalized patients
- Preferred regimen: Ceftriaxone 1 g IV q24h AND (Azithromycin 500 mg PO OR Clarithromycin 500 mg PO) qd
- 6.30.1.3. Empiric therapy for patients at risk of pseudomonas pneumonia
- Preferred regimen: : Piperacillin-Tazobactam 2 g-0.25 g IV q24h AND (Ciprofloxacin 400 mg IV q8–12h OR Levofloxacin 750 mg IV) q24h
- 6.30.1.4. Empiric therapy for patients at risk for methicillin-resistant staphylococcus aureus pneumonia
- Preferred regimen: Amoxicillin 500 mg PO AND (Azithromycin 500 mg PO OR Clarithromycin 500 mg) PO AND Linezolid 600 mg (IV or PO).
- Note (1): Empiric therapy with a macrolide alone is not routinely recommended, because of increasing pneumococcal resistance.
- Note (2): Chemoprophylaxis can be considered for patients with frequent recurrences of serious bacterial pneumonia.
- 6.31. Cryptosporidiosis
- 6.31.1. Treatment
- Note (1): Initiate or optimize ART for immune restoration to CD4 count >100 cells/µL. Aggressive oral or IV rehydration and replacement of electrolyte loss and symptomatic treatment of diarrhea with anti-motility agents.
- Preferred regimen (1): Nitazoxanide 500–1000 mg PO bid for 14 days
- Preferred regimen (2): Paromomycin 500 mg PO qid for 14–21 days
- Note (2): With optimized anti retroviral therapy, symptomatic treatment and rehydration and electrolyte replacement is recommended. Tincture of opium may be more effective than Loperamide in management of diarrhea.
- 6.32. Microsporidiosis
- 6.32.1. Treatment
- 6.32.1.1. For GI infections caused by enterocytozoon bienuesi
- Note: Initiate or optimize anti retroviral therapy as immune restoration to CD4 count >100 cells/µL AND manage severe dehydration, malnutrition, and wasting by fluid support.
- Preferred therapy (1): Fumagillin 60 mg/day PO bid
- Preferred therapy (2): TNP-470 PO bid
- Preferred therapy (3): Nitazoxanide 1000 mg PO bid
- 6.32.1.2. For intestinal and disseminated (not ocular) infections caused by microsporidia other than E. bienuesi and vittaforma corneae
- Preferred regimen: Albendazole 400 mg PO bid, continue until CD4 count >200 cells/µL for >6 months after initiation of anti retroviral therapy
- Alternative regimen: Itraconazole 400 mg PO qd AND Albendazole 400 mg PO bid
- 6.32.1.3. For ocular infection
- Preferred regimen: Topical fumagillin bicylohexylammonium (Fumidil B) eye drops: 3 mg/mL in saline (fumagillin 70 µg/mL)—2 drops q2h for 4 days, then 2 drops qid AND Albendazole 400 mg PO bid, for management of systemic infection
- Note: Therapy should be continued until resolution of ocular symptoms and CD4 count increase to >200 cells/µL for >6 months in response to anti retroviral therapy.
- 6.33. Progressive Multifocal Leukoencephalopathy (PML)
- Note (1): There is no specific antiviral therapy for JC virus infection. The main treatment approach is to reverse the immunosuppression caused by HIV.
- Note (2): Initiate anti retroviral therapy immediately in anti retroviral therapy naive patients.
- Note (3): Optimize anti retroviral therapy in patients who develop PML in phase of HIV viremia on anti retroviral therapy.
- Note (4): Corticosteroids may be used for PML-IRIS characterized by contrast enhancement, edema or mass effect, and with clinical deterioration. | https://www.wikidoc.org/index.php/Sandbox_ID3 | |
a0245c01b7e69f15c4681d10fe0a71b4054d4fc3 | wikidoc | Sandbox MEN | Sandbox MEN
# Overview
# Classification
# Pathophysiology
- The term multiple endocrine neoplasia (MEN) encompasses several distinct syndromes featuring tumors of endocrine glands, each with its own characteristic pattern. In some cases, the tumors are malignant, in others, benign. Benign or malignant tumors of nonendocrine tissues occur as components of some of these tumor syndromes.
- MEN syndromes are inherited as autosomal dominant disorders.
## Comparison
Percentages in table below refer to how large fraction of people with the MEN type develop the neoplasia type.
of patients with MEN1 and gastrinoma
## Associated Conditions
- Von Hippel-Lindau disease
- Carney complex
# Treatment
## Surgery
- Surgery is the mainstay of treatment for tumors of multiple endocrine neoplasia. | Sandbox MEN
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]
# Overview
# Classification
# Pathophysiology
- The term multiple endocrine neoplasia (MEN) encompasses several distinct syndromes featuring tumors of endocrine glands, each with its own characteristic pattern. In some cases, the tumors are malignant, in others, benign. Benign or malignant tumors of nonendocrine tissues occur as components of some of these tumor syndromes.
- MEN syndromes are inherited as autosomal dominant disorders.[1]
## Comparison
Percentages in table below refer to how large fraction of people with the MEN type develop the neoplasia type.
*- of patients with MEN1 and gastrinoma
## Associated Conditions
- Von Hippel-Lindau disease
- Carney complex
# Treatment
## Surgery
- Surgery is the mainstay of treatment for tumors of multiple endocrine neoplasia. | https://www.wikidoc.org/index.php/Sandbox_MEN | |
0ec82da3a497812bcd3353e2f625f140809905c9 | wikidoc | Sandbox MKK | Sandbox MKK
The ACG’s 2007 treatment guideline on the management of H. pylori infection (26) listed the following as established indications for diagnosis and treatment:
## Indications
- Active PUD (gastric or duodenal).
- Confirmed history of PUD (not previously treated for H. pylori)
- Gastric MALT lymphoma (low grade)
- After endoscopic resection of EGC
Recommended first-line treatment for Helicobacter pylori
†: Several PPI, Clarithromycin, and Amoxicillin combinations have achieved FDA approval ,PPI, Clarithromycin, Metronidazole is not an FDA approved treatment regimen.
‡: PPI, Bismuth, Tetracycline and metronidazole prescribed separately is not an FDA approved treatment regimen.However ,Pylera, a combination product containing Bismuth subcitrate,Tetracycline , Metronidazole combination with PPi for 10 days is an FDA approved regimen.
Adjuvant therapy in the treatment of H. pylori infection:
Emerging evidence suggests an inhibitory effect of Lactobacillus
and Bifidobacterium species on H. pylori. Furthermore,
these probiotic strains may also help to reduce the side effects
-f eradication therapies and improve compliance with therapy.
# Selection of firstline Treatment
## Diagnostic testing
The American Journal of Gastroenterology guidelines recommend that endoscopy should be performed to rule out peptic ulcer disease, esophagogastric malignancy, and other rare upper gastrointestinal tract disease in the following settings:
- Dyspeptic patients more than 55 years old OR
- Dyspeptic patients with alarm features
- Bleeding
- Anemia
- Early satiety
- Unexplained weight loss (> 10% body weight)
- Progressive dysphagia
- Odynophagia
- Persistent vomiting
- A family history of gastrointestinal cancer
- Previous esophagogastric malignancy
- Previous documented peptic ulcer, lymphadenopathy, or an abdominal mass
In patients aged 55 years or younger with no alarm features, two management options may be considered:
- Test-and-treat strategy using a validated noninvasive test (urea breathing test or stool antigen test) for H. pylori and a trial of acid suppression if eradication is successful but symptoms do not resolve – preferable in populations with a moderate to high prevalence of H. pylori infection (≥ 10%)
- Empiric trial of acid suppression with a proton pump inhibitor for 4–8 weeks – preferable in low prevalence situations
Repeat endoscopy is not recommended once a firm diagnosis of functional dyspepsia has been established, unless new symptoms or alarm features develop. Testing to prove H. pylori eradication is most accurate if performed 4 weeks after the completion of therapy.
- ↑ Talley, Nicholas J.; Vakil, Nimish; Practice Parameters Committee of the American College of Gastroenterology (2005-10). "Guidelines for the management of dyspepsia". The American Journal of Gastroenterology. 100 (10): 2324–2337. doi:10.1111/j.1572-0241.2005.00225.x. ISSN 0002-9270. PMID 16181387. Check date values in: |date= (help).mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Malfertheiner, Peter; Megraud, Francis; O'Morain, Colm A.; Atherton, John; Axon, Anthony T. R.; Bazzoli, Franco; Gensini, Gian Franco; Gisbert, Javier P.; Graham, David Y.; Rokkas, Theodore; El-Omar, Emad M.; Kuipers, Ernst J.; European Helicobacter Study Group (2012-05). "Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report". Gut. 61 (5): 646–664. doi:10.1136/gutjnl-2012-302084. ISSN 1468-3288. PMID 22491499. Check date values in: |date= (help) | Sandbox MKK
The ACG’s 2007 treatment guideline on the management of H. pylori infection (26) listed the following as established indications for diagnosis and treatment:
## Indications
- Active PUD (gastric or duodenal).
- Confirmed history of PUD (not previously treated for H. pylori)
- Gastric MALT lymphoma (low grade)
- After endoscopic resection of EGC
Recommended first-line treatment for Helicobacter pylori
†: Several PPI, Clarithromycin, and Amoxicillin combinations have achieved FDA approval ,PPI, Clarithromycin, Metronidazole is not an FDA approved treatment regimen.
‡: PPI, Bismuth, Tetracycline and metronidazole prescribed separately is not an FDA approved treatment regimen.However ,Pylera, a combination product containing Bismuth subcitrate,Tetracycline , Metronidazole combination with PPi for 10 days is an FDA approved regimen.
Adjuvant therapy in the treatment of H. pylori infection:
Emerging evidence suggests an inhibitory effect of Lactobacillus
and Bifidobacterium species on H. pylori. Furthermore,
these probiotic strains may also help to reduce the side effects
of eradication therapies and improve compliance with therapy.
# Selection of firstline Treatment
## Diagnostic testing
The American Journal of Gastroenterology guidelines recommend that endoscopy should be performed to rule out peptic ulcer disease, esophagogastric malignancy, and other rare upper gastrointestinal tract disease in the following settings:
- Dyspeptic patients more than 55 years old OR
- Dyspeptic patients with alarm features
- Bleeding
- Anemia
- Early satiety
- Unexplained weight loss (> 10% body weight)
- Progressive dysphagia
- Odynophagia
- Persistent vomiting
- A family history of gastrointestinal cancer
- Previous esophagogastric malignancy
- Previous documented peptic ulcer, lymphadenopathy, or an abdominal mass
In patients aged 55 years or younger with no alarm features, two management options may be considered:
- Test-and-treat strategy using a validated noninvasive test (urea breathing test or stool antigen test) for H. pylori and a trial of acid suppression if eradication is successful but symptoms do not resolve – preferable in populations with a moderate to high prevalence of H. pylori infection (≥ 10%)
- Empiric trial of acid suppression with a proton pump inhibitor for 4–8 weeks – preferable in low prevalence situations
Repeat endoscopy is not recommended once a firm diagnosis of functional dyspepsia has been established, unless new symptoms or alarm features develop.[1] Testing to prove H. pylori eradication is most accurate if performed 4 weeks after the completion of therapy.[2]
- ↑ Talley, Nicholas J.; Vakil, Nimish; Practice Parameters Committee of the American College of Gastroenterology (2005-10). "Guidelines for the management of dyspepsia". The American Journal of Gastroenterology. 100 (10): 2324–2337. doi:10.1111/j.1572-0241.2005.00225.x. ISSN 0002-9270. PMID 16181387. Check date values in: |date= (help).mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Malfertheiner, Peter; Megraud, Francis; O'Morain, Colm A.; Atherton, John; Axon, Anthony T. R.; Bazzoli, Franco; Gensini, Gian Franco; Gisbert, Javier P.; Graham, David Y.; Rokkas, Theodore; El-Omar, Emad M.; Kuipers, Ernst J.; European Helicobacter Study Group (2012-05). "Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report". Gut. 61 (5): 646–664. doi:10.1136/gutjnl-2012-302084. ISSN 1468-3288. PMID 22491499. Check date values in: |date= (help) | https://www.wikidoc.org/index.php/Sandbox_MKK | |
1d6811de3fa9985f52860d35f7ed3e63fa2b2b5a | wikidoc | Sandbox MWH | Sandbox MWH
# Famous Cases
The following are a few famous cases of narcolepsy:
- Jimmy Kimmel, American late-night talk show host, actor, producer, comedian, and writer
- Harold M. Ickes, former deputy White House chief of staff for President Bill Clinton and a leading figure in the His administration's healthcare reform initiative
- Arthur Lowe, a British actor who played iconic Captain Mainwaring in the British sitcom Dad's Army
- Nastassja Aglaia Kinski, German actress, and former model
- George M. Church, molecular geneticist, molecular engineer, and chemist, who is a Professor of Genetics and Professor of Health Sciences at Harvard
- Teresa Nielsen Hayden, American science fiction editor, fanzine writer, and essayist who has a famous weblog, named Making Light
- Franck Bouyer, French former road racing cyclist who was unable to compete or train without treatment with Modafinil
- Gabe Barham, former Drummer for American post-hardcore band Sleeping With Sirens
- Jinkx Monsoon (real name is Jerick Hoffer), Seattle Drag Queen, stage performer, comedian and singer who is the winner of the fifth season of RuPaul's Drag Race
- Aaron Flahavan, former English (Portsmouth) football Goalkeeper
- Paul Gonsalves, Jazz tenor saxophonist | Sandbox MWH
## Famous Cases
The following are a few famous cases of narcolepsy:
- Jimmy Kimmel, American late-night talk show host, actor, producer, comedian, and writer
- Harold M. Ickes, former deputy White House chief of staff for President Bill Clinton and a leading figure in the His administration's healthcare reform initiative
- Arthur Lowe, a British actor who played iconic Captain Mainwaring in the British sitcom Dad's Army
- Nastassja Aglaia Kinski, German actress, and former model
- George M. Church, molecular geneticist, molecular engineer, and chemist, who is a Professor of Genetics and Professor of Health Sciences at Harvard
- Teresa Nielsen Hayden, American science fiction editor, fanzine writer, and essayist who has a famous weblog, named Making Light
- Franck Bouyer, French former road racing cyclist who was unable to compete or train without treatment with Modafinil
- Gabe Barham, former Drummer for American post-hardcore band Sleeping With Sirens
- Jinkx Monsoon (real name is Jerick Hoffer), Seattle Drag Queen, stage performer, comedian and singer who is the winner of the fifth season of RuPaul's Drag Race
- Aaron Flahavan, former English (Portsmouth) football Goalkeeper
- Paul Gonsalves, Jazz tenor saxophonist | https://www.wikidoc.org/index.php/Sandbox_MWH | |
7b855cf2dcf96146ac6c1cc266b12880b66efa9c | wikidoc | Sandbox Rim | Sandbox Rim
# Overview
Unstable angina and non ST elevation myocardial infarction (NSTEMI) belong to two different ends of the spectrum of acute coronary syndrome. These conditions have a similar clinical presentation characterized by an acute onset of chest pain that starts on minimal exertion, rest or sleep, lasts at least 20 minutes (but usually less that half an hour) and, is not relieved by medications or rest. NSTEMI is differentiated from unstable angina by the presence of elevated cardiac biomarkers secondary to myocardial injury. Unstabel angina and NSTEMI might not be differentiated early following the occurrence of symptoms because cardiac biomarkers may require a few hours to rise.
# Causes
## Life Threatening Causes
Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. Unstable angina and NSTEMI are life-threatening conditions and must be treated as such irrespective of the causes.
## Common Causes
### Myocardial Infarction
- Atherosclerotic plaque rupture and subsequent coronary thrombus (most common cause)
- Coronary artery spasm
- Arrhythmia
- Post-myocardial infarction
- Post-percutaneous coronary intervention
Abrupt closure
Loss of side branch
Distal embolization
Restenosis
Stent thrombosis
- Abrupt closure
- Loss of side branch
- Distal embolization
- Restenosis
- Stent thrombosis
- Post-coronary artery bypass graft
Graft closure
New lesion in the graft
- Graft closure
- New lesion in the graft
For a complete list of causes, click here for unstable angina and here for NSTEMI.
# FIRE: Focused Initial Rapid Evaluation
A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients in need of immediate intervention based on the 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction. An invasive strategy is defined as diagnostic angiography with the intention of revascularization.
Boxes in the red color signify that an urgent management is needed.
# Complete Diagnostic Approach
A complete diagnostic approach should be carried out after a focused initial rapid evaluation is conducted and following initiation of any urgent intervention.
Abbreviations: CABG: coronary artery bypass graft; ECG: electrocardiogram; LAD: left anterior descending; LBBB: left bundle branch block; MI: myocardial infarction; PCI: percutaneous coronary intervention; S3: third heart sound; S4: fourth heart sound; VSD: ventricular septal defect
# Pre-Discharge Care
Abbreviations: ACE: angiotensin converting enzyme; LVEF: left ventricular ejection fraction; PCI: percutaneous coronary intervention; PO: per os; VF: ventricular fibrillation; VT: ventricular tachycardia
Abbreviations: ACE: angiotensin converting enzyme; ARB: angiotensin receptor blocker;
# Do's
- Administer a loading dose followed by a maintenance dose of clopidogrel, ticagrelor or prasugrel (if PCI is planned) as initial treatment instead of aspirin among patients with gastrointestinal intolerance or hypersensitivity reaction to aspirin.
- Administer sublingual nitroglycerin in patients with ischemic chest pain; however, administer IV nitroglycerin among patients with persistent chest pain after three sublingual nitroglycerin.
- Discontinue NSAID drugs immediately.
- If fondaparinux is chosen to be administered ad the anticoagulant therapy during PCI, co-administer another antocoagulant with factor IIa activity such as UFH.
# Don'ts
- Do not administer IV GP IIb/IIIa inhibitors to patients with low risk of ischemic events or at high risk of bleeding and who are already on aspirin and P2Y12 receptor inhibitors therapy.
- Do not administer prasugrel among patients with prior history of strokes or TIAs.
- Do not administer IV beta-blockers among hemodynamically unstable patients.
- Do not administer a complete dose of prasugrel among patients under 60kg (132lbs) due to high exposure to the active metabolite. They should receive half the dose of prasugrel although there is no evidence that half the dose is as effective as a complete dose.
- Do not administer fibrinolytic therapy to patients with unstable angina.
- Do not administer abciximab for patients not scheduled for PCI.
- Do not administer 2 P2Y12 receptor inhibitors, even in the presence of hypersensitivity or GI interoperability to aspirin. | Sandbox Rim
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Andrea Tamayo Soto [2]; Rim Halaby, M.D. [3]
# Overview
Unstable angina and non ST elevation myocardial infarction (NSTEMI) belong to two different ends of the spectrum of acute coronary syndrome. These conditions have a similar clinical presentation characterized by an acute onset of chest pain that starts on minimal exertion, rest or sleep, lasts at least 20 minutes (but usually less that half an hour) and, is not relieved by medications or rest. NSTEMI is differentiated from unstable angina by the presence of elevated cardiac biomarkers secondary to myocardial injury. Unstabel angina and NSTEMI might not be differentiated early following the occurrence of symptoms because cardiac biomarkers may require a few hours to rise.
# Causes
## Life Threatening Causes
Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. Unstable angina and NSTEMI are life-threatening conditions and must be treated as such irrespective of the causes.
## Common Causes
### Myocardial Infarction
- Atherosclerotic plaque rupture and subsequent coronary thrombus (most common cause)
- Coronary artery spasm
- Arrhythmia
- Post-myocardial infarction
- Post-percutaneous coronary intervention
Abrupt closure
Loss of side branch
Distal embolization
Restenosis
Stent thrombosis
- Abrupt closure
- Loss of side branch
- Distal embolization
- Restenosis
- Stent thrombosis
- Post-coronary artery bypass graft
Graft closure
New lesion in the graft
- Graft closure
- New lesion in the graft
For a complete list of causes, click here for unstable angina and here for NSTEMI.
# FIRE: Focused Initial Rapid Evaluation
A Focused Initial Rapid Evaluation (FIRE) should be performed to identify patients in need of immediate intervention based on the 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction.[1] An invasive strategy is defined as diagnostic angiography with the intention of revascularization.
Boxes in the red color signify that an urgent management is needed.
# Complete Diagnostic Approach
A complete diagnostic approach should be carried out after a focused initial rapid evaluation is conducted and following initiation of any urgent intervention.[1]
Abbreviations: CABG: coronary artery bypass graft; ECG: electrocardiogram; LAD: left anterior descending; LBBB: left bundle branch block; MI: myocardial infarction; PCI: percutaneous coronary intervention; S3: third heart sound; S4: fourth heart sound; VSD: ventricular septal defect
# Pre-Discharge Care
Abbreviations: ACE: angiotensin converting enzyme; LVEF: left ventricular ejection fraction; PCI: percutaneous coronary intervention; PO: per os; VF: ventricular fibrillation; VT: ventricular tachycardia
Abbreviations: ACE: angiotensin converting enzyme; ARB: angiotensin receptor blocker;
# Do's
- Administer a loading dose followed by a maintenance dose of clopidogrel, ticagrelor or prasugrel (if PCI is planned) as initial treatment instead of aspirin among patients with gastrointestinal intolerance or hypersensitivity reaction to aspirin.
- Administer sublingual nitroglycerin in patients with ischemic chest pain; however, administer IV nitroglycerin among patients with persistent chest pain after three sublingual nitroglycerin.[6]
- Discontinue NSAID drugs immediately. [7] [8]
- If fondaparinux is chosen to be administered ad the anticoagulant therapy during PCI, co-administer another antocoagulant with factor IIa activity such as UFH.
# Don'ts
- Do not administer IV GP IIb/IIIa inhibitors to patients with low risk of ischemic events or at high risk of bleeding and who are already on aspirin and P2Y12 receptor inhibitors therapy.
- Do not administer prasugrel among patients with prior history of strokes or TIAs.
- Do not administer IV beta-blockers among hemodynamically unstable patients.
- Do not administer a complete dose of prasugrel among patients under 60kg (132lbs) due to high exposure to the active metabolite. They should receive half the dose of prasugrel although there is no evidence that half the dose is as effective as a complete dose.
- Do not administer fibrinolytic therapy to patients with unstable angina.[9]
- Do not administer abciximab for patients not scheduled for PCI. [1]
- Do not administer 2 P2Y12 receptor inhibitors, even in the presence of hypersensitivity or GI interoperability to aspirin. | https://www.wikidoc.org/index.php/Sandbox_Rim | |
4be294f086d0805cc6deb9649715e6d5c726be51 | wikidoc | Sandbox SSW | Sandbox SSW
# Differential Diagnosis
- ↑ Hartman DS, Sanders RC (April 1982). "Wilms' tumor versus neuroblastoma: usefulness of ultrasound in differentiation". J Ultrasound Med. 1 (3): 117–22. PMID 6152936..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ De Campo JF (1986). "Ultrasound of Wilms' tumor". Pediatr Radiol. 16 (1): 21–4. PMID 3003660.
- ↑ Cahan LD (1985). "Failure of encephalo-duro-arterio-synangiosis procedure in moyamoya disease". Pediatr Neurosci. 12 (1): 58–62. PMID 4080660.
- ↑ Jolly RD, Stellwagen E, Babul J, Vodkaĭlo LV, Titov VL, Moldomusaev DM, Maianskiĭ AN (November 1975). "Mannosidosis of Angus Cattle: a prototype control program for some genetic diseases". Adv Vet Sci Comp Med. 19 (23): 1–21. PMID 1978.
- ↑ Chapman AB, Devuyst O, Eckardt KU, Gansevoort RT, Harris T, Horie S, Kasiske BL, Odland D, Pei Y, Perrone RD, Pirson Y, Schrier RW, Torra R, Torres VE, Watnick T, Wheeler DC (July 2015). "Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference". Kidney Int. 88 (1): 17–27. doi:10.1038/ki.2015.59. PMC 4913350. PMID 25786098.
- ↑ Pei Y, Obaji J, Dupuis A, Paterson AD, Magistroni R, Dicks E, Parfrey P, Cramer B, Coto E, Torra R, San Millan JL, Gibson R, Breuning M, Peters D, Ravine D (January 2009). "Unified criteria for ultrasonographic diagnosis of ADPKD". J. Am. Soc. Nephrol. 20 (1): 205–12. doi:10.1681/ASN.2008050507. PMC 2615723. PMID 18945943.
- ↑ Stavrou C, Koptides M, Tombazos C, Psara E, Patsias C, Zouvani I, Kyriacou K, Hildebrandt F, Christofides T, Pierides A, Deltas CC (October 2002). "Autosomal-dominant medullary cystic kidney disease type 1: clinical and molecular findings in six large Cypriot families". Kidney Int. 62 (4): 1385–94. doi:10.1111/j.1523-1755.2002.kid581.x. PMID 12234310.
- ↑ Bleyer AJ, Kmoch S, Antignac C, Robins V, Kidd K, Kelsoe JR, Hladik G, Klemmer P, Knohl SJ, Scheinman SJ, Vo N, Santi A, Harris A, Canaday O, Weller N, Hulick PJ, Vogel K, Rahbari-Oskoui FF, Tuazon J, Deltas C, Somers D, Megarbane A, Kimmel PL, Sperati CJ, Orr-Urtreger A, Ben-Shachar S, Waugh DA, McGinn S, Bleyer AJ, Hodanová K, Vylet'al P, Živná M, Hart TC, Hart PS (March 2014). "Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1". Clin J Am Soc Nephrol. 9 (3): 527–35. doi:10.2215/CJN.06380613. PMC 3944763. PMID 24509297.
- ↑ Faguer S, Decramer S, Chassaing N, Bellanné-Chantelot C, Calvas P, Beaufils S, Bessenay L, Lengelé JP, Dahan K, Ronco P, Devuyst O, Chauveau D (October 2011). "Diagnosis, management, and prognosis of HNF1B nephropathy in adulthood". Kidney Int. 80 (7): 768–76. doi:10.1038/ki.2011.225. PMID 21775974.
- ↑ Heidet L, Decramer S, Pawtowski A, Morinière V, Bandin F, Knebelmann B, Lebre AS, Faguer S, Guigonis V, Antignac C, Salomon R (June 2010). "Spectrum of HNF1B mutations in a large cohort of patients who harbor renal diseases". Clin J Am Soc Nephrol. 5 (6): 1079–90. doi:10.2215/CJN.06810909. PMC 2879303. PMID 20378641.
- ↑ Bravo EL (1991). "Pheochromocytoma: new concepts and future trends". Kidney Int. 40 (3): 544–56. PMID 1787652.
- ↑ Whalen RK, Althausen AF, Daniels GH (1992). "Extra-adrenal pheochromocytoma". J Urol. 147 (1): 1–10. PMID 1729490.CS1 maint: Multiple names: authors list (link)
- ↑ Baid SK, Lai EW, Wesley RA, Ling A, Timmers HJ, Adams KT; et al. (2009). "Brief communication: radiographic contrast infusion and catecholamine release in patients with pheochromocytoma". Ann Intern Med. 150 (1): 27–32. PMC 3490128. PMID 19124817.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
- ↑ Bravo EL (1991). "Pheochromocytoma: new concepts and future trends". Kidney Int. 40 (3): 544–56. PMID 1787652.
- ↑ Burkitt lymphoma. MedlinePlus. Accessed on September 30, 2015
- ↑ Bellan C, Lazzi S, De Falco G, Nyongo A, Giordano A, Leoncini L (2003). "Burkitt's lymphoma: new insights into molecular pathogenesis". J. Clin. Pathol. 56 (3): 188–92. PMC 1769902. PMID 12610094. Unknown parameter |month= ignored (help)CS1 maint: Multiple names: authors list (link)
- ↑ Ko HS, Schenk JP, Tröger J, Rohrschneider WK (2007). "Current radiological management of intussusception in children". Eur Radiol. 17 (9): 2411–21. doi:10.1007/s00330-007-0589-y. PMID 17308922.
- ↑ Boyle MJ, Arkell LJ, Williams JT (1993). "Ultrasonic diagnosis of adult intussusception". Am. J. Gastroenterol. 88 (4): 617–8. PMID 8470658. | Sandbox SSW
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2]
# Differential Diagnosis
- ↑ Hartman DS, Sanders RC (April 1982). "Wilms' tumor versus neuroblastoma: usefulness of ultrasound in differentiation". J Ultrasound Med. 1 (3): 117–22. PMID 6152936..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ De Campo JF (1986). "Ultrasound of Wilms' tumor". Pediatr Radiol. 16 (1): 21–4. PMID 3003660.
- ↑ Cahan LD (1985). "Failure of encephalo-duro-arterio-synangiosis procedure in moyamoya disease". Pediatr Neurosci. 12 (1): 58–62. PMID 4080660.
- ↑ Jolly RD, Stellwagen E, Babul J, Vodkaĭlo LV, Titov VL, Moldomusaev DM, Maianskiĭ AN (November 1975). "Mannosidosis of Angus Cattle: a prototype control program for some genetic diseases". Adv Vet Sci Comp Med. 19 (23): 1–21. PMID 1978.
- ↑ Chapman AB, Devuyst O, Eckardt KU, Gansevoort RT, Harris T, Horie S, Kasiske BL, Odland D, Pei Y, Perrone RD, Pirson Y, Schrier RW, Torra R, Torres VE, Watnick T, Wheeler DC (July 2015). "Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference". Kidney Int. 88 (1): 17–27. doi:10.1038/ki.2015.59. PMC 4913350. PMID 25786098.
- ↑ Pei Y, Obaji J, Dupuis A, Paterson AD, Magistroni R, Dicks E, Parfrey P, Cramer B, Coto E, Torra R, San Millan JL, Gibson R, Breuning M, Peters D, Ravine D (January 2009). "Unified criteria for ultrasonographic diagnosis of ADPKD". J. Am. Soc. Nephrol. 20 (1): 205–12. doi:10.1681/ASN.2008050507. PMC 2615723. PMID 18945943.
- ↑ Stavrou C, Koptides M, Tombazos C, Psara E, Patsias C, Zouvani I, Kyriacou K, Hildebrandt F, Christofides T, Pierides A, Deltas CC (October 2002). "Autosomal-dominant medullary cystic kidney disease type 1: clinical and molecular findings in six large Cypriot families". Kidney Int. 62 (4): 1385–94. doi:10.1111/j.1523-1755.2002.kid581.x. PMID 12234310.
- ↑ Bleyer AJ, Kmoch S, Antignac C, Robins V, Kidd K, Kelsoe JR, Hladik G, Klemmer P, Knohl SJ, Scheinman SJ, Vo N, Santi A, Harris A, Canaday O, Weller N, Hulick PJ, Vogel K, Rahbari-Oskoui FF, Tuazon J, Deltas C, Somers D, Megarbane A, Kimmel PL, Sperati CJ, Orr-Urtreger A, Ben-Shachar S, Waugh DA, McGinn S, Bleyer AJ, Hodanová K, Vylet'al P, Živná M, Hart TC, Hart PS (March 2014). "Variable clinical presentation of an MUC1 mutation causing medullary cystic kidney disease type 1". Clin J Am Soc Nephrol. 9 (3): 527–35. doi:10.2215/CJN.06380613. PMC 3944763. PMID 24509297.
- ↑ Faguer S, Decramer S, Chassaing N, Bellanné-Chantelot C, Calvas P, Beaufils S, Bessenay L, Lengelé JP, Dahan K, Ronco P, Devuyst O, Chauveau D (October 2011). "Diagnosis, management, and prognosis of HNF1B nephropathy in adulthood". Kidney Int. 80 (7): 768–76. doi:10.1038/ki.2011.225. PMID 21775974.
- ↑ Heidet L, Decramer S, Pawtowski A, Morinière V, Bandin F, Knebelmann B, Lebre AS, Faguer S, Guigonis V, Antignac C, Salomon R (June 2010). "Spectrum of HNF1B mutations in a large cohort of patients who harbor renal diseases". Clin J Am Soc Nephrol. 5 (6): 1079–90. doi:10.2215/CJN.06810909. PMC 2879303. PMID 20378641.
- ↑ Bravo EL (1991). "Pheochromocytoma: new concepts and future trends". Kidney Int. 40 (3): 544–56. PMID 1787652.
- ↑ Whalen RK, Althausen AF, Daniels GH (1992). "Extra-adrenal pheochromocytoma". J Urol. 147 (1): 1–10. PMID 1729490.CS1 maint: Multiple names: authors list (link)
- ↑ Baid SK, Lai EW, Wesley RA, Ling A, Timmers HJ, Adams KT; et al. (2009). "Brief communication: radiographic contrast infusion and catecholamine release in patients with pheochromocytoma". Ann Intern Med. 150 (1): 27–32. PMC 3490128. PMID 19124817.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
- ↑ Bravo EL (1991). "Pheochromocytoma: new concepts and future trends". Kidney Int. 40 (3): 544–56. PMID 1787652.
- ↑ Burkitt lymphoma. MedlinePlus. https://www.nlm.nih.gov/medlineplus/ency/article/001308.htm Accessed on September 30, 2015
- ↑ Bellan C, Lazzi S, De Falco G, Nyongo A, Giordano A, Leoncini L (2003). "Burkitt's lymphoma: new insights into molecular pathogenesis". J. Clin. Pathol. 56 (3): 188–92. PMC 1769902. PMID 12610094. Unknown parameter |month= ignored (help)CS1 maint: Multiple names: authors list (link)
- ↑ Ko HS, Schenk JP, Tröger J, Rohrschneider WK (2007). "Current radiological management of intussusception in children". Eur Radiol. 17 (9): 2411–21. doi:10.1007/s00330-007-0589-y. PMID 17308922.
- ↑ Boyle MJ, Arkell LJ, Williams JT (1993). "Ultrasonic diagnosis of adult intussusception". Am. J. Gastroenterol. 88 (4): 617–8. PMID 8470658. | https://www.wikidoc.org/index.php/Sandbox_SSW | |
bd734916be486c9c6d0cb10a13f0ce7382c12bf7 | wikidoc | Sandbox Yaz | Sandbox Yaz
# Overview
Treatment is generally recommended for average-risk patients who are symptomatic with positive lab findings for C. difficile infection. For patients with C. difficile risk factors, empiric therapy is recommended for symptomatic patients regardless of lab findings. Antimicrobial therapy is tailored acccording to the clinical severity of the infection. Administration of oral metronidazole is recommended for patients with mild symptoms, whereas oral vancomycin is recommended for severe disease.
# Indications for Treatment
## Symptomatic vs. Asymptomatic Individuals
- Treatment is recommended only for average-risk, symptomatic patients (usually diarrhea) with positive lab findings (either ELISA or PCR) of C. difficile infection
- In contrast, treatment is not recommended for average-risk, asymptomatic individuals OR patients with diarrhea and negative lab findings (either ELISA or PCR).
## Average Risk vs. High Risk Patients
- The negative predictive values of the diagnostic lab tests (either ELISA or PCR) are sufficiently high > 95% for patients among patients with average risk of developing C. difficile infection. Accordingly, empiric therapy is not recommended if diagnostic lab tests yield negative findings among average-risk patients.
- In contrast the negative predictive values of the diagnostic lab tests (either ELISA or PCR) are NOT sufficiently high for patients at high risk of C. difficile infection. Accordingly, empiric therapy is recommended for high risk patients with high pre-test probability even when lab findings yield negative results. Common risk factors for the development of C. difficile infection are history of antibiotic administration within the past 12 weeks, advanced age > 65 years, immunodeficiency, exposure to healthcare facilities, or inflammatory bowel disease.
For more detailed list of C. difficile risk factors, click here
# Principles of Antimicrobial Therapy for Clostridium difficile infection
According to the 2013 practice guidelines for the diagnosis, treatment, and prevention of C. difficile infections, the choice of antimicrobial therapy is based on the severity of the clinical disease. Shown below is a table that defines the severity of C. difficile infection based on clinical features and lab findings:
▸ Click on the following categories to expand treatment regimens.
## Duration of antimicrobial therapy
- Administer antimicrobial therapy for 10-14 days.
- Continue antimicrobial therapy only for 10 days if there is clinical improvement within 5 to 7 days.
## Do's
- Suspend other antibiotic therapies during administration of antibiotics to treat C. difficile infection.
- Administer vancomycin for mild-to-moderate patients who are intolerant/allergic to metronidazole and for pregnant/breastfeeding women..
- Deliver supportive care to patients with severe or severe complicated CDI .
- Perform diagnostic abdominal CT scan for patients with worsening diarrhea and/or abdominal pain to rule out C. difficile-associated complications.
- Request surgical consultation and perform routine pre-surgical work-up for patients suspected to have complicated C. difficile infection. To view indications for surgical management of C. difficile infection, click here.
- Consider fecal microbiota transplant if there is a third recurrence after a pulsed vancomycin regimen.
- Consider vancomycin enema for patients whose oral antibiotic regimen cannot reach a segment of the colon, such as patients with Hartman's pouch, ileostomy, or colon diversion.
- Administer intravenous immunoglobulins for recurrent C. difficile infection only if patient has hypogammaglobulinemia.
- Manage C. difficile infection simultaneously with inflammatory bowel disease (IBD) flare-up among patients with IBD.
- Continue immunosuppressive medications for IBD patients with C. difficile infection.
## Don'ts
- Do not administer metronidazole for a second recurrence episode of CDI or for long-term therapy because of the risk of neurotoxicity.
- Do not administer anti-peristaltic agents to treat diarrhea in patients with CDI.
- Do not administer intravenous immunoglobulins for recurrent C. difficile infection, except if patient has hypogammaglobulinemia.
- Do not increase dose of immunosuppressive medications for IBD patients with untreated C. difficile infection.
# Novel Pharmacologic Therapies
- In 2011, fidaxomicin was FDA-approved for the treatment of C. difficile infection.
Fidaxomicin is a poorly absorbed, bactericidal, macrocyclic antibiotic that acts against anaerobic, gram-positive bacteria.
Fidaxomicin demonstrated non-inferior to vancomycin in the treatment of primary infection.
Fidaxomicin was associated with significantly reduced rate of recurrence compared with vancomycin (15% vs. 25%), except among patients infected with BI/NAP1/027 strain where the recurrence rate was statistically similar between both therapies.
- Fidaxomicin is a poorly absorbed, bactericidal, macrocyclic antibiotic that acts against anaerobic, gram-positive bacteria.
- Fidaxomicin demonstrated non-inferior to vancomycin in the treatment of primary infection.
- Fidaxomicin was associated with significantly reduced rate of recurrence compared with vancomycin (15% vs. 25%), except among patients infected with BI/NAP1/027 strain where the recurrence rate was statistically similar between both therapies.
# Fecal Bacteriotherapy
- Fecal bacteriotherapy is a procedure related to probiotic research. It has been suggested as a potential cure for C. difficile infection.
- It involves infusion of bacterial flora acquired from the feces of a healthy donor in an attempt to reverse bacterial imbalance responsible for the recurring nature of the infection. | Sandbox Yaz
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Guillermo Rodriguez Nava, M.D. [2]; Yazan Daaboul, M.D.
# Overview
Treatment is generally recommended for average-risk patients who are symptomatic with positive lab findings for C. difficile infection. For patients with C. difficile risk factors, empiric therapy is recommended for symptomatic patients regardless of lab findings. Antimicrobial therapy is tailored acccording to the clinical severity of the infection. Administration of oral metronidazole is recommended for patients with mild symptoms, whereas oral vancomycin is recommended for severe disease.
# Indications for Treatment
## Symptomatic vs. Asymptomatic Individuals
- Treatment is recommended only for average-risk, symptomatic patients (usually diarrhea) with positive lab findings (either ELISA or PCR) of C. difficile infection
- In contrast, treatment is not recommended for average-risk, asymptomatic individuals OR patients with diarrhea and negative lab findings (either ELISA or PCR).
## Average Risk vs. High Risk Patients
- The negative predictive values of the diagnostic lab tests (either ELISA or PCR) are sufficiently high > 95% for patients among patients with average risk of developing C. difficile infection. Accordingly, empiric therapy is not recommended if diagnostic lab tests yield negative findings among average-risk patients.
- In contrast the negative predictive values of the diagnostic lab tests (either ELISA or PCR) are NOT sufficiently high for patients at high risk of C. difficile infection. Accordingly, empiric therapy is recommended for high risk patients with high pre-test probability even when lab findings yield negative results.[1] Common risk factors for the development of C. difficile infection are history of antibiotic administration within the past 12 weeks, advanced age > 65 years, immunodeficiency, exposure to healthcare facilities, or inflammatory bowel disease.
For more detailed list of C. difficile risk factors, click here
# Principles of Antimicrobial Therapy for Clostridium difficile infection
According to the 2013 practice guidelines for the diagnosis, treatment, and prevention of C. difficile infections[2], the choice of antimicrobial therapy is based on the severity of the clinical disease. Shown below is a table that defines the severity of C. difficile infection based on clinical features and lab findings:
▸ Click on the following categories to expand treatment regimens.[1][3][2][4][5]
## Duration of antimicrobial therapy
- Administer antimicrobial therapy for 10-14 days.
- Continue antimicrobial therapy only for 10 days if there is clinical improvement within 5 to 7 days.[2]
## Do's
- Suspend other antibiotic therapies during administration of antibiotics to treat C. difficile infection.
- Administer vancomycin for mild-to-moderate patients who are intolerant/allergic to metronidazole and for pregnant/breastfeeding women.[1].
- Deliver supportive care to patients with severe or severe complicated CDI .[1]
- Perform diagnostic abdominal CT scan for patients with worsening diarrhea and/or abdominal pain to rule out C. difficile-associated complications.[1]
- Request surgical consultation and perform routine pre-surgical work-up for patients suspected to have complicated C. difficile infection. To view indications for surgical management of C. difficile infection, click here.
- Consider fecal microbiota transplant if there is a third recurrence after a pulsed vancomycin regimen.[1]
- Consider vancomycin enema for patients whose oral antibiotic regimen cannot reach a segment of the colon, such as patients with Hartman's pouch, ileostomy, or colon diversion.
- Administer intravenous immunoglobulins for recurrent C. difficile infection only if patient has hypogammaglobulinemia.
- Manage C. difficile infection simultaneously with inflammatory bowel disease (IBD) flare-up among patients with IBD.
- Continue immunosuppressive medications for IBD patients with C. difficile infection.
## Don'ts
- Do not administer metronidazole for a second recurrence episode of CDI or for long-term therapy because of the risk of neurotoxicity.[4]
- Do not administer anti-peristaltic agents to treat diarrhea in patients with CDI.[1]
- Do not administer intravenous immunoglobulins for recurrent C. difficile infection, except if patient has hypogammaglobulinemia.
- Do not increase dose of immunosuppressive medications for IBD patients with untreated C. difficile infection.
# Novel Pharmacologic Therapies
- In 2011, fidaxomicin was FDA-approved for the treatment of C. difficile infection.[6]
Fidaxomicin is a poorly absorbed, bactericidal, macrocyclic antibiotic that acts against anaerobic, gram-positive bacteria.[6]
Fidaxomicin demonstrated non-inferior to vancomycin in the treatment of primary infection.[6]
Fidaxomicin was associated with significantly reduced rate of recurrence compared with vancomycin (15% vs. 25%), except among patients infected with BI/NAP1/027 strain where the recurrence rate was statistically similar between both therapies.[6]
- Fidaxomicin is a poorly absorbed, bactericidal, macrocyclic antibiotic that acts against anaerobic, gram-positive bacteria.[6]
- Fidaxomicin demonstrated non-inferior to vancomycin in the treatment of primary infection.[6]
- Fidaxomicin was associated with significantly reduced rate of recurrence compared with vancomycin (15% vs. 25%), except among patients infected with BI/NAP1/027 strain where the recurrence rate was statistically similar between both therapies.[6]
# Fecal Bacteriotherapy
- Fecal bacteriotherapy is a procedure related to probiotic research. It has been suggested as a potential cure for C. difficile infection.
- It involves infusion of bacterial flora acquired from the feces of a healthy donor in an attempt to reverse bacterial imbalance responsible for the recurring nature of the infection. | https://www.wikidoc.org/index.php/Sandbox_Yaz | |
a9d6e61ce07bffe95a7c5522faabc885e5776ed5 | wikidoc | Sandbox aom | Sandbox aom
# Overview
Acute otitis media (AOM) usually follows a viral upper respiratory tract infection leading to Eustachian tube dysfunction with impaired clearance and pressure regulation of the middle ear. Current guidelines recommend observation for children age 6 to 24 months with unilateral AOM without otorrhea or children older than 2 years with unilateral or bilateral AOM without otorrhea. Antibiotics covering common bacterial pathogens (e.g., Streptococcus pneumoniae, Moraxella catarrhalis, and non-typeable Haemophilus influenzae) have been used with success in selected patients to accelerate the recovery and lower the risk of tympanic membrane perforations and contralateral AOM episodes. High-dose amoxicillin (90 mg/kg/day) is the drug of choice for initial antibiotic therapy; high-dose amoxicillin-clavulanate or intramuscular ceftriaxone should be reserved for patients who fail to respond to first-line treatment within 48 to 72 hours. The optimal duration of antibiotics remains uncertain: a 10-day course of antibiotic therapy is recommended for children younger than 2 years and children with severe symptoms. In the absence of severe symptoms, a 7- or 5-day course is advisable for children 2 to 5 years of age or children 6 years and older, respectively. Otalgia is generally managed with acetaminophen, ibuprofen, or narcotic analgesics with codeine.
# Initial Management of Uncomplicated AOM with High Certainty of Diagnosis
† A toxic-appearing child, persistent otalgia more than 48 h, temperature ≥39°C (102.2°F) in the past 48 h, or if there is uncertain access to follow-up after the visit.
# Observation
Due to the self-limited nature of most episodes of AOM (particularly in children 2 years and older), initial observation is advisable for selected patients if close follow-up can be ensured and rescue antibiotics administered for persistent or worsening symptoms in 48 to 72 hours.
# Antibiotic Therapy
## Rationale for Antibiotic Choice
The rationale for antibiotic therapy in children with AOM is based on a high prevalence of bacteria from tympanocentesis cultures. A significant benefit of immediate antibiotic therapy is most evident in bilateral AOM, AOM with severe symptotms, AOM with otorrhea, or Streptococcus pneumoniae infection. Antibiotic therapy is recommended in the following settings:
- AOM (bilateral or unilateral) in children 6 months and older with severe signs or symptoms (i.e., moderate or severe otalgia or otalgia for at least 48 hours, or temperature 39°C or higher)
- Bilateral AOM in children younger than 24 months without severe signs or symptoms
When a decision to treat with antibiotics has been made, high-dose amoxicillin is recommended if all of the following criteria are fulfilled:
- The patient has not received amoxicillin in the past 30 days.
- The patient does not have concurrent purulent conjunctivitis.
- The patient is not allergic to penicillin.
Additional β-lactamase coverage should be considered if any of the following criteria is fulfilled:
- The patient has received amoxicillin in the past 30 days.
- The patient has concurrent purulent conjunctivitis.
- The patient has a history of recurrent AOM unresponsive to amoxicillin.
## Duration of Therapy
The optimal duration of antibiotics remains unsettled. Standard 10-day course of antibiotic therapy is recommended for children younger than 2 years and children with severe symptoms. In the absence of severe symptoms, a 7- or 5-day course is advisable for children 2 to 5 years of age or children 6 years and older, respectively.
## Antibiotic Regimens
### Initial (Immediate or Delayed) Antibiotic Treatment
Amoxicillin (80–90 mg/kg/d bid) OR Amoxicillin (90 mg/kg/d) with Clavulanate (6.4 mg/kg/d)
Cefdinir (14 mg/kg/d qd or bid) OR Cefuroxime (30 mg/kg/d bid) OR Cefpodoxime (10 mg/kg/d bid) OR Ceftriaxone (50 mg IM/IV qd)
### After Failure of Initial Antibiotic Treatment
Amoxicillin (90 mg/kg/d) with Clavulanate (6.4 mg/kg/d) OR Ceftriaxone (50 mg IM/IV qd)
Clindamycin (30–40 mg/kg/d tid) ± 3° Cephalosporin ± Tympanocentesis
# Pain Management
Episodes of AOM are commonly associated with otalgia. Acetaminophen and ibuprofen are the mainstay of management for mild to moderate ear pain. Narcotic analgesia with codeine should be used with caution in the treatment of severe otalgia due to the risk of respiratory depression, altered mental status, gastrointestinal upset, and constipation. | Sandbox aom
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Acute otitis media (AOM) usually follows a viral upper respiratory tract infection leading to Eustachian tube dysfunction with impaired clearance and pressure regulation of the middle ear. Current guidelines recommend observation for children age 6 to 24 months with unilateral AOM without otorrhea or children older than 2 years with unilateral or bilateral AOM without otorrhea.[1] Antibiotics covering common bacterial pathogens (e.g., Streptococcus pneumoniae, Moraxella catarrhalis, and non-typeable Haemophilus influenzae) have been used with success in selected patients to accelerate the recovery and lower the risk of tympanic membrane perforations and contralateral AOM episodes.[2] High-dose amoxicillin (90 mg/kg/day) is the drug of choice for initial antibiotic therapy; high-dose amoxicillin-clavulanate or intramuscular ceftriaxone should be reserved for patients who fail to respond to first-line treatment within 48 to 72 hours. The optimal duration of antibiotics remains uncertain: a 10-day course of antibiotic therapy is recommended for children younger than 2 years and children with severe symptoms. In the absence of severe symptoms, a 7- or 5-day course is advisable for children 2 to 5 years of age or children 6 years and older, respectively. Otalgia is generally managed with acetaminophen, ibuprofen, or narcotic analgesics with codeine.[3]
# Initial Management of Uncomplicated AOM with High Certainty of Diagnosis
† A toxic-appearing child, persistent otalgia more than 48 h, temperature ≥39°C (102.2°F) in the past 48 h, or if there is uncertain access to follow-up after the visit.
# Observation
Due to the self-limited nature of most episodes of AOM (particularly in children 2 years and older), initial observation is advisable for selected patients if close follow-up can be ensured and rescue antibiotics administered for persistent or worsening symptoms in 48 to 72 hours.
# Antibiotic Therapy
## Rationale for Antibiotic Choice
The rationale for antibiotic therapy in children with AOM is based on a high prevalence of bacteria from tympanocentesis cultures. A significant benefit of immediate antibiotic therapy is most evident in bilateral AOM, AOM with severe symptotms, AOM with otorrhea, or Streptococcus pneumoniae infection.[5] Antibiotic therapy is recommended in the following settings:
- AOM (bilateral or unilateral) in children 6 months and older with severe signs or symptoms (i.e., moderate or severe otalgia or otalgia for at least 48 hours, or temperature 39°C [102.2°F] or higher)
- Bilateral AOM in children younger than 24 months without severe signs or symptoms
When a decision to treat with antibiotics has been made, high-dose amoxicillin is recommended if all of the following criteria are fulfilled:[6]
- The patient has not received amoxicillin in the past 30 days.
- The patient does not have concurrent purulent conjunctivitis.
- The patient is not allergic to penicillin.
Additional β-lactamase coverage should be considered if any of the following criteria is fulfilled:[7]
- The patient has received amoxicillin in the past 30 days.
- The patient has concurrent purulent conjunctivitis.
- The patient has a history of recurrent AOM unresponsive to amoxicillin.
## Duration of Therapy
The optimal duration of antibiotics remains unsettled. Standard 10-day course of antibiotic therapy is recommended for children younger than 2 years and children with severe symptoms. In the absence of severe symptoms, a 7- or 5-day course is advisable for children 2 to 5 years of age or children 6 years and older, respectively.
## Antibiotic Regimens
### Initial (Immediate or Delayed) Antibiotic Treatment
Amoxicillin (80–90 mg/kg/d bid) OR Amoxicillin (90 mg/kg/d) with Clavulanate (6.4 mg/kg/d)
Cefdinir (14 mg/kg/d qd or bid) OR Cefuroxime (30 mg/kg/d bid) OR Cefpodoxime (10 mg/kg/d bid) OR Ceftriaxone (50 mg IM/IV qd)
### After Failure of Initial Antibiotic Treatment
Amoxicillin (90 mg/kg/d) with Clavulanate (6.4 mg/kg/d) OR Ceftriaxone (50 mg IM/IV qd)
Clindamycin (30–40 mg/kg/d tid) ± 3° Cephalosporin ± Tympanocentesis
# Pain Management
Episodes of AOM are commonly associated with otalgia. Acetaminophen and ibuprofen are the mainstay of management for mild to moderate ear pain. Narcotic analgesia with codeine should be used with caution in the treatment of severe otalgia due to the risk of respiratory depression, altered mental status, gastrointestinal upset, and constipation.[8] | https://www.wikidoc.org/index.php/Sandbox_aom | |
f572d29c7de302bf2026b5767ba81e58da1840ef | wikidoc | Sandbox bla | Sandbox bla
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Black Box Warning
# Overview
Sandbox bla is a Adrenergic receptor agonist that is FDA approved for the {{{indicationType}}} of a list of indications, separated by commas.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include a list of adverse reactions, separated by commas..
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
### Non–Guideline-Supported Use
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
### Non–Guideline-Supported Use
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
# Contraindications
- Condition 1
- Condition 2
- Condition 3
- Condition 4
- Condition 5
# Warnings
(Description)
(Description)
(Description)
# Adverse Reactions
## Clinical Trials Experience
## Postmarketing Experience
(Description)
# Drug Interactions
- Drug 1
- Drug 2
- Drug 3
- Drug 4
- Drug 5
(Description)
(Description)
(Description)
(Description)
(Description)
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
(Description)
Pregnancy Category (AUS):
(Description)
### Labor and Delivery
(Description)
### Nursing Mothers
(Description)
### Pediatric Use
(Description)
### Geriatic Use
(Description)
### Gender
(Description)
### Race
(Description)
### Renal Impairment
(Description)
### Hepatic Impairment
(Description)
### Females of Reproductive Potential and Males
(Description)
### Immunocompromised Patients
(Description)
### Others
(Description)
# Administration and Monitoring
### Administration
(Oral/Intravenous/etc)
### Monitoring
(Description regarding monitoring, from Warnings section)
(Description regarding monitoring, from Warnings section)
(Description regarding monitoring, from Warnings section)
# IV Compatibility
## Solution
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
## Y-Site
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
## Admixture
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
## Syringe
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
## TPN/TNA
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
# Overdosage
## Acute Overdose
### Signs and Symptoms
(Description)
### Management
(Description)
## Chronic Overdose
### Signs and Symptoms
(Description)
### Management
(Description)
# Pharmacology
## Mechanism of Action
(Description)
## Structure
(Description with picture)
## Pharmacodynamics
(Description)
## Pharmacokinetics
(Description)
## Nonclinical Toxicology
(Description)
# Clinical Studies
(Description)
(Description)
(Description)
# How Supplied
(Description)
## Storage
There is limited information regarding Sandbox bla Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
(Patient Counseling Information)
# Precautions with Alcohol
Alcohol-Sandbox bla interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
# Brand Names
There is limited information regarding Sandbox bla Brand Names in the drug label.
# Look-Alike Drug Names
- (Paired Confused Name 1a) — (Paired Confused Name 1b)
- (Paired Confused Name 2a) — (Paired Confused Name 2b)
- (Paired Confused Name 3a) — (Paired Confused Name 3b)
# Drug Shortage Status
Drug Shortage
# Price | Sandbox bla
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Black Box Warning
# Overview
Sandbox bla is a Adrenergic receptor agonist that is FDA approved for the {{{indicationType}}} of a list of indications, separated by commas.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include a list of adverse reactions, separated by commas..
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
### Non–Guideline-Supported Use
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
### Non–Guideline-Supported Use
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
# Contraindications
- Condition 1
- Condition 2
- Condition 3
- Condition 4
- Condition 5
# Warnings
(Description)
(Description)
(Description)
# Adverse Reactions
## Clinical Trials Experience
## Postmarketing Experience
(Description)
# Drug Interactions
- Drug 1
- Drug 2
- Drug 3
- Drug 4
- Drug 5
(Description)
(Description)
(Description)
(Description)
(Description)
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
(Description)
Pregnancy Category (AUS):
(Description)
### Labor and Delivery
(Description)
### Nursing Mothers
(Description)
### Pediatric Use
(Description)
### Geriatic Use
(Description)
### Gender
(Description)
### Race
(Description)
### Renal Impairment
(Description)
### Hepatic Impairment
(Description)
### Females of Reproductive Potential and Males
(Description)
### Immunocompromised Patients
(Description)
### Others
(Description)
# Administration and Monitoring
### Administration
(Oral/Intravenous/etc)
### Monitoring
(Description regarding monitoring, from Warnings section)
(Description regarding monitoring, from Warnings section)
(Description regarding monitoring, from Warnings section)
# IV Compatibility
## Solution
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
## Y-Site
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
## Admixture
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
## Syringe
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
## TPN/TNA
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
# Overdosage
## Acute Overdose
### Signs and Symptoms
(Description)
### Management
(Description)
## Chronic Overdose
### Signs and Symptoms
(Description)
### Management
(Description)
# Pharmacology
## Mechanism of Action
(Description)
## Structure
(Description with picture)
## Pharmacodynamics
(Description)
## Pharmacokinetics
(Description)
## Nonclinical Toxicology
(Description)
# Clinical Studies
(Description)
(Description)
(Description)
# How Supplied
(Description)
## Storage
There is limited information regarding Sandbox bla Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
(Patient Counseling Information)
# Precautions with Alcohol
Alcohol-Sandbox bla interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
# Brand Names
There is limited information regarding Sandbox bla Brand Names in the drug label.
# Look-Alike Drug Names
- (Paired Confused Name 1a) — (Paired Confused Name 1b)
- (Paired Confused Name 2a) — (Paired Confused Name 2b)
- (Paired Confused Name 3a) — (Paired Confused Name 3b)
# Drug Shortage Status
Drug Shortage
# Price | https://www.wikidoc.org/index.php/Sandbox_bla | |
3f7421b9bc7852db649da402b2676392978f2f5b | wikidoc | Sandbox cdi | Sandbox cdi
# Overview
Clostridium difficile infection is the leading cause to nosocomial diarrhea. Clinical presentation ranges across a broad spectrum from asymptomatic carriage, to diarrheal illness, to complicated disease hallmarked by pseudomembranous colitis, toxic megacolon, or bowel perforation. Diagnosis is established by the presence of diarrheal symptoms coupled with positive stool tests or endoscopic findings. Therapeutic approach and antibiotic choice should be stratified according to severity of disease and risk of recurrence.
# Diagnostic Criteria
## Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)
The diagnosis of C. difficile infection should be based on a combination of clinical and laboratory findings. A case definition for the usual presentation includes the following findings:
- The presence of diarrhea, defined as passage of 3 or more unformed stools in 24 or fewer consecutive hours AND
- A stool test result positive for the presence of toxigenic C. difficile or its toxins OR colonoscopic or histopathologic findings demonstrating pseudomembranous colitis.
The same criteria should be used to diagnose recurrent C. difficile infection.
## European Society of Clinical Microbiology and Infectious Diseases (ESCMID)
Diagnosis of C. difficile infection is based on the following criteria:
- A combination of signs and symptoms, confirmed by microbiological evidence of C. difficile in stools, in the absence of another cause OR
- Colonoscopic or histopathological findings demonstrating pseudomembranous colitis
Diagnostic tests for C. difficile infection include:
- Enzyme immunoassay (EIA): glutamate dehydrogenase (GDH), toxins A and B
- Nucleic acid amplification tests (NAAT): 16S ribosomal RNA, GDH genes, toxin genes
- Cell culture cytoxicity assay (CCA)
- Culture of toxigenic C. difficile
# Classification of Disease Severity
## Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)
Initial episode of C. difficile infection may be stratified by disease severity as follows:
- Mild-to-moderate disease
- Severe disease
- Severe, complicated disease
## European Society of Clinical Microbiology and Infectious Diseases (ESCMID)
Severe disease is defined as an episode of C. difficile infection with:
- One or more specific signs and symptoms of severe colitis OR
- A complicated course of disease, with significant systemic toxin effects and shock, resulting in need for intensive care unit admission, colectomy, or death.
Characteristics that correlate with severity of colitis:
- Physical examination
- Laboratory investigations
- Colonoscopy or sigmoidoscopy
- Imaging
## American College of Gastroenterology (ACG)
Classification of disease severity:
- Mild disease
- Moderate disease
- Severe disease
- Complicated disease
- Recurrent disease
# Risk Factors
The most important risk factor remains antibiotic use. Other established risk factors include:
- Advanced age
- Chemotherapy
- Chronic kidney disease
- Consumption of processed meat
- Contact with active carriers
- Cystic fibrosis
- Diabetes mellitus
- Hypoalbuminemia
- Immunosuppression, immunodeficiency, or human immunodeficiency virus
- Increased risk with prolonged use or multiple antibiotics
- Inflammatory bowel disease
- Liver cirrhosis
- Malignancy
- Malnutrition
- Nursing home or long-term care facility residence
- Presence of comorbid conditions
- Presence of gastrostomy or jejunostomy tube
- Previous gastrointestinal surgery or endoscopic procedure
- Previous hospitalization and prolonged length of hospital stay
- Solid organ or hematopoietic stem cell transplantation
- Use of proton pump inhibitors
Use of the following antibiotics has been associated with C. difficile infection:
- Very common
- Somewhat common
- Uncommon
# Complete Diagnostic Approach
Abbreviations:
ALP, alkaline phosphatase;
ALT, alanine aminotransferase;
AST, aspartate aminotransferase;
CBC, complete blood count;
DC, differential count;
EIA, enzyme immunoassay;
GDH, glutamate dehydrogenase;
NAAT, nucleic acid amplification test;
PCR, polymerase chain reaction;
SMA-7, sequential multiple analysis-7.
# Management
## Asymptomatic carrier
- No treatment indicated
## Mild disease
- Predisposing antibiotic cessation
- Hydration
- Monitoring of clinical status
- Administration of metronidazole (500 mg three times per day) OR
## Moderate disease
- Consideration of hospitalization
- Cessation of predisposing antibiotics
- Hydration
- Monitoring of clinical status
- Administration of metronidazole (500 mg three times per day) OR
## Severe disease
- Hospitalization
- Oral or nasogastric vancomycin (500 mg four times per day) with or without intravenous metronidazole (500 mg three times per day) OR
## Complicated disease
- Antibiotics as for severe infection
- Surgical consultation for subtotal colectomy or a diverting ileostomy with vancomycin colonic lavage
- Consideration of fecal microbial transplantation or additional antibiotics
## First recurrence
- Oral vancomycin (125 mg four times per day for 14 days) OR
## Second or further recurrence
- Vancomycin in a tapered and pulsed regimen OR
- Fecal microbial transplantation OR
- Fidaxomicin (200 mg twice a day for 10 days)
# Dos and Don'ts
## Dos
- Inform the laboratory when testing for Clostridium difficile from formed stools in a patient with ileus.
- Initiate empiric antibiotics regardless of the laboratory results when there is a high index of suspicion for C. difficile infection.
- Vancomycin should be delivered via enema to treat patients in whom oral antibiotics cannot reach a segment of the colon as in Hartmann's pouch, ileostomy, or colonic diversion.
- Test for C. difficile among patients with diarrhea in the context of malignancy, chemotherapy, immunosuppressive therapy, organ transplantation, cirrhosis, inflammatory bowel disease, or pregnancy.
## Don'ts
- Do NOT test for C. difficile in a patient without diarrhea.
- Do NOT repeat test if the results are negative.
- Do NOT perform test of microbiological cure.
- Do NOT treat asymptomatic carriage.
- Do NOT administer antiperistaltic agents to patients with suspected or confirmed C. difficile infection.
# Guidelines
## Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)
- Strategies to Prevent Clostridium difficile Infections in Acute Care Hospitals (2014)
- Clinical Practice Guidelines for Clostridium difficile Infection in Adults (2010)
## American College of Gastroenterology (ACG)
- Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections (2013)
## Association for Professionals in Infection Control and Epidemiology (APIC)
- Preventing Clostridium difficile infections (2011)
## Eastern Association for the Surgery of Trauma (EAST)
- Timing and type of surgical treatment of Clostridium difficile-associated disease (2014)
## American Society of Colon and Rectal Surgeons (ASCRS)
- Practice Parameters for the Management of Clostridium difficile Infection (2015)
## European Society of Clinical Microbiology and Infectious Diseases (ESCMID)
- Update of the Treatment Guidance Document for Clostridium difficile Infection (2014)
## American Academy of Pediatrics (AAP)
- Policy Statement: Clostridium difficile Infection in Infants and Children (2013) | Sandbox cdi
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Clostridium difficile infection is the leading cause to nosocomial diarrhea. Clinical presentation ranges across a broad spectrum from asymptomatic carriage, to diarrheal illness, to complicated disease hallmarked by pseudomembranous colitis, toxic megacolon, or bowel perforation. Diagnosis is established by the presence of diarrheal symptoms coupled with positive stool tests or endoscopic findings. Therapeutic approach and antibiotic choice should be stratified according to severity of disease and risk of recurrence.
# Diagnostic Criteria
## Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)
The diagnosis of C. difficile infection should be based on a combination of clinical and laboratory findings. A case definition for the usual presentation includes the following findings:[1]
- The presence of diarrhea, defined as passage of 3 or more unformed stools in 24 or fewer consecutive hours AND
- A stool test result positive for the presence of toxigenic C. difficile or its toxins OR colonoscopic or histopathologic findings demonstrating pseudomembranous colitis.
The same criteria should be used to diagnose recurrent C. difficile infection.
## European Society of Clinical Microbiology and Infectious Diseases (ESCMID)
Diagnosis of C. difficile infection is based on the following criteria:[2]
- A combination of signs and symptoms, confirmed by microbiological evidence of C. difficile in stools, in the absence of another cause OR
- Colonoscopic or histopathological findings demonstrating pseudomembranous colitis
Diagnostic tests for C. difficile infection include:[3]
- Enzyme immunoassay (EIA): glutamate dehydrogenase (GDH), toxins A and B
- Nucleic acid amplification tests (NAAT): 16S ribosomal RNA, GDH genes, toxin genes
- Cell culture cytoxicity assay (CCA)
- Culture of toxigenic C. difficile
# Classification of Disease Severity
## Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)
Initial episode of C. difficile infection may be stratified by disease severity as follows:[4]
- Mild-to-moderate disease
- Severe disease
- Severe, complicated disease
## European Society of Clinical Microbiology and Infectious Diseases (ESCMID)
Severe disease is defined as an episode of C. difficile infection with:[5]
- One or more specific signs and symptoms of severe colitis OR
- A complicated course of disease, with significant systemic toxin effects and shock, resulting in need for intensive care unit admission, colectomy, or death.
Characteristics that correlate with severity of colitis:[6]
- Physical examination
- Laboratory investigations
- Colonoscopy or sigmoidoscopy
- Imaging
## American College of Gastroenterology (ACG)
Classification of disease severity:[7]
- Mild disease
- Moderate disease
- Severe disease
- Complicated disease
- Recurrent disease
# Risk Factors
The most important risk factor remains antibiotic use. Other established risk factors include:[8]
- Advanced age
- Chemotherapy
- Chronic kidney disease
- Consumption of processed meat
- Contact with active carriers
- Cystic fibrosis
- Diabetes mellitus
- Hypoalbuminemia
- Immunosuppression, immunodeficiency, or human immunodeficiency virus
- Increased risk with prolonged use or multiple antibiotics
- Inflammatory bowel disease
- Liver cirrhosis
- Malignancy
- Malnutrition
- Nursing home or long-term care facility residence
- Presence of comorbid conditions
- Presence of gastrostomy or jejunostomy tube
- Previous gastrointestinal surgery or endoscopic procedure
- Previous hospitalization and prolonged length of hospital stay
- Solid organ or hematopoietic stem cell transplantation
- Use of proton pump inhibitors
Use of the following antibiotics has been associated with C. difficile infection:[9]
- Very common
- Somewhat common
- Uncommon
# Complete Diagnostic Approach
Abbreviations:
ALP, alkaline phosphatase;
ALT, alanine aminotransferase;
AST, aspartate aminotransferase;
CBC, complete blood count;
DC, differential count;
EIA, enzyme immunoassay;
GDH, glutamate dehydrogenase;
NAAT, nucleic acid amplification test;
PCR, polymerase chain reaction;
SMA-7, sequential multiple analysis-7.
# Management
## Asymptomatic carrier
- No treatment indicated
## Mild disease
- Predisposing antibiotic cessation
- Hydration
- Monitoring of clinical status
- Administration of metronidazole (500 mg three times per day) OR
## Moderate disease
- Consideration of hospitalization
- Cessation of predisposing antibiotics
- Hydration
- Monitoring of clinical status
- Administration of metronidazole (500 mg three times per day) OR
## Severe disease
- Hospitalization
- Oral or nasogastric vancomycin (500 mg four times per day) with or without intravenous metronidazole (500 mg three times per day) OR
## Complicated disease
- Antibiotics as for severe infection
- Surgical consultation for subtotal colectomy or a diverting ileostomy with vancomycin colonic lavage
- Consideration of fecal microbial transplantation or additional antibiotics
## First recurrence
- Oral vancomycin (125 mg four times per day for 14 days) OR
## Second or further recurrence
- Vancomycin in a tapered and pulsed regimen OR
- Fecal microbial transplantation OR
- Fidaxomicin (200 mg twice a day for 10 days)[10]
# Dos and Don'ts
## Dos
- Inform the laboratory when testing for Clostridium difficile from formed stools in a patient with ileus.
- Initiate empiric antibiotics regardless of the laboratory results when there is a high index of suspicion for C. difficile infection.
- Vancomycin should be delivered via enema to treat patients in whom oral antibiotics cannot reach a segment of the colon as in Hartmann's pouch, ileostomy, or colonic diversion.
- Test for C. difficile among patients with diarrhea in the context of malignancy, chemotherapy, immunosuppressive therapy, organ transplantation, cirrhosis, inflammatory bowel disease, or pregnancy.
## Don'ts
- Do NOT test for C. difficile in a patient without diarrhea.
- Do NOT repeat test if the results are negative.
- Do NOT perform test of microbiological cure.
- Do NOT treat asymptomatic carriage.
- Do NOT administer antiperistaltic agents to patients with suspected or confirmed C. difficile infection.
# Guidelines
## Infectious Disease Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)
- Strategies to Prevent Clostridium difficile Infections in Acute Care Hospitals (2014)[11]
- Clinical Practice Guidelines for Clostridium difficile Infection in Adults (2010)[12]
## American College of Gastroenterology (ACG)
- Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections (2013)[13]
## Association for Professionals in Infection Control and Epidemiology (APIC)
- Preventing Clostridium difficile infections (2011)[14]
## Eastern Association for the Surgery of Trauma (EAST)
- Timing and type of surgical treatment of Clostridium difficile-associated disease (2014)[15]
## American Society of Colon and Rectal Surgeons (ASCRS)
- Practice Parameters for the Management of Clostridium difficile Infection (2015)[16]
## European Society of Clinical Microbiology and Infectious Diseases (ESCMID)
- Update of the Treatment Guidance Document for Clostridium difficile Infection (2014)[17]
## American Academy of Pediatrics (AAP)
- Policy Statement: Clostridium difficile Infection in Infants and Children (2013)[18] | https://www.wikidoc.org/index.php/Sandbox_cdi | |
eb805b0351e03926afdc924c61c95fbe837caac1 | wikidoc | Sandbox cjp | Sandbox cjp
# Pregnancy
Here is some information about the use of the drug in pregnant women from the FDA.
Here is some information about the use of the drug in pregnant women from Australia.
# Labor and Delivery
Here is some information about the use of the drug in labor and delivery.
# Nursing Mothers
Here is some information about the use of the drug in women who are nursing
# Pediatric Use
Here is some information about the use of the drug in children.
# Geriatic Use
Here is some information about the use of the drug in the elderly.
# Gender
Here is some information about the use of the drug in
# Race
Here is some information about the use of the drug in people of this ethnicity.
# Renal Impairment
Here is some information about the use of the drug in people who with renal impairment.
# Hepatic Impairment
Here is some information about the use of the drug in people with hepatic impairment.
# Females of Reproductive Potential and Males
Here is some information about the use of the drug in women of reproductive potential.
# Immunocompromised Patients
Here is some information about the use of the drug in people who are immunocompromised. | Sandbox cjp
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
## Pregnancy
Here is some information about the use of the drug in pregnant women from the FDA.
Here is some information about the use of the drug in pregnant women from Australia.
## Labor and Delivery
Here is some information about the use of the drug in labor and delivery.
## Nursing Mothers
Here is some information about the use of the drug in women who are nursing
## Pediatric Use
Here is some information about the use of the drug in children.
## Geriatic Use
Here is some information about the use of the drug in the elderly.
## Gender
Here is some information about the use of the drug in
## Race
Here is some information about the use of the drug in people of this ethnicity.
## Renal Impairment
Here is some information about the use of the drug in people who with renal impairment.
## Hepatic Impairment
Here is some information about the use of the drug in people with hepatic impairment.
## Females of Reproductive Potential and Males
Here is some information about the use of the drug in women of reproductive potential.
## Immunocompromised Patients
Here is some information about the use of the drug in people who are immunocompromised. | https://www.wikidoc.org/index.php/Sandbox_cjp | |
a9f3d3f9c159ba351d87762375ee6acc5030e984 | wikidoc | Sandbox dfd | Sandbox dfd
1. BEFORE YOU START
1.1 Resources
1.1.1 DailyMed
1.1.2 Drugs@FDA
1.1.3 Pillbox
1.1.4 Drug Information Portal
1.1.5 MedlinePlus
1.2 Generic name, active ingredient, formulation, combination, trade name, label
1.2.1 What is the generic name?
1.2.2 What is the active ingredient? Is there more than one formulation for the active ingredient?
1.2.3 Is the active ingredient provided as combinations with other active ingredients?
1.2.4 What is the trade name?
1.2.5 Which label should be used?
1.2.6 Example
2. Creating or editing a drug page
2.1 Landing page
2.1.1 Go to WikiDoc.
2.1.2 Search with the generic name.
2.1.3 The generic name page should be organized as a landing page if multiple formulations or combinations exist.
2.1.4 At the top of the landing page, place the links (as headings) of formulations and/or combinations followed by trade names in parentheses (See Section 1.2 for instructions).
2.1.5 Redirect the trade name pages to the generic name with formulation pages.
2.1.6 Create or edit the Overview section and Category section.
2.2 Using the Drug Project Form
2.2.1 To create a drug page, Go to Form:DrugProjectForm.
2.2.2 Use the appropriate title for the drug page.
2.2.3 Enter the title for the drug page in the field and left-click on the "Create or edit a Drug Page" button.
2.2.4 Follow the instructions under each tab to insert contents.
2.2.5 Left-click on the "Save" button after completing each tab to minimize the risk of losing progress.
2.2.6 Quality check the completed section before proceeding to the next section. | Sandbox dfd
1. BEFORE YOU START
1.1 Resources
1.1.1 DailyMed
1.1.2 Drugs@FDA
1.1.3 Pillbox
1.1.4 Drug Information Portal
1.1.5 MedlinePlus
1.2 Generic name, active ingredient, formulation, combination, trade name, label
1.2.1 What is the generic name?
1.2.2 What is the active ingredient? Is there more than one formulation for the active ingredient?
1.2.3 Is the active ingredient provided as combinations with other active ingredients?
1.2.4 What is the trade name?
1.2.5 Which label should be used?
1.2.6 Example
2. Creating or editing a drug page
2.1 Landing page
2.1.1 Go to WikiDoc.
2.1.2 Search with the generic name.
2.1.3 The generic name page should be organized as a landing page if multiple formulations or combinations exist.
2.1.4 At the top of the landing page, place the links (as <h3> headings) of formulations and/or combinations followed by trade names in parentheses (See Section 1.2 for instructions).
2.1.5 Redirect the trade name pages to the generic name with formulation pages.
2.1.6 Create or edit the Overview section and Category section.
2.2 Using the Drug Project Form
2.2.1 To create a drug page, Go to Form:DrugProjectForm.
2.2.2 Use the appropriate title for the drug page.
2.2.3 Enter the title for the drug page in the field and left-click on the "Create or edit a Drug Page" button.
2.2.4 Follow the instructions under each tab to insert contents.
2.2.5 Left-click on the "Save" button after completing each tab to minimize the risk of losing progress.
2.2.6 Quality check the completed section before proceeding to the next section. | https://www.wikidoc.org/index.php/Sandbox_dfd | |
978c6cf618d8c80c99dff8e8c5bf17cb19dd5de9 | wikidoc | Sandbox g06 | Sandbox g06
GLIPIZIDE- glipizide tablet
Northwind Pharmaceuticals
Glipizide
DESCRIPTION
Glipizide is an oral blood-glucose-lowering drug of the sulfonylurea class.
The Chemical Abstracts name of glipizide is 1-cyclohexyl-3-phenyl]sulfonyl]urea. The molecular formula is C21H27N5O4S; the molecular weight is 445.55.
Glipizide is a whitish, odorless powder with a pKa of 5.9. It is insoluble in water and alcohols, but soluble in 0.1 N NaOH; it is freely soluble in dimethylformamide. Glipizide tablets, USP for oral use are available in 5 and 10 mg strengths.
Inert ingredients are: anhydrous lactose; colloidal silicon dioxide; magnesium stearate; sodium starch glycolate.
Meets USP Dissolution Test 2.
CLINICAL PHARMACOLOGY
Mechanism of Action
The primary mode of action of glipizide in experimental animals appears to be the stimulation of insulin secretion from the beta cells of pancreatic islet tissue and is thus dependent on functioning beta cells in the pancreatic islets. In humans, glipizide appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which glipizide lowers blood glucose during long-term administration has not been clearly established. In man, stimulation of insulin secretion by glipizide in response to a meal is undoubtedly of major importance. Fasting insulin levels are not elevated even on long-term glipizide administration, but the postprandial insulin response continues to be enhanced after at least 6 months of treatment. The insulinotropic response to a meal occurs within 30 minutes after an oral dose of glipizide in diabetic patients, but elevated insulin levels do not persist beyond the time of the meal challenge. Extrapancreatic effects may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs.
Blood sugar control persists in some patients for up to 24 hours after a single dose of glipizide, even though plasma levels have declined to a small fraction of peak levels by that time (see Pharmacokinetics below).
Some patients fail to respond initially, or gradually lose their responsiveness to sulfonylurea drugs, including glipizide. Alternatively, glipizide may be effective in some patients who have not responded or have ceased to respond to other sulfonylureas.
Other Effects
It has been shown that glipizide therapy was effective in controlling blood sugar without deleterious changes in the plasma lipoprotein profiles of patients treated for NIDDM.
In a placebo-controlled, crossover study in normal volunteers, glipizide had no antidiuretic activity and, in fact, led to a slight increase in free water clearance.
Pharmacokinetics
Gastrointestinal absorption of glipizide in man is uniform, rapid, and essentially complete. Peak plasma concentrations occur 1 to 3 hours after a single oral dose. The half-life of elimination ranges from 2 to 4 hours in normal subjects, whether given intravenously or orally. The metabolic and excretory patterns are similar with the two routes of administration, indicating that first-pass metabolism is not significant. Glipizide does not accumulate in plasma on repeated oral administration. Total absorption and disposition of an oral dose was unaffected by food in normal volunteers, but absorption was delayed by about 40 minutes. Thus, glipizide was more effective when administered about 30 minutes before, rather than with, a test meal in diabetic patients. Protein binding was studied in serum from volunteers who received either oral or intravenous glipizide and found to be 98 to 99% one hour after either route of administration. The apparent volume of distribution of glipizide after intravenous administration was 11 liters, indicative of localization within the extracellular fluid compartment. In mice, no glipizide or metabolites were detectable autoradiographically in the brain or spinal cord of males or females, nor in the fetuses of pregnant females. In another study, however, very small amounts of radioactivity were detected in the fetuses of rats given labeled drug.
The metabolism of glipizide is extensive and occurs mainly in the liver. The primary metabolites are inactive hydroxylation products and polar conjugates and are excreted mainly in the urine. Less than 10% unchanged glipizide is found in the urine.
INDICATIONS & USAGE
Glipizide tablets, USP are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
CONTRAINDICATIONS
Glipizide is contraindicated in patients with:
1. Known hypersensitivity to the drug.
2. Type 1 diabetes mellitus, diabetic ketoacidosis, with or without coma. This condition should be treated with insulin.
WARNINGS
Special Warning On Increased Risk Of Cardiovascular Mortality
The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who were randomly assigned to one of four treatment groups (Diabetes, 19, supp. 2: 747-830, 1970). UGDP reported that patients treated for 5 to 8 years with diet plus a fixed dose of tolbutamide (1.5 grams per day) had a rate of cardiovascular mortality approximately 21/2 times that of patients treated with diet alone. A significant increase in total mortality was not observed, but the use of tolbutamide was discontinued based on the increase in cardiovascular mortality, thus limiting the opportunity for the study to show an increase in overall mortality. Despite controversy regarding the interpretation of these results, the findings of the UGDP study provide an adequate basis for this warning. The patient should be informed of the potential risks and advantages of glipizide and of alternative modes of therapy.
Although only one drug in the sulfonylurea class (tolbutamide) was included in this study, it is prudent from a safety standpoint to consider that this warning may also apply to other oral hypoglycemic drugs in this class, in view of their close similarities in mode of action and chemical structure.
PRECAUTIONS
General
Macrovascular Outcomes
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with glipizide or any other anti-diabetic drug.
Renal and Hepatic Disease
The metabolism and excretion of glipizide may be slowed in patients with impaired renal and/or hepatic function. If hypoglycemia should occur in such patients, it may be prolonged and appropriate management should be instituted.
Hypoglycemia
All sulfonylurea drugs are capable of producing severe hypoglycemia. Proper patient selection, dosage, and instructions are important to avoid hypoglycemic episodes. Renal or hepatic insufficiency may cause elevated blood levels of glipizide and the latter may also diminish gluconeogenic capacity, both of which increase the risk of serious hypoglycemic reactions. Elderly, debilitated or malnourished patients, and those with adrenal or pituitary insufficiency, are particularly susceptible to the hypoglycemic action of glucose-lowering drugs. Hypoglycemia may be difficult to recognize in the elderly, and in people who are taking beta-adrenergic blocking drugs. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when alcohol is ingested, or when more than one glucose-lowering drug is used.
Loss of Control of Blood Glucose
When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, a loss of control may occur. At such times, it may be necessary to discontinue glipizide and administer insulin.
The effectiveness of any oral hypoglycemic drug, including glipizide, in lowering blood glucose to a desired level decreases in many patients over a period of time, which may be due to progression of the severity of the diabetes or to diminished responsiveness to the drug. This phenomenon is known as secondary failure, to distinguish it from primary failure in which the drug is ineffective in an individual patient when first given.
Hemolytic Anemia
Treatment of patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency with sulfonylurea agents can lead to hemolytic anemia. Because glipizide belongs to the class of sulfonylurea agents, caution should be used in patients with G6PD deficiency and a non-sulfonylurea alternative should be considered. In post-marketing reports, hemolytic anemia has also been reported in patients who did not have known G6PD deficiency.
Laboratory Tests
Blood and urine glucose should be monitored periodically. Measurement of glycosylated hemoglobin may be useful.
Information for Patients
Patients should be informed of the potential risks and advantages of glipizide and of alternative modes of therapy. They should also be informed about the importance of adhering to dietary instructions, of a regular exercise program, and of regular testing of urine and/or blood glucose.
The risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members. Primary and secondary failure should also be explained.
Physician Counseling Information for Patients
In initiating treatment for type 2 diabetes, diet should be emphasized as the primary form of treatment. Caloric restriction and weight loss are essential in the obese diabetic patient. Proper dietary management alone may be effective in controlling the blood glucose and symptoms of hyperglycemia. The importance of regular physical activity should also be stressed, and cardiovascular risk factors should be identified and corrective measures taken where possible. Use of glipizide or other antidiabetic medications must be viewed by both the physician and patient as a treatment in addition to diet and not as a substitution or as a convenient mechanism for avoiding dietary restraint. Furthermore, loss of blood glucose control on diet alone may be transient, thus requiring only short-term administration of glipizide or other antidiabetic medications. Maintenance or discontinuation of glipizide or other antidiabetic medications should be based on clinical judgment using regular clinical and laboratory evaluations.
Drug Interactions
The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents, some azoles, and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta adrenergic blocking agents. When such drugs are administered to a patient receiving glipizide, the patient should be observed closely for hypoglycemia. When such drugs are withdrawn from a patient receiving glipizide, the patient should be observed closely for loss of control. In vitro binding studies with human serum proteins indicate that glipizide binds differently than tolbutamide and does not interact with salicylate or dicumarol. However, caution must be exercised in extrapolating these findings to the clinical situation and in the use of glipizide with these drugs.
Certain drugs tend to produce hyperglycemia and may lead to loss of control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving glipizide, the patient should be closely observed for loss of control. When such drugs are withdrawn from a patient receiving glipizide, the patient should be observed closely for hypoglycemia.
A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the intravenous, topical, or vaginal preparations of miconazole is not known. The effect of concomitant administration of fluconazole and glipizide has been demonstrated in a placebo-controlled crossover study in normal volunteers. All subjects received glipizide alone and following treatment with 100 mg of fluconazole as a single daily oral dose for 7 days. The mean percentage increase in the glipizide AUC after fluconazole administration was 56.9% (range: 35 to 81).
In studies assessing the effect of colesevelam on the pharmacokinetics of glipizide ER in healthy volunteers, reductions in glipizide AUC0-∞ and Cmax of 12% and 13%, respectively were observed when colesevelam was coadministered with glipizide ER. When glipizide ER was administered 4 hours prior to colesevelam, there was no significant change in glipizide AUC0-∞ or Cmax, -4% and 0%, respectively. Therefore, glipizide should be administered at least 4 hours prior to colesevelam to ensure that colesevelam does not reduce the absorption of glipizide.
Carcinogenesis, Mutagenesis, Impairment of Fertility
A twenty month study in rats and an eighteen month study in mice at doses up to 75 times the maximum human dose revealed no evidence of drug-related carcinogenicity. Bacterial and in vivo mutagenicity tests were uniformly negative. Studies in rats of both sexes at doses up to 75 times the human dose showed no effects on fertility.
Pregnancy
Pregnancy Category C
Glipizide was found to be mildly fetotoxic in rat reproductive studies at all dose levels (5 to 50 mg/kg). This fetotoxicity has been similarly noted with other sulfonylureas, such as tolbutamide and tolazamide. The effect is perinatal and believed to be directly related to the pharmacologic (hypoglycemic) action of glipizide. In studies in rats and rabbits, no teratogenic effects were found. There are no adequate and well controlled studies in pregnant women. Glipizide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Because recent information suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities, many experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible.
Nonteratogenic Effects
Prolonged severe hypoglycemia (4 to 10 days) has been reported in neonates born to mothers who were receiving a sulfonylurea drug at the time of delivery. This has been reported more frequently with the use of agents with prolonged half-lives. If glipizide is used during pregnancy, it should be discontinued at least one month before the expected delivery date.
Nursing Mothers
Although it is not known whether glipizide is excreted in human milk, some sulfonylurea drugs are known to be excreted in human milk. Because the potential for hypoglycemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. If the drug is discontinued and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.
Pediatric Use
Safety and effectiveness in children have not been established.
Geriatric Use
A determination has not been made whether controlled clinical studies of glipizide included sufficient numbers of subjects aged 65 and over to define a difference in response from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
ADVERSE REACTIONS
In U.S. and foreign controlled studies, the frequency of serious adverse reactions reported was very low. Of 702 patients, 11.8% reported adverse reactions and in only 1.5% was glipizide discontinued.
Hypoglycemia
See PRECAUTIONS and OVERDOSAGE sections.
Gastrointestinal
Gastrointestinal disturbances are the most common reactions. Gastrointestinal complaints were reported with the following approximate incidence: nausea and diarrhea, one in seventy; constipation and gastralgia, one in one hundred. They appear to be dose-related and may disappear on division or reduction of dosage. Cholestatic jaundice may occur rarely with sulfonylureas: glipizide should be discontinued if this occurs.
Dermatologic
Allergic skin reactions including erythema, morbilliform or maculopapular eruptions, urticaria, pruritus, and eczema have been reported in about one in seventy patients. These may be transient and may disappear despite continued use of glipizide; if skin reactions persist, the drug should be discontinued. Porphyria cutanea tarda and photosensitivity reactions have been reported with sulfonylureas.
Hematologic
Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia (see PRECAUTIONS), aplastic anemia, and pancytopenia have been reported with sulfonylureas.
Metabolic
Hepatic porphyria and disulfiram-like reactions have been reported with sulfonylureas. In the mouse, glipizide pretreatment did not cause an accumulation of acetaldehyde after ethanol administration. Clinical experience to date has shown that glipizide has an extremely low incidence of disulfiram-like alcohol reactions.
Endocrine Reactions
Cases of hyponatremia and the syndrome of inappropriate antidiuretic hormone (SIADH) secretion have been reported with this and other sulfonylureas.
Miscellaneous
Dizziness, drowsiness, and headache have each been reported in about one in fifty patients treated with glipizide. They are usually transient and seldom require discontinuance of therapy.
Laboratory Tests
The pattern of laboratory test abnormalities observed with glipizide was similar to that for other sulfonylureas. Occasional mild to moderate elevations of SGOT, LDH, alkaline phosphatase, BUN, and creatinine were noted. One case of jaundice was reported. The relationship of these abnormalities to glipizide is uncertain, and they have rarely been associated with clinical symptoms.
Post-Marketing Experience
The following adverse events have been reported in post-marketing surveillance:
Hepatobiliary
Cholestatic and hepatocellular forms of liver injury accompanied by jaundice have been reported rarely in association with glipizide; glipizide should be discontinued if this occurs.
OVERDOSAGE
There is no well documented experience with glipizide overdosage. The acute oral toxicity was extremely low in all species tested (LD50 greater than 4 g/kg).
Overdosage of sulfonylureas, including glipizide, can produce hypoglycemia. Mild hypoglycemic symptoms without loss of consciousness or neurologic findings should be treated aggressively with oral glucose and adjustments in drug dosage and/or meal patterns. Close monitoring should continue until the physician is assured that the patient is out of danger. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization. If hypoglycemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of concentrated (50%) glucose solution. This should be followed by a continuous infusion of a more dilute (10%) glucose solution at a rate that will maintain the blood glucose at a level above 100 mg/dL. Patients should be closely monitored for a minimum of 24 to 48 hours since hypoglycemia may recur after apparent clinical recovery. Clearance of glipizide from plasma would be prolonged in persons with liver disease. Because of the extensive protein binding of glipizide, dialysis is unlikely to be of benefit.
DOSAGE & ADMINISTRATION
There is no fixed dosage regimen for the management of diabetes mellitus with glipizide or any other hypoglycemic agent. In addition to the usual monitoring of urinary glucose, the patient's blood glucose must also be monitored periodically to determine the minimum effective dose for the patient; to detect primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication; and to detect secondary failure, i.e., loss of an adequate blood-glucose-lowering response after an initial period of effectiveness. Glycosylated hemoglobin levels may also be of value in monitoring the patient's response to therapy.
Short-term administration of glipizide may be sufficient during periods of transient loss of control in patients usually controlled well on diet.
In general, glipizide tablets should be given approximately 30 minutes before a meal to achieve the greatest reduction in postprandial hyperglycemia.
Initial Dose
The recommended starting dose is 5 mg, given before breakfast. Geriatric patients or those with liver disease may be started on 2.5 mg.
Titration
Dosage adjustments should ordinarily be in increments of 2.5 to 5 mg, as determined by blood glucose response. At least several days should elapse between titration steps. If response to a single dose is not satisfactory, dividing that dose may prove effective. The maximum recommended once daily dose is 15 mg. Doses above 15 mg should ordinarily be divided and given before meals of adequate caloric content. The maximum recommended total daily dose is 40 mg.
Maintenance
Some patients may be effectively controlled on a once-a-day regimen, while others show better response with divided dosing. Total daily doses above 15 mg should ordinarily be divided. Total daily doses above 30 mg have been safely given on a b.i.d. basis to long-term patients.
In elderly patients, debilitated or malnourished patients, and patients with impaired renal or hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycemic reactions (see PRECAUTIONS section).
Patients Receiving Insulin
As with other sulfonylurea-class hypoglycemics, many stable non-insulin-dependent diabetic patients receiving insulin may be safely placed on glipizide. When transferring patients from insulin to glipizide, the following general guidelines should be considered:
For patients whose daily insulin requirement is 20 units or less, insulin may be discontinued and glipizide therapy may begin at usual dosages. Several days should elapse between glipizide titration steps.
For patients whose daily insulin requirement is greater than 20 units, the insulin dose should be reduced by 50% and glipizide therapy may begin at usual dosages. Subsequent reductions in insulin dosage should depend on individual patient response. Several days should elapse between glipizide titration steps.
During the insulin withdrawal period, the patient should test urine samples for sugar and ketone bodies at least three times daily. Patients should be instructed to contact the prescriber immediately if these tests are abnormal. In some cases, especially when patient has been receiving greater than 40 units of insulin daily, it may be advisable to consider hospitalization during the transition period.
Patients Receiving Other Oral Hypoglycemic Agents
As with other sulfonylurea-class hypoglycemics, no transition period is necessary when transferring patients to glipizide. Patients should be observed carefully (1 to 2 weeks) for hypoglycemia when being transferred from longer half-life sulfonylureas (e.g., chlorpropamide) to glipizide due to potential overlapping of drug effect.
When colesevelam is coadministered with glipizide ER, maximum plasma concentration and total exposure to glipizide is reduced. Therefore, glipizide should be administered at least 4 hours prior to colesevelam. | Sandbox g06
GLIPIZIDE- glipizide tablet
Northwind Pharmaceuticals
Glipizide
DESCRIPTION
Glipizide is an oral blood-glucose-lowering drug of the sulfonylurea class.
The Chemical Abstracts name of glipizide is 1-cyclohexyl-3-[[p-[2-(5-methylpyrazine-carboxamido)ethyl]phenyl]sulfonyl]urea. The molecular formula is C21H27N5O4S; the molecular weight is 445.55.
Glipizide is a whitish, odorless powder with a pKa of 5.9. It is insoluble in water and alcohols, but soluble in 0.1 N NaOH; it is freely soluble in dimethylformamide. Glipizide tablets, USP for oral use are available in 5 and 10 mg strengths.
Inert ingredients are: anhydrous lactose; colloidal silicon dioxide; magnesium stearate; sodium starch glycolate.
Meets USP Dissolution Test 2.
CLINICAL PHARMACOLOGY
Mechanism of Action
The primary mode of action of glipizide in experimental animals appears to be the stimulation of insulin secretion from the beta cells of pancreatic islet tissue and is thus dependent on functioning beta cells in the pancreatic islets. In humans, glipizide appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which glipizide lowers blood glucose during long-term administration has not been clearly established. In man, stimulation of insulin secretion by glipizide in response to a meal is undoubtedly of major importance. Fasting insulin levels are not elevated even on long-term glipizide administration, but the postprandial insulin response continues to be enhanced after at least 6 months of treatment. The insulinotropic response to a meal occurs within 30 minutes after an oral dose of glipizide in diabetic patients, but elevated insulin levels do not persist beyond the time of the meal challenge. Extrapancreatic effects may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs.
Blood sugar control persists in some patients for up to 24 hours after a single dose of glipizide, even though plasma levels have declined to a small fraction of peak levels by that time (see Pharmacokinetics below).
Some patients fail to respond initially, or gradually lose their responsiveness to sulfonylurea drugs, including glipizide. Alternatively, glipizide may be effective in some patients who have not responded or have ceased to respond to other sulfonylureas.
Other Effects
It has been shown that glipizide therapy was effective in controlling blood sugar without deleterious changes in the plasma lipoprotein profiles of patients treated for NIDDM.
In a placebo-controlled, crossover study in normal volunteers, glipizide had no antidiuretic activity and, in fact, led to a slight increase in free water clearance.
Pharmacokinetics
Gastrointestinal absorption of glipizide in man is uniform, rapid, and essentially complete. Peak plasma concentrations occur 1 to 3 hours after a single oral dose. The half-life of elimination ranges from 2 to 4 hours in normal subjects, whether given intravenously or orally. The metabolic and excretory patterns are similar with the two routes of administration, indicating that first-pass metabolism is not significant. Glipizide does not accumulate in plasma on repeated oral administration. Total absorption and disposition of an oral dose was unaffected by food in normal volunteers, but absorption was delayed by about 40 minutes. Thus, glipizide was more effective when administered about 30 minutes before, rather than with, a test meal in diabetic patients. Protein binding was studied in serum from volunteers who received either oral or intravenous glipizide and found to be 98 to 99% one hour after either route of administration. The apparent volume of distribution of glipizide after intravenous administration was 11 liters, indicative of localization within the extracellular fluid compartment. In mice, no glipizide or metabolites were detectable autoradiographically in the brain or spinal cord of males or females, nor in the fetuses of pregnant females. In another study, however, very small amounts of radioactivity were detected in the fetuses of rats given labeled drug.
The metabolism of glipizide is extensive and occurs mainly in the liver. The primary metabolites are inactive hydroxylation products and polar conjugates and are excreted mainly in the urine. Less than 10% unchanged glipizide is found in the urine.
INDICATIONS & USAGE
Glipizide tablets, USP are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
CONTRAINDICATIONS
Glipizide is contraindicated in patients with:
1. Known hypersensitivity to the drug.
2. Type 1 diabetes mellitus, diabetic ketoacidosis, with or without coma. This condition should be treated with insulin.
WARNINGS
Special Warning On Increased Risk Of Cardiovascular Mortality
The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who were randomly assigned to one of four treatment groups (Diabetes, 19, supp. 2: 747-830, 1970). UGDP reported that patients treated for 5 to 8 years with diet plus a fixed dose of tolbutamide (1.5 grams per day) had a rate of cardiovascular mortality approximately 21/2 times that of patients treated with diet alone. A significant increase in total mortality was not observed, but the use of tolbutamide was discontinued based on the increase in cardiovascular mortality, thus limiting the opportunity for the study to show an increase in overall mortality. Despite controversy regarding the interpretation of these results, the findings of the UGDP study provide an adequate basis for this warning. The patient should be informed of the potential risks and advantages of glipizide and of alternative modes of therapy.
Although only one drug in the sulfonylurea class (tolbutamide) was included in this study, it is prudent from a safety standpoint to consider that this warning may also apply to other oral hypoglycemic drugs in this class, in view of their close similarities in mode of action and chemical structure.
PRECAUTIONS
General
Macrovascular Outcomes
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with glipizide or any other anti-diabetic drug.
Renal and Hepatic Disease
The metabolism and excretion of glipizide may be slowed in patients with impaired renal and/or hepatic function. If hypoglycemia should occur in such patients, it may be prolonged and appropriate management should be instituted.
Hypoglycemia
All sulfonylurea drugs are capable of producing severe hypoglycemia. Proper patient selection, dosage, and instructions are important to avoid hypoglycemic episodes. Renal or hepatic insufficiency may cause elevated blood levels of glipizide and the latter may also diminish gluconeogenic capacity, both of which increase the risk of serious hypoglycemic reactions. Elderly, debilitated or malnourished patients, and those with adrenal or pituitary insufficiency, are particularly susceptible to the hypoglycemic action of glucose-lowering drugs. Hypoglycemia may be difficult to recognize in the elderly, and in people who are taking beta-adrenergic blocking drugs. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when alcohol is ingested, or when more than one glucose-lowering drug is used.
Loss of Control of Blood Glucose
When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, a loss of control may occur. At such times, it may be necessary to discontinue glipizide and administer insulin.
The effectiveness of any oral hypoglycemic drug, including glipizide, in lowering blood glucose to a desired level decreases in many patients over a period of time, which may be due to progression of the severity of the diabetes or to diminished responsiveness to the drug. This phenomenon is known as secondary failure, to distinguish it from primary failure in which the drug is ineffective in an individual patient when first given.
Hemolytic Anemia
Treatment of patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency with sulfonylurea agents can lead to hemolytic anemia. Because glipizide belongs to the class of sulfonylurea agents, caution should be used in patients with G6PD deficiency and a non-sulfonylurea alternative should be considered. In post-marketing reports, hemolytic anemia has also been reported in patients who did not have known G6PD deficiency.
Laboratory Tests
Blood and urine glucose should be monitored periodically. Measurement of glycosylated hemoglobin may be useful.
Information for Patients
Patients should be informed of the potential risks and advantages of glipizide and of alternative modes of therapy. They should also be informed about the importance of adhering to dietary instructions, of a regular exercise program, and of regular testing of urine and/or blood glucose.
The risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members. Primary and secondary failure should also be explained.
Physician Counseling Information for Patients
In initiating treatment for type 2 diabetes, diet should be emphasized as the primary form of treatment. Caloric restriction and weight loss are essential in the obese diabetic patient. Proper dietary management alone may be effective in controlling the blood glucose and symptoms of hyperglycemia. The importance of regular physical activity should also be stressed, and cardiovascular risk factors should be identified and corrective measures taken where possible. Use of glipizide or other antidiabetic medications must be viewed by both the physician and patient as a treatment in addition to diet and not as a substitution or as a convenient mechanism for avoiding dietary restraint. Furthermore, loss of blood glucose control on diet alone may be transient, thus requiring only short-term administration of glipizide or other antidiabetic medications. Maintenance or discontinuation of glipizide or other antidiabetic medications should be based on clinical judgment using regular clinical and laboratory evaluations.
Drug Interactions
The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents, some azoles, and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta adrenergic blocking agents. When such drugs are administered to a patient receiving glipizide, the patient should be observed closely for hypoglycemia. When such drugs are withdrawn from a patient receiving glipizide, the patient should be observed closely for loss of control. In vitro binding studies with human serum proteins indicate that glipizide binds differently than tolbutamide and does not interact with salicylate or dicumarol. However, caution must be exercised in extrapolating these findings to the clinical situation and in the use of glipizide with these drugs.
Certain drugs tend to produce hyperglycemia and may lead to loss of control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving glipizide, the patient should be closely observed for loss of control. When such drugs are withdrawn from a patient receiving glipizide, the patient should be observed closely for hypoglycemia.
A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the intravenous, topical, or vaginal preparations of miconazole is not known. The effect of concomitant administration of fluconazole and glipizide has been demonstrated in a placebo-controlled crossover study in normal volunteers. All subjects received glipizide alone and following treatment with 100 mg of fluconazole as a single daily oral dose for 7 days. The mean percentage increase in the glipizide AUC after fluconazole administration was 56.9% (range: 35 to 81).
In studies assessing the effect of colesevelam on the pharmacokinetics of glipizide ER in healthy volunteers, reductions in glipizide AUC0-∞ and Cmax of 12% and 13%, respectively were observed when colesevelam was coadministered with glipizide ER. When glipizide ER was administered 4 hours prior to colesevelam, there was no significant change in glipizide AUC0-∞ or Cmax, -4% and 0%, respectively. Therefore, glipizide should be administered at least 4 hours prior to colesevelam to ensure that colesevelam does not reduce the absorption of glipizide.
Carcinogenesis, Mutagenesis, Impairment of Fertility
A twenty month study in rats and an eighteen month study in mice at doses up to 75 times the maximum human dose revealed no evidence of drug-related carcinogenicity. Bacterial and in vivo mutagenicity tests were uniformly negative. Studies in rats of both sexes at doses up to 75 times the human dose showed no effects on fertility.
Pregnancy
Pregnancy Category C
Glipizide was found to be mildly fetotoxic in rat reproductive studies at all dose levels (5 to 50 mg/kg). This fetotoxicity has been similarly noted with other sulfonylureas, such as tolbutamide and tolazamide. The effect is perinatal and believed to be directly related to the pharmacologic (hypoglycemic) action of glipizide. In studies in rats and rabbits, no teratogenic effects were found. There are no adequate and well controlled studies in pregnant women. Glipizide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Because recent information suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities, many experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible.
Nonteratogenic Effects
Prolonged severe hypoglycemia (4 to 10 days) has been reported in neonates born to mothers who were receiving a sulfonylurea drug at the time of delivery. This has been reported more frequently with the use of agents with prolonged half-lives. If glipizide is used during pregnancy, it should be discontinued at least one month before the expected delivery date.
Nursing Mothers
Although it is not known whether glipizide is excreted in human milk, some sulfonylurea drugs are known to be excreted in human milk. Because the potential for hypoglycemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. If the drug is discontinued and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.
Pediatric Use
Safety and effectiveness in children have not been established.
Geriatric Use
A determination has not been made whether controlled clinical studies of glipizide included sufficient numbers of subjects aged 65 and over to define a difference in response from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
ADVERSE REACTIONS
In U.S. and foreign controlled studies, the frequency of serious adverse reactions reported was very low. Of 702 patients, 11.8% reported adverse reactions and in only 1.5% was glipizide discontinued.
Hypoglycemia
See PRECAUTIONS and OVERDOSAGE sections.
Gastrointestinal
Gastrointestinal disturbances are the most common reactions. Gastrointestinal complaints were reported with the following approximate incidence: nausea and diarrhea, one in seventy; constipation and gastralgia, one in one hundred. They appear to be dose-related and may disappear on division or reduction of dosage. Cholestatic jaundice may occur rarely with sulfonylureas: glipizide should be discontinued if this occurs.
Dermatologic
Allergic skin reactions including erythema, morbilliform or maculopapular eruptions, urticaria, pruritus, and eczema have been reported in about one in seventy patients. These may be transient and may disappear despite continued use of glipizide; if skin reactions persist, the drug should be discontinued. Porphyria cutanea tarda and photosensitivity reactions have been reported with sulfonylureas.
Hematologic
Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia (see PRECAUTIONS), aplastic anemia, and pancytopenia have been reported with sulfonylureas.
Metabolic
Hepatic porphyria and disulfiram-like reactions have been reported with sulfonylureas. In the mouse, glipizide pretreatment did not cause an accumulation of acetaldehyde after ethanol administration. Clinical experience to date has shown that glipizide has an extremely low incidence of disulfiram-like alcohol reactions.
Endocrine Reactions
Cases of hyponatremia and the syndrome of inappropriate antidiuretic hormone (SIADH) secretion have been reported with this and other sulfonylureas.
Miscellaneous
Dizziness, drowsiness, and headache have each been reported in about one in fifty patients treated with glipizide. They are usually transient and seldom require discontinuance of therapy.
Laboratory Tests
The pattern of laboratory test abnormalities observed with glipizide was similar to that for other sulfonylureas. Occasional mild to moderate elevations of SGOT, LDH, alkaline phosphatase, BUN, and creatinine were noted. One case of jaundice was reported. The relationship of these abnormalities to glipizide is uncertain, and they have rarely been associated with clinical symptoms.
Post-Marketing Experience
The following adverse events have been reported in post-marketing surveillance:
Hepatobiliary
Cholestatic and hepatocellular forms of liver injury accompanied by jaundice have been reported rarely in association with glipizide; glipizide should be discontinued if this occurs.
OVERDOSAGE
There is no well documented experience with glipizide overdosage. The acute oral toxicity was extremely low in all species tested (LD50 greater than 4 g/kg).
Overdosage of sulfonylureas, including glipizide, can produce hypoglycemia. Mild hypoglycemic symptoms without loss of consciousness or neurologic findings should be treated aggressively with oral glucose and adjustments in drug dosage and/or meal patterns. Close monitoring should continue until the physician is assured that the patient is out of danger. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization. If hypoglycemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of concentrated (50%) glucose solution. This should be followed by a continuous infusion of a more dilute (10%) glucose solution at a rate that will maintain the blood glucose at a level above 100 mg/dL. Patients should be closely monitored for a minimum of 24 to 48 hours since hypoglycemia may recur after apparent clinical recovery. Clearance of glipizide from plasma would be prolonged in persons with liver disease. Because of the extensive protein binding of glipizide, dialysis is unlikely to be of benefit.
DOSAGE & ADMINISTRATION
There is no fixed dosage regimen for the management of diabetes mellitus with glipizide or any other hypoglycemic agent. In addition to the usual monitoring of urinary glucose, the patient's blood glucose must also be monitored periodically to determine the minimum effective dose for the patient; to detect primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication; and to detect secondary failure, i.e., loss of an adequate blood-glucose-lowering response after an initial period of effectiveness. Glycosylated hemoglobin levels may also be of value in monitoring the patient's response to therapy.
Short-term administration of glipizide may be sufficient during periods of transient loss of control in patients usually controlled well on diet.
In general, glipizide tablets should be given approximately 30 minutes before a meal to achieve the greatest reduction in postprandial hyperglycemia.
Initial Dose
The recommended starting dose is 5 mg, given before breakfast. Geriatric patients or those with liver disease may be started on 2.5 mg.
Titration
Dosage adjustments should ordinarily be in increments of 2.5 to 5 mg, as determined by blood glucose response. At least several days should elapse between titration steps. If response to a single dose is not satisfactory, dividing that dose may prove effective. The maximum recommended once daily dose is 15 mg. Doses above 15 mg should ordinarily be divided and given before meals of adequate caloric content. The maximum recommended total daily dose is 40 mg.
Maintenance
Some patients may be effectively controlled on a once-a-day regimen, while others show better response with divided dosing. Total daily doses above 15 mg should ordinarily be divided. Total daily doses above 30 mg have been safely given on a b.i.d. basis to long-term patients.
In elderly patients, debilitated or malnourished patients, and patients with impaired renal or hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycemic reactions (see PRECAUTIONS section).
Patients Receiving Insulin
As with other sulfonylurea-class hypoglycemics, many stable non-insulin-dependent diabetic patients receiving insulin may be safely placed on glipizide. When transferring patients from insulin to glipizide, the following general guidelines should be considered:
For patients whose daily insulin requirement is 20 units or less, insulin may be discontinued and glipizide therapy may begin at usual dosages. Several days should elapse between glipizide titration steps.
For patients whose daily insulin requirement is greater than 20 units, the insulin dose should be reduced by 50% and glipizide therapy may begin at usual dosages. Subsequent reductions in insulin dosage should depend on individual patient response. Several days should elapse between glipizide titration steps.
During the insulin withdrawal period, the patient should test urine samples for sugar and ketone bodies at least three times daily. Patients should be instructed to contact the prescriber immediately if these tests are abnormal. In some cases, especially when patient has been receiving greater than 40 units of insulin daily, it may be advisable to consider hospitalization during the transition period.
Patients Receiving Other Oral Hypoglycemic Agents
As with other sulfonylurea-class hypoglycemics, no transition period is necessary when transferring patients to glipizide. Patients should be observed carefully (1 to 2 weeks) for hypoglycemia when being transferred from longer half-life sulfonylureas (e.g., chlorpropamide) to glipizide due to potential overlapping of drug effect.
When colesevelam is coadministered with glipizide ER, maximum plasma concentration and total exposure to glipizide is reduced. Therefore, glipizide should be administered at least 4 hours prior to colesevelam. | https://www.wikidoc.org/index.php/Sandbox_g06 | |
509165cdccfecf35aa4b6737de7881b250bde6ca | wikidoc | Sandbox g07 | Sandbox g07
ACETAZOLAMIDE- acetazolamide tablet
Taro Pharmaceuticals U.S.A., Inc.
# AcetaZOLAMIDE Tablets USP
Rx only
# DESCRIPTION
Acetazolamide, an inhibitor of the enzyme carbonic anhydrase, is a white to faintly yellowish white crystalline, odorless powder, weakly acidic, very slightly soluble in water and slightly soluble in alcohol. The chemical name for acetazolamide is N-(5-Sulfamoyl-1,3,4-thiadiazol-2-yl)-acetamide and has the following chemical structure:
Chemical Structure
Molecular Weight: 222.25
Molecular Formula: C4H6N4O3S2
Acetazolamide is available as oral tablets containing 125 mg and 250 mg of acetazolamide, respectively, and the following inactive ingredients: corn starch, gelatin, glycerin, lactose monohydrate, magnesium stearate, purified water, sodium starch glycolate and talc.
# CLINICAL PHARMACOLOGY
Acetazolamide is a potent carbonic anhydrase inhibitor, effective in the control of fluid secretion (e.g., some types of glaucoma), in the treatment of certain convulsive disorders (e.g., epilepsy), and in the promotion of diuresis in instances of abnormal fluid retention (e.g., cardiac edema).
Acetazolamide is not a mercurial diuretic. Rather, it is a nonbacteriostatic sulfonamide possessing a chemical structure and pharmacological activity distinctly different from the bacteriostatic sulfonamides.
Acetazolamide is an enzyme inhibitor that acts specifically on carbonic anhydrase, the enzyme that catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In the eye, this inhibitory action of acetazolamide decreases the secretion of aqueous humor and results in a drop in intraocular pressure, a reaction considered desirable in cases of glaucoma and even in certain nonglaucomatous conditions. Evidence seems to indicate that acetazolamide has utility as an adjuvant in the treatment of certain dysfunctions of the central nervous system (e.g., epilepsy). Inhibition of carbonic anhydrase in this area appears to retard abnormal, paroxysmal, excessive discharge from central nervous system neurons. The diuretic effect of acetazolamide is due to its action in the kidney on the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. The result is renal loss of HCO3 ion, which carries out sodium, water, and potassium. Alkalinization of the urine and promotion of diuresis are thus affected. Alteration in ammonia metabolism occurs due to increased reabsorption of ammonia by the renal tubules as a result of urinary alkalinization.
Placebo-controlled clinical trials have shown that prophylactic administration of acetazolamide at a dose of 250 mg every eight to 12 hours (or a 500 mg controlled-release capsule once daily) before and during rapid ascent to altitude results in fewer and/or less severe symptoms (such as headache, nausea, shortness of breath, dizziness, drowsiness, and fatigue) of acute mountain sickness (AMS). Pulmonary function (e.g., minute ventilation, expired vital capacity and peak flow) is greater in the acetazolamide treated group, both in subjects with AMS and asymptomatic subjects. The acetazolamide treated climbers also had less difficulty in sleeping.
# INDICATIONS AND USAGE
For adjunctive treatment of: edema due to congestive heart failure; drug-induced edema; centrencephalic epilepsies (petit mal, unlocalized seizures); chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired in order to lower intraocular pressure. Acetazolamide Tablets are also indicated for the prevention or amelioration of symptoms associated with acute mountain sickness in climbers attempting rapid ascent and in those who are very susceptible to acute mountain sickness despite gradual ascent.
# CONTRAINDICATIONS
Acetazolamide therapy is contraindicated in situations in which sodium and/or potassium blood serum levels are depressed, in cases of marked kidney and liver disease or dysfunction, in suprarenal gland failure, and in hyperchloremic acidosis. It is contraindicated in patients with cirrhosis because of the risk of development of hepatic encephalopathy.
Long-term administration of acetazolamide is contraindicated in patients with chronic non-congestive angle-closure glaucoma since it may permit organic closure of the angle to occur while the worsening glaucoma is masked by lowered intraocular pressure.
# WARNINGS
Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Sensitizations may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of hypersensitivity or other serious reactions occur, discontinue use of this drug.
Caution is advised for patients receiving concomitant high-dose aspirin and acetazolamide, as anorexia, tachypnea, lethargy, coma and death have been reported.
# PRECAUTIONS
# General
Increasing the dose does not increase the diuresis and may increase the incidence of drowsiness and/or paresthesia. Increasing the dose often results in a decrease in diuresis. Under certain circumstances, however, very large doses have been given in conjunction with other diuretics in order to secure diuresis in complete refractory failure.
# Information for Patients
Adverse reactions common to all sulfonamide derivatives may occur: anaphylaxis, fever, rash (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), crystalluria, renal calculus, bone marrow depression, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia and agranulocytosis. Precaution is advised for early detection of such reactions and the drug should be discontinued and appropriate therapy instituted.
In patients with pulmonary obstruction or emphysema where alveolar ventilation may be impaired, acetazolamide, which may precipitate or aggravate acidosis, should be used with caution.
Gradual ascent is desirable to try to avoid acute mountain sickness. If rapid ascent is undertaken and acetazolamide tablets are used, it should be noted that such use does not obviate the need for prompt descent if severe forms of high altitude sickness occur, i.e., high altitude pulmonary edema (HAPE) or high altitude cerebral edema.
Caution is advised for patients receiving concomitant high-dose aspirin and acetazolamide, as anorexia, tachypnea, lethargy, coma and death have been reported (see WARNINGS).
# Laboratory Tests
To monitor for hematologic reactions common to all sulfonamides, it is recommended that a baseline CBC and platelet count be obtained on patients prior to initiating acetazolamide tablet therapy and at regular intervals during therapy. If significant changes occur, early discontinuance and institution of appropriate therapy are important. Periodic monitoring of serum electrolytes is recommended.
# Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals to evaluate the carcinogenic potential of acetazolamide have not been conducted. In a bacterial mutagenicity assay, acetazolamide was not mutagenic when evaluated with and without metabolic activation.
The drug had no effect on fertility when administered in the diet to male and female rats at a daily intake of up to 4 times the recommended human dose of 1000 mg in a 50 kg individual.
# Pregnancy
## Teratogenic Effect
### Pregnancy Category C
Acetazolamide, administered orally or parenterally, has been shown to be teratogenic (defects of the limbs) in mice, rats, hamsters and rabbits. There are no adequate and well-controlled studies in pregnant women. Acetazolamide should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.
# Nursing Mothers
Because of the potential for serious adverse reaction in nursing infants from acetazolamide, a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.
# Pediatric Use
The safety and effectiveness of acetazolamide in pediatric patients has not been established.
# ADVERSE REACTIONS
Adverse reactions, occurring most often early in therapy, include paresthesias, particularly a "tingling" feeling in the extremities, hearing dysfunction or tinnitus, loss of appetite, taste alteration and gastrointestinal disturbances such as nausea, vomiting and diarrhea, polyuria, and occasional instances of drowsiness and confusion.
Metabolic acidosis and electrolyte imbalance may occur.
Transient myopia has been reported. This condition invariably subsides upon diminution or discontinuance of the medication.
Other occasional adverse reactions include urticaria, melena, hematuria, glycosuria, hepatic insufficiency, flaccid paralysis, photosensitivity and convulsions. Also see PRECAUTIONS: Information for Patients for possible reactions common to sulfonamide derivatives. Fatalities have occurred although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias (see WARNINGS).
# OVERDOSAGE
No data are available regarding acetazolamide overdosage in humans as no cases of acute poisoning with this drug have been reported. Animal data suggest that acetazolamide is remarkably nontoxic. No specific antidote is known. Treatment should be symptomatic and supportive.
Electrolyte imbalance, development of an acidotic state, and central nervous effects might be expected to occur. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored.
Supportive measures are required to restore electrolyte and pH balance. The acidotic state can usually be corrected by the administration of bicarbonate.
Despite its high intraerythrocytic distribution and plasma protein binding properties, acetazolamide may be dialyzable. This may be particularly important in the management of acetazolamide overdosage when complicated by the presence of renal failure.
# DOSAGE AND ADMINISTRATION
# Glaucoma
Acetazolamide should be used as an adjunct to the usual therapy. The dosage employed in the treatment of chronic simple (open-angle) glaucoma ranges from 250 mg to 1 g of acetazolamide per 24 hours, usually in divided doses for amounts over 250 mg. It has usually been found that a dosage in excess of 1 g per 24 hours does not produce an increased effect. In all cases, the dosage should be adjusted with careful individual attention both to symptomatology and ocular tension. Continuous supervision by a physician is advisable.
In treatment of secondary glaucoma and in the preoperative treatment of some cases of acute congestive (closed-angle) glaucoma, the preferred dosage is 250 mg every four hours, although some cases have responded to 250 mg twice daily on short-term therapy. In some acute cases, it may be more satisfactory to administer an initial dose of 500 mg followed by 125 mg or 250 mg every four hours depending on the individual case. A complementary effect has been noted when acetazolamide has been used in conjunction with miotics or mydriatics as the case demanded.
# Epilepsy
It is not clearly known whether the beneficial effects observed in epilepsy are due to direct inhibition of carbonic anhydrase in the central nervous system or whether they are due to the slight degree of acidosis produced by the divided dosage. The best results to date have been seen in petit mal in children. Good results, however, have been seen in patients, both children and adult, in other types of seizures such as grand mal, mixed seizure patterns, myoclonic jerk patterns, etc. The suggested total daily dose is 8 to 30 mg per kg in divided doses. Although some patients respond to a low dose, the optimum range appears to be from 375 to 1000 mg daily. However, some investigators feel that daily doses in excess of 1 g do not produce any better results than a 1 g dose. When acetazolamide tablets are given in combination with other anticonvulsants, it is suggested that the starting dose should be 250 mg once daily in addition to the existing medications. This can be increased to levels as indicated above.
The change from other medications to acetazolamide should be gradual and in accordance with usual practice in epilepsy therapy.
# Congestive Heart Failure
For diuresis in congestive heart failure, the starting dose is usually 250 to 375 mg once daily in the morning (5 mg/kg). If, after an initial response, the patient fails to continue to lose edema fluid, do not increase the dose but allow for kidney recovery by skipping medication for a day.
Acetazolamide tablets yield best diuretic results when given on alternate days, or for two days alternating with a day of rest.
Failures in therapy may be due to overdosage or too frequent dosage. The use of acetazolamide does not eliminate the need for other therapy such as digitalis, bed rest, and salt restriction.
# Drug-Induced Edema
Recommended dosage is 250 to 375 mg of acetazolamide once a day for one or two days, alternating with a day of rest.
# Acute Mountain Sickness
Dosage is 500 mg to 1000 mg daily, in divided doses. In circumstances of rapid ascent, such as in rescue or military operations, the higher dose level of 1000 mg is recommended. It is preferable to initiate dosing 24 to 48 hours before ascent and to continue for 48 hours while at high altitude, or longer as necessary to control symptoms.
Note: The dosage recommendations for glaucoma and epilepsy differ considerably from those for congestive heart failure, since the first two conditions are not dependent upon carbonic anhydrase inhibition in the kidney which requires intermittent dosage if it is to recover from the inhibitory effect of the therapeutic agent.
# HOW SUPPLIED
Acetazolamide Tablets USP are supplied as follows:
125 mg - White, round, scored in half, on one side, "T52" engraved on the other side.
NDC 51672-4022-1 - Bottle of 100
250 mg - White, round, scored in quarters, on one side, "T53" engraved on the other side.
NDC 51672-4023-1 - Bottle of 100
Store at 20° to 25°C (68° to 77°F) .
Mfd. by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel 26110
Dist. by: Taro Pharmaceuticals U.S.A., Inc. , Hawthorne, NY 10532
Revised: November, 2013 79429-1113-2
# PRINCIPAL DISPLAY PANEL - 125 mg Tablet Bottle Label
NDC 51672-4022-1
100 Tablets
AcetaZOLAMIDE
Tablets USP,
125 mg
TARO
Rx only
# PRINCIPAL DISPLAY PANEL - 250 mg Tablet Bottle Label
NDC 51672-4023-1
100 Tablets
AcetaZOLAMIDE
Tablets USP,
250 mg
TARO
Rx only | Sandbox g07
ACETAZOLAMIDE- acetazolamide tablet
Taro Pharmaceuticals U.S.A., Inc.
# AcetaZOLAMIDE Tablets USP
Rx only
# DESCRIPTION
Acetazolamide, an inhibitor of the enzyme carbonic anhydrase, is a white to faintly yellowish white crystalline, odorless powder, weakly acidic, very slightly soluble in water and slightly soluble in alcohol. The chemical name for acetazolamide is N-(5-Sulfamoyl-1,3,4-thiadiazol-2-yl)-acetamide and has the following chemical structure:
Chemical Structure
Molecular Weight: 222.25
Molecular Formula: C4H6N4O3S2
Acetazolamide is available as oral tablets containing 125 mg and 250 mg of acetazolamide, respectively, and the following inactive ingredients: corn starch, gelatin, glycerin, lactose monohydrate, magnesium stearate, purified water, sodium starch glycolate and talc.
# CLINICAL PHARMACOLOGY
Acetazolamide is a potent carbonic anhydrase inhibitor, effective in the control of fluid secretion (e.g., some types of glaucoma), in the treatment of certain convulsive disorders (e.g., epilepsy), and in the promotion of diuresis in instances of abnormal fluid retention (e.g., cardiac edema).
Acetazolamide is not a mercurial diuretic. Rather, it is a nonbacteriostatic sulfonamide possessing a chemical structure and pharmacological activity distinctly different from the bacteriostatic sulfonamides.
Acetazolamide is an enzyme inhibitor that acts specifically on carbonic anhydrase, the enzyme that catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In the eye, this inhibitory action of acetazolamide decreases the secretion of aqueous humor and results in a drop in intraocular pressure, a reaction considered desirable in cases of glaucoma and even in certain nonglaucomatous conditions. Evidence seems to indicate that acetazolamide has utility as an adjuvant in the treatment of certain dysfunctions of the central nervous system (e.g., epilepsy). Inhibition of carbonic anhydrase in this area appears to retard abnormal, paroxysmal, excessive discharge from central nervous system neurons. The diuretic effect of acetazolamide is due to its action in the kidney on the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. The result is renal loss of HCO3 ion, which carries out sodium, water, and potassium. Alkalinization of the urine and promotion of diuresis are thus affected. Alteration in ammonia metabolism occurs due to increased reabsorption of ammonia by the renal tubules as a result of urinary alkalinization.
Placebo-controlled clinical trials have shown that prophylactic administration of acetazolamide at a dose of 250 mg every eight to 12 hours (or a 500 mg controlled-release capsule once daily) before and during rapid ascent to altitude results in fewer and/or less severe symptoms (such as headache, nausea, shortness of breath, dizziness, drowsiness, and fatigue) of acute mountain sickness (AMS). Pulmonary function (e.g., minute ventilation, expired vital capacity and peak flow) is greater in the acetazolamide treated group, both in subjects with AMS and asymptomatic subjects. The acetazolamide treated climbers also had less difficulty in sleeping.
# INDICATIONS AND USAGE
For adjunctive treatment of: edema due to congestive heart failure; drug-induced edema; centrencephalic epilepsies (petit mal, unlocalized seizures); chronic simple (open-angle) glaucoma, secondary glaucoma, and preoperatively in acute angle-closure glaucoma where delay of surgery is desired in order to lower intraocular pressure. Acetazolamide Tablets are also indicated for the prevention or amelioration of symptoms associated with acute mountain sickness in climbers attempting rapid ascent and in those who are very susceptible to acute mountain sickness despite gradual ascent.
# CONTRAINDICATIONS
Acetazolamide therapy is contraindicated in situations in which sodium and/or potassium blood serum levels are depressed, in cases of marked kidney and liver disease or dysfunction, in suprarenal gland failure, and in hyperchloremic acidosis. It is contraindicated in patients with cirrhosis because of the risk of development of hepatic encephalopathy.
Long-term administration of acetazolamide is contraindicated in patients with chronic non-congestive angle-closure glaucoma since it may permit organic closure of the angle to occur while the worsening glaucoma is masked by lowered intraocular pressure.
# WARNINGS
Fatalities have occurred, although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Sensitizations may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of hypersensitivity or other serious reactions occur, discontinue use of this drug.
Caution is advised for patients receiving concomitant high-dose aspirin and acetazolamide, as anorexia, tachypnea, lethargy, coma and death have been reported.
# PRECAUTIONS
# General
Increasing the dose does not increase the diuresis and may increase the incidence of drowsiness and/or paresthesia. Increasing the dose often results in a decrease in diuresis. Under certain circumstances, however, very large doses have been given in conjunction with other diuretics in order to secure diuresis in complete refractory failure.
# Information for Patients
Adverse reactions common to all sulfonamide derivatives may occur: anaphylaxis, fever, rash (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), crystalluria, renal calculus, bone marrow depression, thrombocytopenic purpura, hemolytic anemia, leukopenia, pancytopenia and agranulocytosis. Precaution is advised for early detection of such reactions and the drug should be discontinued and appropriate therapy instituted.
In patients with pulmonary obstruction or emphysema where alveolar ventilation may be impaired, acetazolamide, which may precipitate or aggravate acidosis, should be used with caution.
Gradual ascent is desirable to try to avoid acute mountain sickness. If rapid ascent is undertaken and acetazolamide tablets are used, it should be noted that such use does not obviate the need for prompt descent if severe forms of high altitude sickness occur, i.e., high altitude pulmonary edema (HAPE) or high altitude cerebral edema.
Caution is advised for patients receiving concomitant high-dose aspirin and acetazolamide, as anorexia, tachypnea, lethargy, coma and death have been reported (see WARNINGS).
# Laboratory Tests
To monitor for hematologic reactions common to all sulfonamides, it is recommended that a baseline CBC and platelet count be obtained on patients prior to initiating acetazolamide tablet therapy and at regular intervals during therapy. If significant changes occur, early discontinuance and institution of appropriate therapy are important. Periodic monitoring of serum electrolytes is recommended.
# Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals to evaluate the carcinogenic potential of acetazolamide have not been conducted. In a bacterial mutagenicity assay, acetazolamide was not mutagenic when evaluated with and without metabolic activation.
The drug had no effect on fertility when administered in the diet to male and female rats at a daily intake of up to 4 times the recommended human dose of 1000 mg in a 50 kg individual.
# Pregnancy
## Teratogenic Effect
### Pregnancy Category C
Acetazolamide, administered orally or parenterally, has been shown to be teratogenic (defects of the limbs) in mice, rats, hamsters and rabbits. There are no adequate and well-controlled studies in pregnant women. Acetazolamide should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.
# Nursing Mothers
Because of the potential for serious adverse reaction in nursing infants from acetazolamide, a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.
# Pediatric Use
The safety and effectiveness of acetazolamide in pediatric patients has not been established.
# ADVERSE REACTIONS
Adverse reactions, occurring most often early in therapy, include paresthesias, particularly a "tingling" feeling in the extremities, hearing dysfunction or tinnitus, loss of appetite, taste alteration and gastrointestinal disturbances such as nausea, vomiting and diarrhea, polyuria, and occasional instances of drowsiness and confusion.
Metabolic acidosis and electrolyte imbalance may occur.
Transient myopia has been reported. This condition invariably subsides upon diminution or discontinuance of the medication.
Other occasional adverse reactions include urticaria, melena, hematuria, glycosuria, hepatic insufficiency, flaccid paralysis, photosensitivity and convulsions. Also see PRECAUTIONS: Information for Patients for possible reactions common to sulfonamide derivatives. Fatalities have occurred although rarely, due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias (see WARNINGS).
# OVERDOSAGE
No data are available regarding acetazolamide overdosage in humans as no cases of acute poisoning with this drug have been reported. Animal data suggest that acetazolamide is remarkably nontoxic. No specific antidote is known. Treatment should be symptomatic and supportive.
Electrolyte imbalance, development of an acidotic state, and central nervous effects might be expected to occur. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored.
Supportive measures are required to restore electrolyte and pH balance. The acidotic state can usually be corrected by the administration of bicarbonate.
Despite its high intraerythrocytic distribution and plasma protein binding properties, acetazolamide may be dialyzable. This may be particularly important in the management of acetazolamide overdosage when complicated by the presence of renal failure.
# DOSAGE AND ADMINISTRATION
# Glaucoma
Acetazolamide should be used as an adjunct to the usual therapy. The dosage employed in the treatment of chronic simple (open-angle) glaucoma ranges from 250 mg to 1 g of acetazolamide per 24 hours, usually in divided doses for amounts over 250 mg. It has usually been found that a dosage in excess of 1 g per 24 hours does not produce an increased effect. In all cases, the dosage should be adjusted with careful individual attention both to symptomatology and ocular tension. Continuous supervision by a physician is advisable.
In treatment of secondary glaucoma and in the preoperative treatment of some cases of acute congestive (closed-angle) glaucoma, the preferred dosage is 250 mg every four hours, although some cases have responded to 250 mg twice daily on short-term therapy. In some acute cases, it may be more satisfactory to administer an initial dose of 500 mg followed by 125 mg or 250 mg every four hours depending on the individual case. A complementary effect has been noted when acetazolamide has been used in conjunction with miotics or mydriatics as the case demanded.
# Epilepsy
It is not clearly known whether the beneficial effects observed in epilepsy are due to direct inhibition of carbonic anhydrase in the central nervous system or whether they are due to the slight degree of acidosis produced by the divided dosage. The best results to date have been seen in petit mal in children. Good results, however, have been seen in patients, both children and adult, in other types of seizures such as grand mal, mixed seizure patterns, myoclonic jerk patterns, etc. The suggested total daily dose is 8 to 30 mg per kg in divided doses. Although some patients respond to a low dose, the optimum range appears to be from 375 to 1000 mg daily. However, some investigators feel that daily doses in excess of 1 g do not produce any better results than a 1 g dose. When acetazolamide tablets are given in combination with other anticonvulsants, it is suggested that the starting dose should be 250 mg once daily in addition to the existing medications. This can be increased to levels as indicated above.
The change from other medications to acetazolamide should be gradual and in accordance with usual practice in epilepsy therapy.
# Congestive Heart Failure
For diuresis in congestive heart failure, the starting dose is usually 250 to 375 mg once daily in the morning (5 mg/kg). If, after an initial response, the patient fails to continue to lose edema fluid, do not increase the dose but allow for kidney recovery by skipping medication for a day.
Acetazolamide tablets yield best diuretic results when given on alternate days, or for two days alternating with a day of rest.
Failures in therapy may be due to overdosage or too frequent dosage. The use of acetazolamide does not eliminate the need for other therapy such as digitalis, bed rest, and salt restriction.
# Drug-Induced Edema
Recommended dosage is 250 to 375 mg of acetazolamide once a day for one or two days, alternating with a day of rest.
# Acute Mountain Sickness
Dosage is 500 mg to 1000 mg daily, in divided doses. In circumstances of rapid ascent, such as in rescue or military operations, the higher dose level of 1000 mg is recommended. It is preferable to initiate dosing 24 to 48 hours before ascent and to continue for 48 hours while at high altitude, or longer as necessary to control symptoms.
Note: The dosage recommendations for glaucoma and epilepsy differ considerably from those for congestive heart failure, since the first two conditions are not dependent upon carbonic anhydrase inhibition in the kidney which requires intermittent dosage if it is to recover from the inhibitory effect of the therapeutic agent.
# HOW SUPPLIED
Acetazolamide Tablets USP are supplied as follows:
125 mg - White, round, scored in half, on one side, "T52" engraved on the other side.
NDC 51672-4022-1 - Bottle of 100
250 mg - White, round, scored in quarters, on one side, "T53" engraved on the other side.
NDC 51672-4023-1 - Bottle of 100
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Mfd. by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel 26110
Dist. by: Taro Pharmaceuticals U.S.A., Inc. , Hawthorne, NY 10532
Revised: November, 2013 79429-1113-2
# PRINCIPAL DISPLAY PANEL - 125 mg Tablet Bottle Label
NDC 51672-4022-1
100 Tablets
AcetaZOLAMIDE
Tablets USP,
125 mg
TARO
Rx only
# PRINCIPAL DISPLAY PANEL - 250 mg Tablet Bottle Label
NDC 51672-4023-1
100 Tablets
AcetaZOLAMIDE
Tablets USP,
250 mg
TARO
Rx only | https://www.wikidoc.org/index.php/Sandbox_g07 | |
4166dd2f22b501590e7a3d8a35e4f100bd1e5065 | wikidoc | Sandbox g09 | Sandbox g09
- Bacterial pericarditis
- Empiric antimicrobial therapy
- Purulent pericarditis
- Preferred regimen: Vancomycin 1 g IV q12h targeting trough levels of 15–20 μg/mL for 28 days AND Ciprofloxacin 400 mg IV q12h for 28 days
- Alternative regimen (1): Vancomycin 1 g IV q12h targeting trough levels of 15–20 μg/mL for 28 days AND Cefepime 2 g IV q12h for 28 days
- Alternative regimen (2): Vancomycin 1 g IV q12h targeting trough levels of 15–20 μg/mL for 14–42 days AND Ceftriaxone 2 g IV q24h for 14–42 days
- Specific considerations
- Purulent pericarditis with contiguous pneumonia
- Preferred regimen: Vancomycin 1 g IV q12h targeting trough levels of 15–20 μg/mL AND (Ceftriaxone 1–2 g IV q12h OR Cefotaxime 2 g IV q6–8h) AND (Ciprofloxacin 400 mg IV q12h OR Levofloxacin 500–750 mg IV q24h)
- Purulent pericarditis with contiguous head and neck infection
- Preferred regimen: Imipenem 500 mg IV q6–8h OR Ampicillin-Sulbactam 3 g IV q6h
- Purulent pericarditis secondary to infective endocarditis
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h targeting trough levels of 15–20 μg/mL AND Gentamicin 3 mg/kg/day IV q8–12h
- Purulent pericarditis after cardiac surgery, pediatric
- Preferred regimen: Vancomycin 15 mg/kg IV q6h targeting trough levels of 15–20 μg/mL AND (Ceftriaxone 100 mg/kg/day IV q12–24h OR Cefotaxime 200–300 mg/kg/day IV q6–8h) AND Gentamicin 6–7.5 mg/kg/day IV q8h
- Purulent pericarditis in association with genitourinary infection, pediatric
- Preferred regimen: Vancomycin 15 mg/kg IV q6h targeting trough levels of 15–20 μg/mL AND (Ceftriaxone 100 mg/kg/day IV q12–24h OR Cefotaxime 200–300 mg/kg/day IV q6–8h) AND Gentamicin 6–7.5 mg/kg/day IV q8h
- Purulent pericarditis in immunocompromised host, pediatric
- Preferred regimen: Vancomycin 15 mg/kg IV q6h targeting trough levels of 15–20 μg/mL AND (Ceftriaxone 100 mg/kg/day IV q12–24h OR Cefotaxime 200–300 mg/kg/day IV q6–8h) AND Gentamicin 6–7.5 mg/kg/day IV q8h
- Culture-directed antimicrobial therapy
- Bacterial pericarditis caused by penicillin-susceptible Streptococcus pneumoniae
- Preferred regimen: Penicillin G 5–24 MU/day IM/IV q4–6h for 14–42 days OR Cefotaxime 2 g IV q6–8h for 14–42 days OR Ciprofloxacin 400 mg IV q12h for 14–42 days OR Levofloxacin 500–750 mg IV q24h for 14–42 days
- Bacterial pericarditis caused by penicillin-resistant Streptococcus pneumoniae
- Preferred regimen: Ciprofloxacin 400 mg IV q12h for 14–42 days OR Levofloxacin 500–750 mg IV q24h for 14–42 days OR Vancomycin 1 g IV q12h targeting trough levels of 15–20 μg/mL for 14–42 days
- Bacterial pericarditis caused by MSSA
- Preferred regimen: Nafcillin 1–2 g IV q4h for 14–42 days OR Oxacillin 1–2 g IV q4h for 14–42 days OR Cefazolin 1–2 g IV q48h for 14–42 days OR Vancomycin 1 g IV q12h targeting trough levels of 15–20 μg/mL for 14–42 days OR Clindamycin 600–900 mg IV q8h for 14–42 days
- Bacterial pericarditis caused by MRSA
- Preferred regimen: Vancomycin 1 g IV q12h targeting trough levels of 15–20 μg/mL for 14–42 days OR Linezolid 600 mg IV q12h for 14–42 days
- Bacterial pericarditis caused by Neisseria meningitidis
- Preferred regimen: Penicillin G 5–24 MU/day IM/IV q4–6h for 14–42 days OR Cefotaxime 2 g IV q6–8h for 14–42 days OR Ceftriaxone 2 g IV q24h for 14–42 days
- Bacterial pericarditis caused by Gram-negative bacilli
- Preferred regimen: Ciprofloxacin 400 mg IV q12h for 14–42 days OR Levofloxacin 500–750 mg IV q24h for 14–42 days OR Cefepime 2 g IV q12h for 14–42 days
- Bacterial pericarditis caused by anaerobes
- Preferred regimen: Clindamycin 600–900 mg IV q8h for 14–42 days OR Metronidazole 7.5 mg/kg IV q6h for 14–42 days OR Ampicillin-Sulbactam 3 g IV q6h for 14–42 days
- Bacterial pericarditis caused by Mycoplasma pneumoniae
- Preferred regimen: Doxycycline 100 mg IV q12h for 14–42 days OR Azithromycin 500 mg IV q24h for 14–42 days
- Bacterial pericarditis caused by Legionella pneumophila
- Preferred regimen: Ciprofloxacin 400 mg IV q12h for 14–42 days OR Levofloxacin 500–750 mg IV q24h for 14–42 days OR Azithromycin 500 mg IV q24h for 14–42 days
- Viral pericarditis
- CMV pericarditis
- Preferred regimen: immunoglobulin 1 time per day 4 ml/kg on day 0, 4, and 8; 2 ml/kg on day 12 and 16.
- Coxsackie B pericarditis
- Preferred regimen: Interferon alpha or beta 2,5 Mio. IU/m2 surface area s.c. 3×per week.
- Adenovirus and parvovirus B19 perimyocarditis
- Preferred regimen: Immunoglobulin 10 g intravenously at day 1 and 3 for 6–8 hours
- Fungal pericarditis | Sandbox g09
- Bacterial pericarditis
- Empiric antimicrobial therapy[1][2]
- Purulent pericarditis
- Preferred regimen: Vancomycin 1 g IV q12h targeting trough levels of 15–20 μg/mL for 28 days AND Ciprofloxacin 400 mg IV q12h for 28 days
- Alternative regimen (1): Vancomycin 1 g IV q12h targeting trough levels of 15–20 μg/mL for 28 days AND Cefepime 2 g IV q12h for 28 days
- Alternative regimen (2): Vancomycin 1 g IV q12h targeting trough levels of 15–20 μg/mL for 14–42 days AND Ceftriaxone 2 g IV q24h for 14–42 days
- Specific considerations[3][4][5][6]
- Purulent pericarditis with contiguous pneumonia
- Preferred regimen: Vancomycin 1 g IV q12h targeting trough levels of 15–20 μg/mL AND (Ceftriaxone 1–2 g IV q12h OR Cefotaxime 2 g IV q6–8h) AND (Ciprofloxacin 400 mg IV q12h OR Levofloxacin 500–750 mg IV q24h)
- Purulent pericarditis with contiguous head and neck infection
- Preferred regimen: Imipenem 500 mg IV q6–8h OR Ampicillin-Sulbactam 3 g IV q6h
- Purulent pericarditis secondary to infective endocarditis
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h targeting trough levels of 15–20 μg/mL AND Gentamicin 3 mg/kg/day IV q8–12h
- Purulent pericarditis after cardiac surgery, pediatric
- Preferred regimen: Vancomycin 15 mg/kg IV q6h targeting trough levels of 15–20 μg/mL AND (Ceftriaxone 100 mg/kg/day IV q12–24h OR Cefotaxime 200–300 mg/kg/day IV q6–8h) AND Gentamicin 6–7.5 mg/kg/day IV q8h
- Purulent pericarditis in association with genitourinary infection, pediatric
- Preferred regimen: Vancomycin 15 mg/kg IV q6h targeting trough levels of 15–20 μg/mL AND (Ceftriaxone 100 mg/kg/day IV q12–24h OR Cefotaxime 200–300 mg/kg/day IV q6–8h) AND Gentamicin 6–7.5 mg/kg/day IV q8h
- Purulent pericarditis in immunocompromised host, pediatric
- Preferred regimen: Vancomycin 15 mg/kg IV q6h targeting trough levels of 15–20 μg/mL AND (Ceftriaxone 100 mg/kg/day IV q12–24h OR Cefotaxime 200–300 mg/kg/day IV q6–8h) AND Gentamicin 6–7.5 mg/kg/day IV q8h
- Culture-directed antimicrobial therapy[7]
- Bacterial pericarditis caused by penicillin-susceptible Streptococcus pneumoniae
- Preferred regimen: Penicillin G 5–24 MU/day IM/IV q4–6h for 14–42 days OR Cefotaxime 2 g IV q6–8h for 14–42 days OR Ciprofloxacin 400 mg IV q12h for 14–42 days OR Levofloxacin 500–750 mg IV q24h for 14–42 days
- Bacterial pericarditis caused by penicillin-resistant Streptococcus pneumoniae
- Preferred regimen: Ciprofloxacin 400 mg IV q12h for 14–42 days OR Levofloxacin 500–750 mg IV q24h for 14–42 days OR Vancomycin 1 g IV q12h targeting trough levels of 15–20 μg/mL for 14–42 days
- Bacterial pericarditis caused by MSSA
- Preferred regimen: Nafcillin 1–2 g IV q4h for 14–42 days OR Oxacillin 1–2 g IV q4h for 14–42 days OR Cefazolin 1–2 g IV q48h for 14–42 days OR Vancomycin 1 g IV q12h targeting trough levels of 15–20 μg/mL for 14–42 days OR Clindamycin 600–900 mg IV q8h for 14–42 days
- Bacterial pericarditis caused by MRSA
- Preferred regimen: Vancomycin 1 g IV q12h targeting trough levels of 15–20 μg/mL for 14–42 days OR Linezolid 600 mg IV q12h for 14–42 days
- Bacterial pericarditis caused by Neisseria meningitidis
- Preferred regimen: Penicillin G 5–24 MU/day IM/IV q4–6h for 14–42 days OR Cefotaxime 2 g IV q6–8h for 14–42 days OR Ceftriaxone 2 g IV q24h for 14–42 days
- Bacterial pericarditis caused by Gram-negative bacilli
- Preferred regimen: Ciprofloxacin 400 mg IV q12h for 14–42 days OR Levofloxacin 500–750 mg IV q24h for 14–42 days OR Cefepime 2 g IV q12h for 14–42 days
- Bacterial pericarditis caused by anaerobes
- Preferred regimen: Clindamycin 600–900 mg IV q8h for 14–42 days OR Metronidazole 7.5 mg/kg IV q6h for 14–42 days OR Ampicillin-Sulbactam 3 g IV q6h for 14–42 days
- Bacterial pericarditis caused by Mycoplasma pneumoniae
- Preferred regimen: Doxycycline 100 mg IV q12h for 14–42 days OR Azithromycin 500 mg IV q24h for 14–42 days
- Bacterial pericarditis caused by Legionella pneumophila
- Preferred regimen: Ciprofloxacin 400 mg IV q12h for 14–42 days OR Levofloxacin 500–750 mg IV q24h for 14–42 days OR Azithromycin 500 mg IV q24h for 14–42 days
- Viral pericarditis
- CMV pericarditis
- Preferred regimen: immunoglobulin 1 time per day 4 ml/kg on day 0, 4, and 8; 2 ml/kg on day 12 and 16.
- Coxsackie B pericarditis
- Preferred regimen: Interferon alpha or beta 2,5 Mio. IU/m2 surface area s.c. 3×per week.
- Adenovirus and parvovirus B19 perimyocarditis
- Preferred regimen: Immunoglobulin 10 g intravenously at day 1 and 3 for 6–8 hours
- Fungal pericarditis | https://www.wikidoc.org/index.php/Sandbox_g09 | |
0c5461572068936675b312c3a2f605ac3af4e064 | wikidoc | Sandbox g12 | Sandbox g12
- Risk categories for antimicrobial agents known to have an association with TdP
- Drugs with known TdP risk
- Azithromycin (Zithromax®, Zmax®)
- Chloroquine (Aralen®)
- Ciprofloxacin (Cipro®, Cipro-XR®, Neofloxin®)
- Clarithromycin (Biaxin®, Prevpac®)
- Erythromycin (A/T/S®, Akne-Mycin®, Emgel®, Ery-Tab®, Eryc®, Erycette®, Eryderm®, Erygel®)
- Fluconazole (Diflucan®, Trican®)
- Halofantrine (Halfan®)
- Levofloxacin (Levaquin®, Tavanic®)
- Moxifloxacin (Avelox®, Avalox®, Avelon®)
- Pentamidine (Pentam®)
- Sparfloxacin (Zagam®)
- Drugs with possible TdP risk
- Atazanavir (Reyataz®)
- Bedaquiline (Sirturo®)
- Dihydroartemisinin-Piperaquine (Eurartesim®)
- Foscarnet (Foscavir®)
- Gatifloxacin (Tequin®)
- Gemifloxacin (Factive®)
- Norfloxacin (Noroxin®, Ambigram®)
- Ofloxacin (Floxin®)
- Rilpivirine (Edurant®, Complera®, Eviplera®)
- Roxithromycin (Rulide®, Xthrocin®, Roxl-150®, Roxo®, Surlid®, Rulide®, Biaxsig®, Roxar®, Roximycinv®, Roxomycin®, Rulid®, Tirabicin®, Coroxin®)
- Saquinavir (Invirase®(combo))
- Telavancin (Vibativ®)
- Telithromycin (Ketek®)
- Drugs with conditional TdP risk
- Amantadine (Symmetrel®, Symadine®)
- Hydroxychloroquine (Plaquenil®, Quineprox®)
- Itraconazole (Sporanox®, Onmel®)
- Ketoconazole (Nizoral®, Sebizole®, Ketomed®, Keton®)
- Metronidazole (Flagyl® and many others)
- Nelfinavir (Viracept®)
- Posaconazole (Noxafil®, Posamol®)
- Quinine sulfate (Qualaquin®)
- Ritonavir (Norvir®)
- Telaprevir (Incivek®, Incivo®)
- Voriconazole (VFend®)
- Drugs to be avoided by congenital Long QT
- Trimethoprim-Sulfamethoxazole (Septra®, Bactrim®, Sulfatrim®, Biseptol®, Co-trimoxazole®, Cotrim®, Septrin®, Trisul®)
- Torsades de pointes risk stratification schedules for antimicrobial agents
- Schedule I (Highest TdP risk, potent IKr blockers, TdP risk >1%)
- Not available
- Schedule II (Significant risk for TdP, particularly when coadministered with CYP inhibitors, relatively potent IKr blockade)
- Not available
- Schedule III (Risk for TdP is described, IKr blockade, particularly when coadministered with CYP inhibitors)
- Clarithromycin (Biaxin®, Prevpac®)
- Erythromycin (A/T/S®, Akne-Mycin®, Emgel®, Ery-Tab®, Eryc®, Erycette®, Eryderm®, Erygel®)
- Itraconazole (Sporanox®, Onmel®)
- Ketoconazole (Nizoral®, Sebizole®, Ketomed®, Keton®)
- Pentamidine (Pentam®)
- Sparfloxacin (Zagam®)
- Schedule IV (Minimal risk for TdP, case reports of TdP, mild IKr blockade, may have CYP interactions)
- Fluconazole (Diflucan®, Trican®)
- Gatifloxacin (Tequin®)
- Gemifloxacin (Factive®)
- Levofloxacin (Levaquin®, Tavanic®)
- Moxifloxacin (Avelox®, Avalox®, Avelon®)
- Telithromycin (Ketek®)
- Voriconazole (VFend®)
- Schedule V (Questionable or minimal risk for QT interval prolongation or TdP)
- Azithromycin (Zithromax®, Zmax®)
- Ciprofloxacin (Cipro®, Cipro-XR®, Neofloxin®)
- Trimethoprim-Sulfamethoxazole (Septra®, Bactrim®, Sulfatrim®, Biseptol®, Co-trimoxazole®, Cotrim®, Septrin®, Trisul®) | Sandbox g12
- Risk categories for antimicrobial agents known to have an association with TdP[1]
- Drugs with known TdP risk
- Azithromycin (Zithromax®, Zmax®)
- Chloroquine (Aralen®)
- Ciprofloxacin (Cipro®, Cipro-XR®, Neofloxin®)
- Clarithromycin (Biaxin®, Prevpac®)
- Erythromycin (A/T/S®, Akne-Mycin®, Emgel®, Ery-Tab®, Eryc®, Erycette®, Eryderm®, Erygel®)
- Fluconazole (Diflucan®, Trican®)
- Halofantrine (Halfan®)
- Levofloxacin (Levaquin®, Tavanic®)
- Moxifloxacin (Avelox®, Avalox®, Avelon®)
- Pentamidine (Pentam®)
- Sparfloxacin (Zagam®)
- Drugs with possible TdP risk
- Atazanavir (Reyataz®)
- Bedaquiline (Sirturo®)
- Dihydroartemisinin-Piperaquine (Eurartesim®)
- Foscarnet (Foscavir®)
- Gatifloxacin (Tequin®)
- Gemifloxacin (Factive®)
- Norfloxacin (Noroxin®, Ambigram®)
- Ofloxacin (Floxin®)
- Rilpivirine (Edurant®, Complera®, Eviplera®)
- Roxithromycin (Rulide®, Xthrocin®, Roxl-150®, Roxo®, Surlid®, Rulide®, Biaxsig®, Roxar®, Roximycinv®, Roxomycin®, Rulid®, Tirabicin®, Coroxin®)
- Saquinavir (Invirase®(combo))
- Telavancin (Vibativ®)
- Telithromycin (Ketek®)
- Drugs with conditional TdP risk
- Amantadine (Symmetrel®, Symadine®)
- Hydroxychloroquine (Plaquenil®, Quineprox®)
- Itraconazole (Sporanox®, Onmel®)
- Ketoconazole (Nizoral®, Sebizole®, Ketomed®, Keton®)
- Metronidazole (Flagyl® and many others)
- Nelfinavir (Viracept®)
- Posaconazole (Noxafil®, Posamol®)
- Quinine sulfate (Qualaquin®)
- Ritonavir (Norvir®)
- Telaprevir (Incivek®, Incivo®)
- Voriconazole (VFend®)
- Drugs to be avoided by congenital Long QT
- Trimethoprim-Sulfamethoxazole (Septra®, Bactrim®, Sulfatrim®, Biseptol®, Co-trimoxazole®, Cotrim®, Septrin®, Trisul®)
- Torsades de pointes risk stratification schedules for antimicrobial agents[2]
- Schedule I (Highest TdP risk, potent IKr blockers, TdP risk >1%)
- Not available
- Schedule II (Significant risk for TdP, particularly when coadministered with CYP inhibitors, relatively potent IKr blockade)
- Not available
- Schedule III (Risk for TdP is described, IKr blockade, particularly when coadministered with CYP inhibitors)
- Clarithromycin (Biaxin®, Prevpac®)
- Erythromycin (A/T/S®, Akne-Mycin®, Emgel®, Ery-Tab®, Eryc®, Erycette®, Eryderm®, Erygel®)
- Itraconazole (Sporanox®, Onmel®)
- Ketoconazole (Nizoral®, Sebizole®, Ketomed®, Keton®)
- Pentamidine (Pentam®)
- Sparfloxacin (Zagam®)
- Schedule IV (Minimal risk for TdP, case reports of TdP, mild IKr blockade, may have CYP interactions)
- Fluconazole (Diflucan®, Trican®)
- Gatifloxacin (Tequin®)
- Gemifloxacin (Factive®)
- Levofloxacin (Levaquin®, Tavanic®)
- Moxifloxacin (Avelox®, Avalox®, Avelon®)
- Telithromycin (Ketek®)
- Voriconazole (VFend®)
- Schedule V (Questionable or minimal risk for QT interval prolongation or TdP)
- Azithromycin (Zithromax®, Zmax®)
- Ciprofloxacin (Cipro®, Cipro-XR®, Neofloxin®)
- Trimethoprim-Sulfamethoxazole (Septra®, Bactrim®, Sulfatrim®, Biseptol®, Co-trimoxazole®, Cotrim®, Septrin®, Trisul®) | https://www.wikidoc.org/index.php/Sandbox_g12 | |
5978b4bb6a758a16ef6081d53d2f4df26b1eb828 | wikidoc | Sandbox g14 | Sandbox g14
# Epidural abscess
- Spinal epidural abscess
- Empiric antimicrobial therapy
- Preferred regimen: Vancomycin loading dose 25–30 mg/kg IV followed by 15–20 mg/kg IV q8–12h for 2–4 weeks, then PO to complete 6–8 weeks AND Ceftriaxone 2 g Iv q24h for 2–4 weeks, then PO to complete 6–8 weeks
- Culture-directed antimicrobial therapy
- Penicillin-susceptible Staphylococcus aureus or Streptococcus
- Preferred regimen: Penicillin G 4 MU IV q4h for 2–4 weeks, then PO to complete 6–8 weeks
- Methicillin-susceptible Staphylococcus aureus or Streptococcus
- Preferred regimen: Cefazolin 2 g IV q8h for 2–4 weeks, then PO to complete 6–8 weeks OR Nafcillin 2 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks OR Oxacillin 2 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks
- Alternative regimen: Clindamycin 600 mg IV q6h for 2–4 weeks, then PO to complete 6–8 weeks
- Methicillin-resistant Staphylococcus aureus
- Preferred regimen: Vancomycin loading dose 25–30 mg/kg IV followed by 15–20 mg/kg IV q8–12h for 2–4 weeks, then PO to complete 6–8 weeks
- Streptococcus
- Preferred regimen: Penicillin G 3–4 MU IV q4h for 2–4 weeks, then PO to complete 6–8 weeks OR Ampicillin 2 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks
- Enterococcus
- Preferred regimen: Penicillin G 3–4 MU IV q4h for 2–4 weeks, then PO to complete 6–8 weeks OR Ampicillin 2 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks
- Enterobacteriaceae
- Preferred regimen: Ceftriaxone 1–2 g IV q12h for 2–4 weeks, then PO to complete 6–8 weeks OR Cefotaxime 2 g IV q6–8h for 2–4 weeks, then PO to complete 6–8 weeks
- Gram-negative bacteria
- Preferred regimen:Ceftazidime 2 g IV q8h for 2–4 weeks, then PO to complete 6–8 weeks OR Cefepime 2 g IV q12h for 2–4 weeks, then PO to complete 6–8 weeks
- Alternative regimen: Ciprofloxacin 400 mg IV q12h for 2–4 weeks, then PO to complete 6–8 weeks OR Levofloxacin 750 mg IV q24h for 2–4 weeks, then PO to complete 6–8 weeks OR Moxifloxacin 400 mg IV q24h for 2–4 weeks, then PO to complete 6–8 weeks
- Anaerobes
- Preferred regimen: Metronidazole 500 mg IV q6h for 2–4 weeks, then PO to complete 6–8 weeks
- Staphylococcus, Gram-negative bacteria, and anaerobes (mixed infection)
- Preferred regimen: Ampicillin-Sulbactam 3 g IV q6h for 2–4 weeks, then PO to complete 6–8 weeks OR Ticarcillin-Clavulanate 3.1 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks OR Piperacillin-Tazobactam 3.375 g IV q4–6h for 2–4 weeks, then PO to complete 6–8 weeks
- Alternative regimen: Imipenem 500–1000 mg IV q6h for 2–4 weeks, then PO to complete 6–8 weeks OR Meropenem 1–2 g IV q8h for 2–4 weeks, then PO to complete 6–8 weeks
# Brain abscess
- Brain abscess, bacterial
- Empiric antimicrobial therapy (unknown source of infection)
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h for 6–8 weeks, then orally for 2–3 months AND (Cefotaxime 2 g IV q4h for 6–8 weeks, then orally for 2–3 months OR Ceftriaxone 2 g IV q12h for 6–8 weeks, then orally for 2–3 months) AND Metronidazole 7.5 mg/kg IV q6h or 15 mg/kg IV q12h for 6–8 weeks, then orally for 2–3 months
- Alternative regimen: Penicillin G 3–4 MU IV q4h for 6–8 weeks, then orally for 2–3 months AND (Cefotaxime 2 g IV q4h for 6–8 weeks, then orally for 2–3 months OR Ceftriaxone 2 g IV q12h for 6–8 weeks, then orally for 2–3 months) AND Metronidazole 7.5 mg/kg IV q6h or 15 mg/kg IV q12h for 6–8 weeks, then orally for 2–3 months
- Specific considerations
- Culture-directed antimicrobial therapy
- Nocardia
- Preferred regimen: (TMP-SMX 15 mg/kg/day of TMP component and 75 mg/kg/day of SMX component IV/PO q6–12h AND Imipenem 500 mg IV q6h) ± Amikacin 7.5 mg/kg IV q12h if multiple organ involvement
- Alternative regimen: Linezolid 600 mg IV/PO q12h AND Meropenem 2 gm IV q8h
- Brain abscess, tuberculous
- Brain abscess, fungal | Sandbox g14
## Epidural abscess
- Spinal epidural abscess[1][2][3]
- Empiric antimicrobial therapy
- Preferred regimen: Vancomycin loading dose 25–30 mg/kg IV followed by 15–20 mg/kg IV q8–12h for 2–4 weeks, then PO to complete 6–8 weeks AND Ceftriaxone 2 g Iv q24h for 2–4 weeks, then PO to complete 6–8 weeks
- Culture-directed antimicrobial therapy
- Penicillin-susceptible Staphylococcus aureus or Streptococcus
- Preferred regimen: Penicillin G 4 MU IV q4h for 2–4 weeks, then PO to complete 6–8 weeks
- Methicillin-susceptible Staphylococcus aureus or Streptococcus
- Preferred regimen: Cefazolin 2 g IV q8h for 2–4 weeks, then PO to complete 6–8 weeks OR Nafcillin 2 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks OR Oxacillin 2 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks
- Alternative regimen: Clindamycin 600 mg IV q6h for 2–4 weeks, then PO to complete 6–8 weeks
- Methicillin-resistant Staphylococcus aureus
- Preferred regimen: Vancomycin loading dose 25–30 mg/kg IV followed by 15–20 mg/kg IV q8–12h for 2–4 weeks, then PO to complete 6–8 weeks
- Streptococcus
- Preferred regimen: Penicillin G 3–4 MU IV q4h for 2–4 weeks, then PO to complete 6–8 weeks OR Ampicillin 2 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks
- Enterococcus
- Preferred regimen: Penicillin G 3–4 MU IV q4h for 2–4 weeks, then PO to complete 6–8 weeks OR Ampicillin 2 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks
- Enterobacteriaceae
- Preferred regimen: Ceftriaxone 1–2 g IV q12h for 2–4 weeks, then PO to complete 6–8 weeks OR Cefotaxime 2 g IV q6–8h for 2–4 weeks, then PO to complete 6–8 weeks
- Gram-negative bacteria
- Preferred regimen:Ceftazidime 2 g IV q8h for 2–4 weeks, then PO to complete 6–8 weeks OR Cefepime 2 g IV q12h for 2–4 weeks, then PO to complete 6–8 weeks
- Alternative regimen: Ciprofloxacin 400 mg IV q12h for 2–4 weeks, then PO to complete 6–8 weeks OR Levofloxacin 750 mg IV q24h for 2–4 weeks, then PO to complete 6–8 weeks OR Moxifloxacin 400 mg IV q24h for 2–4 weeks, then PO to complete 6–8 weeks
- Anaerobes
- Preferred regimen: Metronidazole 500 mg IV q6h for 2–4 weeks, then PO to complete 6–8 weeks
- Staphylococcus, Gram-negative bacteria, and anaerobes (mixed infection)
- Preferred regimen: Ampicillin-Sulbactam 3 g IV q6h for 2–4 weeks, then PO to complete 6–8 weeks OR Ticarcillin-Clavulanate 3.1 g IV q4h for 2–4 weeks, then PO to complete 6–8 weeks OR Piperacillin-Tazobactam 3.375 g IV q4–6h for 2–4 weeks, then PO to complete 6–8 weeks
- Alternative regimen: Imipenem 500–1000 mg IV q6h for 2–4 weeks, then PO to complete 6–8 weeks OR Meropenem 1–2 g IV q8h for 2–4 weeks, then PO to complete 6–8 weeks
## Brain abscess
- Brain abscess, bacterial[4]
- Empiric antimicrobial therapy (unknown source of infection)
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h for 6–8 weeks, then orally for 2–3 months AND (Cefotaxime 2 g IV q4h for 6–8 weeks, then orally for 2–3 months OR Ceftriaxone 2 g IV q12h for 6–8 weeks, then orally for 2–3 months) AND Metronidazole 7.5 mg/kg IV q6h or 15 mg/kg IV q12h for 6–8 weeks, then orally for 2–3 months
- Alternative regimen: Penicillin G 3–4 MU IV q4h for 6–8 weeks, then orally for 2–3 months AND (Cefotaxime 2 g IV q4h for 6–8 weeks, then orally for 2–3 months OR Ceftriaxone 2 g IV q12h for 6–8 weeks, then orally for 2–3 months) AND Metronidazole 7.5 mg/kg IV q6h or 15 mg/kg IV q12h for 6–8 weeks, then orally for 2–3 months
- Specific considerations
-
- Culture-directed antimicrobial therapy
- Nocardia
- Preferred regimen: (TMP-SMX 15 mg/kg/day of TMP component and 75 mg/kg/day of SMX component IV/PO q6–12h AND Imipenem 500 mg IV q6h) ± Amikacin 7.5 mg/kg IV q12h if multiple organ involvement
- Alternative regimen: Linezolid 600 mg IV/PO q12h AND Meropenem 2 gm IV q8h
- Brain abscess, tuberculous
- Brain abscess, fungal | https://www.wikidoc.org/index.php/Sandbox_g14 | |
5c226df6ae1408bb20a7aa4f7dffe00068d27289 | wikidoc | Sandbox g18 | Sandbox g18
# R00–R69 – Symptoms and signs
## (R00–R09) Circulatory and respiratory systems
- (R00) Abnormalities of heart beat
(R00.0) Tachycardia, unspecified
(R00.1) Bradycardia, unspecified
(R00.2) Palpitations
(R00.8) Other and unspecified abnormalities of heart beat
- (R00.0) Tachycardia, unspecified
- (R00.1) Bradycardia, unspecified
- (R00.2) Palpitations
- (R00.8) Other and unspecified abnormalities of heart beat
- (R01) Cardiac murmurs and other cardiac sounds
(R01.0) Benign and innocent cardiac murmurs
(R01.1) Cardiac murmur, unspecified
Cardiac bruit NOS
(R01.2) Other cardiac sounds
- (R01.0) Benign and innocent cardiac murmurs
- (R01.1) Cardiac murmur, unspecified
Cardiac bruit NOS
- Cardiac bruit NOS
- (R01.2) Other cardiac sounds
- (R02) Gangrene, not elsewhere classified
- (R03) Abnormal blood-pressure reading, without diagnosis
(R03.0) Elevated blood-pressure reading, without diagnosis of hypertension
(R03.1) Nonspecific low blood-pressure reading
- (R03.0) Elevated blood-pressure reading, without diagnosis of hypertension
- (R03.1) Nonspecific low blood-pressure reading
- (R04) Haemorrhage from respiratory passages
(R04.0) Epistaxis
(R04.1) Haemorrhage from throat
(R04.2) Haemoptysis
(R04.8) Haemorrhage from other sites in respiratory passages
(R04.9) Haemorrhage from respiratory passages, unspecified
- (R04.0) Epistaxis
- (R04.1) Haemorrhage from throat
- (R04.2) Haemoptysis
- (R04.8) Haemorrhage from other sites in respiratory passages
- (R04.9) Haemorrhage from respiratory passages, unspecified
- (R05) Cough
- (R06) Abnormalities of breathing
(R06.0) Dyspnoea
Orthopnoea
(R06.1) Stridor
(R06.2) Wheezing
(R06.3) Periodic breathing
Cheyne-Stokes respiration
(R06.4) Hyperventilation
(R06.5) Mouth breathing
Snoring
(R06.6) Hiccough
(R06.7) Sneezing
(R06.8) Other and unspecified abnormalities of breathing
Choking sensation
- (R06.0) Dyspnoea
Orthopnoea
- Orthopnoea
- (R06.1) Stridor
- (R06.2) Wheezing
- (R06.3) Periodic breathing
Cheyne-Stokes respiration
- Cheyne-Stokes respiration
- (R06.4) Hyperventilation
- (R06.5) Mouth breathing
Snoring
- Snoring
- (R06.6) Hiccough
- (R06.7) Sneezing
- (R06.8) Other and unspecified abnormalities of breathing
Choking sensation
- Choking sensation
- (R07) Pain in throat and chest
(R07.0) Pain in throat
(R07.1) Chest pain on breathing
(R07.2) Precordial pain
(R07.3) Other chest pain
(R07.4) Chest pain, unspecified
- (R07.0) Pain in throat
- (R07.1) Chest pain on breathing
- (R07.2) Precordial pain
- (R07.3) Other chest pain
- (R07.4) Chest pain, unspecified
- (R09) Other symptoms and signs involving the circulatory and respiratory systems
(R09.0) Asphyxia
(R09.1) Pleurisy
(R09.2) Respiratory arrest
(R09.3) Abnormal sputum
(R09.8) Other specified symptoms and signs involving the circulatory and respiratory systems
Rales
Arterial Bruit
- (R09.0) Asphyxia
- (R09.1) Pleurisy
- (R09.2) Respiratory arrest
- (R09.3) Abnormal sputum
- (R09.8) Other specified symptoms and signs involving the circulatory and respiratory systems
Rales
Arterial Bruit
- Rales
- Arterial Bruit
## (R10–R19) Digestive system and abdomen
- (R10) Abdominal and pelvic pain
(R10.0) Acute abdomen
(R10.1) Pain localized to upper abdomen
(R10.2) Pelvic and perineal pain
(R10.3) Pain localized to other parts of lower abdomen
(R10.4) Other and unspecified abdominal pain
Abdominal tenderness NOS
Colic, NOS
infantile colic
- (R10.0) Acute abdomen
- (R10.1) Pain localized to upper abdomen
- (R10.2) Pelvic and perineal pain
- (R10.3) Pain localized to other parts of lower abdomen
- (R10.4) Other and unspecified abdominal pain
Abdominal tenderness NOS
Colic, NOS
infantile colic
- Abdominal tenderness NOS
- Colic, NOS
- infantile colic
- (R11) Nausea and vomiting
- (R12) Heartburn
- (R13) Dysphagia
- (R14) Flatulence and related conditions
Abdominal distension (gaseous)
Bloating
Eructation
Gas pain
Tympanites (abdominal)(intestinal)
- Abdominal distension (gaseous)
- Bloating
- Eructation
- Gas pain
- Tympanites (abdominal)(intestinal)
- (R15) Faecal incontinence
Encopresis
- Encopresis
- (R16) Hepatomegaly and splenomegaly, not elsewhere classified
(R16.0) Hepatomegaly, not elsewhere classified
(R16.1) Splenomegaly, not elsewhere classified
(R16.2) Hepatomegaly with splenomegaly, not elsewhere classified
Hepatosplenomegaly NOS
- (R16.0) Hepatomegaly, not elsewhere classified
- (R16.1) Splenomegaly, not elsewhere classified
- (R16.2) Hepatomegaly with splenomegaly, not elsewhere classified
Hepatosplenomegaly NOS
- Hepatosplenomegaly NOS
- (R17) Unspecified jaundice
- (R18) Ascites
- (R19) Other symptoms and signs involving the digestive system and abdomen
(R19.0) Intra-abdominal and pelvic swelling, mass and lump
(R19.1) Abnormal bowel sounds
(R19.2) Visible peristalsis
(R19.3) Abdominal rigidity
(R19.4) Change in bowel habit
(R19.5) Other faecal abnormalities
(R19.6) Halitosis
(R19.8) Other specified symptoms and signs involving the digestive system and abdomen
- (R19.0) Intra-abdominal and pelvic swelling, mass and lump
- (R19.1) Abnormal bowel sounds
- (R19.2) Visible peristalsis
- (R19.3) Abdominal rigidity
- (R19.4) Change in bowel habit
- (R19.5) Other faecal abnormalities
- (R19.6) Halitosis
- (R19.8) Other specified symptoms and signs involving the digestive system and abdomen
## (R20–R23) Skin and subcutaneous tissue
- (R20) Disturbances of skin sensation
(R20.0) Anaesthesia of skin
(R20.1) Hypoaesthesia of skin
(R20.2) Paraesthesia of skin
(R20.3) Hyperaesthesia
(R20.8) Other and unspecified disturbances of skin sensation
- (R20.0) Anaesthesia of skin
- (R20.1) Hypoaesthesia of skin
- (R20.2) Paraesthesia of skin
- (R20.3) Hyperaesthesia
- (R20.8) Other and unspecified disturbances of skin sensation
- (R21) Rash and other nonspecific skin eruption
- (R22) Localized swelling, mass and lump of skin and subcutaneous tissue
(R22.0) Localized swelling, mass and lump, head
(R22.1) Localized swelling, mass and lump, neck
(R22.2) Localized swelling, mass and lump, trunk
(R22.3) Localized swelling, mass and lump, upper limb
(R22.4) Localized swelling, mass and lump, lower limb
(R22.7) Localized swelling, mass and lump, multiple sites
(R22.9) Localized swelling, mass and lump, unspecified
- (R22.0) Localized swelling, mass and lump, head
- (R22.1) Localized swelling, mass and lump, neck
- (R22.2) Localized swelling, mass and lump, trunk
- (R22.3) Localized swelling, mass and lump, upper limb
- (R22.4) Localized swelling, mass and lump, lower limb
- (R22.7) Localized swelling, mass and lump, multiple sites
- (R22.9) Localized swelling, mass and lump, unspecified
- (R23) Other skin changes
(R23.0) Cyanosis
(R23.1) Pallor
(R23.2) Flushing
(R23.3) Spontaneous ecchymoses
Petechiae
(R23.4) Changes in skin texture
Desquamation
Induration
(R23.8) Other and unspecified skin changes
- (R23.0) Cyanosis
- (R23.1) Pallor
- (R23.2) Flushing
- (R23.3) Spontaneous ecchymoses
Petechiae
- Petechiae
- (R23.4) Changes in skin texture
Desquamation
Induration
- Desquamation
- Induration
- (R23.8) Other and unspecified skin changes
## (R25–R29) Nervous and musculoskeletal systems
- (R25) Abnormal involuntary movements
(R25.0) Abnormal head movements
(R25.1) Tremor, unspecified
(R25.2) Cramp and spasm
(R25.3) Fasciculation
(R25.8) Other and unspecified abnormal involuntary movements
- (R25.0) Abnormal head movements
- (R25.1) Tremor, unspecified
- (R25.2) Cramp and spasm
- (R25.3) Fasciculation
- (R25.8) Other and unspecified abnormal involuntary movements
- (R26) Abnormalities of gait and mobility
(R26.0) Ataxic gait
(R26.1) Paralytic gait
(R26.2) Difficulty in walking, not elsewhere classified
(R26.8) Other and unspecified abnormalities of gait and mobility
- (R26.0) Ataxic gait
- (R26.1) Paralytic gait
- (R26.2) Difficulty in walking, not elsewhere classified
- (R26.8) Other and unspecified abnormalities of gait and mobility
- (R27) Other lack of coordination
(R27.0) Ataxia, unspecified
(R27.8) Other and unspecified lack of coordination
- (R27.0) Ataxia, unspecified
- (R27.8) Other and unspecified lack of coordination
- (R29) Other symptoms and signs involving the nervous and musculoskeletal systems
(R29.0) Tetany
(R29.1) Meningismus
(R29.2) Abnormal reflex
Hyperreflexia
(R29.3) Abnormal posture
(R29.4) Clicking hip
(R29.8) Other and unspecified symptoms and signs involving the nervous and musculoskeletal systems
- (R29.0) Tetany
- (R29.1) Meningismus
- (R29.2) Abnormal reflex
Hyperreflexia
- Hyperreflexia
- (R29.3) Abnormal posture
- (R29.4) Clicking hip
- (R29.8) Other and unspecified symptoms and signs involving the nervous and musculoskeletal systems
## (R30–R39) Urinary system
- (R30) Pain associated with micturition
(R30.0) Dysuria
(R30.1) Vesical tenesmus
(R30.9) Painful micturition, unspecified
- (R30.0) Dysuria
- (R30.1) Vesical tenesmus
- (R30.9) Painful micturition, unspecified
- (R31) Unspecified haematuria
- (R32) Unspecified urinary incontinence
- (R33) Retention of urine
- (R34) Anuria and oliguria
- (R35) Polyuria
Nocturia
- Nocturia
- (R36) Urethral discharge
- (R39) Other symptoms and signs involving the urinary system
(R39.0) Extravasation of urine
(R39.1) Other difficulties with micturition
(R39.2) Extrarenal uraemia
(R39.8) Other and unspecified symptoms and signs involving the urinary system
- (R39.0) Extravasation of urine
- (R39.1) Other difficulties with micturition
- (R39.2) Extrarenal uraemia
- (R39.8) Other and unspecified symptoms and signs involving the urinary system
## (R40–R46) Cognition, perception, emotional state and behaviour
- (R40) Somnolence, stupor and coma
(R40.0) Somnolence
(R40.1) Stupor
(R40.2) Coma, unspecified
- (R40.0) Somnolence
- (R40.1) Stupor
- (R40.2) Coma, unspecified
- (R41) Other symptoms and signs involving cognitive functions and awareness
(R41.0) Disorientation, unspecified
(R41.1) Anterograde amnesia
(R41.2) Retrograde amnesia
(R41.3) Other amnesia
(R41.8) Other and unspecified symptoms and signs involving cognitive functions and awareness
- (R41.0) Disorientation, unspecified
- (R41.1) Anterograde amnesia
- (R41.2) Retrograde amnesia
- (R41.3) Other amnesia
- (R41.8) Other and unspecified symptoms and signs involving cognitive functions and awareness
- (R42) Dizziness and giddiness
Vertigo NOS
- Vertigo NOS
- (R43) Disturbances of smell and taste
(R43.0) Anosmia
(R43.1) Parosmia
(R43.2) Parageusia
(R43.8) Other and unspecified disturbances of smell and taste
- (R43.0) Anosmia
- (R43.1) Parosmia
- (R43.2) Parageusia
- (R43.8) Other and unspecified disturbances of smell and taste
- (R44) Other symptoms and signs involving general sensations and perceptions
(R44.0) Auditory hallucinations
(R44.1) Visual hallucinations
(R44.2) Other hallucinations
(R44.3) Hallucinations, unspecified
(R44.8) Other and unspecified symptoms and signs involving general sensations and perceptions
- (R44.0) Auditory hallucinations
- (R44.1) Visual hallucinations
- (R44.2) Other hallucinations
- (R44.3) Hallucinations, unspecified
- (R44.8) Other and unspecified symptoms and signs involving general sensations and perceptions
- (R45) Symptoms and signs involving emotional state
(R45.0) Nervousness
(R45.1) Restlessness and agitation
(R45.2) Unhappiness
(R45.3) Demoralization and apathy
(R45.4) Irritability and anger
(R45.5) Hostility
(R45.6) Physical violence
(R45.7) State of emotional shock and stress, unspecified
(R45.8) Other symptoms and signs involving emotional state
Suicidal ideation (tendencies)
- (R45.0) Nervousness
- (R45.1) Restlessness and agitation
- (R45.2) Unhappiness
- (R45.3) Demoralization and apathy
- (R45.4) Irritability and anger
- (R45.5) Hostility
- (R45.6) Physical violence
- (R45.7) State of emotional shock and stress, unspecified
- (R45.8) Other symptoms and signs involving emotional state
Suicidal ideation (tendencies)
- Suicidal ideation (tendencies)
- (R46) Symptoms and signs involving appearance and behaviour
(R46.0) Very low level of personal hygiene
(R46.1) Bizarre personal appearance
(R46.2) Strange and inexplicable behaviour
(R46.3) Overactivity
(R46.4) Slowness and poor responsiveness
(R46.5) Suspiciousness and marked evasiveness
(R46.6) Undue concern and preoccupation with stressful events
(R46.7) Verbosity and circumstantial detail obscuring reason for contact
(R46.8) Other symptoms and signs involving appearance and behaviour
- (R46.0) Very low level of personal hygiene
- (R46.1) Bizarre personal appearance
- (R46.2) Strange and inexplicable behaviour
- (R46.3) Overactivity
- (R46.4) Slowness and poor responsiveness
- (R46.5) Suspiciousness and marked evasiveness
- (R46.6) Undue concern and preoccupation with stressful events
- (R46.7) Verbosity and circumstantial detail obscuring reason for contact
- (R46.8) Other symptoms and signs involving appearance and behaviour
## (R47–R49) Speech and voice
- (R47) Speech disturbances, not elsewhere classified
(R47.0) Dysphasia and aphasia
(R47.1) Dysarthria and anarthria
(R47.8) Other and unspecified speech disturbances
- (R47.0) Dysphasia and aphasia
- (R47.1) Dysarthria and anarthria
- (R47.8) Other and unspecified speech disturbances
- (R48) Dyslexia and other Symbolic dysfunctions, not elsewhere classified
(R48.0) Dyslexia and alexia
(R48.1) Agnosia
(R48.2) Apraxia
(R48.8) Other and unspecified Symbolic dysfunctions
Acalculia
Agraphia
- (R48.0) Dyslexia and alexia
- (R48.1) Agnosia
- (R48.2) Apraxia
- (R48.8) Other and unspecified Symbolic dysfunctions
Acalculia
Agraphia
- Acalculia
- Agraphia
- (R49) Voice disturbances
(R49.0) Dysphonia
(R49.1) Aphonia
(R49.2) Hypernasality and hyponasality
(R49.8) Other and unspecified voice disturbances
- (R49.0) Dysphonia
- (R49.1) Aphonia
- (R49.2) Hypernasality and hyponasality
- (R49.8) Other and unspecified voice disturbances
## (R50–R69) General symptoms and signs
- (R50) Fever of unknown origin
(R50.0) Fever with chills
(R50.1) Persistent fever
(R50.9) Fever, unspecified
- (R50.0) Fever with chills
- (R50.1) Persistent fever
- (R50.9) Fever, unspecified
- (R51) Headache
- (R52) Pain, not elsewhere classified
(R52.0) Acute pain
(R52.1) Chronic intractable pain
(R52.2) Other chronic pain
(R52.9) Pain, unspecified
- (R52.0) Acute pain
- (R52.1) Chronic intractable pain
- (R52.2) Other chronic pain
- (R52.9) Pain, unspecified
- (R53) Malaise and fatigue
Asthenia NOS
Debility NOS
General physical deterioration
Lethargy
Tiredness
- Asthenia NOS
- Debility NOS
- General physical deterioration
- Lethargy
- Tiredness
- (R54) Senility
- (R55) Syncope and collapse
- (R56) Convulsions, not elsewhere classified
(R56.0) Febrile convulsions
(R56.8) Other and unspecified convulsions
Fit NOS
Seizure (convulsive) NOS
- (R56.0) Febrile convulsions
- (R56.8) Other and unspecified convulsions
Fit NOS
Seizure (convulsive) NOS
- Fit NOS
- Seizure (convulsive) NOS
- (R57) Shock, not elsewhere classified
(R57.0) Cardiogenic shock
(R57.1) Hypovolaemic shock
(R57.8) Other shock
(R57.9) Shock, unspecified
- (R57.0) Cardiogenic shock
- (R57.1) Hypovolaemic shock
- (R57.8) Other shock
- (R57.9) Shock, unspecified
- (R58) Haemorrhage, not elsewhere classified
- (R59) Enlarged lymph nodes
(R59.0) Localized enlarged lymph nodes
(R59.1) Generalized enlarged lymph nodes
Lymphadenopathy NOS
- (R59.0) Localized enlarged lymph nodes
- (R59.1) Generalized enlarged lymph nodes
Lymphadenopathy NOS
- Lymphadenopathy NOS
- (R60) Oedema, not elsewhere classified
(R60.0) Localized oedema
Peripheral edema
(R60.1) Generalized oedema
(R60.9) Oedema, unspecified
- (R60.0) Localized oedema
Peripheral edema
- Peripheral edema
- (R60.1) Generalized oedema
- (R60.9) Oedema, unspecified
- (R61) Hyperhidrosis
(R61.0) Localized hyperhidrosis
(R61.1) Generalized hyperhidrosis
(R61.9) Hyperhidrosis, unspecified
Night sweats
- (R61.0) Localized hyperhidrosis
- (R61.1) Generalized hyperhidrosis
- (R61.9) Hyperhidrosis, unspecified
Night sweats
- Night sweats
- (R62) Lack of expected normal physiological development
(R62.0) Delayed milestone
(R62.8) Other lack of expected normal physiological development
Failure to gain weight
Failure to thrive
Infantilism NOS
Lack of growth
Physical retardation
(R62.9) Lack of expected normal physiological development, unspecified
- (R62.0) Delayed milestone
- (R62.8) Other lack of expected normal physiological development
Failure to gain weight
Failure to thrive
Infantilism NOS
Lack of growth
Physical retardation
- Failure to gain weight
- Failure to thrive
- Infantilism NOS
- Lack of growth
- Physical retardation
- (R62.9) Lack of expected normal physiological development, unspecified
- (R63) Symptoms and signs concerning food and fluid intake
(R63.0) Anorexia
(R63.1) Polydipsia
(R63.2) Polyphagia
(R63.3) Feeding difficulties and mismanagement
(R63.4) Abnormal weight loss
(R63.5) Abnormal weight gain
(R63.8) Other symptoms and signs concerning food and fluid intake
- (R63.0) Anorexia
- (R63.1) Polydipsia
- (R63.2) Polyphagia
- (R63.3) Feeding difficulties and mismanagement
- (R63.4) Abnormal weight loss
- (R63.5) Abnormal weight gain
- (R63.8) Other symptoms and signs concerning food and fluid intake
- (R64) Cachexia
- (R68) Other general symptoms and signs
(R68.0) Hypothermia, not associated with low environmental temperature
(R68.1) Nonspecific symptoms peculiar to infancy
(R68.2) Dry mouth, unspecified
(R68.3) Clubbing of fingers
(R68.8) Other specified general symptoms and signs
- (R68.0) Hypothermia, not associated with low environmental temperature
- (R68.1) Nonspecific symptoms peculiar to infancy
- (R68.2) Dry mouth, unspecified
- (R68.3) Clubbing of fingers
- (R68.8) Other specified general symptoms and signs
- (R69) Unknown and unspecified causes of morbidity
# R70–R94 – Abnormal clinical and laboratory findings, not elsewhere classified
## (R70–R79) On examination of blood, without diagnosis
- (R70) Elevated erythrocyte sedimentation rate and abnormality of plasma viscosity
(R70.0) Elevated erythrocyte sedimentation rate
(R70.1) Abnormal plasma viscosity
- (R70.0) Elevated erythrocyte sedimentation rate
- (R70.1) Abnormal plasma viscosity
- (R71) Abnormality of red blood cells
Anisocytosis
Poikilocytosis
- Anisocytosis
- Poikilocytosis
- (R72) Abnormality of white blood cells, not elsewhere classified
- (R73) Elevated blood glucose level
(R73.0) Abnormal glucose tolerance test
Impaired glucose tolerance
Prediabetes
(R73.9) Hyperglycaemia, unspecified
- (R73.0) Abnormal glucose tolerance test
Impaired glucose tolerance
Prediabetes
- Impaired glucose tolerance
- Prediabetes
- (R73.9) Hyperglycaemia, unspecified
- (R74) Abnormal serum enzyme levels
(R74.0) Elevation of levels of transaminase and lactic acid dehydrogenase (LDH)
(R74.8) Abnormal levels of other serum enzymes
acid phosphatase
alkaline phosphatase
amylase
lipase (triacylglycerol lipase)
(R74.9) Abnormal level of unspecified serum enzyme
- (R74.0) Elevation of levels of transaminase and lactic acid dehydrogenase (LDH)
- (R74.8) Abnormal levels of other serum enzymes
acid phosphatase
alkaline phosphatase
amylase
lipase (triacylglycerol lipase)
- acid phosphatase
- alkaline phosphatase
- amylase
- lipase (triacylglycerol lipase)
- (R74.9) Abnormal level of unspecified serum enzyme
- (R75) Laboratory evidence of human immunodeficiency virus (HIV)
- (R76) Other abnormal immunological findings in serum
(R76.0) Raised antibody titre
(R76.1) Abnormal reaction to tuberculin test
(R76.2) False-positive serological test for syphilis
(R76.8) Other specified abnormal immunological findings in serum
(R76.9) Abnormal immunological finding in serum, unspecified
- (R76.0) Raised antibody titre
- (R76.1) Abnormal reaction to tuberculin test
- (R76.2) False-positive serological test for syphilis
- (R76.8) Other specified abnormal immunological findings in serum
- (R76.9) Abnormal immunological finding in serum, unspecified
- (R77) Other abnormalities of plasma proteins
(R77.0) Abnormality of albumin
(R77.1) Abnormality of globulin
(R77.2) Abnormality of alphafetoprotein
(R77.8) Other specified abnormalities of plasma proteins
(R77.9) Abnormality of plasma protein, unspecified
- (R77.0) Abnormality of albumin
- (R77.1) Abnormality of globulin
- (R77.2) Abnormality of alphafetoprotein
- (R77.8) Other specified abnormalities of plasma proteins
- (R77.9) Abnormality of plasma protein, unspecified
- (R78) Findings of drugs and other substances, not normally found in blood
(R78.0) Finding of alcohol in blood
(R78.1) Finding of opiate drug in blood
(R78.2) Finding of cocaine in blood
(R78.3) Finding of hallucinogen in blood
(R78.4) Finding of other drugs of addictive potential in blood
(R78.5) Finding of psychotropic drug in blood
(R78.6) Finding of steroid agent in blood
(R78.7) Finding of abnormal level of heavy metals in blood
(R78.8) Finding of other specified substances, not normally found in blood
(R78.9) Finding of unspecified substance, not normally found in blood
- (R78.0) Finding of alcohol in blood
- (R78.1) Finding of opiate drug in blood
- (R78.2) Finding of cocaine in blood
- (R78.3) Finding of hallucinogen in blood
- (R78.4) Finding of other drugs of addictive potential in blood
- (R78.5) Finding of psychotropic drug in blood
- (R78.6) Finding of steroid agent in blood
- (R78.7) Finding of abnormal level of heavy metals in blood
- (R78.8) Finding of other specified substances, not normally found in blood
- (R78.9) Finding of unspecified substance, not normally found in blood
- (R79) Other abnormal findings of blood chemistry
(R79.0) Abnormal level of blood mineral
(R79.8) Other specified abnormal findings of blood chemistry
Abnormal blood-gas level
(R79.9) Abnormal finding of blood chemistry, unspecified
- (R79.0) Abnormal level of blood mineral
- (R79.8) Other specified abnormal findings of blood chemistry
Abnormal blood-gas level
- Abnormal blood-gas level
- (R79.9) Abnormal finding of blood chemistry, unspecified
## (R80–R82) On examination of urine, without diagnosis
- (R80) Isolated proteinuria
Albuminuria
- Albuminuria
- (R81) Glycosuria
- (R82) Other abnormal findings in urine
(R82.0) Chyluria
(R82.1) Myoglobinuria
(R82.2) Biliuria
(R82.3) Haemoglobinuria
(R82.4) Acetonuria
Ketonuria
(R82.5) Elevated urine levels of drugs, medicaments and biological substances
(R82.6) Abnormal urine levels of substances chiefly nonmedicinal as to source
(R82.7) Abnormal findings on microbiological examination of urine
(R82.8) Abnormal findings on cytological and histological examination of urine
(R82.9) Other and unspecified abnormal findings in urine
Cells and casts in urine
Crystalluria
Melanuria
- (R82.0) Chyluria
- (R82.1) Myoglobinuria
- (R82.2) Biliuria
- (R82.3) Haemoglobinuria
- (R82.4) Acetonuria
Ketonuria
- Ketonuria
- (R82.5) Elevated urine levels of drugs, medicaments and biological substances
- (R82.6) Abnormal urine levels of substances chiefly nonmedicinal as to source
- (R82.7) Abnormal findings on microbiological examination of urine
- (R82.8) Abnormal findings on cytological and histological examination of urine
- (R82.9) Other and unspecified abnormal findings in urine
Cells and casts in urine
Crystalluria
Melanuria
- Cells and casts in urine
- Crystalluria
- Melanuria
## (R83–R89) On examination of other body fluids, substances and tissues, without diagnosis
- (R83) Abnormal findings in cerebrospinal fluid
- (R84) Abnormal findings in specimens from respiratory organs and thorax
- (R85) Abnormal findings in specimens from digestive organs and abdominal cavity
- (R86) Abnormal findings in specimens from male genital organs
- (R87) Abnormal findings in specimens from female genital organs
- (R89) Abnormal findings in specimens from other organs, systems and tissues
## (R90–R94) On diagnostic imaging and in function studies, without diagnosis
- (R90) Abnormal findings on diagnostic imaging of central nervous system
(R90.0) Intracranial space-occupying lesion
(R90.8) Other abnormal findings on diagnostic imaging of central nervous system
- (R90.0) Intracranial space-occupying lesion
- (R90.8) Other abnormal findings on diagnostic imaging of central nervous system
- (R91) Abnormal findings on diagnostic imaging of lung
- (R92) Abnormal findings on diagnostic imaging of breast
- (R93) Abnormal findings on diagnostic imaging of other body structures
(R93.0) Abnormal findings on diagnostic imaging of skull and head, not elsewhere classified
(R93.1) Abnormal findings on diagnostic imaging of heart and coronary circulation
(R93.2) Abnormal findings on diagnostic imaging of liver and biliary tract
(R93.3) Abnormal findings on diagnostic imaging of other parts of digestive tract
(R93.4) Abnormal findings on diagnostic imaging of urinary organs
(R93.5) Abnormal findings on diagnostic imaging of other abdominal regions, including retroperitoneum
(R93.6) Abnormal findings on diagnostic imaging of limbs
(R93.7) Abnormal findings on diagnostic imaging of other parts of musculoskeletal system
(R93.8) Abnormal findings on diagnostic imaging of other specified body structures
- (R93.0) Abnormal findings on diagnostic imaging of skull and head, not elsewhere classified
- (R93.1) Abnormal findings on diagnostic imaging of heart and coronary circulation
- (R93.2) Abnormal findings on diagnostic imaging of liver and biliary tract
- (R93.3) Abnormal findings on diagnostic imaging of other parts of digestive tract
- (R93.4) Abnormal findings on diagnostic imaging of urinary organs
- (R93.5) Abnormal findings on diagnostic imaging of other abdominal regions, including retroperitoneum
- (R93.6) Abnormal findings on diagnostic imaging of limbs
- (R93.7) Abnormal findings on diagnostic imaging of other parts of musculoskeletal system
- (R93.8) Abnormal findings on diagnostic imaging of other specified body structures
- (R94) Abnormal results of function studies
(R94.0) Abnormal results of function studies of central nervous system
Abnormal electroencephalogram
(R94.1) Abnormal results of function studies of peripheral nervous system and special senses
(R94.2) Abnormal results of pulmonary function studies
Reduced vital capacity
(R94.3) Abnormal results of cardiovascular function studies
Abnormal electrocardiogram
(R94.4) Abnormal results of kidney function studies
Abnormal renal function test
(R94.5) Abnormal results of liver function studies
(R94.6) Abnormal results of thyroid function studies
(R94.7) Abnormal results of other endocrine function studies
(R94.8) Abnormal results of function studies of other organs and systems
Abnormal basal metabolic rate (BMR)
- (R94.0) Abnormal results of function studies of central nervous system
Abnormal electroencephalogram
- Abnormal electroencephalogram
- (R94.1) Abnormal results of function studies of peripheral nervous system and special senses
- (R94.2) Abnormal results of pulmonary function studies
Reduced vital capacity
- Reduced vital capacity
- (R94.3) Abnormal results of cardiovascular function studies
Abnormal electrocardiogram
- Abnormal electrocardiogram
- (R94.4) Abnormal results of kidney function studies
Abnormal renal function test
- Abnormal renal function test
- (R94.5) Abnormal results of liver function studies
- (R94.6) Abnormal results of thyroid function studies
- (R94.7) Abnormal results of other endocrine function studies
- (R94.8) Abnormal results of function studies of other organs and systems
Abnormal basal metabolic rate (BMR)
- Abnormal basal metabolic rate (BMR)
# R95–R99 – Ill-defined and unknown causes of mortality
- (R95) Sudden infant death syndrome
- (R96) Other sudden death, cause unknown
(R96.0) Instantaneous death
(R96.1) Death occurring less than 24 hours from onset of symptoms, not otherwise explained
- (R96.0) Instantaneous death
- (R96.1) Death occurring less than 24 hours from onset of symptoms, not otherwise explained
- (R98) Unattended death
- (R99) Other ill-defined and unspecified causes of mortality
# Excludes
- Abnormal findings on antennatal screening of mother (O28.-)
- Certain conditions originating in the perinatal period (P00-P96)
- Signs and symptoms classified in the body system chapters
- Signs and symptoms of breast (N63, N64.5) | Sandbox g18
Template:ICD-10
# R00–R69 – Symptoms and signs
## (R00–R09) Circulatory and respiratory systems
- (R00) Abnormalities of heart beat
(R00.0) Tachycardia, unspecified
(R00.1) Bradycardia, unspecified
(R00.2) Palpitations
(R00.8) Other and unspecified abnormalities of heart beat
- (R00.0) Tachycardia, unspecified
- (R00.1) Bradycardia, unspecified
- (R00.2) Palpitations
- (R00.8) Other and unspecified abnormalities of heart beat
- (R01) Cardiac murmurs and other cardiac sounds
(R01.0) Benign and innocent cardiac murmurs
(R01.1) Cardiac murmur, unspecified
Cardiac bruit NOS
(R01.2) Other cardiac sounds
- (R01.0) Benign and innocent cardiac murmurs
- (R01.1) Cardiac murmur, unspecified
Cardiac bruit NOS
- Cardiac bruit NOS
- (R01.2) Other cardiac sounds
- (R02) Gangrene, not elsewhere classified
- (R03) Abnormal blood-pressure reading, without diagnosis
(R03.0) Elevated blood-pressure reading, without diagnosis of hypertension
(R03.1) Nonspecific low blood-pressure reading
- (R03.0) Elevated blood-pressure reading, without diagnosis of hypertension
- (R03.1) Nonspecific low blood-pressure reading
- (R04) Haemorrhage from respiratory passages
(R04.0) Epistaxis
(R04.1) Haemorrhage from throat
(R04.2) Haemoptysis
(R04.8) Haemorrhage from other sites in respiratory passages
(R04.9) Haemorrhage from respiratory passages, unspecified
- (R04.0) Epistaxis
- (R04.1) Haemorrhage from throat
- (R04.2) Haemoptysis
- (R04.8) Haemorrhage from other sites in respiratory passages
- (R04.9) Haemorrhage from respiratory passages, unspecified
- (R05) Cough
- (R06) Abnormalities of breathing
(R06.0) Dyspnoea
Orthopnoea
(R06.1) Stridor
(R06.2) Wheezing
(R06.3) Periodic breathing
Cheyne-Stokes respiration
(R06.4) Hyperventilation
(R06.5) Mouth breathing
Snoring
(R06.6) Hiccough
(R06.7) Sneezing
(R06.8) Other and unspecified abnormalities of breathing
Choking sensation
- (R06.0) Dyspnoea
Orthopnoea
- Orthopnoea
- (R06.1) Stridor
- (R06.2) Wheezing
- (R06.3) Periodic breathing
Cheyne-Stokes respiration
- Cheyne-Stokes respiration
- (R06.4) Hyperventilation
- (R06.5) Mouth breathing
Snoring
- Snoring
- (R06.6) Hiccough
- (R06.7) Sneezing
- (R06.8) Other and unspecified abnormalities of breathing
Choking sensation
- Choking sensation
- (R07) Pain in throat and chest
(R07.0) Pain in throat
(R07.1) Chest pain on breathing
(R07.2) Precordial pain
(R07.3) Other chest pain
(R07.4) Chest pain, unspecified
- (R07.0) Pain in throat
- (R07.1) Chest pain on breathing
- (R07.2) Precordial pain
- (R07.3) Other chest pain
- (R07.4) Chest pain, unspecified
- (R09) Other symptoms and signs involving the circulatory and respiratory systems
(R09.0) Asphyxia
(R09.1) Pleurisy
(R09.2) Respiratory arrest
(R09.3) Abnormal sputum
(R09.8) Other specified symptoms and signs involving the circulatory and respiratory systems
Rales
Arterial Bruit
- (R09.0) Asphyxia
- (R09.1) Pleurisy
- (R09.2) Respiratory arrest
- (R09.3) Abnormal sputum
- (R09.8) Other specified symptoms and signs involving the circulatory and respiratory systems
Rales
Arterial Bruit
- Rales
- Arterial Bruit
## (R10–R19) Digestive system and abdomen
- (R10) Abdominal and pelvic pain
(R10.0) Acute abdomen
(R10.1) Pain localized to upper abdomen
(R10.2) Pelvic and perineal pain
(R10.3) Pain localized to other parts of lower abdomen
(R10.4) Other and unspecified abdominal pain
Abdominal tenderness NOS
Colic, NOS
infantile colic
- (R10.0) Acute abdomen
- (R10.1) Pain localized to upper abdomen
- (R10.2) Pelvic and perineal pain
- (R10.3) Pain localized to other parts of lower abdomen
- (R10.4) Other and unspecified abdominal pain
Abdominal tenderness NOS
Colic, NOS
infantile colic
- Abdominal tenderness NOS
- Colic, NOS
- infantile colic
- (R11) Nausea and vomiting
- (R12) Heartburn
- (R13) Dysphagia
- (R14) Flatulence and related conditions
Abdominal distension (gaseous)
Bloating
Eructation
Gas pain
Tympanites (abdominal)(intestinal)
- Abdominal distension (gaseous)
- Bloating
- Eructation
- Gas pain
- Tympanites (abdominal)(intestinal)
- (R15) Faecal incontinence
Encopresis
- Encopresis
- (R16) Hepatomegaly and splenomegaly, not elsewhere classified
(R16.0) Hepatomegaly, not elsewhere classified
(R16.1) Splenomegaly, not elsewhere classified
(R16.2) Hepatomegaly with splenomegaly, not elsewhere classified
Hepatosplenomegaly NOS
- (R16.0) Hepatomegaly, not elsewhere classified
- (R16.1) Splenomegaly, not elsewhere classified
- (R16.2) Hepatomegaly with splenomegaly, not elsewhere classified
Hepatosplenomegaly NOS
- Hepatosplenomegaly NOS
- (R17) Unspecified jaundice
- (R18) Ascites
- (R19) Other symptoms and signs involving the digestive system and abdomen
(R19.0) Intra-abdominal and pelvic swelling, mass and lump
(R19.1) Abnormal bowel sounds
(R19.2) Visible peristalsis
(R19.3) Abdominal rigidity
(R19.4) Change in bowel habit
(R19.5) Other faecal abnormalities
(R19.6) Halitosis
(R19.8) Other specified symptoms and signs involving the digestive system and abdomen
- (R19.0) Intra-abdominal and pelvic swelling, mass and lump
- (R19.1) Abnormal bowel sounds
- (R19.2) Visible peristalsis
- (R19.3) Abdominal rigidity
- (R19.4) Change in bowel habit
- (R19.5) Other faecal abnormalities
- (R19.6) Halitosis
- (R19.8) Other specified symptoms and signs involving the digestive system and abdomen
## (R20–R23) Skin and subcutaneous tissue
- (R20) Disturbances of skin sensation
(R20.0) Anaesthesia of skin
(R20.1) Hypoaesthesia of skin
(R20.2) Paraesthesia of skin
(R20.3) Hyperaesthesia
(R20.8) Other and unspecified disturbances of skin sensation
- (R20.0) Anaesthesia of skin
- (R20.1) Hypoaesthesia of skin
- (R20.2) Paraesthesia of skin
- (R20.3) Hyperaesthesia
- (R20.8) Other and unspecified disturbances of skin sensation
- (R21) Rash and other nonspecific skin eruption
- (R22) Localized swelling, mass and lump of skin and subcutaneous tissue
(R22.0) Localized swelling, mass and lump, head
(R22.1) Localized swelling, mass and lump, neck
(R22.2) Localized swelling, mass and lump, trunk
(R22.3) Localized swelling, mass and lump, upper limb
(R22.4) Localized swelling, mass and lump, lower limb
(R22.7) Localized swelling, mass and lump, multiple sites
(R22.9) Localized swelling, mass and lump, unspecified
- (R22.0) Localized swelling, mass and lump, head
- (R22.1) Localized swelling, mass and lump, neck
- (R22.2) Localized swelling, mass and lump, trunk
- (R22.3) Localized swelling, mass and lump, upper limb
- (R22.4) Localized swelling, mass and lump, lower limb
- (R22.7) Localized swelling, mass and lump, multiple sites
- (R22.9) Localized swelling, mass and lump, unspecified
- (R23) Other skin changes
(R23.0) Cyanosis
(R23.1) Pallor
(R23.2) Flushing
(R23.3) Spontaneous ecchymoses
Petechiae
(R23.4) Changes in skin texture
Desquamation
Induration
(R23.8) Other and unspecified skin changes
- (R23.0) Cyanosis
- (R23.1) Pallor
- (R23.2) Flushing
- (R23.3) Spontaneous ecchymoses
Petechiae
- Petechiae
- (R23.4) Changes in skin texture
Desquamation
Induration
- Desquamation
- Induration
- (R23.8) Other and unspecified skin changes
## (R25–R29) Nervous and musculoskeletal systems
- (R25) Abnormal involuntary movements
(R25.0) Abnormal head movements
(R25.1) Tremor, unspecified
(R25.2) Cramp and spasm
(R25.3) Fasciculation
(R25.8) Other and unspecified abnormal involuntary movements
- (R25.0) Abnormal head movements
- (R25.1) Tremor, unspecified
- (R25.2) Cramp and spasm
- (R25.3) Fasciculation
- (R25.8) Other and unspecified abnormal involuntary movements
- (R26) Abnormalities of gait and mobility
(R26.0) Ataxic gait
(R26.1) Paralytic gait
(R26.2) Difficulty in walking, not elsewhere classified
(R26.8) Other and unspecified abnormalities of gait and mobility
- (R26.0) Ataxic gait
- (R26.1) Paralytic gait
- (R26.2) Difficulty in walking, not elsewhere classified
- (R26.8) Other and unspecified abnormalities of gait and mobility
- (R27) Other lack of coordination
(R27.0) Ataxia, unspecified
(R27.8) Other and unspecified lack of coordination
- (R27.0) Ataxia, unspecified
- (R27.8) Other and unspecified lack of coordination
- (R29) Other symptoms and signs involving the nervous and musculoskeletal systems
(R29.0) Tetany
(R29.1) Meningismus
(R29.2) Abnormal reflex
Hyperreflexia
(R29.3) Abnormal posture
(R29.4) Clicking hip
(R29.8) Other and unspecified symptoms and signs involving the nervous and musculoskeletal systems
- (R29.0) Tetany
- (R29.1) Meningismus
- (R29.2) Abnormal reflex
Hyperreflexia
- Hyperreflexia
- (R29.3) Abnormal posture
- (R29.4) Clicking hip
- (R29.8) Other and unspecified symptoms and signs involving the nervous and musculoskeletal systems
## (R30–R39) Urinary system
- (R30) Pain associated with micturition
(R30.0) Dysuria
(R30.1) Vesical tenesmus
(R30.9) Painful micturition, unspecified
- (R30.0) Dysuria
- (R30.1) Vesical tenesmus
- (R30.9) Painful micturition, unspecified
- (R31) Unspecified haematuria
- (R32) Unspecified urinary incontinence
- (R33) Retention of urine
- (R34) Anuria and oliguria
- (R35) Polyuria
Nocturia
- Nocturia
- (R36) Urethral discharge
- (R39) Other symptoms and signs involving the urinary system
(R39.0) Extravasation of urine
(R39.1) Other difficulties with micturition
(R39.2) Extrarenal uraemia
(R39.8) Other and unspecified symptoms and signs involving the urinary system
- (R39.0) Extravasation of urine
- (R39.1) Other difficulties with micturition
- (R39.2) Extrarenal uraemia
- (R39.8) Other and unspecified symptoms and signs involving the urinary system
## (R40–R46) Cognition, perception, emotional state and behaviour
- (R40) Somnolence, stupor and coma
(R40.0) Somnolence
(R40.1) Stupor
(R40.2) Coma, unspecified
- (R40.0) Somnolence
- (R40.1) Stupor
- (R40.2) Coma, unspecified
- (R41) Other symptoms and signs involving cognitive functions and awareness
(R41.0) Disorientation, unspecified
(R41.1) Anterograde amnesia
(R41.2) Retrograde amnesia
(R41.3) Other amnesia
(R41.8) Other and unspecified symptoms and signs involving cognitive functions and awareness
- (R41.0) Disorientation, unspecified
- (R41.1) Anterograde amnesia
- (R41.2) Retrograde amnesia
- (R41.3) Other amnesia
- (R41.8) Other and unspecified symptoms and signs involving cognitive functions and awareness
- (R42) Dizziness and giddiness
Vertigo NOS
- Vertigo NOS
- (R43) Disturbances of smell and taste
(R43.0) Anosmia
(R43.1) Parosmia
(R43.2) Parageusia
(R43.8) Other and unspecified disturbances of smell and taste
- (R43.0) Anosmia
- (R43.1) Parosmia
- (R43.2) Parageusia
- (R43.8) Other and unspecified disturbances of smell and taste
- (R44) Other symptoms and signs involving general sensations and perceptions
(R44.0) Auditory hallucinations
(R44.1) Visual hallucinations
(R44.2) Other hallucinations
(R44.3) Hallucinations, unspecified
(R44.8) Other and unspecified symptoms and signs involving general sensations and perceptions
- (R44.0) Auditory hallucinations
- (R44.1) Visual hallucinations
- (R44.2) Other hallucinations
- (R44.3) Hallucinations, unspecified
- (R44.8) Other and unspecified symptoms and signs involving general sensations and perceptions
- (R45) Symptoms and signs involving emotional state
(R45.0) Nervousness
(R45.1) Restlessness and agitation
(R45.2) Unhappiness
(R45.3) Demoralization and apathy
(R45.4) Irritability and anger
(R45.5) Hostility
(R45.6) Physical violence
(R45.7) State of emotional shock and stress, unspecified
(R45.8) Other symptoms and signs involving emotional state
Suicidal ideation (tendencies)
- (R45.0) Nervousness
- (R45.1) Restlessness and agitation
- (R45.2) Unhappiness
- (R45.3) Demoralization and apathy
- (R45.4) Irritability and anger
- (R45.5) Hostility
- (R45.6) Physical violence
- (R45.7) State of emotional shock and stress, unspecified
- (R45.8) Other symptoms and signs involving emotional state
Suicidal ideation (tendencies)
- Suicidal ideation (tendencies)
- (R46) Symptoms and signs involving appearance and behaviour
(R46.0) Very low level of personal hygiene
(R46.1) Bizarre personal appearance
(R46.2) Strange and inexplicable behaviour
(R46.3) Overactivity
(R46.4) Slowness and poor responsiveness
(R46.5) Suspiciousness and marked evasiveness
(R46.6) Undue concern and preoccupation with stressful events
(R46.7) Verbosity and circumstantial detail obscuring reason for contact
(R46.8) Other symptoms and signs involving appearance and behaviour
- (R46.0) Very low level of personal hygiene
- (R46.1) Bizarre personal appearance
- (R46.2) Strange and inexplicable behaviour
- (R46.3) Overactivity
- (R46.4) Slowness and poor responsiveness
- (R46.5) Suspiciousness and marked evasiveness
- (R46.6) Undue concern and preoccupation with stressful events
- (R46.7) Verbosity and circumstantial detail obscuring reason for contact
- (R46.8) Other symptoms and signs involving appearance and behaviour
## (R47–R49) Speech and voice
- (R47) Speech disturbances, not elsewhere classified
(R47.0) Dysphasia and aphasia
(R47.1) Dysarthria and anarthria
(R47.8) Other and unspecified speech disturbances
- (R47.0) Dysphasia and aphasia
- (R47.1) Dysarthria and anarthria
- (R47.8) Other and unspecified speech disturbances
- (R48) Dyslexia and other Symbolic dysfunctions, not elsewhere classified
(R48.0) Dyslexia and alexia
(R48.1) Agnosia
(R48.2) Apraxia
(R48.8) Other and unspecified Symbolic dysfunctions
Acalculia
Agraphia
- (R48.0) Dyslexia and alexia
- (R48.1) Agnosia
- (R48.2) Apraxia
- (R48.8) Other and unspecified Symbolic dysfunctions
Acalculia
Agraphia
- Acalculia
- Agraphia
- (R49) Voice disturbances
(R49.0) Dysphonia
(R49.1) Aphonia
(R49.2) Hypernasality and hyponasality
(R49.8) Other and unspecified voice disturbances
- (R49.0) Dysphonia
- (R49.1) Aphonia
- (R49.2) Hypernasality and hyponasality
- (R49.8) Other and unspecified voice disturbances
## (R50–R69) General symptoms and signs
- (R50) Fever of unknown origin
(R50.0) Fever with chills
(R50.1) Persistent fever
(R50.9) Fever, unspecified
- (R50.0) Fever with chills
- (R50.1) Persistent fever
- (R50.9) Fever, unspecified
- (R51) Headache
- (R52) Pain, not elsewhere classified
(R52.0) Acute pain
(R52.1) Chronic intractable pain
(R52.2) Other chronic pain
(R52.9) Pain, unspecified
- (R52.0) Acute pain
- (R52.1) Chronic intractable pain
- (R52.2) Other chronic pain
- (R52.9) Pain, unspecified
- (R53) Malaise and fatigue
Asthenia NOS
Debility NOS
General physical deterioration
Lethargy
Tiredness
- Asthenia NOS
- Debility NOS
- General physical deterioration
- Lethargy
- Tiredness
- (R54) Senility
- (R55) Syncope and collapse
- (R56) Convulsions, not elsewhere classified
(R56.0) Febrile convulsions
(R56.8) Other and unspecified convulsions
Fit NOS
Seizure (convulsive) NOS
- (R56.0) Febrile convulsions
- (R56.8) Other and unspecified convulsions
Fit NOS
Seizure (convulsive) NOS
- Fit NOS
- Seizure (convulsive) NOS
- (R57) Shock, not elsewhere classified
(R57.0) Cardiogenic shock
(R57.1) Hypovolaemic shock
(R57.8) Other shock
(R57.9) Shock, unspecified
- (R57.0) Cardiogenic shock
- (R57.1) Hypovolaemic shock
- (R57.8) Other shock
- (R57.9) Shock, unspecified
- (R58) Haemorrhage, not elsewhere classified
- (R59) Enlarged lymph nodes
(R59.0) Localized enlarged lymph nodes
(R59.1) Generalized enlarged lymph nodes
Lymphadenopathy NOS
- (R59.0) Localized enlarged lymph nodes
- (R59.1) Generalized enlarged lymph nodes
Lymphadenopathy NOS
- Lymphadenopathy NOS
- (R60) Oedema, not elsewhere classified
(R60.0) Localized oedema
Peripheral edema
(R60.1) Generalized oedema
(R60.9) Oedema, unspecified
- (R60.0) Localized oedema
Peripheral edema
- Peripheral edema
- (R60.1) Generalized oedema
- (R60.9) Oedema, unspecified
- (R61) Hyperhidrosis
(R61.0) Localized hyperhidrosis
(R61.1) Generalized hyperhidrosis
(R61.9) Hyperhidrosis, unspecified
Night sweats
- (R61.0) Localized hyperhidrosis
- (R61.1) Generalized hyperhidrosis
- (R61.9) Hyperhidrosis, unspecified
Night sweats
- Night sweats
- (R62) Lack of expected normal physiological development
(R62.0) Delayed milestone
(R62.8) Other lack of expected normal physiological development
Failure to gain weight
Failure to thrive
Infantilism NOS
Lack of growth
Physical retardation
(R62.9) Lack of expected normal physiological development, unspecified
- (R62.0) Delayed milestone
- (R62.8) Other lack of expected normal physiological development
Failure to gain weight
Failure to thrive
Infantilism NOS
Lack of growth
Physical retardation
- Failure to gain weight
- Failure to thrive
- Infantilism NOS
- Lack of growth
- Physical retardation
- (R62.9) Lack of expected normal physiological development, unspecified
- (R63) Symptoms and signs concerning food and fluid intake
(R63.0) Anorexia
(R63.1) Polydipsia
(R63.2) Polyphagia
(R63.3) Feeding difficulties and mismanagement
(R63.4) Abnormal weight loss
(R63.5) Abnormal weight gain
(R63.8) Other symptoms and signs concerning food and fluid intake
- (R63.0) Anorexia
- (R63.1) Polydipsia
- (R63.2) Polyphagia
- (R63.3) Feeding difficulties and mismanagement
- (R63.4) Abnormal weight loss
- (R63.5) Abnormal weight gain
- (R63.8) Other symptoms and signs concerning food and fluid intake
- (R64) Cachexia
- (R68) Other general symptoms and signs
(R68.0) Hypothermia, not associated with low environmental temperature
(R68.1) Nonspecific symptoms peculiar to infancy
(R68.2) Dry mouth, unspecified
(R68.3) Clubbing of fingers
(R68.8) Other specified general symptoms and signs
- (R68.0) Hypothermia, not associated with low environmental temperature
- (R68.1) Nonspecific symptoms peculiar to infancy
- (R68.2) Dry mouth, unspecified
- (R68.3) Clubbing of fingers
- (R68.8) Other specified general symptoms and signs
- (R69) Unknown and unspecified causes of morbidity
# R70–R94 – Abnormal clinical and laboratory findings, not elsewhere classified
## (R70–R79) On examination of blood, without diagnosis
- (R70) Elevated erythrocyte sedimentation rate and abnormality of plasma viscosity
(R70.0) Elevated erythrocyte sedimentation rate
(R70.1) Abnormal plasma viscosity
- (R70.0) Elevated erythrocyte sedimentation rate
- (R70.1) Abnormal plasma viscosity
- (R71) Abnormality of red blood cells
Anisocytosis
Poikilocytosis
- Anisocytosis
- Poikilocytosis
- (R72) Abnormality of white blood cells, not elsewhere classified
- (R73) Elevated blood glucose level
(R73.0) Abnormal glucose tolerance test
Impaired glucose tolerance
Prediabetes
(R73.9) Hyperglycaemia, unspecified
- (R73.0) Abnormal glucose tolerance test
Impaired glucose tolerance
Prediabetes
- Impaired glucose tolerance
- Prediabetes
- (R73.9) Hyperglycaemia, unspecified
- (R74) Abnormal serum enzyme levels
(R74.0) Elevation of levels of transaminase and lactic acid dehydrogenase (LDH)
(R74.8) Abnormal levels of other serum enzymes
acid phosphatase
alkaline phosphatase
amylase
lipase (triacylglycerol lipase[disambiguation needed])
(R74.9) Abnormal level of unspecified serum enzyme
- (R74.0) Elevation of levels of transaminase and lactic acid dehydrogenase (LDH)
- (R74.8) Abnormal levels of other serum enzymes
acid phosphatase
alkaline phosphatase
amylase
lipase (triacylglycerol lipase[disambiguation needed])
- acid phosphatase
- alkaline phosphatase
- amylase
- lipase (triacylglycerol lipase[disambiguation needed])
- (R74.9) Abnormal level of unspecified serum enzyme
- (R75) Laboratory evidence of human immunodeficiency virus (HIV)
- (R76) Other abnormal immunological findings in serum
(R76.0) Raised antibody titre
(R76.1) Abnormal reaction to tuberculin test
(R76.2) False-positive serological test for syphilis
(R76.8) Other specified abnormal immunological findings in serum
(R76.9) Abnormal immunological finding in serum, unspecified
- (R76.0) Raised antibody titre
- (R76.1) Abnormal reaction to tuberculin test
- (R76.2) False-positive serological test for syphilis
- (R76.8) Other specified abnormal immunological findings in serum
- (R76.9) Abnormal immunological finding in serum, unspecified
- (R77) Other abnormalities of plasma proteins
(R77.0) Abnormality of albumin
(R77.1) Abnormality of globulin
(R77.2) Abnormality of alphafetoprotein
(R77.8) Other specified abnormalities of plasma proteins
(R77.9) Abnormality of plasma protein, unspecified
- (R77.0) Abnormality of albumin
- (R77.1) Abnormality of globulin
- (R77.2) Abnormality of alphafetoprotein
- (R77.8) Other specified abnormalities of plasma proteins
- (R77.9) Abnormality of plasma protein, unspecified
- (R78) Findings of drugs and other substances, not normally found in blood
(R78.0) Finding of alcohol in blood
(R78.1) Finding of opiate drug in blood
(R78.2) Finding of cocaine in blood
(R78.3) Finding of hallucinogen in blood
(R78.4) Finding of other drugs of addictive potential in blood
(R78.5) Finding of psychotropic drug in blood
(R78.6) Finding of steroid agent in blood
(R78.7) Finding of abnormal level of heavy metals in blood
(R78.8) Finding of other specified substances, not normally found in blood
(R78.9) Finding of unspecified substance, not normally found in blood
- (R78.0) Finding of alcohol in blood
- (R78.1) Finding of opiate drug in blood
- (R78.2) Finding of cocaine in blood
- (R78.3) Finding of hallucinogen in blood
- (R78.4) Finding of other drugs of addictive potential in blood
- (R78.5) Finding of psychotropic drug in blood
- (R78.6) Finding of steroid agent in blood
- (R78.7) Finding of abnormal level of heavy metals in blood
- (R78.8) Finding of other specified substances, not normally found in blood
- (R78.9) Finding of unspecified substance, not normally found in blood
- (R79) Other abnormal findings of blood chemistry
(R79.0) Abnormal level of blood mineral
(R79.8) Other specified abnormal findings of blood chemistry
Abnormal blood-gas level
(R79.9) Abnormal finding of blood chemistry, unspecified
- (R79.0) Abnormal level of blood mineral
- (R79.8) Other specified abnormal findings of blood chemistry
Abnormal blood-gas level
- Abnormal blood-gas level
- (R79.9) Abnormal finding of blood chemistry, unspecified
## (R80–R82) On examination of urine, without diagnosis
- (R80) Isolated proteinuria
Albuminuria
- Albuminuria
- (R81) Glycosuria
- (R82) Other abnormal findings in urine
(R82.0) Chyluria
(R82.1) Myoglobinuria
(R82.2) Biliuria
(R82.3) Haemoglobinuria
(R82.4) Acetonuria
Ketonuria
(R82.5) Elevated urine levels of drugs, medicaments and biological substances
(R82.6) Abnormal urine levels of substances chiefly nonmedicinal as to source
(R82.7) Abnormal findings on microbiological examination of urine
(R82.8) Abnormal findings on cytological and histological examination of urine
(R82.9) Other and unspecified abnormal findings in urine
Cells and casts in urine
Crystalluria
Melanuria
- (R82.0) Chyluria
- (R82.1) Myoglobinuria
- (R82.2) Biliuria
- (R82.3) Haemoglobinuria
- (R82.4) Acetonuria
Ketonuria
- Ketonuria
- (R82.5) Elevated urine levels of drugs, medicaments and biological substances
- (R82.6) Abnormal urine levels of substances chiefly nonmedicinal as to source
- (R82.7) Abnormal findings on microbiological examination of urine
- (R82.8) Abnormal findings on cytological and histological examination of urine
- (R82.9) Other and unspecified abnormal findings in urine
Cells and casts in urine
Crystalluria
Melanuria
- Cells and casts in urine
- Crystalluria
- Melanuria
## (R83–R89) On examination of other body fluids, substances and tissues, without diagnosis
- (R83) Abnormal findings in cerebrospinal fluid
- (R84) Abnormal findings in specimens from respiratory organs and thorax
- (R85) Abnormal findings in specimens from digestive organs and abdominal cavity
- (R86) Abnormal findings in specimens from male genital organs
- (R87) Abnormal findings in specimens from female genital organs
- (R89) Abnormal findings in specimens from other organs, systems and tissues
## (R90–R94) On diagnostic imaging and in function studies, without diagnosis
- (R90) Abnormal findings on diagnostic imaging of central nervous system
(R90.0) Intracranial space-occupying lesion
(R90.8) Other abnormal findings on diagnostic imaging of central nervous system
- (R90.0) Intracranial space-occupying lesion
- (R90.8) Other abnormal findings on diagnostic imaging of central nervous system
- (R91) Abnormal findings on diagnostic imaging of lung
- (R92) Abnormal findings on diagnostic imaging of breast
- (R93) Abnormal findings on diagnostic imaging of other body structures
(R93.0) Abnormal findings on diagnostic imaging of skull and head, not elsewhere classified
(R93.1) Abnormal findings on diagnostic imaging of heart and coronary circulation
(R93.2) Abnormal findings on diagnostic imaging of liver and biliary tract
(R93.3) Abnormal findings on diagnostic imaging of other parts of digestive tract
(R93.4) Abnormal findings on diagnostic imaging of urinary organs
(R93.5) Abnormal findings on diagnostic imaging of other abdominal regions, including retroperitoneum
(R93.6) Abnormal findings on diagnostic imaging of limbs
(R93.7) Abnormal findings on diagnostic imaging of other parts of musculoskeletal system
(R93.8) Abnormal findings on diagnostic imaging of other specified body structures
- (R93.0) Abnormal findings on diagnostic imaging of skull and head, not elsewhere classified
- (R93.1) Abnormal findings on diagnostic imaging of heart and coronary circulation
- (R93.2) Abnormal findings on diagnostic imaging of liver and biliary tract
- (R93.3) Abnormal findings on diagnostic imaging of other parts of digestive tract
- (R93.4) Abnormal findings on diagnostic imaging of urinary organs
- (R93.5) Abnormal findings on diagnostic imaging of other abdominal regions, including retroperitoneum
- (R93.6) Abnormal findings on diagnostic imaging of limbs
- (R93.7) Abnormal findings on diagnostic imaging of other parts of musculoskeletal system
- (R93.8) Abnormal findings on diagnostic imaging of other specified body structures
- (R94) Abnormal results of function studies
(R94.0) Abnormal results of function studies of central nervous system
Abnormal electroencephalogram
(R94.1) Abnormal results of function studies of peripheral nervous system and special senses
(R94.2) Abnormal results of pulmonary function studies
Reduced vital capacity
(R94.3) Abnormal results of cardiovascular function studies
Abnormal electrocardiogram
(R94.4) Abnormal results of kidney function studies
Abnormal renal function test
(R94.5) Abnormal results of liver function studies
(R94.6) Abnormal results of thyroid function studies
(R94.7) Abnormal results of other endocrine function studies
(R94.8) Abnormal results of function studies of other organs and systems
Abnormal basal metabolic rate (BMR)
- (R94.0) Abnormal results of function studies of central nervous system
Abnormal electroencephalogram
- Abnormal electroencephalogram
- (R94.1) Abnormal results of function studies of peripheral nervous system and special senses
- (R94.2) Abnormal results of pulmonary function studies
Reduced vital capacity
- Reduced vital capacity
- (R94.3) Abnormal results of cardiovascular function studies
Abnormal electrocardiogram
- Abnormal electrocardiogram
- (R94.4) Abnormal results of kidney function studies
Abnormal renal function test
- Abnormal renal function test
- (R94.5) Abnormal results of liver function studies
- (R94.6) Abnormal results of thyroid function studies
- (R94.7) Abnormal results of other endocrine function studies
- (R94.8) Abnormal results of function studies of other organs and systems
Abnormal basal metabolic rate (BMR)
- Abnormal basal metabolic rate (BMR)
# R95–R99 – Ill-defined and unknown causes of mortality
- (R95) Sudden infant death syndrome
- (R96) Other sudden death, cause unknown
(R96.0) Instantaneous death
(R96.1) Death occurring less than 24 hours from onset of symptoms, not otherwise explained
- (R96.0) Instantaneous death
- (R96.1) Death occurring less than 24 hours from onset of symptoms, not otherwise explained
- (R98) Unattended death
- (R99) Other ill-defined and unspecified causes of mortality
# Excludes
- Abnormal findings on antennatal screening of mother (O28.-)
- Certain conditions originating in the perinatal period (P00-P96)
- Signs and symptoms classified in the body system chapters
- Signs and symptoms of breast (N63, N64.5)
Template:Cognition, perception, emotional state and behaviour symptoms and signs
Template:General symptoms and signs
Template:Nervous and musculoskeletal system symptoms and signs
Template:Skin and subcutaneous tissue symptoms and signs
Template:Speech and voice symptoms and signs
Template:Urinary system symptoms and signs | https://www.wikidoc.org/index.php/Sandbox_g18 | |
9da3065ade905d8843db326d9268916b012f57d7 | wikidoc | Sandbox g19 | Sandbox g19
# Brain abscess
- Empiric antimicrobial therapy
- Brain abscess in otherwise healthy patients
- Preferred regimen: (Cefotaxime 8–12 g/day IV q4–6h OR Ceftriaxone 4 g/day IV q12h) AND Metronidazole 30 mg/kg/day IV q6h
- Alternative regimen: Meropenem 6 g/day IV q8h
- Brain abscess with comorbidities
- Otitis media, mastoiditis, or sinusitis
- Preferred regimen: (Cefotaxime 8–12 g/day q4–6h OR Ceftriaxone 4 g/day q12h) AND Metronidazole 30 mg/kg/day q6h
- Dental infection
- Preferred regimen: Penicillin G 4 MU IV q4h AND Metronidazole 30 mg/kg/day q6h
- Penetrating trauma or post-neurosurgy
- Preferred regimen: (Cefotaxime 8–12 g/day q4–6h OR Ceftriaxone 4 g/day q12h OR Cefepime 2 g IV q12h) AND Vancomycin 30–45 mg/kg/day q8–12h
- Lung abscess, empyema, or bronchiectasis
- Preferred regimen: Penicillin G 4 MU IV q4h AND Metronidazole 30 mg/kg/day q6h AND TMP-SMZ 10–20 mg/kg/day q6–12h
- Bacterial endocarditis
- Preferred regimen: Vancomycin 30–45 mg/kg/day q8–12h AND Gentamicin 5 mg/kg/day IV q8h
- Congenital heart disease
- Preferred regimen: Cefotaxime 8–12 g/day q4–6h OR Ceftriaxone 4 g/day q12h
- Transplant recipients
- Preferred regimen: (Cefotaxime 8–12 g/day q4–6h OR Ceftriaxone 4 g/day q12h) AND Metronidazole 30 mg/kg/day q6h AND Voriconazole 8 mg/kg/day q12h AND (TMP-SMZ 10–20 mg/kg/day q6–12h OR Sulfadiazine 4–6 g/day q6h)
- Patients with HIV/AIDS
- Preferred regimen: (Cefotaxime 8–12 g/day q4–6h OR Ceftriaxone 4 g/day q12h) AND Sulfadiazine 4–6 g/day q6h AND Pyrimethamine 25–100 mg/day qd
- Staphylococcus aureus coverage
- Preferred regimen: Vancomycin 30–45 mg/kg/day q8–12h
- Mycobacterium tuberculosis coverage
- Preferred regimen: Isoniazid 300 mg qd AND Rifampin 600 mg qd AND Pyrazinamide 15–30 mg qd AND Ethambutol 15 mg/kg/day qd
- Pathogen-directed antimicrobial therapy
- Bacteria
- Actinomyces
- Preferred regimen: Penicillin G 4 MU IV q4h
- Alternative regimen: Clindamycin 2400–4800 mg/day IV q6h
- Bacteroides fragilis
- Preferred regimen: Metronidazole 30 mg/kg/day IV q6h
- Alternative regimen: Clindamycin 2400–4800 mg/day IV q6h
- Enterobacteriaceae
- Preferred regimen: Cefotaxime 2 g IV q4-6h OR Ceftriaxone 2 g IV q12h OR Cefepime 2 g IV q12h
- Alternative regimen: Aztreonam 6–8 g/day IV q6–8h OR TMP-SMZ 10–20 mg/kg/day q6–12h OR Ciprofloxacin 800–1200 mg/day IV q8–12h OR Meropenem 2 g IV q8h
- Fusobacterium
- Preferred regimen: Metronidazole 30 mg/kg/day q6h
- Alternative regimen: Clindamycin 2400–4800 mg/day IV q6h OR Meropenem 2 g IV q8h
- Haemophilus
- Preferred regimen: Cefotaxime 2 g IV q4-6h OR Ceftriaxone 2 g IV q12h OR Cefepime 2 g IV q12h
- Alternative regimen: Aztreonam 6–8 g/day IV q6–8h OR TMP-SMZ 10–20 mg/kg/day q6–12h
- Listeria monocytogenes
- Preferred regimen: Ampicillin 12 g/day q4h OR Penicillin G 4 MU IV q4h
- Alternative regimen: TMP-SMZ 10–20 mg/kg/day q6–12h
- Nocardia
- Preferred regimen: TMP-SMZ 10–20 mg/kg/day q6–12h OR Sulfadiazine 4–6 g/day q6h
- Alternative regimen: Meropenem 2 g IV q8h OR Cefotaxime 2 g IV q4-6h OR Ceftriaxone 2 g IV q12h OR Amikacin 15 mg/kg/day IV q8h
- Prevotella melaninogenica
- Preferred regimen: Metronidazole 30 mg/kg/day q6h
- Alternative regimen: Clindamycin 2400–4800 mg/day IV q6h OR Meropenem 2 g IV q8h
- Pseudomonas aeruginosa
- Preferred regimen: Ceftazidime 6 g/day q8h OR Cefepime 6 g/day q8h
- Alternative regimen: Aztreonam 6–8 g/day IV q6–8h OR Ciprofloxacin 800–1200 mg/day IV q8–12h OR Meropenem 2 g IV q8h
- Staphylococcus aureus, methicillin-susceptible
- Preferred regimen: Nafcillin 2 g IV q4h OR Oxacillin 2 g IV q4h
- Alternative regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
- Staphylococcus aureus, methicillin-resistant
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
- Alternative regimen: TMP-SMZ 10–20 mg/kg/day q6–12h
- Streptococcus
- Preferred regimen: Penicillin G 4 MU IV q4h OR Ampicillin 2 g IV q4h
- Alternative regimen: Cefotaxime 2 g IV q4-6h OR Ceftriaxone 2 g IV q12h OR Vancomycin 30–45 mg/kg/day IV q8–12h
- Fungi
- Aspergillus
- Preferred regimen: Voriconazole 8 mg/kg/day q12h
- Alternative regimen: Amphotericin B deoxycholate 0.6–1.0 mg/kg/day IV q24h OR Amphotericin B lipid complex 5 mg/kg/day IV q24h OR Itraconazole 400–600 mg/day IV q12h OR Posaconazole 800 mg/kg/day IV q6–12h
- Candida
- Preferred regimen: Amphotericin B lipid complex 5 mg/kd/day q24h OR Amphotericin B deoxycholate 15 mg/kg/day q8h
- Alternative regimen: Fluconazole 400–800 mg/day IV q24h
- Cryptococcus neoformans
- Preferred regimen: Amphotericin B lipid complex 5 mg/kd/day q24h OR Amphotericin B deoxycholate 15 mg/kg/day q8h
- Alternative regimen: Fluconazole 400–800 mg/day IV q24h
- Mucorales
- Preferred regimen: Amphotericin B lipid complex 5 mg/kd/day q24h OR Amphotericin B deoxycholate 15 mg/kg/day q8h
- Alternative regimen: Posaconazole 800 mg/kg/day IV q6–12h
- Pseudallescheria boydii (Scedosporium apiospermum)
- Preferred regimen: Voriconazole 8 mg/kg/day q12h
- Alternative regimen: Itraconazole 400–600 mg/day IV q12h OR Posaconazole 800 mg/kg/day IV q6–12h
- Protozoa
- Toxoplasma gondii
- Preferred regimen: Sulfadiazine 4–6 g/day q6h AND Pyrimethamine 25–100 mg/day qd
- Alternative regimen (1): Pyrimethamine 25–100 mg/day qd AND Clindamycin 2400–4800 mg/day IV q6h
- Alternative regimen (2): Pyrimethamine 25–100 mg/day qd AND (Azithromycin 1200–1500 mg/day IV q24h OR Atovaquone 750 mg IV q6h OR Dapsone 100 mg PO q24h)
- Alternative regimen (3): TMP-SMZ 10–20 mg/kg/day q6–12h | Sandbox g19
## Brain abscess
- Empiric antimicrobial therapy[1]
- Brain abscess in otherwise healthy patients
- Preferred regimen: (Cefotaxime 8–12 g/day IV q4–6h OR Ceftriaxone 4 g/day IV q12h) AND Metronidazole 30 mg/kg/day IV q6h
- Alternative regimen: Meropenem 6 g/day IV q8h
- Brain abscess with comorbidities
- Otitis media, mastoiditis, or sinusitis
- Preferred regimen: (Cefotaxime 8–12 g/day q4–6h OR Ceftriaxone 4 g/day q12h) AND Metronidazole 30 mg/kg/day q6h
- Dental infection
- Preferred regimen: Penicillin G 4 MU IV q4h AND Metronidazole 30 mg/kg/day q6h
- Penetrating trauma or post-neurosurgy
- Preferred regimen: (Cefotaxime 8–12 g/day q4–6h OR Ceftriaxone 4 g/day q12h OR Cefepime 2 g IV q12h) AND Vancomycin 30–45 mg/kg/day q8–12h
- Lung abscess, empyema, or bronchiectasis
- Preferred regimen: Penicillin G 4 MU IV q4h AND Metronidazole 30 mg/kg/day q6h AND TMP-SMZ 10–20 mg/kg/day q6–12h
- Bacterial endocarditis
- Preferred regimen: Vancomycin 30–45 mg/kg/day q8–12h AND Gentamicin 5 mg/kg/day IV q8h
- Congenital heart disease
- Preferred regimen: Cefotaxime 8–12 g/day q4–6h OR Ceftriaxone 4 g/day q12h
- Transplant recipients
- Preferred regimen: (Cefotaxime 8–12 g/day q4–6h OR Ceftriaxone 4 g/day q12h) AND Metronidazole 30 mg/kg/day q6h AND Voriconazole 8 mg/kg/day q12h AND (TMP-SMZ 10–20 mg/kg/day q6–12h OR Sulfadiazine 4–6 g/day q6h)
- Patients with HIV/AIDS
- Preferred regimen: (Cefotaxime 8–12 g/day q4–6h OR Ceftriaxone 4 g/day q12h) AND Sulfadiazine 4–6 g/day q6h AND Pyrimethamine 25–100 mg/day qd
- Staphylococcus aureus coverage
- Preferred regimen: Vancomycin 30–45 mg/kg/day q8–12h
- Mycobacterium tuberculosis coverage
- Preferred regimen: Isoniazid 300 mg qd AND Rifampin 600 mg qd AND Pyrazinamide 15–30 mg qd AND Ethambutol 15 mg/kg/day qd
- Pathogen-directed antimicrobial therapy[2]
- Bacteria
- Actinomyces
- Preferred regimen: Penicillin G 4 MU IV q4h
- Alternative regimen: Clindamycin 2400–4800 mg/day IV q6h
- Bacteroides fragilis
- Preferred regimen: Metronidazole 30 mg/kg/day IV q6h
- Alternative regimen: Clindamycin 2400–4800 mg/day IV q6h
- Enterobacteriaceae
- Preferred regimen: Cefotaxime 2 g IV q4-6h OR Ceftriaxone 2 g IV q12h OR Cefepime 2 g IV q12h
- Alternative regimen: Aztreonam 6–8 g/day IV q6–8h OR TMP-SMZ 10–20 mg/kg/day q6–12h OR Ciprofloxacin 800–1200 mg/day IV q8–12h OR Meropenem 2 g IV q8h
- Fusobacterium
- Preferred regimen: Metronidazole 30 mg/kg/day q6h
- Alternative regimen: Clindamycin 2400–4800 mg/day IV q6h OR Meropenem 2 g IV q8h
- Haemophilus
- Preferred regimen: Cefotaxime 2 g IV q4-6h OR Ceftriaxone 2 g IV q12h OR Cefepime 2 g IV q12h
- Alternative regimen: Aztreonam 6–8 g/day IV q6–8h OR TMP-SMZ 10–20 mg/kg/day q6–12h
- Listeria monocytogenes
- Preferred regimen: Ampicillin 12 g/day q4h OR Penicillin G 4 MU IV q4h
- Alternative regimen: TMP-SMZ 10–20 mg/kg/day q6–12h
- Nocardia
- Preferred regimen: TMP-SMZ 10–20 mg/kg/day q6–12h OR Sulfadiazine 4–6 g/day q6h
- Alternative regimen: Meropenem 2 g IV q8h OR Cefotaxime 2 g IV q4-6h OR Ceftriaxone 2 g IV q12h OR Amikacin 15 mg/kg/day IV q8h
- Prevotella melaninogenica
- Preferred regimen: Metronidazole 30 mg/kg/day q6h
- Alternative regimen: Clindamycin 2400–4800 mg/day IV q6h OR Meropenem 2 g IV q8h
- Pseudomonas aeruginosa
- Preferred regimen: Ceftazidime 6 g/day q8h OR Cefepime 6 g/day q8h
- Alternative regimen: Aztreonam 6–8 g/day IV q6–8h OR Ciprofloxacin 800–1200 mg/day IV q8–12h OR Meropenem 2 g IV q8h
- Staphylococcus aureus, methicillin-susceptible
- Preferred regimen: Nafcillin 2 g IV q4h OR Oxacillin 2 g IV q4h
- Alternative regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
- Staphylococcus aureus, methicillin-resistant
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
- Alternative regimen: TMP-SMZ 10–20 mg/kg/day q6–12h
- Streptococcus
- Preferred regimen: Penicillin G 4 MU IV q4h OR Ampicillin 2 g IV q4h
- Alternative regimen: Cefotaxime 2 g IV q4-6h OR Ceftriaxone 2 g IV q12h OR Vancomycin 30–45 mg/kg/day IV q8–12h
- Fungi
- Aspergillus
- Preferred regimen: Voriconazole 8 mg/kg/day q12h
- Alternative regimen: Amphotericin B deoxycholate 0.6–1.0 mg/kg/day IV q24h OR Amphotericin B lipid complex 5 mg/kg/day IV q24h OR Itraconazole 400–600 mg/day IV q12h OR Posaconazole 800 mg/kg/day IV q6–12h
- Candida
- Preferred regimen: Amphotericin B lipid complex 5 mg/kd/day q24h OR Amphotericin B deoxycholate 15 mg/kg/day q8h
- Alternative regimen: Fluconazole 400–800 mg/day IV q24h
- Cryptococcus neoformans
- Preferred regimen: Amphotericin B lipid complex 5 mg/kd/day q24h OR Amphotericin B deoxycholate 15 mg/kg/day q8h
- Alternative regimen: Fluconazole 400–800 mg/day IV q24h
- Mucorales
- Preferred regimen: Amphotericin B lipid complex 5 mg/kd/day q24h OR Amphotericin B deoxycholate 15 mg/kg/day q8h
- Alternative regimen: Posaconazole 800 mg/kg/day IV q6–12h
- Pseudallescheria boydii (Scedosporium apiospermum)
- Preferred regimen: Voriconazole 8 mg/kg/day q12h
- Alternative regimen: Itraconazole 400–600 mg/day IV q12h OR Posaconazole 800 mg/kg/day IV q6–12h
- Protozoa
- Toxoplasma gondii
- Preferred regimen: Sulfadiazine 4–6 g/day q6h AND Pyrimethamine 25–100 mg/day qd
- Alternative regimen (1): Pyrimethamine 25–100 mg/day qd AND Clindamycin 2400–4800 mg/day IV q6h
- Alternative regimen (2): Pyrimethamine 25–100 mg/day qd AND (Azithromycin 1200–1500 mg/day IV q24h OR Atovaquone 750 mg IV q6h OR Dapsone 100 mg PO q24h)
- Alternative regimen (3): TMP-SMZ 10–20 mg/kg/day q6–12h | https://www.wikidoc.org/index.php/Sandbox_g19 | |
4b813a7dbaaa7b8cbfa8bb3579b286b887336af2 | wikidoc | Sandbox g20 | Sandbox g20
- Cerebrospinal fluid shunt infection
- Empiric antimicrobial therapy
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Cefepime 2 g IV q8h OR Ceftazidime 2 g IV q8h OR Meropenem 2 g IV q8h)
- Pathogen-directed antimicrobial therapy
- Enterococcus
- Preferred regimen: (Penicillin G 4 MU IV q4h OR Ampicillin 2 g IV q4h) AND Gentamicin 1–1.7 mg/kg IV q8h
- Gram-negative bacilli
- Preferred regimen: Ceftriaxone 2 g IV q12h OR Cefepime 2 g IV q12h OR Meropenem 2 g IV q8h OR Aztreonam 2 g IV q6h
- Propionibacterium acnes
- Preferred regimen: (Penicillin G 4 MU IV q4h OR Ampicillin 2 g IV q4h) ± Gentamicin 1–1.7 mg/kg IV q8h
- Staphylococcus, coagulase-negative
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h ± Rifampin 600 mg IV/PO q24h
- Staphylococcus aureus, methicillin-resistant
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h ± Rifampin 600 mg IV/PO q24h
- Staphylococcus aureus, methicillin-susceptible
- Preferred regimen: (Nafcillin 2 g IV q4h OR Oxacillin 2 g IV q4h) ± Rifampin 600 mg IV/PO q24h
- Streptococcus agalactiae
- Preferred regimen: (Penicillin G 4 MU IV q4h OR Ampicillin 2 g IV q4h) AND Gentamicin 1–1.7 mg/kg IV q8h
- Fungi
- Preferred regimen: Amphotericin B 0.6–1.0 mg/kg IV q24h OR Amphotericin B liposomal 5 mg/kg/day IV q24h | Sandbox g20
- Cerebrospinal fluid shunt infection[1][2]
- Empiric antimicrobial therapy
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Cefepime 2 g IV q8h OR Ceftazidime 2 g IV q8h OR Meropenem 2 g IV q8h)
- Pathogen-directed antimicrobial therapy
- Enterococcus
- Preferred regimen: (Penicillin G 4 MU IV q4h OR Ampicillin 2 g IV q4h) AND Gentamicin 1–1.7 mg/kg IV q8h
- Gram-negative bacilli
- Preferred regimen: Ceftriaxone 2 g IV q12h OR Cefepime 2 g IV q12h OR Meropenem 2 g IV q8h OR Aztreonam 2 g IV q6h
- Propionibacterium acnes
- Preferred regimen: (Penicillin G 4 MU IV q4h OR Ampicillin 2 g IV q4h) ± Gentamicin 1–1.7 mg/kg IV q8h
- Staphylococcus, coagulase-negative
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h ± Rifampin 600 mg IV/PO q24h
- Staphylococcus aureus, methicillin-resistant
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h ± Rifampin 600 mg IV/PO q24h
- Staphylococcus aureus, methicillin-susceptible
- Preferred regimen: (Nafcillin 2 g IV q4h OR Oxacillin 2 g IV q4h) ± Rifampin 600 mg IV/PO q24h
- Streptococcus agalactiae
- Preferred regimen: (Penicillin G 4 MU IV q4h OR Ampicillin 2 g IV q4h) AND Gentamicin 1–1.7 mg/kg IV q8h
- Fungi
- Preferred regimen: Amphotericin B 0.6–1.0 mg/kg IV q24h OR Amphotericin B liposomal 5 mg/kg/day IV q24h | https://www.wikidoc.org/index.php/Sandbox_g20 | |
73a40bce5258c05428c9cb397968e179ee1de70a | wikidoc | Sandbox g22 | Sandbox g22
# Tropical sprue
- Tropical sprue
- Preferred regimen: Folic acid 5 mg PO bid for 2 weeks, followed by 1 mg PO tid AND (Tetracycline 250 mg PO qid OR Doxycycline 100 mg PO qd for 4–6 weeks, up to 6 months in residents of the tropics who have had long-term disease)
- Alternative regimen: Folic acid 5 mg PO bid for 2 weeks, followed by 1 mg PO tid AND Ampicillin 500 mg bid for ≥ 4 weeks
- ↑ Guerra, R.; Wheby, M. S.; Bayless, T. M. (1965-10). "Long-term antibiotic therapy in tropical sprue". Annals of Internal Medicine. 63 (4): 619–634. ISSN 0003-4819. PMID 5838328. Check date values in: |date= (help).mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Ferri, Fred (2015). Ferri's Clinical Advisor 2016 5 Books in 1. City: Elsevier Science Health Science. ISBN 978-0323280471. | Sandbox g22
## Tropical sprue
- Tropical sprue[1][2]
- Preferred regimen: Folic acid 5 mg PO bid for 2 weeks, followed by 1 mg PO tid AND (Tetracycline 250 mg PO qid OR Doxycycline 100 mg PO qd for 4–6 weeks, up to 6 months in residents of the tropics who have had long-term disease)
- Alternative regimen: Folic acid 5 mg PO bid for 2 weeks, followed by 1 mg PO tid AND Ampicillin 500 mg bid for ≥ 4 weeks
- ↑ Guerra, R.; Wheby, M. S.; Bayless, T. M. (1965-10). "Long-term antibiotic therapy in tropical sprue". Annals of Internal Medicine. 63 (4): 619–634. ISSN 0003-4819. PMID 5838328. Check date values in: |date= (help).mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Ferri, Fred (2015). Ferri's Clinical Advisor 2016 5 Books in 1. City: Elsevier Science Health Science. ISBN 978-0323280471. | https://www.wikidoc.org/index.php/Sandbox_g22 | |
cc3686a3d49535ce494417bfc1ab6ab4c65709da | wikidoc | Sandbox g23 | Sandbox g23
# Encephalitis
- Empiric antimicrobial therapy
- Preferred regimen: Acyclovir 10 mg/kg IV q8h for 14–21 days
- Specific epidemiologic considerations
- Agammaglobulinemia — Enteroviruses, Mycoplasma pneumoniae
- Age
- Neonates — Herpes simplex virus type 2, cytomegalovirus, rubella virus, Listeria monocytogenes, Treponema pallidum, Toxoplasma gondii
- Infants and children — Eastern equine encephalitis virus, Japanese encephalitis virus, Murray Valley encephalitis virus, influenza virus, La Crosse virus
- Elderly persons — Eastern equine encephalitis virus, St. Louis encephalitis virus, West Nile virus, sporadic CJD, L. monocytogenes
- Animal contact
- Bats — Rabies virus, Nipah virus
- Birds — West Nile virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Japanese encephalitis virus, Cryptococcus neoformans (bird droppings)
- Cats — Rabies virus, Coxiella burnetii, Bartonella henselae, T. gondii
- Dogs — Rabies virus
- Horses — Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Hendra virus
- Old World primates — B virus
- Raccoons — Rabies virus, Baylisascaris procyonis
- Rodents — Eastern equine encephalitis virus (South America), Venezuelan equine encephalitis virus, tickborne encephalitis virus, Powassan virus (woodchucks), La Crosse virus (chipmunks and squirrels), Bartonella quintana
- Sheep and goats — C. burnetii
- Skunks — Rabies virus
- Swine — Japanese encephalitis virus, Nipah virus
- White-tailed deer — Borrelia burgdorferi
- Immunocompromised persons — Varicella zoster virus, cytomegalovirus, human herpesvirus 6, West Nile virus, HIV, JC virus, L. monocytogenes, Mycobacterium tuberculosis, C. neoformans, Coccidioides species, Histoplasma capsulatum, T. gondii
- Ingestion
- Raw or partially cooked meat — T. gondii
- Raw meat, fish, or reptiles — Gnanthostoma species
- Unpasteurized milk — Tickborne encephalitis virus, L. monocytogenes, C. burnetii
- Insect contact
- Mosquitoes — Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Japanese encephalitis virus, West Nile virus, La Crosse virus, Plasmodium falciparum
- Sandflies — Bartonella bacilliformis
- Ticks — Tickborne encephalitis virus, Powassan virus, Rickettsia rickettsii, Ehrlichia chaffeensis, Anaplasma phagocytophilum, C. burnetii (rare), B. burgdorferi
- Tsetse flies — Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense
- Occupation
- Exposure to animals — Rabies virus, C. burnetii, Bartonella species
- Exposure to horses — Hendra virus
- Exposure to Old World primates — B virus
- Laboratory workers — West Nile virus, HIV, C. burnetii, Coccidioides species
- Physicians and health care workers — Varicella zoster virus, HIV, influenza virus, measles virus, M. tuberculosis
- Veterinarians — Rabies virus, Bartonella species, C. burnetii
- Person-to-person transmission — Herpes simplex virus (neonatal), varicella zoster virus, Venezuelan equine encephalitis virus (rare), poliovirus, nonpolio enteroviruses, measles virus, Nipah virus, mumps virus, rubella virus, Epstein-Barr virus, human herpesvirus 6, B virus, West Nile virus (transfusion, transplantation, breast feeding), HIV, rabies virus (transplantation), influenza virus, M. pneumoniae, M. tuberculosis, T. pallidum
- Recent vaccination — Acute disseminated encephalomyelitis
- Recreational activities
- Camping/hunting — Agents transmitted by mosquitoes and ticks
- Sexual contact — HIV, T. pallidum
- Spelunking — Rabies virus, H. capsulatum
- Swimming — Enteroviruses, Naegleria fowleri
- Season
- Late summer/early fall — Agents transmitted by mosquitoes and ticks, enteroviruses
- Winter — Influenza virus
- Transfusion and transplantation — Cytomegalovirus, Epstein-Barr virus, West Nile virus, HIV, tickborne encephalitis virus, rabies virus, iatrogenic CJD, T. pallidum, A. phagocytophilum, R. rickettsii, C. neoformans, Coccidioides species, H. capsulatum, T. gondii
- Travel
- Africa — Rabies virus, West Nile virus, P. falciparum, T. brucei gambiense, T. brucei rhodesiense
- Australia — Murray Valley encephalitis virus, Japanese encephalitis virus, Hendra virus
- Central America — Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, R. rickettsii, P. falciparum, Taenia solium
- Europe — West Nile virus, tickborne encephalitis virus, A. phagocytophilum, B. burgdorferi
- India, Nepal — Rabies virus, Japanese encephalitis virus, P. falciparum
- Middle East — West Nile virus, P. falciparum
- Russia — Tickborne encephalitis virus
- South America — Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, R. rickettsii, B. bacilliformis (Andes mountains), P. falciparum, T. solium
- Southeast Asia, China, Pacific Rim — Japanese encephalitis virus, tickborne encephalitis virus, Nipah virus, P. falciparum, Gnanthostoma species, T. solium
- Unvaccinated status — Varicella zoster virus, Japanese encephalitis virus, poliovirus, measles virus, mumps virus, rubella virus
- Specific clinical considerations
- General findings
- Hepatitis — Coxiella burnetii
- Lymphadenopathy — HIV, Epstein-Barr virus, cytomegalovirus, measles virus, rubella virus, West Nile virus, Treponema pallidum, Bartonella henselae and other Bartonella species, Mycobacterium tuberculosis, Toxoplasma gondii, Trypanosoma brucei gambiense
- Parotitis — Mumps virus
- Rash — Varicella zoster virus, B virus, human herpesvirus 6, West Nile virus, rubella virus, some enteroviruses, HIV, Rickettsia rickettsii, Mycoplasma pneumoniae, Borrelia burgdorferi, T. pallidum, Ehrlichia chaffeensis, Anaplasma phagocytophilum
- Respiratory tract findings — Venezuelan equine encephalitis virus, Nipah virus, Hendra virus, influenza virus, adenovirus, M. pneumoniae, C. burnetii, M. tuberculosis, Histoplasma capsulatum
- Retinitis — Cytomegalovirus, West Nile virus, B. henselae, T. pallidum
- Urinary symptoms — St. Louis encephalitis virus
- Neurologic findings
- Cerebellar ataxia — Varicella zoster virus (children), Epstein-Barr virus, mumps virus, St. Louis encephalitis virus, Tropheryma whipplei, T. brucei gambiense
- Cranial nerve abnormalities — Herpes simplex virus, Epstein-Barr virus, Listeria monocytogenes, M. tuberculosis, T. pallidum, B. burgdorferi, T. whipplei, Cryptococcus neoformans, Coccidioides species, H. capsulatum
- Dementia — HIV, human transmissible spongiform encephalopathies (sCJD and vCJD), measles virus (SSPE), T. pallidum, T. whipplei
- Myorhythmia — T. whipplei (oculomasticatory)
- Parkinsonism — Japanese encephalitis virus, St. Louis encephalitis virus, West Nile virus, Nipah virus, T. gondii, T. brucei gambiense
- Poliomyelitis-like flaccid paralysis — Japanese encephalitis virus, West Nile virus, tickborne encephalitis virus; enteroviruses (enterovirus-71, coxsackieviruses), poliovirus
- Rhombencephalitis — Herpes simplex virus, West Nile virus, enterovirus 71, L. monocytogenes
- Pathogen-directed antimicrobial therapy
- Viruses
- Adenovirus
- Preferred regimen: supportive
- B virus (herpes B virus)
- Established disease
- Preferred regimen: Valacyclovir 1,000 mg PO tid OR Ganciclovir 5 mg/kg IV q12h for ≥ 14 days until resolution of neurologic symptoms, then Acyclovir 800 mg PO 5 times daily indefinitely OR Valacyclovir 1 g PO tid indefinitely
- Alternative regimen: Acyclovir 15 mg/kg IV q8h for ≥ 14 days until resolution of neurologic symptoms, then Acyclovir 800 mg PO 5 times daily OR Valacyclovir 1 g PO tid indefinitely
- Prophylaxis after bite or scratch
- Preferred regimen: Valacyclovir 1,000 mg PO tid
- Cytomegalovirus (CMV)
- Preferred regimen: Ganciclovir 5 mg/kg IV q12h for 14–21 days, followed by 5 mg/kg IV qd for maintenance AND Foscarnet 90 mg/kg IV q12h for 14–21 days, followed by 90-120 mg/kg IV qd for maintenance
- Eastern equine encephalitis virus
- Preferred regimen: supportive
- Epstein-Barr virus (EBV)
- Preferred regimen: supportive ± Corticosteroids
- Hendra virus
- Preferred regimen: supportive
- HSV-1 and HSV-2
- Preferred regimen: Acyclovir 10 mg/kg IV q8h for 14–21 days
- Preferred regimen (neonates): Acyclovir 20 mg/kg IV q8h for 21 days
- Human herpesvirus 6 (HHV-6)
- Preferred regimen: Ganciclovir 5 mg/kg IV q12h for 14–21 days, followed by 5 mg/kg IV qd for maintenance OR Foscarnet 90 mg/kg IV q12h for 14–21 days, followed by 90-120 mg/kg IV qd for maintenance
- Human immunodeficiency virus (HIV)
- Preferred regimen: HAART
- Influenza virus
- Preferred regimen: Oseltamivir 75 mg PO bid
- Japanese encephalitis virus
- Preferred regimen: supportive
- JC virus
- Preferred regimen: Reversal or control of immunosuppression OR HAART in patients with AIDS
- La Crosse virus
- Preferred regimen: supportive
- Measles virus
- Life-threatening disease
- Preferred regimen: Ribavirin
- SSPE
- Preferred regimen: Ribavirin intrathecal
- Mumps virus
- Preferred regimen: supportive
- Murray Valley encephalitis virus
- Preferred regimen: supportive
- Nipah virus
- Preferred regimen: supportive
- Alternative regimen: Ribavirin
- Nonpolio enteroviruses
- Preferred regimen: supportive
- Poliovirus
- Preferred regimen: supportive
- Powassan virus
- Preferred regimen: supportive
- Rabies virus
- Preferred regimen: supportive
- Rubella virus
- Preferred regimen: supportive
- St. Louis encephalitis virus
- Preferred regimen: supportive
- Alternative regimen: IFN-α-2b
- Tickborne encephalitis virus
- Preferred regimen: supportive
- Vaccinia
- Preferred regimen: supportive ± Corticosteroids (if suggestive of post-immunization)
- Venezuelan equine encephalitis virus
- Preferred regimen: supportive
- Varicella zoster virus (VZV)
- Preferred regimen: Acyclovir 10–15 mg/kg IV q8h for 10–14 days ± Corticosteroids
- Alternative regimen: Ganciclovir 5 mg/kg IV q12h for 14–21 days, followed by 5 mg/kg IV qd for maintenance ± Corticosteroids
- West Nile virus
- Preferred regimen: supportive
- Western equine encephalitis virus
- Preferred regimen: supportive
- Bacteria
- Anaplasma phagocytophilum (human granulocytotrophic ehrlichiosis)
- Preferred regimen: Doxycycline
- Bartonella bacilliformis (Oroya fever, Carrion's disease)
- Preferred regimen: Chloramphenicol OR Ciprofloxacin] OR Doxycycline OR Ampicillin OR Trimethoprim-Sulfamethoxazole
- Bartonella henselae (cat scratch disease)
- Preferred regimen: Doxycycline OR Azithromycin ± Rifampin
- Borrelia burgdorferi (Lyme disease)
- Preferred regimen: Ceftriaxone OR Cefotaxime OR Penicillin G
- Coxiella burnetii (Q fever)
- Preferred regimen: Doxycycline AND Fluoroquinolone AND Rifampin
- Ehrlichia chaffeensis (human monocytotrophic ehrlichiosis)
- Preferred regimen: Doxycycline
- Listeria monocytogenes
- Preferred regimen: Ampicillin AND Gentamicin
- Alternative regimen: Trimethoprim-Sulfamethoxazole
- Mycobacterium tuberculosis
- Preferred regimen: (Isoniazid AND Rifampin AND Pyrazinamide AND Ethambutol) ± Dexamethasone (if suggestive of meningitis)
- Mycoplasma pneumoniae
- Preferred regimen: Azithromycin OR Doxycycline OR Fluoroquinolone
- Rickettsia rickettsii (Rocky Mountain spotted fever)
- Preferred regimen: Doxycycline
- Alternative regimen: Chloramphenicol (for pregnant patients)
- Treponema pallidum (syphilis)
- Preferred regimen: Penicillin G
- Alternative regimen: Ceftriaxone
- Tropheryma whipplei (Whipple's disease)
- Preferred regimen: Ceftriaxone for 2–4 weeks, followed by Trimethoprim-Sulfamethoxazole for 1–2 years OR Cefixime for 1–2 years
- Fungi
- Coccidioides
- Preferred regimen: Fluconazole
- Alternative regimen: Itraconazole OR Voriconazole OR Amphotericin B (intravenous and intrathecal)
- Cryptococcus neoformans
- Preferred regimen (1): Amphotericin B deoxycholate AND Flucytosine for 2 weeks, followed by Fluconazole for 8 weeks
- Preferred regimen (2): Amphotericin B lipid complex AND Flucytosine for 2 weeks, followed by Fluconazole for 8 weeks
- Preferred regimen (3): Amphotericin B deoxycholate AND Flucytosine for 6–10 weeks, followed by Fluconazole for 8 weeks
- Histoplasma capsulatum
- Preferred regimen: Amphotericin B liposomal for 4–6 weeks, followed by Itraconazole for at least 1 year and until resolution of CSF abnormalities
- Protozoa
- Acanthamoeba
- Preferred regimen (1): Trimethoprim-Sulfamethoxazole AND Rifampin AND Ketoconazole
- Preferred regimen (2): Fluconazole AND Sulfadiazine AND Pyrimethamine
- Balamuthia mandrillaris
- Preferred regimen: (Azithromycin OR Clarithromycin) AND Pentamidine AND Flucytosine AND Fluconazole AND Sulfadiazine AND (Thioridazine OR Trifluoperazine)
- Naegleria fowleri
- Preferred regimen: Amphotericin B (intravenous and intrathecal) AND Rifampin AND (Azithromycin OR Sulfisoxazole OR Miconazole)
- Plasmodium falciparum
- Preferred regimen: Quinine OR Quinidine OR Artesunate OR Artemether
- Alternative regimen (1): Atovaquone-Proguanil
- Alternative regimen (2): Exchange transfusion (for > 10% parasitemia or cerebral malaria)
- Toxoplasma gondii
- Preferred regimen: Pyrimethamine AND Sulfadiazine OR Clindamycin
- Alternative regimen (1): Trimethoprim-sulfamethoxazole
- Alternative regimen (2): Pyrimethamine AND (Atovaquone OR Clarithromycin OR Azithromycin OR Dapsone
- Trypanosoma brucei gambiense (West African trypanosomiasis)
- Preferred regimen: Eflornithine OR Melarsoprol
- Trypanosoma brucei rhodesiense (East African trypanosomiasis)
- Preferred regimen: Melarsoprol
- Helminths
- Baylisascaris procyonis
- Preferred regimen: Albendazole AND Diethylcarbamazine AND Corticosteroids
- Gnathostoma
- Preferred regimen: Albendazole OR Ivermectin
- Taenia solium (cysticercosis)
- Preferred regimen: Albendazole AND Corticosteroids
- Alternative regimen: Praziquantel AND Corticosteroids
- Prion
- Human transmissible spongiform encephalopathy
- Preferred regimen: supportive
- ↑ Tunkel, Allan R.; Glaser, Carol A.; Bloch, Karen C.; Sejvar, James J.; Marra, Christina M.; Roos, Karen L.; Hartman, Barry J.; Kaplan, Sheldon L.; Scheld, W. Michael; Whitley, Richard J.; Infectious Diseases Society of America (2008-08-01). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (3): 303–327. doi:10.1086/589747. ISSN 1537-6591. PMID 18582201..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Tunkel, Allan R.; Glaser, Carol A.; Bloch, Karen C.; Sejvar, James J.; Marra, Christina M.; Roos, Karen L.; Hartman, Barry J.; Kaplan, Sheldon L.; Scheld, W. Michael; Whitley, Richard J.; Infectious Diseases Society of America (2008-08-01). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (3): 303–327. doi:10.1086/589747. ISSN 1537-6591. PMID 18582201.
- ↑ Tunkel, Allan R.; Glaser, Carol A.; Bloch, Karen C.; Sejvar, James J.; Marra, Christina M.; Roos, Karen L.; Hartman, Barry J.; Kaplan, Sheldon L.; Scheld, W. Michael; Whitley, Richard J.; Infectious Diseases Society of America (2008-08-01). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (3): 303–327. doi:10.1086/589747. ISSN 1537-6591. PMID 18582201.
- ↑ Tunkel, Allan R.; Glaser, Carol A.; Bloch, Karen C.; Sejvar, James J.; Marra, Christina M.; Roos, Karen L.; Hartman, Barry J.; Kaplan, Sheldon L.; Scheld, W. Michael; Whitley, Richard J.; Infectious Diseases Society of America (2008-08-01). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (3): 303–327. doi:10.1086/589747. ISSN 1537-6591. PMID 18582201. | Sandbox g23
## Encephalitis
- Empiric antimicrobial therapy[1]
- Preferred regimen: Acyclovir 10 mg/kg IV q8h for 14–21 days
- Specific epidemiologic considerations[2]
- Agammaglobulinemia — Enteroviruses, Mycoplasma pneumoniae
- Age
- Neonates — Herpes simplex virus type 2, cytomegalovirus, rubella virus, Listeria monocytogenes, Treponema pallidum, Toxoplasma gondii
- Infants and children — Eastern equine encephalitis virus, Japanese encephalitis virus, Murray Valley encephalitis virus, influenza virus, La Crosse virus
- Elderly persons — Eastern equine encephalitis virus, St. Louis encephalitis virus, West Nile virus, sporadic CJD, L. monocytogenes
- Animal contact
- Bats — Rabies virus, Nipah virus
- Birds — West Nile virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Japanese encephalitis virus, Cryptococcus neoformans (bird droppings)
- Cats — Rabies virus, Coxiella burnetii, Bartonella henselae, T. gondii
- Dogs — Rabies virus
- Horses — Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Hendra virus
- Old World primates — B virus
- Raccoons — Rabies virus, Baylisascaris procyonis
- Rodents — Eastern equine encephalitis virus (South America), Venezuelan equine encephalitis virus, tickborne encephalitis virus, Powassan virus (woodchucks), La Crosse virus (chipmunks and squirrels), Bartonella quintana
- Sheep and goats — C. burnetii
- Skunks — Rabies virus
- Swine — Japanese encephalitis virus, Nipah virus
- White-tailed deer — Borrelia burgdorferi
- Immunocompromised persons — Varicella zoster virus, cytomegalovirus, human herpesvirus 6, West Nile virus, HIV, JC virus, L. monocytogenes, Mycobacterium tuberculosis, C. neoformans, Coccidioides species, Histoplasma capsulatum, T. gondii
- Ingestion
- Raw or partially cooked meat — T. gondii
- Raw meat, fish, or reptiles — Gnanthostoma species
- Unpasteurized milk — Tickborne encephalitis virus, L. monocytogenes, C. burnetii
- Insect contact
- Mosquitoes — Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Japanese encephalitis virus, West Nile virus, La Crosse virus, Plasmodium falciparum
- Sandflies — Bartonella bacilliformis
- Ticks — Tickborne encephalitis virus, Powassan virus, Rickettsia rickettsii, Ehrlichia chaffeensis, Anaplasma phagocytophilum, C. burnetii (rare), B. burgdorferi
- Tsetse flies — Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense
- Occupation
- Exposure to animals — Rabies virus, C. burnetii, Bartonella species
- Exposure to horses — Hendra virus
- Exposure to Old World primates — B virus
- Laboratory workers — West Nile virus, HIV, C. burnetii, Coccidioides species
- Physicians and health care workers — Varicella zoster virus, HIV, influenza virus, measles virus, M. tuberculosis
- Veterinarians — Rabies virus, Bartonella species, C. burnetii
- Person-to-person transmission — Herpes simplex virus (neonatal), varicella zoster virus, Venezuelan equine encephalitis virus (rare), poliovirus, nonpolio enteroviruses, measles virus, Nipah virus, mumps virus, rubella virus, Epstein-Barr virus, human herpesvirus 6, B virus, West Nile virus (transfusion, transplantation, breast feeding), HIV, rabies virus (transplantation), influenza virus, M. pneumoniae, M. tuberculosis, T. pallidum
- Recent vaccination — Acute disseminated encephalomyelitis
- Recreational activities
- Camping/hunting — Agents transmitted by mosquitoes and ticks
- Sexual contact — HIV, T. pallidum
- Spelunking — Rabies virus, H. capsulatum
- Swimming — Enteroviruses, Naegleria fowleri
- Season
- Late summer/early fall — Agents transmitted by mosquitoes and ticks, enteroviruses
- Winter — Influenza virus
- Transfusion and transplantation — Cytomegalovirus, Epstein-Barr virus, West Nile virus, HIV, tickborne encephalitis virus, rabies virus, iatrogenic CJD, T. pallidum, A. phagocytophilum, R. rickettsii, C. neoformans, Coccidioides species, H. capsulatum, T. gondii
- Travel
- Africa — Rabies virus, West Nile virus, P. falciparum, T. brucei gambiense, T. brucei rhodesiense
- Australia — Murray Valley encephalitis virus, Japanese encephalitis virus, Hendra virus
- Central America — Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, R. rickettsii, P. falciparum, Taenia solium
- Europe — West Nile virus, tickborne encephalitis virus, A. phagocytophilum, B. burgdorferi
- India, Nepal — Rabies virus, Japanese encephalitis virus, P. falciparum
- Middle East — West Nile virus, P. falciparum
- Russia — Tickborne encephalitis virus
- South America — Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, R. rickettsii, B. bacilliformis (Andes mountains), P. falciparum, T. solium
- Southeast Asia, China, Pacific Rim — Japanese encephalitis virus, tickborne encephalitis virus, Nipah virus, P. falciparum, Gnanthostoma species, T. solium
- Unvaccinated status — Varicella zoster virus, Japanese encephalitis virus, poliovirus, measles virus, mumps virus, rubella virus
- Specific clinical considerations[3]
- General findings
- Hepatitis — Coxiella burnetii
- Lymphadenopathy — HIV, Epstein-Barr virus, cytomegalovirus, measles virus, rubella virus, West Nile virus, Treponema pallidum, Bartonella henselae and other Bartonella species, Mycobacterium tuberculosis, Toxoplasma gondii, Trypanosoma brucei gambiense
- Parotitis — Mumps virus
- Rash — Varicella zoster virus, B virus, human herpesvirus 6, West Nile virus, rubella virus, some enteroviruses, HIV, Rickettsia rickettsii, Mycoplasma pneumoniae, Borrelia burgdorferi, T. pallidum, Ehrlichia chaffeensis, Anaplasma phagocytophilum
- Respiratory tract findings — Venezuelan equine encephalitis virus, Nipah virus, Hendra virus, influenza virus, adenovirus, M. pneumoniae, C. burnetii, M. tuberculosis, Histoplasma capsulatum
- Retinitis — Cytomegalovirus, West Nile virus, B. henselae, T. pallidum
- Urinary symptoms — St. Louis encephalitis virus
- Neurologic findings
- Cerebellar ataxia — Varicella zoster virus (children), Epstein-Barr virus, mumps virus, St. Louis encephalitis virus, Tropheryma whipplei, T. brucei gambiense
- Cranial nerve abnormalities — Herpes simplex virus, Epstein-Barr virus, Listeria monocytogenes, M. tuberculosis, T. pallidum, B. burgdorferi, T. whipplei, Cryptococcus neoformans, Coccidioides species, H. capsulatum
- Dementia — HIV, human transmissible spongiform encephalopathies (sCJD and vCJD), measles virus (SSPE), T. pallidum, T. whipplei
- Myorhythmia — T. whipplei (oculomasticatory)
- Parkinsonism — Japanese encephalitis virus, St. Louis encephalitis virus, West Nile virus, Nipah virus, T. gondii, T. brucei gambiense
- Poliomyelitis-like flaccid paralysis — Japanese encephalitis virus, West Nile virus, tickborne encephalitis virus; enteroviruses (enterovirus-71, coxsackieviruses), poliovirus
- Rhombencephalitis — Herpes simplex virus, West Nile virus, enterovirus 71, L. monocytogenes
- Pathogen-directed antimicrobial therapy[4]
- Viruses
- Adenovirus
- Preferred regimen: supportive
- B virus (herpes B virus)
- Established disease
- Preferred regimen: Valacyclovir 1,000 mg PO tid OR Ganciclovir 5 mg/kg IV q12h for ≥ 14 days until resolution of neurologic symptoms, then Acyclovir 800 mg PO 5 times daily indefinitely OR Valacyclovir 1 g PO tid indefinitely
- Alternative regimen: Acyclovir 15 mg/kg IV q8h for ≥ 14 days until resolution of neurologic symptoms, then Acyclovir 800 mg PO 5 times daily OR Valacyclovir 1 g PO tid indefinitely
- Prophylaxis after bite or scratch
- Preferred regimen: Valacyclovir 1,000 mg PO tid
- Cytomegalovirus (CMV)
- Preferred regimen: Ganciclovir 5 mg/kg IV q12h for 14–21 days, followed by 5 mg/kg IV qd for maintenance AND Foscarnet 90 mg/kg IV q12h for 14–21 days, followed by 90-120 mg/kg IV qd for maintenance
- Eastern equine encephalitis virus
- Preferred regimen: supportive
- Epstein-Barr virus (EBV)
- Preferred regimen: supportive ± Corticosteroids
- Hendra virus
- Preferred regimen: supportive
- HSV-1 and HSV-2
- Preferred regimen: Acyclovir 10 mg/kg IV q8h for 14–21 days
- Preferred regimen (neonates): Acyclovir 20 mg/kg IV q8h for 21 days
- Human herpesvirus 6 (HHV-6)
- Preferred regimen: Ganciclovir 5 mg/kg IV q12h for 14–21 days, followed by 5 mg/kg IV qd for maintenance OR Foscarnet 90 mg/kg IV q12h for 14–21 days, followed by 90-120 mg/kg IV qd for maintenance
- Human immunodeficiency virus (HIV)
- Preferred regimen: HAART
- Influenza virus
- Preferred regimen: Oseltamivir 75 mg PO bid
- Japanese encephalitis virus
- Preferred regimen: supportive
- JC virus
- Preferred regimen: Reversal or control of immunosuppression OR HAART in patients with AIDS
- La Crosse virus
- Preferred regimen: supportive
- Measles virus
- Life-threatening disease
- Preferred regimen: Ribavirin
- SSPE
- Preferred regimen: Ribavirin intrathecal
- Mumps virus
- Preferred regimen: supportive
- Murray Valley encephalitis virus
- Preferred regimen: supportive
- Nipah virus
- Preferred regimen: supportive
- Alternative regimen: Ribavirin
- Nonpolio enteroviruses
- Preferred regimen: supportive
- Poliovirus
- Preferred regimen: supportive
- Powassan virus
- Preferred regimen: supportive
- Rabies virus
- Preferred regimen: supportive
- Rubella virus
- Preferred regimen: supportive
- St. Louis encephalitis virus
- Preferred regimen: supportive
- Alternative regimen: IFN-α-2b
- Tickborne encephalitis virus
- Preferred regimen: supportive
- Vaccinia
- Preferred regimen: supportive ± Corticosteroids (if suggestive of post-immunization)
- Venezuelan equine encephalitis virus
- Preferred regimen: supportive
- Varicella zoster virus (VZV)
- Preferred regimen: Acyclovir 10–15 mg/kg IV q8h for 10–14 days ± Corticosteroids
- Alternative regimen: Ganciclovir 5 mg/kg IV q12h for 14–21 days, followed by 5 mg/kg IV qd for maintenance ± Corticosteroids
- West Nile virus
- Preferred regimen: supportive
- Western equine encephalitis virus
- Preferred regimen: supportive
- Bacteria
- Anaplasma phagocytophilum (human granulocytotrophic ehrlichiosis)
- Preferred regimen: Doxycycline
- Bartonella bacilliformis (Oroya fever, Carrion's disease)
- Preferred regimen: Chloramphenicol OR Ciprofloxacin] OR Doxycycline OR Ampicillin OR Trimethoprim-Sulfamethoxazole
- Bartonella henselae (cat scratch disease)
- Preferred regimen: Doxycycline OR Azithromycin ± Rifampin
- Borrelia burgdorferi (Lyme disease)
- Preferred regimen: Ceftriaxone OR Cefotaxime OR Penicillin G
- Coxiella burnetii (Q fever)
- Preferred regimen: Doxycycline AND Fluoroquinolone AND Rifampin
- Ehrlichia chaffeensis (human monocytotrophic ehrlichiosis)
- Preferred regimen: Doxycycline
- Listeria monocytogenes
- Preferred regimen: Ampicillin AND Gentamicin
- Alternative regimen: Trimethoprim-Sulfamethoxazole
- Mycobacterium tuberculosis
- Preferred regimen: (Isoniazid AND Rifampin AND Pyrazinamide AND Ethambutol) ± Dexamethasone (if suggestive of meningitis)
- Mycoplasma pneumoniae
- Preferred regimen: Azithromycin OR Doxycycline OR Fluoroquinolone
- Rickettsia rickettsii (Rocky Mountain spotted fever)
- Preferred regimen: Doxycycline
- Alternative regimen: Chloramphenicol (for pregnant patients)
- Treponema pallidum (syphilis)
- Preferred regimen: Penicillin G
- Alternative regimen: Ceftriaxone
- Tropheryma whipplei (Whipple's disease)
- Preferred regimen: Ceftriaxone for 2–4 weeks, followed by Trimethoprim-Sulfamethoxazole for 1–2 years OR Cefixime for 1–2 years
- Fungi
- Coccidioides
- Preferred regimen: Fluconazole
- Alternative regimen: Itraconazole OR Voriconazole OR Amphotericin B (intravenous and intrathecal)
- Cryptococcus neoformans
- Preferred regimen (1): Amphotericin B deoxycholate AND Flucytosine for 2 weeks, followed by Fluconazole for 8 weeks
- Preferred regimen (2): Amphotericin B lipid complex AND Flucytosine for 2 weeks, followed by Fluconazole for 8 weeks
- Preferred regimen (3): Amphotericin B deoxycholate AND Flucytosine for 6–10 weeks, followed by Fluconazole for 8 weeks
- Histoplasma capsulatum
- Preferred regimen: Amphotericin B liposomal for 4–6 weeks, followed by Itraconazole for at least 1 year and until resolution of CSF abnormalities
- Protozoa
- Acanthamoeba
- Preferred regimen (1): Trimethoprim-Sulfamethoxazole AND Rifampin AND Ketoconazole
- Preferred regimen (2): Fluconazole AND Sulfadiazine AND Pyrimethamine
- Balamuthia mandrillaris
- Preferred regimen: (Azithromycin OR Clarithromycin) AND Pentamidine AND Flucytosine AND Fluconazole AND Sulfadiazine AND (Thioridazine OR Trifluoperazine)
- Naegleria fowleri
- Preferred regimen: Amphotericin B (intravenous and intrathecal) AND Rifampin AND (Azithromycin OR Sulfisoxazole OR Miconazole)
- Plasmodium falciparum
- Preferred regimen: Quinine OR Quinidine OR Artesunate OR Artemether
- Alternative regimen (1): Atovaquone-Proguanil
- Alternative regimen (2): Exchange transfusion (for > 10% parasitemia or cerebral malaria)
- Toxoplasma gondii
- Preferred regimen: Pyrimethamine AND Sulfadiazine OR Clindamycin
- Alternative regimen (1): Trimethoprim-sulfamethoxazole
- Alternative regimen (2): Pyrimethamine AND (Atovaquone OR Clarithromycin OR Azithromycin OR Dapsone
- Trypanosoma brucei gambiense (West African trypanosomiasis)
- Preferred regimen: Eflornithine OR Melarsoprol
- Trypanosoma brucei rhodesiense (East African trypanosomiasis)
- Preferred regimen: Melarsoprol
- Helminths
- Baylisascaris procyonis
- Preferred regimen: Albendazole AND Diethylcarbamazine AND Corticosteroids
- Gnathostoma
- Preferred regimen: Albendazole OR Ivermectin
- Taenia solium (cysticercosis)
- Preferred regimen: Albendazole AND Corticosteroids
- Alternative regimen: Praziquantel AND Corticosteroids
- Prion
- Human transmissible spongiform encephalopathy
- Preferred regimen: supportive
- ↑ Tunkel, Allan R.; Glaser, Carol A.; Bloch, Karen C.; Sejvar, James J.; Marra, Christina M.; Roos, Karen L.; Hartman, Barry J.; Kaplan, Sheldon L.; Scheld, W. Michael; Whitley, Richard J.; Infectious Diseases Society of America (2008-08-01). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (3): 303–327. doi:10.1086/589747. ISSN 1537-6591. PMID 18582201..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Tunkel, Allan R.; Glaser, Carol A.; Bloch, Karen C.; Sejvar, James J.; Marra, Christina M.; Roos, Karen L.; Hartman, Barry J.; Kaplan, Sheldon L.; Scheld, W. Michael; Whitley, Richard J.; Infectious Diseases Society of America (2008-08-01). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (3): 303–327. doi:10.1086/589747. ISSN 1537-6591. PMID 18582201.
- ↑ Tunkel, Allan R.; Glaser, Carol A.; Bloch, Karen C.; Sejvar, James J.; Marra, Christina M.; Roos, Karen L.; Hartman, Barry J.; Kaplan, Sheldon L.; Scheld, W. Michael; Whitley, Richard J.; Infectious Diseases Society of America (2008-08-01). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (3): 303–327. doi:10.1086/589747. ISSN 1537-6591. PMID 18582201.
- ↑ Tunkel, Allan R.; Glaser, Carol A.; Bloch, Karen C.; Sejvar, James J.; Marra, Christina M.; Roos, Karen L.; Hartman, Barry J.; Kaplan, Sheldon L.; Scheld, W. Michael; Whitley, Richard J.; Infectious Diseases Society of America (2008-08-01). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (3): 303–327. doi:10.1086/589747. ISSN 1537-6591. PMID 18582201. | https://www.wikidoc.org/index.php/Sandbox_g23 | |
0102b547fa73f632ebe159f256cac038683c7f21 | wikidoc | Sandbox g24 | Sandbox g24
- Empiric antimicrobial therapy
- Preferred regimen: Acyclovir 10 mg/kg IV q8h for 14–21 days
- Specific epidemiologic considerations
- Agammaglobulinemia — Enteroviruses, Mycoplasma pneumoniae
- Age
- Neonates — Herpes simplex virus type 2, cytomegalovirus, rubella virus, Listeria monocytogenes, Treponema pallidum, Toxoplasma gondii
- Infants and children — Eastern equine encephalitis virus, Japanese encephalitis virus, Murray Valley encephalitis virus, influenza virus, La Crosse virus
- Elderly persons — Eastern equine encephalitis virus, St. Louis encephalitis virus, West Nile virus, sporadic CJD, L. monocytogenes
- Animal contact
- Bats — Rabies virus, Nipah virus
- Birds — West Nile virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Japanese encephalitis virus, Cryptococcus neoformans (bird droppings)
- Cats — Rabies virus, Coxiella burnetii, Bartonella henselae, T. gondii
- Dogs — Rabies virus
- Horses — Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Hendra virus
- Old World primates — B virus
- Raccoons — Rabies virus, Baylisascaris procyonis
- Rodents — Eastern equine encephalitis virus (South America), Venezuelan equine encephalitis virus, tickborne encephalitis virus, Powassan virus (woodchucks), La Crosse virus (chipmunks and squirrels), Bartonella quintana
- Sheep and goats — C. burnetii
- Skunks — Rabies virus
- Swine — Japanese encephalitis virus, Nipah virus
- White-tailed deer — Borrelia burgdorferi
- Immunocompromised persons — Varicella zoster virus, cytomegalovirus, human herpesvirus 6, West Nile virus, HIV, JC virus, L. monocytogenes, Mycobacterium tuberculosis, C. neoformans, Coccidioides species, Histoplasma capsulatum, T. gondii
- Ingestion
- Raw or partially cooked meat — T. gondii
- Raw meat, fish, or reptiles — Gnanthostoma species
- Unpasteurized milk — Tickborne encephalitis virus, L. monocytogenes, C. burnetii
- Insect contact
- Mosquitoes — Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Japanese encephalitis virus, West Nile virus, La Crosse virus, Plasmodium falciparum
- Sandflies — Bartonella bacilliformis
- Ticks — Tickborne encephalitis virus, Powassan virus, Rickettsia rickettsii, Ehrlichia chaffeensis, Anaplasma phagocytophilum, C. burnetii (rare), B. burgdorferi
- Tsetse flies — Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense
- Occupation
- Exposure to animals — Rabies virus, C. burnetii, Bartonella species
- Exposure to horses — Hendra virus
- Exposure to Old World primates — B virus
- Laboratory workers — West Nile virus, HIV, C. burnetii, Coccidioides species
- Physicians and health care workers — Varicella zoster virus, HIV, influenza virus, measles virus, M. tuberculosis
- Veterinarians — Rabies virus, Bartonella species, C. burnetii
- Person-to-person transmission — Herpes simplex virus (neonatal), varicella zoster virus, Venezuelan equine encephalitis virus (rare), poliovirus, nonpolio enteroviruses, measles virus, Nipah virus, mumps virus, rubella virus, Epstein-Barr virus, human herpesvirus 6, B virus, West Nile virus (transfusion, transplantation, breast feeding), HIV, rabies virus (transplantation), influenza virus, M. pneumoniae, M. tuberculosis, T. pallidum
- Recent vaccination — Acute disseminated encephalomyelitis
- Recreational activities
- Camping/hunting — Agents transmitted by mosquitoes and ticks
- Sexual contact — HIV, T. pallidum
- Spelunking — Rabies virus, H. capsulatum
- Swimming — Enteroviruses, Naegleria fowleri
- Season
- Late summer/early fall — Agents transmitted by mosquitoes and ticks, enteroviruses
- Winter — Influenza virus
- Transfusion and transplantation — Cytomegalovirus, Epstein-Barr virus, West Nile virus, HIV, tickborne encephalitis virus, rabies virus, iatrogenic CJD, T. pallidum, A. phagocytophilum, R. rickettsii, C. neoformans, Coccidioides species, H. capsulatum, T. gondii
- Travel
- Africa — Rabies virus, West Nile virus, P. falciparum, T. brucei gambiense, T. brucei rhodesiense
- Australia — Murray Valley encephalitis virus, Japanese encephalitis virus, Hendra virus
- Central America — Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, R. rickettsii, P. falciparum, Taenia solium
- Europe — West Nile virus, tickborne encephalitis virus, A. phagocytophilum, B. burgdorferi
- India, Nepal — Rabies virus, Japanese encephalitis virus, P. falciparum
- Middle East — West Nile virus, P. falciparum
- Russia — Tickborne encephalitis virus
- South America — Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, R. rickettsii, B. bacilliformis (Andes mountains), P. falciparum, T. solium
- Southeast Asia, China, Pacific Rim — Japanese encephalitis virus, tickborne encephalitis virus, Nipah virus, P. falciparum, Gnanthostoma species, T. solium
- Unvaccinated status — Varicella zoster virus, Japanese encephalitis virus, poliovirus, measles virus, mumps virus, rubella virus
- Specific clinical considerations
- General findings
- Hepatitis — Coxiella burnetii
- Lymphadenopathy — HIV, Epstein-Barr virus, cytomegalovirus, measles virus, rubella virus, West Nile virus, Treponema pallidum, Bartonella henselae and other Bartonella species, Mycobacterium tuberculosis, Toxoplasma gondii, Trypanosoma brucei gambiense
- Parotitis — Mumps virus
- Rash — Varicella zoster virus, B virus, human herpesvirus 6, West Nile virus, rubella virus, some enteroviruses, HIV, Rickettsia rickettsii, Mycoplasma pneumoniae, Borrelia burgdorferi, T. pallidum, Ehrlichia chaffeensis, Anaplasma phagocytophilum
- Respiratory tract findings — Venezuelan equine encephalitis virus, Nipah virus, Hendra virus, influenza virus, adenovirus, M. pneumoniae, C. burnetii, M. tuberculosis, Histoplasma capsulatum
- Retinitis — Cytomegalovirus, West Nile virus, B. henselae, T. pallidum
- Urinary symptoms — St. Louis encephalitis virus
- Neurologic findings
- Cerebellar ataxia — Varicella zoster virus (children), Epstein-Barr virus, mumps virus, St. Louis encephalitis virus, Tropheryma whipplei, T. brucei gambiense
- Cranial nerve abnormalities — Herpes simplex virus, Epstein-Barr virus, Listeria monocytogenes, M. tuberculosis, T. pallidum, B. burgdorferi, T. whipplei, Cryptococcus neoformans, Coccidioides species, H. capsulatum
- Dementia — HIV, human transmissible spongiform encephalopathies (sCJD and vCJD), measles virus (SSPE), T. pallidum, T. whipplei
- Myorhythmia — T. whipplei (oculomasticatory)
- Parkinsonism — Japanese encephalitis virus, St. Louis encephalitis virus, West Nile virus, Nipah virus, T. gondii, T. brucei gambiense
- Poliomyelitis-like flaccid paralysis — Japanese encephalitis virus, West Nile virus, tickborne encephalitis virus; enteroviruses (enterovirus-71, coxsackieviruses), poliovirus
- Rhombencephalitis — Herpes simplex virus, West Nile virus, enterovirus 71, L. monocytogenes
- ↑ Tunkel, Allan R.; Glaser, Carol A.; Bloch, Karen C.; Sejvar, James J.; Marra, Christina M.; Roos, Karen L.; Hartman, Barry J.; Kaplan, Sheldon L.; Scheld, W. Michael; Whitley, Richard J.; Infectious Diseases Society of America (2008-08-01). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (3): 303–327. doi:10.1086/589747. ISSN 1537-6591. PMID 18582201..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Tunkel, Allan R.; Glaser, Carol A.; Bloch, Karen C.; Sejvar, James J.; Marra, Christina M.; Roos, Karen L.; Hartman, Barry J.; Kaplan, Sheldon L.; Scheld, W. Michael; Whitley, Richard J.; Infectious Diseases Society of America (2008-08-01). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (3): 303–327. doi:10.1086/589747. ISSN 1537-6591. PMID 18582201.
- ↑ Tunkel, Allan R.; Glaser, Carol A.; Bloch, Karen C.; Sejvar, James J.; Marra, Christina M.; Roos, Karen L.; Hartman, Barry J.; Kaplan, Sheldon L.; Scheld, W. Michael; Whitley, Richard J.; Infectious Diseases Society of America (2008-08-01). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (3): 303–327. doi:10.1086/589747. ISSN 1537-6591. PMID 18582201. | Sandbox g24
- Empiric antimicrobial therapy[1]
- Preferred regimen: Acyclovir 10 mg/kg IV q8h for 14–21 days
- Specific epidemiologic considerations[2]
- Agammaglobulinemia — Enteroviruses, Mycoplasma pneumoniae
- Age
- Neonates — Herpes simplex virus type 2, cytomegalovirus, rubella virus, Listeria monocytogenes, Treponema pallidum, Toxoplasma gondii
- Infants and children — Eastern equine encephalitis virus, Japanese encephalitis virus, Murray Valley encephalitis virus, influenza virus, La Crosse virus
- Elderly persons — Eastern equine encephalitis virus, St. Louis encephalitis virus, West Nile virus, sporadic CJD, L. monocytogenes
- Animal contact
- Bats — Rabies virus, Nipah virus
- Birds — West Nile virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Japanese encephalitis virus, Cryptococcus neoformans (bird droppings)
- Cats — Rabies virus, Coxiella burnetii, Bartonella henselae, T. gondii
- Dogs — Rabies virus
- Horses — Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Hendra virus
- Old World primates — B virus
- Raccoons — Rabies virus, Baylisascaris procyonis
- Rodents — Eastern equine encephalitis virus (South America), Venezuelan equine encephalitis virus, tickborne encephalitis virus, Powassan virus (woodchucks), La Crosse virus (chipmunks and squirrels), Bartonella quintana
- Sheep and goats — C. burnetii
- Skunks — Rabies virus
- Swine — Japanese encephalitis virus, Nipah virus
- White-tailed deer — Borrelia burgdorferi
- Immunocompromised persons — Varicella zoster virus, cytomegalovirus, human herpesvirus 6, West Nile virus, HIV, JC virus, L. monocytogenes, Mycobacterium tuberculosis, C. neoformans, Coccidioides species, Histoplasma capsulatum, T. gondii
- Ingestion
- Raw or partially cooked meat — T. gondii
- Raw meat, fish, or reptiles — Gnanthostoma species
- Unpasteurized milk — Tickborne encephalitis virus, L. monocytogenes, C. burnetii
- Insect contact
- Mosquitoes — Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Japanese encephalitis virus, West Nile virus, La Crosse virus, Plasmodium falciparum
- Sandflies — Bartonella bacilliformis
- Ticks — Tickborne encephalitis virus, Powassan virus, Rickettsia rickettsii, Ehrlichia chaffeensis, Anaplasma phagocytophilum, C. burnetii (rare), B. burgdorferi
- Tsetse flies — Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense
- Occupation
- Exposure to animals — Rabies virus, C. burnetii, Bartonella species
- Exposure to horses — Hendra virus
- Exposure to Old World primates — B virus
- Laboratory workers — West Nile virus, HIV, C. burnetii, Coccidioides species
- Physicians and health care workers — Varicella zoster virus, HIV, influenza virus, measles virus, M. tuberculosis
- Veterinarians — Rabies virus, Bartonella species, C. burnetii
- Person-to-person transmission — Herpes simplex virus (neonatal), varicella zoster virus, Venezuelan equine encephalitis virus (rare), poliovirus, nonpolio enteroviruses, measles virus, Nipah virus, mumps virus, rubella virus, Epstein-Barr virus, human herpesvirus 6, B virus, West Nile virus (transfusion, transplantation, breast feeding), HIV, rabies virus (transplantation), influenza virus, M. pneumoniae, M. tuberculosis, T. pallidum
- Recent vaccination — Acute disseminated encephalomyelitis
- Recreational activities
- Camping/hunting — Agents transmitted by mosquitoes and ticks
- Sexual contact — HIV, T. pallidum
- Spelunking — Rabies virus, H. capsulatum
- Swimming — Enteroviruses, Naegleria fowleri
- Season
- Late summer/early fall — Agents transmitted by mosquitoes and ticks, enteroviruses
- Winter — Influenza virus
- Transfusion and transplantation — Cytomegalovirus, Epstein-Barr virus, West Nile virus, HIV, tickborne encephalitis virus, rabies virus, iatrogenic CJD, T. pallidum, A. phagocytophilum, R. rickettsii, C. neoformans, Coccidioides species, H. capsulatum, T. gondii
- Travel
- Africa — Rabies virus, West Nile virus, P. falciparum, T. brucei gambiense, T. brucei rhodesiense
- Australia — Murray Valley encephalitis virus, Japanese encephalitis virus, Hendra virus
- Central America — Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, R. rickettsii, P. falciparum, Taenia solium
- Europe — West Nile virus, tickborne encephalitis virus, A. phagocytophilum, B. burgdorferi
- India, Nepal — Rabies virus, Japanese encephalitis virus, P. falciparum
- Middle East — West Nile virus, P. falciparum
- Russia — Tickborne encephalitis virus
- South America — Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, R. rickettsii, B. bacilliformis (Andes mountains), P. falciparum, T. solium
- Southeast Asia, China, Pacific Rim — Japanese encephalitis virus, tickborne encephalitis virus, Nipah virus, P. falciparum, Gnanthostoma species, T. solium
- Unvaccinated status — Varicella zoster virus, Japanese encephalitis virus, poliovirus, measles virus, mumps virus, rubella virus
- Specific clinical considerations[3]
- General findings
- Hepatitis — Coxiella burnetii
- Lymphadenopathy — HIV, Epstein-Barr virus, cytomegalovirus, measles virus, rubella virus, West Nile virus, Treponema pallidum, Bartonella henselae and other Bartonella species, Mycobacterium tuberculosis, Toxoplasma gondii, Trypanosoma brucei gambiense
- Parotitis — Mumps virus
- Rash — Varicella zoster virus, B virus, human herpesvirus 6, West Nile virus, rubella virus, some enteroviruses, HIV, Rickettsia rickettsii, Mycoplasma pneumoniae, Borrelia burgdorferi, T. pallidum, Ehrlichia chaffeensis, Anaplasma phagocytophilum
- Respiratory tract findings — Venezuelan equine encephalitis virus, Nipah virus, Hendra virus, influenza virus, adenovirus, M. pneumoniae, C. burnetii, M. tuberculosis, Histoplasma capsulatum
- Retinitis — Cytomegalovirus, West Nile virus, B. henselae, T. pallidum
- Urinary symptoms — St. Louis encephalitis virus
- Neurologic findings
- Cerebellar ataxia — Varicella zoster virus (children), Epstein-Barr virus, mumps virus, St. Louis encephalitis virus, Tropheryma whipplei, T. brucei gambiense
- Cranial nerve abnormalities — Herpes simplex virus, Epstein-Barr virus, Listeria monocytogenes, M. tuberculosis, T. pallidum, B. burgdorferi, T. whipplei, Cryptococcus neoformans, Coccidioides species, H. capsulatum
- Dementia — HIV, human transmissible spongiform encephalopathies (sCJD and vCJD), measles virus (SSPE), T. pallidum, T. whipplei
- Myorhythmia — T. whipplei (oculomasticatory)
- Parkinsonism — Japanese encephalitis virus, St. Louis encephalitis virus, West Nile virus, Nipah virus, T. gondii, T. brucei gambiense
- Poliomyelitis-like flaccid paralysis — Japanese encephalitis virus, West Nile virus, tickborne encephalitis virus; enteroviruses (enterovirus-71, coxsackieviruses), poliovirus
- Rhombencephalitis — Herpes simplex virus, West Nile virus, enterovirus 71, L. monocytogenes
- ↑ Tunkel, Allan R.; Glaser, Carol A.; Bloch, Karen C.; Sejvar, James J.; Marra, Christina M.; Roos, Karen L.; Hartman, Barry J.; Kaplan, Sheldon L.; Scheld, W. Michael; Whitley, Richard J.; Infectious Diseases Society of America (2008-08-01). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (3): 303–327. doi:10.1086/589747. ISSN 1537-6591. PMID 18582201..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Tunkel, Allan R.; Glaser, Carol A.; Bloch, Karen C.; Sejvar, James J.; Marra, Christina M.; Roos, Karen L.; Hartman, Barry J.; Kaplan, Sheldon L.; Scheld, W. Michael; Whitley, Richard J.; Infectious Diseases Society of America (2008-08-01). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (3): 303–327. doi:10.1086/589747. ISSN 1537-6591. PMID 18582201.
- ↑ Tunkel, Allan R.; Glaser, Carol A.; Bloch, Karen C.; Sejvar, James J.; Marra, Christina M.; Roos, Karen L.; Hartman, Barry J.; Kaplan, Sheldon L.; Scheld, W. Michael; Whitley, Richard J.; Infectious Diseases Society of America (2008-08-01). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (3): 303–327. doi:10.1086/589747. ISSN 1537-6591. PMID 18582201. | https://www.wikidoc.org/index.php/Sandbox_g24 | |
44ec58f9fd26103f61d9cfc6f6de7cdec607548b | wikidoc | Sandbox g28 | Sandbox g28
- Subdural empyema
- Causative pathogens
- More common
- Streptococcus milleri
- Other streptococci and enterococci
- Aerobic Gram-negative bacilli (Haemophilus influenzae, Proteus, Escherichia coli, Pseudomonas, Klebsiella, Acinetobacter, Salmonella, Morganella, Eikenella)
- No growth
- Less common
- Streptococcus pneumoniae
- Staphylococcus aureus, coagulase-negative staphylococci
- Anaerobic Gram-positive cocci (Veillonella, Peptostreptococcus, others)
- Anaerobic Gram-negative bacilli (Bacteroides, Fusobacterium, Prevotella)
- Empiric antimicrobial therapy
- Intracranial subdural empyema with unclear source of infection
- Preferred regimen: (Nafcillin 2 g IV q4h or Oxacillin 2 g IV q4h) AND (Ceftriaxone 2 g IV q12h or Cefotaxime 8–12 g/day IV q4–6h) AND Metronidazole 7.5 mg/kg IV q6h
- Intracranial subdural empyema associated with sinusitis or otitis media
- Preferred regimen: (Nafcillin 2 g IV q4h or Oxacillin 2 g IV q4h) AND (Ceftriaxone 2 g IV q12h or Cefotaxime 8–12 g/day IV q4–6h) AND Metronidazole 7.5 mg/kg IV q6h
- Intracranial subdural empyema after cranial trauma
- Preferred regimen: Nafcillin 2 g IV q4h or Oxacillin 2 g IV q4h
- Intracranial subdural empyema after neurosurgical procedures
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Ceftazidime 2 g IV q8h
- Intracranial subdural empyema in neonates (usually associated with meningitis)
- Infants < 1 month
- Preferred regimen: Ampicillin 200 mg/kg/day IV q4h AND Cefotaxime 200 mg/kg/day IV q6h
- Infants 1–3 months
- Preferred regimen: Ampicillin 200 mg/kg/day IV q4h AND (Cefotaxime 200 mg/kg/day IV q6h OR Ceftriaxone 100 mg/kg/day IV q12h)
- Infants > 3 months
- Preferred regimen: Vancomycin 60 mg/kg/day IV q6h AND (Cefotaxime 200 mg/kg/day IV q6h OR Ceftriaxone 100 mg/kg/day IV q12h OR Cefepime 150 mg/kg/day IV q8h)
- Spinal subdural empyema
- Preferred regimen: Nafcillin 2 g IV q4h or Oxacillin 2 g IV q4h
- Pathogen-directed antimicrobial therapy
- Staphylococcus aureus, methicillin-resistant (MRSA)
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 4–6 weeks
- Alternative regimen: Linezolid 600 mg PO/IV q12h for 4–6 weeks OR TMP-SMX 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks
- Pediatric dose: Vancomycin 15 mg/kg/dose IV q6h OR Linezolid 10 mg/kg/dose PO/IV q8h
- ↑ Osborn, Melissa K.; Steinberg, James P. (2007-01). "Subdural empyema and other suppurative complications of paranasal sinusitis". The Lancet. Infectious Diseases. 7 (1): 62–67. doi:10.1016/S1473-3099(06)70688-0. ISSN 1473-3099. PMID 17182345. Check date values in: |date= (help).mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Greenlee, John E. (2003-01). "Subdural Empyema". Current Treatment Options in Neurology. 5 (1): 13–22. ISSN 1092-8480. PMID 12521560. Check date values in: |date= (help) | Sandbox g28
- Subdural empyema[1][2]
- Causative pathogens
- More common
- Streptococcus milleri
- Other streptococci and enterococci
- Aerobic Gram-negative bacilli (Haemophilus influenzae, Proteus, Escherichia coli, Pseudomonas, Klebsiella, Acinetobacter, Salmonella, Morganella, Eikenella)
- No growth
- Less common
- Streptococcus pneumoniae
- Staphylococcus aureus, coagulase-negative staphylococci
- Anaerobic Gram-positive cocci (Veillonella, Peptostreptococcus, others)
- Anaerobic Gram-negative bacilli (Bacteroides, Fusobacterium, Prevotella)
- Empiric antimicrobial therapy
- Intracranial subdural empyema with unclear source of infection
- Preferred regimen: (Nafcillin 2 g IV q4h or Oxacillin 2 g IV q4h) AND (Ceftriaxone 2 g IV q12h or Cefotaxime 8–12 g/day IV q4–6h) AND Metronidazole 7.5 mg/kg IV q6h
- Intracranial subdural empyema associated with sinusitis or otitis media
- Preferred regimen: (Nafcillin 2 g IV q4h or Oxacillin 2 g IV q4h) AND (Ceftriaxone 2 g IV q12h or Cefotaxime 8–12 g/day IV q4–6h) AND Metronidazole 7.5 mg/kg IV q6h
- Intracranial subdural empyema after cranial trauma
- Preferred regimen: Nafcillin 2 g IV q4h or Oxacillin 2 g IV q4h
- Intracranial subdural empyema after neurosurgical procedures
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Ceftazidime 2 g IV q8h
- Intracranial subdural empyema in neonates (usually associated with meningitis)
- Infants < 1 month
- Preferred regimen: Ampicillin 200 mg/kg/day IV q4h AND Cefotaxime 200 mg/kg/day IV q6h
- Infants 1–3 months
- Preferred regimen: Ampicillin 200 mg/kg/day IV q4h AND (Cefotaxime 200 mg/kg/day IV q6h OR Ceftriaxone 100 mg/kg/day IV q12h)
- Infants > 3 months
- Preferred regimen: Vancomycin 60 mg/kg/day IV q6h AND (Cefotaxime 200 mg/kg/day IV q6h OR Ceftriaxone 100 mg/kg/day IV q12h OR Cefepime 150 mg/kg/day IV q8h)
- Spinal subdural empyema
- Preferred regimen: Nafcillin 2 g IV q4h or Oxacillin 2 g IV q4h
- Pathogen-directed antimicrobial therapy
- Staphylococcus aureus, methicillin-resistant (MRSA)
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 4–6 weeks
- Alternative regimen: Linezolid 600 mg PO/IV q12h for 4–6 weeks OR TMP-SMX 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks
- Pediatric dose: Vancomycin 15 mg/kg/dose IV q6h OR Linezolid 10 mg/kg/dose PO/IV q8h
- ↑ Osborn, Melissa K.; Steinberg, James P. (2007-01). "Subdural empyema and other suppurative complications of paranasal sinusitis". The Lancet. Infectious Diseases. 7 (1): 62–67. doi:10.1016/S1473-3099(06)70688-0. ISSN 1473-3099. PMID 17182345. Check date values in: |date= (help).mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Greenlee, John E. (2003-01). "Subdural Empyema". Current Treatment Options in Neurology. 5 (1): 13–22. ISSN 1092-8480. PMID 12521560. Check date values in: |date= (help) | https://www.wikidoc.org/index.php/Sandbox_g28 | |
0bcfd8a8848ac23647079accc8f4200f39829c41 | wikidoc | Sandbox g29 | Sandbox g29
- Septic thrombosis of cavernous or dural venous sinus
- Empiric antimicrobial therapy
- Preferred regimen: (Nafcillin 2 g IV q4h or Oxacillin 2 g IV q4h) AND (Ceftriaxone 2 g IV q12h or Cefotaxime 8–12 g/day IV q4–6h) AND Metronidazole 7.5 mg/kg IV q6h
- Specific considerations
- Cavernous sinus
- Preferred regimen: Vancomycin 30–45 mg/kg IV q8–12h AND (Ceftriaxone 2 g IV q12h or Cefotaxime 8–12 g/day IV q4–6h) AND Metronidazole 7.5 mg/kg IV q6h
- Lateral sinus
- Preferred regimen: Cefepime 2 g IV q8h AND Metronidazole 500 mg IV q8h AND Vancomycin 15-20 IV mg/kg
- Alternative regimen: Meropenem 1-2 g IV q8h AND Linezolid 600 mg IV q12h
- Superior sagittal sinus
- Preferred regimen: Ceftriaxone 2 g IV q12h AND Vancomycin 15–20 mg/kg AND Dexamethasone
- Alternative regimen: Meropenem 1–2 g IV q8h AND Vancomycin 15–20 mg/kg AND Dexamethasone
- Pathogen-directed antimicrobial therapy
- Staphylococcus aureus, methicillin-resistant (MRSA)
- Preferred regimen: Vancomycin 15–20 mg/kg/dose IV q8–12h for 4–6 weeks
- Alternative regimen: Linezolid 600 mg PO/IV q12h for 4–6 weeks OR TMP-SMX 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks
- Pediatric dose: Vancomycin 15 mg/kg/dose IV q6h OR Linezolid 10 mg/kg/dose PO/IV q8h
- ↑ Saposnik, Gustavo; Barinagarrementeria, Fernando; Brown, Robert D.; Bushnell, Cheryl D.; Cucchiara, Brett; Cushman, Mary; deVeber, Gabrielle; Ferro, Jose M.; Tsai, Fong Y.; American Heart Association Stroke Council and the Council on Epidemiology and Prevention (2011-04). "Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association". Stroke; a Journal of Cerebral Circulation. 42 (4): 1158–1192. doi:10.1161/STR.0b013e31820a8364. ISSN 1524-4628. PMID 21293023. Check date values in: |date= (help).mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Ebright, J. R.; Pace, M. T.; Niazi, A. F. (2001-12-10). "Septic thrombosis of the cavernous sinuses". Archives of Internal Medicine. 161 (22): 2671–2676. ISSN 0003-9926. PMID 11732931.
- ↑ Liu, Catherine; Bayer, Arnold; Cosgrove, Sara E.; Daum, Robert S.; Fridkin, Scott K.; Gorwitz, Rachel J.; Kaplan, Sheldon L.; Karchmer, Adolf W.; Levine, Donald P.; Murray, Barbara E.; J Rybak, Michael; Talan, David A.; Chambers, Henry F.; Infectious Diseases Society of America (2011-02-01). "Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 52 (3): –18-55. doi:10.1093/cid/ciq146. ISSN 1537-6591. PMID 21208910. | Sandbox g29
- Septic thrombosis of cavernous or dural venous sinus
- Empiric antimicrobial therapy[1][2]
- Preferred regimen: (Nafcillin 2 g IV q4h or Oxacillin 2 g IV q4h) AND (Ceftriaxone 2 g IV q12h or Cefotaxime 8–12 g/day IV q4–6h) AND Metronidazole 7.5 mg/kg IV q6h
- Specific considerations
- Cavernous sinus
- Preferred regimen: Vancomycin 30–45 mg/kg IV q8–12h AND (Ceftriaxone 2 g IV q12h or Cefotaxime 8–12 g/day IV q4–6h) AND Metronidazole 7.5 mg/kg IV q6h
- Lateral sinus
- Preferred regimen: Cefepime 2 g IV q8h AND Metronidazole 500 mg IV q8h AND Vancomycin 15-20 IV mg/kg
- Alternative regimen: Meropenem 1-2 g IV q8h AND Linezolid 600 mg IV q12h
- Superior sagittal sinus
- Preferred regimen: Ceftriaxone 2 g IV q12h AND Vancomycin 15–20 mg/kg AND Dexamethasone
- Alternative regimen: Meropenem 1–2 g IV q8h AND Vancomycin 15–20 mg/kg AND Dexamethasone
- Pathogen-directed antimicrobial therapy
- Staphylococcus aureus, methicillin-resistant (MRSA)[3]
- Preferred regimen: Vancomycin 15–20 mg/kg/dose IV q8–12h for 4–6 weeks
- Alternative regimen: Linezolid 600 mg PO/IV q12h for 4–6 weeks OR TMP-SMX 5 mg/kg/dose PO/IV q8–12h for 4–6 weeks
- Pediatric dose: Vancomycin 15 mg/kg/dose IV q6h OR Linezolid 10 mg/kg/dose PO/IV q8h
- ↑ Saposnik, Gustavo; Barinagarrementeria, Fernando; Brown, Robert D.; Bushnell, Cheryl D.; Cucchiara, Brett; Cushman, Mary; deVeber, Gabrielle; Ferro, Jose M.; Tsai, Fong Y.; American Heart Association Stroke Council and the Council on Epidemiology and Prevention (2011-04). "Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association". Stroke; a Journal of Cerebral Circulation. 42 (4): 1158–1192. doi:10.1161/STR.0b013e31820a8364. ISSN 1524-4628. PMID 21293023. Check date values in: |date= (help).mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Ebright, J. R.; Pace, M. T.; Niazi, A. F. (2001-12-10). "Septic thrombosis of the cavernous sinuses". Archives of Internal Medicine. 161 (22): 2671–2676. ISSN 0003-9926. PMID 11732931.
- ↑ Liu, Catherine; Bayer, Arnold; Cosgrove, Sara E.; Daum, Robert S.; Fridkin, Scott K.; Gorwitz, Rachel J.; Kaplan, Sheldon L.; Karchmer, Adolf W.; Levine, Donald P.; Murray, Barbara E.; J Rybak, Michael; Talan, David A.; Chambers, Henry F.; Infectious Diseases Society of America (2011-02-01). "Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 52 (3): –18-55. doi:10.1093/cid/ciq146. ISSN 1537-6591. PMID 21208910. | https://www.wikidoc.org/index.php/Sandbox_g29 | |
e818e825610560d364185b220b4a1d61c5175fe0 | wikidoc | Sandbox g30 | Sandbox g30
- Tuberculous meningitis
- First-line therapy (dosing information: )
- Isoniazid
- Rifampin
- Rifabutin
- Pyrazinamide
- Ethambutol
- Second-line therapy (dosing information: )
- Cycloserine
- Ethionamide
- Streptomycin
- Amikacin
- Kanamycin
- Capreomycin
- p-Aminosalicylic acid
- Levofloxacin
- Moxifloxacin
- Gatifloxacin
- Tuberculous meningitis caused by susceptible Mycobacterium tuberculosis
- Intensive phase (adult)
- Preferred regimen: Isoniazid 5 mg/kg (max: 300 mg) for 2 months AND Rifampin 10 mg/kg (max: 600 mg) for 2 months AND Pyrazinamide 15–30 mg/kg (max: 2 g) for 2 months AND Ethambutol 15–20 mg/kg (max: 1 g) for 2 months
- Continuation phase (adult)
- Preferred regimen: Isoniazid 5 mg/kg (max: 300 mg) for 7–10 months AND Rifampin 10 mg/kg (max: 600 mg) for 7–10 months
- Intensive phase (pediatric)
- Preferred regimen: Isoniazid 10–15 mg/kg (max: 300 mg) for 2 months AND Rifampin 10–20 mg/kg (max: 600 mg) for 2 months AND Pyrazinamide 15–30 mg/kg (max: 2 g) for 2 months AND Ethambutol 15–20 mg/kg (max: 1 g) for 2 months
- Continuation phase (pediatric)
- Preferred regimen: Isoniazid 10–15 mg/kg (max: 300 mg) for 7–10 months AND Rifampin 10–20 mg/kg (max: 600 mg) for 7–10 months
- Tuberculous meningitis caused by Mycobacterium tuberculosis resistant to isoniazid or rifampin
- Isoniazid monoresistance
- Substitute fluoroquinolone for isoniazid in intensive phase regimen.
- Continue treatment with rifampin, pyrazinamide, and fluoroquinolone for 12 months.
- Rifampin monoresistance
- Substitute Fluoroquinolones for Rifampin in intensive phase regimen.
- Continue treatment with isoniazid, pyrazinamide, and fluoroquinolone for 18 months.
- MDR-TB (resistant to Isoniazid and Rifampin)
- MDR tuberculosis therapy should be considered if there is a history of prior tuberculosis treatment, contact with a patient with MDR tuberculosis, or a poor clinical response to first-line TB therapy within 2 weeks despite a firm diagnosis and an adequate adherence to treatment.
- Second-line agents such as Aminoglycosides penetrate the BBB only in the presence of inflamed meninges, and Fluoroquinolones, while able to penetrate into the CNS, have lower CSF levels than in the serum or brain parenchyma.
- Consult infectious disease specialist.
- XDR-TB (resistant to Isoniazid, Rifampin, Fluoroquinolones, and either Capreomycin, Kanamycin, or Amikacin)
- Consider Ethionamide or Cycloserine to build the treatment regimen.
- Consult infectious disease specialist.
- ↑ Blumberg, Henry M.; Burman, William J.; Chaisson, Richard E.; Daley, Charles L.; Etkind, Sue C.; Friedman, Lloyd N.; Fujiwara, Paula; Grzemska, Malgosia; Hopewell, Philip C.; Iseman, Michael D.; Jasmer, Robert M.; Koppaka, Venkatarama; Menzies, Richard I.; O'Brien, Richard J.; Reves, Randall R.; Reichman, Lee B.; Simone, Patricia M.; Starke, Jeffrey R.; Vernon, Andrew A.; American Thoracic Society, Centers for Disease Control and Prevention and the Infectious Diseases Society (2003-02-15). "American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis". American Journal of Respiratory and Critical Care Medicine. 167 (4): 603–662. doi:10.1164/rccm.167.4.603. ISSN 1073-449X. PMID 12588714..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)CS1 maint: PMC format (link)
- ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
- ↑ American Thoracic Society; CDC; Infectious Diseases Society of America (2003-06-20). "Treatment of tuberculosis". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 52 (RR-11): 1–77. ISSN 1057-5987. PMID 12836625.
- ↑ Treatment of Tuberculosis: Guidelines. WHO Guidelines Approved by the Guidelines Review Committee (4th ed.). Geneva: World Health Organization. 2010. ISBN 9789241547833. PMID 23741786. Retrieved 2015-06-08.
- ↑ Treatment of Tuberculosis: Guidelines. WHO Guidelines Approved by the Guidelines Review Committee (4th ed.). Geneva: World Health Organization. 2010. ISBN 9789241547833. PMID 23741786. Retrieved 2015-06-08.
- ↑ American Thoracic Society; CDC; Infectious Diseases Society of America (2003-06-20). "Treatment of tuberculosis". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 52 (RR-11): 1–77. ISSN 1057-5987. PMID 12836625.
- ↑ Thwaites, Guy E.; Nguyen, Duc Bang; Nguyen, Huy Dung; Hoang, Thi Quy; Do, Thi Tuong Oanh; Nguyen, Thi Cam Thoa; Nguyen, Quang Hien; Nguyen, Tri Thuc; Nguyen, Ngoc Hai; Nguyen, Thi Ngoc Lan; Nguyen, Ngoc Lan; Nguyen, Hong Duc; Vu, Ngoc Tuan; Cao, Huu Hiep; Tran, Thi Hong Chau; Pham, Phuong Mai; Nguyen, Thi Dung; Stepniewska, Kasia; White, Nicholas J.; Tran, Tinh Hien; Farrar, Jeremy J. (2004-10-21). "Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults". The New England Journal of Medicine. 351 (17): 1741–1751. doi:10.1056/NEJMoa040573. ISSN 1533-4406. PMID 15496623.
- ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
- ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
- ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
- ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
- ↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)CS1 maint: PMC format (link)
- ↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)CS1 maint: PMC format (link) | Sandbox g30
- Tuberculous meningitis
- First-line therapy (dosing information: [1][2][3])
- Isoniazid
- Rifampin
- Rifabutin
- Pyrazinamide
- Ethambutol
- Second-line therapy (dosing information: [4][5][6])
- Cycloserine
- Ethionamide
- Streptomycin
- Amikacin
- Kanamycin
- Capreomycin
- p-Aminosalicylic acid
- Levofloxacin
- Moxifloxacin
- Gatifloxacin
- Tuberculous meningitis caused by susceptible Mycobacterium tuberculosis[1][2][3][4]
- Intensive phase (adult)
- Preferred regimen: Isoniazid 5 mg/kg (max: 300 mg) for 2 months AND Rifampin 10 mg/kg (max: 600 mg) for 2 months AND Pyrazinamide 15–30 mg/kg (max: 2 g) for 2 months AND Ethambutol 15–20 mg/kg (max: 1 g) for 2 months
- Continuation phase (adult)
- Preferred regimen: Isoniazid 5 mg/kg (max: 300 mg) for 7–10 months AND Rifampin 10 mg/kg (max: 600 mg) for 7–10 months
- Intensive phase (pediatric)
- Preferred regimen: Isoniazid 10–15 mg/kg (max: 300 mg) for 2 months AND Rifampin 10–20 mg/kg (max: 600 mg) for 2 months AND Pyrazinamide 15–30 mg/kg (max: 2 g) for 2 months AND Ethambutol 15–20 mg/kg (max: 1 g) for 2 months
- Continuation phase (pediatric)
- Preferred regimen: Isoniazid 10–15 mg/kg (max: 300 mg) for 7–10 months AND Rifampin 10–20 mg/kg (max: 600 mg) for 7–10 months
- Tuberculous meningitis caused by Mycobacterium tuberculosis resistant to isoniazid or rifampin
- Isoniazid monoresistance[11]
- Substitute fluoroquinolone for isoniazid in intensive phase regimen.
- Continue treatment with rifampin, pyrazinamide, and fluoroquinolone for 12 months.
- Rifampin monoresistance[12]
- Substitute Fluoroquinolones for Rifampin in intensive phase regimen.
- Continue treatment with isoniazid, pyrazinamide, and fluoroquinolone for 18 months.
- MDR-TB (resistant to Isoniazid and Rifampin)[13]
- MDR tuberculosis therapy should be considered if there is a history of prior tuberculosis treatment, contact with a patient with MDR tuberculosis, or a poor clinical response to first-line TB therapy within 2 weeks despite a firm diagnosis and an adequate adherence to treatment.
- Second-line agents such as Aminoglycosides penetrate the BBB only in the presence of inflamed meninges, and Fluoroquinolones, while able to penetrate into the CNS, have lower CSF levels than in the serum or brain parenchyma.
- Consult infectious disease specialist.
- XDR-TB (resistant to Isoniazid, Rifampin, Fluoroquinolones, and either Capreomycin, Kanamycin, or Amikacin)[14]
- Consider Ethionamide or Cycloserine to build the treatment regimen.
- Consult infectious disease specialist.
- ↑ Blumberg, Henry M.; Burman, William J.; Chaisson, Richard E.; Daley, Charles L.; Etkind, Sue C.; Friedman, Lloyd N.; Fujiwara, Paula; Grzemska, Malgosia; Hopewell, Philip C.; Iseman, Michael D.; Jasmer, Robert M.; Koppaka, Venkatarama; Menzies, Richard I.; O'Brien, Richard J.; Reves, Randall R.; Reichman, Lee B.; Simone, Patricia M.; Starke, Jeffrey R.; Vernon, Andrew A.; American Thoracic Society, Centers for Disease Control and Prevention and the Infectious Diseases Society (2003-02-15). "American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis". American Journal of Respiratory and Critical Care Medicine. 167 (4): 603–662. doi:10.1164/rccm.167.4.603. ISSN 1073-449X. PMID 12588714..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)CS1 maint: PMC format (link)
- ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
- ↑ American Thoracic Society; CDC; Infectious Diseases Society of America (2003-06-20). "Treatment of tuberculosis". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 52 (RR-11): 1–77. ISSN 1057-5987. PMID 12836625.
- ↑ Treatment of Tuberculosis: Guidelines. WHO Guidelines Approved by the Guidelines Review Committee (4th ed.). Geneva: World Health Organization. 2010. ISBN 9789241547833. PMID 23741786. Retrieved 2015-06-08.
- ↑ Treatment of Tuberculosis: Guidelines. WHO Guidelines Approved by the Guidelines Review Committee (4th ed.). Geneva: World Health Organization. 2010. ISBN 9789241547833. PMID 23741786. Retrieved 2015-06-08.
- ↑ American Thoracic Society; CDC; Infectious Diseases Society of America (2003-06-20). "Treatment of tuberculosis". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 52 (RR-11): 1–77. ISSN 1057-5987. PMID 12836625.
- ↑ Thwaites, Guy E.; Nguyen, Duc Bang; Nguyen, Huy Dung; Hoang, Thi Quy; Do, Thi Tuong Oanh; Nguyen, Thi Cam Thoa; Nguyen, Quang Hien; Nguyen, Tri Thuc; Nguyen, Ngoc Hai; Nguyen, Thi Ngoc Lan; Nguyen, Ngoc Lan; Nguyen, Hong Duc; Vu, Ngoc Tuan; Cao, Huu Hiep; Tran, Thi Hong Chau; Pham, Phuong Mai; Nguyen, Thi Dung; Stepniewska, Kasia; White, Nicholas J.; Tran, Tinh Hien; Farrar, Jeremy J. (2004-10-21). "Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults". The New England Journal of Medicine. 351 (17): 1741–1751. doi:10.1056/NEJMoa040573. ISSN 1533-4406. PMID 15496623.
- ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
- ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
- ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
- ↑ Thwaites, Guy; Fisher, Martin; Hemingway, Cheryl; Scott, Geoff; Solomon, Tom; Innes, John; British Infection Society (2009-09). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". The Journal of Infection. 59 (3): 167–187. doi:10.1016/j.jinf.2009.06.011. ISSN 1532-2742. PMID 19643501. Check date values in: |date= (help)
- ↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)CS1 maint: PMC format (link)
- ↑ Rock, R. Bryan; Olin, Michael; Baker, Cristina A.; Molitor, Thomas W.; Peterson, Phillip K. (2008-04). "Central nervous system tuberculosis: pathogenesis and clinical aspects". Clinical Microbiology Reviews. 21 (2): 243–261, table of contents. doi:10.1128/CMR.00042-07. ISSN 1098-6618. PMC 2292571. PMID 18400795. Check date values in: |date= (help)CS1 maint: PMC format (link) | https://www.wikidoc.org/index.php/Sandbox_g30 | |
701a93a9c2bba5b8959c8329eaca024ad8a69237 | wikidoc | Sandbox g31 | Sandbox g31
# Meningitis, MRSA
- Meningitis caused by methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 2 weeks
- Alternative regimen: Linezolid 600 mg PO/IV q12h OR TMP-SMX 10–20 mg/kg/day IV q6–12h
- Pediatric regimen: Vancomycin 15–20 mg/kg IV q6h OR Linezolid 10 mg/kg PO/IV q8h | Sandbox g31
## Meningitis, MRSA
- Meningitis caused by methicillin-resistant Staphylococcus aureus (MRSA)
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h for 2 weeks
- Alternative regimen: Linezolid 600 mg PO/IV q12h OR TMP-SMX 10–20 mg/kg/day IV q6–12h
- Pediatric regimen: Vancomycin 15–20 mg/kg IV q6h OR Linezolid 10 mg/kg PO/IV q8h | https://www.wikidoc.org/index.php/Sandbox_g31 | |
bf8eea0a9515dbd70a9d933053ea5f91babd77dd | wikidoc | Sandbox g32 | Sandbox g32
- Bacterial meningitis
- Empiric antimicrobial therapy based on specific predisposing factors
- Age
- Age < 1 month
- Common causative pathogens: Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, Klebsiella species
- Preferred regimen: Ampicillin 12 g/day IV q4h AND (Cefotaxime 8–12 g/day q4–6h OR Amikacin 15 mg/kg/day IV q8h OR Gentamicin 5 mg/kg/day IV q8h OR Tobramycin 5 mg/kg/day IV q8h)
- Age 1–23 months
- Common causative pathogens: Streptococcus pneumoniae, Neisseria meningitidis, S. agalactiae, Haemophilus influenzae, E. coli
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
- Age 2–50 years
- Common causative pathogens: N . meningitidis, S. pneumoniae
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
- Age > 50 years
- Common causative pathogens: S. pneumoniae, N. meningitidis, L. monocytogenes, aerobic Gram-negative bacilli
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Ampicillin 12 g/day IV q4h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
- Head trauma
- Basilar skull fracture
- Common causative pathogens: S. pneumoniae, H. influenzae, group A β-hemolytic streptococci
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
- Penetrating trauma
- Common causative pathogens: Staphylococcus aureus, coagulase-negative staphylococci (especially Staphylococcus epidermidis), aerobic Gram-negative bacilli (including Pseudomonas aeruginosa)
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Cefepime 6 g/day IV q8h OR Ceftazidime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h
- Postneurosurgery
- Common causative pathogens: Aerobic Gram-negative bacilli (including P. aeruginosa), S. aureus, coagulase-negative staphylococci (especially S. epidermidis)
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Cefepime 6 g/day IV q8h OR Ceftazidime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h
- CSF shunt
- Common causative pathogens: Coagulase-negative staphylococci (especially S. epidermidis), S. aureus, aerobic Gram-negative bacilli (including P. aeruginosa), Propionibacterium acnes
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Cefepime 6 g/day IV q8h OR Ceftazidime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h
- CSF Gram stain-directed antimicrobial therapy
- Gram positive, lancet-shaped diplococci suggestive of Streptococcus pneumoniae
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
- Alternative regimen: Meropenem 6 g/day IV q8h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h
- Gram negative diplococci suggestive of Neisseria meningitidis
- Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Alternative regimen: Penicillin G 24 MU/day IV q4h OR Ampicillin 12 g/day IV q4h OR Chloramphenicol 4–6 g/day IV q6h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h OR Aztreonam 6–8 g/day IV q6–8h
- Gram positive, short bacilli suggestive of Listeria monocytogenes
- Preferred regimen: (Ampicillin 12 g/day IV q4h OR Penicillin G 24 MU/day IV q4h) ± (Amikacin 15 mg/kg/day IV q8h OR Gentamicin 5 mg/kg/day IV q8h OR Tobramycin 5 mg/kg/day IV q8h)
- Alternative regimen: Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h OR Meropenem 6 g/day IV q8h
- Gram positive cocci in short chains suggestive of Streptococcus agalactiae
- Preferred regimen: (Ampicillin 12 g/day IV q4h OR Penicillin G 24 MU/day IV q4h) ± (Amikacin 15 mg/kg/day IV q8h OR Gentamicin 5 mg/kg/day IV q8h OR Tobramycin 5 mg/kg/day IV q8h)
- Alternative regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Gram negative coccobacilli suggestive of Haemophilus influenzae
- Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Alternative regimen: Chloramphenicol 4–6 g/day IV q6h OR Cefepime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h
- Gram negative bacilli suggestive of Escherichia coli
- Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Alternative regimen: Cefepime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h OR Aztreonam 6–8 g/day IV q6–8h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h OR Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h
- Pathogen-directed antimicrobial therapy
- Streptococcus pneumoniae
- Penicillin MIC < 0.1 μg/mL
- Preferred regimen: Penicillin G 24 MU/day IV q4h OR Ampicillin 12 g/day IV q4h
- Alternative regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h OR Chloramphenicol 4–6 g/day IV q6h
- Penicillin MIC 0.1–1.0 μg/mL
- Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Alternative regimen: Cefepime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h
- Penicillin MIC ≥ 2.0 μg/mL
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
- Alternative regimen: Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h
- Cefotaxime or ceftriaxone MIC ≥ 1.0 μg/mL
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
- Alternative regimen: Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h
- Neisseria meningitidis
- Penicillin MIC < 0.1 μg/mL
- Preferred regimen: Penicillin G 24 MU/day IV q4h OR Ampicillin 12 g/day IV q4h
- Alternative regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h OR Chloramphenicol 4–6 g/day IV q6h
- Penicillin MIC 0.1–1.0 μg/mL
- Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Alternative regimen: Chloramphenicol 4–6 g/day IV q6h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h OR Meropenem 6 g/day IV q8h
- Listeria monocytogenes
- Preferred regimen: Ampicillin 12 g/day IV q4h OR Penicillin G 24 MU/day IV q4h
- Alternative regimen: Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h OR Meropenem 6 g/day IV q8h
- Streptococcus agalactiae
- Preferred regimen: Ampicillin 12 g/day IV q4h OR Penicillin G 24 MU/day IV q4h
- Alternative regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Escherichia coli and other Enterobacteriaceae
- Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Alternative regimen: Aztreonam 6–8 g/day IV q6–8h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h OR Meropenem 6 g/day IV q8h OR Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h OR Ampicillin 12 g/day IV q4h
- Pseudomonas aeruginosa
- Preferred regimen: Cefepime 6 g/day IV q8h OR Ceftazidime 6 g/day IV q8h
- Alternative regimen: Aztreonam 6–8 g/day IV q6–8h OR Ciprofloxacin 800–1200 mg IV q8–12h OR Meropenem 6 g/day IV q8h
- Haemophilus influenzae
- β-Lactamase negative
- Preferred regimen: Ampicillin 12 g/day IV q4h
- Alternative regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h OR Cefepime 6 g/day IV q8h OR Chloramphenicol 4–6 g/day IV q6h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h
- β-Lactamase positive
- Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Alternative regimen: Cefepime 6 g/day IV q8h OR Chloramphenicol 4–6 g/day IV q6h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h
- Staphylococcus aureus
- Methicillin susceptible
- Preferred regimen: Nafcillin 9–12 g/day IV q4h OR Oxacillin 9–12 g/day IV q4h
- Alternative regimen: Vancomycin 30–45 mg/kg/day IV q8–12h OR Meropenem 6 g/day IV q8h
- Methicillin resistant
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
- Alternative regimen: Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h OR Linezolid 600 mg IV q12h
- Staphylococcus epidermidis
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
- Alternative regimen: Linezolid 600 mg IV q12h
- Enterococcus species
- Ampicillin susceptible
- Preferred regimen: Ampicillin 12 g/day IV q4h AND Gentamicin 5 mg/kg/day IV q8h
- Ampicillin resistant
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Gentamicin 5 mg/kg/day IV q8h
- Ampicillin and vancomycin resistant
- Preferred regimen: Linezolid 600 mg IV q12h
- Pediatric dose:
- Amikacin
- Neonates age 0–7 days: 15–20 mg/kg/day q12h
- Neonates age 8–28 days: 30 mg/kg/day q8h
- Infants and children: 20–30 mg/kg/day q8h
- Ampicillin
- Neonates age 0–7 days: 150 mg/kg/day q8h
- Neonates age 8–28 days: 200 mg/kg/day q6–8h
- Infants and children: 300 mg/kg/day q6h
- Cefepime
- Infants and children: 150 mg/kg/day q8h
- Cefotaxime
- Neonates age 0–7 days: 100–150 mg/kg/day q8–12h
- Neonates age 8–28 days: 150–200 mg/kg/day q6–8h
- Infants and children: 225–300 mg/kg/day q6–8h
- Ceftazidime
- Neonates age 0–7 days: 100–150 mg/kg/day q8–12h
- Neonates age 8–28 days: 150 mg/kg q8h
- Infants and children: 150 mg/kg
- Ceftriaxone
- Infants and children: 80–100 mg/kg/day q12–24h
- Chloramphenicol
- Neonates age 0–7 days: 25 mg/kg/day q24h
- Neonates age 8–28 days: 50 mg/kg/day q12–24h
- Infants and children: 75–100 mg/kg/day q6h
- Gentamicin
- Neonates age 0–7 days: 5 mg/kg/day q12h
- Neonates age 8–28 days: 7.5 mg/kg/day q8h
- Infants and children: 7.5 mg/kg/day q8h
- Meropenem
- Infants and children: 120 mg/kg/day q8h
- Nafcillin
- Neonates age 0–7 days: 75 mg/kg/day q8–12h
- Neonates age 8–28 days: 100–150 mg/kg/day q6–8h
- Infants and children: 200 mg/kg/day q6h
- Oxacillin
- Neonates age 0–7 days: 75 mg/kg/day q8–12h
- Neonates age 8–28 days: 150–200 mg/kg/day q6–8h
- Infants and children: 200 mg/kg/day q6h
- Penicillin G
- Neonates age 0–7 days: 0.15 MU/kg/day q8–12h
- Neonates age 8–28 days: 0.2 MU/kg/day q6–8h
- Infants and children: 0.3 MU/kg/day q4–6h
- Rifampin
- Neonates age 8–28 days: 10–20 mg/kg/day q12h
- Infants and children: 10–20 mg/kg/day q12–24h
- Tobramycin
- Neonates age 0–7 days: 5 mg/kg/day q12h
- Neonates age 8–28 days: 7.5 mg/kg/day q8h
- Infants and children: 7.5 mg/kg/day q8h
- Trimethoprim-Sulfamethoxazole
- Infants and children: 10–20 mg/kg q6–12h
- Vancomycin
- Neonates age 0–7 days: 20–30 mg/kg/day q8–12h
- Neonates age 8–28 days: 30–45 mg/kg/day q6–8h
- Infants and children: 60 mg/kg/day q6h
- ↑ Tunkel, Allan R.; Hartman, Barry J.; Kaplan, Sheldon L.; Kaufman, Bruce A.; Roos, Karen L.; Scheld, W. Michael; Whitley, Richard J. (2004-11-01). "Practice guidelines for the management of bacterial meningitis". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 39 (9): 1267–1284. doi:10.1086/425368. ISSN 1537-6591. PMID 15494903..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | Sandbox g32
- Bacterial meningitis[1]
- Empiric antimicrobial therapy based on specific predisposing factors
- Age
- Age < 1 month
- Common causative pathogens: Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, Klebsiella species
- Preferred regimen: Ampicillin 12 g/day IV q4h AND (Cefotaxime 8–12 g/day q4–6h OR Amikacin 15 mg/kg/day IV q8h OR Gentamicin 5 mg/kg/day IV q8h OR Tobramycin 5 mg/kg/day IV q8h)
- Age 1–23 months
- Common causative pathogens: Streptococcus pneumoniae, Neisseria meningitidis, S. agalactiae, Haemophilus influenzae, E. coli
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
- Age 2–50 years
- Common causative pathogens: N . meningitidis, S. pneumoniae
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
- Age > 50 years
- Common causative pathogens: S. pneumoniae, N. meningitidis, L. monocytogenes, aerobic Gram-negative bacilli
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Ampicillin 12 g/day IV q4h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
- Head trauma
- Basilar skull fracture
- Common causative pathogens: S. pneumoniae, H. influenzae, group A β-hemolytic streptococci
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
- Penetrating trauma
- Common causative pathogens: Staphylococcus aureus, coagulase-negative staphylococci (especially Staphylococcus epidermidis), aerobic Gram-negative bacilli (including Pseudomonas aeruginosa)
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Cefepime 6 g/day IV q8h OR Ceftazidime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h
- Postneurosurgery
- Common causative pathogens: Aerobic Gram-negative bacilli (including P. aeruginosa), S. aureus, coagulase-negative staphylococci (especially S. epidermidis)
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Cefepime 6 g/day IV q8h OR Ceftazidime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h
- CSF shunt
- Common causative pathogens: Coagulase-negative staphylococci (especially S. epidermidis), S. aureus, aerobic Gram-negative bacilli (including P. aeruginosa), Propionibacterium acnes
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Cefepime 6 g/day IV q8h OR Ceftazidime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h
- CSF Gram stain-directed antimicrobial therapy
- Gram positive, lancet-shaped diplococci suggestive of Streptococcus pneumoniae
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
- Alternative regimen: Meropenem 6 g/day IV q8h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h
- Gram negative diplococci suggestive of Neisseria meningitidis
- Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Alternative regimen: Penicillin G 24 MU/day IV q4h OR Ampicillin 12 g/day IV q4h OR Chloramphenicol 4–6 g/day IV q6h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h OR Aztreonam 6–8 g/day IV q6–8h
- Gram positive, short bacilli suggestive of Listeria monocytogenes
- Preferred regimen: (Ampicillin 12 g/day IV q4h OR Penicillin G 24 MU/day IV q4h) ± (Amikacin 15 mg/kg/day IV q8h OR Gentamicin 5 mg/kg/day IV q8h OR Tobramycin 5 mg/kg/day IV q8h)
- Alternative regimen: Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h OR Meropenem 6 g/day IV q8h
- Gram positive cocci in short chains suggestive of Streptococcus agalactiae
- Preferred regimen: (Ampicillin 12 g/day IV q4h OR Penicillin G 24 MU/day IV q4h) ± (Amikacin 15 mg/kg/day IV q8h OR Gentamicin 5 mg/kg/day IV q8h OR Tobramycin 5 mg/kg/day IV q8h)
- Alternative regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Gram negative coccobacilli suggestive of Haemophilus influenzae
- Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Alternative regimen: Chloramphenicol 4–6 g/day IV q6h OR Cefepime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h
- Gram negative bacilli suggestive of Escherichia coli
- Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Alternative regimen: Cefepime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h OR Aztreonam 6–8 g/day IV q6–8h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h OR Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h
- Pathogen-directed antimicrobial therapy
- Streptococcus pneumoniae
- Penicillin MIC < 0.1 μg/mL
- Preferred regimen: Penicillin G 24 MU/day IV q4h OR Ampicillin 12 g/day IV q4h
- Alternative regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h OR Chloramphenicol 4–6 g/day IV q6h
- Penicillin MIC 0.1–1.0 μg/mL
- Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Alternative regimen: Cefepime 6 g/day IV q8h OR Meropenem 6 g/day IV q8h
- Penicillin MIC ≥ 2.0 μg/mL
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
- Alternative regimen: Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h
- Cefotaxime or ceftriaxone MIC ≥ 1.0 μg/mL
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND (Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h)
- Alternative regimen: Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h
- Neisseria meningitidis
- Penicillin MIC < 0.1 μg/mL
- Preferred regimen: Penicillin G 24 MU/day IV q4h OR Ampicillin 12 g/day IV q4h
- Alternative regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h OR Chloramphenicol 4–6 g/day IV q6h
- Penicillin MIC 0.1–1.0 μg/mL
- Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Alternative regimen: Chloramphenicol 4–6 g/day IV q6h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h OR Meropenem 6 g/day IV q8h
- Listeria monocytogenes
- Preferred regimen: Ampicillin 12 g/day IV q4h OR Penicillin G 24 MU/day IV q4h
- Alternative regimen: Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h OR Meropenem 6 g/day IV q8h
- Streptococcus agalactiae
- Preferred regimen: Ampicillin 12 g/day IV q4h OR Penicillin G 24 MU/day IV q4h
- Alternative regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Escherichia coli and other Enterobacteriaceae
- Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Alternative regimen: Aztreonam 6–8 g/day IV q6–8h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h OR Meropenem 6 g/day IV q8h OR Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h OR Ampicillin 12 g/day IV q4h
- Pseudomonas aeruginosa
- Preferred regimen: Cefepime 6 g/day IV q8h OR Ceftazidime 6 g/day IV q8h
- Alternative regimen: Aztreonam 6–8 g/day IV q6–8h OR Ciprofloxacin 800–1200 mg IV q8–12h OR Meropenem 6 g/day IV q8h
- Haemophilus influenzae
- β-Lactamase negative
- Preferred regimen: Ampicillin 12 g/day IV q4h
- Alternative regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h OR Cefepime 6 g/day IV q8h OR Chloramphenicol 4–6 g/day IV q6h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h
- β-Lactamase positive
- Preferred regimen: Ceftriaxone 4 g IV q12–24h OR Cefotaxime 8–12 g/day q4–6h
- Alternative regimen: Cefepime 6 g/day IV q8h OR Chloramphenicol 4–6 g/day IV q6h OR Gatifloxacin 400 mg/day IV q24h OR Moxifloxacin 400 mg/day IV q24h
- Staphylococcus aureus
- Methicillin susceptible
- Preferred regimen: Nafcillin 9–12 g/day IV q4h OR Oxacillin 9–12 g/day IV q4h
- Alternative regimen: Vancomycin 30–45 mg/kg/day IV q8–12h OR Meropenem 6 g/day IV q8h
- Methicillin resistant
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
- Alternative regimen: Trimethoprim-Sulfamethoxazole 10–20 mg/kg/day q6–12h OR Linezolid 600 mg IV q12h
- Staphylococcus epidermidis
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h
- Alternative regimen: Linezolid 600 mg IV q12h
- Enterococcus species
- Ampicillin susceptible
- Preferred regimen: Ampicillin 12 g/day IV q4h AND Gentamicin 5 mg/kg/day IV q8h
- Ampicillin resistant
- Preferred regimen: Vancomycin 30–45 mg/kg/day IV q8–12h AND Gentamicin 5 mg/kg/day IV q8h
- Ampicillin and vancomycin resistant
- Preferred regimen: Linezolid 600 mg IV q12h
- Pediatric dose:
- Amikacin
- Neonates age 0–7 days: 15–20 mg/kg/day q12h
- Neonates age 8–28 days: 30 mg/kg/day q8h
- Infants and children: 20–30 mg/kg/day q8h
- Ampicillin
- Neonates age 0–7 days: 150 mg/kg/day q8h
- Neonates age 8–28 days: 200 mg/kg/day q6–8h
- Infants and children: 300 mg/kg/day q6h
- Cefepime
- Infants and children: 150 mg/kg/day q8h
- Cefotaxime
- Neonates age 0–7 days: 100–150 mg/kg/day q8–12h
- Neonates age 8–28 days: 150–200 mg/kg/day q6–8h
- Infants and children: 225–300 mg/kg/day q6–8h
- Ceftazidime
- Neonates age 0–7 days: 100–150 mg/kg/day q8–12h
- Neonates age 8–28 days: 150 mg/kg q8h
- Infants and children: 150 mg/kg
- Ceftriaxone
- Infants and children: 80–100 mg/kg/day q12–24h
- Chloramphenicol
- Neonates age 0–7 days: 25 mg/kg/day q24h
- Neonates age 8–28 days: 50 mg/kg/day q12–24h
- Infants and children: 75–100 mg/kg/day q6h
- Gentamicin
- Neonates age 0–7 days: 5 mg/kg/day q12h
- Neonates age 8–28 days: 7.5 mg/kg/day q8h
- Infants and children: 7.5 mg/kg/day q8h
- Meropenem
- Infants and children: 120 mg/kg/day q8h
- Nafcillin
- Neonates age 0–7 days: 75 mg/kg/day q8–12h
- Neonates age 8–28 days: 100–150 mg/kg/day q6–8h
- Infants and children: 200 mg/kg/day q6h
- Oxacillin
- Neonates age 0–7 days: 75 mg/kg/day q8–12h
- Neonates age 8–28 days: 150–200 mg/kg/day q6–8h
- Infants and children: 200 mg/kg/day q6h
- Penicillin G
- Neonates age 0–7 days: 0.15 MU/kg/day q8–12h
- Neonates age 8–28 days: 0.2 MU/kg/day q6–8h
- Infants and children: 0.3 MU/kg/day q4–6h
- Rifampin
- Neonates age 8–28 days: 10–20 mg/kg/day q12h
- Infants and children: 10–20 mg/kg/day q12–24h
- Tobramycin
- Neonates age 0–7 days: 5 mg/kg/day q12h
- Neonates age 8–28 days: 7.5 mg/kg/day q8h
- Infants and children: 7.5 mg/kg/day q8h
- Trimethoprim-Sulfamethoxazole
- Infants and children: 10–20 mg/kg q6–12h
- Vancomycin
- Neonates age 0–7 days: 20–30 mg/kg/day q8–12h
- Neonates age 8–28 days: 30–45 mg/kg/day q6–8h
- Infants and children: 60 mg/kg/day q6h
- ↑ Tunkel, Allan R.; Hartman, Barry J.; Kaplan, Sheldon L.; Kaufman, Bruce A.; Roos, Karen L.; Scheld, W. Michael; Whitley, Richard J. (2004-11-01). "Practice guidelines for the management of bacterial meningitis". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 39 (9): 1267–1284. doi:10.1086/425368. ISSN 1537-6591. PMID 15494903..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | https://www.wikidoc.org/index.php/Sandbox_g32 | |
b0c0c76c988ca6f8c30a0ea25c5f6089b6896c5f | wikidoc | Sandbox g34 | Sandbox g34
- ↑ Nishimura, Rick A.; Otto, Catherine M.; Bonow, Robert O.; Carabello, Blase A.; Erwin, John P.; Guyton, Robert A.; O'Gara, Patrick T.; Ruiz, Carlos E.; Skubas, Nikolaos J.; Sorajja, Paul; Sundt, Thoralf M.; Thomas, James D.; American College of Cardiology/American Heart Association Task Force on Practice Guidelines (2014-06-10). "2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines". Journal of the American College of Cardiology. 63 (22): –57-185. doi:10.1016/j.jacc.2014.02.536. ISSN 1558-3597. PMID 24603191..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Nishimura, Rick A.; Carabello, Blase A.; Faxon, David P.; Freed, Michael D.; Lytle, Bruce W.; O'Gara, Patrick T.; O'Rourke, Robert A.; Shah, Pravin M. (2008-08-19). "ACC/AHA 2008 Guideline update on valvular heart disease: focused update on infective endocarditis: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons". Journal of the American College of Cardiology. 52 (8): 676–685. doi:10.1016/j.jacc.2008.05.008. ISSN 1558-3597. PMID 18702976.
- ↑ Habib, Gilbert; Hoen, Bruno; Tornos, Pilar; Thuny, Franck; Prendergast, Bernard; Vilacosta, Isidre; Moreillon, Philippe; de Jesus Antunes, Manuel; Thilen, Ulf; Lekakis, John; Lengyel, Maria; Müller, Ludwig; Naber, Christoph K.; Nihoyannopoulos, Petros; Moritz, Anton; Zamorano, Jose Luis; ESC Committee for Practice Guidelines (2009-10). "Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC) for Infection and Cancer". European Heart Journal. 30 (19): 2369–2413. doi:10.1093/eurheartj/ehp285. ISSN 1522-9645. PMID 19713420. Check date values in: |date= (help)
- ↑ Wilson, Walter; Taubert, Kathryn A.; Gewitz, Michael; Lockhart, Peter B.; Baddour, Larry M.; Levison, Matthew; Bolger, Ann; Cabell, Christopher H.; Takahashi, Masato; Baltimore, Robert S.; Newburger, Jane W.; Strom, Brian L.; Tani, Lloyd Y.; Gerber, Michael; Bonow, Robert O.; Pallasch, Thomas; Shulman, Stanford T.; Rowley, Anne H.; Burns, Jane C.; Ferrieri, Patricia; Gardner, Timothy; Goff, David; Durack, David T.; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; American Heart Association Council on Cardiovascular Disease in the Young; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Cardiovascular Surgery and Anesthesia; Quality of Care and Outcomes Research Interdisciplinary Working Group (2007-10-09). "Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group". Circulation. 116 (15): 1736–1754. doi:10.1161/CIRCULATIONAHA.106.183095. ISSN 1524-4539. PMID 17446442.CS1 maint: Multiple names: authors list (link) | Sandbox g34
[1][2][3][4]
- ↑ Nishimura, Rick A.; Otto, Catherine M.; Bonow, Robert O.; Carabello, Blase A.; Erwin, John P.; Guyton, Robert A.; O'Gara, Patrick T.; Ruiz, Carlos E.; Skubas, Nikolaos J.; Sorajja, Paul; Sundt, Thoralf M.; Thomas, James D.; American College of Cardiology/American Heart Association Task Force on Practice Guidelines (2014-06-10). "2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines". Journal of the American College of Cardiology. 63 (22): –57-185. doi:10.1016/j.jacc.2014.02.536. ISSN 1558-3597. PMID 24603191..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Nishimura, Rick A.; Carabello, Blase A.; Faxon, David P.; Freed, Michael D.; Lytle, Bruce W.; O'Gara, Patrick T.; O'Rourke, Robert A.; Shah, Pravin M. (2008-08-19). "ACC/AHA 2008 Guideline update on valvular heart disease: focused update on infective endocarditis: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons". Journal of the American College of Cardiology. 52 (8): 676–685. doi:10.1016/j.jacc.2008.05.008. ISSN 1558-3597. PMID 18702976.
- ↑ Habib, Gilbert; Hoen, Bruno; Tornos, Pilar; Thuny, Franck; Prendergast, Bernard; Vilacosta, Isidre; Moreillon, Philippe; de Jesus Antunes, Manuel; Thilen, Ulf; Lekakis, John; Lengyel, Maria; Müller, Ludwig; Naber, Christoph K.; Nihoyannopoulos, Petros; Moritz, Anton; Zamorano, Jose Luis; ESC Committee for Practice Guidelines (2009-10). "Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC) for Infection and Cancer". European Heart Journal. 30 (19): 2369–2413. doi:10.1093/eurheartj/ehp285. ISSN 1522-9645. PMID 19713420. Check date values in: |date= (help)
- ↑ Wilson, Walter; Taubert, Kathryn A.; Gewitz, Michael; Lockhart, Peter B.; Baddour, Larry M.; Levison, Matthew; Bolger, Ann; Cabell, Christopher H.; Takahashi, Masato; Baltimore, Robert S.; Newburger, Jane W.; Strom, Brian L.; Tani, Lloyd Y.; Gerber, Michael; Bonow, Robert O.; Pallasch, Thomas; Shulman, Stanford T.; Rowley, Anne H.; Burns, Jane C.; Ferrieri, Patricia; Gardner, Timothy; Goff, David; Durack, David T.; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee; American Heart Association Council on Cardiovascular Disease in the Young; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Cardiovascular Surgery and Anesthesia; Quality of Care and Outcomes Research Interdisciplinary Working Group (2007-10-09). "Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group". Circulation. 116 (15): 1736–1754. doi:10.1161/CIRCULATIONAHA.106.183095. ISSN 1524-4539. PMID 17446442.CS1 maint: Multiple names: authors list (link) | https://www.wikidoc.org/index.php/Sandbox_g34 | |
3fe768f9872e17111e87792ad4e08219c647d61d | wikidoc | Sandbox g37 | Sandbox g37
- Deep neck infection
- Empiric antimicrobial therapy
- Community-acquired deep neck infection
- Preferred regimen: Ampicillin-Sulbactam 1.5–3.0 g IV q6h OR Clindamycin 600–900 mg IV q8h OR Moxifloxacin 400 mg daily (if Eikenella is suspected)
- Nosocomial deep neck infection or immunocompromised host
- Preferred regimen: Ticarcillin-Clavulanate 3.0 g IV q6h OR Piperacillin-Tazobactam 3.0 g IV q6h OR Imipenem-Cilastatin 500 mg IV q6h OR Ciprofloxacin 400 mg IV q12h OR Levofloxacin 750 mg IV q24h
- Deep neck infection with high-risk of MRSA
- Preferred regimen: (Clindamycin 600–900 mg IV q8h OR Trimethoprim-Sulfamethoxazole 10 mg/kg/day IV q8h) AND Vancomycin 1.0 g IV q12h
- Necrotizing fasciitis
- Preferred regimen: Ceftriaxone 2.0 g IV q8h AND Clindamycin 600–900 mg IV q8h AND Metronidazole 500 mg IV q6h
- Specific anatomic considerations
- Submandibular space infections including Ludwig angina
- Causative pathogens
- Viridans and other streptococci
- Peptostreptococcus
- Bacteroides
- Other oral anaerobes
- Preferred regimen (immunocompetent host): (Penicillin G 2–4 MU IV q4–6h AND Tobramycin 2 mg/kg IV q8h) OR Ampicillin-Sulbactam 2 g IV q4h OR Clindamycin 600 mg IV q6h OR Doxycycline 200 mg IV q12h OR Cefoxitin 2 g IV q6h OR Cefotetan 2 g IV q12h
- Preferred regimen (immunocomppromised host): Cefotaxime 2 g IV q6h OR Ceftizoxime 4 g IV q8h OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h OR Meropenem 1 g IV q8h OR Gatifloxacin 200 mg IV q24h
- Lateral pharyngeal or retropharyngeal space infections (odontogenic)
- Causative pathogens
- Viridans and other streptococci
- Staphylococcus
- Peptostreptococcus
- Bacteroides
- Other oral anaerobes
- Preferred regimen (immunocompetent host): (Penicillin G 2–4 MU IV q4–6h AND Metronidazole 0.5 g IV q6h) OR Ampicillin-Sulbactam 2 g IV q4h OR Clindamycin 600 mg IV q6h
- Preferred regimen (immunocomppromised host): Cefotaxime 2 g IV q6h OR Ceftizoxime 4 g IV q8h OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h OR Imipenem 500 mg IV q6h OR Gatifloxacin 400 mg IV q24h
- Lateral pharyngeal or retropharyngeal space infections (rhinogenic)
- Causative pathogens
- Streptococcus pyogenes
- Fusobacterium
- Peptostreptococcus
- Other oral anaerobes
- Preferred regimen (immunocompetent host): Penicillin G 2–4 MU IV q4–6h OR (Ciprofloxacin 200 mg q12h AND Metronidazole 0.5 g IV q6h) OR Gatifloxacin 400 mg IV q24h OR Clindamycin 600 mg IV q6h
- Preferred regimen (immunocomppromised host): Cefotaxime 2 g IV q6h OR Ceftizoxime 4 g IV q8h OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h OR Imipenem 500 mg IV q6h OR Gatifloxacin 400 mg IV q24h
- Lateral pharyngeal or retropharyngeal space infections (otogenic)
- Causative pathogens
- Streptococcus pneumoniae
- Haemophilus influenzae
- Viridans and other streptococci
- Peptostreptococcus
- Bacteroides
- Other oral anaerobes
- Preferred regimen (immunocompetent host): Penicillin G 2–4 MU IV q4–6h OR (Ciprofloxacin 200 mg q12h AND Metronidazole 0.5 g IV q6h) OR Gatifloxacin 400 mg IV q24h OR Clindamycin 600 mg IV q6h
- Preferred regimen (immunocomppromised host): Cefotaxime 2 g IV q6h OR Ceftizoxime 4 g IV q8h OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h OR Imipenem 500 mg IV q6h OR Gatifloxacin 400 mg IV q24h
- Peritonsillar abscess (quinsy)
- Causative pathogens
- Viridans and other streptococci
- Peptostreptococcus
- Bacteroides
- Other oral anaerobes
- Preferred regimen (immunocompetent host): (Penicillin G 2–4 MU IV q4–6h AND Metronidazole 0.5 g IV q6h) OR Ampicillin-Sulbactam 2 g IV q4h OR Clindamycin 600 mg IV q6h OR Cefoxitin 2 g IV q6h
- Preferred regimen (immunocomppromised host): Cefotaxime 2 g IV q6h OR Ceftizoxime 4 g IV q8h OR Piperacillin 3 g IV q4h
- Suppurative parotitis
- Causative pathogens
- Staphylococcus
- Viridans and other streptococci
- Bacteroides
- Peptostreptococcus
- Other oral anaerobes
- Preferred regimen (immunocompetent host): (Nafcillin 1.5 g IV q4–6h AND Metronidazole 0.5 g IV q6h) OR Clindamycin 600 mg IV q6h
- Preferred regimen (immunocomppromised host): (Vancomycin 0.5 g IV q6h AND Cefotaxime 2 g IV q6h) OR Ceftizoxime 4 g IV q8h OR Piperacillin 3 g IV q4h
- Extension of osteomyelitis from prevertebral space infection
- Causative pathogens
- Staphylococcus
- Facultative gram-negative bacilli
- Preferred regimen (immunocompetent host): (Nafcillin 1.5 g IV q4–6h AND Metronidazole 0.5 g IV q6h) OR Ciprofloxacin 200 mg q12h
- Preferred regimen (immunocomppromised host): (Vancomycin 0.5 g IV q6h AND Cefotaxime 2 g IV q6h) OR Ceftizoxime 4 g IV q8h OR Imipenem 500 mg IV q6h
- Pott's puffy tumor (frontal osteitis)
- Causative pathogens
- Streptococcus pyogenes
- Fusobacterium
- Peptostreptococcus
- Other oral anaerobes
- Preferred regimen (immunocompetent host): Penicillin G 2–4 MU IV q4–6h OR (Ciprofloxacin 200 mg q12h AND Metronidazole 0.5 g IV q6h) OR Gatifloxacin 400 mg IV q24h OR Clindamycin 600 mg IV q6h
- Preferred regimen (immunocomppromised host): Cefotaxime 2 g IV q6h OR Ceftizoxime 4 g IV q8h OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h OR Imipenem 500 mg IV q6h OR Gatifloxacin 400 mg IV q24h
- Malignant otitis media
- Causative pathogens
- Pseudomonas aeruginosa
- Preferred regimen (immunocompetent host): Ciprofloxacin 200 mg q12h OR (Tobramycin 2 mg/kg IV q8h AND Ceftazidime 2 g IV q6h) OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h
- Preferred regimen (immunocomppromised host): (Tobramycin 2 mg/kg IV q8h AND Ceftazidime 2 g IV q6h) OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h OR Imipenem 500 mg IV q6h
- Petrous osteitis
- Causative pathogens
- Pseudomonas aeruginosa
- Preferred regimen (immunocompetent host): Ciprofloxacin 200 mg q12h OR (Tobramycin 2 mg/kg IV q8h AND Ceftazidime 2 g IV q6h) OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h
- Preferred regimen (immunocomppromised host): (Tobramycin 2 mg/kg IV q8h AND Ceftazidime 2 g IV q6h) OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h OR Imipenem 500 mg IV q6h
- Septic jugular thrombophlebitis (Lemierre syndrome)
- Causative pathogens
- Fusobacterium
- Viridans and other streptococci
- Staphylococcus
- Peptostreptococcus
- Bacteroides
- Other oral anaerobes
- Preferred regimen (immunocompetent host): (Penicillin G 2–4 MU IV q4–6h AND Metronidazole 0.5 g IV q6h) OR Ampicillin-Sulbactam 2 g IV q4h OR Clindamycin 600 mg IV q6h
- Preferred regimen (immunocomppromised host): Cefotaxime 2 g IV q6h OR Ceftizoxime 4 g IV q8h OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h OR Imipenem 500 mg IV q6h OR Gatifloxacin 400 mg IV q24h
- ↑ Flint, Paul (2010). Cummings otolaryngology head & neck surgery. Philadelphia, PA: Mosby/Elsevier. ISBN 978-0323052832..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Vieira, Francisco; Allen, Shawn M.; Stocks, Rose Mary S.; Thompson, Jerome W. (2008-06). "Deep neck infection". Otolaryngologic Clinics of North America. 41 (3): 459–483, vii. doi:10.1016/j.otc.2008.01.002. ISSN 0030-6665. PMID 18435993. Check date values in: |date= (help)
- ↑ Hall, Jesse (2015). Principles of critical care. New York: McGraw-Hill Education. ISBN 978-0071738811. | Sandbox g37
- Deep neck infection
- Empiric antimicrobial therapy[1][2]
- Community-acquired deep neck infection
- Preferred regimen: Ampicillin-Sulbactam 1.5–3.0 g IV q6h OR Clindamycin 600–900 mg IV q8h OR Moxifloxacin 400 mg daily (if Eikenella is suspected)
- Nosocomial deep neck infection or immunocompromised host
- Preferred regimen: Ticarcillin-Clavulanate 3.0 g IV q6h OR Piperacillin-Tazobactam 3.0 g IV q6h OR Imipenem-Cilastatin 500 mg IV q6h OR Ciprofloxacin 400 mg IV q12h OR Levofloxacin 750 mg IV q24h
- Deep neck infection with high-risk of MRSA
- Preferred regimen: (Clindamycin 600–900 mg IV q8h OR Trimethoprim-Sulfamethoxazole 10 mg/kg/day IV q8h) AND Vancomycin 1.0 g IV q12h
- Necrotizing fasciitis
- Preferred regimen: Ceftriaxone 2.0 g IV q8h AND Clindamycin 600–900 mg IV q8h AND Metronidazole 500 mg IV q6h
- Specific anatomic considerations[3]
- Submandibular space infections including Ludwig angina
- Causative pathogens
- Viridans and other streptococci
- Peptostreptococcus
- Bacteroides
- Other oral anaerobes
- Preferred regimen (immunocompetent host): (Penicillin G 2–4 MU IV q4–6h AND Tobramycin 2 mg/kg IV q8h) OR Ampicillin-Sulbactam 2 g IV q4h OR Clindamycin 600 mg IV q6h OR Doxycycline 200 mg IV q12h OR Cefoxitin 2 g IV q6h OR Cefotetan 2 g IV q12h
- Preferred regimen (immunocomppromised host): Cefotaxime 2 g IV q6h OR Ceftizoxime 4 g IV q8h OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h OR Meropenem 1 g IV q8h OR Gatifloxacin 200 mg IV q24h
- Lateral pharyngeal or retropharyngeal space infections (odontogenic)
- Causative pathogens
- Viridans and other streptococci
- Staphylococcus
- Peptostreptococcus
- Bacteroides
- Other oral anaerobes
- Preferred regimen (immunocompetent host): (Penicillin G 2–4 MU IV q4–6h AND Metronidazole 0.5 g IV q6h) OR Ampicillin-Sulbactam 2 g IV q4h OR Clindamycin 600 mg IV q6h
- Preferred regimen (immunocomppromised host): Cefotaxime 2 g IV q6h OR Ceftizoxime 4 g IV q8h OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h OR Imipenem 500 mg IV q6h OR Gatifloxacin 400 mg IV q24h
- Lateral pharyngeal or retropharyngeal space infections (rhinogenic)
- Causative pathogens
- Streptococcus pyogenes
- Fusobacterium
- Peptostreptococcus
- Other oral anaerobes
- Preferred regimen (immunocompetent host): Penicillin G 2–4 MU IV q4–6h OR (Ciprofloxacin 200 mg q12h AND Metronidazole 0.5 g IV q6h) OR Gatifloxacin 400 mg IV q24h OR Clindamycin 600 mg IV q6h
- Preferred regimen (immunocomppromised host): Cefotaxime 2 g IV q6h OR Ceftizoxime 4 g IV q8h OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h OR Imipenem 500 mg IV q6h OR Gatifloxacin 400 mg IV q24h
- Lateral pharyngeal or retropharyngeal space infections (otogenic)
- Causative pathogens
- Streptococcus pneumoniae
- Haemophilus influenzae
- Viridans and other streptococci
- Peptostreptococcus
- Bacteroides
- Other oral anaerobes
- Preferred regimen (immunocompetent host): Penicillin G 2–4 MU IV q4–6h OR (Ciprofloxacin 200 mg q12h AND Metronidazole 0.5 g IV q6h) OR Gatifloxacin 400 mg IV q24h OR Clindamycin 600 mg IV q6h
- Preferred regimen (immunocomppromised host): Cefotaxime 2 g IV q6h OR Ceftizoxime 4 g IV q8h OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h OR Imipenem 500 mg IV q6h OR Gatifloxacin 400 mg IV q24h
- Peritonsillar abscess (quinsy)
- Causative pathogens
- Viridans and other streptococci
- Peptostreptococcus
- Bacteroides
- Other oral anaerobes
- Preferred regimen (immunocompetent host): (Penicillin G 2–4 MU IV q4–6h AND Metronidazole 0.5 g IV q6h) OR Ampicillin-Sulbactam 2 g IV q4h OR Clindamycin 600 mg IV q6h OR Cefoxitin 2 g IV q6h
- Preferred regimen (immunocomppromised host): Cefotaxime 2 g IV q6h OR Ceftizoxime 4 g IV q8h OR Piperacillin 3 g IV q4h
- Suppurative parotitis
- Causative pathogens
- Staphylococcus
- Viridans and other streptococci
- Bacteroides
- Peptostreptococcus
- Other oral anaerobes
- Preferred regimen (immunocompetent host): (Nafcillin 1.5 g IV q4–6h AND Metronidazole 0.5 g IV q6h) OR Clindamycin 600 mg IV q6h
- Preferred regimen (immunocomppromised host): (Vancomycin 0.5 g IV q6h AND Cefotaxime 2 g IV q6h) OR Ceftizoxime 4 g IV q8h OR Piperacillin 3 g IV q4h
- Extension of osteomyelitis from prevertebral space infection
- Causative pathogens
- Staphylococcus
- Facultative gram-negative bacilli
- Preferred regimen (immunocompetent host): (Nafcillin 1.5 g IV q4–6h AND Metronidazole 0.5 g IV q6h) OR Ciprofloxacin 200 mg q12h
- Preferred regimen (immunocomppromised host): (Vancomycin 0.5 g IV q6h AND Cefotaxime 2 g IV q6h) OR Ceftizoxime 4 g IV q8h OR Imipenem 500 mg IV q6h
- Pott's puffy tumor (frontal osteitis)
- Causative pathogens
- Streptococcus pyogenes
- Fusobacterium
- Peptostreptococcus
- Other oral anaerobes
- Preferred regimen (immunocompetent host): Penicillin G 2–4 MU IV q4–6h OR (Ciprofloxacin 200 mg q12h AND Metronidazole 0.5 g IV q6h) OR Gatifloxacin 400 mg IV q24h OR Clindamycin 600 mg IV q6h
- Preferred regimen (immunocomppromised host): Cefotaxime 2 g IV q6h OR Ceftizoxime 4 g IV q8h OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h OR Imipenem 500 mg IV q6h OR Gatifloxacin 400 mg IV q24h
- Malignant otitis media
- Causative pathogens
- Pseudomonas aeruginosa
- Preferred regimen (immunocompetent host): Ciprofloxacin 200 mg q12h OR (Tobramycin 2 mg/kg IV q8h AND Ceftazidime 2 g IV q6h) OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h
- Preferred regimen (immunocomppromised host): (Tobramycin 2 mg/kg IV q8h AND Ceftazidime 2 g IV q6h) OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h OR Imipenem 500 mg IV q6h
- Petrous osteitis
- Causative pathogens
- Pseudomonas aeruginosa
- Preferred regimen (immunocompetent host): Ciprofloxacin 200 mg q12h OR (Tobramycin 2 mg/kg IV q8h AND Ceftazidime 2 g IV q6h) OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h
- Preferred regimen (immunocomppromised host): (Tobramycin 2 mg/kg IV q8h AND Ceftazidime 2 g IV q6h) OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h OR Imipenem 500 mg IV q6h
- Septic jugular thrombophlebitis (Lemierre syndrome)
- Causative pathogens
- Fusobacterium
- Viridans and other streptococci
- Staphylococcus
- Peptostreptococcus
- Bacteroides
- Other oral anaerobes
- Preferred regimen (immunocompetent host): (Penicillin G 2–4 MU IV q4–6h AND Metronidazole 0.5 g IV q6h) OR Ampicillin-Sulbactam 2 g IV q4h OR Clindamycin 600 mg IV q6h
- Preferred regimen (immunocomppromised host): Cefotaxime 2 g IV q6h OR Ceftizoxime 4 g IV q8h OR Piperacillin 3 g IV q4h OR Imipenem 500 mg IV q6h OR Imipenem 500 mg IV q6h OR Gatifloxacin 400 mg IV q24h
- ↑ Flint, Paul (2010). Cummings otolaryngology head & neck surgery. Philadelphia, PA: Mosby/Elsevier. ISBN 978-0323052832..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Vieira, Francisco; Allen, Shawn M.; Stocks, Rose Mary S.; Thompson, Jerome W. (2008-06). "Deep neck infection". Otolaryngologic Clinics of North America. 41 (3): 459–483, vii. doi:10.1016/j.otc.2008.01.002. ISSN 0030-6665. PMID 18435993. Check date values in: |date= (help)
- ↑ Hall, Jesse (2015). Principles of critical care. New York: McGraw-Hill Education. ISBN 978-0071738811. | https://www.wikidoc.org/index.php/Sandbox_g37 | |
1ef3b24ad1c2c4e7a4b51a6f7394a41a827834a3 | wikidoc | Sandbox g38 | Sandbox g38
# Sterile pyuria
- Sterile pyuria
- Definitions
- Pyuria: the presence of 10 or more white cells per cubic millimeter in a urine specimen, 3 or more white cells per high-power field of unspun urine, a positive result on Gram’s stain of an unspun urine specimen, or a urinary dipstick test that is positive for leukocyte esterase
- Sterile pyuria: the persistent finding of white cells in the urine in the absence of bacteria, as determined by means of aerobic laboratory techniques (on a 5% sheep-blood agar plate and MacConkey agar plate)
- Bacteriuria: bacterial colony counts of more than 1000 colony-forming units (CFU) per milliliter in urine
- Causes
- Infectious etiologies
- Gynecologic infection
- Urethritis due to chlamydia, Neisseria gonorrhoeae, mycoplasma, or ureaplasma
- Prostatitis
- Balanitis
- Appendicitis
- Viral infection of the lower genitourinary tract
- Genitourinary tuberculosis
- Fungal infection
- Parasitic disease such as trichomoniasis or schistosomiasis
- Non-infectious etiologies
- Current use of antibiotics
- Recently treated urinary tract infection (within past 2 weeks)
- Presence or recent use of a urinary catheter
- Recent cystoscopy or urologic endoscopy
- Urinary tract stones
- Foreign body such as surgical mesh in the urethra or a retained stent
- Urinary tract neoplasm
- Pelvic irradiation
- Urinary fistula
- Polycystic kidney
- Rejection of a renal transplant
- Renal-vein thrombosis
- Interstitial nephritis or analgesic nephropathy
- Papillary necrosis
- Interstitial cystitis
- Inflammatory disease such as systemic lupus erythematosus or Kawasaki’s disease
- Pathogen-directed antimicrobial therapy
- Tuberculosis
- Preferred regimen: Isoniazid AND Rifampin AND Ethambutol AND Pyrazinamide for 3–6 months
- Gonorrhea
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose, then (Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days)
- Chlamydia
- Preferred regimen: Azithromycin 1 g PO in single dose OR Doxycycline 100 mg PO bid for 7 days
- Alternative regimen: Erythromycin base 500 mg PO qid for 7 days
- Mycoplasma and ureaplasma
- Preferred regimen: Azithromycin OR Levofloxacin OR Moxifloxacin
- Genital herpes
- Preferred regimen: Acyclovir 400 mg PO tid for 7–10 days or Acyclovir 200 mg PO five times a day for 7–10 days OR Famciclovir 250 mg PO tid for 7–10 days OR Valacyclovir 1 g PO bid for 7 days
- Trichomoniasis
- Preferred regimen: Metronidazole 2 g PO in a single dose) OR Tinidazole 2 g PO in a single dose
- Fungal infections
- Preferred regimen: Fluconazole OR Posaconazole OR Echinocandins OR Amphotericin B
- Schistosomiasis
- Preferred regimen: Praziquantel 20 mg/kg PO bid for 1–2 days | Sandbox g38
## Sterile pyuria
- Sterile pyuria
- Definitions
- Pyuria: the presence of 10 or more white cells per cubic millimeter in a urine specimen, 3 or more white cells per high-power field of unspun urine, a positive result on Gram’s stain of an unspun urine specimen, or a urinary dipstick test that is positive for leukocyte esterase[1]
- Sterile pyuria: the persistent finding of white cells in the urine in the absence of bacteria, as determined by means of aerobic laboratory techniques (on a 5% sheep-blood agar plate and MacConkey agar plate)[2]
- Bacteriuria: bacterial colony counts of more than 1000 colony-forming units (CFU) per milliliter in urine[3]
- Causes[4]
- Infectious etiologies
- Gynecologic infection
- Urethritis due to chlamydia, Neisseria gonorrhoeae, mycoplasma, or ureaplasma
- Prostatitis
- Balanitis
- Appendicitis
- Viral infection of the lower genitourinary tract
- Genitourinary tuberculosis
- Fungal infection
- Parasitic disease such as trichomoniasis or schistosomiasis
- Non-infectious etiologies
- Current use of antibiotics
- Recently treated urinary tract infection (within past 2 weeks)
- Presence or recent use of a urinary catheter
- Recent cystoscopy or urologic endoscopy
- Urinary tract stones
- Foreign body such as surgical mesh in the urethra or a retained stent
- Urinary tract neoplasm
- Pelvic irradiation
- Urinary fistula
- Polycystic kidney
- Rejection of a renal transplant
- Renal-vein thrombosis
- Interstitial nephritis or analgesic nephropathy
- Papillary necrosis
- Interstitial cystitis
- Inflammatory disease such as systemic lupus erythematosus or Kawasaki’s disease
- Pathogen-directed antimicrobial therapy[5]
- Tuberculosis
- Preferred regimen: Isoniazid AND Rifampin AND Ethambutol AND Pyrazinamide for 3–6 months
- Gonorrhea
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose, then (Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days)
- Chlamydia
- Preferred regimen: Azithromycin 1 g PO in single dose OR Doxycycline 100 mg PO bid for 7 days
- Alternative regimen: Erythromycin base 500 mg PO qid for 7 days
- Mycoplasma and ureaplasma
- Preferred regimen: Azithromycin OR Levofloxacin OR Moxifloxacin
- Genital herpes
- Preferred regimen: Acyclovir 400 mg PO tid for 7–10 days or Acyclovir 200 mg PO five times a day for 7–10 days OR Famciclovir 250 mg PO tid for 7–10 days OR Valacyclovir 1 g PO bid for 7 days
- Trichomoniasis
- Preferred regimen: Metronidazole 2 g PO in a single dose) OR Tinidazole 2 g PO in a single dose
- Fungal infections
- Preferred regimen: Fluconazole OR Posaconazole OR Echinocandins OR Amphotericin B
- Schistosomiasis
- Preferred regimen: Praziquantel 20 mg/kg PO bid for 1–2 days | https://www.wikidoc.org/index.php/Sandbox_g38 | |
3845c5f53cae4036d6749b5a6a421331de02ac0f | wikidoc | Sandbox g41 | Sandbox g41
# Asymptomatic bacteriuria
- Asymptomatic bacteriuria
- Definitions
- For women: two consecutive voided urine specimens with isolation of the same bacterial strain in quantitative counts ≥ 105 cfu/mL
- For men: a single, clean-catch voided urine specimen with 1 bacterial species isolated in a quantitative count ≥ 105 cfu/mL
- For catheterized urine specimen: a single catheterized urine specimen with 1 bacterial species isolated in a quantitative count ≥ 10>2 cfu/mL
- Causative pathogens
- Escherichia coli
- Klebsiella pneumoniae
- Coagulase-negative staphylococci
- Enterococcus
- Group B streptococci
- Gardnerella vaginalis
- Pseudomonas aeruginosa, Proteus mirabilis, Providencia stuartii, Morganella morganii (common in patients with long-term urologic device in place)
- Empiric antimicrobial therapy
- Treatment of asymptomatic bacteriuria is not recommended for the following persons:
- Premenopausal, nonpregnant women
- Diabetic women
- Older persons residing in the community
- Elderly, institutionalized subjects
- Persons with spinal cord injury
- Catheterized patients while the catheter remains in situ
- Specific considerations
- Men
- Screening for or treatment of asymptomatic bacteriuria in men is not recommended.
- Women, premenopausal, nonpregnant
- Screening for or treatment of asymptomatic bacteriuria in premenopausal, nonpregnant women is not indicated.
- Women, pregnant
- Preferred regimen (1): Nitrofurantoin 100 mg PO bid for 3–5 days (avoid in glucose-6-phosphate dehydrogenase deficiency)
- Preferred regimen (2): Amoxicillin 500 mg tid for 3–5 days
- Preferred regimen (3): Amoxicillin-Clavulanate 500 mg bid for 3–5 days
- Preferred regimen (4): Cephalexin 500 mg tid for 3–5 days
- Preferred regimen (5): Fosfomycin 3 g as a single dose
- Preferred regimen (6): Trimethoprim bid for 3–5 days (only after first trimester)
- Women, diabetic
- Screening for or treatment of asymptomatic bacteriuria in diabetic women is not recommended.
- Older persons residing in the community
- Screening for or treatment of asymptomatic bacteriuria in older persons residing in the community is not recommended.
- Elderly institutionalized subjects
- Screening for or treatment of asymptomatic bacteriuria in elderly institutionalized residents of longterm care facilities is not recommended.
- Subjects with spinal cord injuries
- Screening for or treatment of asymptomatic bacteriuria in subjects with spinal cord injuries is not recommended.
- Patients with indwelling urethral catheters
- Screening for or treatment of asymptomatic bacteriuria in patients with indwelling urethral catheters is not recommended.
- Urologic interventions
- Screening for or treatment of asymptomatic bacteriuria before transurethral resection of the prostate is recommended.
- Preferred regimen: Trimethoprim-Sulfamethoxazole DS 1 tab bid for 3 days after obtaining urine cultures
# Ectoparasitic Infections
## Pediculosis Pubis
- Preferred regime: Permethrin 1% cream rinse applied to affected areas and washed off after 10 minutes OR Pyrethrins with piperonyl butoxide applied to the affected area and washed off after 10 minutes
- Alternative regime: Malathion 0.5% lotion applied for 8--12 hours and washed off OR Ivermectin 250 µg/kg orally, repeated in 2 weeks
## Scabies
- Preferred regime: Permethrin cream (5%) applied to all areas of the body from the neck down and washed off after 8--14 hours OR Ivermectin 200ug/kg orally, repeated in 2 weeks
- Alternative regime: Lindane (1%) 1 oz. of lotion (or 30 g of cream) applied in a thin layer to all areas of the body from the neck down and thoroughly washed off after 8 hours
# Human papillomavirus infection
## Genital Warts
- Patient-Applied:
- Preferred regime: Podofilox 0.5% solution or gel OR Imiquimod 5% cream OR Sinecatechins 15% ointment
- Provider--Administered:
- Preferred regime: Cryotherapy with liquid nitrogen or cryoprobe, repeat applications every 1-2 weeks OR Podophyllin resin 10%-25% in a compound tincture of benzoin OR Trichloroacetic acid (TCA) OR Bichloroacetic acid (BCA) 80%-90% OR Surgical removal either by tangential scissor excision, tangential shave excision, curettage, or electrosurgery.
- Alternative regime: intralesional interferon, photodynamic therapy, and topical .
- Preferred regime: For women who have exophytic cervical warts, a biopsy evaluation to exclude high-grade SIL must be performed before treatment is initiated. Management of exophytic cervical warts should include consultation with a specialist.
- Preferred regime: Cryotherapy with liquid nitrogen. The use of a cryoprobe in the vagina is not recommended because of the risk for vaginal perforation and fistula formation OR TCA or BCA 80%--90% applied to warts. A small amount should be applied only to warts and allowed to dry, at which time a white frosting develops. If an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate, or liquid soap preparations to remove unreacted acid. This treatment can be repeated weekly, if necessary.
- Preferred regime: Cryotherapy with liquid nitrogen OR Podophyllin 10%--25% in compound tincture of benzoin. The treatment area and adjacent normal skin must be dry before contact with podophyllin. This treatment can be repeated weekly, if necessary. The safety of podophyllin during pregnancy has not been established. Data are limited on the use of podofilox and imiquimod for treatment of distal meatal warts.
- Preferred regime: Cryotherapy with liquid nitrogen OR TCA or BCA 80%--90% applied to warts. A small amount should be applied only to warts and allowed to dry, at which time a white frosting develops. If an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate, or liquid soap preparations to remove unreacted acid. This treatment can be repeated weekly, if necessary. OR Surgical removal
# Vaginal infection
## Bacterial vaginosis
- Preferred regime: Metronidazole 500 mg orally twice a day for 7 days OR Metronidazole gel 0.75%, one full applicator (5 g) intravaginally, once a day for 5 days OR Clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7 days
- Alternative regime (1): Tinidazole 2 g orally once daily for 3 days
- Alternative regime (2): Tinidazole 1 g orally once daily for 5 days
- Alternative regime (3): Clindamycin 300 mg orally twice daily for 7 days
- Alternative regime (4): Clindamycin ovules 100 mg intravaginally once at bedtime for 3 days
- Preferred regime: Metronidazole 500 mg orally twice a day for 7 days OR Metronidazole 250 mg orally three times a day for 7 days OR Clindamycin 300 mg orally twice a day for 7 days
## Trichomoniasis
T. vaginalis
- Preferred regime: Metronidazole 2 g orally in a single dose OR Tinidazole 2 g orally in a single dose
- Alternative regime: Metronidazole 500 mg orally twice a day for 7 days
- Preferred regime: 2 g Metronidazole in a single dose at any stage of pregnancy, withholding breastfeeding during treatment and for 12--24 hours after the last dose will reduce the exposure of the infant to metronidazole.
## Vulvovaginal candidiasis
- Preferred regime:
- Over-the-Counter Intravaginal Agents: Butoconazole 2% cream 5 g intravaginally for 3 days OR Clotrimazole 1% cream 5 g intravaginally for 7--14 days OR Clotrimazole 2% cream 5 g intravaginally for 3 days OR ] 2% cream 5 g intravaginally for 7 days OR Miconazole 4% cream 5 g intravaginally for 3 days OR Miconazole 100 mg vaginal suppository, one suppository for 7 days OR Miconazole 200 mg vaginal suppository, one suppository for 3 days OR Miconazole 1,200 mg vaginal suppository, one suppository for 1 day OR Tioconazole 6.5% ointment 5 g intravaginally in a single application
- Prescription Intravaginal Agents: Butoconazole 2% cream (single dose bioadhesive product), 5 g intravaginally for 1 day OR Nystatin 100,000-unit vaginal tablet, one tablet for 14 days OR Terconazole 0.4% cream 5 g intravaginally for 7 days OR Terconazole 0.8% cream 5 g intravaginally for 3 days OR Terconazole 80 mg vaginal suppository, one suppository for 3 days
- Oral Agent: Fluconazole 150 mg oral tablet, one tablet in single dose
- Recurrent Vulvovaginal Candidiasis (RVVC)
- Preferred regime: 7-14 days of topical therapy OR a 100-mg, 150-mg, or 200-mg oral dose of Fluconazole every third day for a total of 3 doses followed by Oral Fluconazole (i.e., 100-mg, 150-mg, or 200-mg dose) weekly for 6 months
- Severe VVC
- Preferred regime: Topical Azole for 7-14 days OR 150 mg of Fluconazole in two sequential doses (second dose 72 hours after initial dose.
- Nonalbicans VVC
- Preferred regime: nonfluconazole Azole drug (oral or topical) for 7-14 days.
- Preferred regime: topical Azole therapies for 7 days
# Cervicitis
- Cervicitis
- Preferred regimen: Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
# Chancroid
- Chancroid (Haemophilus ducreyi infection)
- Preferred regimen: Azithromycin 1 g PO as a single dose OR Ceftriaxone 250 mg IM as a single dose OR Ciprofloxacin 500 mg PO bid for 3 days OR Erythromycin 500 mg PO tid for 7 days
# Chlamydial infections
- Chlamydial infections
- Chlamydial infections in adolescents and adults
- Preferred regimen: Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
- Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days
- Chlamydial infections during pregnancy
- Preferred regimen: Azithromycin 1 g PO in a single dose OR Amoxicillin 500 mg PO tid for 7 days
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin base 250 mg PO qid for 14 days
- Alternative regimen (3): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (4): Erythromycin ethylsuccinate 400 mg PO qid for 14 days
- Chlamydial infections among infants and children
- Ophthalmia neonatorum caused by C. trachomatis
- Preferred regimen: Erythromycin base or ethylsuccinate 50 mg/kg/day PO divided into 4 doses daily for 14 days
- Pneumonia caused by C. trachomatis
- Preferred regimen (< 45 kg): Erythromycin base or ethylsuccinate 50 mg/kg/day PO divided into 4 doses daily for 14 days
- Preferred regimen (≥ 45 kg & < 8 years): Azithromycin 1 g PO in a single dose
- Preferred regimen (≥ 8 years): Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
# Chorioamnionitis
- Antibiotics
- Preferred regime: Ampicillin 2 g intravenously every 6 h OR Penicillin 5x106 units intravenously every 6 h AND Gentamicin 1.5 mg/kg every 8 h
- NOTE (1): Cephalosporins are generally recommended for women with chorioamnionitis who are allergic to Penicillin
- NOTE (2): In women with anaphylaxis to Penicillin a recommendation is to substitute Clindamycin 900 mg every 8 h
- NOTE (3): In the non-obstetric population, daily dosing of Gentamicin appears to be more effective, convenient, and cost-effective as well as less toxic.
- NOTE (4): Recommends the addition of a drug with enhanced anaerobic coverage, such as Clindamycin every 8 hours OR Metronidazole, in those cases of chorioamnionitis that require cesarean delivery
- NOTE (5): chorioamnionitis is a contraindication to the administration of Corticosteroids. Women with intra-amniotic infection have traditionally been excluded from randomized trials of corticosteroid therapy.
- Supportive measures
- Preferred regime: Antipyretics (Acetaminophen)
- Prevention
- Preferred regime: Macrolide (Erythromycin OR Azithromycin) AND Ampicillin for 7–10 days via intravenous (2 days) followed by oral routes.
- NOTE: Induction of labor and delivery for preterm premature rupture of membranes (PPROM) after 34 weeks’ gestation is recommended.
# Cystitis
- Acute Uncomplicated Cystitis
- Preferred regime: Nitrofurantoin monohydrate/macrocrystals 100 mg bid 5 days (avoid if early pyelonephritis suspected) OR Trimethoprim-sulfamethoxazole 160/800 mg (one DS tablet) bid 3 days (avoid if resistance prevalence is known to exceed 20 or if used for UTI in previous 3 months) OR Fosfomycin trometamol 3 gm single dose (lower efficacy than some other recommended agents; avoid if early pyelonephritis suspected) OR Pivmecillinam 400 mg bid 5 days (lower efficacy than some other recommended agents; avoid if early pyelonephritis suspected)
- Alternative regime (1): Fluoroquinolones, Ofloxacin, Ciprofloxacin, and Levofloxacin, use for 3 days.
- Alternative regime (2): β-Lactam agents, including Amoxicillin-clavulanate, Cefdinir, Cefaclor, and Cefpodoxime-proxetil, for 3–7-days
# Epididymitis
- Preferred regime: Ceftriaxone 250 mg IM in a single dose AND Doxycycline 100 mg orally twice a day for 10 days
- For acute epididymitis most likely caused by enteric organisms
- Preferred regime: 500 mg orally once daily for 10 days OR Ofloxacin 300 mg orally twice a day for 10 days
- NOTE: Patients who have uncomplicated acute epididymitis and also are infected with HIV should receive the same treatment regimen as those who are HIV negative.
# Genital herpes
- Genital herpes
- First episode of genital herpes
- Preferred regimen: Acyclovir 400 mg PO tid for 7–10 days OR Acyclovir 200 mg PO five times a day for 7–10 days OR Famciclovir 250 mg PO tid for 7–10 days OR Valacyclovir 1 g PO bid for 7–10 days
- Recurrent genital herpes
- Suppressive therapy
- Preferred regimen: Acyclovir 400 mg PO bid for 7–10 days OR Famciclovir 250 mg PO bid for 7–10 days OR Valacyclovir 1000 mg PO qd for 7–10 days OR Valacyclovir 500 mg PO qd for 7–10 days
- Episodic therapy
- Preferred regimen: Acyclovir 400 mg PO tid for 5 days OR Acyclovir 800 mg PO bid a day for 5 days OR Acyclovir 800 mg PO tid for 2 days OR Famciclovir 125 mg PO bid for 5 days OR Famciclovir 1000 mg PO bid for 1 day OR Famciclovir 500 mg PO once, followed by 250 mg PO bid for 2 days OR Valacyclovir 500 mg PO bid for 3 days OR Valacyclovir 1000 mg PO qd for 5 days
- Severe genital herpes
- Preferred regimen: Acyclovir 5–10 mg/kg IV q8h for 2–7 days or until clinical improvement is observed, followed by PO antiviral therapy to complete at least 10 days of total therapy.
- Genital herpes in HIV-infected patients
- Suppressive therapy
- Preferred regimen: Acyclovir 400–800 mg PO bid–tid OR Famciclovir 500 mg PO bid OR Valacyclovir 500 mg PO bid
- Episodic therapy
- Preferred regimen: Acyclovir 400 mg PO tid for 5–10 days OR Famciclovir 500 mg PO bid for 5–10 days OR Valacyclovir 1000 mg PO bid for 5–10 days
- Acyclovir-resistant genital herpes
- Preferred regimen: Foscarnet 40 mg/kg IV q8h until clinical resolution is attained,
- Alternative regimen: Cidofovir 5 mg/kg once weekly OR Imiquimod topically qd for 5 days
- Genital herpes in pregnancy
- Acyclovir can be administered orally to pregnant women with first episode of genital herpes or recurrent genital herpes.
- Acyclovir should be administered IV to pregnant women with severe genital herpes.
- Neonatal herpes, known or suspected
- Disease limited to the skin and mucous membranes
- Preferred regimen: Acyclovir 20 mg/kg IV q8h for 14 days
- Disseminated and CNS disease
- Preferred regimen: Acyclovir 20 mg/kg IV q8h for 21 days
# Gonococcal infections
- Neisseria gonorrhoeae, treatment
- 1. Gonococcal infections in adolescents and adults
- 1.1 Uncomplicated gonococcal infections of the cervix, urethra, and rectum
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- Alternative regimen: Cefixime 400 mg PO in a single dose AND Azithromycin 1 g PO in a single dose (if ceftriaxone is not available)
- 1.2 Uncomplicated gonococcal infections of the pharynx
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.2.1 Management of sex partners
- Expedited partner therapy: Cefixime 400 mg PO in a single dose AND Azithromycin 1 g PO in a single dose
- Recent sex partners (i.e., persons having sexual contact with the infected patient within the 60 days preceding onset of symptoms or gonorrhea diagnosis) should be referred for evaluation, testing, and presumptive dual treatment.
- If the patient’s last potential sexual exposure was >60 days before onset of symptoms or diagnosis, the most recent sex partner should be treated.
- To avoid reinfection, sex partners should be instructed to abstain from unprotected sexual intercourse for 7 days after they and their sexual partner(s) have completed treatment and after resolution of symptoms, if present.
- 1.2.2 Allergy, intolerance, and adverse reactions
- Preferred regimen (1): Gemifloxacin 320 mg PO in a single dose AND Azithromycin 2 g PO in a single dose
- Preferred regimen (2): Gentamicin 240 mg IM in a single dose AND Azithromycin 2 g PO in a single dose
- 1.2.3 Pregnancy
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.2.4 Suspected cephalosporin treatment failure
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Gemifloxacin 320 mg PO single dose AND Azithromycin 2 g PO single dose (when isolates have elevated cephalosporin MICs)
- Alternative regimen (2): Gentamicin 240 mg IM single dose AND Azithromycin 2 g PO single dose (when isolates have elevated cephalosporin MICs)
- Alternative regimen (3): Ceftriaxone 250 mg IM as a single dose AND Azithromycin 2 g PO as a single dose (failure after treatment with cefixime and azithromycin)
- 1.3 Gonococcal conjunctivitis
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.3.1 Management of sex partners
- Patients should be instructed to refer their sex partners for evaluation and treatment.
- 1.4 Disseminated gonococcal infection
- 1.4.1 Arthritis and arthritis-dermatitis syndrome
- Preferred regimen: Ceftriaxone 1 g IM/IV q24h for 7 days AND Azithromycin 1 g PO in a single dose
- Alternative regimen: Cefotaxime 1 g IV q8h for 7 days OR Ceftizoxime 1 g IV q 8 h for 7 days AND Azithromycin 1 g PO in a single dose
- 1.4.2 Gonococcal meningitis and endocarditis
- Preferred regimen : Ceftriaxone 1-2 g IV q 12-24 h for 10-14 days AND Azithromycin 1 g PO in a single dose
- 2. Gonococcal infections among neonates
- 2.1 Ophthalmia neonatorum caused by N. gonorrhoeae
- Preferred regimen: Ceftriaxone 25-50 mg/kg IV or IM in a single dose, not to exceed 125 mg
- 2.1.1 Management of mothers and their sex partners
- Mothers of infants with ophthalmia neonatorum caused by N. gonorrhoeae should be evaluated, tested, and presumptively treated for gonorrhea, along with their sex partner(s).
- 2.2 Disseminated gonococcal infection and gonococcal scalp abscesses in neonates
- Preferred regimen: Ceftriaxone 25-50 mg/kg/day IM/IV qd for 7 days OR Cefotaxime 25 mg/kg IV /IM q12h for 7 days.
- 2.2.1 Management of mothers and their sex partners
- Mothers of infants who have DGI or scalp abscesses caused by N. gonorrhoeae should be evaluated, tested, and presumptively treated for gonorrhea, along with their sex partner(s).
- 2.3 Neonates born to mothers who have gonococcal infection
- Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg
- 2.3.1 Management of mothers and their sex partners
- Mothers who have gonorrhea and their sex partners should be evaluated, tested, and presumptively treated for gonorrhea.
- 3. Gonococcal infections among infants and children
- 3.1 Infants and children who weigh ≤ 45 kg and who have uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis
- Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg
- 3.2 Children who weigh > 45 kg and who have uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1g PO in a single dose
- Alternative regimen: Cefixime 400 mg PO single dose AND Azithromycin 1 g PO single dose.(If ceftriaxone is not available)
- 3.3 Children who weigh ≤ 45 kg and who have bacteremia or arthritis
- Preferred regimen: Ceftriaxone 50 mg/kg (maximum dose: 1 g) IM/IV q24h for 7 days
- 3.4 Children who weigh > 45 kg and who have bacteremia or arthritis
- Preferred regimen: Ceftriaxone 1 g IM/IV q24h for 7 days
- Neisseria gonorrhoeae, prophylaxis
- 1. Ophthalmia neonatorum
- Preferred regimen: Erythromycin 0.5% ophthalmic ointment in each eye in a single application at birth
- Alternative regimen: Ceftriaxone 25–50 mg/kg IV/IM in a single dose, not to exceed 125 mg (if erythromycin ointment is not available)
# Granuloma inguinale
- Granuloma inguinale (donovanosis)
- Preferred regimen: Doxycycline 100 mg PO bid for at least 3 weeks and until all lesions have completely healed
- Alternative regimen (1): Azithromycin 1 g PO once per week for at least 3 weeks and until all lesions have completely healed
- Alternative regimen (2): Ciprofloxacin 750 mg PO bid for at least 3 weeks and until all lesions have completely healed
- Alternative regimen (3): Erythromycin base 500 mg PO qid for at least 3 weeks and until all lesions have completely healed
- Alternative regimen (4): Trimethoprim-Sulfamethoxazole double-strength (160 mg/800 mg) one tablet PO bid for at least 3 weeks and until all lesions have completely healed
# Lymphogranuloma venereum
- Lymphogranuloma venereum (Chlamydia trachomatis serovars L1, L2, or L3 infection)
- Preferred regimen: Doxycycline 100 mg PO bid for 21 days
- Alternative regimen: Erythromycin base 500 mg PO qid for 21 days
# Pelvic inflammatory disease
- Parenteral Treatment
- Preferred regime (1): Cefotetan 2 g IV every 12 hours OR Cefoxitin 2 g IV every 6 hours AND Doxycycline 100 mg orally or IV every 12 hours.
- Preferred regime (2): Clindamycin 900 mg IV every 8 hours AND Gentamicin loading dose IV or IM (2 mg/kg of body weight), followed by a maintenance dose (1.5 mg/kg) every 8 hours. Single daily dosing (3--5 mg/kg) can be substituted.
- Alternative regime: Ampicillin/Sulbactam 3 g IV every 6 hours AND Doxycycline 100 mg orally or IV every 12 hours.
- Oral Treatment
- Preferred regime (1): Ceftriaxone 250 mg IM in a single dose AND Doxycycline 100 mg orally twice a day for 14 days ± Metronidazole 500 mg orally twice a day for 14 days
- Preferred regime (2): Cefoxitin 2 g IM in a single dose and Probenecid, 1 g orally administered concurrently in a single dose AND Doxycycline 100 mg orally twice a day for 14 days ± Metronidazole 500 mg orally twice a day for 14 days
- Preferred regime (3): Other parenteral third-generation cephalosporin (e.g., ceftizoxime OR cefotaxime) AND Doxycycline 100 mg orally twice a day for 14 days ± Metronidazole 500 mg orally twice a day for 14 days
- Alternative regime (1): Ceftriaxone 250 mg IM single dose and Azithromycin 1 g orally once a week for 2 weeks.
- Alternative regime (2): Levofloxacin 500 mg orally once daily or Ofloxacin 400 mg twice daily for 14 days {{withorwithout]] Metronidazole 500 mg orally twice daily for 14 days.
# Proctocolitis
- Proctitis
- Preferred regime: Ceftriaxone 250 mg IM AND Doxycycline 100 mg orally twice a day for 7 days
# Prostatitis
## Acute Bacterial Prostatitis
- Uncomplicated (with low risk of STD pathogens)
- Preferred regime: Ciprofloxacin 400 mg iv or 500 mg po BID or Levofloxacin 500–750 mg iv/po QD
- Alternative regime: TMP-SMX DS (160 mg TMP) BID
- NOTE: 2 weeks duration of therapy may be sufficient; if patient remains symptomatic, extend to 4 weeks
- Preferred regime: Ampicillin 1–2 g IV every 4 h OR Vancomycin 15 mg/kg every 12 h
- Alternative regime: Levofloxacin 750 po QD OR Linezolid 600 mg every 12 h
- NOTE: Use intravenous therapy if systemically ill; switch to oral therapy when stable
- Preferred regime: Ciprofloxacin 400 mg TID
- Alternative regime: Piperacillin-tazobactam 4.5 g iv every 6 h
- Uncomplicated (with risk of STD pathogens)
- Preferred regime: Ceftriaxone 250 mg IM OR Cefixime 400 mg po x 1 dose AND Doxycycline 100 mg po BID OR Azithromycin 500 mg po QD
- Alternative regime: Fluoroquinolones not recommended for gonococcal infection
- NOTE: Treat for 2 weeks in most cases. Obtain urine nucleicacid amplification test for N.gonorrhoeae and C.trachomatis
- Uncomplicated, with risk of antibiotic resistant pathogen
- Preferred regime: Ertapenem 1 g iv QD
- Alternative regime: Ceftriaxone 1 g iv QD or Imipenem 500mg iv every 6 h OR Tigecycline 100 mg iv x 1 dose then 50 mg iv every 12 h
- Preferred regime: Ertapenem 1 g iv QD
- Alternative regime: Cefepime 2g iv every 12 h OR Imipenem 500 mg iv every 6 h OR Tigecycline 100 mg iv x 1 dose then 50 mg iv every 12 h
- Preferred regime: Imipenem 500 mg iv every 6 h
- Alternative regime: Meropenem 500 mg iv every 8 h
- Complicated by bacteremia or suspected prostatic abscess
- Preferred regime: Ciprofloxacin 400 mg iv every 12 h OR Levofloxacin 500 mg iv every 24 h
- Alternative regime: Ceftriaxone 1–2 g iv every 24 h AND Levofloxacin 500–750 mg po QD OR Ertapenem 1 g iv every 24 h OR piperacillin-tazobactam 3.375 g iv every 6 h
- NOTE: Treat for 4 weeks. Obtain blood cultures; Consider genitourinary imaging; Change iv to po regimen when blood cultures are sterile and abscess drained.
## Chronic Bacterial Prostatitis
- Preferred regime: Ciprofloxacin 400 mg iv every 12 h OR Levofloxacin 500 mg iv every 24 h
- Alternative regime: TMP-SMX x 1 dose DS BID
- Preferred regime: Azithromycin 500 mg po QD
- Alternative regime: Doxycycline 100 mg BID
# Pyelonephritis
- Condition 1: patients not requiring hospitalization where the prevalence of resistance of community uropathogens to fluoroquinolones is not known to exceed 10%
- Preferred regime: Ciprofloxacin orally 500 mg twice daily for 7 days ± an initial 400-mg dose of intravenous Ciprofloxacin
- NOTE (1): If an initial one-time intravenous agent is used, a long-acting antimicrobial, such as 1 g of Ceftriaxone or a consolidated 24-h dose of an Aminoglycoside, could be used in lieu of an intravenous fluoroquinolone
- NOTE (2): If the prevalence of fluoroquinolone resistance is thought to exceed 10%, an initial one-time intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of ceftriaxone or a consolidated 24-h dose of an aminoglycoside, is recommended.
- Alternative regime: A once-daily oral fluoroquinolone, including Ciprofloxacin 1000 mg extended release for 7 days OR Levofloxacin 750 mg for 5 days.
- NOTE: If the prevalence of fluoroquinolone resistance is thought to exceed 10%, an initial intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of Ceftriaxone or a consolidated 24-h dose of an Aminoglycoside, is recommended.
- Condition 2: When the uropathogen is known to be susceptible
- Preferred regime: Trimethoprim-sulfamethoxazole 160/800 mg (1 double-strength tablet) bid orally for 14 days.
- NOTE: If trimethoprim-sulfamethoxazole is used when the susceptibility is not known, an initial intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of ceftriaxone OR a consolidated 24-h dose of an aminoglycoside, is recommended.
- NOTE: Oral β-lactam agents are less effective than other available agents for treatment of pyelonephritis. If an oral β-lactam agent is used, an initial intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of ceftriaxone OR a consolidated 24-h dose of an aminoglycoside, is recommended.
- Condition 3: Patients require hospitalization (high fever, high white blood cell count, vomiting, dehydration, or evidence of sepsis)
- Preferred regime: intravenous antimicrobial regimen, such as a Fluoroquinolone; an Aminoglycoside ± Ampicillin; an extended-spectrum Cephalosporin or extended-spectrum Penicillin ± an Aminoglycoside; Carbapenem
- NOTE: The choice between these agents should be based on local resistance data, and the regimen should be tailored on the basis of susceptibility results.
# Sterile pyuria
- Sterile pyuria
- Definitions
- Pyuria: the presence of 10 or more white cells per cubic millimeter in a urine specimen, 3 or more white cells per high-power field of unspun urine, a positive result on Gram’s stain of an unspun urine specimen, or a urinary dipstick test that is positive for leukocyte esterase
- Sterile pyuria: the persistent finding of white cells in the urine in the absence of bacteria, as determined by means of aerobic laboratory techniques (on a 5% sheep-blood agar plate and MacConkey agar plate)
- Bacteriuria: bacterial colony counts of more than 1000 colony-forming units (CFU) per milliliter in urine
- Causes
- Infectious etiologies
- Gynecologic infection
- Urethritis due to chlamydia, Neisseria gonorrhoeae, mycoplasma, or ureaplasma
- Prostatitis
- Balanitis
- Appendicitis
- Viral infection of the lower genitourinary tract
- Genitourinary tuberculosis
- Fungal infection
- Parasitic disease such as trichomoniasis or schistosomiasis
- Non-infectious etiologies
- Current use of antibiotics
- Recently treated urinary tract infection (within past 2 weeks)
- Presence or recent use of a urinary catheter
- Recent cystoscopy or urologic endoscopy
- Urinary tract stones
- Foreign body such as surgical mesh in the urethra or a retained stent
- Urinary tract neoplasm
- Pelvic irradiation
- Urinary fistula
- Polycystic kidney
- Rejection of a renal transplant
- Renal-vein thrombosis
- Interstitial nephritis or analgesic nephropathy
- Papillary necrosis
- Interstitial cystitis
- Inflammatory disease such as systemic lupus erythematosus or Kawasaki’s disease
- Pathogen-directed antimicrobial therapy
- Tuberculosis
- Preferred regimen: Isoniazid AND Rifampin AND Ethambutol AND Pyrazinamide for 3–6 months
- Gonorrhea
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose, then (Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days)
- Chlamydia
- Preferred regimen: Azithromycin 1 g PO in single dose OR Doxycycline 100 mg PO bid for 7 days
- Alternative regimen: Erythromycin base 500 mg PO qid for 7 days
- Mycoplasma and ureaplasma
- Preferred regimen: Azithromycin OR Levofloxacin OR Moxifloxacin
- Genital herpes
- Preferred regimen: Acyclovir 400 mg PO tid for 7–10 days or Acyclovir 200 mg PO five times a day for 7–10 days OR Famciclovir 250 mg PO tid for 7–10 days OR Valacyclovir 1 g PO bid for 7 days
- Trichomoniasis
- Preferred regimen: Metronidazole 2 g PO in a single dose) OR Tinidazole 2 g PO in a single dose
- Fungal infections
- Preferred regimen: Fluconazole OR Posaconazole OR Echinocandins OR Amphotericin B
- Schistosomiasis
- Preferred regimen: Praziquantel 20 mg/kg PO bid for 1–2 days
# Syphilis
- Syphilis (Treponema pallidum)
- Non–HIV-infected persons
- Primary and secondary syphilis
- Preferred regimen (adult): Benzathine penicillin G 2.4 MU IM in a single dose
- Preferred regimen (pediatric): Benzathine penicillin G 50,000 units/kg (up to 2.4 MU) IM in a single dose
- Latent syphilis
- Early latent syphilis
- Preferred regimen (adult): Benzathine penicillin G 2.4 MU IM in a single dose
- Preferred regimen (pediatric): Benzathine penicillin G 50,000 units/kg (up to 2.4 MU) IM in a single dose
- Late latent syphilis or unknown duration
- Preferred regimen (adult): Benzathine penicillin G 2.4 MU IM for 3 doses, each at 1-week intervals
- Preferred regimen (pediatric): Benzathine penicillin G 50,000 units/kg (up to 2.4 MU) IM, administered as 3 doses at 1-week intervals
- Tertiary syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM for 3 doses, each at 1-week intervals
- Neurosyphilis
- Preferred regimen: Aqueous crystalline penicillin G 3–4 MU IV q4h or continuously for 10–14 days
- Alternative regimen: Procaine penicillin G 2.4 MU IM q24h for 10–14 days AND Probenecid 500 mg PO qid for 10–14 days
- HIV-infected persons
- Primary and secondary syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM in a single dose
- Latent syphilis
- Early latent syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM in a single dose
- Late latent syphilis or unknown duration
- Preferred regimen: Benzathine penicillin G 2.4 MU IM for 3 doses, each at 1-week intervals
- Tertiary syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM for 3 doses, each at 1-week intervals
- Neurosyphilis
- Preferred regimen: Penicillin G 3–4 MU IV q4h or continuously for 10–14 days
- Alternative regimen: Procaine penicillin G 2.4 MU IM q24h for 10–14 days AND Probenecid 500 mg PO qid for 10–14 days
- During pregnancy
- Preferred regimen: Pregnant women should be treated with the Penicillin regimen appropriate for their stage of infection.
- Congenital syphilis
- Infants with proven or highly probable disease AND (abnormal physical examination consistent with congenital syphilis OR nontreponemal serologic titer fourfold higher than the mother's titer OR a positive darkfield test of body fluids)
- Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days OR Procaine penicillin G 50,000 U/kg IM in a single daily dose for 10 days
- Infants who have a normal physical examination AND nontreponemal serologic titer the same or less than fourfold the maternal titer AND (mother was not treated adequately OR mother has no documentation of having received treatment OR mother was treated with Erythromycin or another non-Penicillin regimen OR mother received treatment < 4 weeks before delivery)
- Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days OR Procaine penicillin G 50,000 U/kg IM in a single daily dose for 10 days OR Benzathine penicillin G 50,000 U/kg IM in a single dose
- Infants who have a normal physical examination AND nontreponemal serologic titer the same or less than fourfold the maternal titer AND mother was treated during pregnancy AND treatment was appropriate for the stage of infection AND treatment administered > 4 weeks before delivery AND mother has no evidence of reinfection or relapse
- Preferred regimen: Benzathine penicillin G 50,000 U/kg IM in a single dose
- Infants who have a normal physical examination AND nontreponemal serologic titer the same or less than fourfold the maternal titer AND mother's treatment was adequate before pregnancy AND mother's nontreponemal serologic titer remained low and stable before and during pregnancy and at delivery (VDRL < 1:2; RPR < 1:4)
- Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg q4–6h for 10 days
# Urethritis
- Urethritis
- Nongonococcal urethritis
- Preferred regimen: Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
- Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days
- Recurrent and persistent urethritis
- Preferred regimen: Metronidazole 2 g PO in a single dose OR Tinidazole 2 g PO in a single dose AND Azithromycin 1 g PO in a single dose | Sandbox g41
## Asymptomatic bacteriuria
- Asymptomatic bacteriuria[1][2]
- Definitions
- For women: two consecutive voided urine specimens with isolation of the same bacterial strain in quantitative counts ≥ 105 cfu/mL
- For men: a single, clean-catch voided urine specimen with 1 bacterial species isolated in a quantitative count ≥ 105 cfu/mL
- For catheterized urine specimen: a single catheterized urine specimen with 1 bacterial species isolated in a quantitative count ≥ 10>2 cfu/mL
- Causative pathogens
- Escherichia coli
- Klebsiella pneumoniae
- Coagulase-negative staphylococci
- Enterococcus
- Group B streptococci
- Gardnerella vaginalis
- Pseudomonas aeruginosa, Proteus mirabilis, Providencia stuartii, Morganella morganii (common in patients with long-term urologic device in place)
- Empiric antimicrobial therapy
- Treatment of asymptomatic bacteriuria is not recommended for the following persons:
- Premenopausal, nonpregnant women
- Diabetic women
- Older persons residing in the community
- Elderly, institutionalized subjects
- Persons with spinal cord injury
- Catheterized patients while the catheter remains in situ
- Specific considerations
- Men
- Screening for or treatment of asymptomatic bacteriuria in men is not recommended.
- Women, premenopausal, nonpregnant
- Screening for or treatment of asymptomatic bacteriuria in premenopausal, nonpregnant women is not indicated.
- Women, pregnant[3]
- Preferred regimen (1): Nitrofurantoin 100 mg PO bid for 3–5 days (avoid in glucose-6-phosphate dehydrogenase deficiency)
- Preferred regimen (2): Amoxicillin 500 mg tid for 3–5 days
- Preferred regimen (3): Amoxicillin-Clavulanate 500 mg bid for 3–5 days
- Preferred regimen (4): Cephalexin 500 mg tid for 3–5 days
- Preferred regimen (5): Fosfomycin 3 g as a single dose
- Preferred regimen (6): Trimethoprim bid for 3–5 days (only after first trimester)
- Women, diabetic
- Screening for or treatment of asymptomatic bacteriuria in diabetic women is not recommended.
- Older persons residing in the community
- Screening for or treatment of asymptomatic bacteriuria in older persons residing in the community is not recommended.
- Elderly institutionalized subjects
- Screening for or treatment of asymptomatic bacteriuria in elderly institutionalized residents of longterm care facilities is not recommended.
- Subjects with spinal cord injuries
- Screening for or treatment of asymptomatic bacteriuria in subjects with spinal cord injuries is not recommended.
- Patients with indwelling urethral catheters
- Screening for or treatment of asymptomatic bacteriuria in patients with indwelling urethral catheters is not recommended.
- Urologic interventions[4]
- Screening for or treatment of asymptomatic bacteriuria before transurethral resection of the prostate is recommended.
- Preferred regimen: Trimethoprim-Sulfamethoxazole DS 1 tab bid for 3 days after obtaining urine cultures
## Ectoparasitic Infections
### Pediculosis Pubis
- Preferred regime: Permethrin 1% cream rinse applied to affected areas and washed off after 10 minutes OR Pyrethrins with piperonyl butoxide applied to the affected area and washed off after 10 minutes
- Alternative regime: Malathion 0.5% lotion applied for 8--12 hours and washed off OR Ivermectin 250 µg/kg orally, repeated in 2 weeks
### Scabies
- Preferred regime: Permethrin cream (5%) applied to all areas of the body from the neck down and washed off after 8--14 hours OR Ivermectin 200ug/kg orally, repeated in 2 weeks
- Alternative regime: Lindane (1%) 1 oz. of lotion (or 30 g of cream) applied in a thin layer to all areas of the body from the neck down and thoroughly washed off after 8 hours
## Human papillomavirus infection
### Genital Warts
- Patient-Applied:
- Preferred regime: Podofilox 0.5% solution or gel OR Imiquimod 5% cream OR Sinecatechins 15% ointment
- Provider--Administered:
- Preferred regime: Cryotherapy with liquid nitrogen or cryoprobe, repeat applications every 1-2 weeks OR Podophyllin resin 10%-25% in a compound tincture of benzoin OR Trichloroacetic acid (TCA) OR Bichloroacetic acid (BCA) 80%-90% OR Surgical removal either by tangential scissor excision, tangential shave excision, curettage, or electrosurgery.
- Alternative regime: intralesional interferon, photodynamic therapy, and topical [[Cidofovir].
- Preferred regime: For women who have exophytic cervical warts, a biopsy evaluation to exclude high-grade SIL must be performed before treatment is initiated. Management of exophytic cervical warts should include consultation with a specialist.
- Preferred regime: Cryotherapy with liquid nitrogen. The use of a cryoprobe in the vagina is not recommended because of the risk for vaginal perforation and fistula formation OR TCA or BCA 80%--90% applied to warts. A small amount should be applied only to warts and allowed to dry, at which time a white frosting develops. If an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate, or liquid soap preparations to remove unreacted acid. This treatment can be repeated weekly, if necessary.
- Preferred regime: Cryotherapy with liquid nitrogen OR Podophyllin 10%--25% in compound tincture of benzoin. The treatment area and adjacent normal skin must be dry before contact with podophyllin. This treatment can be repeated weekly, if necessary. The safety of podophyllin during pregnancy has not been established. Data are limited on the use of podofilox and imiquimod for treatment of distal meatal warts.
- Preferred regime: Cryotherapy with liquid nitrogen OR TCA or BCA 80%--90% applied to warts. A small amount should be applied only to warts and allowed to dry, at which time a white frosting develops. If an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate, or liquid soap preparations to remove unreacted acid. This treatment can be repeated weekly, if necessary. OR Surgical removal
## Vaginal infection
### Bacterial vaginosis
- Preferred regime: Metronidazole 500 mg orally twice a day for 7 days OR Metronidazole gel 0.75%, one full applicator (5 g) intravaginally, once a day for 5 days OR Clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7 days
- Alternative regime (1): Tinidazole 2 g orally once daily for 3 days
- Alternative regime (2): Tinidazole 1 g orally once daily for 5 days
- Alternative regime (3): Clindamycin 300 mg orally twice daily for 7 days
- Alternative regime (4): Clindamycin ovules 100 mg intravaginally once at bedtime for 3 days
- Preferred regime: Metronidazole 500 mg orally twice a day for 7 days OR Metronidazole 250 mg orally three times a day for 7 days OR Clindamycin 300 mg orally twice a day for 7 days
### Trichomoniasis
T. vaginalis
- Preferred regime: Metronidazole 2 g orally in a single dose OR Tinidazole 2 g orally in a single dose
- Alternative regime: Metronidazole 500 mg orally twice a day for 7 days
- Preferred regime: 2 g Metronidazole in a single dose at any stage of pregnancy, withholding breastfeeding during treatment and for 12--24 hours after the last dose will reduce the exposure of the infant to metronidazole.
### Vulvovaginal candidiasis
- Preferred regime:
- Over-the-Counter Intravaginal Agents: Butoconazole 2% cream 5 g intravaginally for 3 days OR Clotrimazole 1% cream 5 g intravaginally for 7--14 days OR Clotrimazole 2% cream 5 g intravaginally for 3 days OR [Miconazole]] 2% cream 5 g intravaginally for 7 days OR Miconazole 4% cream 5 g intravaginally for 3 days OR Miconazole 100 mg vaginal suppository, one suppository for 7 days OR Miconazole 200 mg vaginal suppository, one suppository for 3 days OR Miconazole 1,200 mg vaginal suppository, one suppository for 1 day OR Tioconazole 6.5% ointment 5 g intravaginally in a single application
- Prescription Intravaginal Agents: Butoconazole 2% cream (single dose bioadhesive product), 5 g intravaginally for 1 day OR Nystatin 100,000-unit vaginal tablet, one tablet for 14 days OR Terconazole 0.4% cream 5 g intravaginally for 7 days OR Terconazole 0.8% cream 5 g intravaginally for 3 days OR Terconazole 80 mg vaginal suppository, one suppository for 3 days
- Oral Agent: Fluconazole 150 mg oral tablet, one tablet in single dose
- Recurrent Vulvovaginal Candidiasis (RVVC)
- Preferred regime: 7-14 days of topical therapy OR a 100-mg, 150-mg, or 200-mg oral dose of Fluconazole every third day for a total of 3 doses followed by Oral Fluconazole (i.e., 100-mg, 150-mg, or 200-mg dose) weekly for 6 months
- Severe VVC
- Preferred regime: Topical Azole for 7-14 days OR 150 mg of Fluconazole in two sequential doses (second dose 72 hours after initial dose.
- Nonalbicans VVC
- Preferred regime: nonfluconazole Azole drug (oral or topical) for 7-14 days.
- Preferred regime: topical Azole therapies for 7 days
## Cervicitis
- Cervicitis[5]
- Preferred regimen: Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
## Chancroid
- Chancroid (Haemophilus ducreyi infection)[6]
- Preferred regimen: Azithromycin 1 g PO as a single dose OR Ceftriaxone 250 mg IM as a single dose OR Ciprofloxacin 500 mg PO bid for 3 days OR Erythromycin 500 mg PO tid for 7 days
## Chlamydial infections
- Chlamydial infections[7]
- Chlamydial infections in adolescents and adults
- Preferred regimen: Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
- Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days
- Chlamydial infections during pregnancy
- Preferred regimen: Azithromycin 1 g PO in a single dose OR Amoxicillin 500 mg PO tid for 7 days
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin base 250 mg PO qid for 14 days
- Alternative regimen (3): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (4): Erythromycin ethylsuccinate 400 mg PO qid for 14 days
- Chlamydial infections among infants and children
- Ophthalmia neonatorum caused by C. trachomatis
- Preferred regimen: Erythromycin base or ethylsuccinate 50 mg/kg/day PO divided into 4 doses daily for 14 days
- Pneumonia caused by C. trachomatis
- Preferred regimen (< 45 kg): Erythromycin base or ethylsuccinate 50 mg/kg/day PO divided into 4 doses daily for 14 days
- Preferred regimen (≥ 45 kg & < 8 years): Azithromycin 1 g PO in a single dose
- Preferred regimen (≥ 8 years): Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
## Chorioamnionitis
- Antibiotics [8]
- Preferred regime: Ampicillin 2 g intravenously every 6 h OR Penicillin 5x106 units intravenously every 6 h AND Gentamicin 1.5 mg/kg every 8 h
- NOTE (1): Cephalosporins are generally recommended for women with chorioamnionitis who are allergic to Penicillin
- NOTE (2): In women with anaphylaxis to Penicillin a recommendation is to substitute Clindamycin 900 mg every 8 h
- NOTE (3): In the non-obstetric population, daily dosing of Gentamicin appears to be more effective, convenient, and cost-effective as well as less toxic.
- NOTE (4): Recommends the addition of a drug with enhanced anaerobic coverage, such as Clindamycin every 8 hours OR Metronidazole, in those cases of chorioamnionitis that require cesarean delivery
- NOTE (5): chorioamnionitis is a contraindication to the administration of Corticosteroids. Women with intra-amniotic infection have traditionally been excluded from randomized trials of corticosteroid therapy.
- Supportive measures
- Preferred regime: Antipyretics (Acetaminophen)
- Prevention [9]
- Preferred regime: Macrolide (Erythromycin OR Azithromycin) AND Ampicillin for 7–10 days via intravenous (2 days) followed by oral routes.
- NOTE: Induction of labor and delivery for preterm premature rupture of membranes (PPROM) after 34 weeks’ gestation is recommended.
## Cystitis
- Acute Uncomplicated Cystitis
- Preferred regime: Nitrofurantoin monohydrate/macrocrystals 100 mg bid 5 days (avoid if early pyelonephritis suspected) OR Trimethoprim-sulfamethoxazole 160/800 mg (one DS tablet) bid 3 days (avoid if resistance prevalence is known to exceed 20 or if used for UTI in previous 3 months) OR Fosfomycin trometamol 3 gm single dose (lower efficacy than some other recommended agents; avoid if early pyelonephritis suspected) OR Pivmecillinam 400 mg bid 5 days (lower efficacy than some other recommended agents; avoid if early pyelonephritis suspected)
- Alternative regime (1): Fluoroquinolones, Ofloxacin, Ciprofloxacin, and Levofloxacin, use for 3 days.
- Alternative regime (2): β-Lactam agents, including Amoxicillin-clavulanate, Cefdinir, Cefaclor, and Cefpodoxime-proxetil, for 3–7-days
## Epididymitis
- Preferred regime: Ceftriaxone 250 mg IM in a single dose AND Doxycycline 100 mg orally twice a day for 10 days
- For acute epididymitis most likely caused by enteric organisms
- Preferred regime: [[Levofloxacin] 500 mg orally once daily for 10 days OR Ofloxacin 300 mg orally twice a day for 10 days
- NOTE: Patients who have uncomplicated acute epididymitis and also are infected with HIV should receive the same treatment regimen as those who are HIV negative.
## Genital herpes
- Genital herpes[10]
- First episode of genital herpes
- Preferred regimen: Acyclovir 400 mg PO tid for 7–10 days OR Acyclovir 200 mg PO five times a day for 7–10 days OR Famciclovir 250 mg PO tid for 7–10 days OR Valacyclovir 1 g PO bid for 7–10 days
- Recurrent genital herpes
- Suppressive therapy
- Preferred regimen: Acyclovir 400 mg PO bid for 7–10 days OR Famciclovir 250 mg PO bid for 7–10 days OR Valacyclovir 1000 mg PO qd for 7–10 days OR Valacyclovir 500 mg PO qd for 7–10 days
- Episodic therapy
- Preferred regimen: Acyclovir 400 mg PO tid for 5 days OR Acyclovir 800 mg PO bid a day for 5 days OR Acyclovir 800 mg PO tid for 2 days OR Famciclovir 125 mg PO bid for 5 days OR Famciclovir 1000 mg PO bid for 1 day OR Famciclovir 500 mg PO once, followed by 250 mg PO bid for 2 days OR Valacyclovir 500 mg PO bid for 3 days OR Valacyclovir 1000 mg PO qd for 5 days
- Severe genital herpes
- Preferred regimen: Acyclovir 5–10 mg/kg IV q8h for 2–7 days or until clinical improvement is observed, followed by PO antiviral therapy to complete at least 10 days of total therapy.
- Genital herpes in HIV-infected patients
- Suppressive therapy
- Preferred regimen: Acyclovir 400–800 mg PO bid–tid OR Famciclovir 500 mg PO bid OR Valacyclovir 500 mg PO bid
- Episodic therapy
- Preferred regimen: Acyclovir 400 mg PO tid for 5–10 days OR Famciclovir 500 mg PO bid for 5–10 days OR Valacyclovir 1000 mg PO bid for 5–10 days
- Acyclovir-resistant genital herpes
- Preferred regimen: Foscarnet 40 mg/kg IV q8h until clinical resolution is attained,
- Alternative regimen: Cidofovir 5 mg/kg once weekly OR Imiquimod topically qd for 5 days
- Genital herpes in pregnancy
- Acyclovir can be administered orally to pregnant women with first episode of genital herpes or recurrent genital herpes.
- Acyclovir should be administered IV to pregnant women with severe genital herpes.
- Neonatal herpes, known or suspected
- Disease limited to the skin and mucous membranes
- Preferred regimen: Acyclovir 20 mg/kg IV q8h for 14 days
- Disseminated and CNS disease
- Preferred regimen: Acyclovir 20 mg/kg IV q8h for 21 days
## Gonococcal infections
- Neisseria gonorrhoeae, treatment[11]
- 1. Gonococcal infections in adolescents and adults
- 1.1 Uncomplicated gonococcal infections of the cervix, urethra, and rectum
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- Alternative regimen: Cefixime 400 mg PO in a single dose AND Azithromycin 1 g PO in a single dose (if ceftriaxone is not available)
- 1.2 Uncomplicated gonococcal infections of the pharynx
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.2.1 Management of sex partners
- Expedited partner therapy: Cefixime 400 mg PO in a single dose AND Azithromycin 1 g PO in a single dose
- Recent sex partners (i.e., persons having sexual contact with the infected patient within the 60 days preceding onset of symptoms or gonorrhea diagnosis) should be referred for evaluation, testing, and presumptive dual treatment.
- If the patient’s last potential sexual exposure was >60 days before onset of symptoms or diagnosis, the most recent sex partner should be treated.
- To avoid reinfection, sex partners should be instructed to abstain from unprotected sexual intercourse for 7 days after they and their sexual partner(s) have completed treatment and after resolution of symptoms, if present.
- 1.2.2 Allergy, intolerance, and adverse reactions
- Preferred regimen (1): Gemifloxacin 320 mg PO in a single dose AND Azithromycin 2 g PO in a single dose
- Preferred regimen (2): Gentamicin 240 mg IM in a single dose AND Azithromycin 2 g PO in a single dose
- 1.2.3 Pregnancy
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.2.4 Suspected cephalosporin treatment failure
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- Alternative regimen (1): Gemifloxacin 320 mg PO single dose AND Azithromycin 2 g PO single dose (when isolates have elevated cephalosporin MICs)
- Alternative regimen (2): Gentamicin 240 mg IM single dose AND Azithromycin 2 g PO single dose (when isolates have elevated cephalosporin MICs)
- Alternative regimen (3): Ceftriaxone 250 mg IM as a single dose AND Azithromycin 2 g PO as a single dose (failure after treatment with cefixime and azithromycin)
- 1.3 Gonococcal conjunctivitis
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1 g PO in a single dose
- 1.3.1 Management of sex partners
- Patients should be instructed to refer their sex partners for evaluation and treatment.
- 1.4 Disseminated gonococcal infection
- 1.4.1 Arthritis and arthritis-dermatitis syndrome
- Preferred regimen: Ceftriaxone 1 g IM/IV q24h for 7 days AND Azithromycin 1 g PO in a single dose
- Alternative regimen: Cefotaxime 1 g IV q8h for 7 days OR Ceftizoxime 1 g IV q 8 h for 7 days AND Azithromycin 1 g PO in a single dose
- 1.4.2 Gonococcal meningitis and endocarditis
- Preferred regimen : Ceftriaxone 1-2 g IV q 12-24 h for 10-14 days AND Azithromycin 1 g PO in a single dose
- 2. Gonococcal infections among neonates
- 2.1 Ophthalmia neonatorum caused by N. gonorrhoeae
- Preferred regimen: Ceftriaxone 25-50 mg/kg IV or IM in a single dose, not to exceed 125 mg
- 2.1.1 Management of mothers and their sex partners
- Mothers of infants with ophthalmia neonatorum caused by N. gonorrhoeae should be evaluated, tested, and presumptively treated for gonorrhea, along with their sex partner(s).
- 2.2 Disseminated gonococcal infection and gonococcal scalp abscesses in neonates
- Preferred regimen: Ceftriaxone 25-50 mg/kg/day IM/IV qd for 7 days OR Cefotaxime 25 mg/kg IV /IM q12h for 7 days.
- 2.2.1 Management of mothers and their sex partners
- Mothers of infants who have DGI or scalp abscesses caused by N. gonorrhoeae should be evaluated, tested, and presumptively treated for gonorrhea, along with their sex partner(s).
- 2.3 Neonates born to mothers who have gonococcal infection
- Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg
- 2.3.1 Management of mothers and their sex partners
- Mothers who have gonorrhea and their sex partners should be evaluated, tested, and presumptively treated for gonorrhea.
- 3. Gonococcal infections among infants and children
- 3.1 Infants and children who weigh ≤ 45 kg and who have uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis
- Preferred regimen: Ceftriaxone 25-50 mg/kg IM/IV in a single dose, not to exceed 125 mg
- 3.2 Children who weigh > 45 kg and who have uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND Azithromycin 1g PO in a single dose
- Alternative regimen: Cefixime 400 mg PO single dose AND Azithromycin 1 g PO single dose.(If ceftriaxone is not available)
- 3.3 Children who weigh ≤ 45 kg and who have bacteremia or arthritis
- Preferred regimen: Ceftriaxone 50 mg/kg (maximum dose: 1 g) IM/IV q24h for 7 days
- 3.4 Children who weigh > 45 kg and who have bacteremia or arthritis
- Preferred regimen: Ceftriaxone 1 g IM/IV q24h for 7 days
- Neisseria gonorrhoeae, prophylaxis[12]
- 1. Ophthalmia neonatorum
- Preferred regimen: Erythromycin 0.5% ophthalmic ointment in each eye in a single application at birth
- Alternative regimen: Ceftriaxone 25–50 mg/kg IV/IM in a single dose, not to exceed 125 mg (if erythromycin ointment is not available)
## Granuloma inguinale
- Granuloma inguinale (donovanosis)[13]
- Preferred regimen: Doxycycline 100 mg PO bid for at least 3 weeks and until all lesions have completely healed
- Alternative regimen (1): Azithromycin 1 g PO once per week for at least 3 weeks and until all lesions have completely healed
- Alternative regimen (2): Ciprofloxacin 750 mg PO bid for at least 3 weeks and until all lesions have completely healed
- Alternative regimen (3): Erythromycin base 500 mg PO qid for at least 3 weeks and until all lesions have completely healed
- Alternative regimen (4): Trimethoprim-Sulfamethoxazole double-strength (160 mg/800 mg) one tablet PO bid for at least 3 weeks and until all lesions have completely healed
## Lymphogranuloma venereum
- Lymphogranuloma venereum (Chlamydia trachomatis serovars L1, L2, or L3 infection)[14]
- Preferred regimen: Doxycycline 100 mg PO bid for 21 days
- Alternative regimen: Erythromycin base 500 mg PO qid for 21 days
## Pelvic inflammatory disease
- Parenteral Treatment
- Preferred regime (1): Cefotetan 2 g IV every 12 hours OR Cefoxitin 2 g IV every 6 hours AND Doxycycline 100 mg orally or IV every 12 hours.
- Preferred regime (2): Clindamycin 900 mg IV every 8 hours AND Gentamicin loading dose IV or IM (2 mg/kg of body weight), followed by a maintenance dose (1.5 mg/kg) every 8 hours. Single daily dosing (3--5 mg/kg) can be substituted.
- Alternative regime: Ampicillin/Sulbactam 3 g IV every 6 hours AND Doxycycline 100 mg orally or IV every 12 hours.
- Oral Treatment
- Preferred regime (1): Ceftriaxone 250 mg IM in a single dose AND Doxycycline 100 mg orally twice a day for 14 days ± Metronidazole 500 mg orally twice a day for 14 days
- Preferred regime (2): Cefoxitin 2 g IM in a single dose and Probenecid, 1 g orally administered concurrently in a single dose AND Doxycycline 100 mg orally twice a day for 14 days ± Metronidazole 500 mg orally twice a day for 14 days
- Preferred regime (3): Other parenteral third-generation cephalosporin (e.g., ceftizoxime OR cefotaxime) AND Doxycycline 100 mg orally twice a day for 14 days ± Metronidazole 500 mg orally twice a day for 14 days
- Alternative regime (1): Ceftriaxone 250 mg IM single dose and Azithromycin 1 g orally once a week for 2 weeks.
- Alternative regime (2): Levofloxacin 500 mg orally once daily or Ofloxacin 400 mg twice daily for 14 days {{withorwithout]] Metronidazole 500 mg orally twice daily for 14 days.
## Proctocolitis
- Proctitis
- Preferred regime: Ceftriaxone 250 mg IM AND Doxycycline 100 mg orally twice a day for 7 days
## Prostatitis
### Acute Bacterial Prostatitis
- Uncomplicated (with low risk of STD pathogens)[15]
- Preferred regime: Ciprofloxacin 400 mg iv or 500 mg po BID or Levofloxacin 500–750 mg iv/po QD
- Alternative regime: TMP-SMX DS (160 mg TMP) BID
- NOTE: 2 weeks duration of therapy may be sufficient; if patient remains symptomatic, extend to 4 weeks
- Preferred regime: Ampicillin 1–2 g IV every 4 h OR Vancomycin 15 mg/kg every 12 h
- Alternative regime: Levofloxacin 750 po QD OR Linezolid 600 mg every 12 h
- NOTE: Use intravenous therapy if systemically ill; switch to oral therapy when stable
- Preferred regime: Ciprofloxacin 400 mg TID
- Alternative regime: Piperacillin-tazobactam 4.5 g iv every 6 h
- Uncomplicated (with risk of STD pathogens)
- Preferred regime: Ceftriaxone 250 mg IM OR Cefixime 400 mg po x 1 dose AND Doxycycline 100 mg po BID OR Azithromycin 500 mg po QD
- Alternative regime: Fluoroquinolones not recommended for gonococcal infection
- NOTE: Treat for 2 weeks in most cases. Obtain urine nucleicacid amplification test for N.gonorrhoeae and C.trachomatis
- Uncomplicated, with risk of antibiotic resistant pathogen
- Preferred regime: Ertapenem 1 g iv QD
- Alternative regime: Ceftriaxone 1 g iv QD or Imipenem 500mg iv every 6 h OR Tigecycline 100 mg iv x 1 dose then 50 mg iv every 12 h
- Preferred regime: Ertapenem 1 g iv QD
- Alternative regime: Cefepime 2g iv every 12 h OR Imipenem 500 mg iv every 6 h OR Tigecycline 100 mg iv x 1 dose then 50 mg iv every 12 h
- Preferred regime: Imipenem 500 mg iv every 6 h
- Alternative regime: Meropenem 500 mg iv every 8 h
- Complicated by bacteremia or suspected prostatic abscess
- Preferred regime: Ciprofloxacin 400 mg iv every 12 h OR Levofloxacin 500 mg iv every 24 h
- Alternative regime: Ceftriaxone 1–2 g iv every 24 h AND Levofloxacin 500–750 mg po QD OR Ertapenem 1 g iv every 24 h OR piperacillin-tazobactam 3.375 g iv every 6 h
- NOTE: Treat for 4 weeks. Obtain blood cultures; Consider genitourinary imaging; Change iv to po regimen when blood cultures are sterile and abscess drained.
### Chronic Bacterial Prostatitis
- Preferred regime: Ciprofloxacin 400 mg iv every 12 h OR Levofloxacin 500 mg iv every 24 h
- Alternative regime: TMP-SMX x 1 dose DS BID
- Preferred regime: Azithromycin 500 mg po QD
- Alternative regime: Doxycycline 100 mg BID
## Pyelonephritis
- Condition 1: patients not requiring hospitalization where the prevalence of resistance of community uropathogens to fluoroquinolones is not known to exceed 10%
- Preferred regime: Ciprofloxacin orally 500 mg twice daily for 7 days ± an initial 400-mg dose of intravenous Ciprofloxacin
- NOTE (1): If an initial one-time intravenous agent is used, a long-acting antimicrobial, such as 1 g of Ceftriaxone or a consolidated 24-h dose of an Aminoglycoside, could be used in lieu of an intravenous fluoroquinolone
- NOTE (2): If the prevalence of fluoroquinolone resistance is thought to exceed 10%, an initial one-time intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of ceftriaxone or a consolidated 24-h dose of an aminoglycoside, is recommended.
- Alternative regime: A once-daily oral fluoroquinolone, including Ciprofloxacin 1000 mg extended release for 7 days OR Levofloxacin 750 mg for 5 days.
- NOTE: If the prevalence of fluoroquinolone resistance is thought to exceed 10%, an initial intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of Ceftriaxone or a consolidated 24-h dose of an Aminoglycoside, is recommended.
- Condition 2: When the uropathogen is known to be susceptible
- Preferred regime: Trimethoprim-sulfamethoxazole 160/800 mg (1 double-strength tablet) bid orally for 14 days.
- NOTE: If trimethoprim-sulfamethoxazole is used when the susceptibility is not known, an initial intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of ceftriaxone OR a consolidated 24-h dose of an aminoglycoside, is recommended.
- NOTE: Oral β-lactam agents are less effective than other available agents for treatment of pyelonephritis. If an oral β-lactam agent is used, an initial intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of ceftriaxone OR a consolidated 24-h dose of an aminoglycoside, is recommended.
- Condition 3: Patients require hospitalization (high fever, high white blood cell count, vomiting, dehydration, or evidence of sepsis)
- Preferred regime: intravenous antimicrobial regimen, such as a Fluoroquinolone; an Aminoglycoside ± Ampicillin; an extended-spectrum Cephalosporin or extended-spectrum Penicillin ± an Aminoglycoside; Carbapenem
- NOTE: The choice between these agents should be based on local resistance data, and the regimen should be tailored on the basis of susceptibility results.
## Sterile pyuria
- Sterile pyuria
- Definitions
- Pyuria: the presence of 10 or more white cells per cubic millimeter in a urine specimen, 3 or more white cells per high-power field of unspun urine, a positive result on Gram’s stain of an unspun urine specimen, or a urinary dipstick test that is positive for leukocyte esterase[16]
- Sterile pyuria: the persistent finding of white cells in the urine in the absence of bacteria, as determined by means of aerobic laboratory techniques (on a 5% sheep-blood agar plate and MacConkey agar plate)[17]
- Bacteriuria: bacterial colony counts of more than 1000 colony-forming units (CFU) per milliliter in urine[18]
- Causes[19]
- Infectious etiologies
- Gynecologic infection
- Urethritis due to chlamydia, Neisseria gonorrhoeae, mycoplasma, or ureaplasma
- Prostatitis
- Balanitis
- Appendicitis
- Viral infection of the lower genitourinary tract
- Genitourinary tuberculosis
- Fungal infection
- Parasitic disease such as trichomoniasis or schistosomiasis
- Non-infectious etiologies
- Current use of antibiotics
- Recently treated urinary tract infection (within past 2 weeks)
- Presence or recent use of a urinary catheter
- Recent cystoscopy or urologic endoscopy
- Urinary tract stones
- Foreign body such as surgical mesh in the urethra or a retained stent
- Urinary tract neoplasm
- Pelvic irradiation
- Urinary fistula
- Polycystic kidney
- Rejection of a renal transplant
- Renal-vein thrombosis
- Interstitial nephritis or analgesic nephropathy
- Papillary necrosis
- Interstitial cystitis
- Inflammatory disease such as systemic lupus erythematosus or Kawasaki’s disease
- Pathogen-directed antimicrobial therapy[20]
- Tuberculosis
- Preferred regimen: Isoniazid AND Rifampin AND Ethambutol AND Pyrazinamide for 3–6 months
- Gonorrhea
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose, then (Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days)
- Chlamydia
- Preferred regimen: Azithromycin 1 g PO in single dose OR Doxycycline 100 mg PO bid for 7 days
- Alternative regimen: Erythromycin base 500 mg PO qid for 7 days
- Mycoplasma and ureaplasma
- Preferred regimen: Azithromycin OR Levofloxacin OR Moxifloxacin
- Genital herpes
- Preferred regimen: Acyclovir 400 mg PO tid for 7–10 days or Acyclovir 200 mg PO five times a day for 7–10 days OR Famciclovir 250 mg PO tid for 7–10 days OR Valacyclovir 1 g PO bid for 7 days
- Trichomoniasis
- Preferred regimen: Metronidazole 2 g PO in a single dose) OR Tinidazole 2 g PO in a single dose
- Fungal infections
- Preferred regimen: Fluconazole OR Posaconazole OR Echinocandins OR Amphotericin B
- Schistosomiasis
- Preferred regimen: Praziquantel 20 mg/kg PO bid for 1–2 days
## Syphilis
- Syphilis (Treponema pallidum)[21]
- Non–HIV-infected persons
- Primary and secondary syphilis
- Preferred regimen (adult): Benzathine penicillin G 2.4 MU IM in a single dose
- Preferred regimen (pediatric): Benzathine penicillin G 50,000 units/kg (up to 2.4 MU) IM in a single dose
- Latent syphilis
- Early latent syphilis
- Preferred regimen (adult): Benzathine penicillin G 2.4 MU IM in a single dose
- Preferred regimen (pediatric): Benzathine penicillin G 50,000 units/kg (up to 2.4 MU) IM in a single dose
- Late latent syphilis or unknown duration
- Preferred regimen (adult): Benzathine penicillin G 2.4 MU IM for 3 doses, each at 1-week intervals
- Preferred regimen (pediatric): Benzathine penicillin G 50,000 units/kg (up to 2.4 MU) IM, administered as 3 doses at 1-week intervals
- Tertiary syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM for 3 doses, each at 1-week intervals
- Neurosyphilis
- Preferred regimen: Aqueous crystalline penicillin G 3–4 MU IV q4h or continuously for 10–14 days
- Alternative regimen: Procaine penicillin G 2.4 MU IM q24h for 10–14 days AND Probenecid 500 mg PO qid for 10–14 days
- HIV-infected persons
- Primary and secondary syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM in a single dose
- Latent syphilis
- Early latent syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM in a single dose
- Late latent syphilis or unknown duration
- Preferred regimen: Benzathine penicillin G 2.4 MU IM for 3 doses, each at 1-week intervals
- Tertiary syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM for 3 doses, each at 1-week intervals
- Neurosyphilis
- Preferred regimen: Penicillin G 3–4 MU IV q4h or continuously for 10–14 days
- Alternative regimen: Procaine penicillin G 2.4 MU IM q24h for 10–14 days AND Probenecid 500 mg PO qid for 10–14 days
- During pregnancy
- Preferred regimen: Pregnant women should be treated with the Penicillin regimen appropriate for their stage of infection.
- Congenital syphilis
- Infants with proven or highly probable disease AND (abnormal physical examination consistent with congenital syphilis OR nontreponemal serologic titer fourfold higher than the mother's titer OR a positive darkfield test of body fluids)
- Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days OR Procaine penicillin G 50,000 U/kg IM in a single daily dose for 10 days
- Infants who have a normal physical examination AND nontreponemal serologic titer the same or less than fourfold the maternal titer AND (mother was not treated adequately OR mother has no documentation of having received treatment OR mother was treated with Erythromycin or another non-Penicillin regimen OR mother received treatment < 4 weeks before delivery)
- Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days OR Procaine penicillin G 50,000 U/kg IM in a single daily dose for 10 days OR Benzathine penicillin G 50,000 U/kg IM in a single dose
- Infants who have a normal physical examination AND nontreponemal serologic titer the same or less than fourfold the maternal titer AND mother was treated during pregnancy AND treatment was appropriate for the stage of infection AND treatment administered > 4 weeks before delivery AND mother has no evidence of reinfection or relapse
- Preferred regimen: Benzathine penicillin G 50,000 U/kg IM in a single dose
- Infants who have a normal physical examination AND nontreponemal serologic titer the same or less than fourfold the maternal titer AND mother's treatment was adequate before pregnancy AND mother's nontreponemal serologic titer remained low and stable before and during pregnancy and at delivery (VDRL < 1:2; RPR < 1:4)
- Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg q4–6h for 10 days
## Urethritis
- Urethritis[22]
- Nongonococcal urethritis
- Preferred regimen: Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
- Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days
- Recurrent and persistent urethritis
- Preferred regimen: Metronidazole 2 g PO in a single dose OR Tinidazole 2 g PO in a single dose AND Azithromycin 1 g PO in a single dose | https://www.wikidoc.org/index.php/Sandbox_g41 | |
bb67a857c949b682b7274e9c6ed6d8d19fe3ab1e | wikidoc | Sandbox g42 | Sandbox g42
# Asymptomatic bacteriuria
- Asymptomatic bacteriuria
- Definitions
- For women: two consecutive voided urine specimens with isolation of the same bacterial strain in quantitative counts ≥ 105 cfu/mL
- For men: a single, clean-catch voided urine specimen with 1 bacterial species isolated in a quantitative count ≥ 105 cfu/mL
- For catheterized urine specimen: a single catheterized urine specimen with 1 bacterial species isolated in a quantitative count ≥ 10>2 cfu/mL
- Causative pathogens
- Escherichia coli
- Klebsiella pneumoniae
- Coagulase-negative staphylococci
- Enterococcus
- Group B streptococci
- Gardnerella vaginalis
- Pseudomonas aeruginosa, Proteus mirabilis, Providencia stuartii, Morganella morganii (common in patients with long-term urologic device in place)
- Empiric antimicrobial therapy
- Treatment of asymptomatic bacteriuria is not recommended for the following persons:
- Premenopausal, nonpregnant women
- Diabetic women
- Older persons residing in the community
- Elderly, institutionalized subjects
- Persons with spinal cord injury
- Catheterized patients while the catheter remains in situ
- Specific considerations
- Men
- Screening for or treatment of asymptomatic bacteriuria in men is not recommended.
- Women, premenopausal, nonpregnant
- Screening for or treatment of asymptomatic bacteriuria in premenopausal, nonpregnant women is not indicated.
- Women, pregnant
- Preferred regimen (1): Nitrofurantoin 100 mg PO bid for 3–5 days (avoid in glucose-6-phosphate dehydrogenase deficiency)
- Preferred regimen (2): Amoxicillin 500 mg tid for 3–5 days
- Preferred regimen (3): Amoxicillin-Clavulanate 500 mg bid for 3–5 days
- Preferred regimen (4): Cephalexin 500 mg tid for 3–5 days
- Preferred regimen (5): Fosfomycin 3 g as a single dose
- Preferred regimen (6): Trimethoprim bid for 3–5 days (only after first trimester)
- Women, diabetic
- Screening for or treatment of asymptomatic bacteriuria in diabetic women is not recommended.
- Older persons residing in the community
- Screening for or treatment of asymptomatic bacteriuria in older persons residing in the community is not recommended.
- Elderly institutionalized subjects
- Screening for or treatment of asymptomatic bacteriuria in elderly institutionalized residents of longterm care facilities is not recommended.
- Subjects with spinal cord injuries
- Screening for or treatment of asymptomatic bacteriuria in subjects with spinal cord injuries is not recommended.
- Patients with indwelling urethral catheters
- Screening for or treatment of asymptomatic bacteriuria in patients with indwelling urethral catheters is not recommended.
- Urologic interventions
- Screening for or treatment of asymptomatic bacteriuria before transurethral resection of the prostate is recommended.
- Preferred regimen: Trimethoprim-Sulfamethoxazole DS 1 tab bid for 3 days after obtaining urine cultures
# Ectoparasitic Infections
## Pediculosis Pubis
- Preferred regime: Permethrin 1% cream rinse applied to affected areas and washed off after 10 minutes OR Pyrethrins with piperonyl butoxide applied to the affected area and washed off after 10 minutes
- Alternative regime: Malathion 0.5% lotion applied for 8--12 hours and washed off OR Ivermectin 250 µg/kg orally, repeated in 2 weeks
## Scabies
- Preferred regime: Permethrin cream (5%) applied to all areas of the body from the neck down and washed off after 8--14 hours OR Ivermectin 200ug/kg orally, repeated in 2 weeks
- Alternative regime: Lindane (1%) 1 oz. of lotion (or 30 g of cream) applied in a thin layer to all areas of the body from the neck down and thoroughly washed off after 8 hours
# Human papillomavirus infection
## Genital Warts
- Patient-Applied:
- Preferred regime: Podofilox 0.5% solution or gel OR Imiquimod 5% cream OR Sinecatechins 15% ointment
- Provider--Administered:
- Preferred regime: Cryotherapy with liquid nitrogen or cryoprobe, repeat applications every 1-2 weeks OR Podophyllin resin 10%-25% in a compound tincture of benzoin OR Trichloroacetic acid (TCA) OR Bichloroacetic acid (BCA) 80%-90% OR Surgical removal either by tangential scissor excision, tangential shave excision, curettage, or electrosurgery.
- Alternative regime: intralesional interferon, photodynamic therapy, and topical .
- Preferred regime: For women who have exophytic cervical warts, a biopsy evaluation to exclude high-grade SIL must be performed before treatment is initiated. Management of exophytic cervical warts should include consultation with a specialist.
- Preferred regime: Cryotherapy with liquid nitrogen. The use of a cryoprobe in the vagina is not recommended because of the risk for vaginal perforation and fistula formation OR TCA or BCA 80%--90% applied to warts. A small amount should be applied only to warts and allowed to dry, at which time a white frosting develops. If an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate, or liquid soap preparations to remove unreacted acid. This treatment can be repeated weekly, if necessary.
- Preferred regime: Cryotherapy with liquid nitrogen OR Podophyllin 10%--25% in compound tincture of benzoin. The treatment area and adjacent normal skin must be dry before contact with podophyllin. This treatment can be repeated weekly, if necessary. The safety of podophyllin during pregnancy has not been established. Data are limited on the use of podofilox and imiquimod for treatment of distal meatal warts.
- Preferred regime: Cryotherapy with liquid nitrogen OR TCA or BCA 80%--90% applied to warts. A small amount should be applied only to warts and allowed to dry, at which time a white frosting develops. If an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate, or liquid soap preparations to remove unreacted acid. This treatment can be repeated weekly, if necessary. OR Surgical removal
# Vaginal infection
## Bacterial vaginosis
- Preferred regime: Metronidazole 500 mg orally twice a day for 7 days OR Metronidazole gel 0.75%, one full applicator (5 g) intravaginally, once a day for 5 days OR Clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7 days
- Alternative regime (1): Tinidazole 2 g orally once daily for 3 days
- Alternative regime (2): Tinidazole 1 g orally once daily for 5 days
- Alternative regime (3): Clindamycin 300 mg orally twice daily for 7 days
- Alternative regime (4): Clindamycin ovules 100 mg intravaginally once at bedtime for 3 days
- Preferred regime: Metronidazole 500 mg orally twice a day for 7 days OR Metronidazole 250 mg orally three times a day for 7 days OR Clindamycin 300 mg orally twice a day for 7 days
## Trichomoniasis
T. vaginalis
- Preferred regime: Metronidazole 2 g orally in a single dose OR Tinidazole 2 g orally in a single dose
- Alternative regime: Metronidazole 500 mg orally twice a day for 7 days
- Preferred regime: 2 g Metronidazole in a single dose at any stage of pregnancy, withholding breastfeeding during treatment and for 12--24 hours after the last dose will reduce the exposure of the infant to metronidazole.
## Vulvovaginal candidiasis
- Preferred regime:
- Over-the-Counter Intravaginal Agents: Butoconazole 2% cream 5 g intravaginally for 3 days OR Clotrimazole 1% cream 5 g intravaginally for 7--14 days OR Clotrimazole 2% cream 5 g intravaginally for 3 days OR ] 2% cream 5 g intravaginally for 7 days OR Miconazole 4% cream 5 g intravaginally for 3 days OR Miconazole 100 mg vaginal suppository, one suppository for 7 days OR Miconazole 200 mg vaginal suppository, one suppository for 3 days OR Miconazole 1,200 mg vaginal suppository, one suppository for 1 day OR Tioconazole 6.5% ointment 5 g intravaginally in a single application
- Prescription Intravaginal Agents: Butoconazole 2% cream (single dose bioadhesive product), 5 g intravaginally for 1 day OR Nystatin 100,000-unit vaginal tablet, one tablet for 14 days OR Terconazole 0.4% cream 5 g intravaginally for 7 days OR Terconazole 0.8% cream 5 g intravaginally for 3 days OR Terconazole 80 mg vaginal suppository, one suppository for 3 days
- Oral Agent: Fluconazole 150 mg oral tablet, one tablet in single dose
- Recurrent Vulvovaginal Candidiasis (RVVC)
- Preferred regime: 7-14 days of topical therapy OR a 100-mg, 150-mg, or 200-mg oral dose of Fluconazole every third day for a total of 3 doses followed by Oral Fluconazole (i.e., 100-mg, 150-mg, or 200-mg dose) weekly for 6 months
- Severe VVC
- Preferred regime: Topical Azole for 7-14 days OR 150 mg of Fluconazole in two sequential doses (second dose 72 hours after initial dose.
- Nonalbicans VVC
- Preferred regime: nonfluconazole Azole drug (oral or topical) for 7-14 days.
- Preferred regime: topical Azole therapies for 7 days
# Cervicitis
- Cervicitis
- Preferred regimen: Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
# Chancroid
- Chancroid (Haemophilus ducreyi infection)
- Preferred regimen: Azithromycin 1 g PO as a single dose OR Ceftriaxone 250 mg IM as a single dose OR Ciprofloxacin 500 mg PO bid for 3 days OR Erythromycin 500 mg PO tid for 7 days
# Chlamydial infections
- Chlamydial infections
- Chlamydial infections in adolescents and adults
- Preferred regimen: Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
- Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days
- Chlamydial infections during pregnancy
- Preferred regimen: Azithromycin 1 g PO in a single dose OR Amoxicillin 500 mg PO tid for 7 days
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin base 250 mg PO qid for 14 days
- Alternative regimen (3): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (4): Erythromycin ethylsuccinate 400 mg PO qid for 14 days
- Chlamydial infections among infants
- Ophthalmia neonatorum caused by C. trachomatis
- Preferred regimen: Erythromycin base or ethylsuccinate 50 mg/kg/day PO divided into 4 doses daily for 14 days
- Infant pneumonia caused by C. trachomatis
- Preferred regimen (< 45 kg): Erythromycin base or ethylsuccinate 50 mg/kg/day PO divided into 4 doses daily for 14 days
- Preferred regimen (≥ 45 kg & < 8 years): Azithromycin 1 g PO in a single dose
- Preferred regimen (≥ 8 years): Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
# Chorioamnionitis
- Antibiotics
- Preferred regime: Ampicillin 2 g intravenously every 6 h OR Penicillin 5x106 units intravenously every 6 h AND Gentamicin 1.5 mg/kg every 8 h
- NOTE (1): Cephalosporins are generally recommended for women with chorioamnionitis who are allergic to Penicillin
- NOTE (2): In women with anaphylaxis to Penicillin a recommendation is to substitute Clindamycin 900 mg every 8 h
- NOTE (3): In the non-obstetric population, daily dosing of Gentamicin appears to be more effective, convenient, and cost-effective as well as less toxic.
- NOTE (4): Recommends the addition of a drug with enhanced anaerobic coverage, such as Clindamycin every 8 hours OR Metronidazole, in those cases of chorioamnionitis that require cesarean delivery
- NOTE (5): chorioamnionitis is a contraindication to the administration of Corticosteroids. Women with intra-amniotic infection have traditionally been excluded from randomized trials of corticosteroid therapy.
- Supportive measures
- Preferred regime: Antipyretics (Acetaminophen)
- Prevention
- Preferred regime: Macrolide (Erythromycin OR Azithromycin) AND Ampicillin for 7–10 days via intravenous (2 days) followed by oral routes.
- NOTE: Induction of labor and delivery for preterm premature rupture of membranes (PPROM) after 34 weeks’ gestation is recommended.
# Cystitis
- Acute Uncomplicated Cystitis
- Preferred regime: Nitrofurantoin monohydrate/macrocrystals 100 mg bid 5 days (avoid if early pyelonephritis suspected) OR Trimethoprim-sulfamethoxazole 160/800 mg (one DS tablet) bid 3 days (avoid if resistance prevalence is known to exceed 20 or if used for UTI in previous 3 months) OR Fosfomycin trometamol 3 gm single dose (lower efficacy than some other recommended agents; avoid if early pyelonephritis suspected) OR Pivmecillinam 400 mg bid 5 days (lower efficacy than some other recommended agents; avoid if early pyelonephritis suspected)
- Alternative regime (1): Fluoroquinolones, Ofloxacin, Ciprofloxacin, and Levofloxacin, use for 3 days.
- Alternative regime (2): β-Lactam agents, including Amoxicillin-clavulanate, Cefdinir, Cefaclor, and Cefpodoxime-proxetil, for 3–7-days
# Epididymitis
- Preferred regime: Ceftriaxone 250 mg IM in a single dose AND Doxycycline 100 mg orally twice a day for 10 days
- For acute epididymitis most likely caused by enteric organisms
- Preferred regime: 500 mg orally once daily for 10 days OR Ofloxacin 300 mg orally twice a day for 10 days
- NOTE: Patients who have uncomplicated acute epididymitis and also are infected with HIV should receive the same treatment regimen as those who are HIV negative.
# Genital herpes
- Genital herpes
- First episode of genital herpes
- Preferred regimen: Acyclovir 400 mg PO tid for 7–10 days OR Acyclovir 200 mg PO five times a day for 7–10 days OR Famciclovir 250 mg PO tid for 7–10 days OR Valacyclovir 1 g PO bid for 7–10 days
- Recurrent genital herpes
- Suppressive therapy
- Preferred regimen: Acyclovir 400 mg PO bid for 7–10 days OR Famciclovir 250 mg PO bid for 7–10 days OR Valacyclovir 1000 mg PO qd for 7–10 days OR Valacyclovir 500 mg PO qd for 7–10 days
- Episodic therapy
- Preferred regimen: Acyclovir 400 mg PO tid for 5 days OR Acyclovir 800 mg PO bid a day for 5 days OR Acyclovir 800 mg PO tid for 2 days OR Famciclovir 125 mg PO bid for 5 days OR Famciclovir 1000 mg PO bid for 1 day OR Famciclovir 500 mg PO once, followed by 250 mg PO bid for 2 days OR Valacyclovir 500 mg PO bid for 3 days OR Valacyclovir 1000 mg PO qd for 5 days
- Severe genital herpes
- Preferred regimen: Acyclovir 5–10 mg/kg IV q8h for 2–7 days or until clinical improvement is observed, followed by PO antiviral therapy to complete at least 10 days of total therapy.
- Genital herpes in HIV-infected patients
- Suppressive therapy
- Preferred regimen: Acyclovir 400–800 mg PO bid–tid OR Famciclovir 500 mg PO bid OR Valacyclovir 500 mg PO bid
- Episodic therapy
- Preferred regimen: Acyclovir 400 mg PO tid for 5–10 days OR Famciclovir 500 mg PO bid for 5–10 days OR Valacyclovir 1000 mg PO bid for 5–10 days
- Acyclovir-resistant genital herpes
- Preferred regimen: Foscarnet 40 mg/kg IV q8h until clinical resolution is attained,
- Alternative regimen: Cidofovir 5 mg/kg once weekly OR Imiquimod topically qd for 5 days
- Genital herpes in pregnancy
- Acyclovir can be administered orally to pregnant women with first episode of genital herpes or recurrent genital herpes.
- Acyclovir should be administered IV to pregnant women with severe genital herpes.
- Neonatal herpes, known or suspected
- Disease limited to the skin and mucous membranes
- Preferred regimen: Acyclovir 20 mg/kg IV q8h for 14 days
- Disseminated and CNS disease
- Preferred regimen: Acyclovir 20 mg/kg IV q8h for 21 days
# Gonococcal infections
- Gonococcal infections (Neisseria gonorrhoeae infection)
- Gonococcal infections in adolescents and adults
- Uncomplicated gonococcal infections of the cervix, urethra, and rectum
- Preferred regimen (1): Ceftriaxone 250 mg IM as a single dose
- Preferred regimen (2): Cefixime 400 mg PO as a single dose
- Preferred regimen (3): Cephalosporin single-dose injectable regimen AND (Azithromycin 1 g PO as a single dose OR Doxycycline 100 mg PO bid for 7 days)
- Alternative regimen: Cefpodoxime 400 mg PO as a single dose OR Azithromycin 2 g PO as a single dose
- Uncomplicated gonococcal infections of the pharynx
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND (Azithromycin 1 g PO as a single dose OR Doxycycline 100 mg PO bid for 7 days)
- Gonococcal conjunctivitis
- Preferred regimen: Ceftriaxone 1 g IM in a single dose
- Disseminated gonococcal infection
- Preferred regimen: Ceftriaxone 1 g IV/IM q24h
- Alternative regimen: Cefotaxime 1 g IV q8h OR Ceftizoxime 1 g IV q8h
- Gonococcal meningitis
- Preferred regimen: Ceftriaxone 1–2 g IV q12h for 10–14 days
- Gonococcal endocarditis
- Preferred regimen: Ceftriaxone 1–2 g IV q12h for at least 4 weeks
- Gonococcal infections among children
- Uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis
- Preferred regimen (> 45 kg): Ceftriaxone 250 mg IM as a single dose OR Cefixime 400 mg PO as a single dose
- Preferred regimen (≤ 45 kg): Ceftriaxone 125 mg IM in a single dose
- Bacteremia or arthritis
- Preferred regimen (> 45 kg): Ceftriaxone 50 mg/kg IM/IV q24h for 7 days
- Preferred regimen (≤ 45 kg): Ceftriaxone 50 mg/kg (maximum dose: 1 g) IM/IV q24h for 7 days
- Gonococcal infections among infants
- Disseminated gonococcal infection and gonococcal scalp abscesses in newborns
- Preferred regimen: Ceftriaxone 25–50 mg/kg IV/IM q24h for 7 days (10–14 days if meningitis is documented) OR Cefotaxime 25 mg/kg IV/IM q12h for 7 days (10–14 days if meningitis is documented)
- Prophylactic treatment for infants whose mothers have gonococcal infection
- Preferred regimen: Ceftriaxone 25–50 mg/kg IV/IM, not to exceed 125 mg
- Ophthalmia neonatorum
- Preferred regimen: Ceftriaxone 25–50 mg/kg IV/IM in a single dose, not to exceed 125 mg
- Ophthalmia neonatorum prophylaxis
- Preferred regimen: Erythromycin (0.5%) ophthalmic ointment in each eye in a single application
# Granuloma inguinale
- Granuloma inguinale (donovanosis)
- Preferred regimen: Doxycycline 100 mg PO bid for at least 3 weeks and until all lesions have completely healed
- Alternative regimen (1): Azithromycin 1 g PO once per week for at least 3 weeks and until all lesions have completely healed
- Alternative regimen (2): Ciprofloxacin 750 mg PO bid for at least 3 weeks and until all lesions have completely healed
- Alternative regimen (3): Erythromycin base 500 mg PO qid for at least 3 weeks and until all lesions have completely healed
- Alternative regimen (4): Trimethoprim-Sulfamethoxazole double-strength (160 mg/800 mg) one tablet PO bid for at least 3 weeks and until all lesions have completely healed
# Lymphogranuloma venereum
- Lymphogranuloma venereum (Chlamydia trachomatis serovars L1, L2, or L3 infection)
- Preferred regimen: Doxycycline 100 mg PO bid for 21 days
- Alternative regimen: Erythromycin base 500 mg PO qid for 21 days
# Pelvic inflammatory disease
- Parenteral Treatment
- Preferred regime (1): Cefotetan 2 g IV every 12 hours OR Cefoxitin 2 g IV every 6 hours AND Doxycycline 100 mg orally or IV every 12 hours.
- Preferred regime (2): Clindamycin 900 mg IV every 8 hours AND Gentamicin loading dose IV or IM (2 mg/kg of body weight), followed by a maintenance dose (1.5 mg/kg) every 8 hours. Single daily dosing (3--5 mg/kg) can be substituted.
- Alternative regime: Ampicillin/Sulbactam 3 g IV every 6 hours AND Doxycycline 100 mg orally or IV every 12 hours.
- Oral Treatment
- Preferred regime (1): Ceftriaxone 250 mg IM in a single dose AND Doxycycline 100 mg orally twice a day for 14 days ± Metronidazole 500 mg orally twice a day for 14 days
- Preferred regime (2): Cefoxitin 2 g IM in a single dose and Probenecid, 1 g orally administered concurrently in a single dose AND Doxycycline 100 mg orally twice a day for 14 days ± Metronidazole 500 mg orally twice a day for 14 days
- Preferred regime (3): Other parenteral third-generation cephalosporin (e.g., ceftizoxime OR cefotaxime) AND Doxycycline 100 mg orally twice a day for 14 days ± Metronidazole 500 mg orally twice a day for 14 days
- Alternative regime (1): Ceftriaxone 250 mg IM single dose and Azithromycin 1 g orally once a week for 2 weeks.
- Alternative regime (2): Levofloxacin 500 mg orally once daily or Ofloxacin 400 mg twice daily for 14 days {{withorwithout]] Metronidazole 500 mg orally twice daily for 14 days.
# Proctocolitis
- Proctitis
- Preferred regime: Ceftriaxone 250 mg IM AND Doxycycline 100 mg orally twice a day for 7 days
# Prostatitis
## Acute Bacterial Prostatitis
- Uncomplicated (with low risk of STD pathogens)
- Preferred regime: Ciprofloxacin 400 mg iv or 500 mg po BID or Levofloxacin 500–750 mg iv/po QD
- Alternative regime: TMP-SMX DS (160 mg TMP) BID
- NOTE: 2 weeks duration of therapy may be sufficient; if patient remains symptomatic, extend to 4 weeks
- Preferred regime: Ampicillin 1–2 g IV every 4 h OR Vancomycin 15 mg/kg every 12 h
- Alternative regime: Levofloxacin 750 po QD OR Linezolid 600 mg every 12 h
- NOTE: Use intravenous therapy if systemically ill; switch to oral therapy when stable
- Preferred regime: Ciprofloxacin 400 mg TID
- Alternative regime: Piperacillin-tazobactam 4.5 g iv every 6 h
- Uncomplicated (with risk of STD pathogens)
- Preferred regime: Ceftriaxone 250 mg IM OR Cefixime 400 mg po x 1 dose AND Doxycycline 100 mg po BID OR Azithromycin 500 mg po QD
- Alternative regime: Fluoroquinolones not recommended for gonococcal infection
- NOTE: Treat for 2 weeks in most cases. Obtain urine nucleicacid amplification test for N.gonorrhoeae and C.trachomatis
- Uncomplicated, with risk of antibiotic resistant pathogen
- Preferred regime: Ertapenem 1 g iv QD
- Alternative regime: Ceftriaxone 1 g iv QD or Imipenem 500mg iv every 6 h OR Tigecycline 100 mg iv x 1 dose then 50 mg iv every 12 h
- Preferred regime: Ertapenem 1 g iv QD
- Alternative regime: Cefepime 2g iv every 12 h OR Imipenem 500 mg iv every 6 h OR Tigecycline 100 mg iv x 1 dose then 50 mg iv every 12 h
- Preferred regime: Imipenem 500 mg iv every 6 h
- Alternative regime: Meropenem 500 mg iv every 8 h
- Complicated by bacteremia or suspected prostatic abscess
- Preferred regime: Ciprofloxacin 400 mg iv every 12 h OR Levofloxacin 500 mg iv every 24 h
- Alternative regime: Ceftriaxone 1–2 g iv every 24 h AND Levofloxacin 500–750 mg po QD OR Ertapenem 1 g iv every 24 h OR piperacillin-tazobactam 3.375 g iv every 6 h
- NOTE: Treat for 4 weeks. Obtain blood cultures; Consider genitourinary imaging; Change iv to po regimen when blood cultures are sterile and abscess drained.
## Chronic Bacterial Prostatitis
- Preferred regime: Ciprofloxacin 400 mg iv every 12 h OR Levofloxacin 500 mg iv every 24 h
- Alternative regime: TMP-SMX x 1 dose DS BID
- Preferred regime: Azithromycin 500 mg po QD
- Alternative regime: Doxycycline 100 mg BID
# Pyelonephritis
- Condition 1: patients not requiring hospitalization where the prevalence of resistance of community uropathogens to fluoroquinolones is not known to exceed 10%
- Preferred regime: Ciprofloxacin orally 500 mg twice daily for 7 days ± an initial 400-mg dose of intravenous Ciprofloxacin
- NOTE (1): If an initial one-time intravenous agent is used, a long-acting antimicrobial, such as 1 g of Ceftriaxone or a consolidated 24-h dose of an Aminoglycoside, could be used in lieu of an intravenous fluoroquinolone
- NOTE (2): If the prevalence of fluoroquinolone resistance is thought to exceed 10%, an initial one-time intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of ceftriaxone or a consolidated 24-h dose of an aminoglycoside, is recommended.
- Alternative regime: A once-daily oral fluoroquinolone, including Ciprofloxacin 1000 mg extended release for 7 days OR Levofloxacin 750 mg for 5 days.
- NOTE: If the prevalence of fluoroquinolone resistance is thought to exceed 10%, an initial intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of Ceftriaxone or a consolidated 24-h dose of an Aminoglycoside, is recommended.
- Condition 2: When the uropathogen is known to be susceptible
- Preferred regime: Trimethoprim-sulfamethoxazole 160/800 mg (1 double-strength tablet) bid orally for 14 days.
- NOTE: If trimethoprim-sulfamethoxazole is used when the susceptibility is not known, an initial intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of ceftriaxone OR a consolidated 24-h dose of an aminoglycoside, is recommended.
- NOTE: Oral β-lactam agents are less effective than other available agents for treatment of pyelonephritis. If an oral β-lactam agent is used, an initial intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of ceftriaxone OR a consolidated 24-h dose of an aminoglycoside, is recommended.
- Condition 3: Patients require hospitalization (high fever, high white blood cell count, vomiting, dehydration, or evidence of sepsis)
- Preferred regime: intravenous antimicrobial regimen, such as a Fluoroquinolone; an Aminoglycoside ± Ampicillin; an extended-spectrum Cephalosporin or extended-spectrum Penicillin ± an Aminoglycoside; Carbapenem
- NOTE: The choice between these agents should be based on local resistance data, and the regimen should be tailored on the basis of susceptibility results.
# Sterile pyuria
- Sterile pyuria
- Definitions
- Pyuria: the presence of 10 or more white cells per cubic millimeter in a urine specimen, 3 or more white cells per high-power field of unspun urine, a positive result on Gram’s stain of an unspun urine specimen, or a urinary dipstick test that is positive for leukocyte esterase
- Sterile pyuria: the persistent finding of white cells in the urine in the absence of bacteria, as determined by means of aerobic laboratory techniques (on a 5% sheep-blood agar plate and MacConkey agar plate)
- Bacteriuria: bacterial colony counts of more than 1000 colony-forming units (CFU) per milliliter in urine
- Causes
- Infectious etiologies
- Gynecologic infection
- Urethritis due to chlamydia, Neisseria gonorrhoeae, mycoplasma, or ureaplasma
- Prostatitis
- Balanitis
- Appendicitis
- Viral infection of the lower genitourinary tract
- Genitourinary tuberculosis
- Fungal infection
- Parasitic disease such as trichomoniasis or schistosomiasis
- Non-infectious etiologies
- Current use of antibiotics
- Recently treated urinary tract infection (within past 2 weeks)
- Presence or recent use of a urinary catheter
- Recent cystoscopy or urologic endoscopy
- Urinary tract stones
- Foreign body such as surgical mesh in the urethra or a retained stent
- Urinary tract neoplasm
- Pelvic irradiation
- Urinary fistula
- Polycystic kidney
- Rejection of a renal transplant
- Renal-vein thrombosis
- Interstitial nephritis or analgesic nephropathy
- Papillary necrosis
- Interstitial cystitis
- Inflammatory disease such as systemic lupus erythematosus or Kawasaki’s disease
- Pathogen-directed antimicrobial therapy
- Tuberculosis
- Preferred regimen: Isoniazid AND Rifampin AND Ethambutol AND Pyrazinamide for 3–6 months
- Gonorrhea
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose, then (Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days)
- Chlamydia
- Preferred regimen: Azithromycin 1 g PO in single dose OR Doxycycline 100 mg PO bid for 7 days
- Alternative regimen: Erythromycin base 500 mg PO qid for 7 days
- Mycoplasma and ureaplasma
- Preferred regimen: Azithromycin OR Levofloxacin OR Moxifloxacin
- Genital herpes
- Preferred regimen: Acyclovir 400 mg PO tid for 7–10 days or Acyclovir 200 mg PO five times a day for 7–10 days OR Famciclovir 250 mg PO tid for 7–10 days OR Valacyclovir 1 g PO bid for 7 days
- Trichomoniasis
- Preferred regimen: Metronidazole 2 g PO in a single dose) OR Tinidazole 2 g PO in a single dose
- Fungal infections
- Preferred regimen: Fluconazole OR Posaconazole OR Echinocandins OR Amphotericin B
- Schistosomiasis
- Preferred regimen: Praziquantel 20 mg/kg PO bid for 1–2 days
# Syphilis
- Syphilis (Treponema pallidum)
- Non–HIV-infected persons
- Primary and secondary syphilis
- Preferred regimen (adult): Benzathine penicillin G 2.4 MU IM in a single dose
- Preferred regimen (pediatric): Benzathine penicillin G 50,000 units/kg (up to 2.4 MU) IM in a single dose
- Latent syphilis
- Early latent syphilis
- Preferred regimen (adult): Benzathine penicillin G 2.4 MU IM in a single dose
- Preferred regimen (pediatric): Benzathine penicillin G 50,000 units/kg (up to 2.4 MU) IM in a single dose
- Late latent syphilis or unknown duration
- Preferred regimen (adult): Benzathine penicillin G 2.4 MU IM for 3 doses, each at 1-week intervals
- Preferred regimen (pediatric): Benzathine penicillin G 50,000 units/kg (up to 2.4 MU) IM, administered as 3 doses at 1-week intervals
- Tertiary syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM for 3 doses, each at 1-week intervals
- Neurosyphilis
- Preferred regimen: Aqueous crystalline penicillin G 3–4 MU IV q4h or continuously for 10–14 days
- Alternative regimen: Procaine penicillin G 2.4 MU IM q24h for 10–14 days AND Probenecid 500 mg PO qid for 10–14 days
- HIV-infected persons
- Primary and secondary syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM in a single dose
- Latent syphilis
- Early latent syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM in a single dose
- Late latent syphilis or unknown duration
- Preferred regimen: Benzathine penicillin G 2.4 MU IM for 3 doses, each at 1-week intervals
- Tertiary syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM for 3 doses, each at 1-week intervals
- Neurosyphilis
- Preferred regimen: Penicillin G 3–4 MU IV q4h or continuously for 10–14 days
- Alternative regimen: Procaine penicillin G 2.4 MU IM q24h for 10–14 days AND Probenecid 500 mg PO qid for 10–14 days
- During pregnancy
- Preferred regimen: Pregnant women should be treated with the Penicillin regimen appropriate for their stage of infection.
- Congenital syphilis
- Infants with proven or highly probable disease AND (abnormal physical examination consistent with congenital syphilis OR nontreponemal serologic titer fourfold higher than the mother's titer OR a positive darkfield test of body fluids)
- Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days OR Procaine penicillin G 50,000 U/kg IM in a single daily dose for 10 days
- Infants who have a normal physical examination AND nontreponemal serologic titer the same or less than fourfold the maternal titer AND (mother was not treated adequately OR mother has no documentation of having received treatment OR mother was treated with Erythromycin or another non-Penicillin regimen OR mother received treatment < 4 weeks before delivery)
- Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days OR Procaine penicillin G 50,000 U/kg IM in a single daily dose for 10 days OR Benzathine penicillin G 50,000 U/kg IM in a single dose
- Infants who have a normal physical examination AND nontreponemal serologic titer the same or less than fourfold the maternal titer AND mother was treated during pregnancy AND treatment was appropriate for the stage of infection AND treatment administered > 4 weeks before delivery AND mother has no evidence of reinfection or relapse
- Preferred regimen: Benzathine penicillin G 50,000 U/kg IM in a single dose
- Infants who have a normal physical examination AND nontreponemal serologic titer the same or less than fourfold the maternal titer AND mother's treatment was adequate before pregnancy AND mother's nontreponemal serologic titer remained low and stable before and during pregnancy and at delivery (VDRL < 1:2; RPR < 1:4)
- Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg q4–6h for 10 days
# Urethritis
- Urethritis
- Nongonococcal urethritis
- Preferred regimen: Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
- Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days
- Recurrent and persistent urethritis
- Preferred regimen: Metronidazole 2 g PO in a single dose OR Tinidazole 2 g PO in a single dose AND Azithromycin 1 g PO in a single dose | Sandbox g42
## Asymptomatic bacteriuria
- Asymptomatic bacteriuria[1][2]
- Definitions
- For women: two consecutive voided urine specimens with isolation of the same bacterial strain in quantitative counts ≥ 105 cfu/mL
- For men: a single, clean-catch voided urine specimen with 1 bacterial species isolated in a quantitative count ≥ 105 cfu/mL
- For catheterized urine specimen: a single catheterized urine specimen with 1 bacterial species isolated in a quantitative count ≥ 10>2 cfu/mL
- Causative pathogens
- Escherichia coli
- Klebsiella pneumoniae
- Coagulase-negative staphylococci
- Enterococcus
- Group B streptococci
- Gardnerella vaginalis
- Pseudomonas aeruginosa, Proteus mirabilis, Providencia stuartii, Morganella morganii (common in patients with long-term urologic device in place)
- Empiric antimicrobial therapy
- Treatment of asymptomatic bacteriuria is not recommended for the following persons:
- Premenopausal, nonpregnant women
- Diabetic women
- Older persons residing in the community
- Elderly, institutionalized subjects
- Persons with spinal cord injury
- Catheterized patients while the catheter remains in situ
- Specific considerations
- Men
- Screening for or treatment of asymptomatic bacteriuria in men is not recommended.
- Women, premenopausal, nonpregnant
- Screening for or treatment of asymptomatic bacteriuria in premenopausal, nonpregnant women is not indicated.
- Women, pregnant[3]
- Preferred regimen (1): Nitrofurantoin 100 mg PO bid for 3–5 days (avoid in glucose-6-phosphate dehydrogenase deficiency)
- Preferred regimen (2): Amoxicillin 500 mg tid for 3–5 days
- Preferred regimen (3): Amoxicillin-Clavulanate 500 mg bid for 3–5 days
- Preferred regimen (4): Cephalexin 500 mg tid for 3–5 days
- Preferred regimen (5): Fosfomycin 3 g as a single dose
- Preferred regimen (6): Trimethoprim bid for 3–5 days (only after first trimester)
- Women, diabetic
- Screening for or treatment of asymptomatic bacteriuria in diabetic women is not recommended.
- Older persons residing in the community
- Screening for or treatment of asymptomatic bacteriuria in older persons residing in the community is not recommended.
- Elderly institutionalized subjects
- Screening for or treatment of asymptomatic bacteriuria in elderly institutionalized residents of longterm care facilities is not recommended.
- Subjects with spinal cord injuries
- Screening for or treatment of asymptomatic bacteriuria in subjects with spinal cord injuries is not recommended.
- Patients with indwelling urethral catheters
- Screening for or treatment of asymptomatic bacteriuria in patients with indwelling urethral catheters is not recommended.
- Urologic interventions[4]
- Screening for or treatment of asymptomatic bacteriuria before transurethral resection of the prostate is recommended.
- Preferred regimen: Trimethoprim-Sulfamethoxazole DS 1 tab bid for 3 days after obtaining urine cultures
## Ectoparasitic Infections
### Pediculosis Pubis
- Preferred regime: Permethrin 1% cream rinse applied to affected areas and washed off after 10 minutes OR Pyrethrins with piperonyl butoxide applied to the affected area and washed off after 10 minutes
- Alternative regime: Malathion 0.5% lotion applied for 8--12 hours and washed off OR Ivermectin 250 µg/kg orally, repeated in 2 weeks
### Scabies
- Preferred regime: Permethrin cream (5%) applied to all areas of the body from the neck down and washed off after 8--14 hours OR Ivermectin 200ug/kg orally, repeated in 2 weeks
- Alternative regime: Lindane (1%) 1 oz. of lotion (or 30 g of cream) applied in a thin layer to all areas of the body from the neck down and thoroughly washed off after 8 hours
## Human papillomavirus infection
### Genital Warts
- Patient-Applied:
- Preferred regime: Podofilox 0.5% solution or gel OR Imiquimod 5% cream OR Sinecatechins 15% ointment
- Provider--Administered:
- Preferred regime: Cryotherapy with liquid nitrogen or cryoprobe, repeat applications every 1-2 weeks OR Podophyllin resin 10%-25% in a compound tincture of benzoin OR Trichloroacetic acid (TCA) OR Bichloroacetic acid (BCA) 80%-90% OR Surgical removal either by tangential scissor excision, tangential shave excision, curettage, or electrosurgery.
- Alternative regime: intralesional interferon, photodynamic therapy, and topical [[Cidofovir].
- Preferred regime: For women who have exophytic cervical warts, a biopsy evaluation to exclude high-grade SIL must be performed before treatment is initiated. Management of exophytic cervical warts should include consultation with a specialist.
- Preferred regime: Cryotherapy with liquid nitrogen. The use of a cryoprobe in the vagina is not recommended because of the risk for vaginal perforation and fistula formation OR TCA or BCA 80%--90% applied to warts. A small amount should be applied only to warts and allowed to dry, at which time a white frosting develops. If an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate, or liquid soap preparations to remove unreacted acid. This treatment can be repeated weekly, if necessary.
- Preferred regime: Cryotherapy with liquid nitrogen OR Podophyllin 10%--25% in compound tincture of benzoin. The treatment area and adjacent normal skin must be dry before contact with podophyllin. This treatment can be repeated weekly, if necessary. The safety of podophyllin during pregnancy has not been established. Data are limited on the use of podofilox and imiquimod for treatment of distal meatal warts.
- Preferred regime: Cryotherapy with liquid nitrogen OR TCA or BCA 80%--90% applied to warts. A small amount should be applied only to warts and allowed to dry, at which time a white frosting develops. If an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate, or liquid soap preparations to remove unreacted acid. This treatment can be repeated weekly, if necessary. OR Surgical removal
## Vaginal infection
### Bacterial vaginosis
- Preferred regime: Metronidazole 500 mg orally twice a day for 7 days OR Metronidazole gel 0.75%, one full applicator (5 g) intravaginally, once a day for 5 days OR Clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7 days
- Alternative regime (1): Tinidazole 2 g orally once daily for 3 days
- Alternative regime (2): Tinidazole 1 g orally once daily for 5 days
- Alternative regime (3): Clindamycin 300 mg orally twice daily for 7 days
- Alternative regime (4): Clindamycin ovules 100 mg intravaginally once at bedtime for 3 days
- Preferred regime: Metronidazole 500 mg orally twice a day for 7 days OR Metronidazole 250 mg orally three times a day for 7 days OR Clindamycin 300 mg orally twice a day for 7 days
### Trichomoniasis
T. vaginalis
- Preferred regime: Metronidazole 2 g orally in a single dose OR Tinidazole 2 g orally in a single dose
- Alternative regime: Metronidazole 500 mg orally twice a day for 7 days
- Preferred regime: 2 g Metronidazole in a single dose at any stage of pregnancy, withholding breastfeeding during treatment and for 12--24 hours after the last dose will reduce the exposure of the infant to metronidazole.
### Vulvovaginal candidiasis
- Preferred regime:
- Over-the-Counter Intravaginal Agents: Butoconazole 2% cream 5 g intravaginally for 3 days OR Clotrimazole 1% cream 5 g intravaginally for 7--14 days OR Clotrimazole 2% cream 5 g intravaginally for 3 days OR [Miconazole]] 2% cream 5 g intravaginally for 7 days OR Miconazole 4% cream 5 g intravaginally for 3 days OR Miconazole 100 mg vaginal suppository, one suppository for 7 days OR Miconazole 200 mg vaginal suppository, one suppository for 3 days OR Miconazole 1,200 mg vaginal suppository, one suppository for 1 day OR Tioconazole 6.5% ointment 5 g intravaginally in a single application
- Prescription Intravaginal Agents: Butoconazole 2% cream (single dose bioadhesive product), 5 g intravaginally for 1 day OR Nystatin 100,000-unit vaginal tablet, one tablet for 14 days OR Terconazole 0.4% cream 5 g intravaginally for 7 days OR Terconazole 0.8% cream 5 g intravaginally for 3 days OR Terconazole 80 mg vaginal suppository, one suppository for 3 days
- Oral Agent: Fluconazole 150 mg oral tablet, one tablet in single dose
- Recurrent Vulvovaginal Candidiasis (RVVC)
- Preferred regime: 7-14 days of topical therapy OR a 100-mg, 150-mg, or 200-mg oral dose of Fluconazole every third day for a total of 3 doses followed by Oral Fluconazole (i.e., 100-mg, 150-mg, or 200-mg dose) weekly for 6 months
- Severe VVC
- Preferred regime: Topical Azole for 7-14 days OR 150 mg of Fluconazole in two sequential doses (second dose 72 hours after initial dose.
- Nonalbicans VVC
- Preferred regime: nonfluconazole Azole drug (oral or topical) for 7-14 days.
- Preferred regime: topical Azole therapies for 7 days
## Cervicitis
- Cervicitis[5]
- Preferred regimen: Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
## Chancroid
- Chancroid (Haemophilus ducreyi infection)[6]
- Preferred regimen: Azithromycin 1 g PO as a single dose OR Ceftriaxone 250 mg IM as a single dose OR Ciprofloxacin 500 mg PO bid for 3 days OR Erythromycin 500 mg PO tid for 7 days
## Chlamydial infections
- Chlamydial infections[7]
- Chlamydial infections in adolescents and adults
- Preferred regimen: Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
- Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days
- Chlamydial infections during pregnancy
- Preferred regimen: Azithromycin 1 g PO in a single dose OR Amoxicillin 500 mg PO tid for 7 days
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin base 250 mg PO qid for 14 days
- Alternative regimen (3): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (4): Erythromycin ethylsuccinate 400 mg PO qid for 14 days
- Chlamydial infections among infants
- Ophthalmia neonatorum caused by C. trachomatis
- Preferred regimen: Erythromycin base or ethylsuccinate 50 mg/kg/day PO divided into 4 doses daily for 14 days
- Infant pneumonia caused by C. trachomatis
- Preferred regimen (< 45 kg): Erythromycin base or ethylsuccinate 50 mg/kg/day PO divided into 4 doses daily for 14 days
- Preferred regimen (≥ 45 kg & < 8 years): Azithromycin 1 g PO in a single dose
- Preferred regimen (≥ 8 years): Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
## Chorioamnionitis
- Antibiotics [8]
- Preferred regime: Ampicillin 2 g intravenously every 6 h OR Penicillin 5x106 units intravenously every 6 h AND Gentamicin 1.5 mg/kg every 8 h
- NOTE (1): Cephalosporins are generally recommended for women with chorioamnionitis who are allergic to Penicillin
- NOTE (2): In women with anaphylaxis to Penicillin a recommendation is to substitute Clindamycin 900 mg every 8 h
- NOTE (3): In the non-obstetric population, daily dosing of Gentamicin appears to be more effective, convenient, and cost-effective as well as less toxic.
- NOTE (4): Recommends the addition of a drug with enhanced anaerobic coverage, such as Clindamycin every 8 hours OR Metronidazole, in those cases of chorioamnionitis that require cesarean delivery
- NOTE (5): chorioamnionitis is a contraindication to the administration of Corticosteroids. Women with intra-amniotic infection have traditionally been excluded from randomized trials of corticosteroid therapy.
- Supportive measures
- Preferred regime: Antipyretics (Acetaminophen)
- Prevention [9]
- Preferred regime: Macrolide (Erythromycin OR Azithromycin) AND Ampicillin for 7–10 days via intravenous (2 days) followed by oral routes.
- NOTE: Induction of labor and delivery for preterm premature rupture of membranes (PPROM) after 34 weeks’ gestation is recommended.
## Cystitis
- Acute Uncomplicated Cystitis
- Preferred regime: Nitrofurantoin monohydrate/macrocrystals 100 mg bid 5 days (avoid if early pyelonephritis suspected) OR Trimethoprim-sulfamethoxazole 160/800 mg (one DS tablet) bid 3 days (avoid if resistance prevalence is known to exceed 20 or if used for UTI in previous 3 months) OR Fosfomycin trometamol 3 gm single dose (lower efficacy than some other recommended agents; avoid if early pyelonephritis suspected) OR Pivmecillinam 400 mg bid 5 days (lower efficacy than some other recommended agents; avoid if early pyelonephritis suspected)
- Alternative regime (1): Fluoroquinolones, Ofloxacin, Ciprofloxacin, and Levofloxacin, use for 3 days.
- Alternative regime (2): β-Lactam agents, including Amoxicillin-clavulanate, Cefdinir, Cefaclor, and Cefpodoxime-proxetil, for 3–7-days
## Epididymitis
- Preferred regime: Ceftriaxone 250 mg IM in a single dose AND Doxycycline 100 mg orally twice a day for 10 days
- For acute epididymitis most likely caused by enteric organisms
- Preferred regime: [[Levofloxacin] 500 mg orally once daily for 10 days OR Ofloxacin 300 mg orally twice a day for 10 days
- NOTE: Patients who have uncomplicated acute epididymitis and also are infected with HIV should receive the same treatment regimen as those who are HIV negative.
## Genital herpes
- Genital herpes[10]
- First episode of genital herpes
- Preferred regimen: Acyclovir 400 mg PO tid for 7–10 days OR Acyclovir 200 mg PO five times a day for 7–10 days OR Famciclovir 250 mg PO tid for 7–10 days OR Valacyclovir 1 g PO bid for 7–10 days
- Recurrent genital herpes
- Suppressive therapy
- Preferred regimen: Acyclovir 400 mg PO bid for 7–10 days OR Famciclovir 250 mg PO bid for 7–10 days OR Valacyclovir 1000 mg PO qd for 7–10 days OR Valacyclovir 500 mg PO qd for 7–10 days
- Episodic therapy
- Preferred regimen: Acyclovir 400 mg PO tid for 5 days OR Acyclovir 800 mg PO bid a day for 5 days OR Acyclovir 800 mg PO tid for 2 days OR Famciclovir 125 mg PO bid for 5 days OR Famciclovir 1000 mg PO bid for 1 day OR Famciclovir 500 mg PO once, followed by 250 mg PO bid for 2 days OR Valacyclovir 500 mg PO bid for 3 days OR Valacyclovir 1000 mg PO qd for 5 days
- Severe genital herpes
- Preferred regimen: Acyclovir 5–10 mg/kg IV q8h for 2–7 days or until clinical improvement is observed, followed by PO antiviral therapy to complete at least 10 days of total therapy.
- Genital herpes in HIV-infected patients
- Suppressive therapy
- Preferred regimen: Acyclovir 400–800 mg PO bid–tid OR Famciclovir 500 mg PO bid OR Valacyclovir 500 mg PO bid
- Episodic therapy
- Preferred regimen: Acyclovir 400 mg PO tid for 5–10 days OR Famciclovir 500 mg PO bid for 5–10 days OR Valacyclovir 1000 mg PO bid for 5–10 days
- Acyclovir-resistant genital herpes
- Preferred regimen: Foscarnet 40 mg/kg IV q8h until clinical resolution is attained,
- Alternative regimen: Cidofovir 5 mg/kg once weekly OR Imiquimod topically qd for 5 days
- Genital herpes in pregnancy
- Acyclovir can be administered orally to pregnant women with first episode of genital herpes or recurrent genital herpes.
- Acyclovir should be administered IV to pregnant women with severe genital herpes.
- Neonatal herpes, known or suspected
- Disease limited to the skin and mucous membranes
- Preferred regimen: Acyclovir 20 mg/kg IV q8h for 14 days
- Disseminated and CNS disease
- Preferred regimen: Acyclovir 20 mg/kg IV q8h for 21 days
## Gonococcal infections
- Gonococcal infections (Neisseria gonorrhoeae infection)[11][12]
- Gonococcal infections in adolescents and adults
- Uncomplicated gonococcal infections of the cervix, urethra, and rectum
- Preferred regimen (1): Ceftriaxone 250 mg IM as a single dose
- Preferred regimen (2): Cefixime 400 mg PO as a single dose
- Preferred regimen (3): Cephalosporin single-dose injectable regimen AND (Azithromycin 1 g PO as a single dose OR Doxycycline 100 mg PO bid for 7 days)
- Alternative regimen: Cefpodoxime 400 mg PO as a single dose OR Azithromycin 2 g PO as a single dose
- Uncomplicated gonococcal infections of the pharynx
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose AND (Azithromycin 1 g PO as a single dose OR Doxycycline 100 mg PO bid for 7 days)
- Gonococcal conjunctivitis
- Preferred regimen: Ceftriaxone 1 g IM in a single dose
- Disseminated gonococcal infection
- Preferred regimen: Ceftriaxone 1 g IV/IM q24h
- Alternative regimen: Cefotaxime 1 g IV q8h OR Ceftizoxime 1 g IV q8h
- Gonococcal meningitis
- Preferred regimen: Ceftriaxone 1–2 g IV q12h for 10–14 days
- Gonococcal endocarditis
- Preferred regimen: Ceftriaxone 1–2 g IV q12h for at least 4 weeks
- Gonococcal infections among children
- Uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis
- Preferred regimen (> 45 kg): Ceftriaxone 250 mg IM as a single dose OR Cefixime 400 mg PO as a single dose
- Preferred regimen (≤ 45 kg): Ceftriaxone 125 mg IM in a single dose
- Bacteremia or arthritis
- Preferred regimen (> 45 kg): Ceftriaxone 50 mg/kg IM/IV q24h for 7 days
- Preferred regimen (≤ 45 kg): Ceftriaxone 50 mg/kg (maximum dose: 1 g) IM/IV q24h for 7 days
- Gonococcal infections among infants
- Disseminated gonococcal infection and gonococcal scalp abscesses in newborns
- Preferred regimen: Ceftriaxone 25–50 mg/kg IV/IM q24h for 7 days (10–14 days if meningitis is documented) OR Cefotaxime 25 mg/kg IV/IM q12h for 7 days (10–14 days if meningitis is documented)
- Prophylactic treatment for infants whose mothers have gonococcal infection
- Preferred regimen: Ceftriaxone 25–50 mg/kg IV/IM, not to exceed 125 mg
- Ophthalmia neonatorum
- Preferred regimen: Ceftriaxone 25–50 mg/kg IV/IM in a single dose, not to exceed 125 mg
- Ophthalmia neonatorum prophylaxis
- Preferred regimen: Erythromycin (0.5%) ophthalmic ointment in each eye in a single application
## Granuloma inguinale
- Granuloma inguinale (donovanosis)[13]
- Preferred regimen: Doxycycline 100 mg PO bid for at least 3 weeks and until all lesions have completely healed
- Alternative regimen (1): Azithromycin 1 g PO once per week for at least 3 weeks and until all lesions have completely healed
- Alternative regimen (2): Ciprofloxacin 750 mg PO bid for at least 3 weeks and until all lesions have completely healed
- Alternative regimen (3): Erythromycin base 500 mg PO qid for at least 3 weeks and until all lesions have completely healed
- Alternative regimen (4): Trimethoprim-Sulfamethoxazole double-strength (160 mg/800 mg) one tablet PO bid for at least 3 weeks and until all lesions have completely healed
## Lymphogranuloma venereum
- Lymphogranuloma venereum (Chlamydia trachomatis serovars L1, L2, or L3 infection)[14]
- Preferred regimen: Doxycycline 100 mg PO bid for 21 days
- Alternative regimen: Erythromycin base 500 mg PO qid for 21 days
## Pelvic inflammatory disease
- Parenteral Treatment
- Preferred regime (1): Cefotetan 2 g IV every 12 hours OR Cefoxitin 2 g IV every 6 hours AND Doxycycline 100 mg orally or IV every 12 hours.
- Preferred regime (2): Clindamycin 900 mg IV every 8 hours AND Gentamicin loading dose IV or IM (2 mg/kg of body weight), followed by a maintenance dose (1.5 mg/kg) every 8 hours. Single daily dosing (3--5 mg/kg) can be substituted.
- Alternative regime: Ampicillin/Sulbactam 3 g IV every 6 hours AND Doxycycline 100 mg orally or IV every 12 hours.
- Oral Treatment
- Preferred regime (1): Ceftriaxone 250 mg IM in a single dose AND Doxycycline 100 mg orally twice a day for 14 days ± Metronidazole 500 mg orally twice a day for 14 days
- Preferred regime (2): Cefoxitin 2 g IM in a single dose and Probenecid, 1 g orally administered concurrently in a single dose AND Doxycycline 100 mg orally twice a day for 14 days ± Metronidazole 500 mg orally twice a day for 14 days
- Preferred regime (3): Other parenteral third-generation cephalosporin (e.g., ceftizoxime OR cefotaxime) AND Doxycycline 100 mg orally twice a day for 14 days ± Metronidazole 500 mg orally twice a day for 14 days
- Alternative regime (1): Ceftriaxone 250 mg IM single dose and Azithromycin 1 g orally once a week for 2 weeks.
- Alternative regime (2): Levofloxacin 500 mg orally once daily or Ofloxacin 400 mg twice daily for 14 days {{withorwithout]] Metronidazole 500 mg orally twice daily for 14 days.
## Proctocolitis
- Proctitis
- Preferred regime: Ceftriaxone 250 mg IM AND Doxycycline 100 mg orally twice a day for 7 days
## Prostatitis
### Acute Bacterial Prostatitis
- Uncomplicated (with low risk of STD pathogens)[15]
- Preferred regime: Ciprofloxacin 400 mg iv or 500 mg po BID or Levofloxacin 500–750 mg iv/po QD
- Alternative regime: TMP-SMX DS (160 mg TMP) BID
- NOTE: 2 weeks duration of therapy may be sufficient; if patient remains symptomatic, extend to 4 weeks
- Preferred regime: Ampicillin 1–2 g IV every 4 h OR Vancomycin 15 mg/kg every 12 h
- Alternative regime: Levofloxacin 750 po QD OR Linezolid 600 mg every 12 h
- NOTE: Use intravenous therapy if systemically ill; switch to oral therapy when stable
- Preferred regime: Ciprofloxacin 400 mg TID
- Alternative regime: Piperacillin-tazobactam 4.5 g iv every 6 h
- Uncomplicated (with risk of STD pathogens)
- Preferred regime: Ceftriaxone 250 mg IM OR Cefixime 400 mg po x 1 dose AND Doxycycline 100 mg po BID OR Azithromycin 500 mg po QD
- Alternative regime: Fluoroquinolones not recommended for gonococcal infection
- NOTE: Treat for 2 weeks in most cases. Obtain urine nucleicacid amplification test for N.gonorrhoeae and C.trachomatis
- Uncomplicated, with risk of antibiotic resistant pathogen
- Preferred regime: Ertapenem 1 g iv QD
- Alternative regime: Ceftriaxone 1 g iv QD or Imipenem 500mg iv every 6 h OR Tigecycline 100 mg iv x 1 dose then 50 mg iv every 12 h
- Preferred regime: Ertapenem 1 g iv QD
- Alternative regime: Cefepime 2g iv every 12 h OR Imipenem 500 mg iv every 6 h OR Tigecycline 100 mg iv x 1 dose then 50 mg iv every 12 h
- Preferred regime: Imipenem 500 mg iv every 6 h
- Alternative regime: Meropenem 500 mg iv every 8 h
- Complicated by bacteremia or suspected prostatic abscess
- Preferred regime: Ciprofloxacin 400 mg iv every 12 h OR Levofloxacin 500 mg iv every 24 h
- Alternative regime: Ceftriaxone 1–2 g iv every 24 h AND Levofloxacin 500–750 mg po QD OR Ertapenem 1 g iv every 24 h OR piperacillin-tazobactam 3.375 g iv every 6 h
- NOTE: Treat for 4 weeks. Obtain blood cultures; Consider genitourinary imaging; Change iv to po regimen when blood cultures are sterile and abscess drained.
### Chronic Bacterial Prostatitis
- Preferred regime: Ciprofloxacin 400 mg iv every 12 h OR Levofloxacin 500 mg iv every 24 h
- Alternative regime: TMP-SMX x 1 dose DS BID
- Preferred regime: Azithromycin 500 mg po QD
- Alternative regime: Doxycycline 100 mg BID
## Pyelonephritis
- Condition 1: patients not requiring hospitalization where the prevalence of resistance of community uropathogens to fluoroquinolones is not known to exceed 10%
- Preferred regime: Ciprofloxacin orally 500 mg twice daily for 7 days ± an initial 400-mg dose of intravenous Ciprofloxacin
- NOTE (1): If an initial one-time intravenous agent is used, a long-acting antimicrobial, such as 1 g of Ceftriaxone or a consolidated 24-h dose of an Aminoglycoside, could be used in lieu of an intravenous fluoroquinolone
- NOTE (2): If the prevalence of fluoroquinolone resistance is thought to exceed 10%, an initial one-time intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of ceftriaxone or a consolidated 24-h dose of an aminoglycoside, is recommended.
- Alternative regime: A once-daily oral fluoroquinolone, including Ciprofloxacin 1000 mg extended release for 7 days OR Levofloxacin 750 mg for 5 days.
- NOTE: If the prevalence of fluoroquinolone resistance is thought to exceed 10%, an initial intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of Ceftriaxone or a consolidated 24-h dose of an Aminoglycoside, is recommended.
- Condition 2: When the uropathogen is known to be susceptible
- Preferred regime: Trimethoprim-sulfamethoxazole 160/800 mg (1 double-strength tablet) bid orally for 14 days.
- NOTE: If trimethoprim-sulfamethoxazole is used when the susceptibility is not known, an initial intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of ceftriaxone OR a consolidated 24-h dose of an aminoglycoside, is recommended.
- NOTE: Oral β-lactam agents are less effective than other available agents for treatment of pyelonephritis. If an oral β-lactam agent is used, an initial intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of ceftriaxone OR a consolidated 24-h dose of an aminoglycoside, is recommended.
- Condition 3: Patients require hospitalization (high fever, high white blood cell count, vomiting, dehydration, or evidence of sepsis)
- Preferred regime: intravenous antimicrobial regimen, such as a Fluoroquinolone; an Aminoglycoside ± Ampicillin; an extended-spectrum Cephalosporin or extended-spectrum Penicillin ± an Aminoglycoside; Carbapenem
- NOTE: The choice between these agents should be based on local resistance data, and the regimen should be tailored on the basis of susceptibility results.
## Sterile pyuria
- Sterile pyuria
- Definitions
- Pyuria: the presence of 10 or more white cells per cubic millimeter in a urine specimen, 3 or more white cells per high-power field of unspun urine, a positive result on Gram’s stain of an unspun urine specimen, or a urinary dipstick test that is positive for leukocyte esterase[16]
- Sterile pyuria: the persistent finding of white cells in the urine in the absence of bacteria, as determined by means of aerobic laboratory techniques (on a 5% sheep-blood agar plate and MacConkey agar plate)[17]
- Bacteriuria: bacterial colony counts of more than 1000 colony-forming units (CFU) per milliliter in urine[18]
- Causes[19]
- Infectious etiologies
- Gynecologic infection
- Urethritis due to chlamydia, Neisseria gonorrhoeae, mycoplasma, or ureaplasma
- Prostatitis
- Balanitis
- Appendicitis
- Viral infection of the lower genitourinary tract
- Genitourinary tuberculosis
- Fungal infection
- Parasitic disease such as trichomoniasis or schistosomiasis
- Non-infectious etiologies
- Current use of antibiotics
- Recently treated urinary tract infection (within past 2 weeks)
- Presence or recent use of a urinary catheter
- Recent cystoscopy or urologic endoscopy
- Urinary tract stones
- Foreign body such as surgical mesh in the urethra or a retained stent
- Urinary tract neoplasm
- Pelvic irradiation
- Urinary fistula
- Polycystic kidney
- Rejection of a renal transplant
- Renal-vein thrombosis
- Interstitial nephritis or analgesic nephropathy
- Papillary necrosis
- Interstitial cystitis
- Inflammatory disease such as systemic lupus erythematosus or Kawasaki’s disease
- Pathogen-directed antimicrobial therapy[20]
- Tuberculosis
- Preferred regimen: Isoniazid AND Rifampin AND Ethambutol AND Pyrazinamide for 3–6 months
- Gonorrhea
- Preferred regimen: Ceftriaxone 250 mg IM in a single dose, then (Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days)
- Chlamydia
- Preferred regimen: Azithromycin 1 g PO in single dose OR Doxycycline 100 mg PO bid for 7 days
- Alternative regimen: Erythromycin base 500 mg PO qid for 7 days
- Mycoplasma and ureaplasma
- Preferred regimen: Azithromycin OR Levofloxacin OR Moxifloxacin
- Genital herpes
- Preferred regimen: Acyclovir 400 mg PO tid for 7–10 days or Acyclovir 200 mg PO five times a day for 7–10 days OR Famciclovir 250 mg PO tid for 7–10 days OR Valacyclovir 1 g PO bid for 7 days
- Trichomoniasis
- Preferred regimen: Metronidazole 2 g PO in a single dose) OR Tinidazole 2 g PO in a single dose
- Fungal infections
- Preferred regimen: Fluconazole OR Posaconazole OR Echinocandins OR Amphotericin B
- Schistosomiasis
- Preferred regimen: Praziquantel 20 mg/kg PO bid for 1–2 days
## Syphilis
- Syphilis (Treponema pallidum)[21]
- Non–HIV-infected persons
- Primary and secondary syphilis
- Preferred regimen (adult): Benzathine penicillin G 2.4 MU IM in a single dose
- Preferred regimen (pediatric): Benzathine penicillin G 50,000 units/kg (up to 2.4 MU) IM in a single dose
- Latent syphilis
- Early latent syphilis
- Preferred regimen (adult): Benzathine penicillin G 2.4 MU IM in a single dose
- Preferred regimen (pediatric): Benzathine penicillin G 50,000 units/kg (up to 2.4 MU) IM in a single dose
- Late latent syphilis or unknown duration
- Preferred regimen (adult): Benzathine penicillin G 2.4 MU IM for 3 doses, each at 1-week intervals
- Preferred regimen (pediatric): Benzathine penicillin G 50,000 units/kg (up to 2.4 MU) IM, administered as 3 doses at 1-week intervals
- Tertiary syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM for 3 doses, each at 1-week intervals
- Neurosyphilis
- Preferred regimen: Aqueous crystalline penicillin G 3–4 MU IV q4h or continuously for 10–14 days
- Alternative regimen: Procaine penicillin G 2.4 MU IM q24h for 10–14 days AND Probenecid 500 mg PO qid for 10–14 days
- HIV-infected persons
- Primary and secondary syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM in a single dose
- Latent syphilis
- Early latent syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM in a single dose
- Late latent syphilis or unknown duration
- Preferred regimen: Benzathine penicillin G 2.4 MU IM for 3 doses, each at 1-week intervals
- Tertiary syphilis
- Preferred regimen: Benzathine penicillin G 2.4 MU IM for 3 doses, each at 1-week intervals
- Neurosyphilis
- Preferred regimen: Penicillin G 3–4 MU IV q4h or continuously for 10–14 days
- Alternative regimen: Procaine penicillin G 2.4 MU IM q24h for 10–14 days AND Probenecid 500 mg PO qid for 10–14 days
- During pregnancy
- Preferred regimen: Pregnant women should be treated with the Penicillin regimen appropriate for their stage of infection.
- Congenital syphilis
- Infants with proven or highly probable disease AND (abnormal physical examination consistent with congenital syphilis OR nontreponemal serologic titer fourfold higher than the mother's titer OR a positive darkfield test of body fluids)
- Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days OR Procaine penicillin G 50,000 U/kg IM in a single daily dose for 10 days
- Infants who have a normal physical examination AND nontreponemal serologic titer the same or less than fourfold the maternal titer AND (mother was not treated adequately OR mother has no documentation of having received treatment OR mother was treated with Erythromycin or another non-Penicillin regimen OR mother received treatment < 4 weeks before delivery)
- Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg IV q12h during the first 7 days of life and q8h thereafter for a total of 10 days OR Procaine penicillin G 50,000 U/kg IM in a single daily dose for 10 days OR Benzathine penicillin G 50,000 U/kg IM in a single dose
- Infants who have a normal physical examination AND nontreponemal serologic titer the same or less than fourfold the maternal titer AND mother was treated during pregnancy AND treatment was appropriate for the stage of infection AND treatment administered > 4 weeks before delivery AND mother has no evidence of reinfection or relapse
- Preferred regimen: Benzathine penicillin G 50,000 U/kg IM in a single dose
- Infants who have a normal physical examination AND nontreponemal serologic titer the same or less than fourfold the maternal titer AND mother's treatment was adequate before pregnancy AND mother's nontreponemal serologic titer remained low and stable before and during pregnancy and at delivery (VDRL < 1:2; RPR < 1:4)
- Preferred regimen: Aqueous crystalline penicillin G 50,000 U/kg q4–6h for 10 days
## Urethritis
- Urethritis[22]
- Nongonococcal urethritis
- Preferred regimen: Azithromycin 1 g PO in a single dose OR Doxycycline 100 mg PO bid for 7 days
- Alternative regimen (1): Erythromycin base 500 mg PO qid for 7 days
- Alternative regimen (2): Erythromycin ethylsuccinate 800 mg PO qid for 7 days
- Alternative regimen (3): Levofloxacin 500 mg PO qd for 7 days
- Alternative regimen (4): Ofloxacin 300 mg PO bid for 7 days
- Recurrent and persistent urethritis
- Preferred regimen: Metronidazole 2 g PO in a single dose OR Tinidazole 2 g PO in a single dose AND Azithromycin 1 g PO in a single dose | https://www.wikidoc.org/index.php/Sandbox_g42 | |
7fe9ebc92fa9f4394cd793dea35ab2dcdfb1b1f4 | wikidoc | Sandbox g43 | Sandbox g43
- Bacillus subtilis
- 1. Food poisoning
- Preferred regimen: supportive treatment
- 2. Other infections
- Preferred regimen: Vancomycin OR Clindamycin
- Alternative regimen: Ciprofloxacin OR Imipenem
- ↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
- ↑ Andrews, J. M.; Wise, R. (2002-06). "Susceptibility testing of Bacillus species". The Journal of Antimicrobial Chemotherapy. 49 (6): 1040–1042. ISSN 0305-7453. PMID 12039902. Check date values in: |date= (help) | Sandbox g43
- Bacillus subtilis[1][2][3]
- 1. Food poisoning
- Preferred regimen: supportive treatment
- 2. Other infections
- Preferred regimen: Vancomycin OR Clindamycin
- Alternative regimen: Ciprofloxacin OR Imipenem
- ↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Gilbert, David (2015). The Sanford guide to antimicrobial therapy. Sperryville, Va: Antimicrobial Therapy. ISBN 978-1930808843.
- ↑ Andrews, J. M.; Wise, R. (2002-06). "Susceptibility testing of Bacillus species". The Journal of Antimicrobial Chemotherapy. 49 (6): 1040–1042. ISSN 0305-7453. PMID 12039902. Check date values in: |date= (help) | https://www.wikidoc.org/index.php/Sandbox_g43 | |
7429db1aed5553b7f19f63c68b31a9ba848acb60 | wikidoc | Sandbox g44 | Sandbox g44
# WikiDoc Infectious Disease Project — Pathogen-Based Infections
## Pathogens of Public Health Significance
## Pathogens of Clinical Significance
- 1. Chancroid
- Preferred regimen: Azithromycin 1 g PO as a single dose OR Ceftriaxone 250 mg IM as a single dose OR Ciprofloxacin 500 mg PO bid for 3 days OR Erythromycin base 500 mg PO tid for 7 days
- Note (1): The combination of a painful genital ulcer and tender suppurative inguinal adenopathy suggests the diagnosis of chancroid. For both clinical and surveillance purposes, a probable diagnosis of chancroid can be made if all of the following criteria are met: 1) the patient has one or more painful genital ulcers; 2) the clinical presentation, appearance of genital ulcers and, if present, regional lymphadenopathy are typical for chancroid; 3) the patient has no evidence of T. pallidum infection by darkfield examination of ulcer exudate or by a serologic test for syphilis performed at least 7 days after onset of ulcers; and 4) an HSV PCR test or HSV culture performed on the ulcer exudate is negative.
- Note (2): Patients should be tested for HIV infection at the time chancroid is diagnosed. If the initial test results were negative, a serologic test for syphilis and HIV infection should be performed 3 months after the diagnosis of chancroid.
- Note (3): Patients should be re-examined 3–7 days after initiation of therapy. If treatment is successful, ulcers usually improve symptomatically within 3 days and objectively within 7 days after therapy. If no clinical improvement is evident, the clinician must consider whether 1) the diagnosis is correct, 2) the patient is coinfected with another STD, 3) the patient is infected with HIV, 4) the treatment was not used as instructed, or 5) the H. ducreyi strain causing the infection is resistant to the prescribed antimicrobial.
- 2. Specific considerations
- 2.1 Management of sex partners
- Regardless of whether symptoms of the disease are present, sex partners of patients who have chancroid should be examined and treated if they had sexual contact with the patient during the 10 days preceding the patient’s onset of symptoms.
- 2.2 Pregnancy
- Ciprofloxacin may present a low risk to the fetus during pregnancy, with a potential for toxicity during breastfeeding. Alternative drugs should be used during pregnancy and lactation.
- 2.3 HIV infection
- Persons with HIV infection who have chancroid should be monitored closely because they are more likely to experience treatment failure and to have ulcers that heal slowly. Persons with HIV infection might require repeated or longer courses of therapy, and treatment failures can occur with any regimen.
- 1. Urethritis and cervicitis
- Preferred regimen (macrolide-susceptible strains): Azithromycin 1 g PO as a single dose OR Azithromycin 500 mg PO as a dose followed by 250 mg PO qd for 4 days
- Preferred regimen (for patients with previous treatment failures): Moxifloxacin 400 mg PO qd for 7–14 days
- 2. Pelvic inflammatory disease
- Preferred regimen: Moxifloxacin 400 mg PO qd for 14 days
- 3. Specific considerations
- 3.1 Management of sex partners
- Sex partners should be managed according to guidelines for patients with nongonococcal urethritis, cervicitis, and pelvic inflammatory disease.
- 3.2 HIV infection
- Persons who have an M. genitalium infection and HIV infection should receive the same treatment regimen as those who are HIV negative. | Sandbox g44
# WikiDoc Infectious Disease Project — Pathogen-Based Infections
## Pathogens of Public Health Significance
## Pathogens of Clinical Significance
- 1. Chancroid[1]
- Preferred regimen: Azithromycin 1 g PO as a single dose OR Ceftriaxone 250 mg IM as a single dose OR Ciprofloxacin 500 mg PO bid for 3 days OR Erythromycin base 500 mg PO tid for 7 days
- Note (1): The combination of a painful genital ulcer and tender suppurative inguinal adenopathy suggests the diagnosis of chancroid. For both clinical and surveillance purposes, a probable diagnosis of chancroid can be made if all of the following criteria are met: 1) the patient has one or more painful genital ulcers; 2) the clinical presentation, appearance of genital ulcers and, if present, regional lymphadenopathy are typical for chancroid; 3) the patient has no evidence of T. pallidum infection by darkfield examination of ulcer exudate or by a serologic test for syphilis performed at least 7 days after onset of ulcers; and 4) an HSV PCR test or HSV culture performed on the ulcer exudate is negative.
- Note (2): Patients should be tested for HIV infection at the time chancroid is diagnosed. If the initial test results were negative, a serologic test for syphilis and HIV infection should be performed 3 months after the diagnosis of chancroid.
- Note (3): Patients should be re-examined 3–7 days after initiation of therapy. If treatment is successful, ulcers usually improve symptomatically within 3 days and objectively within 7 days after therapy. If no clinical improvement is evident, the clinician must consider whether 1) the diagnosis is correct, 2) the patient is coinfected with another STD, 3) the patient is infected with HIV, 4) the treatment was not used as instructed, or 5) the H. ducreyi strain causing the infection is resistant to the prescribed antimicrobial.
- 2. Specific considerations
- 2.1 Management of sex partners
- Regardless of whether symptoms of the disease are present, sex partners of patients who have chancroid should be examined and treated if they had sexual contact with the patient during the 10 days preceding the patient’s onset of symptoms.
- 2.2 Pregnancy
- Ciprofloxacin may present a low risk to the fetus during pregnancy, with a potential for toxicity during breastfeeding. Alternative drugs should be used during pregnancy and lactation.
- 2.3 HIV infection
- Persons with HIV infection who have chancroid should be monitored closely because they are more likely to experience treatment failure and to have ulcers that heal slowly. Persons with HIV infection might require repeated or longer courses of therapy, and treatment failures can occur with any regimen.
- 1. Urethritis and cervicitis[2]
- Preferred regimen (macrolide-susceptible strains): Azithromycin 1 g PO as a single dose OR Azithromycin 500 mg PO as a dose followed by 250 mg PO qd for 4 days
- Preferred regimen (for patients with previous treatment failures): Moxifloxacin 400 mg PO qd for 7–14 days
- 2. Pelvic inflammatory disease[3]
- Preferred regimen: Moxifloxacin 400 mg PO qd for 14 days
- 3. Specific considerations
- 3.1 Management of sex partners
- Sex partners should be managed according to guidelines for patients with nongonococcal urethritis, cervicitis, and pelvic inflammatory disease.
- 3.2 HIV infection
- Persons who have an M. genitalium infection and HIV infection should receive the same treatment regimen as those who are HIV negative. | https://www.wikidoc.org/index.php/Sandbox_g44 | |
3b0748cd930caebb6e1f9bcc1b78b9f53cf6de2d | wikidoc | Sandbox g52 | Sandbox g52
- Klebsiella rhinoscleromatis Return to Top
- 1. Rhinoscleroma
- Preferred regimen (1): Ciprofloxacin 500–750 mg PO bid for 2–3 months OR Levofloxacin 750 mg PO qd for 2–3 months
- Preferred regimen (2): Trimethoprim-Sulfamethoxazole 1 DS tab PO bid for 3 months AND Rifampicin 300 mg PO bid for 3 months
- Alternative regimen: Tetracycline OR Streptomycin OR Doxycycline OR Ceftriaxone OR Ofloxacin
- Note (1): The optimal duration of antimicrobial therapy remains unclear. A 6-week to 6-month cours of antibiotics until histology exams and cultures are negative may be required.
- Note (2): Use of topical antiseptics such as Acriflavinium and Rifampin ointment has been reported with resolution of symptoms. | Sandbox g52
- Klebsiella rhinoscleromatis Return to Top
- 1. Rhinoscleroma[1][2][3]
- Preferred regimen (1): Ciprofloxacin 500–750 mg PO bid for 2–3 months OR Levofloxacin 750 mg PO qd for 2–3 months
- Preferred regimen (2): Trimethoprim-Sulfamethoxazole 1 DS tab PO bid for 3 months AND Rifampicin 300 mg PO bid for 3 months
- Alternative regimen: Tetracycline OR Streptomycin OR Doxycycline OR Ceftriaxone OR Ofloxacin
- Note (1): The optimal duration of antimicrobial therapy remains unclear. A 6-week to 6-month cours of antibiotics until histology exams and cultures are negative may be required.
- Note (2): Use of topical antiseptics such as Acriflavinium and Rifampin ointment has been reported with resolution of symptoms.[4] | https://www.wikidoc.org/index.php/Sandbox_g52 | |
0d86dac23ad1eff36d7fb3236a88a41014f43f86 | wikidoc | Sandbox g53 | Sandbox g53
- HHV-7 Return to Top
- Most patients with infection with HHV-7 will be asymptomatic. It is unknown whether treatment in asymptomatic patients will lead to a reduction in subsequent infection. (15504215)
- Immunocompetent hosts with uncomplicated skin manifestations associated with HHV-7, particularly roseola infantum and pityriasis rosea, need only symptomatic management. (22819486)
- For HIV-positive patients, antiretroviral therapy may be advisable. (sanford)
- There are no defined circumstances that warrant specific antiviral therapy for HHV-7. (10578120)
- The most active antiviral compounds against HHV-7 are Cidofovir and Foscarnet. (11747000) | Sandbox g53
- HHV-7 Return to Top
- Most patients with infection with HHV-7 will be asymptomatic. It is unknown whether treatment in asymptomatic patients will lead to a reduction in subsequent infection. (15504215)
- Immunocompetent hosts with uncomplicated skin manifestations associated with HHV-7, particularly roseola infantum and pityriasis rosea, need only symptomatic management. (22819486)
- For HIV-positive patients, antiretroviral therapy may be advisable. (sanford)
- There are no defined circumstances that warrant specific antiviral therapy for HHV-7. (10578120)
- The most active antiviral compounds against HHV-7 are Cidofovir and Foscarnet. (11747000) | https://www.wikidoc.org/index.php/Sandbox_g53 | |
da30adecbf0f6b4365a4dd0692345262f7f14c62 | wikidoc | Sandbox g54 | Sandbox g54
- Mycoplasma pneumoniae Return to Top
- 1. Mycoplasma pneumoniae infections
- Preferred regimen (1): Azithromycin 500 mg PO qd on day 1 and 250 mg PO qd on days 2 to 5
- Preferred regimen (2): Doxycycline 100 mg PO bid for 14 days
- Preferred regimen (3): Moxifloxacin 400 mg PO qd for 14 days
- Preferred regimen (4): Levofloxacin 750 mg PO qd for 14 days
- Preferred regimen (4): Clarithromycin 500 mg PO qd for 14 days
- ↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | Sandbox g54
- Mycoplasma pneumoniae Return to Top
- 1. Mycoplasma pneumoniae infections[1]
- Preferred regimen (1): Azithromycin 500 mg PO qd on day 1 and 250 mg PO qd on days 2 to 5
- Preferred regimen (2): Doxycycline 100 mg PO bid for 14 days
- Preferred regimen (3): Moxifloxacin 400 mg PO qd for 14 days
- Preferred regimen (4): Levofloxacin 750 mg PO qd for 14 days
- Preferred regimen (4): Clarithromycin 500 mg PO qd for 14 days
- ↑ Bennett, John (2015). Mandell, Douglas, and Bennett's principles and practice of infectious diseases. Philadelphia, PA: Elsevier/Saunders. ISBN 978-1455748013..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | https://www.wikidoc.org/index.php/Sandbox_g54 | |
86a2d83433c0b985e211e29b4837c8a3dd862dfa | wikidoc | Sandbox g55 | Sandbox g55
- Acanthamoeba Return to Top
- 1. Granulomatous amoebic encephalitis, meningitis, and disseminated Acanthamoeba disease
- Preferred regimen (1): Pentamidine AND Itraconazole AND Sulfadiazine AND Flucytosine
- Preferred regimen (2): Sulfadiazine AND Fluconazole AND Pyrimethamine
- Preferred regimen (3): Sulfadiazine AND Flucytosine AND TMP-SMX
- Preferred regimen (4): TMP-SMX AND Rifampin AND Ketoconazole
- Preferred regimen (5): Miltefosine AND Amikacin
- Preferred regimen (6): Miltefosine AND Voriconazole
- Preferred regimen (7): Pentamidine AND Itraconazole AND Flucytosine AND Levofloxacin AND Amphotericin B AND Rifampin
- Preferred regimen (8): Pentamidine AND Fluconazole AND Miltefosine
- Note: The mainstay of successful treatment includes early diagnosis and combination therapy with pentamidine, azole, sulfonamide, miltefosine, and possibly flucytosine.
- 2. Cutaneous acanthamoebiasis
- Preferred regimen: Pentamidine AND Sulfadiazine AND Flucytosine AND (Itraconazole OR Fluconazole) AND Chlorhexidine topical AND Ketoconazole topical
- 3. Acanthamoeba keratitis
- Preferred regimen: (Polyhexamethylene biguanide topical OR Chlorhexidine topical) ± (Propamidine topical OR Hexamidine topical)
- Note (1): Azole antifungal drugs (Ketoconazole, Itraconazole, Voriconazole) may be considered as oral or topical adjuncts.
- Note (2): The duration of therapy for Acanthamoeba keratitis may last six months to a year.
- Note (3): Pain control can be helped by topical cyclopegic solutions and oral nonsteroidal medications.
- Note (4): The use of corticosteroids to control inflammation is controversial.
- Note (5): Penetrating keratoplasty may help restore visual acuity.
- Balamuthia mandrillaris Return to Top
- 1. Granulomatous Amebic Encephalitis
- Preferred regimen (1): Pentamidine AND Flucytosine AND Fluconazole AND Sulfadiazine AND (Azithromycin OR Clarithromycin)
- Preferred regimen (2): Pentamidine AND Albendazole AND (Itraconazole OR Fluconazole) AND Miltefosine
- Enterobacter Return to Top
- Enterobacter species including E. aerogenes and E. cloacae
- 1. Empiric antimicrobial therapy pending in vitro susceptibility
- 1.1 Non–life-threatening infections or MDR-GNB prevalence < 20%
- Preferred regimen: Piperacillin-Tazobactam 3.375 g IV q6h ± Aminoglycosides
- Alternative regimen: Ciprofloxacin 400 mg IV q8–12h
- 1.2 Life-threatening infections or MDR-GNB prevalence > 20%
- Preferred regimen: Meropenem 0.5–1 g IV q8h
- Alternative regimen (1): Colistin AND Meropenem 0.5–1 g IV q8h
- Alternative regimen (2): Colistin AND Imipenem 500 mg IV q6h
- Alternative regimen (3): Colistin AND Doripenem 500 mg IV q8h
- Alternative regimen (4): Colistin AND Ertapenem 1 g IV q24h
- Alternative regimen (5): Colistin AND Fosfomycin 6 g IV q6h
- 2. In vitro susceptibility available
- 2.1 Susceptible to all tested agents
- Preferred regimen: Piperacillin-Tazobactam 3.375 g IV q6h
- Alternative regimen (1): Ciprofloxacin 400 mg IV q8–12h
- Alternative regimen (2): Cefepime 2 g IV q8h (if MIC ≤ 1 μg/mL)
- 2.2 Extended spectrum beta-lactamase (ESBL)-producing Enterobacter spp.
- Preferred regimen: Meropenem 0.5–1 g IV q8h
- Alternative regimen (1): Imipenem 500 mg IV q6h
- Alternative regimen (2): Doripenem 500 mg IV q8h
- Alternative regimen (3): Ertapenem 1 g IV q24h
- Alternative regimen (4): Cefepime 2 g IV q8h (if MIC ≤ 1 μg/mL)
- 2.3 Resistant to all tested agents
- Preferred regimen: Colistin AND Meropenem 0.5–1 g IV q8h
- Alternative regimen (1): Colistin AND Imipenem 500 mg IV q6h
- Alternative regimen (2): Colistin AND Doripenem 500 mg IV q8h
- Alternative regimen (3): Colistin AND Ertapenem 1 g IV q24h
- Alternative regimen (4): Colistin AND Minocycline 100 mg IV q12h | Sandbox g55
- Acanthamoeba Return to Top
- 1. Granulomatous amoebic encephalitis, meningitis, and disseminated Acanthamoeba disease[1][2]
- Preferred regimen (1): Pentamidine AND Itraconazole AND Sulfadiazine AND Flucytosine
- Preferred regimen (2): Sulfadiazine AND Fluconazole AND Pyrimethamine
- Preferred regimen (3): Sulfadiazine AND Flucytosine AND TMP-SMX
- Preferred regimen (4): TMP-SMX AND Rifampin AND Ketoconazole
- Preferred regimen (5): Miltefosine AND Amikacin
- Preferred regimen (6): Miltefosine AND Voriconazole
- Preferred regimen (7): Pentamidine AND Itraconazole AND Flucytosine AND Levofloxacin AND Amphotericin B AND Rifampin
- Preferred regimen (8): Pentamidine AND Fluconazole AND Miltefosine
- Note: The mainstay of successful treatment includes early diagnosis and combination therapy with pentamidine, azole, sulfonamide, miltefosine, and possibly flucytosine.
- 2. Cutaneous acanthamoebiasis[3][4][5]
- Preferred regimen: Pentamidine AND Sulfadiazine AND Flucytosine AND (Itraconazole OR Fluconazole) AND Chlorhexidine topical AND Ketoconazole topical
- 3. Acanthamoeba keratitis[6]
- Preferred regimen: (Polyhexamethylene biguanide topical OR Chlorhexidine topical) ± (Propamidine topical OR Hexamidine topical)
- Note (1): Azole antifungal drugs (Ketoconazole, Itraconazole, Voriconazole) may be considered as oral or topical adjuncts.
- Note (2): The duration of therapy for Acanthamoeba keratitis may last six months to a year.
- Note (3): Pain control can be helped by topical cyclopegic solutions and oral nonsteroidal medications.
- Note (4): The use of corticosteroids to control inflammation is controversial.
- Note (5): Penetrating keratoplasty may help restore visual acuity.
- Balamuthia mandrillaris Return to Top
- 1. Granulomatous Amebic Encephalitis[7][8]
- Preferred regimen (1): Pentamidine AND Flucytosine AND Fluconazole AND Sulfadiazine AND (Azithromycin OR Clarithromycin)
- Preferred regimen (2): Pentamidine AND Albendazole AND (Itraconazole OR Fluconazole) AND Miltefosine
- Enterobacter Return to Top
- Enterobacter species including E. aerogenes and E. cloacae[9][10][11][12][13]
- 1. Empiric antimicrobial therapy pending in vitro susceptibility
- 1.1 Non–life-threatening infections or MDR-GNB prevalence < 20%
- Preferred regimen: Piperacillin-Tazobactam 3.375 g IV q6h ± Aminoglycosides
- Alternative regimen: Ciprofloxacin 400 mg IV q8–12h
- 1.2 Life-threatening infections or MDR-GNB prevalence > 20%
- Preferred regimen: Meropenem 0.5–1 g IV q8h
- Alternative regimen (1): Colistin AND Meropenem 0.5–1 g IV q8h
- Alternative regimen (2): Colistin AND Imipenem 500 mg IV q6h
- Alternative regimen (3): Colistin AND Doripenem 500 mg IV q8h
- Alternative regimen (4): Colistin AND Ertapenem 1 g IV q24h
- Alternative regimen (5): Colistin AND Fosfomycin 6 g IV q6h
- 2. In vitro susceptibility available
- 2.1 Susceptible to all tested agents
- Preferred regimen: Piperacillin-Tazobactam 3.375 g IV q6h
- Alternative regimen (1): Ciprofloxacin 400 mg IV q8–12h
- Alternative regimen (2): Cefepime 2 g IV q8h (if MIC ≤ 1 μg/mL)
- 2.2 Extended spectrum beta-lactamase (ESBL)-producing Enterobacter spp.
- Preferred regimen: Meropenem 0.5–1 g IV q8h
- Alternative regimen (1): Imipenem 500 mg IV q6h
- Alternative regimen (2): Doripenem 500 mg IV q8h
- Alternative regimen (3): Ertapenem 1 g IV q24h
- Alternative regimen (4): Cefepime 2 g IV q8h (if MIC ≤ 1 μg/mL)
- 2.3 Resistant to all tested agents
- Preferred regimen: Colistin AND Meropenem 0.5–1 g IV q8h
- Alternative regimen (1): Colistin AND Imipenem 500 mg IV q6h
- Alternative regimen (2): Colistin AND Doripenem 500 mg IV q8h
- Alternative regimen (3): Colistin AND Ertapenem 1 g IV q24h
- Alternative regimen (4): Colistin AND Minocycline 100 mg IV q12h | https://www.wikidoc.org/index.php/Sandbox_g55 | |
f6dc2c4fe54d1c5919d026a0687f0cc49799143a | wikidoc | Sandbox g56 | Sandbox g56
- Staphylococcus haemolyticus Return to Top
- 1. Methicillin-susceptible strain
- Preferred regimen (1): Nafcillin 1–2 g IV q4-6h (maximum 12 g/day)
- Preferred regimen (2): Oxacillin 1–2 g IVq4-6h (maximum 12 g/day)
- Preferred regimen (3): Cefazolin 0.5–2 g IV q6-8h
- Alternative regimen (1): TMP-SMX 4–5 mg/kg IV q6–12h
- Alternative regimen (2): Doxycycline 100–200 mg IV q12-24h
- 2. Methicillin-resistant, Glycopeptide-susceptible strain
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h
- 3. Methicillin-resistant, Glycopeptide-resistant strain
- Preferred regimen (1): Daptomycin 4–6 mg/kg IV q24h
- Preferred regimen (2): Linezolid 600 mg PO/IV q12h
- Staphylococcus saprophyticus Return to Top
- 1. Urinary tract infections
- Preferred regimen (1): Cephalexin 500 mg PO qid
- Preferred regimen (2): Amoxicillin-Clavulanate 875/125 mg PO bid
- Preferred regimen (3): TMP-SMX 160–800 mg PO bid
- Alternative regimen: Levofloxacin 500 mg PO qd
- Streptococcus anginosus Return to Top
- 1. Dental abscess
- Preferred regimen: Penicillin V 500 mg PO qid
- Alternative regimen: Vancomycin 15–20 mg/kg IV q8–12h
- 2. Brain abscess
- Preferred regimen (1): Penicillin G 18–24 MU/day IV q4–6h
- Preferred regimen (2): Ceftriaxone 2 g IV q12h
- Alternative regimen: Vancomycin 15–20 mg/kg IV q8–12h
- Bacillus cereus Return to Top
- 1. Food poisoning
- Preferred regimen: Food poisoning is usually self-limited and requires no antibiotic therapy.
- 2. Bacteremia
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- Note (1): Bacillus cereus is commonly resistant to beta-lactams.
- Note (2): Pseudobacteremia is transient and usually results from contaminated blood cultures, gloves, or syringes.
- 3. Meningitis or brain abscess
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- Note: Blood culture isolates are mostly contaminates until proven otherwise, especially in intravenous drug user population.
- 4. Endophthalmitis
- Preferred regimen: Clindamycin 450 μg intravitreal AND Gentamicin 400 μg intravitreal OR Dexamethasone intravitreal AND Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- Note: Ophthalmological consultation, culture ocular fluids, early vitrectomy, and intravitreal antibiotics are necessary.
- 5. Endocarditis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Note: Most blood cultures in intravenous drug users are contaminates or represent transient bacteremia.
- 6. Soft tissue infection
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- 7. Pneumonia
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- Elizabethkingia meningoseptica Return to Top
- 1. Bacteremia
- Preferred regimen (1): Levofloxacin 750 mg IV/PO q24h
- Preferred regimen (2): TMP-SMX 8–10 mg/kg/day IV divided q6–8h
- Alternative regimen (1): Ciprofloxacin 400 mg IV q12h
- Alternative regimen (2): TMP-SMX 8–10 mg/kg/day IV divided q6–8h | Sandbox g56
- Staphylococcus haemolyticus Return to Top
- 1. Methicillin-susceptible strain[1][2]
- Preferred regimen (1): Nafcillin 1–2 g IV q4-6h (maximum 12 g/day)
- Preferred regimen (2): Oxacillin 1–2 g IVq4-6h (maximum 12 g/day)
- Preferred regimen (3): Cefazolin 0.5–2 g IV q6-8h
- Alternative regimen (1): TMP-SMX 4–5 mg/kg IV q6–12h
- Alternative regimen (2): Doxycycline 100–200 mg IV q12-24h
- 2. Methicillin-resistant, Glycopeptide-susceptible strain
- Preferred regimen: Vancomycin 15–20 mg/kg IV q8–12h
- 3. Methicillin-resistant, Glycopeptide-resistant strain
- Preferred regimen (1): Daptomycin 4–6 mg/kg IV q24h
- Preferred regimen (2): Linezolid 600 mg PO/IV q12h
- Staphylococcus saprophyticus Return to Top
- 1. Urinary tract infections[3]
- Preferred regimen (1): Cephalexin 500 mg PO qid
- Preferred regimen (2): Amoxicillin-Clavulanate 875/125 mg PO bid
- Preferred regimen (3): TMP-SMX 160–800 mg PO bid
- Alternative regimen: Levofloxacin 500 mg PO qd
- Streptococcus anginosus Return to Top
- 1. Dental abscess[4]
- Preferred regimen: Penicillin V 500 mg PO qid
- Alternative regimen: Vancomycin 15–20 mg/kg IV q8–12h
- 2. Brain abscess
- Preferred regimen (1): Penicillin G 18–24 MU/day IV q4–6h
- Preferred regimen (2): Ceftriaxone 2 g IV q12h
- Alternative regimen: Vancomycin 15–20 mg/kg IV q8–12h
- Bacillus cereus Return to Top
- 1. Food poisoning[5]
- Preferred regimen: Food poisoning is usually self-limited and requires no antibiotic therapy.
- 2. Bacteremia
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- Note (1): Bacillus cereus is commonly resistant to beta-lactams.
- Note (2): Pseudobacteremia is transient and usually results from contaminated blood cultures, gloves, or syringes.
- 3. Meningitis or brain abscess
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- Note: Blood culture isolates are mostly contaminates until proven otherwise, especially in intravenous drug user population.
- 4. Endophthalmitis
- Preferred regimen: Clindamycin 450 μg intravitreal AND Gentamicin 400 μg intravitreal OR Dexamethasone intravitreal AND Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- Note: Ophthalmological consultation, culture ocular fluids, early vitrectomy, and intravitreal antibiotics are necessary.
- 5. Endocarditis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Note: Most blood cultures in intravenous drug users are contaminates or represent transient bacteremia.
- 6. Soft tissue infection
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- 7. Pneumonia
- Preferred regimen: Vancomycin 15 mg/kg IV q12h
- Alternative regimen: Clindamycin 600 mg IV q8h
- Elizabethkingia meningoseptica Return to Top
- 1. Bacteremia[6][7]
- Preferred regimen (1): Levofloxacin 750 mg IV/PO q24h
- Preferred regimen (2): TMP-SMX 8–10 mg/kg/day IV divided q6–8h
- Alternative regimen (1): Ciprofloxacin 400 mg IV q12h
- Alternative regimen (2): TMP-SMX 8–10 mg/kg/day IV divided q6–8h | https://www.wikidoc.org/index.php/Sandbox_g56 | |
2381a4ad97bb8d89f682473348cb1e224d366aff | wikidoc | Sandbox g57 | Sandbox g57
# Differential Diagnosis Project
# Differentiating Legionnaires' disease from other diseases
# Distinctive features of Legionnaires' disease
## Clinical manifestations
- High grade fever
- Dry cough
- Progressive dyspnea
- Bronchial breath sounds
- Adult respiratory distress syndrome
## Laboratory abnormalities
- Legionella urinary antigen positive
- Alveolar consolidation on chest radiograph
- Lobar consolidation on chest radiograph
# Distinctive features of Acute interstitial pneumonia
## Clinical manifestations
- Dry cough
- Progressive dyspnea
- Adult respiratory distress syndrome
## Laboratory abnormalities
- Disseminated consolidation on chest radiograph
- Interstitial infiltrate on chest radiograph
- Increased uptake on Gallium scan
# Distinctive features of Mycoplasma pneumonia
## Clinical manifestations
- Dry cough
- Pleuritic chest pain
- Inflammed, opaque, hypomobile tympanic membrane
- Bronchial breath sounds
## Laboratory abnormalities
- Lymphocytosis
- Cold agglutinins positive
- Alveolar consolidation on chest radiograph
- Interstitial infiltrate on chest radiograph
- Lobar consolidation on chest radiograph
# Distinctive features of Pneumococcal pneumonia
## Clinical manifestations
- Hemoptysis
- Fine rales
- Pleuritic chest pain
- Increased breath sounds
- Bronchial breath sounds
- Dullness on chest percussion
- Purulent sputum
- Shallow respiration
- Pectoriloquy
- Increased tactile fremitus
- Productive cough
- Egophony
- High grade fever
## Laboratory abnormalities
- Pleural effusion (exudative)
- Respiratory alkalosis
- Parenchymal hyperlucency on chest radiograph
- Increased uptake on Gallium scan
- Unilateral diaphragm elevation on chest radiograph
- Alveolar consolidation on chest radiograph
- Lobar consolidation on chest radiograph
- Gram positive diplococci on sputum Gram stain
# Distinctive features of Pneumocystis carinii pneumonia
## Clinical manifestations
- Immunosuppressive state
- Mediastinal emphysema
- Subcutaneous emphysema
- Hacking cough
- Progressive dyspnea
## Laboratory abnormalities
- Respiratory alkalosis
- Serum beta-D-glucan elevated
- Alveolar consolidation on chest radiograph
- Lobar consolidation on chest radiograph
- Interstitial infiltrate on chest radiograph
# Distinctive features of Pulmonary embolism
## Clinical manifestations
- Calf pain / swelling
- Decreased pulse pressure
- Dyspnea with normal chest X-ray
- Hemoptysis
- Hyperventilation
- Immobility
- Increased pulmonic component of heart sound
- Pleuritic chest pain
- Prior DVT
- Pulmonary hypertension
- Right ventricular heave
- Right ventricular hypertrophy
- Right-to-left shunt
- Substernal chest pain
- Tachypnea
- Thrombophlebitis
- Unilateral lower extremity edema
- Venous stasis
## Laboratory abnormalities
- Atrial fibrillation
- Bone fracture
- Atelectasis on chest radiograph
- Lobar consolidation on chest radiograph
- Prominent pulmonary artery on chest radiograph
- Hampton's hump on chest radiograph
- D-dimer elevated
- Right ventricular enlargement on echocardiography
- Thrombus on echocardiography
- Hypocapnia
- Hypoxia
- Segmental perfusion defect on lung scan
- V/Q mismatch on lung scan
- Pleural effusion (exudative / bloody)
- RVH on ECG
- Right axis deviation on ECG
# Distinctive features of Streptococcal pneumonia
## Clinical manifestations
- Pectoriloquy
- Bronchial breath sounds
- Empyema
- Erythema nodosum
- Purulent sputum
- Shallow respiration
- Increased tactile fremitus
- Pleuritic chest pain
- Egophony
## Laboratory abnormalities
- Respiratory alkalosis
- Pleural effusion (exudative)
- Increased uptake on Gallium scan
- Gram-positive cocci in chains on sputum Gram stain
- Alveolar consolidation on chest radiograph
- Lobar consolidation on chest radiograph
# Distinctive features of Viral pneumonia
## Clinical manifestations
- Pleuritic chest pain
- Bronchial breath sounds
- Influenza
- Fine rales
- Bronchovesicular breath sounds
## Laboratory abnormalities
- Lymphocytosis
- Respiratory alkalosis
- Lobar consolidation on chest radiograph
- Interstitial infiltrate on chest radiograph
- ↑ Ferri, Fred (2011). Ferri's differential diagnosis: a practical guide to the differential diagnosis of symptoms, signs, and clinical disorders. Philadelphia, PA: Elsevier/Mosby. ISBN 978-0323076999..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Siegenthaler, Walter (2007). Differential diagnosis in internal medicine: from symptom to diagnosis. Stuttgart New York: Thieme. ISBN 978-1588905512.
- ↑ Mesko, Dusan (2002). Differential diagnosis by laboratory medicine: a quick reference for physicians. Berlin New York: Springer-Verlag. ISBN 978-3540430575.
- ↑ Reeder and Felson's gamuts in radiology: comprehensive lists of roentgen differential diagnosis. Place of publication not identified: Springer. 2014. ISBN 978-1475781229.
- ↑ Burgener, Francis (2008). Differential diagnosis in conventional radiology. Stuttgart New York: Thieme. ISBN 978-1588902757.
- ↑ Gattuso, Paolo (2015). Differential diagnosis in surgical pathology. Philadelphia, PA: Saunders/Elsevier. ISBN 978-1455770137.
- ↑ "DXplain". | Sandbox g57
# Differential Diagnosis Project
# Differentiating Legionnaires' disease from other diseases
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Mahshid Mir, M.D. [2]
Template:WikiDoc Sources
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3] Mahshid Mir, M.D. [4]
Template:WikiDoc Sources
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [5] Mahshid Mir, M.D. [6]
Template:WikiDoc Sources
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [7] Mahshid Mir, M.D. [8]
Template:WikiDoc Sources
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [9] Mahshid Mir, M.D. [10]
Template:WikiDoc Sources
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [11] Mahshid Mir, M.D. [12]
Template:WikiDoc Sources
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [13] Mahshid Mir, M.D. [14]
Template:WikiDoc Sources
# Distinctive features of Legionnaires' disease
## Clinical manifestations
- High grade fever
- Dry cough
- Progressive dyspnea
- Bronchial breath sounds
- Adult respiratory distress syndrome
## Laboratory abnormalities
- Legionella urinary antigen positive
- Alveolar consolidation on chest radiograph
- Lobar consolidation on chest radiograph
# Distinctive features of Acute interstitial pneumonia
## Clinical manifestations
- Dry cough
- Progressive dyspnea
- Adult respiratory distress syndrome
## Laboratory abnormalities
- Disseminated consolidation on chest radiograph
- Interstitial infiltrate on chest radiograph
- Increased uptake on Gallium scan
# Distinctive features of Mycoplasma pneumonia
## Clinical manifestations
- Dry cough
- Pleuritic chest pain
- Inflammed, opaque, hypomobile tympanic membrane
- Bronchial breath sounds
## Laboratory abnormalities
- Lymphocytosis
- Cold agglutinins positive
- Alveolar consolidation on chest radiograph
- Interstitial infiltrate on chest radiograph
- Lobar consolidation on chest radiograph
# Distinctive features of Pneumococcal pneumonia
## Clinical manifestations
- Hemoptysis
- Fine rales
- Pleuritic chest pain
- Increased breath sounds
- Bronchial breath sounds
- Dullness on chest percussion
- Purulent sputum
- Shallow respiration
- Pectoriloquy
- Increased tactile fremitus
- Productive cough
- Egophony
- High grade fever
## Laboratory abnormalities
- Pleural effusion (exudative)
- Respiratory alkalosis
- Parenchymal hyperlucency on chest radiograph
- Increased uptake on Gallium scan
- Unilateral diaphragm elevation on chest radiograph
- Alveolar consolidation on chest radiograph
- Lobar consolidation on chest radiograph
- Gram positive diplococci on sputum Gram stain
# Distinctive features of Pneumocystis carinii pneumonia
## Clinical manifestations
- Immunosuppressive state
- Mediastinal emphysema
- Subcutaneous emphysema
- Hacking cough
- Progressive dyspnea
## Laboratory abnormalities
- Respiratory alkalosis
- Serum beta-D-glucan elevated
- Alveolar consolidation on chest radiograph
- Lobar consolidation on chest radiograph
- Interstitial infiltrate on chest radiograph
# Distinctive features of Pulmonary embolism
## Clinical manifestations
- Calf pain / swelling
- Decreased pulse pressure
- Dyspnea with normal chest X-ray
- Hemoptysis
- Hyperventilation
- Immobility
- Increased pulmonic component of heart sound
- Pleuritic chest pain
- Prior DVT
- Pulmonary hypertension
- Right ventricular heave
- Right ventricular hypertrophy
- Right-to-left shunt
- Substernal chest pain
- Tachypnea
- Thrombophlebitis
- Unilateral lower extremity edema
- Venous stasis
## Laboratory abnormalities
- Atrial fibrillation
- Bone fracture
- Atelectasis on chest radiograph
- Lobar consolidation on chest radiograph
- Prominent pulmonary artery on chest radiograph
- Hampton's hump on chest radiograph
- D-dimer elevated
- Right ventricular enlargement on echocardiography
- Thrombus on echocardiography
- Hypocapnia
- Hypoxia
- Segmental perfusion defect on lung scan
- V/Q mismatch on lung scan
- Pleural effusion (exudative / bloody)
- RVH on ECG
- Right axis deviation on ECG
# Distinctive features of Streptococcal pneumonia
## Clinical manifestations
- Pectoriloquy
- Bronchial breath sounds
- Empyema
- Erythema nodosum
- Purulent sputum
- Shallow respiration
- Increased tactile fremitus
- Pleuritic chest pain
- Egophony
## Laboratory abnormalities
- Respiratory alkalosis
- Pleural effusion (exudative)
- Increased uptake on Gallium scan
- Gram-positive cocci in chains on sputum Gram stain
- Alveolar consolidation on chest radiograph
- Lobar consolidation on chest radiograph
# Distinctive features of Viral pneumonia
## Clinical manifestations
- Pleuritic chest pain
- Bronchial breath sounds
- Influenza
- Fine rales
- Bronchovesicular breath sounds
## Laboratory abnormalities
- Lymphocytosis
- Respiratory alkalosis
- Lobar consolidation on chest radiograph
- Interstitial infiltrate on chest radiograph
- ↑ Ferri, Fred (2011). Ferri's differential diagnosis: a practical guide to the differential diagnosis of symptoms, signs, and clinical disorders. Philadelphia, PA: Elsevier/Mosby. ISBN 978-0323076999..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Siegenthaler, Walter (2007). Differential diagnosis in internal medicine: from symptom to diagnosis. Stuttgart New York: Thieme. ISBN 978-1588905512.
- ↑ Mesko, Dusan (2002). Differential diagnosis by laboratory medicine: a quick reference for physicians. Berlin New York: Springer-Verlag. ISBN 978-3540430575.
- ↑ Reeder and Felson's gamuts in radiology: comprehensive lists of roentgen differential diagnosis. Place of publication not identified: Springer. 2014. ISBN 978-1475781229.
- ↑ Burgener, Francis (2008). Differential diagnosis in conventional radiology. Stuttgart New York: Thieme. ISBN 978-1588902757.
- ↑ Gattuso, Paolo (2015). Differential diagnosis in surgical pathology. Philadelphia, PA: Saunders/Elsevier. ISBN 978-1455770137.
- ↑ "DXplain". | https://www.wikidoc.org/index.php/Sandbox_g57 | |
3ce164032977ff2a525444405a339abdcb2864f3 | wikidoc | Sandbox gc4 | Sandbox gc4
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# Overview
Sandbox gc4 is an adenosine nucleotide prodrug that is FDA authorized for the treatment of suspected or laboratory confirmed SARS-CoV-2 infection in adults and pediatric patients hospitalized with severe disease under an Emergency Use Authorization (EUA). Common adverse reactions include nausea, constipation, pyrexia, acute respiratory failure, anemia (decreased hemoglobin), acute kidney injury (decreased eGFR, decreased creatinine clearance, or increased creatinine), hyperglycemia (increased blood glucose), and increased transaminases.
# Adult Indications and Dosage
## Indications and Dosage (Adult)
### Suspected or Laboratory Confirmed SARS-CoV-2 Infection and Severe Disease
Remdesivir is authorized for use under an EUA for treatment of patients hospitalized with suspected or laboratory confirmed SARS-CoV-2 infection and severe disease. Severe disease is defined as patients with an oxygen saturation (SpO2) ≤94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO). Specifically, remdesivir is only authorized for hospitalized adult and pediatric patients for whom use of an intravenous (IV) agent is clinically appropriate.
### Dosage
- The recommended dosage in adults is a single loading dose of remdesivir 200 mg on Day 1 followed by once-daily maintenance doses of remdesivir 100 mg from Day 2 via IV infusion.
- For patients requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 10 days.
- For patients not requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days (i.e., up to a total of 10 days).
- Administer remdesivir via IV infusion in a total volume of up to 250 mL 0.9% sodium chloride over 30 to 120 minutes.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Sandbox gc4 in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Sandbox gc4 in adult patients.
# Pediatric Indications and Dosage
## Indications and Dosage (Pediatric)
### Suspected or Laboratory Confirmed SARS-CoV-2 Infection and Severe Disease
Remdesivir is authorized for use under an EUA for treatment of patients hospitalized with suspected or laboratory confirmed SARS-CoV-2 infection and severe disease. Severe disease is defined as patients with an oxygen saturation (SpO2) ≤94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO). Specifically, remdesivir is only authorized for hospitalized adult and pediatric patients for whom use of an intravenous (IV) agent is clinically appropriate.
### Dosage
For pediatric patients weighing 3.5 kg to less than 40 kg, the dose should be calculated using the mg/kg dose according to the patient’s weight.
- For pediatric patients weighing 3.5 kg to less than 40 kg, use remdesivir for injection, 100 mg, lyophilized powder only. Do not use remdesivir injection, 100 mg/20 mL (5 mg/mL), for pediatric patients weighing 3.5 kg to less than 40 kg due to the higher amount of sulfobutylether-β-cyclodextrin sodium salt (SBECD) present and resulting higher tonicity of the solution concentrate compared to the lyophilized formulation.
- Refer to the table below for recommended dosage form and dosage in pediatric patients according to weight.
- For pediatric patients requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 10 days.
- For pediatric patients not requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days (i.e., up to a total of 10 days).
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Sandbox gc4 in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Sandbox gc4 in pediatric patients.
# Contraindications
Remdesivir is contraindicated in patients with known hypersensitivity to any ingredient of remdesivir.
# Warnings
There are limited clinical data available for remdesivir. Serious and unexpected adverse events may occur that have not been previously reported with remdesivir use.
## Hypersensitivity Including Infusion-Related and Anaphylactic Reactions
Hypersensitivity reactions including infusion-related and anaphylactic reactions have been observed during and following administration of remdesivir. Signs and symptoms may include hypotension, tachycardia, bradycardia, dyspnea, wheezing, angioedema, rash, nausea, vomiting, diaphoresis, and shivering. Slower infusion rates, with a maximum infusion time of up to 120 minutes, can be considered to potentially prevent these signs and symptoms. If signs and symptoms of a clinically significant hypersensitivity reaction occur, immediately discontinue administration of remdesivir and initiate appropriate treatment. The use of remdesivir is contraindicated in patients with known hypersensitivity to remdesivir.
## Increased Risk of Transaminase Elevations
Transaminase elevations have been observed in healthy volunteers who received 200 mg of remdesivir followed by 100 mg doses for 5-10 days. Transaminase elevations have also been reported in patients with COVID-19 who received remdesivir in clinical trials. As transaminase elevations have been reported as a component of COVID-19, including in patients receiving placebo in clinical trials of remdesivir, discerning the contribution of remdesivir to transaminase elevations in this patient population is challenging.
Hepatic laboratory testing should be performed in all patients prior to starting remdesivir and daily while receiving remdesivir.
- Remdesivir should not be initiated in patients with ALT greater than or equal to 5 times the upper limit of normal at baseline.
- Remdesivir should be discontinued in patients who develop:
- ALT greater than or equal to 5 times the upper limit of normal during treatment with remdesivir. Remdesivir may be restarted when ALT is less than 5 times the upper limit of normal.
- ALT elevation accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR.
## Risk of Reduced Antiviral Activity When Coadministered with Chloroquine or Hydroxychloroquine
Coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on in vitro data demonstrating an antagonistic effect of chloroquine on the intracellular metabolic activation and antiviral activity of remdesivir.
# Adverse Reactions
## Clinical Trials Experience
### 1. Overall Safety Summary
In healthy subjects and hospitalized patients with PCR-confirmed SARS-CoV-2 infection, graded elevations in ALT and AST have been observed with a loading dose of remdesivir 200 mg administered intravenously on Day 1 followed by 100 mg administered intravenously once daily for up to 9 days. The mechanism of these elevations is unknown.
Patients should have appropriate clinical and laboratory monitoring to aid in early detection of any potential adverse events. The decision to continue or discontinue remdesivir after development of an adverse event should be made based on the clinical risk benefit assessment for the individual.
1.1 Clinical Studies in Healthy Adults
Remdesivir was evaluated in four Phase 1 studies in 138 healthy adult volunteers (Studies GS-US-399-1812, GS-US-399-1954, GS-US-399-4231, and GS-US-399-5505). In these studies, transient graded elevations in ALT and AST were observed at repeated once-daily doses of remdesivir.
1.2 NIAID ACTT-1 Trial
In a randomized, double-blind, placebo-controlled clinical trial (ACTT-1) of remdesivir in 1,063 hospitalized subjects with COVID-19 treated with remdesivir (n=541) or placebo (n=522) for 10 days, serious adverse events (SAEs) were reported in 21% and 27% of subjects, respectively, and Grade ≥3 non-serious adverse events were reported in 29% and 33% of subjects, respectively. The most common SAE was respiratory failure reported in 5% of subjects treated with remdesivir and 8% of subjects treated with placebo. The most common Grade ≥3 non-serious adverse events in the remdesivir treatment arm are shown below.
1.3 Study GS-US-540-5773
In a randomized, open-label clinical trial (Study GS-US-540-5773) of remdesivir in 397 hospitalized subjects with severe COVID-19 treated with remdesivir for 5 (n=200) or 10 days (n=197), adverse events were reported in 70% and 74% of subjects, respectively, SAEs were reported in 21% and 35% of subjects, respectively, and Grade ≥3 adverse events were reported in 30% and 43% of subjects, respectively. The most common adverse events were nausea (10% in the 5-day group vs 9% in the 10-day group), acute respiratory failure (6% vs 11%), ALT increased (6% vs 8%), and constipation (7% in both groups). Nine (4%) subjects in the 5-day group and 20 (10%) subjects in the 10-day group discontinued treatment due to an adverse event. All-cause mortality at Day 28 was 10% vs 13% in the 5- and 10-day treatment groups, respectively.
### 2. Hepatic Adverse Reactions
2.1 Experience in Healthy Volunteers
Grade 1 and 2 transaminase elevations were observed in healthy volunteers in Study GS-US-399-5505 (200 mg followed by 100 mg dosing for 5–10 days) and Study GS-US-399-1954 (150 mg daily for 7 or 14 days), which resolved after discontinuation of remdesivir.
2.2 NIAID ACTT-1 trial
Grade ≥3 non-serious adverse events of increased aminotransferase levels including ALT, AST, or both were reported in 4% of subjects receiving remdesivir compared with 6% receiving placebo.
2.3 Study GS-US-540-5773
Grade ≥3 hepatic laboratory abnormalities reported in subjects treated with remdesivir for 5 (n=200) or 10 days (n=197) are shown below.
2.4 Compassionate Use Experience
In the compassionate use program in patients with severe or critical illness with COVID-19, liver function test abnormalities were reported in 12% (19/163) of patients. Time to onset from first dose ranged from 1-16 days. Four of these patients discontinued remdesivir treatment with elevated transaminases occurring on Day 5 of remdesivir treatment as per protocol.
Seven cases of serious liver-related laboratory abnormality were identified. There was one SAE of blood bilirubin increased in a critically ill patient with septic shock and multiorgan failure. None of the other cases had reported adverse events suggestive of hyperbilirubinemia or symptoms of hepatitis.
## Postmarketing Experience
There is limited information regarding Sandbox gc4 Postmarketing Experience.
# Drug Interactions
Drug-drug interaction trials of remdesivir and other concomitant medications have not been conducted in humans. Due to antagonism observed in vitro, concomitant use of remdesivir with chloroquine phosphate or hydroxychloroquine sulfate is not recommended.
In vitro, remdesivir is a substrate for drug metabolizing enzymes CYP2C8, CYP2D6, and CYP3A4, and is a substrate for Organic Anion Transporting Polypeptides 1B1 (OATP1B1) and P-glycoprotein (P-gp) transporters. In vitro, remdesivir is an inhibitor of CYP3A4, OATP1B1, OATP1B3, BSEP, MRP4, and NTCP. The clinical relevance of these in vitro assessments has not been established.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
Risk Summary
No adequate and well-controlled studies of remdesivir use in pregnant women have been conducted. Remdesivir should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.
In nonclinical reproductive toxicity studies, remdesivir demonstrated no adverse effect on embryofetal development when administered to pregnant animals at systemic exposures (AUC) of the predominant circulating metabolite of remdesivir (GS-441524) that were 4 times (rats and rabbits) the exposure in humans at the recommended human dose (RHD).
Animal Data
Remdesivir was administered via intravenous injection to pregnant rats and rabbits (up to 20 mg/kg/day) on Gestation Days 6 through 17, and 7 through 20, respectively, and also to rats from Gestation Day 6 to Lactation/Post-partum Day 20. No adverse effects on embryo-fetal (rats and rabbits) or pre/postnatal (rats) development were observed in rats and rabbits at nontoxic doses in pregnant animals. During organogenesis, exposures to the predominant circulating metabolite (GS-441524) were 4 (rats and rabbits) times higher than the exposure in humans at the RHD. In a pre/postnatal development study, exposures to the predominant circulating metabolite of remdesivir (GS-441524) were similar to the human exposures at the RHD.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Sandbox gc4 in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Sandbox gc4 during labor and delivery.
### Nursing Mothers
Risk Summary
There is no information regarding the presence of remdesivir in human milk, the effects on the breastfed infant, or the effects on milk production. In animal studies, remdesivir and metabolites have been detected in the nursing pups of mothers given remdesivir, likely due to the presence of remdesivir in milk. Because of the potential for viral transmission to SARS-CoV-2-negative infants and adverse reactions from the drug in breastfeeding infants, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for remdesivir and any potential adverse effects on the breastfed child from remdesivir or from the underlying maternal condition.
Animal Data
Remdesivir and its metabolites were detected in the plasma of nursing rat pups, likely due to the presence of remdesivir and/or its metabolites in milk, following daily intravenous administration of remdesivir to pregnant mothers from Gestation Day 6 to Lactation Day 20. Exposures in nursing pups were approximately 1% that of maternal exposure on lactation day 10.
### Pediatric Use
The safety, effectiveness, or pharmacokinetics of remdesivir for treatment of COVID-19 have not been assessed in pediatric patients. Physiologically-based pharmacokinetics (PBPK) modeling of pharmacokinetic data from healthy adults was used to derive pediatric doses. Pediatric doses are expected to result in comparable steady-state exposures of remdesivir and metabolites as observed in healthy adults following administration of the recommended dosage regimen.
For pediatric patients with weighing 3.5 kg to less than 40 kg, use remdesivir for injection, 100 mg, lyophilized powder only. Remdesivir injection, 100/20 mL (5 mg/mL), should not be used for pediatric patients weighing 3.5 kg to less than 40 kg due to the higher amount of SBECD present and resulting higher tonicity of the solution concentrate compared to the lyophilized formulation.
Pediatric patients (older than 28 days) must have eGFR determined and full-term neonates (at least 7 days to less than or equal to 28 days) must have serum creatinine determined before dosing and daily while receiving remdesivir. Pediatric patients should be monitored for renal function and consideration given for stopping therapy in the setting of substantial decline.
Because the excipient SBECD is renally cleared and accumulates in patients with decreased renal function, administration of drugs formulated with SBECD (such as remdesivir) is not recommended in adults and pediatric patients (older than 28 days old) with eGFR less than 30 mL/min or in full-term neonates (at least 7 days and less than or equal to 28 days old) with serum creatinine greater than or equal to 1 mg/dL unless the potential benefit outweighs the potential risk.
### Geriatic Use
The pharmacokinetics of remdesivir have not been evaluated in patients >65 years of age. In general, appropriate caution should be exercised in the administration of remdesivir and monitoring of elderly patients, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
### Gender
There is no FDA guidance on the use of Sandbox gc4 with respect to specific gender.
### Race
There is no FDA guidance on the use of Sandbox gc4 with respect to specific race.
### Renal Impairment
Patients with eGFR greater than or equal to 30 mL/min have received remdesivir for treatment of COVID-19 with no dose adjustment. The safety and efficacy of remdesivir have not been assessed in patients with severe renal impairment or ESRD. The pharmacokinetics of remdesivir have not been evaluated in patients with renal impairment. Remdesivir is not recommended in adults and pediatric patients (at least 28 days old) with eGFR less than 30 mL/min or in full-term neonates (at least 7 days and less than or equal to 28 days old) with serum creatinine greater than or equal to 1 mg/dL unless the potential benefit outweighs the potential risk.
Adult and pediatric patients (greater than 28 days old) must have an eGFR determined and full-term neonates (at least 7 days to less than or equal to 28 days old) must have serum creatinine determined before dosing and daily while receiving remdesivir.
Adults
- eGFR, Male: (140 – age in years) × (weight in kg) / 72 × (serum creatinine in mg/dL)
- eGFR, Female: (140 – age in years) × (weight in kg) × 0.85 / 72 × (serum creatinine in mg/dL)
Pediatric patients (greater than 28 days old to less than 1 year of age)
- eGFR: 0.45 × (height in cm) / serum creatinine in mg/dL
Pediatric patients (at least 1 year of age to less than 18 years of age)
- eGFR = 0.413 x (height or length)/Scr) if height/length is expressed in centimeters OR 41.3 x (height or length)/Scr) if height/length is expressed in meters
Because the excipient SBECD is renally cleared and accumulates in patients with decreased renal function, administration of drugs formulated with SBECD with serum creatinine greater than or equal to 1 mg/dL unless the potential benefit outweighs the potential risk.
### Hepatic Impairment
The pharmacokinetics of remdesivir have not been evaluated in patients with hepatic impairment.
It is not known if dosage adjustment is needed in patients with hepatic impairment, and remdesivir should only be used in patients with hepatic impairment if the potential benefit outweighs the potential risk.
Hepatic laboratory testing should be performed in all patients prior to starting remdesivir and daily while receiving remdesivir.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Sandbox gc4 in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Sandbox gc4 in patients who are immunocompromised.
# Administration and Monitoring
### Administration
### Important Testing Prior to and During Treatment and Route of Administration
- Adult and pediatric patients (greater than 28 days old) must have an eGFR determined and full-term neonates (at least 7 days to less than or equal to 28 days old) must have serum creatinine determined before dosing of remdesivir and daily while receiving remdesivir.
- Hepatic laboratory testing should be performed in all patients prior to starting remdesivir and daily while receiving remdesivir.
- Remdesivir should be administered via IV infusion only. Do not administer as an intramuscular (IM) injection.
### Dose Preparation and Administration, Adults and Pediatric Patients Weighing 40 kg and Higher
Adults and pediatric patients weighing 40 kg and higher can use remdesivir for injection, 100 mg, lyophilized powder and remdesivir injection, 100 mg/20 mL (5 mg/mL), solution. See below for different preparation and administration instructions for the two dosage formulations.
Reconstitution Instructions
Remove the required number of single-dose vial(s) from storage. For each vial:
- Aseptically reconstitute remdesivir lyophilized powder by addition of 19 mL of Sterile Water for Injection using a suitably sized syringe and needle per vial.
- Discard the vial if a vacuum does not pull the Sterile Water for Injection into the vial.
- Immediately shake the vial for 30 seconds.
- Allow the contents of the vial to settle for 2 to 3 minutes. A clear solution should result.
- If the contents of the vial are not completely dissolved, shake the vial again for 30 seconds and allow the contents to settle for 2 to 3 minutes. Repeat this procedure as necessary until the contents of the vial are completely dissolved.
- Following reconstitution, each vial contains 100 mg/20 mL (5 mg/mL) of remdesivir solution.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
- After reconstitution, the total storage time before administration should not exceed 4 hours at room temperature or 24 hours at refrigerated temperature (2°C to 8°C ).
Dilution Instructions
Care should be taken during admixture to prevent inadvertent microbial contamination. As there is no preservative or bacteriostatic agent present in this product, aseptic technique must be used in preparation of the final parenteral solution. It is always recommended to administer IV medication immediately after preparation when possible.
- The reconstituted remdesivir lyophilized powder for injection, containing 100 mg/20 mL remdesivir solution, should be further diluted in 100 mL or 250 mL 0.9% sodium chloride infusion bags.
- Using the table below, determine the volume of 0.9% sodium chloride to withdraw from the infusion bag.
- Withdraw and discard the required volume of 0.9% sodium chloride from the bag using an appropriately sized syringe and needle.
- Withdraw the required volume of reconstituted remdesivir for injection from the remdesivir vial using an appropriately sized syringe. Discard any unused portion remaining in the remdesivir vial.
- Transfer the required volume of reconstituted remdesivir for injection to the selected infusion bag.
- Gently invert the bag 20 times to mix the solution in the bag. Do not shake.
- The prepared diluted solution is stable for 4 hours at room temperature (20°C to 25°C ) or 24 hours in the refrigerator at 2°C to 8°C (36°F to 46°F).
Administration Instructions
The prepared diluted solution should not be administered simultaneously with any other IV medication. The compatibility of remdesivir injection with IV solutions and medications other than 0.9% sodium chloride is not known.
Administer the diluted solution with the infusion rate described in the table below.
Dilution Instructions
Care should be taken during admixture to prevent inadvertent microbial contamination. As there is no preservative or bacteriostatic agent present in this product, aseptic technique must be used in preparation of the final parenteral solution. It is always recommended to administer IV medication immediately after preparation when possible.
- Remove the required number of single-dose vial(s) from storage. Each vial contains 100 mg of remdesivir. For each vial:
- Equilibrate to room temperature (20°C to 25°C ). Sealed vials can be stored up to 12 hours at room temperature prior to dilution.
- Inspect the vial to ensure the container closure is free from defects and the solution is free of particulate matter.
- Using the table below, determine the volume of 0.9% sodium chloride to withdraw from the infusion bag
- Withdraw and discard the required volume of 0.9% sodium chloride from the bag using an appropriately sized syringe and needle.
- Withdraw the required volume of remdesivir injection solution from the remdesivir vial using an appropriately sized syringe.
- Pull the syringe plunger rod back to fill the syringe with approximately 10 mL of air.
- Inject the air into the remdesivir injection vial above the level of the solution.
- Invert the vial and withdraw the required volume of remdesivir injection solution into the syringe. The last 5 mL of solution requires more force to withdraw.
- Discard any unused solution remaining in the remdesivir vial.
- Transfer the required volume of remdesivir injection solution to the infusion bag.
- Gently invert the bag 20 times to mix the solution in the bag. Do not shake.
- The prepared diluted solution is stable for 4 hours at room temperature (20°C to 25°C ) or 24 hours in the refrigerator at 2°C to 8°C (36°F to 46°F).
Administration Instructions
The prepared diluted solution should not be administered simultaneously with any other medication. The compatibility of remdesivir injection with IV solutions and medications other than 0.9% sodium chloride is not known.
Administer the diluted solution with the infusion rate described in the table below.
### Dose Preparation and Administration, Pediatric Patients Weighing 3.5 kg to Less Than 40 kg
For pediatric patients weighing 3.5 kg to less than 40 kg, use remdesivir for injection, 100 mg, lyophilized powder only. Remdesivir injection, 100 mg/20 mL (5 mg/mL), should not be used for pediatric patients weighing 3.5 kg to less than 40 kg due to the higher amount of SBECD present and resulting higher tonicity of the solution concentrate compared to the lyophilized formulation.
Remdesivir for Injection, 100 mg, Lyophilized Powder
Reconstitution Instructions
Remove the required number of single-dose vial(s) from storage. For each vial:
- Aseptically reconstitute remdesivir lyophilized powder by addition of 19 mL of Sterile Water for Injection using a suitably sized syringe and needle per vial.
- Discard the vial if a vacuum does not pull the Sterile Water for Injection into the vial.
- Immediately shake the vial for 30 seconds.
- Allow the contents of the vial to settle for 2 to 3 minutes. A clear solution should result.
- If the contents of the vial are not completely dissolved, shake the vial again for 30 seconds and allow the contents to settle for 2 to 3 minutes. Repeat this procedure as necessary until the contents of the vial are completely dissolved.
- Following reconstitution, each vial contains 100 mg/20 mL (5 mg/mL) of remdesivir solution.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
- After reconstitution, the total storage time before administration should not exceed 4 hours at room temperature or 24 hours at refrigerated temperature (2°C to 8°C ).
Dilution Instructions
- Care should be taken during admixture to prevent inadvertent microbial contamination. As there is no preservative or bacteriostatic agent present in this product, aseptic technique must be used in preparation of the final parenteral solution. It is always recommended to administer IV medication immediately after preparation when possible. Following reconstitution as instructed above, each vial will contain a 100 mg/20 mL (5 mg/mL) remdesivir concentrated solution. For pediatric patients weighing 3.5 kg to less than 40 kg, the 100 mg/20 mL (5 mg/mL) remdesivir concentrate should be further diluted to a fixed concentration of 1.25 mg/mL using 0.9% sodium chloride.
- The total required infusion volume of the 1.25 mg/mL remdesivir solution for infusion is calculated from the pediatric weight-based dosing regimens of 5 mg/kg for the Loading Dose and 2.5 mg/kg for each Maintenance Dose.
- Small 0.9% sodium chloride infusion bags (e.g., 25, 50, or 100 mL) or an appropriately sized syringe should be used for pediatric dosing. The recommended dose is administered via IV infusion in a total volume dependent on the dose to yield the target remdesivir concentration of 1.25 mg/mL.
- A syringe may be used for delivering volumes less than 50 mL.
Infusion with IV Bag
- Prepare an IV bag of 0.9% sodium chloride with volume equal to the total infusion volume minus the volume of reconstituted remdesivir solution that will be diluted to achieve a 1.25 mg/mL solution.
- Withdraw the required volume of reconstituted solution containing remdesivir for injection into an appropriately sized syringe.
- Transfer the required volume of reconstituted remdesivir for injection to the 0.9% sodium chloride infusion bag.
- Gently invert the bag 20 times to mix the solution in the bag. Do not shake.
Infusion with Syringe
- Select an appropriately sized syringe equal to or larger than the calculated total infusion volume of 1.25 mg/mL remdesivir solution needed.
- Withdraw the required volume of 100 mg/20 mL (5 mg/mL) reconstituted remdesivir solution from the vial into the syringe followed by the required volume of 0.9% sodium chloride needed to achieve a 1.25 mg/mL remdesivir solution.
- Mix the syringe by inversion 20 times.
- The prepared diluted solution is stable for 4 hours at room temperature (20°C to 25°C ) or 24 hours in the refrigerator at 2°C to 8°C (36°F to 46°F) (including any time before dilution into intravenous infusion fluids).
Administration Instructions
The prepared diluted solution should not be administered simultaneously with any other medication. The compatibility of remdesivir injection with IV solutions and medications other than 0.9% sodium chloride is not known.
Administer the diluted solution with the infusion rate described in the table below.
† Rate of infusion may be adjusted based on total volume to be infused.
### Storage of Prepared Dosages
Lyophilized Powder
After reconstitution, vials can be stored up to 4 hours at room temperature (20°C to 25°C ) prior to administration or 24 hours at refrigerated temperature (2°C to 8°C ). Dilute within the same day as administration.
Injection Solution
Prior to dilution, equilibrate remdesivir injection to room temperature (20°C to 25°C ). Sealed vials can be stored up to 12 hours at room temperature prior to dilution.
Diluted Infusion Solution
Store diluted remdesivir solution for infusion up to 4 hours at room temperature (20°C to 25°C ) or 24 hours at refrigerated temperature (2°C to 8°C ).
IMPORTANT: This product contains no preservative. Any unused portion of a single-dose remdesivir vial should be discarded after a diluted solution is prepared. Maintain adequate records showing receipt, use, and disposition of remdesivir. For unused intact vials, maintain adequate records showing disposition of remdesivir; do not discard unused intact vials
### Dosage Forms and Strengths
- Remdesivir for injection, 100 mg: Each single-dose vial of remdesivir for injection,100 mg, contains a sterile, preservative-free white to off-white to yellow lyophilized powder that is to be reconstituted with 19 mL of Sterile Water for Injection and further diluted into 0.9% sodium chloride infusion bag prior to administration by intravenous infusion. Following reconstitution, each vial contains 100 mg/20 mL (5 mg/mL) remdesivir reconcentrated solution.
- Remdesivir injection, 100 mg/20 mL (5 mg/mL): Each single-dose vial of remdesivir injection contains 100 mg/20 mL (5 mg/mL) of remdesivir as a clear, colorless to yellow, aqueous-based concentrated solution that is to be diluted into 0.9% sodium chloride infusion bag prior to administration by intravenous infusion.
### Monitoring
### Patient Monitoring Recommendations
Given the limited experience with remdesivir at the recommended dose and duration, patients should have appropriate clinical and laboratory monitoring to aid in early detection of any potential adverse events while receiving remdesivir. Additionally, completion of FDA MedWatch Form to report all medication errors and serious adverse events is mandatory.
For mandatory reporting requirements, please see MANDATORY REQUIREMENTS FOR REMDESIVIR ADMINISTRATION UNDER EMERGENCY USE AUTHORIZATION below.
### ADVERSE REACTIONS AND MEDICATION ERRORS REPORTING REQUIREMENTS AND INSTRUCTIONS
The prescribing health care provider and/or the provider’s designee are/is responsible for the mandatory reporting of all medication errors and the following selected adverse events occurring during remdesivir use and considered to be potentially attributable to remdesivir. These adverse events must be reported within 7 calendar days from the onset of the event:
- Deaths
- Serious Adverse Events
Serious Adverse Events are defined as:
- death;
- a life-threatening adverse event;
- inpatient hospitalization or prolongation of existing hospitalization;
- a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions;
- a congenital anomaly/birth defect;
- a medical or surgical intervention to prevent death, a life-threatening event, hospitalization, disability, or congenital anomaly.
If a serious and unexpected adverse event occurs and appears to be associated with the use of remdesivir, the prescribing health care provider and/or the provider’s designee should complete and submit a MedWatch form to FDA using one of the following methods:
- Complete and submit the report online: www.fda.gov/medwatch/report.htm, or
- Use a postage-paid Form FDA 3500 (available at ) and returning by mail (MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787), or by fax (1-800-FDA-0178), or
- Call 1-800-FDA-1088 to request a reporting form
IMPORTANT: When reporting adverse events or medication errors to MedWatch, please complete the entire form with detailed information. It is important that the information reported to FDA be as detailed and complete as possible. Information to include:
- Patient demographics (e.g., patient initials, date of birth)
- Pertinent medical history
- Pertinent details regarding admission and course of illness
- Concomitant medications
- Timing of adverse event(s) in relationship to administration of remdesivir
- Pertinent laboratory and virology information
- Outcome of the event and any additional follow-up information if it is available at the time of the MedWatch report. Subsequent reporting of follow-up information should be completed if additional details become available.
The following steps are highlighted to provide the necessary information for safety tracking:
- In section A, box 1, provide the patient’s initials in the Patient Identifier
- In section A, box 2, provide the patient’s date of birth
- In section B, box 5, description of the event:
Write “Remdesivir EUA” as the first line
Provide a detailed report of medication error and/or adverse event. It is important to provide detailed information regarding the patient and adverse event/medication error for ongoing safety evaluation of this unapproved drug. Please see information to include listed above.
- Write “Remdesivir EUA” as the first line
- Provide a detailed report of medication error and/or adverse event. It is important to provide detailed information regarding the patient and adverse event/medication error for ongoing safety evaluation of this unapproved drug. Please see information to include listed above.
- In section G, box 1, name and address:
Provide the name and contact information of the prescribing health care provider or institutional designee who is responsible for the report.
Provide the address of the treating institution (NOT the health care provider’s office address).
- Provide the name and contact information of the prescribing health care provider or institutional designee who is responsible for the report.
- Provide the address of the treating institution (NOT the health care provider’s office address).
### INSTRUCTIONS FOR HEALTH CARE PROVIDERS
As the health care provider, you must communicate to your patient or parent/caregiver information consistent with the Fact Sheet for Patients and Parents/Caregivers (and provide a copy of the Fact Sheet) prior to the patient receiving remdesivir, including:
- FDA has authorized the emergency use of remdesivir, which is not an FDA approved drug.
- The patient or parent/caregiver has the option to accept or refuse remdesivir.
- The significant known and potential risks and benefits of remdesivir, and the extent to which such risks and benefits are unknown.
- Information on available alternative treatments and the risks and benefits of those alternatives.
If providing this information will delay the administration of remdesivir to a degree that would endanger the lives of patients, the information must be provided to the patients as soon as practicable after remdesivir is administered.
For information on clinical trials that are testing the use of remdesivir for COVID-19, please see .
### MANDATORY REQUIREMENTS FOR REMDESIVIR ADMINISTRATION UNDER EMERGENCY USE AUTHORIZATION
In order to mitigate the risks of using this unapproved product under EUA and to optimize the potential benefit of remdesivir, the following items are required. Use of unapproved remdesivir under this EUA is limited to the following (all requirements must be met):
- Treatment of suspected or laboratory confirmed coronavirus disease 2019 (COVID-19) in adults and pediatric patients hospitalized with severe disease. Severe disease is defined as patients with an oxygen saturation (SpO2) ≤94% on room air or requiring supplemental oxygen or requiring invasive mechanical ventilation, or requiring ECMO. Specifically, remdesivir is authorized only for the following patients who are admitted to a hospital and under the care or consultation of a licensed clinician (skilled in the diagnosis and management of patients with potentially life-threatening illness and the ability to recognize and manage medication-related adverse events):
Adult patients for whom use of an IV agent is clinically appropriate.
Pediatric patients for whom use of an IV agent is clinically appropriate.
- Adult patients for whom use of an IV agent is clinically appropriate.
- Pediatric patients for whom use of an IV agent is clinically appropriate.
- As the health care provider, communicate to your patient or parent/caregiver information consistent with the Fact Sheet for Patients and Parents/Caregivers prior to the patient receiving remdesivir. Health care providers (to the extent practicable given the circumstances of the emergency) must document in the patient’s medical record that the patient/caregiver has been:
Given the Fact Sheet for Patients and Parents/Caregivers,
Informed of alternatives to receiving remdesivir, and
Informed that remdesivir is an unapproved drug that is authorized for use under EUA.
- Given the Fact Sheet for Patients and Parents/Caregivers,
- Informed of alternatives to receiving remdesivir, and
- Informed that remdesivir is an unapproved drug that is authorized for use under EUA.
- Adult and pediatric patients (greater than 28 days old) must have an eGFR determined and full-term neonates (at least 7 days to less than or equal to 28 days old) must have serum creatinine determined prior to remdesivir first administration and daily while receiving remdesivir.
- Hepatic laboratory testing should be performed in all patients prior to starting remdesivir and daily while receiving remdesivir.
- Patients with known hypersensitivity to any ingredient of remdesivir must not receive remdesivir.
- The prescribing health care provider and/or the provider’s designee are/is responsible for mandatory responses to requests from FDA for information about adverse events and medication errors following receipt of remdesivir.
- The prescribing health care provider and/or the provider’s designee are/is responsible for mandatory reporting of all medication errors and adverse events (death, serious adverse events*) considered to be potentially related to remdesivir occurring during remdesivir treatment within 7 calendar days from the onset of the event. The reports should include unique identifiers and the words “Remdesivir under Emergency Use Authorization (EUA)” in the description section of the report.
- Submit adverse event reports to FDA MedWatch using one of the following methods:
Complete and submit the report online: www.fda.gov/medwatch/report.htm, or
By using a postage-paid Form FDA 3500 (available at ) and returning by mail (MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787), or by fax (1-800-FDA-0178), or
Call 1-800-FDA-1088 to request a reporting form
Submitted reports should include in the field name, “Describe Event, Problem, or Product Use/Medication Error” a statement “Remdesivir under Emergency Use Authorization (EUA).”
- Complete and submit the report online: www.fda.gov/medwatch/report.htm, or
- By using a postage-paid Form FDA 3500 (available at ) and returning by mail (MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787), or by fax (1-800-FDA-0178), or
- Call 1-800-FDA-1088 to request a reporting form
- Submitted reports should include in the field name, “Describe Event, Problem, or Product Use/Medication Error” a statement “Remdesivir under Emergency Use Authorization (EUA).”
### OTHER REPORTING REQUIREMENTS
In addition please provide a copy of all FDA MedWatch forms to:
Gilead Pharmacovigilance and Epidemiology
Fax: 1-650-522-5477
E-mail: [email protected]
### APPROVED AVAILABLE ALTERNATIVES
There is no approved available alternative product. There are EUAs for other COVID-19 treatments. Additional information on COVID-19 treatments can be found at . The health care provider should visit / to determine whether the patient may be eligible for enrollment in a clinical trial.
### AUTHORITY FOR ISSUANCE OF THE EUA
The Secretary of HHS has declared a public health emergency that justifies the emergency use of remdesivir to treat COVID-19 caused by SARS-CoV-2. In response, the FDA has issued an EUA for the unapproved product, remdesivir, for the treatment of COVID-19.† As a health care provider, you must comply with the MANDATORY REQUIREMENTS of the EUA (see above).
FDA issued this EUA, requested by Gilead Sciences, Inc. and based on their submitted data.
Although limited scientific information is available, based on the totality of the scientific evidence available to date, it is reasonable to believe that remdesivir may be effective for the treatment of COVID-19 in patients as specified in this Fact Sheet. You may be contacted and asked to provide information to help with the assessment of the use of the product during this emergency.
This EUA for remdesivir will end when the Secretary determines that the circumstances justifying the EUA no longer exist or when there is a change in the approval status of the product such that an EUA is no longer needed.
† The health care provider should visit clinicaltrials.gov to determine whether there is an active clinical trial for the product in this disease/condition and whether enrollment of the patient(s) in a clinical trial is more appropriate than product use under this EUA.
# IV Compatibility
There is limited information regarding the compatibility of Sandbox gc4 and IV administrations.
# Overdosage
There is no human experience of acute overdosage with remdesivir. Treatment of overdose with remdesivir should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with remdesivir.
# Pharmacology
## Mechanism of Action
Remdesivir is an adenosine nucleotide prodrug that distributes into cells where it is metabolized to form the pharmacologically active nucleoside triphosphate metabolite. Metabolism of remdesivir to remdesivir triphosphate has been demonstrated in multiple cell types. Remdesivir triphosphate acts as an analog of adenosine triphosphate (ATP) and competes with the natural ATP substrate for incorporation into nascent RNA chains by the SARS-CoV-2 RNA-dependent RNA polymerase, which results in delayed chain termination during replication of the viral RNA. Remdesivir triphosphate is a weak inhibitor of mammalian DNA and RNA polymerases with low potential for mitochondrial toxicity.
## Structure
Remdesivir is a nucleoside ribonucleic acid (RNA) polymerase inhibitor.
The chemical name for remdesivir is 2-ethylbutyl N-{(S)-triazin-7-yl)-2,5-anhydro-d-altrononitril-6-O-yl]phenoxyphosphoryl}-L-alaninate. It has a molecular formula of C27H35N6O8P and a molecular weight of 602.6 g/mol. Remdesivir has the following structural formula:
## Physical Appearance
Lyophilized Powder
Remdesivir for injection, 100 mg, is a sterile, preservative-free lyophilized powder that is to be reconstituted with 19 mL of Sterile Water for Injection and further diluted into 0.9% sodium chloride infusion bag prior to administration by intravenous infusion. Remdesivir for injection, 100 mg, is supplied in a single-dose clear glass vial.
The appearance of the lyophilized powder is white to off-white to yellow.
Injection Solution
Remdesivir injection, 100 mg/20 mL (5 mg/mL), is a sterile, preservative-free, clear, colorless to yellow, aqueous-based concentrated solution that is to be diluted into 0.9% sodium chloride infusion bag prior to administration by intravenous infusion. Remdesivir injection, 100 mg/20 mL (5 mg/mL), is supplied in a single-dose clear glass vial.
13.2 Inactive Ingredients
The inactive ingredients are sulfobutylether-β-cyclodextrin sodium salt (SBECD), Water for Injection, USP, and may include hydrochloric acid and/or sodium hydroxide for pH adjustment. Remdesivir for injection, 100 mg, contains 3 g SBECD, and remdesivir injection, 100 mg/20 mL (5 mg/mL), contains 6 g SBECD.
## Pharmacodynamics
There is limited information regarding Sandbox gc4 Pharmacodynamics.
## Pharmacokinetics
The pharmacokinetics (PK) of remdesivir have been evaluated in adults in several Phase 1 trials.
- The pharmacokinetics of remdesivir and metabolites have not been in evaluated in patients with COVID-19.
- Following single-dose, 2-hour IV administration of remdesivir solution formulation at doses ranging from 3 to 225 mg, remdesivir exhibited a linear PK profile.
- Following single-dose, 2-hour IV administration of remdesivir at doses of 75 and 150 mg, both the lyophilized and solution formulations provided comparable PK parameters (AUCinf, AUClast, and Cmax), indicating similar formulation performance.
- Remdesivir 75 mg lyophilized formulation administered IV over 30 minutes provided similar peripheral blood mononuclear cell (PBMC) exposure of the active triphosphate metabolite GS-443902 as remdesivir 150 mg lyophilized formulation administered IV over 2 hours.
- Following a single 150 mg intravenous dose of -remdesivir, mean total recovery of the dose was >92%, consisting of approximately 74% and 18% recovered in urine and feces, respectively. The majority of remdesivir dose recovered in urine was metabolite GS-441524 (49%), while 10% was recovered as remdesivir.
Specific Populations
Sex, Race and Age
Pharmacokinetic differences based on sex, race, and age have not been evaluated.
Pediatric Patients
The pharmacokinetics of remdesivir in pediatric patients has not been evaluated.
PBPK modeling of pharmacokinetic data from healthy adults was used to derive pediatric doses. PBPK modeling incorporated in vitro data for remdesivir and other similar compounds along with age-dependent changes in physiology (e.g., organ volume/function, blood flow), metabolism, distribution, and elimination of remdesivir. Pediatric doses are expected to result in comparable steady-state exposures of remdesivir and metabolites as observed in healthy adults following administration of the recommended dosage regimen.
Renal Impairment
Because the excipient SBECD is renally cleared and accumulates in patients with decreased renal function, administration of drugs formulated with SBECD (such as remdesivir) is not recommended in adult and pediatric patients (greater than 28 days old) with eGFR less than 30 mL/min or in full-term neonates (at least 7 days and less than or equal to 28 days old) with serum creatinine greater than or equal to 1 mg/dL unless the potential benefit outweighs the potential risk.
### Microbiology/Resistance Information
Antiviral Activity
Remdesivir exhibited cell culture antiviral activity against a clinical isolate of SARS-CoV-2 in primary human airway epithelial (HAE) cells with a 50% effective concentration (EC50) of 9.9 nM after 48 hours of treatment. The EC50 values of remdesivir against SARS-CoV-2 in Vero cells was 137 nM at 24 hours and 750 nM at 48 hours post-treatment. The antiviral activity of remdesivir was antagonized by chloroquine phosphate in a dose-dependent manner when the two drugs were co-incubated at clinically relevant concentrations in HEp-2 cells infected with respiratory syncytial virus (RSV). Higher remdesivir EC50 values were observed with increasing concentrations of chloroquine phosphate. Increasing concentrations of chloroquine phosphate reduced formation of remdesivir triphosphate in normal human bronchial epithelial cells.
Resistance
No clinical data are available on the development of SARS-CoV-2 resistance to remdesivir. The cell culture development of SARS-CoV-2 resistance to remdesivir has not been assessed to date.
Cell culture resistance profiling of remdesivir using the rodent CoV murine hepatitis virus identified 2 substitutions (F476L and V553L) in the viral RNA-dependent RNA polymerase at residues conserved across CoVs that conferred a 5.6-fold reduced susceptibility to remdesivir. The mutant viruses showed reduced viral fitness in cell culture and introduction of the corresponding substitutions (F480L and V557L) into SARS-CoV resulted in 6-fold reduced susceptibility to remdesivir in cell culture and attenuated SARS-CoV pathogenesis in a mouse model.
## Nonclinical Toxicology
Carcinogenesis
Given the short-term administration of remdesivir for the treatment of COVID-19, long-term animal studies to evaluate the carcinogenic potential of remdesivir are not required.
Mutagenesis
Remdesivir was not genotoxic in a battery of assays, including bacterial mutagenicity, chromosome aberration using human peripheral blood lymphocytes and in vivo rat micronucleus assays.
Impairment of Fertility
Nonclinical toxicity studies in rats demonstrated no adverse effect on male fertility at exposures of the predominant circulating metabolite (GS-441524) approximately 2 times the exposure in humans at the RHD.
Reproductive toxicity, including decreases in corpora lutea, numbers of implantation sites, and viable embryos, was seen when remdesivir was administered intravenous daily at a systemically toxic dose (10 mg/kg) in female rats 14 days prior to mating and during conception; exposures of the predominant circulating metabolite (GS-441524) were 1.3 times the exposure in humans at the RHD.
Animal Toxicology and/or Pharmacology
Intravenous administration (slow bolus) of remdesivir to male rhesus monkeys at dosage levels of 5, 10, and 20 mg/kg/day for 7 days resulted, at all dose levels, in increased mean urea nitrogen and increased mean creatinine, renal tubular atrophy, and basophilia and casts.
Intravenous administration (slow bolus) of remdesivir to rats at dosage levels of ≥3 mg/kg/day for up to 4 weeks resulted in findings indicative of kidney injury and/or dysfunction.
### Animal Pharmacologic and Efficacy Data
It is unknown, at present, how the observed antiviral activity of remdesivir in animal models of SARS-CoV-2 infection will translate into clinical efficacy in patients with symptomatic disease. Key attributes of the remdesivir nonclinical profile supporting its development for the treatment of COVID-19 are provided below:
- Remdesivir showed cell culture antiviral activity against a clinical isolate of SARS-CoV-2 in primary HAE cells (EC50 value= 9.9 nM). The EC50 values of remdesivir against SARS-CoV-2 in Vero cells has been reported to be 137 nM at 24 hours and 750 nM at 48 hours post-treatment.
- Remdesivir showed antiviral activity in SARS-CoV-2-infected rhesus monkeys. Administration of remdesivir at 10/5 mg/kg (10 mg/kg first dose, followed by 5 mg/kg once daily thereafter) using IV bolus injection initiated 12 hours post-inoculation with SARS-CoV-2 resulted in a reduction in clinical signs of respiratory disease, lung pathology and gross lung lesions, and lung viral RNA levels compared with vehicle-treated animals.
# Clinical Studies
Remdesivir is an unapproved antiviral drug with available data from two randomized clinical trials in patients with COVID-19.
Clinical Trials in Subjects with COVID-19
NIAID ACTT-1 Trial in Subjects with Mild/Moderate and Severe COVID-19
A randomized, double-blind, placebo-controlled clinical trial evaluated remdesivir 200 mg once daily for 1 day followed by remdesivir 100 mg once daily for 9 days (for a total of up to 10 days of intravenously administered therapy) in hospitalized adult subjects with COVID-19 with evidence of lower respiratory tract involvement. The trial enrolled 1,063 subjects: 120 subjects with mild/moderate disease and 943 subjects with severe disease. A total of 272 subjects (25.6%) (n=125 received remdesivir) were on mechanical ventilation/ECMO. Subjects were randomized in a 1:1 manner, stratified by disease severity at enrollment, to receive remdesivir (n=541) or placebo (n=522), plus standard of care. The primary clinical endpoint was time to recovery within 28 days after randomization, defined as either discharged from the hospital or hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care. In a preliminary analysis of the primary endpoint performed after 607 recoveries were attained (n=1,059; 538 remdesivir, 521 placebo), the median time to recovery was 11 days in the remdesivir group compared to 15 days in the placebo group (recovery rate ratio 1.32; 95% CI 1.12 to 1.55, p<0.001); 14-day mortality was 7.1% for the remdesivir group versus 11.9% for the placebo group (hazard ratio 0.70 , p=0.07). Among subjects with mild/moderate disease at enrollment (n=119), the median time to recovery was 5 days in both the remdesivir and placebo groups (recovery rate ratio 1.09; ). Among subjects with severe disease at enrollment (n=940), the median time to recovery was 12 days in the remdesivir group compared to 18 days in the placebo group (recovery rate ratio, 1.37; ; p<0.001; n=940) and 14-day mortality was 7.7% and 13%, respectively (hazard ratio, 0.71; ).
Overall, the odds of improvement in the ordinal scale were higher in the remdesivir group at Day 15 when compared to the placebo group (odds ratio, 1.50; , p=0.001; n=844).
Study GS-US-540-5773 in Subjects with Severe COVID-19
A randomized, open-label multi-center clinical trial (Study GS-US-540-5773) of hospitalized subjects at least 12 years of age with confirmed SARS-CoV-2 infection, oxygen saturation of ≤94% on room air, and radiological evidence of pneumonia compared 197 subjects who received IV remdesivir for 5 days with 200 subjects who received IV remdesivir for 10 days. Patients on mechanical ventilation at screening were excluded. All subjects received 200 mg of remdesivir on Day 1 and 100 mg once daily on subsequent days, plus standard of care. The primary endpoint was clinical status on Day 14 assessed on a 7-point ordinal scale ranging from hospital discharge to increasing levels of oxygen and ventilatory support to death. After adjusting for between-group differences at baseline, patients receiving a 10-day course of remdesivir had similar clinical status at Day 14 as those receiving a 5-day course (odds ratio for improvement: 0.75; ).
Clinical improvement was defined as an improvement of two or more points from baseline on the 7-point ordinal scale. Subjects achieved clinical recovery if they no longer required oxygen support or were discharged from the hospital. At Day 14, observed rates between the 5- and 10-day treatment groups were 65% vs 54% for clinical improvement, 70% vs 59% for clinical recovery, and 8% vs 11% for mortality.
# How Supplied
### How Supplied
Lyophilized Powder
Remdesivir for injection, 100 mg, is supplied as a single-dose vial containing a sterile, preservative-free white to off-white to yellow lyophilized powder that is to be reconstituted with 19 mL of Sterile Water for Injection and further diluted into 0.9% sodium chloride infusion bag prior to administration by intravenous infusion. Following reconstitution, each vial contains 100 mg/20 mL (5 mg/mL) remdesivir reconcentrated solution.
Discard unused portion.
The container closure is not made with natural rubber latex.
Injection Solution
Remdesivir injection is supplied as a single dose vial containing 100 mg/20 mL (5 mg/mL) of remdesivir per vial for dilution into 0.9% sodium chloride infusion bag.
Discard unused portion.
The container closure is not made with natural rubber latex.
### Storage and Handling
Do not reuse or save unused remdesivir lyophilized powder, injection solution, or diluted solution for infusion for future use. This product contains no preservative.
Lyophilized Powder
Store remdesivir for injection, 100 mg, vials below 30°C (below 86°F) until required for use. Do not use after expiration date.
After reconstitution, vials can be stored up to 4 hours at room temperature (20°C to 25°C ) prior to administration or 24 hours at refrigerated temperature (2°C to 8°C ). Dilute within the same day as administration.
Injection Solution
Store remdesivir injection, 100 mg/20 mL (5 mg/mL), vials at refrigerated temperature (2°C to 8°C ) until required for use. Do not use after expiration date. Dilute within the same day as administration.
Prior to dilution, equilibrate remdesivir injection to room temperature (20°C to 25°C ). Sealed vials can be stored up to 12 hours at room temperature prior to dilution.
Diluted Solution for Infusion
Store diluted remdesivir solution for infusion up to 4 hours at room temperature (20°C to 25°C ) or 24 hours at refrigerated temperature (2°C to 8°C ).
# Patient Counseling Information
You are being given a medicine called remdesivir for the treatment of coronavirus disease 2019 (COVID-19).
This Fact Sheet contains information to help you understand the potential risks and potential benefits of taking remdesivir, which you have received or may receive.
There is no U.S. Food and Drug Administration (FDA) approved product available to treat COVID-19. Receiving remdesivir may benefit certain people in the hospital with COVID-19.
Read this Fact Sheet for information about remdesivir. Talk to your healthcare provider if you have questions. It is your choice to receive remdesivir or stop it at any time.
### What is COVID-19?
COVID-19 is caused by a virus called a coronavirus. This type of coronavirus has not been seen before.
This new coronavirus was first found in people in Wuhan, Hubei Province, China in December 2019. Person-to-person spread was reported outside Hubei and in countries outside China, including in the United States. You can get COVID-19 through contact with another person who has the virus.
COVID-19 illnesses have ranged from very mild (including some with no reported symptoms) to severe, including illness resulting in death. While information so far suggests that most COVID-19 illness is mild, serious illness can happen and may cause some of your other medical conditions to become worse. Older people and people of all ages with severe, long-lasting (chronic) medical conditions like heart disease, lung disease, and diabetes, for example, seem to be at higher risk of being hospitalized for COVID-19.
### What are the symptoms of COVID-19?
The symptoms of COVID-19 are fever, cough, and shortness of breath, which may appear 2 to 14 days after exposure. Serious illness including breathing problems can occur and may cause your other medical conditions to become worse.
### What is remdesivir?
Remdesivir is an investigational antiviral medicine used for the treatment of certain people in the hospital with COVID-19. Remdesivir is investigational because it is still being studied. There is limited information known about the safety and effectiveness of using remdesivir to treat people in the hospital with COVID-19. Remdesivir was shown in a clinical trial to shorten the time to recovery in some people. There are no medicines approved by the FDA as safe and effective to treat people in the hospital who have COVID-19. Therefore, the FDA has authorized the emergency use of remdesivir for the treatment of COVID-19 under an Emergency Use Authorization (EUA).
For more information on EUA, see the What is an Emergency Use Authorization (EUA) section at the end of this Fact Sheet.
### What should I tell my healthcare provider before I receive remdesivir?
Tell your healthcare provider about all of your medical conditions, including if you:
- Have any allergies
- Have kidney or liver problems
- Are pregnant or plan to become pregnant
- Are breastfeeding or plan to breastfeed
- Have any serious illnesses
- Are taking any medicines (prescription, over-the-counter, vitamins, or herbal products). Remdesivir may affect the way other medicines work, and other medicines may affect how remdesivir works.
- Especially tell your healthcare provider if you are taking the medicines chloroquine phosphate or hydroxychloroquine sulfate.
### How will I receive remdesivir?
Remdesivir is given to you through a vein (intravenous or IV) one time each day for up to 10 days depending on what your healthcare provider thinks is best for you. Remdesivir may help decrease the amount of the coronavirus in your body. This may help you to get better faster.
### What are the important possible side effects of remdesivir?
Possible side effects of remdesivir are:
- Allergic reactions. Remdesivir can cause allergic reactions, including serious reactions, during and after infusion. Tell your healthcare provider or nurse, or get medical help right away if you get any of the following signs and symptoms of allergic reactions: low blood pressure, changes in your heartbeat, shortness of breath, wheezing, swelling of your lips, face, or throat, rash, nausea, vomiting, sweating, or shivering.
- Increases in levels of liver enzymes. Increases in levels of liver enzymes have been seen in people who have received remdesivir, which may be a sign of inflammation or damage to cells in the liver. Your healthcare provider will do blood tests to check your liver before you receive remdesivir and daily while receiving remdesivir.
These are not all the possible side effects of remdesivir. Remdesivir is still being studied so it is possible that all of the risks are not known at this time.
Not a lot of people have taken remdesivir. Serious and unexpected side effects may happen. The side effects of getting any medicine by vein may include brief pain, bleeding, bruising of the skin, soreness, swelling, and possible infection at the injection site.
### What other treatment choices are there?
Like remdesivir, FDA may allow for the emergency use of other medicines to treat people in the hospital with COVID-19. Go to for information on the emergency use of other medicines that are not approved by FDA to treat people in the hospital with COVID-19. Your healthcare provider may talk with you about clinical trials you may be eligible for.
It is your choice to be treated or not to be treated with remdesivir. Should you decide not to receive it or stop it at any time, it will not change your standard medical care.
### What if I am pregnant or breastfeeding?
There is limited experience giving remdesivir to pregnant women or breastfeeding mothers. For a mother and unborn baby, the benefit of receiving remdesivir may be greater than the risk from the treatment. If you are pregnant or breastfeeding, discuss your options and specific situation with your healthcare provider.
### How do I report side effects with remdesivir?
Tell your healthcare provider right away if you have any side effect that bothers you or does not go away. Report side effects to FDA MedWatch at or call 1-800-FDA-1088.
### How can I learn more?
- Ask your healthcare provider.
- Visit
- Contact your local or state public health department.
### What is an Emergency Use Authorization (EUA)
The United States FDA has made remdesivir available under an emergency access mechanism called an EUA. The EUA is supported by a Secretary of Health and Human Service (HHS) declaration that circumstances exist to justify the emergency use of drugs and biological products during the COVID-19 pandemic. Remdesivir has not undergone the same type of review as an FDA-approved or cleared product. FDA may issue an EUA when certain criteria are met, which includes that there are no adequate, approved, available alternatives. In addition, the FDA decision is based on the totality of scientific evidence available showing that it is reasonable to believe that the product meets certain criteria for safety, performance, and labeling and may be effective in treatment of patients during the COVID-19 pandemic. All of these criteria must be met to allow for the product to be used in the treatment of patients during the COVID-19 pandemic.
The EUA for remdesivir is in effect for the duration of the COVID-19 declaration justifying emergency use of these products, unless terminated or revoked (after which the products may no longer be used)
Source: Fact Sheet for Patients and Parents/Caregivers
# Precautions with Alcohol
Alcohol-Sandbox gc4 interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
# Brand Names
Veklury®
# Look-Alike Drug Names
There is limited information regarding Sandbox gc4 Look-Alike Drug Names.
# Drug Shortage Status | Sandbox gc4
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gerald Chi, M.D.
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Sandbox gc4 is an adenosine nucleotide prodrug that is FDA authorized for the treatment of suspected or laboratory confirmed SARS-CoV-2 infection in adults and pediatric patients hospitalized with severe disease under an Emergency Use Authorization (EUA). Common adverse reactions include nausea, constipation, pyrexia, acute respiratory failure, anemia (decreased hemoglobin), acute kidney injury (decreased eGFR, decreased creatinine clearance, or increased creatinine), hyperglycemia (increased blood glucose), and increased transaminases.
# Adult Indications and Dosage
## Indications and Dosage (Adult)
### Suspected or Laboratory Confirmed SARS-CoV-2 Infection and Severe Disease
Remdesivir is authorized for use under an EUA for treatment of patients hospitalized with suspected or laboratory confirmed SARS-CoV-2 infection and severe disease. Severe disease is defined as patients with an oxygen saturation (SpO2) ≤94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO). Specifically, remdesivir is only authorized for hospitalized adult and pediatric patients for whom use of an intravenous (IV) agent is clinically appropriate.
### Dosage
- The recommended dosage in adults is a single loading dose of remdesivir 200 mg on Day 1 followed by once-daily maintenance doses of remdesivir 100 mg from Day 2 via IV infusion.
- For patients requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 10 days.
- For patients not requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days (i.e., up to a total of 10 days).
- Administer remdesivir via IV infusion in a total volume of up to 250 mL 0.9% sodium chloride over 30 to 120 minutes.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Sandbox gc4 in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Sandbox gc4 in adult patients.
# Pediatric Indications and Dosage
## Indications and Dosage (Pediatric)
### Suspected or Laboratory Confirmed SARS-CoV-2 Infection and Severe Disease
Remdesivir is authorized for use under an EUA for treatment of patients hospitalized with suspected or laboratory confirmed SARS-CoV-2 infection and severe disease. Severe disease is defined as patients with an oxygen saturation (SpO2) ≤94% on room air or requiring supplemental oxygen or requiring mechanical ventilation or requiring extracorporeal membrane oxygenation (ECMO). Specifically, remdesivir is only authorized for hospitalized adult and pediatric patients for whom use of an intravenous (IV) agent is clinically appropriate.
### Dosage
For pediatric patients weighing 3.5 kg to less than 40 kg, the dose should be calculated using the mg/kg dose according to the patient’s weight.
- For pediatric patients weighing 3.5 kg to less than 40 kg, use remdesivir for injection, 100 mg, lyophilized powder only. Do not use remdesivir injection, 100 mg/20 mL (5 mg/mL), for pediatric patients weighing 3.5 kg to less than 40 kg due to the higher amount of sulfobutylether-β-cyclodextrin sodium salt (SBECD) present and resulting higher tonicity of the solution concentrate compared to the lyophilized formulation.
- Refer to the table below for recommended dosage form and dosage in pediatric patients according to weight.
- For pediatric patients requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 10 days.
- For pediatric patients not requiring invasive mechanical ventilation and/or ECMO, total treatment duration is 5 days. If a patient does not demonstrate clinical improvement, treatment may be extended for up to 5 additional days (i.e., up to a total of 10 days).
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Sandbox gc4 in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Sandbox gc4 in pediatric patients.
# Contraindications
Remdesivir is contraindicated in patients with known hypersensitivity to any ingredient of remdesivir.
# Warnings
There are limited clinical data available for remdesivir. Serious and unexpected adverse events may occur that have not been previously reported with remdesivir use.
## Hypersensitivity Including Infusion-Related and Anaphylactic Reactions
Hypersensitivity reactions including infusion-related and anaphylactic reactions have been observed during and following administration of remdesivir. Signs and symptoms may include hypotension, tachycardia, bradycardia, dyspnea, wheezing, angioedema, rash, nausea, vomiting, diaphoresis, and shivering. Slower infusion rates, with a maximum infusion time of up to 120 minutes, can be considered to potentially prevent these signs and symptoms. If signs and symptoms of a clinically significant hypersensitivity reaction occur, immediately discontinue administration of remdesivir and initiate appropriate treatment. The use of remdesivir is contraindicated in patients with known hypersensitivity to remdesivir.
## Increased Risk of Transaminase Elevations
Transaminase elevations have been observed in healthy volunteers who received 200 mg of remdesivir followed by 100 mg doses for 5-10 days. Transaminase elevations have also been reported in patients with COVID-19 who received remdesivir in clinical trials. As transaminase elevations have been reported as a component of COVID-19, including in patients receiving placebo in clinical trials of remdesivir, discerning the contribution of remdesivir to transaminase elevations in this patient population is challenging.
Hepatic laboratory testing should be performed in all patients prior to starting remdesivir and daily while receiving remdesivir.
- Remdesivir should not be initiated in patients with ALT greater than or equal to 5 times the upper limit of normal at baseline.
- Remdesivir should be discontinued in patients who develop:
- ALT greater than or equal to 5 times the upper limit of normal during treatment with remdesivir. Remdesivir may be restarted when ALT is less than 5 times the upper limit of normal.
- ALT elevation accompanied by signs or symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR.
## Risk of Reduced Antiviral Activity When Coadministered with Chloroquine or Hydroxychloroquine
Coadministration of remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not recommended based on in vitro data demonstrating an antagonistic effect of chloroquine on the intracellular metabolic activation and antiviral activity of remdesivir.
# Adverse Reactions
## Clinical Trials Experience
### 1. Overall Safety Summary
In healthy subjects and hospitalized patients with PCR-confirmed SARS-CoV-2 infection, graded elevations in ALT and AST have been observed with a loading dose of remdesivir 200 mg administered intravenously on Day 1 followed by 100 mg administered intravenously once daily for up to 9 days. The mechanism of these elevations is unknown.
Patients should have appropriate clinical and laboratory monitoring to aid in early detection of any potential adverse events. The decision to continue or discontinue remdesivir after development of an adverse event should be made based on the clinical risk benefit assessment for the individual.
1.1 Clinical Studies in Healthy Adults
Remdesivir was evaluated in four Phase 1 studies in 138 healthy adult volunteers (Studies GS-US-399-1812, GS-US-399-1954, GS-US-399-4231, and GS-US-399-5505). In these studies, transient graded elevations in ALT and AST were observed at repeated once-daily doses of remdesivir.
1.2 NIAID ACTT-1 Trial
In a randomized, double-blind, placebo-controlled clinical trial (ACTT-1) of remdesivir in 1,063 hospitalized subjects with COVID-19 treated with remdesivir (n=541) or placebo (n=522) for 10 days, serious adverse events (SAEs) were reported in 21% and 27% of subjects, respectively, and Grade ≥3 non-serious adverse events were reported in 29% and 33% of subjects, respectively. The most common SAE was respiratory failure reported in 5% of subjects treated with remdesivir and 8% of subjects treated with placebo. The most common Grade ≥3 non-serious adverse events in the remdesivir treatment arm are shown below.
1.3 Study GS-US-540-5773
In a randomized, open-label clinical trial (Study GS-US-540-5773) of remdesivir in 397 hospitalized subjects with severe COVID-19 treated with remdesivir for 5 (n=200) or 10 days (n=197), adverse events were reported in 70% and 74% of subjects, respectively, SAEs were reported in 21% and 35% of subjects, respectively, and Grade ≥3 adverse events were reported in 30% and 43% of subjects, respectively. The most common adverse events were nausea (10% in the 5-day group vs 9% in the 10-day group), acute respiratory failure (6% vs 11%), ALT increased (6% vs 8%), and constipation (7% in both groups). Nine (4%) subjects in the 5-day group and 20 (10%) subjects in the 10-day group discontinued treatment due to an adverse event. All-cause mortality at Day 28 was 10% vs 13% in the 5- and 10-day treatment groups, respectively.
### 2. Hepatic Adverse Reactions
2.1 Experience in Healthy Volunteers
Grade 1 and 2 transaminase elevations were observed in healthy volunteers in Study GS-US-399-5505 (200 mg followed by 100 mg dosing for 5–10 days) and Study GS-US-399-1954 (150 mg daily for 7 or 14 days), which resolved after discontinuation of remdesivir.
2.2 NIAID ACTT-1 trial
Grade ≥3 non-serious adverse events of increased aminotransferase levels including ALT, AST, or both were reported in 4% of subjects receiving remdesivir compared with 6% receiving placebo.
2.3 Study GS-US-540-5773
Grade ≥3 hepatic laboratory abnormalities reported in subjects treated with remdesivir for 5 (n=200) or 10 days (n=197) are shown below.
2.4 Compassionate Use Experience
In the compassionate use program in patients with severe or critical illness with COVID-19, liver function test abnormalities were reported in 12% (19/163) of patients. Time to onset from first dose ranged from 1-16 days. Four of these patients discontinued remdesivir treatment with elevated transaminases occurring on Day 5 of remdesivir treatment as per protocol.
Seven cases of serious liver-related laboratory abnormality were identified. There was one SAE of blood bilirubin increased in a critically ill patient with septic shock and multiorgan failure. None of the other cases had reported adverse events suggestive of hyperbilirubinemia or symptoms of hepatitis.
## Postmarketing Experience
There is limited information regarding Sandbox gc4 Postmarketing Experience.
# Drug Interactions
Drug-drug interaction trials of remdesivir and other concomitant medications have not been conducted in humans. Due to antagonism observed in vitro, concomitant use of remdesivir with chloroquine phosphate or hydroxychloroquine sulfate is not recommended.
In vitro, remdesivir is a substrate for drug metabolizing enzymes CYP2C8, CYP2D6, and CYP3A4, and is a substrate for Organic Anion Transporting Polypeptides 1B1 (OATP1B1) and P-glycoprotein (P-gp) transporters. In vitro, remdesivir is an inhibitor of CYP3A4, OATP1B1, OATP1B3, BSEP, MRP4, and NTCP. The clinical relevance of these in vitro assessments has not been established.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
Risk Summary
No adequate and well-controlled studies of remdesivir use in pregnant women have been conducted. Remdesivir should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the fetus.
In nonclinical reproductive toxicity studies, remdesivir demonstrated no adverse effect on embryofetal development when administered to pregnant animals at systemic exposures (AUC) of the predominant circulating metabolite of remdesivir (GS-441524) that were 4 times (rats and rabbits) the exposure in humans at the recommended human dose (RHD).
Animal Data
Remdesivir was administered via intravenous injection to pregnant rats and rabbits (up to 20 mg/kg/day) on Gestation Days 6 through 17, and 7 through 20, respectively, and also to rats from Gestation Day 6 to Lactation/Post-partum Day 20. No adverse effects on embryo-fetal (rats and rabbits) or pre/postnatal (rats) development were observed in rats and rabbits at nontoxic doses in pregnant animals. During organogenesis, exposures to the predominant circulating metabolite (GS-441524) were 4 (rats and rabbits) times higher than the exposure in humans at the RHD. In a pre/postnatal development study, exposures to the predominant circulating metabolite of remdesivir (GS-441524) were similar to the human exposures at the RHD.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Sandbox gc4 in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Sandbox gc4 during labor and delivery.
### Nursing Mothers
Risk Summary
There is no information regarding the presence of remdesivir in human milk, the effects on the breastfed infant, or the effects on milk production. In animal studies, remdesivir and metabolites have been detected in the nursing pups of mothers given remdesivir, likely due to the presence of remdesivir in milk. Because of the potential for viral transmission to SARS-CoV-2-negative infants and adverse reactions from the drug in breastfeeding infants, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for remdesivir and any potential adverse effects on the breastfed child from remdesivir or from the underlying maternal condition.
Animal Data
Remdesivir and its metabolites were detected in the plasma of nursing rat pups, likely due to the presence of remdesivir and/or its metabolites in milk, following daily intravenous administration of remdesivir to pregnant mothers from Gestation Day 6 to Lactation Day 20. Exposures in nursing pups were approximately 1% that of maternal exposure on lactation day 10.
### Pediatric Use
The safety, effectiveness, or pharmacokinetics of remdesivir for treatment of COVID-19 have not been assessed in pediatric patients. Physiologically-based pharmacokinetics (PBPK) modeling of pharmacokinetic data from healthy adults was used to derive pediatric doses. Pediatric doses are expected to result in comparable steady-state exposures of remdesivir and metabolites as observed in healthy adults following administration of the recommended dosage regimen.
For pediatric patients with weighing 3.5 kg to less than 40 kg, use remdesivir for injection, 100 mg, lyophilized powder only. Remdesivir injection, 100/20 mL (5 mg/mL), should not be used for pediatric patients weighing 3.5 kg to less than 40 kg due to the higher amount of SBECD present and resulting higher tonicity of the solution concentrate compared to the lyophilized formulation.
Pediatric patients (older than 28 days) must have eGFR determined and full-term neonates (at least 7 days to less than or equal to 28 days) must have serum creatinine determined before dosing and daily while receiving remdesivir. Pediatric patients should be monitored for renal function and consideration given for stopping therapy in the setting of substantial decline.
Because the excipient SBECD is renally cleared and accumulates in patients with decreased renal function, administration of drugs formulated with SBECD (such as remdesivir) is not recommended in adults and pediatric patients (older than 28 days old) with eGFR less than 30 mL/min or in full-term neonates (at least 7 days and less than or equal to 28 days old) with serum creatinine greater than or equal to 1 mg/dL unless the potential benefit outweighs the potential risk.
### Geriatic Use
The pharmacokinetics of remdesivir have not been evaluated in patients >65 years of age. In general, appropriate caution should be exercised in the administration of remdesivir and monitoring of elderly patients, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
### Gender
There is no FDA guidance on the use of Sandbox gc4 with respect to specific gender.
### Race
There is no FDA guidance on the use of Sandbox gc4 with respect to specific race.
### Renal Impairment
Patients with eGFR greater than or equal to 30 mL/min have received remdesivir for treatment of COVID-19 with no dose adjustment. The safety and efficacy of remdesivir have not been assessed in patients with severe renal impairment or ESRD. The pharmacokinetics of remdesivir have not been evaluated in patients with renal impairment. Remdesivir is not recommended in adults and pediatric patients (at least 28 days old) with eGFR less than 30 mL/min or in full-term neonates (at least 7 days and less than or equal to 28 days old) with serum creatinine greater than or equal to 1 mg/dL unless the potential benefit outweighs the potential risk.
Adult and pediatric patients (greater than 28 days old) must have an eGFR determined and full-term neonates (at least 7 days to less than or equal to 28 days old) must have serum creatinine determined before dosing and daily while receiving remdesivir.
Adults
- eGFR, Male: (140 – age in years) × (weight in kg) / 72 × (serum creatinine in mg/dL)
- eGFR, Female: (140 – age in years) × (weight in kg) × 0.85 / 72 × (serum creatinine in mg/dL)
Pediatric patients (greater than 28 days old to less than 1 year of age)
- eGFR: 0.45 × (height in cm) / serum creatinine in mg/dL
Pediatric patients (at least 1 year of age to less than 18 years of age)
- eGFR = 0.413 x (height or length)/Scr) if height/length is expressed in centimeters OR 41.3 x (height or length)/Scr) if height/length is expressed in meters
Because the excipient SBECD is renally cleared and accumulates in patients with decreased renal function, administration of drugs formulated with SBECD [such as remdesivir is not recommended in adults and pediatric patients (greater than 28 days old) with eGFR less than 30 mL/min or in full-term neonates (at least 7 days and less than or equal to 28 days old)] with serum creatinine greater than or equal to 1 mg/dL unless the potential benefit outweighs the potential risk.
### Hepatic Impairment
The pharmacokinetics of remdesivir have not been evaluated in patients with hepatic impairment.
It is not known if dosage adjustment is needed in patients with hepatic impairment, and remdesivir should only be used in patients with hepatic impairment if the potential benefit outweighs the potential risk.
Hepatic laboratory testing should be performed in all patients prior to starting remdesivir and daily while receiving remdesivir.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Sandbox gc4 in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Sandbox gc4 in patients who are immunocompromised.
# Administration and Monitoring
### Administration
### Important Testing Prior to and During Treatment and Route of Administration
- Adult and pediatric patients (greater than 28 days old) must have an eGFR determined and full-term neonates (at least 7 days to less than or equal to 28 days old) must have serum creatinine determined before dosing of remdesivir and daily while receiving remdesivir.
- Hepatic laboratory testing should be performed in all patients prior to starting remdesivir and daily while receiving remdesivir.
- Remdesivir should be administered via IV infusion only. Do not administer as an intramuscular (IM) injection.
### Dose Preparation and Administration, Adults and Pediatric Patients Weighing 40 kg and Higher
Adults and pediatric patients weighing 40 kg and higher can use remdesivir for injection, 100 mg, lyophilized powder and remdesivir injection, 100 mg/20 mL (5 mg/mL), solution. See below for different preparation and administration instructions for the two dosage formulations.
Reconstitution Instructions
Remove the required number of single-dose vial(s) from storage. For each vial:
- Aseptically reconstitute remdesivir lyophilized powder by addition of 19 mL of Sterile Water for Injection using a suitably sized syringe and needle per vial.
- Discard the vial if a vacuum does not pull the Sterile Water for Injection into the vial.
- Immediately shake the vial for 30 seconds.
- Allow the contents of the vial to settle for 2 to 3 minutes. A clear solution should result.
- If the contents of the vial are not completely dissolved, shake the vial again for 30 seconds and allow the contents to settle for 2 to 3 minutes. Repeat this procedure as necessary until the contents of the vial are completely dissolved.
- Following reconstitution, each vial contains 100 mg/20 mL (5 mg/mL) of remdesivir solution.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
• After reconstitution, the total storage time before administration should not exceed 4 hours at room temperature or 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]).
Dilution Instructions
Care should be taken during admixture to prevent inadvertent microbial contamination. As there is no preservative or bacteriostatic agent present in this product, aseptic technique must be used in preparation of the final parenteral solution. It is always recommended to administer IV medication immediately after preparation when possible.
- The reconstituted remdesivir lyophilized powder for injection, containing 100 mg/20 mL remdesivir solution, should be further diluted in 100 mL or 250 mL 0.9% sodium chloride infusion bags.
- Using the table below, determine the volume of 0.9% sodium chloride to withdraw from the infusion bag.
- Withdraw and discard the required volume of 0.9% sodium chloride from the bag using an appropriately sized syringe and needle.
- Withdraw the required volume of reconstituted remdesivir for injection from the remdesivir vial using an appropriately sized syringe. Discard any unused portion remaining in the remdesivir vial.
- Transfer the required volume of reconstituted remdesivir for injection to the selected infusion bag.
- Gently invert the bag 20 times to mix the solution in the bag. Do not shake.
- The prepared diluted solution is stable for 4 hours at room temperature (20°C to 25°C [68°F to 77°F]) or 24 hours in the refrigerator at 2°C to 8°C (36°F to 46°F).
Administration Instructions
The prepared diluted solution should not be administered simultaneously with any other IV medication. The compatibility of remdesivir injection with IV solutions and medications other than 0.9% sodium chloride is not known.
Administer the diluted solution with the infusion rate described in the table below.
Dilution Instructions
Care should be taken during admixture to prevent inadvertent microbial contamination. As there is no preservative or bacteriostatic agent present in this product, aseptic technique must be used in preparation of the final parenteral solution. It is always recommended to administer IV medication immediately after preparation when possible.
- Remove the required number of single-dose vial(s) from storage. Each vial contains 100 mg of remdesivir. For each vial:
- Equilibrate to room temperature (20°C to 25°C [68°F to 77°F]). Sealed vials can be stored up to 12 hours at room temperature prior to dilution.
- Inspect the vial to ensure the container closure is free from defects and the solution is free of particulate matter.
- Using the table below, determine the volume of 0.9% sodium chloride to withdraw from the infusion bag
- Withdraw and discard the required volume of 0.9% sodium chloride from the bag using an appropriately sized syringe and needle.
- Withdraw the required volume of remdesivir injection solution from the remdesivir vial using an appropriately sized syringe.
- Pull the syringe plunger rod back to fill the syringe with approximately 10 mL of air.
- Inject the air into the remdesivir injection vial above the level of the solution.
- Invert the vial and withdraw the required volume of remdesivir injection solution into the syringe. The last 5 mL of solution requires more force to withdraw.
- Discard any unused solution remaining in the remdesivir vial.
- Transfer the required volume of remdesivir injection solution to the infusion bag.
- Gently invert the bag 20 times to mix the solution in the bag. Do not shake.
- The prepared diluted solution is stable for 4 hours at room temperature (20°C to 25°C [68°F to 77°F]) or 24 hours in the refrigerator at 2°C to 8°C (36°F to 46°F).
Administration Instructions
The prepared diluted solution should not be administered simultaneously with any other medication. The compatibility of remdesivir injection with IV solutions and medications other than 0.9% sodium chloride is not known.
Administer the diluted solution with the infusion rate described in the table below.
### Dose Preparation and Administration, Pediatric Patients Weighing 3.5 kg to Less Than 40 kg
For pediatric patients weighing 3.5 kg to less than 40 kg, use remdesivir for injection, 100 mg, lyophilized powder only. Remdesivir injection, 100 mg/20 mL (5 mg/mL), should not be used for pediatric patients weighing 3.5 kg to less than 40 kg due to the higher amount of SBECD present and resulting higher tonicity of the solution concentrate compared to the lyophilized formulation.
Remdesivir for Injection, 100 mg, Lyophilized Powder
Reconstitution Instructions
Remove the required number of single-dose vial(s) from storage. For each vial:
- Aseptically reconstitute remdesivir lyophilized powder by addition of 19 mL of Sterile Water for Injection using a suitably sized syringe and needle per vial.
- Discard the vial if a vacuum does not pull the Sterile Water for Injection into the vial.
- Immediately shake the vial for 30 seconds.
- Allow the contents of the vial to settle for 2 to 3 minutes. A clear solution should result.
- If the contents of the vial are not completely dissolved, shake the vial again for 30 seconds and allow the contents to settle for 2 to 3 minutes. Repeat this procedure as necessary until the contents of the vial are completely dissolved.
- Following reconstitution, each vial contains 100 mg/20 mL (5 mg/mL) of remdesivir solution.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
- After reconstitution, the total storage time before administration should not exceed 4 hours at room temperature or 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]).
Dilution Instructions
- Care should be taken during admixture to prevent inadvertent microbial contamination. As there is no preservative or bacteriostatic agent present in this product, aseptic technique must be used in preparation of the final parenteral solution. It is always recommended to administer IV medication immediately after preparation when possible. Following reconstitution as instructed above, each vial will contain a 100 mg/20 mL (5 mg/mL) remdesivir concentrated solution. For pediatric patients weighing 3.5 kg to less than 40 kg, the 100 mg/20 mL (5 mg/mL) remdesivir concentrate should be further diluted to a fixed concentration of 1.25 mg/mL using 0.9% sodium chloride.
- The total required infusion volume of the 1.25 mg/mL remdesivir solution for infusion is calculated from the pediatric weight-based dosing regimens of 5 mg/kg for the Loading Dose and 2.5 mg/kg for each Maintenance Dose.
- Small 0.9% sodium chloride infusion bags (e.g., 25, 50, or 100 mL) or an appropriately sized syringe should be used for pediatric dosing. The recommended dose is administered via IV infusion in a total volume dependent on the dose to yield the target remdesivir concentration of 1.25 mg/mL.
- A syringe may be used for delivering volumes less than 50 mL.
Infusion with IV Bag
- Prepare an IV bag of 0.9% sodium chloride with volume equal to the total infusion volume minus the volume of reconstituted remdesivir solution that will be diluted to achieve a 1.25 mg/mL solution.
- Withdraw the required volume of reconstituted solution containing remdesivir for injection into an appropriately sized syringe.
- Transfer the required volume of reconstituted remdesivir for injection to the 0.9% sodium chloride infusion bag.
- Gently invert the bag 20 times to mix the solution in the bag. Do not shake.
Infusion with Syringe
- Select an appropriately sized syringe equal to or larger than the calculated total infusion volume of 1.25 mg/mL remdesivir solution needed.
- Withdraw the required volume of 100 mg/20 mL (5 mg/mL) reconstituted remdesivir solution from the vial into the syringe followed by the required volume of 0.9% sodium chloride needed to achieve a 1.25 mg/mL remdesivir solution.
- Mix the syringe by inversion 20 times.
- The prepared diluted solution is stable for 4 hours at room temperature (20°C to 25°C [68°F to 77°F]) or 24 hours in the refrigerator at 2°C to 8°C (36°F to 46°F) (including any time before dilution into intravenous infusion fluids).
Administration Instructions
The prepared diluted solution should not be administered simultaneously with any other medication. The compatibility of remdesivir injection with IV solutions and medications other than 0.9% sodium chloride is not known.
Administer the diluted solution with the infusion rate described in the table below.
† Rate of infusion may be adjusted based on total volume to be infused.
### Storage of Prepared Dosages
Lyophilized Powder
After reconstitution, vials can be stored up to 4 hours at room temperature (20°C to 25°C [68°F to 77°F]) prior to administration or 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]). Dilute within the same day as administration.
Injection Solution
Prior to dilution, equilibrate remdesivir injection to room temperature (20°C to 25°C [68°F to 77°F]). Sealed vials can be stored up to 12 hours at room temperature prior to dilution.
Diluted Infusion Solution
Store diluted remdesivir solution for infusion up to 4 hours at room temperature (20°C to 25°C [68°F to 77°F]) or 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]).
IMPORTANT: This product contains no preservative. Any unused portion of a single-dose remdesivir vial should be discarded after a diluted solution is prepared. Maintain adequate records showing receipt, use, and disposition of remdesivir. For unused intact vials, maintain adequate records showing disposition of remdesivir; do not discard unused intact vials
### Dosage Forms and Strengths
- Remdesivir for injection, 100 mg: Each single-dose vial of remdesivir for injection,100 mg, contains a sterile, preservative-free white to off-white to yellow lyophilized powder that is to be reconstituted with 19 mL of Sterile Water for Injection and further diluted into 0.9% sodium chloride infusion bag prior to administration by intravenous infusion. Following reconstitution, each vial contains 100 mg/20 mL (5 mg/mL) remdesivir reconcentrated solution.
- Remdesivir injection, 100 mg/20 mL (5 mg/mL): Each single-dose vial of remdesivir injection contains 100 mg/20 mL (5 mg/mL) of remdesivir as a clear, colorless to yellow, aqueous-based concentrated solution that is to be diluted into 0.9% sodium chloride infusion bag prior to administration by intravenous infusion.
### Monitoring
### Patient Monitoring Recommendations
Given the limited experience with remdesivir at the recommended dose and duration, patients should have appropriate clinical and laboratory monitoring to aid in early detection of any potential adverse events while receiving remdesivir. Additionally, completion of FDA MedWatch Form to report all medication errors and serious adverse events is mandatory.
For mandatory reporting requirements, please see MANDATORY REQUIREMENTS FOR REMDESIVIR ADMINISTRATION UNDER EMERGENCY USE AUTHORIZATION below.
### ADVERSE REACTIONS AND MEDICATION ERRORS REPORTING REQUIREMENTS AND INSTRUCTIONS
The prescribing health care provider and/or the provider’s designee are/is responsible for the mandatory reporting of all medication errors and the following selected adverse events occurring during remdesivir use and considered to be potentially attributable to remdesivir. These adverse events must be reported within 7 calendar days from the onset of the event:
- Deaths
- Serious Adverse Events
Serious Adverse Events are defined as:
- death;
- a life-threatening adverse event;
- inpatient hospitalization or prolongation of existing hospitalization;
- a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions;
- a congenital anomaly/birth defect;
- a medical or surgical intervention to prevent death, a life-threatening event, hospitalization, disability, or congenital anomaly.
If a serious and unexpected adverse event occurs and appears to be associated with the use of remdesivir, the prescribing health care provider and/or the provider’s designee should complete and submit a MedWatch form to FDA using one of the following methods:
- Complete and submit the report online: www.fda.gov/medwatch/report.htm, or
- Use a postage-paid Form FDA 3500 (available at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM163919.pdf) and returning by mail (MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787), or by fax (1-800-FDA-0178), or
- Call 1-800-FDA-1088 to request a reporting form
IMPORTANT: When reporting adverse events or medication errors to MedWatch, please complete the entire form with detailed information. It is important that the information reported to FDA be as detailed and complete as possible. Information to include:
- Patient demographics (e.g., patient initials, date of birth)
- Pertinent medical history
- Pertinent details regarding admission and course of illness
- Concomitant medications
- Timing of adverse event(s) in relationship to administration of remdesivir
- Pertinent laboratory and virology information
- Outcome of the event and any additional follow-up information if it is available at the time of the MedWatch report. Subsequent reporting of follow-up information should be completed if additional details become available.
The following steps are highlighted to provide the necessary information for safety tracking:
- In section A, box 1, provide the patient’s initials in the Patient Identifier
- In section A, box 2, provide the patient’s date of birth
- In section B, box 5, description of the event:
Write “Remdesivir EUA” as the first line
Provide a detailed report of medication error and/or adverse event. It is important to provide detailed information regarding the patient and adverse event/medication error for ongoing safety evaluation of this unapproved drug. Please see information to include listed above.
- Write “Remdesivir EUA” as the first line
- Provide a detailed report of medication error and/or adverse event. It is important to provide detailed information regarding the patient and adverse event/medication error for ongoing safety evaluation of this unapproved drug. Please see information to include listed above.
- In section G, box 1, name and address:
Provide the name and contact information of the prescribing health care provider or institutional designee who is responsible for the report.
Provide the address of the treating institution (NOT the health care provider’s office address).
- Provide the name and contact information of the prescribing health care provider or institutional designee who is responsible for the report.
- Provide the address of the treating institution (NOT the health care provider’s office address).
### INSTRUCTIONS FOR HEALTH CARE PROVIDERS
As the health care provider, you must communicate to your patient or parent/caregiver information consistent with the Fact Sheet for Patients and Parents/Caregivers (and provide a copy of the Fact Sheet) prior to the patient receiving remdesivir, including:
- FDA has authorized the emergency use of remdesivir, which is not an FDA approved drug.
- The patient or parent/caregiver has the option to accept or refuse remdesivir.
- The significant known and potential risks and benefits of remdesivir, and the extent to which such risks and benefits are unknown.
- Information on available alternative treatments and the risks and benefits of those alternatives.
If providing this information will delay the administration of remdesivir to a degree that would endanger the lives of patients, the information must be provided to the patients as soon as practicable after remdesivir is administered.
For information on clinical trials that are testing the use of remdesivir for COVID-19, please see http://www.clinicaltrials.gov.
### MANDATORY REQUIREMENTS FOR REMDESIVIR ADMINISTRATION UNDER EMERGENCY USE AUTHORIZATION
In order to mitigate the risks of using this unapproved product under EUA and to optimize the potential benefit of remdesivir, the following items are required. Use of unapproved remdesivir under this EUA is limited to the following (all requirements must be met):
- Treatment of suspected or laboratory confirmed coronavirus disease 2019 (COVID-19) in adults and pediatric patients hospitalized with severe disease. Severe disease is defined as patients with an oxygen saturation (SpO2) ≤94% on room air or requiring supplemental oxygen or requiring invasive mechanical ventilation, or requiring ECMO. Specifically, remdesivir is authorized only for the following patients who are admitted to a hospital and under the care or consultation of a licensed clinician (skilled in the diagnosis and management of patients with potentially life-threatening illness and the ability to recognize and manage medication-related adverse events):
Adult patients for whom use of an IV agent is clinically appropriate.
Pediatric patients for whom use of an IV agent is clinically appropriate.
- Adult patients for whom use of an IV agent is clinically appropriate.
- Pediatric patients for whom use of an IV agent is clinically appropriate.
- As the health care provider, communicate to your patient or parent/caregiver information consistent with the Fact Sheet for Patients and Parents/Caregivers prior to the patient receiving remdesivir. Health care providers (to the extent practicable given the circumstances of the emergency) must document in the patient’s medical record that the patient/caregiver has been:
Given the Fact Sheet for Patients and Parents/Caregivers,
Informed of alternatives to receiving remdesivir, and
Informed that remdesivir is an unapproved drug that is authorized for use under EUA.
- Given the Fact Sheet for Patients and Parents/Caregivers,
- Informed of alternatives to receiving remdesivir, and
- Informed that remdesivir is an unapproved drug that is authorized for use under EUA.
- Adult and pediatric patients (greater than 28 days old) must have an eGFR determined and full-term neonates (at least 7 days to less than or equal to 28 days old) must have serum creatinine determined prior to remdesivir first administration and daily while receiving remdesivir.
- Hepatic laboratory testing should be performed in all patients prior to starting remdesivir and daily while receiving remdesivir.
- Patients with known hypersensitivity to any ingredient of remdesivir must not receive remdesivir.
- The prescribing health care provider and/or the provider’s designee are/is responsible for mandatory responses to requests from FDA for information about adverse events and medication errors following receipt of remdesivir.
- The prescribing health care provider and/or the provider’s designee are/is responsible for mandatory reporting of all medication errors and adverse events (death, serious adverse events*) considered to be potentially related to remdesivir occurring during remdesivir treatment within 7 calendar days from the onset of the event. The reports should include unique identifiers and the words “Remdesivir under Emergency Use Authorization (EUA)” in the description section of the report.
- Submit adverse event reports to FDA MedWatch using one of the following methods:
Complete and submit the report online: www.fda.gov/medwatch/report.htm, or
By using a postage-paid Form FDA 3500 (available at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM163919.pdf) and returning by mail (MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787), or by fax (1-800-FDA-0178), or
Call 1-800-FDA-1088 to request a reporting form
Submitted reports should include in the field name, “Describe Event, Problem, or Product Use/Medication Error” a statement “Remdesivir under Emergency Use Authorization (EUA).”
- Complete and submit the report online: www.fda.gov/medwatch/report.htm, or
- By using a postage-paid Form FDA 3500 (available at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM163919.pdf) and returning by mail (MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787), or by fax (1-800-FDA-0178), or
- Call 1-800-FDA-1088 to request a reporting form
- Submitted reports should include in the field name, “Describe Event, Problem, or Product Use/Medication Error” a statement “Remdesivir under Emergency Use Authorization (EUA).”
### OTHER REPORTING REQUIREMENTS
In addition please provide a copy of all FDA MedWatch forms to:
Gilead Pharmacovigilance and Epidemiology
Fax: 1-650-522-5477
E-mail: [email protected]
### APPROVED AVAILABLE ALTERNATIVES
There is no approved available alternative product. There are EUAs for other COVID-19 treatments. Additional information on COVID-19 treatments can be found at https://www.cdc.gov/coronavirus/2019-ncov/index.html. The health care provider should visit https://clinicaltrials.gov/ to determine whether the patient may be eligible for enrollment in a clinical trial.
### AUTHORITY FOR ISSUANCE OF THE EUA
The Secretary of HHS has declared a public health emergency that justifies the emergency use of remdesivir to treat COVID-19 caused by SARS-CoV-2. In response, the FDA has issued an EUA for the unapproved product, remdesivir, for the treatment of COVID-19.† As a health care provider, you must comply with the MANDATORY REQUIREMENTS of the EUA (see above).
FDA issued this EUA, requested by Gilead Sciences, Inc. and based on their submitted data.
Although limited scientific information is available, based on the totality of the scientific evidence available to date, it is reasonable to believe that remdesivir may be effective for the treatment of COVID-19 in patients as specified in this Fact Sheet. You may be contacted and asked to provide information to help with the assessment of the use of the product during this emergency.
This EUA for remdesivir will end when the Secretary determines that the circumstances justifying the EUA no longer exist or when there is a change in the approval status of the product such that an EUA is no longer needed.
† The health care provider should visit clinicaltrials.gov to determine whether there is an active clinical trial for the product in this disease/condition and whether enrollment of the patient(s) in a clinical trial is more appropriate than product use under this EUA.
# IV Compatibility
There is limited information regarding the compatibility of Sandbox gc4 and IV administrations.
# Overdosage
There is no human experience of acute overdosage with remdesivir. Treatment of overdose with remdesivir should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with remdesivir.
# Pharmacology
## Mechanism of Action
Remdesivir is an adenosine nucleotide prodrug that distributes into cells where it is metabolized to form the pharmacologically active nucleoside triphosphate metabolite. Metabolism of remdesivir to remdesivir triphosphate has been demonstrated in multiple cell types. Remdesivir triphosphate acts as an analog of adenosine triphosphate (ATP) and competes with the natural ATP substrate for incorporation into nascent RNA chains by the SARS-CoV-2 RNA-dependent RNA polymerase, which results in delayed chain termination during replication of the viral RNA. Remdesivir triphosphate is a weak inhibitor of mammalian DNA and RNA polymerases with low potential for mitochondrial toxicity.
## Structure
Remdesivir is a nucleoside ribonucleic acid (RNA) polymerase inhibitor.
The chemical name for remdesivir is 2-ethylbutyl N-{(S)-[2-C-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2,5-anhydro-d-altrononitril-6-O-yl]phenoxyphosphoryl}-L-alaninate. It has a molecular formula of C27H35N6O8P and a molecular weight of 602.6 g/mol. Remdesivir has the following structural formula:
## Physical Appearance
Lyophilized Powder
Remdesivir for injection, 100 mg, is a sterile, preservative-free lyophilized powder that is to be reconstituted with 19 mL of Sterile Water for Injection and further diluted into 0.9% sodium chloride infusion bag prior to administration by intravenous infusion. Remdesivir for injection, 100 mg, is supplied in a single-dose clear glass vial.
The appearance of the lyophilized powder is white to off-white to yellow.
Injection Solution
Remdesivir injection, 100 mg/20 mL (5 mg/mL), is a sterile, preservative-free, clear, colorless to yellow, aqueous-based concentrated solution that is to be diluted into 0.9% sodium chloride infusion bag prior to administration by intravenous infusion. Remdesivir injection, 100 mg/20 mL (5 mg/mL), is supplied in a single-dose clear glass vial.
13.2 Inactive Ingredients
The inactive ingredients are sulfobutylether-β-cyclodextrin sodium salt (SBECD), Water for Injection, USP, and may include hydrochloric acid and/or sodium hydroxide for pH adjustment. Remdesivir for injection, 100 mg, contains 3 g SBECD, and remdesivir injection, 100 mg/20 mL (5 mg/mL), contains 6 g SBECD.
## Pharmacodynamics
There is limited information regarding Sandbox gc4 Pharmacodynamics.
## Pharmacokinetics
The pharmacokinetics (PK) of remdesivir have been evaluated in adults in several Phase 1 trials.
- The pharmacokinetics of remdesivir and metabolites have not been in evaluated in patients with COVID-19.
- Following single-dose, 2-hour IV administration of remdesivir solution formulation at doses ranging from 3 to 225 mg, remdesivir exhibited a linear PK profile.
- Following single-dose, 2-hour IV administration of remdesivir at doses of 75 and 150 mg, both the lyophilized and solution formulations provided comparable PK parameters (AUCinf, AUClast, and Cmax), indicating similar formulation performance.
- Remdesivir 75 mg lyophilized formulation administered IV over 30 minutes provided similar peripheral blood mononuclear cell (PBMC) exposure of the active triphosphate metabolite GS-443902 as remdesivir 150 mg lyophilized formulation administered IV over 2 hours.
- Following a single 150 mg intravenous dose of [14C]-remdesivir, mean total recovery of the dose was >92%, consisting of approximately 74% and 18% recovered in urine and feces, respectively. The majority of remdesivir dose recovered in urine was metabolite GS-441524 (49%), while 10% was recovered as remdesivir.
Specific Populations
Sex, Race and Age
Pharmacokinetic differences based on sex, race, and age have not been evaluated.
Pediatric Patients
The pharmacokinetics of remdesivir in pediatric patients has not been evaluated.
PBPK modeling of pharmacokinetic data from healthy adults was used to derive pediatric doses. PBPK modeling incorporated in vitro data for remdesivir and other similar compounds along with age-dependent changes in physiology (e.g., organ volume/function, blood flow), metabolism, distribution, and elimination of remdesivir. Pediatric doses are expected to result in comparable steady-state exposures of remdesivir and metabolites as observed in healthy adults following administration of the recommended dosage regimen.
Renal Impairment
Because the excipient SBECD is renally cleared and accumulates in patients with decreased renal function, administration of drugs formulated with SBECD (such as remdesivir) is not recommended in adult and pediatric patients (greater than 28 days old) with eGFR less than 30 mL/min or in full-term neonates (at least 7 days and less than or equal to 28 days old) with serum creatinine greater than or equal to 1 mg/dL unless the potential benefit outweighs the potential risk.
### Microbiology/Resistance Information
Antiviral Activity
Remdesivir exhibited cell culture antiviral activity against a clinical isolate of SARS-CoV-2 in primary human airway epithelial (HAE) cells with a 50% effective concentration (EC50) of 9.9 nM after 48 hours of treatment. The EC50 values of remdesivir against SARS-CoV-2 in Vero cells was 137 nM at 24 hours and 750 nM at 48 hours post-treatment. The antiviral activity of remdesivir was antagonized by chloroquine phosphate in a dose-dependent manner when the two drugs were co-incubated at clinically relevant concentrations in HEp-2 cells infected with respiratory syncytial virus (RSV). Higher remdesivir EC50 values were observed with increasing concentrations of chloroquine phosphate. Increasing concentrations of chloroquine phosphate reduced formation of remdesivir triphosphate in normal human bronchial epithelial cells.
Resistance
No clinical data are available on the development of SARS-CoV-2 resistance to remdesivir. The cell culture development of SARS-CoV-2 resistance to remdesivir has not been assessed to date.
Cell culture resistance profiling of remdesivir using the rodent CoV murine hepatitis virus identified 2 substitutions (F476L and V553L) in the viral RNA-dependent RNA polymerase at residues conserved across CoVs that conferred a 5.6-fold reduced susceptibility to remdesivir. The mutant viruses showed reduced viral fitness in cell culture and introduction of the corresponding substitutions (F480L and V557L) into SARS-CoV resulted in 6-fold reduced susceptibility to remdesivir in cell culture and attenuated SARS-CoV pathogenesis in a mouse model.
## Nonclinical Toxicology
Carcinogenesis
Given the short-term administration of remdesivir for the treatment of COVID-19, long-term animal studies to evaluate the carcinogenic potential of remdesivir are not required.
Mutagenesis
Remdesivir was not genotoxic in a battery of assays, including bacterial mutagenicity, chromosome aberration using human peripheral blood lymphocytes and in vivo rat micronucleus assays.
Impairment of Fertility
Nonclinical toxicity studies in rats demonstrated no adverse effect on male fertility at exposures of the predominant circulating metabolite (GS-441524) approximately 2 times the exposure in humans at the RHD.
Reproductive toxicity, including decreases in corpora lutea, numbers of implantation sites, and viable embryos, was seen when remdesivir was administered intravenous daily at a systemically toxic dose (10 mg/kg) in female rats 14 days prior to mating and during conception; exposures of the predominant circulating metabolite (GS-441524) were 1.3 times the exposure in humans at the RHD.
Animal Toxicology and/or Pharmacology
Intravenous administration (slow bolus) of remdesivir to male rhesus monkeys at dosage levels of 5, 10, and 20 mg/kg/day for 7 days resulted, at all dose levels, in increased mean urea nitrogen and increased mean creatinine, renal tubular atrophy, and basophilia and casts.
Intravenous administration (slow bolus) of remdesivir to rats at dosage levels of ≥3 mg/kg/day for up to 4 weeks resulted in findings indicative of kidney injury and/or dysfunction.
### Animal Pharmacologic and Efficacy Data
It is unknown, at present, how the observed antiviral activity of remdesivir in animal models of SARS-CoV-2 infection will translate into clinical efficacy in patients with symptomatic disease. Key attributes of the remdesivir nonclinical profile supporting its development for the treatment of COVID-19 are provided below:
- Remdesivir showed cell culture antiviral activity against a clinical isolate of SARS-CoV-2 in primary HAE cells (EC50 value= 9.9 nM). The EC50 values of remdesivir against SARS-CoV-2 in Vero cells has been reported to be 137 nM at 24 hours and 750 nM at 48 hours post-treatment.
- Remdesivir showed antiviral activity in SARS-CoV-2-infected rhesus monkeys. Administration of remdesivir at 10/5 mg/kg (10 mg/kg first dose, followed by 5 mg/kg once daily thereafter) using IV bolus injection initiated 12 hours post-inoculation with SARS-CoV-2 resulted in a reduction in clinical signs of respiratory disease, lung pathology and gross lung lesions, and lung viral RNA levels compared with vehicle-treated animals.
# Clinical Studies
Remdesivir is an unapproved antiviral drug with available data from two randomized clinical trials in patients with COVID-19.
Clinical Trials in Subjects with COVID-19
NIAID ACTT-1 Trial in Subjects with Mild/Moderate and Severe COVID-19
A randomized, double-blind, placebo-controlled clinical trial evaluated remdesivir 200 mg once daily for 1 day followed by remdesivir 100 mg once daily for 9 days (for a total of up to 10 days of intravenously administered therapy) in hospitalized adult subjects with COVID-19 with evidence of lower respiratory tract involvement. The trial enrolled 1,063 subjects: 120 [11.3%] subjects with mild/moderate disease and 943 [88.7%] subjects with severe disease. A total of 272 subjects (25.6%) (n=125 received remdesivir) were on mechanical ventilation/ECMO. Subjects were randomized in a 1:1 manner, stratified by disease severity at enrollment, to receive remdesivir (n=541) or placebo (n=522), plus standard of care. The primary clinical endpoint was time to recovery within 28 days after randomization, defined as either discharged from the hospital or hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care. In a preliminary analysis of the primary endpoint performed after 607 recoveries were attained (n=1,059; 538 remdesivir, 521 placebo), the median time to recovery was 11 days in the remdesivir group compared to 15 days in the placebo group (recovery rate ratio 1.32; 95% CI 1.12 to 1.55, p<0.001); 14-day mortality was 7.1% for the remdesivir group versus 11.9% for the placebo group (hazard ratio 0.70 [95% CI 0.47, 1.04], p=0.07). Among subjects with mild/moderate disease at enrollment (n=119), the median time to recovery was 5 days in both the remdesivir and placebo groups (recovery rate ratio 1.09; [95% CI 0.73 to 1.62]). Among subjects with severe disease at enrollment (n=940), the median time to recovery was 12 days in the remdesivir group compared to 18 days in the placebo group (recovery rate ratio, 1.37; [95% CI, 1.15 to 1.63]; p<0.001; n=940) and 14-day mortality was 7.7% and 13%, respectively (hazard ratio, 0.71; [95% CI, 0.48 to 1.05]).
Overall, the odds of improvement in the ordinal scale were higher in the remdesivir group at Day 15 when compared to the placebo group (odds ratio, 1.50; [95% CI, 1.18 to 1.91], p=0.001; n=844).
Study GS-US-540-5773 in Subjects with Severe COVID-19
A randomized, open-label multi-center clinical trial (Study GS-US-540-5773) of hospitalized subjects at least 12 years of age with confirmed SARS-CoV-2 infection, oxygen saturation of ≤94% on room air, and radiological evidence of pneumonia compared 197 subjects who received IV remdesivir for 5 days with 200 subjects who received IV remdesivir for 10 days. Patients on mechanical ventilation at screening were excluded. All subjects received 200 mg of remdesivir on Day 1 and 100 mg once daily on subsequent days, plus standard of care. The primary endpoint was clinical status on Day 14 assessed on a 7-point ordinal scale ranging from hospital discharge to increasing levels of oxygen and ventilatory support to death. After adjusting for between-group differences at baseline, patients receiving a 10-day course of remdesivir had similar clinical status at Day 14 as those receiving a 5-day course (odds ratio for improvement: 0.75; [95% CI 0.51 to 1.12]).
Clinical improvement was defined as an improvement of two or more points from baseline on the 7-point ordinal scale. Subjects achieved clinical recovery if they no longer required oxygen support or were discharged from the hospital. At Day 14, observed rates between the 5- and 10-day treatment groups were 65% vs 54% for clinical improvement, 70% vs 59% for clinical recovery, and 8% vs 11% for mortality.
# How Supplied
### How Supplied
Lyophilized Powder
Remdesivir for injection, 100 mg, is supplied as a single-dose vial containing a sterile, preservative-free white to off-white to yellow lyophilized powder that is to be reconstituted with 19 mL of Sterile Water for Injection and further diluted into 0.9% sodium chloride infusion bag prior to administration by intravenous infusion. Following reconstitution, each vial contains 100 mg/20 mL (5 mg/mL) remdesivir reconcentrated solution.
Discard unused portion.
The container closure is not made with natural rubber latex.
Injection Solution
Remdesivir injection is supplied as a single dose vial containing 100 mg/20 mL (5 mg/mL) of remdesivir per vial for dilution into 0.9% sodium chloride infusion bag.
Discard unused portion.
The container closure is not made with natural rubber latex.
### Storage and Handling
Do not reuse or save unused remdesivir lyophilized powder, injection solution, or diluted solution for infusion for future use. This product contains no preservative.
Lyophilized Powder
Store remdesivir for injection, 100 mg, vials below 30°C (below 86°F) until required for use. Do not use after expiration date.
After reconstitution, vials can be stored up to 4 hours at room temperature (20°C to 25°C [68°F to 77°F]) prior to administration or 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]). Dilute within the same day as administration.
Injection Solution
Store remdesivir injection, 100 mg/20 mL (5 mg/mL), vials at refrigerated temperature (2°C to 8°C [36°F to 46°F]) until required for use. Do not use after expiration date. Dilute within the same day as administration.
Prior to dilution, equilibrate remdesivir injection to room temperature (20°C to 25°C [68°F to 77°F]). Sealed vials can be stored up to 12 hours at room temperature prior to dilution.
Diluted Solution for Infusion
Store diluted remdesivir solution for infusion up to 4 hours at room temperature (20°C to 25°C [68°F to 77°F]) or 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]).
# Patient Counseling Information
You are being given a medicine called remdesivir for the treatment of coronavirus disease 2019 (COVID-19).
This Fact Sheet contains information to help you understand the potential risks and potential benefits of taking remdesivir, which you have received or may receive.
There is no U.S. Food and Drug Administration (FDA) approved product available to treat COVID-19. Receiving remdesivir may benefit certain people in the hospital with COVID-19.
Read this Fact Sheet for information about remdesivir. Talk to your healthcare provider if you have questions. It is your choice to receive remdesivir or stop it at any time.
### What is COVID-19?
COVID-19 is caused by a virus called a coronavirus. This type of coronavirus has not been seen before.
This new coronavirus was first found in people in Wuhan, Hubei Province, China in December 2019. Person-to-person spread was reported outside Hubei and in countries outside China, including in the United States. You can get COVID-19 through contact with another person who has the virus.
COVID-19 illnesses have ranged from very mild (including some with no reported symptoms) to severe, including illness resulting in death. While information so far suggests that most COVID-19 illness is mild, serious illness can happen and may cause some of your other medical conditions to become worse. Older people and people of all ages with severe, long-lasting (chronic) medical conditions like heart disease, lung disease, and diabetes, for example, seem to be at higher risk of being hospitalized for COVID-19.
### What are the symptoms of COVID-19?
The symptoms of COVID-19 are fever, cough, and shortness of breath, which may appear 2 to 14 days after exposure. Serious illness including breathing problems can occur and may cause your other medical conditions to become worse.
### What is remdesivir?
Remdesivir is an investigational antiviral medicine used for the treatment of certain people in the hospital with COVID-19. Remdesivir is investigational because it is still being studied. There is limited information known about the safety and effectiveness of using remdesivir to treat people in the hospital with COVID-19. Remdesivir was shown in a clinical trial to shorten the time to recovery in some people. There are no medicines approved by the FDA as safe and effective to treat people in the hospital who have COVID-19. Therefore, the FDA has authorized the emergency use of remdesivir for the treatment of COVID-19 under an Emergency Use Authorization (EUA).
For more information on EUA, see the What is an Emergency Use Authorization (EUA) section at the end of this Fact Sheet.
### What should I tell my healthcare provider before I receive remdesivir?
Tell your healthcare provider about all of your medical conditions, including if you:
- Have any allergies
- Have kidney or liver problems
- Are pregnant or plan to become pregnant
- Are breastfeeding or plan to breastfeed
- Have any serious illnesses
- Are taking any medicines (prescription, over-the-counter, vitamins, or herbal products). Remdesivir may affect the way other medicines work, and other medicines may affect how remdesivir works.
- Especially tell your healthcare provider if you are taking the medicines chloroquine phosphate or hydroxychloroquine sulfate.
### How will I receive remdesivir?
Remdesivir is given to you through a vein (intravenous or IV) one time each day for up to 10 days depending on what your healthcare provider thinks is best for you. Remdesivir may help decrease the amount of the coronavirus in your body. This may help you to get better faster.
### What are the important possible side effects of remdesivir?
Possible side effects of remdesivir are:
- Allergic reactions. Remdesivir can cause allergic reactions, including serious reactions, during and after infusion. Tell your healthcare provider or nurse, or get medical help right away if you get any of the following signs and symptoms of allergic reactions: low blood pressure, changes in your heartbeat, shortness of breath, wheezing, swelling of your lips, face, or throat, rash, nausea, vomiting, sweating, or shivering.
- Increases in levels of liver enzymes. Increases in levels of liver enzymes have been seen in people who have received remdesivir, which may be a sign of inflammation or damage to cells in the liver. Your healthcare provider will do blood tests to check your liver before you receive remdesivir and daily while receiving remdesivir.
These are not all the possible side effects of remdesivir. Remdesivir is still being studied so it is possible that all of the risks are not known at this time.
Not a lot of people have taken remdesivir. Serious and unexpected side effects may happen. The side effects of getting any medicine by vein may include brief pain, bleeding, bruising of the skin, soreness, swelling, and possible infection at the injection site.
### What other treatment choices are there?
Like remdesivir, FDA may allow for the emergency use of other medicines to treat people in the hospital with COVID-19. Go to http://www.cdc.gov/COVID19 for information on the emergency use of other medicines that are not approved by FDA to treat people in the hospital with COVID-19. Your healthcare provider may talk with you about clinical trials you may be eligible for.
It is your choice to be treated or not to be treated with remdesivir. Should you decide not to receive it or stop it at any time, it will not change your standard medical care.
### What if I am pregnant or breastfeeding?
There is limited experience giving remdesivir to pregnant women or breastfeeding mothers. For a mother and unborn baby, the benefit of receiving remdesivir may be greater than the risk from the treatment. If you are pregnant or breastfeeding, discuss your options and specific situation with your healthcare provider.
### How do I report side effects with remdesivir?
Tell your healthcare provider right away if you have any side effect that bothers you or does not go away. Report side effects to FDA MedWatch at http://www.fda.gov/medwatch or call 1-800-FDA-1088.
### How can I learn more?
- Ask your healthcare provider.
- Visit http://www.cdc.gov/COVID19
- Contact your local or state public health department.
### What is an Emergency Use Authorization (EUA)
The United States FDA has made remdesivir available under an emergency access mechanism called an EUA. The EUA is supported by a Secretary of Health and Human Service (HHS) declaration that circumstances exist to justify the emergency use of drugs and biological products during the COVID-19 pandemic. Remdesivir has not undergone the same type of review as an FDA-approved or cleared product. FDA may issue an EUA when certain criteria are met, which includes that there are no adequate, approved, available alternatives. In addition, the FDA decision is based on the totality of scientific evidence available showing that it is reasonable to believe that the product meets certain criteria for safety, performance, and labeling and may be effective in treatment of patients during the COVID-19 pandemic. All of these criteria must be met to allow for the product to be used in the treatment of patients during the COVID-19 pandemic.
The EUA for remdesivir is in effect for the duration of the COVID-19 declaration justifying emergency use of these products, unless terminated or revoked (after which the products may no longer be used)
Source: Fact Sheet for Patients and Parents/Caregivers
# Precautions with Alcohol
Alcohol-Sandbox gc4 interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
# Brand Names
Veklury®
# Look-Alike Drug Names
There is limited information regarding Sandbox gc4 Look-Alike Drug Names.
# Drug Shortage Status | https://www.wikidoc.org/index.php/Sandbox_gc4 | |
79d8542dc4620fb66c4134eec0df66fbcf5ca840 | wikidoc | Sandbox mir | Sandbox mir
Chest pain
First determine which sort of angina it can be classified as based on the explanation of pain by patient and your physical exam:
- Typical angina characteristics = 3:
Long duration > 20 minutes + Quality: Pressure or crushing
Provoked by physical or emotional stress
Relieved by rest or Nitroglycerin tablets
- Long duration > 20 minutes + Quality: Pressure or crushing
- Provoked by physical or emotional stress
- Relieved by rest or Nitroglycerin tablets
If 2 or 3 of the following criteria is present, the it is typical angina, if 0-1 present, it is atypical angina.
Then calculate the "pretest probability of coronary artery disease" based on:
- Patient's age
- Patient's angina type
- Patient's gender
Now based on "pretest probability of coronary artery disease", manage patient based on the following table:
## Side effects of drugs:
- Nephrotoxicity → Cephalosporins
- Ototoxicity → Loop diuretics
- Both nephron and ototoxicity→ Aminoglycosides, vancomycin, loop diuretics and cisplatin
- Pseudomembranous colitis → Ampicillin, Clindamycin
## DNA
DNA contains phosphate group, so it is negatively charged because of the negatively charged phosphate groups
DNA is composed of nucleotides, which classifies based on their properties to purines and pyrimidines:
Purine synthesis:
- You need glycine, glutamine and aspartate + tetrahydrofolate (Folic acid) + CO2
- Rate limiting step : Glutamine PRPP amidotransferase
- Carbon sources:
CO2, glycine, tetrahydrofolate
- CO2, glycine, tetrahydrofolate
- Nitrogen sources
Aspartate + Glutamine
- Aspartate + Glutamine
Pyrimidines synthesis:
Aspartate + carbamoyl phosphate (1 carbon and 1 nitrogen ) + ATP
- Carbamoyl phosphate → Has 1 carbon and 1 nitrogen
- You need aspartate + CO2 + glutamine + ATP (Last 3 come from carbamoyl phosphate)
- Carbamoyl phosphate synthetase 2 (RATE LIMITING STEP)
- Start with orotic acid then add a base
- Carbon sources:
Aspartate
CO2
- Aspartate
- CO2
- Glutamine → Gives nitrogen
Major bases in DNA: Guanine (G), Cytosine (C), Adennine (A), Thimine (T)
- G-C : 3 Hydrogen bonds. Higher melting points
- A-T: 2 Bonds
Histones are groups of basic proteins found in chromatin. Histone → Contain lysine and arginine
Cytosine minus aminogroup = Uracil (Deamination)
# RNA
Ribosomes are synthesized in the nucleus and transported into the cytoplasm.
Ribosomes are made of proteins and rRNA
- Eukaryotes → 60 and 40s = 80s
- Prokaryotes → 50 s and 30 s = 70 s
Have 23s in 50s
- Have 23s in 50s
Translation
- Initiation
IF1, IF2, If3
Assist in assembly of smaller ribosomal subunit to first trna molecule
Methionine is always the start
f-Methionine in prokaryotes
IF-2 first binds to 30s and then to methionine tRNA. Then when 50s comes along, it hydrolyzes GTP on IF2 and allows 50s to attach to 30s
A site → Incoming aminoacyl TRNA binds
P site → Polypeptide binds (Growing chain)
First tRNA binds here
E site → Free tRNA (exit)
- IF1, IF2, If3
Assist in assembly of smaller ribosomal subunit to first trna molecule
Methionine is always the start
f-Methionine in prokaryotes
IF-2 first binds to 30s and then to methionine tRNA. Then when 50s comes along, it hydrolyzes GTP on IF2 and allows 50s to attach to 30s
- Assist in assembly of smaller ribosomal subunit to first trna molecule
- Methionine is always the start
- f-Methionine in prokaryotes
- IF-2 first binds to 30s and then to methionine tRNA. Then when 50s comes along, it hydrolyzes GTP on IF2 and allows 50s to attach to 30s
- A site → Incoming aminoacyl TRNA binds
- P site → Polypeptide binds (Growing chain)
First tRNA binds here
- First tRNA binds here
- E site → Free tRNA (exit)
- Elongation
Incoming charged aminoacyl TRNA binds to A site
Elongation factor help incoming trna to bind to A site (Uses GTP)
50s has peptidyl transferase transfers AA from p site to A site
In prokaryotes, activity is in 23s subunit of 50s rRNA
Translocation
Ribosome complex moves 3 nucleotides
tRNA + Peptide is moved from A site to P site
Newly uncharged tRNA from P side to E side
EF-G → Eukaryotes
EF-2 in eukaryotes
Diptheria and exotoxin (Pseudomonas) inhibit this
- Incoming charged aminoacyl TRNA binds to A site
- Elongation factor help incoming trna to bind to A site (Uses GTP)
- 50s has peptidyl transferase transfers AA from p site to A site
In prokaryotes, activity is in 23s subunit of 50s rRNA
- In prokaryotes, activity is in 23s subunit of 50s rRNA
- Translocation
Ribosome complex moves 3 nucleotides
tRNA + Peptide is moved from A site to P site
Newly uncharged tRNA from P side to E side
EF-G → Eukaryotes
EF-2 in eukaryotes
Diptheria and exotoxin (Pseudomonas) inhibit this
- Ribosome complex moves 3 nucleotides
- tRNA + Peptide is moved from A site to P site
- Newly uncharged tRNA from P side to E side
- EF-G → Eukaryotes
- EF-2 in eukaryotes
Diptheria and exotoxin (Pseudomonas) inhibit this
- Diptheria and exotoxin (Pseudomonas) inhibit this
- Termination
Stop codons
UGA, UAA and UAG
Signal to STOP
No new TRNA coming
Release factor binds to MRNA and hydrolyzes GTP and new polypeptide is released.
- Stop codons
UGA, UAA and UAG
Signal to STOP
No new TRNA coming
Release factor binds to MRNA and hydrolyzes GTP and new polypeptide is released.
- UGA, UAA and UAG
- Signal to STOP
- No new TRNA coming
- Release factor binds to MRNA and hydrolyzes GTP and new polypeptide is released.
### Orotic aciduria
- Deficiency of UMP synthase
- AR
- Elevated oritic acid
- Megaloblastic anemia
Not corrected with B12 or folic acid
- Not corrected with B12 or folic acid
- No hyperammonemia
- Treat with uridine
### Ornithine Transcarbomylase Deficiency
- Causes hyperammonemia
- Elevated orotic acid
- Problem with urea cycle
Inhibit reuptake of norepinephrine:
- Cocaine
- TCA
## GLUT receptors
### GLUT 1
- Red blood cell, endothelium of RBB
Low level basal glucose uptake
No effect from insulin
- Red blood cell, endothelium of RBB
- Low level basal glucose uptake
- No effect from insulin
### GLUT 2
- Regulate glucose
Beta pancreatic and hepatocytes
- Regulate glucose
- Beta pancreatic and hepatocytes
### GLUT 3
- Neurons and placenta
- Neurons and placenta
### GLUT 4
- Skeletal muscle and adipose tissue
Insulin DEPENDENT
- Skeletal muscle and adipose tissue
- Insulin DEPENDENT
### GLUT 5
- Fructose uptake (In GI tract)
- Fructose uptake (In GI tract)
## Glucolysis
Hexokinase and glucokinase → Produce glucose 6 phosphate
- Hexokinase → All cells
Low KM (High affinity)
Low VMAX
- Low KM (High affinity)
- Low VMAX
- Glucokinase→ Only in regulators (Liver and beta cells of pancreas)
High KM
High VMAX
Induced by insulin
- High KM
- High VMAX
- Induced by insulin
### Pyruvate kinase deficiency
- Hemolytic anemia
- Inability to maintain Na K ATP ase
### PFK1 deficiency
- Elevated fructose 6-P
- Low pyruvate
- High glycogen
Regulation of Glycolysis
- Fructose 2, 6 biphosphate → From PFK2
- Insulin → Increases PFK2
Indirectly stimulates PFK1
- Indirectly stimulates PFK1
- Glucagon DECREASES glycolysis
Stimulates FBPase 2 (Fructose 6 biphophatase 2 → Converts from Fructose 2, 6 BP to Glucose 6 P
- Stimulates FBPase 2 (Fructose 6 biphophatase 2 → Converts from Fructose 2, 6 BP to Glucose 6 P
## Fasting state
- Glucagon rises → Activates CAMP → Activation of Protein kinase A
Phosphorylates FBP2/PFK2 complex → Activating FBP2 and inactivating PFK2
FBP2 → Fructose biphosphatase
Increases F6P and gluconeogenesis
- Phosphorylates FBP2/PFK2 complex → Activating FBP2 and inactivating PFK2
FBP2 → Fructose biphosphatase
- FBP2 → Fructose biphosphatase
- Increases F6P and gluconeogenesis
- Well fed state → High insulin → Stimulates PFK2 → Higher levels of F2,6 BP
## Lead poisoning
- Inhibits delta ALA dehydratase and ferrochelatase
- Degradation of ribosomal RNA
Basophilic stippling
- Basophilic stippling
Pathology of atherosclerosis
- Endothelial dysfunction
Increasing vascular permeability, thrombosis and increased adhesion
- Increasing vascular permeability, thrombosis and increased adhesion
- Accumulation of lipoproteins
Accumulation of oxidized LDL
- Accumulation of oxidized LDL
- Monocyte adhesion to endothelium
Migration of monocytes into intima (Transformed to macrophages and foam cells)
Foam cells → Macrophages full of lipids
- Migration of monocytes into intima (Transformed to macrophages and foam cells)
Foam cells → Macrophages full of lipids
- Foam cells → Macrophages full of lipids
- Factor release
Inflammation and cytokines
- Inflammation and cytokines
- Smooth muscle cell proliferation
Extracellular matrix deposition
Migration of smooth muscle cells into intima
- Extracellular matrix deposition
- Migration of smooth muscle cells into intima
- Lipid accumulation
Continued accumulation of lipids extracellularly and within macrophages and smooth muscle cells
Can rupture
- Continued accumulation of lipids extracellularly and within macrophages and smooth muscle cells
- Can rupture
## Prinzmetal Angina
- Coronary vasospasm
- Major risk factor: Smoking
Seen in younger patients
- Seen in younger patients
- Pain at rest occurring at night
- Indistinguishable from classic angina
- Diagnosed by coronary ateriography
- Transient ST elevation with no sign of stenosis on arteriography
- Calcium channel blockers → FIRST LINE. Diltiazem
Nitrates → Second line
- Nitrates → Second line
- Smoking cessation
## Cytochrome P450
### CYP450 Inhibitors
- Ciprofloxacin
Ritonavir
Amiodarone
Cimetidine
Ketoconazole
Acute alcohol use
Macrolides
Isoniazid
Grapefruit Juice
Omeprazole
Sulfanamides
- Ciprofloxacin
- Ritonavir
- Amiodarone
- Cimetidine
- Ketoconazole
- Acute alcohol use
- Macrolides
- Isoniazid
- Grapefruit Juice
- Omeprazole
- Sulfanamides
### CYP450 Inducers
- Phenytoin
Carbemazepine
Griseofulvin
Barbiturates
Rifampin
St John’s wart
Chronic alcoholism
- Phenytoin
- Carbemazepine
- Griseofulvin
- Barbiturates
- Rifampin
- St John’s wart
- Chronic alcoholism
Disulfiram Reaction
- Inhibition of acetaldehyde dehydrogenase
Increase aldehyde
Flushing, sweating, nausea, headache, hypotension
- Increase aldehyde
- Flushing, sweating, nausea, headache, hypotension
- Causes
Metronidazole
Certain cephalosporins
Cefotetan
Cefamandole
Cefoperazone
1st gen sulphonylurea
Tolbutamide
- Metronidazole
- Certain cephalosporins
Cefotetan
Cefamandole
Cefoperazone
- Cefotetan
- Cefamandole
- Cefoperazone
- 1st gen sulphonylurea
Tolbutamide
- Tolbutamide
Renin
- Stimulated by Beta 1 receptors in kidney
- Macula densa sense reduced sodium in glomerular filtrate
- JG apparatus sensing low BP
- Renin cleaves angiotensinogen into angiotensin 1
- Angiotensin 1 becomes 2
Enzyme: ACE (Angiotensin converting enzyme)
Produced in the lungs and kidneys
- Enzyme: ACE (Angiotensin converting enzyme)
- Produced in the lungs and kidneys
- Angiotensinogen produced by the liver
Angiotensin II
- Vasoconstrictor
- Stimulates aldosterone secretion
Causes sodium and water reabsorption
- Causes sodium and water reabsorption
BNP
- Causes vasodilation
- Increased excretion of sodium and water in urine
Splitting
- A2 P2 →Increased split during inspiration
Hand grip
- Increases SVR and after load
- Makes MR louder
Val salva
- Decreases venous return
- Reduces preload and afterload
- Makes HOCM louder
Patent Ductus Arteriosis
- Associated with rubella
- Indomethacin closes it
Carbidopa
- Inhibits Dopa decarboxylase
- Prevents conversion from DOPA to dopamine
## Heart Valve problems
### Aortic stenosis
- Ejection click
- Crescendo decrescendo
### Mitral regurgitation
- Increased by hand grip and squatting
### Mitral valve prolapse
- Midsystolic click
- Possible systolic crescendo murmur after click
- Valsalva makes murmur start earlier
### Mitral valve stenosis
- Small pause in the beginning
Due to initial isovolumetric contraction
- Due to initial isovolumetric contraction
- Opening snap
- Heard in apex
In left lateral decubitus
S3, S4, MR heard better on left lateral decubitus
- In left lateral decubitus
S3, S4, MR heard better on left lateral decubitus
- S3, S4, MR heard better on left lateral decubitus
- Caused by rheumatic heart disease
- PCWP is higher than LV diastolic pressure
PCWP normally < 12
LA pressure < 12
Left ventricular diastolic pressure – Around 10 mm Hg
Pressure in left atrium is higher → Increasing PCWP pressure
- PCWP normally < 12
- LA pressure < 12
- Left ventricular diastolic pressure – Around 10 mm Hg
- Pressure in left atrium is higher → Increasing PCWP pressure
### Aortic Regurgitation
- Diastolic murmur
- Immediately after S2
- Left side of sternum
- Wide pulse pressure
- Water hammer pulse
- Causes
Dilated aortic root → Syphillis
Marfan’s
Bicuspid aortic valve
Most commonly causes AS though
Rheumatic fever
- Dilated aortic root → Syphillis
- Marfan’s
- Bicuspid aortic valve
Most commonly causes AS though
- Most commonly causes AS though
- Rheumatic fever
## Ventricular action potential:
- Phase 0 → Increased sodium permeability
- Phase 1→ Repolarization. In-activation of sodium channels. K+ channels begin to open
- Phase 2 → Plataeu → K+ open, Ca2+ open
Causes calcium release from SR and myocyte contraction
- Causes calcium release from SR and myocyte contraction
- Phase 3 → K+ permeability increased. Closing of calcium channels
K+ efflux causes repolarization
- K+ efflux causes repolarization
- ERP
Cannot potentiate another action potential
- Cannot potentiate another action potential
## Pacemaker Action Potential
- Phase 0 → Voltage gated calcium channels open after reaching threshold
Not due to sodium such as in myocytes
- Not due to sodium such as in myocytes
- Phase 3 → Increased potassium permeability
- Phase 4 → Freely permeable to potassium. Gradual depolarization due to sodium channel conductance
Smooth ER makes steroids, lipids, phospholipids. Involved in detoxifying as well
# Pretest probability of coronary artery disease | Sandbox mir
Chest pain
First determine which sort of angina it can be classified as based on the explanation of pain by patient and your physical exam:
- Typical angina characteristics = 3:
Long duration > 20 minutes + Quality: Pressure or crushing
Provoked by physical or emotional stress
Relieved by rest or Nitroglycerin tablets
- Long duration > 20 minutes + Quality: Pressure or crushing
- Provoked by physical or emotional stress
- Relieved by rest or Nitroglycerin tablets
If 2 or 3 of the following criteria is present, the it is typical angina, if 0-1 present, it is atypical angina.
Then calculate the "pretest probability of coronary artery disease" based on:
- Patient's age
- Patient's angina type
- Patient's gender
Now based on "pretest probability of coronary artery disease", manage patient based on the following table:
## Side effects of drugs:
- Nephrotoxicity → Cephalosporins
- Ototoxicity → Loop diuretics
- Both nephron and ototoxicity→ Aminoglycosides, vancomycin, loop diuretics and cisplatin
- Pseudomembranous colitis → Ampicillin, Clindamycin
## DNA
DNA contains phosphate group, so it is negatively charged because of the negatively charged phosphate groups
DNA is composed of nucleotides, which classifies based on their properties to purines and pyrimidines:
Purine synthesis:
- You need glycine, glutamine and aspartate + tetrahydrofolate (Folic acid) + CO2
- Rate limiting step : Glutamine PRPP amidotransferase
- Carbon sources:
CO2, glycine, tetrahydrofolate
- CO2, glycine, tetrahydrofolate
- Nitrogen sources
Aspartate + Glutamine
- Aspartate + Glutamine
Pyrimidines synthesis:
Aspartate + carbamoyl phosphate (1 carbon and 1 nitrogen [glutamine]) + ATP
- Carbamoyl phosphate → Has 1 carbon and 1 nitrogen
- You need aspartate + CO2 + glutamine + ATP (Last 3 come from carbamoyl phosphate)
- Carbamoyl phosphate synthetase 2 (RATE LIMITING STEP)
- Start with orotic acid then add a base
- Carbon sources:
Aspartate
CO2
- Aspartate
- CO2
- Glutamine → Gives nitrogen
Major bases in DNA: Guanine (G), Cytosine (C), Adennine (A), Thimine (T)
- G-C : 3 Hydrogen bonds. Higher melting points
- A-T: 2 Bonds
Histones are groups of basic proteins found in chromatin. Histone → Contain lysine and arginine
Cytosine minus aminogroup = Uracil (Deamination)
# RNA
Ribosomes are synthesized in the nucleus and transported into the cytoplasm.
Ribosomes are made of proteins and rRNA
- Eukaryotes → 60 and 40s = 80s
- Prokaryotes → 50 s and 30 s = 70 s
Have 23s in 50s
- Have 23s in 50s
Translation
- Initiation
IF1, IF2, If3
Assist in assembly of smaller ribosomal subunit to first trna molecule
Methionine is always the start
f-Methionine in prokaryotes
IF-2 first binds to 30s and then to methionine tRNA. Then when 50s comes along, it hydrolyzes GTP on IF2 and allows 50s to attach to 30s
A site → Incoming aminoacyl TRNA binds
P site → Polypeptide binds (Growing chain)
First tRNA binds here
E site → Free tRNA (exit)
- IF1, IF2, If3
Assist in assembly of smaller ribosomal subunit to first trna molecule
Methionine is always the start
f-Methionine in prokaryotes
IF-2 first binds to 30s and then to methionine tRNA. Then when 50s comes along, it hydrolyzes GTP on IF2 and allows 50s to attach to 30s
- Assist in assembly of smaller ribosomal subunit to first trna molecule
- Methionine is always the start
- f-Methionine in prokaryotes
- IF-2 first binds to 30s and then to methionine tRNA. Then when 50s comes along, it hydrolyzes GTP on IF2 and allows 50s to attach to 30s
- A site → Incoming aminoacyl TRNA binds
- P site → Polypeptide binds (Growing chain)
First tRNA binds here
- First tRNA binds here
- E site → Free tRNA (exit)
- Elongation
Incoming charged aminoacyl TRNA binds to A site
Elongation factor help incoming trna to bind to A site (Uses GTP)
50s has peptidyl transferase transfers AA from p site to A site
In prokaryotes, activity is in 23s subunit of 50s rRNA
Translocation
Ribosome complex moves 3 nucleotides
tRNA + Peptide is moved from A site to P site
Newly uncharged tRNA from P side to E side
EF-G → Eukaryotes
EF-2 in eukaryotes
Diptheria and exotoxin (Pseudomonas) inhibit this
- Incoming charged aminoacyl TRNA binds to A site
- Elongation factor help incoming trna to bind to A site (Uses GTP)
- 50s has peptidyl transferase transfers AA from p site to A site
In prokaryotes, activity is in 23s subunit of 50s rRNA
- In prokaryotes, activity is in 23s subunit of 50s rRNA
- Translocation
Ribosome complex moves 3 nucleotides
tRNA + Peptide is moved from A site to P site
Newly uncharged tRNA from P side to E side
EF-G → Eukaryotes
EF-2 in eukaryotes
Diptheria and exotoxin (Pseudomonas) inhibit this
- Ribosome complex moves 3 nucleotides
- tRNA + Peptide is moved from A site to P site
- Newly uncharged tRNA from P side to E side
- EF-G → Eukaryotes
- EF-2 in eukaryotes
Diptheria and exotoxin (Pseudomonas) inhibit this
- Diptheria and exotoxin (Pseudomonas) inhibit this
- Termination
Stop codons
UGA, UAA and UAG
Signal to STOP
No new TRNA coming
Release factor binds to MRNA and hydrolyzes GTP and new polypeptide is released.
- Stop codons
UGA, UAA and UAG
Signal to STOP
No new TRNA coming
Release factor binds to MRNA and hydrolyzes GTP and new polypeptide is released.
- UGA, UAA and UAG
- Signal to STOP
- No new TRNA coming
- Release factor binds to MRNA and hydrolyzes GTP and new polypeptide is released.
### Orotic aciduria
- Deficiency of UMP synthase
- AR
- Elevated oritic acid
- Megaloblastic anemia
Not corrected with B12 or folic acid
- Not corrected with B12 or folic acid
- No hyperammonemia
- Treat with uridine
### Ornithine Transcarbomylase Deficiency
- Causes hyperammonemia
- Elevated orotic acid
- Problem with urea cycle
Inhibit reuptake of norepinephrine:
- Cocaine
- TCA
## GLUT receptors
### GLUT 1
- Red blood cell, endothelium of RBB
Low level basal glucose uptake
No effect from insulin
- Red blood cell, endothelium of RBB
- Low level basal glucose uptake
- No effect from insulin
### GLUT 2
- Regulate glucose
Beta pancreatic and hepatocytes
- Regulate glucose
- Beta pancreatic and hepatocytes
### GLUT 3
- Neurons and placenta
- Neurons and placenta
### GLUT 4
- Skeletal muscle and adipose tissue
Insulin DEPENDENT
- Skeletal muscle and adipose tissue
- Insulin DEPENDENT
### GLUT 5
- Fructose uptake (In GI tract)
- Fructose uptake (In GI tract)
## Glucolysis
Hexokinase and glucokinase → Produce glucose 6 phosphate
- Hexokinase → All cells
Low KM (High affinity)
Low VMAX
- Low KM (High affinity)
- Low VMAX
- Glucokinase→ Only in regulators (Liver and beta cells of pancreas)
High KM
High VMAX
Induced by insulin
- High KM
- High VMAX
- Induced by insulin
### Pyruvate kinase deficiency
- Hemolytic anemia
- Inability to maintain Na K ATP ase
### PFK1 deficiency
- Elevated fructose 6-P
- Low pyruvate
- High glycogen
Regulation of Glycolysis
- Fructose 2, 6 biphosphate → From PFK2
- Insulin → Increases PFK2
Indirectly stimulates PFK1
- Indirectly stimulates PFK1
- Glucagon DECREASES glycolysis
Stimulates FBPase 2 (Fructose 6 biphophatase 2 → Converts from Fructose 2, 6 BP to Glucose 6 P
- Stimulates FBPase 2 (Fructose 6 biphophatase 2 → Converts from Fructose 2, 6 BP to Glucose 6 P
## Fasting state
- Glucagon rises → Activates CAMP → Activation of Protein kinase A
Phosphorylates FBP2/PFK2 complex → Activating FBP2 and inactivating PFK2
FBP2 → Fructose biphosphatase
Increases F6P and gluconeogenesis
- Phosphorylates FBP2/PFK2 complex → Activating FBP2 and inactivating PFK2
FBP2 → Fructose biphosphatase
- FBP2 → Fructose biphosphatase
- Increases F6P and gluconeogenesis
- Well fed state → High insulin → Stimulates PFK2 → Higher levels of F2,6 BP
## Lead poisoning
- Inhibits delta ALA dehydratase and ferrochelatase
- Degradation of ribosomal RNA
Basophilic stippling
- Basophilic stippling
Pathology of atherosclerosis
- Endothelial dysfunction
Increasing vascular permeability, thrombosis and increased adhesion
- Increasing vascular permeability, thrombosis and increased adhesion
- Accumulation of lipoproteins
Accumulation of oxidized LDL
- Accumulation of oxidized LDL
- Monocyte adhesion to endothelium
Migration of monocytes into intima (Transformed to macrophages and foam cells)
Foam cells → Macrophages full of lipids
- Migration of monocytes into intima (Transformed to macrophages and foam cells)
Foam cells → Macrophages full of lipids
- Foam cells → Macrophages full of lipids
- Factor release
Inflammation and cytokines
- Inflammation and cytokines
- Smooth muscle cell proliferation
Extracellular matrix deposition
Migration of smooth muscle cells into intima
- Extracellular matrix deposition
- Migration of smooth muscle cells into intima
- Lipid accumulation
Continued accumulation of lipids extracellularly and within macrophages and smooth muscle cells
Can rupture
- Continued accumulation of lipids extracellularly and within macrophages and smooth muscle cells
- Can rupture
## Prinzmetal Angina
- Coronary vasospasm
- Major risk factor: Smoking
Seen in younger patients
- Seen in younger patients
- Pain at rest occurring at night
- Indistinguishable from classic angina
- Diagnosed by coronary ateriography
- Transient ST elevation with no sign of stenosis on arteriography
- Calcium channel blockers → FIRST LINE. Diltiazem
Nitrates → Second line
- Nitrates → Second line
- Smoking cessation
## Cytochrome P450
### CYP450 Inhibitors
- Ciprofloxacin
Ritonavir
Amiodarone
Cimetidine
Ketoconazole
Acute alcohol use
Macrolides
Isoniazid
Grapefruit Juice
Omeprazole
Sulfanamides
- Ciprofloxacin
- Ritonavir
- Amiodarone
- Cimetidine
- Ketoconazole
- Acute alcohol use
- Macrolides
- Isoniazid
- Grapefruit Juice
- Omeprazole
- Sulfanamides
### CYP450 Inducers
- Phenytoin
Carbemazepine
Griseofulvin
Barbiturates
Rifampin
St John’s wart
Chronic alcoholism
- Phenytoin
- Carbemazepine
- Griseofulvin
- Barbiturates
- Rifampin
- St John’s wart
- Chronic alcoholism
Disulfiram Reaction
- Inhibition of acetaldehyde dehydrogenase
Increase aldehyde
Flushing, sweating, nausea, headache, hypotension
- Increase aldehyde
- Flushing, sweating, nausea, headache, hypotension
- Causes
Metronidazole
Certain cephalosporins
Cefotetan
Cefamandole
Cefoperazone
1st gen sulphonylurea
Tolbutamide
- Metronidazole
- Certain cephalosporins
Cefotetan
Cefamandole
Cefoperazone
- Cefotetan
- Cefamandole
- Cefoperazone
- 1st gen sulphonylurea
Tolbutamide
- Tolbutamide
Renin
- Stimulated by Beta 1 receptors in kidney
- Macula densa sense reduced sodium in glomerular filtrate
- JG apparatus sensing low BP
- Renin cleaves angiotensinogen into angiotensin 1
- Angiotensin 1 becomes 2
Enzyme: ACE (Angiotensin converting enzyme)
Produced in the lungs and kidneys
- Enzyme: ACE (Angiotensin converting enzyme)
- Produced in the lungs and kidneys
- Angiotensinogen produced by the liver
Angiotensin II
- Vasoconstrictor
- Stimulates aldosterone secretion
Causes sodium and water reabsorption
- Causes sodium and water reabsorption
BNP
- Causes vasodilation
- Increased excretion of sodium and water in urine
Splitting
- A2 P2 →Increased split during inspiration
Hand grip
- Increases SVR and after load
- Makes MR louder
Val salva
- Decreases venous return
- Reduces preload and afterload
- Makes HOCM louder
Patent Ductus Arteriosis
- Associated with rubella
- Indomethacin closes it
Carbidopa
- Inhibits Dopa decarboxylase
- Prevents conversion from DOPA to dopamine
## Heart Valve problems
### Aortic stenosis
- Ejection click
- Crescendo decrescendo
### Mitral regurgitation
- Increased by hand grip and squatting
### Mitral valve prolapse
- Midsystolic click
- Possible systolic crescendo murmur after click
- Valsalva makes murmur start earlier
### Mitral valve stenosis
- Small pause in the beginning
Due to initial isovolumetric contraction
- Due to initial isovolumetric contraction
- Opening snap
- Heard in apex
In left lateral decubitus
S3, S4, MR heard better on left lateral decubitus
- In left lateral decubitus
S3, S4, MR heard better on left lateral decubitus
- S3, S4, MR heard better on left lateral decubitus
- Caused by rheumatic heart disease
- PCWP is higher than LV diastolic pressure
PCWP normally < 12
LA pressure < 12
Left ventricular diastolic pressure – Around 10 mm Hg
Pressure in left atrium is higher → Increasing PCWP pressure
- PCWP normally < 12
- LA pressure < 12
- Left ventricular diastolic pressure – Around 10 mm Hg
- Pressure in left atrium is higher → Increasing PCWP pressure
### Aortic Regurgitation
- Diastolic murmur
- Immediately after S2
- Left side of sternum
- Wide pulse pressure
- Water hammer pulse
- Causes
Dilated aortic root → Syphillis
Marfan’s
Bicuspid aortic valve
Most commonly causes AS though
Rheumatic fever
- Dilated aortic root → Syphillis
- Marfan’s
- Bicuspid aortic valve
Most commonly causes AS though
- Most commonly causes AS though
- Rheumatic fever
## Ventricular action potential:
- Phase 0 → Increased sodium permeability
- Phase 1→ Repolarization. In-activation of sodium channels. K+ channels begin to open
- Phase 2 → Plataeu → K+ open, Ca2+ open
Causes calcium release from SR and myocyte contraction
- Causes calcium release from SR and myocyte contraction
- Phase 3 → K+ permeability increased. Closing of calcium channels
K+ efflux causes repolarization
- K+ efflux causes repolarization
- ERP
Cannot potentiate another action potential
- Cannot potentiate another action potential
## Pacemaker Action Potential
- Phase 0 → Voltage gated calcium channels open after reaching threshold
Not due to sodium such as in myocytes
- Not due to sodium such as in myocytes
- Phase 3 → Increased potassium permeability
- Phase 4 → Freely permeable to potassium. Gradual depolarization due to sodium channel conductance
-
Smooth ER makes steroids, lipids, phospholipids. Involved in detoxifying as well
# Pretest probability of coronary artery disease | https://www.wikidoc.org/index.php/Sandbox_mir | |
c2b4514b7727edfe1ddfb4ac4794ec2879fe9432 | wikidoc | Sandbox mkk | Sandbox mkk
Peptic ulcer disease symptoms
A positive history of epigastric pain ,loss of appetite and weight loss are suggestive of peptic ulcer disease .
Common symptoms :
- Epigastric pain(gastric ulcer -pain increased with taking food and duodenal ulcer decreased with food intake )
- Indigestion
- Nausea, vomiting
- Hematemesis (blood in the vomitus )
- Blood in stools
- Loss of appetite
- Weight loss
# Preferred Template Statements
IF there is one particularly identifiable symptom of the disease:
- The hallmark of is . A positive history of and is suggestive of . The most common symptoms of include , , and .
IF there are many equally recognizable symptoms of the disease:
- Symptoms of include , , and .
IF it makes sense to distinguish between common and less-common symptoms:
- On the overview page, use a full sentence:
Common symptoms of include , , and .
Less common symptoms of include , , and .
- Common symptoms of include , , and .
- Less common symptoms of include , , and .
- On the History and Symptoms microchapter, use bullet points:
Common symptoms of include:
- Common symptoms of include:
IF symptoms are usually not present:
- The majority of patients with are asymptomatic.
# History
- Here you should describe the important components in the patients history that should be given particular focus. Remember to include pertinent points from the past medical history, family history, social history (including occupational, alcohol use with amount and frequency, smoking, drug use) and allergies.
- Remember this is not the section to describe the natural history of the disease or the historical perspective.
- For an example of the history section within the history and symptoms page, click here.
==Common Symptom:
- Epigastric pain(gastric ulcer -pain increased with taking food and duodenal ulcer decreased with food intake )
- Indigestion
- Nausea, vomiting
- Hematemesis (blood in the vomitus )
- Blood in stools
- Loss of appetite
- Weight loss
# Less Common Symptoms
- In this section you can list the less common symptoms that the patient may experience.
- For an example of the the less common symptoms section within a history and symptoms page, click here. | Sandbox mkk
Peptic ulcer disease symptoms
A positive history of epigastric pain ,loss of appetite and weight loss are suggestive of peptic ulcer disease .
Common symptoms :
- Epigastric pain(gastric ulcer -pain increased with taking food and duodenal ulcer decreased with food intake )
- Indigestion
- Nausea, vomiting
- Hematemesis (blood in the vomitus )
- Blood in stools
- Loss of appetite
- Weight loss
# Preferred Template Statements
IF there is one particularly identifiable symptom of the disease:
- The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].
IF there are many equally recognizable symptoms of the disease:
- Symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].
IF it makes sense to distinguish between common and less-common symptoms:
- On the overview page, use a full sentence:
Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3].
Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].
- Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3].
- Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].
- On the History and Symptoms microchapter, use bullet points:
Common symptoms of [disease] include:
[symptom 1]
[symptom 2]
[symptom 3]
- Common symptoms of [disease] include:
[symptom 1]
[symptom 2]
[symptom 3]
- [symptom 1]
- [symptom 2]
- [symptom 3]
IF symptoms are usually not present:
- The majority of patients with [disease name] are asymptomatic.
# History
- Here you should describe the important components in the patients history that should be given particular focus. Remember to include pertinent points from the past medical history, family history, social history (including occupational, alcohol use with amount and frequency, smoking, drug use) and allergies.
- Remember this is not the section to describe the natural history of the disease or the historical perspective.
- For an example of the history section within the history and symptoms page, click here.
==Common Symptom:
- Epigastric pain(gastric ulcer -pain increased with taking food and duodenal ulcer decreased with food intake )
- Indigestion
- Nausea, vomiting
- Hematemesis (blood in the vomitus )
- Blood in stools
- Loss of appetite
- Weight loss
# Less Common Symptoms
- In this section you can list the less common symptoms that the patient may experience.
- For an example of the the less common symptoms section within a history and symptoms page, click here. | https://www.wikidoc.org/index.php/Sandbox_mkk | |
31529cad87658b4de69fc0495fa5c71de69568c8 | wikidoc | Sandbox pud | Sandbox pud
# Overview
Eradication of Helicobacter pylori with antimicrobial agents is indicated for patients with gastric or duodenal peptic ulceration who are colonized with Helicobacter pylori and patients with MALT lymphoma. Eradication therapy should also be considered for patients with immune thrombocytopenic purpura who are H. pylori positive or patients who have undergone resection for early-stage gastric cancer. The use of antibiotics is discouraged in asymptomatic carriers.
# Medical Therapy
## Diagnostic testing
The American Journal of Gastroenterology guidelines recommend that endoscopy should be performed to rule out peptic ulcer disease, esophagogastric malignancy, and other rare upper gastrointestinal tract disease in the following settings:
- Dyspeptic patients more than 55 years old OR
- Dyspeptic patients with alarm features
- Bleeding
- Anemia
- Early satiety
- Unexplained weight loss (> 10% body weight)
- Progressive dysphagia
- Odynophagia
- Persistent vomiting
- A family history of gastrointestinal cancer
- Previous esophagogastric malignancy
- Previous documented peptic ulcer, lymphadenopathy, or an abdominal mass
In patients aged 55 years or younger with no alarm features, two management options may be considered:
- Test-and-treat strategy using a validated noninvasive test (urea breathing test or stool antigen test) for H. pylori and a trial of acid suppression if eradication is successful but symptoms do not resolve – preferable in populations with a moderate to high prevalence of H. pylori infection (≥ 10%)
- Empiric trial of acid suppression with a proton pump inhibitor for 4–8 weeks – preferable in low prevalence situations
Repeat endoscopy is not recommended once a firm diagnosis of functional dyspepsia has been established, unless new symptoms or alarm features develop. Testing to prove H. pylori eradication is most accurate if performed 4 weeks after the completion of therapy.
## Treatment strategies
- The use of high-dose (twice a day) proton pump inhibitor (PPI) increases the efficacy of triple therapy.
- In areas of low clarithromycin resistance, clarithromycin-containing treatments (PCA or PCM) are recommended for first-line empirical treatment. Bismuth-containing quadruple treatment is also an alternative.
- In areas of high clarithromycin resistance, bismuth-containing quadruple treatment is recommended for first-line empirical treatment. If this regimen is not available, sequential treatment is recommended.
- Extending the duration of triple treatment from 7 to 10–14 days improves the eradication success rate and may be considered.
- After failure of a PPI-clarithromycin containing therapy, either a bismuth-containing quadruple treatment or levofloxacin-containing triple therapy (PLA) is recommended.
- After failure of second-line treatment, treatment should be guided by antimicrobial susceptibility testing whenever possible.
- The urea breath test or a laboratory based validated monoclonal stool test are both recommended as non-invasive tests for determining the success of eradication treatment.
# Eradication Therapy for Helicobacter pylori Infection
## First-line therapies
- Triple therapy (PCA or PCM regimen)
Proton pump inhibitor (standard dose twice daily) for 7–14 days AND
Clarithromycin (500 mg twice daily) for 7–14 days AND
Amoxicillin (1 g twice daily) for 7–14 days OR Metronidazole (250 mg four times daily) for 7–14 days
- Proton pump inhibitor (standard dose twice daily) for 7–14 days AND
- Clarithromycin (500 mg twice daily) for 7–14 days AND
- Amoxicillin (1 g twice daily) for 7–14 days OR Metronidazole (250 mg four times daily) for 7–14 days
- Quadruple therapy
Proton pump inhibitor (standard dose twice daily) for 10–14 days AND
Metronidazole (250 mg four times daily) for 10–14 days AND
Tetracycline (500 mg four times daily) for 10–14 days AND
Bismuth (dose depends on preparation) for 10–14 days
- Proton pump inhibitor (standard dose twice daily) for 10–14 days AND
- Metronidazole (250 mg four times daily) for 10–14 days AND
- Tetracycline (500 mg four times daily) for 10–14 days AND
- Bismuth (dose depends on preparation) for 10–14 days
- Sequential therapy
Proton pump inhibitor (standard dose twice daily) for 5 days AND
Amoxicillin (1 g twice times daily) for 5 daysFOLLOWED BY
Proton pump inhibitor (standard dose twice daily) for another 5 days AND
Clarithromycin (500 mg twice daily) for another 5 days AND
Tinidazole (500 mg twice daily) for another 5 days
- Proton pump inhibitor (standard dose twice daily) for 5 days AND
- Amoxicillin (1 g twice times daily) for 5 daysFOLLOWED BY
- Proton pump inhibitor (standard dose twice daily) for another 5 days AND
- Clarithromycin (500 mg twice daily) for another 5 days AND
- Tinidazole (500 mg twice daily) for another 5 days
## Second-line therapies
- Triple therapy (PLA regimen)
Proton pump inhibitor (standard dose twice daily) for 10 days AND
Levofloxacin (500 mg twice daily) for 10 days AND
Amoxicillin (1 g twice daily) for 10 days
- Proton pump inhibitor (standard dose twice daily) for 10 days AND
- Levofloxacin (500 mg twice daily) for 10 days AND
- Amoxicillin (1 g twice daily) for 10 days
- Triple therapy (PMA regimen)
Proton pump inhibitor (standard dose twice daily) for 7–14 days AND
Metronidazole (250 mg four times daily) for 7–14 days AND
Amoxicillin (1 g twice daily) for 7–14 days
- Proton pump inhibitor (standard dose twice daily) for 7–14 days AND
- Metronidazole (250 mg four times daily) for 7–14 days AND
- Amoxicillin (1 g twice daily) for 7–14 days
- Triple therapy (PRA regimen)
Proton pump inhibitor (standard dose twice daily) for 10 days AND
Rifabutin (150–300 mg/day) for 10 days AND
Amoxicillin (1 g twice daily) for 10 days
- Proton pump inhibitor (standard dose twice daily) for 10 days AND
- Rifabutin (150–300 mg/day) for 10 days AND
- Amoxicillin (1 g twice daily) for 10 days
# Algorithm for the Approach to Dyspepsia
# Contraindicated Medications
Bleeding peptic ulcer is considered an absolute contraindication to the use of the following medications:
- Ketorolac tromethamine
- Mefenamic acid
- Ticlopidine
- Prasugrel
- Reserpine
- Streptokinase
- Vorapaxar
# Guidelines and Resources
- American College of Gastroenterology (ACG) – Guidelines for the management of dyspepsia.
- American Society for Gastrointestinal Endoscopy (ASGE) – The role of endoscopy in dyspepsia.
- American Society for Gastrointestinal Endoscopy (ASGE) – The role of endoscopy in gastroduodenal obstruction and gastroparesis.
- American College of Cardiology Foundation/American College of Gastroenterology/American Heart Association (ACCF/ACG/AHA) – Reducing the gastrointestinal risks of antiplatelet therapy and NSAID use.
- The European Helicobacter Study Group (EHSG) – Management of Helicobacter pylori infection. | Sandbox pud
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Gerald Chi, M.D.
# Overview
Eradication of Helicobacter pylori with antimicrobial agents is indicated for patients with gastric or duodenal peptic ulceration who are colonized with Helicobacter pylori and patients with MALT lymphoma. Eradication therapy should also be considered for patients with immune thrombocytopenic purpura who are H. pylori positive or patients who have undergone resection for early-stage gastric cancer. The use of antibiotics is discouraged in asymptomatic carriers.
# Medical Therapy
## Diagnostic testing
The American Journal of Gastroenterology guidelines recommend that endoscopy should be performed to rule out peptic ulcer disease, esophagogastric malignancy, and other rare upper gastrointestinal tract disease in the following settings:
- Dyspeptic patients more than 55 years old OR
- Dyspeptic patients with alarm features
- Bleeding
- Anemia
- Early satiety
- Unexplained weight loss (> 10% body weight)
- Progressive dysphagia
- Odynophagia
- Persistent vomiting
- A family history of gastrointestinal cancer
- Previous esophagogastric malignancy
- Previous documented peptic ulcer, lymphadenopathy, or an abdominal mass
In patients aged 55 years or younger with no alarm features, two management options may be considered:
- Test-and-treat strategy using a validated noninvasive test (urea breathing test or stool antigen test) for H. pylori and a trial of acid suppression if eradication is successful but symptoms do not resolve – preferable in populations with a moderate to high prevalence of H. pylori infection (≥ 10%)
- Empiric trial of acid suppression with a proton pump inhibitor for 4–8 weeks – preferable in low prevalence situations
Repeat endoscopy is not recommended once a firm diagnosis of functional dyspepsia has been established, unless new symptoms or alarm features develop.[1] Testing to prove H. pylori eradication is most accurate if performed 4 weeks after the completion of therapy.[2]
## Treatment strategies
- The use of high-dose (twice a day) proton pump inhibitor (PPI) increases the efficacy of triple therapy.
- In areas of low clarithromycin resistance, clarithromycin-containing treatments (PCA or PCM) are recommended for first-line empirical treatment. Bismuth-containing quadruple treatment is also an alternative.
- In areas of high clarithromycin resistance, bismuth-containing quadruple treatment is recommended for first-line empirical treatment. If this regimen is not available, sequential treatment is recommended.
- Extending the duration of triple treatment from 7 to 10–14 days improves the eradication success rate and may be considered.
- After failure of a PPI-clarithromycin containing therapy, either a bismuth-containing quadruple treatment or levofloxacin-containing triple therapy (PLA) is recommended.
- After failure of second-line treatment, treatment should be guided by antimicrobial susceptibility testing whenever possible.
- The urea breath test or a laboratory based validated monoclonal stool test are both recommended as non-invasive tests for determining the success of eradication treatment.[3]
# Eradication Therapy for Helicobacter pylori Infection
## First-line therapies
- Triple therapy (PCA or PCM regimen)
Proton pump inhibitor (standard dose twice daily) for 7–14 days AND
Clarithromycin (500 mg twice daily) for 7–14 days AND
Amoxicillin (1 g twice daily) for 7–14 days OR Metronidazole (250 mg four times daily) for 7–14 days
- Proton pump inhibitor (standard dose twice daily) for 7–14 days AND
- Clarithromycin (500 mg twice daily) for 7–14 days AND
- Amoxicillin (1 g twice daily) for 7–14 days OR Metronidazole (250 mg four times daily) for 7–14 days
- Quadruple therapy
Proton pump inhibitor (standard dose twice daily) for 10–14 days AND
Metronidazole (250 mg four times daily) for 10–14 days AND
Tetracycline (500 mg four times daily) for 10–14 days AND
Bismuth (dose depends on preparation) for 10–14 days
- Proton pump inhibitor (standard dose twice daily) for 10–14 days AND
- Metronidazole (250 mg four times daily) for 10–14 days AND
- Tetracycline (500 mg four times daily) for 10–14 days AND
- Bismuth (dose depends on preparation) for 10–14 days
- Sequential therapy
Proton pump inhibitor (standard dose twice daily) for 5 days AND
Amoxicillin (1 g twice times daily) for 5 daysFOLLOWED BY
Proton pump inhibitor (standard dose twice daily) for another 5 days AND
Clarithromycin (500 mg twice daily) for another 5 days AND
Tinidazole (500 mg twice daily) for another 5 days
- Proton pump inhibitor (standard dose twice daily) for 5 days AND
- Amoxicillin (1 g twice times daily) for 5 daysFOLLOWED BY
- Proton pump inhibitor (standard dose twice daily) for another 5 days AND
- Clarithromycin (500 mg twice daily) for another 5 days AND
- Tinidazole (500 mg twice daily) for another 5 days
## Second-line therapies
- Triple therapy (PLA regimen)
Proton pump inhibitor (standard dose twice daily) for 10 days AND
Levofloxacin (500 mg twice daily) for 10 days AND
Amoxicillin (1 g twice daily) for 10 days
- Proton pump inhibitor (standard dose twice daily) for 10 days AND
- Levofloxacin (500 mg twice daily) for 10 days AND
- Amoxicillin (1 g twice daily) for 10 days
- Triple therapy (PMA regimen)
Proton pump inhibitor (standard dose twice daily) for 7–14 days AND
Metronidazole (250 mg four times daily) for 7–14 days AND
Amoxicillin (1 g twice daily) for 7–14 days
- Proton pump inhibitor (standard dose twice daily) for 7–14 days AND
- Metronidazole (250 mg four times daily) for 7–14 days AND
- Amoxicillin (1 g twice daily) for 7–14 days
- Triple therapy (PRA regimen)
Proton pump inhibitor (standard dose twice daily) for 10 days AND
Rifabutin (150–300 mg/day) for 10 days AND
Amoxicillin (1 g twice daily) for 10 days
- Proton pump inhibitor (standard dose twice daily) for 10 days AND
- Rifabutin (150–300 mg/day) for 10 days AND
- Amoxicillin (1 g twice daily) for 10 days
# Algorithm for the Approach to Dyspepsia
# Contraindicated Medications
Bleeding peptic ulcer is considered an absolute contraindication to the use of the following medications:
- Ketorolac tromethamine
- Mefenamic acid
- Ticlopidine
- Prasugrel
- Reserpine
- Streptokinase
- Vorapaxar
# Guidelines and Resources
- American College of Gastroenterology (ACG) – Guidelines for the management of dyspepsia.[4]
- American Society for Gastrointestinal Endoscopy (ASGE) – The role of endoscopy in dyspepsia.[5]
- American Society for Gastrointestinal Endoscopy (ASGE) – The role of endoscopy in gastroduodenal obstruction and gastroparesis.[6]
- American College of Cardiology Foundation/American College of Gastroenterology/American Heart Association (ACCF/ACG/AHA) – Reducing the gastrointestinal risks of antiplatelet therapy and NSAID use.[7]
- The European Helicobacter Study Group (EHSG) – Management of Helicobacter pylori infection.[8] | https://www.wikidoc.org/index.php/Sandbox_pud | |
4c21201246b40701052f01f40985a2c0d8a4bf5c | wikidoc | Sandbox sss | Sandbox sss
# Streptococcus pneumoniae
# Neisseria meningitidis
# Listeria Monocytogenes and Streptococcus agalactiae
# Haemophilus influenzae
# Staphylococcus aureus
# Staphylococcus epidermidis and Acinetobacter baumanniiΩ
# Enterobacteriaceae and Pseudomonas aeruginosa
† MIC = minimum inhibitory concentration.‡Addition of rifampicin can be considered if the organism is susceptible, the expected clinical or bacteriological response is delayed, or the cefotaxime/ceftriaxone MIC of the pneumococcal isolate is >4.0 μg/mL organism is susceptible, the expected clinical or bacteriological response is delayed, or the cefotaxime/ceftriaxone MIC.
Φ No clinical data exist for use of this agent in patients with pneumococcal meningitis; recommendation is based on cerebrospinal fluid penetration and in-vitro activity against S. pneumoniae.
£ Addition of an aminoglycoside should be considered; might need intraventricular or intrathecal administration in Gram-negative meningitis.
ǁ Addition of rifampicin should be considered.
Ω Choice of a specific agent should be based on in-vitro susceptibility testing.
†† Might also need to be administered by the intraventricular or intrathecal routes.
ǂ Might also need to be administered by the intraventricular or intrathecal routes.
₦ Addition of rifampicin should be considered.
Δ The fluoroquinolones gatifloxacin and moxifloxacin pene trate the CSF effectively and have greater in-vitro activity against Gram-positive bacteria than do their earlier counterparts (eg, ciprofloxacin). Findings from experi mental meningitis models suggested their efficacy in S. pneumoniae meningitis, including that caused by penicillin-resistant and cephalosporin-resistant strains. Although one controlled trial suggested the fluoroquinolone trovafl -oxacin mesilate to be as eff ective as ceftriaxone, with or without the addition of vancomycin, for paediatric bacterial meningitis, no clinical trials describe the use of gatifloxacin or moxifloxacin to treat bacterial meningitis in human beings. Trovafloxacin and gatifloxacin have been asso ciated with serious hepatic toxicity and dysglycaemia, respectively, and were with drawn from many markets. The IDSA guidelines recommend moxifloxacin as an alternative to third-generation cephalosporins plus vancomycin for meningitis caused by S. pneumoniae strains resistant to penicillin and third-generation cephalosporins, although some experts recom mend that this agent should not be used alone but rather should be combined with another drug (either vancomycin or a third-generation cephalosporin), because of the absence of clinical data supporting its use. | Sandbox sss
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
### Streptococcus pneumoniae
### Neisseria meningitidis
### Listeria Monocytogenes and Streptococcus agalactiae
### Haemophilus influenzae
### Staphylococcus aureus
### Staphylococcus epidermidis and Acinetobacter baumanniiΩ
### Enterobacteriaceae and Pseudomonas aeruginosa
† MIC = minimum inhibitory concentration.‡Addition of rifampicin can be considered if the organism is susceptible, the expected clinical or bacteriological response is delayed, or the cefotaxime/ceftriaxone MIC of the pneumococcal isolate is >4.0 μg/mL organism is susceptible, the expected clinical or bacteriological response is delayed, or the cefotaxime/ceftriaxone MIC.
Φ No clinical data exist for use of this agent in patients with pneumococcal meningitis; recommendation is based on cerebrospinal fluid penetration and in-vitro activity against S. pneumoniae.
£ Addition of an aminoglycoside should be considered; might need intraventricular or intrathecal administration in Gram-negative meningitis.
ǁ Addition of rifampicin should be considered.
Ω Choice of a specific agent should be based on in-vitro susceptibility testing.
†† Might also need to be administered by the intraventricular or intrathecal routes.
ǂ Might also need to be administered by the intraventricular or intrathecal routes.
₦ Addition of rifampicin should be considered.
Δ The fluoroquinolones gatifloxacin and moxifloxacin pene trate the CSF effectively and have greater in-vitro activity against Gram-positive bacteria than do their earlier counterparts (eg, ciprofloxacin). Findings from experi mental meningitis models suggested their efficacy in S. pneumoniae meningitis, including that caused by penicillin-resistant and cephalosporin-resistant strains. Although one controlled trial suggested the fluoroquinolone trovafl -oxacin mesilate to be as eff ective as ceftriaxone, with or without the addition of vancomycin, for paediatric bacterial meningitis, no clinical trials describe the use of gatifloxacin or moxifloxacin to treat bacterial meningitis in human beings. Trovafloxacin and gatifloxacin have been asso ciated with serious hepatic toxicity and dysglycaemia, respectively, and were with drawn from many markets. The IDSA guidelines recommend moxifloxacin as an alternative to third-generation cephalosporins plus vancomycin for meningitis caused by S. pneumoniae strains resistant to penicillin and third-generation cephalosporins, although some experts recom mend that this agent should not be used alone but rather should be combined with another drug (either vancomycin or a third-generation cephalosporin), because of the absence of clinical data supporting its use. | https://www.wikidoc.org/index.php/Sandbox_sss | |
9cc26aec813b3881e5c372a6fe3e2bb0279d6763 | wikidoc | Sandboxtest | Sandboxtest
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Black Box Warning
# Overview
Sandboxtest is a Adrenergic receptor agonist that is FDA approved for the {{{indicationType}}} of a list of indications, separated by commas.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include a list of adverse reactions, separated by commas..
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
### Non–Guideline-Supported Use
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
## Off-Label Use and Dosage (Pediatric)
# Contraindications
- Condition 1
- Condition 2
- Condition 3
- Condition 4
- Condition 5
# Warnings
(Description)
(Description)
(Description)
# Adverse Reactions
## Clinical Trials Experience
## Postmarketing Experience
(Description)
# Drug Interactions
- Drug 1
- Drug 2
- Drug 3
- Drug 4
- Drug 5
(Description)
(Description)
(Description)
(Description)
(Description)
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
(Description)
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Sandboxtest in women who are pregnant.
### Labor and Delivery
(Description)
### Nursing Mothers
(Description)
### Pediatric Use
(Description)
### Geriatic Use
(Description)
### Gender
(Description)
### Race
(Description)
### Renal Impairment
(Description)
### Hepatic Impairment
(Description)
### Females of Reproductive Potential and Males
(Description)
### Immunocompromised Patients
(Description)
### Others
(Description)
# Administration and Monitoring
### Administration
(Oral/Intravenous/etc)
### Monitoring
(Description regarding monitoring, from Warnings section)
(Description regarding monitoring, from Warnings section)
(Description regarding monitoring, from Warnings section)
# IV Compatibility
## Solution
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
## Y-Site
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
## Admixture
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
## Syringe
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
## TPN/TNA
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
# Overdosage
## Acute Overdose
### Signs and Symptoms
(Description)
### Management
(Description)
## Chronic Overdose
### Signs and Symptoms
(Description)
### Management
(Description)
# Pharmacology
## Mechanism of Action
(Description)
## Structure
(Description with picture)
## Pharmacodynamics
(Description)
## Pharmacokinetics
(Description)
## Nonclinical Toxicology
(Description)
# Clinical Studies
(Description)
(Description)
(Description)
# How Supplied
(Description)
## Storage
There is limited information regarding Sandboxtest Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
(Patient Counseling Information)
# Precautions with Alcohol
Alcohol-Sandboxtest interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
# Brand Names
There is limited information regarding Sandboxtest Brand Names in the drug label.
# Look-Alike Drug Names
- (Paired Confused Name 1a) — (Paired Confused Name 1b)
- (Paired Confused Name 2a) — (Paired Confused Name 2b)
- (Paired Confused Name 3a) — (Paired Confused Name 3b)
# Drug Shortage Status
Drug Shortage
# Price | Sandboxtest
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Black Box Warning
# Overview
Sandboxtest is a Adrenergic receptor agonist that is FDA approved for the {{{indicationType}}} of a list of indications, separated by commas.. There is a Black Box Warning for this drug as shown here. Common adverse reactions include a list of adverse reactions, separated by commas..
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
- Developed by: (Organisation)
- Class of Recommendation: (Class) (Link)
- Strength of Evidence: (Category A/B/C) (Link)
- Dosing Information/Recommendation
- (Dosage)
### Non–Guideline-Supported Use
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- Dosing Information
- (Dosage)
- Dosing Information
- (Dosage)
## Off-Label Use and Dosage (Pediatric)
# Contraindications
- Condition 1
- Condition 2
- Condition 3
- Condition 4
- Condition 5
# Warnings
(Description)
(Description)
(Description)
# Adverse Reactions
## Clinical Trials Experience
## Postmarketing Experience
(Description)
# Drug Interactions
- Drug 1
- Drug 2
- Drug 3
- Drug 4
- Drug 5
(Description)
(Description)
(Description)
(Description)
(Description)
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
(Description)
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Sandboxtest in women who are pregnant.
### Labor and Delivery
(Description)
### Nursing Mothers
(Description)
### Pediatric Use
(Description)
### Geriatic Use
(Description)
### Gender
(Description)
### Race
(Description)
### Renal Impairment
(Description)
### Hepatic Impairment
(Description)
### Females of Reproductive Potential and Males
(Description)
### Immunocompromised Patients
(Description)
### Others
(Description)
# Administration and Monitoring
### Administration
(Oral/Intravenous/etc)
### Monitoring
(Description regarding monitoring, from Warnings section)
(Description regarding monitoring, from Warnings section)
(Description regarding monitoring, from Warnings section)
# IV Compatibility
## Solution
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
## Y-Site
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
## Admixture
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
## Syringe
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
## TPN/TNA
### Compatible
- Solution 1
- Solution 2
- Solution 3
### Not Tested
- Solution 1
- Solution 2
- Solution 3
### Variable
- Solution 1
- Solution 2
- Solution 3
### Incompatible
- Solution 1
- Solution 2
- Solution 3
# Overdosage
## Acute Overdose
### Signs and Symptoms
(Description)
### Management
(Description)
## Chronic Overdose
### Signs and Symptoms
(Description)
### Management
(Description)
# Pharmacology
## Mechanism of Action
(Description)
## Structure
(Description with picture)
## Pharmacodynamics
(Description)
## Pharmacokinetics
(Description)
## Nonclinical Toxicology
(Description)
# Clinical Studies
(Description)
(Description)
(Description)
# How Supplied
(Description)
## Storage
There is limited information regarding Sandboxtest Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
(Patient Counseling Information)
# Precautions with Alcohol
Alcohol-Sandboxtest interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
# Brand Names
There is limited information regarding Sandboxtest Brand Names in the drug label.
# Look-Alike Drug Names
- (Paired Confused Name 1a) — (Paired Confused Name 1b)
- (Paired Confused Name 2a) — (Paired Confused Name 2b)
- (Paired Confused Name 3a) — (Paired Confused Name 3b)
# Drug Shortage Status
Drug Shortage
# Price | https://www.wikidoc.org/index.php/Sandboxtest | |
fad36cdd13ed6e1ba13163fbef085447af19b95a | wikidoc | Sapropterin | Sapropterin
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Sapropterin is a phenylalanine hydroxylase activator that is FDA approved for the treatment of high blood phenylalanine (Phe) levels in patients with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU). Sapropterin is to be used in conjunction with a Phe-restricted diet.. Common adverse reactions include headache, rhinorrhea, pharyngolaryngeal pain, diarrhea, vomiting, cough, and nasal congestion.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
### Indication
- Sapropterin is indicated to reduce blood phenylalanine (Phe) levels in patients with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU). Sapropterin is to be used in conjunction with a Phe-restricted diet.
### Dosage
- Patients 7 years and older: The recommended starting dose of Sapropterin is 10 to 20 mg/kg taken once daily.
- If a 10 mg/kg per day starting dose is used then response to therapy is determined by change in blood Phe following treatment with Sapropterin at 10 mg/kg per day for a period of up to 1 month. Blood Phe levels should be checked after 1 week of Sapropterin treatment and periodically for up to a month. If blood Phe does not decrease from baseline at 10 mg/kg per day, the dose may be increased to 20 mg/kg per day. Patients whose blood Phe does not decrease after 1 month of treatment at 20 mg/kg per day are non-responders and treatment with Sapropterin should be discontinued in these patients.
- If a 20 mg/kg per day starting dose is used then response to therapy is determined by change in blood Phe following treatment with Sapropterin at 20 mg/kg per day for a period of 1 month. Blood Phe levels should be checked after 1 week of Sapropterin treatment and periodically during the first month. Treatment should be discontinued in patients who do not respond to Sapropterin.
- Once responsiveness to Sapropterin has been established, the dosage may be adjusted within the range of 5 to 20 mg/kg per day according to response to therapy. Periodic blood Phe monitoring is recommended to assess blood Phe control.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Sapropterin in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Sapropterin in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
### Indication
- Sapropterin indicated to reduce blood phenylalanine (Phe) levels in patients with hyperphenylalaninemia (HPA)
### Dosage
- Patients 1 month to 6 years: The recommended starting dose of Sapropterin is 10 mg/kg taken once daily.
- Patients 7 years and older: The recommended starting dose of Sapropterin is 10 to 20 mg/kg taken once daily.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Sapropterin in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Sapropterin in pediatric patients.
# Contraindications
None.
# Warnings
### Hypersensitivity Reactions Including Anaphylaxis
Sapropterin is not recommended in patients with a history of anaphylaxis to Sapropterin. Hypersensitivity reactions, including anaphylaxis and rash, have occurred. Signs of anaphylaxis include wheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash. Discontinue treatment with Sapropterin in patients who experience anaphylaxis and initiate appropriate medical treatment. Continue dietary Phe restrictions in patients who experience anaphylaxis.
### Gastritis
During clinical studies, gastritis was reported as a serious adverse reaction. Monitor patients for signs and symptoms of gastritis.
### Hypophenylalaninemia
In clinical trials, some patients have experienced low blood Phe levels. Children younger than 7 years treated with Sapropterin doses of 20 mg/kg per day are at increased risk for low levels of blood Phe compared with patients 7 years and older.
### Monitor Blood Phe Levels During Treatment
Treatment with Sapropterin should be directed by physicians knowledgeable in the management of PKU. Prolonged elevations in blood phe levels in patients with PKU can result in severe neurologic damage, including severe mental retardation, microcephaly, delayed speech, seizures, and behavioral abnormalities. Conversely, prolonged levels of blood Phe that are too low have been associated with catabolism and protein breakdown. Active management of dietary Phe intake while taking Sapropterin is required to ensure adequate Phe control and nutritional balance. Monitor blood Phe levels during treatment to ensure adequate blood Phe level control. Frequent blood monitoring is recommended in the pediatric population.
### Identify Non-Responders to Sapropterin Treatment
Not all patients with PKU respond to treatment with Sapropterin. In two clinical trials at a dose of 20 mg/kg per day, 56% to 75% of pediatric PKU patients responded to treatment with Sapropterin, and in one clinical trial at a dose of 10 mg/kg per day, 20% of adult and pediatric PKU patients responded to treatment with Sapropterin.
Response to treatment cannot be pre-determined by laboratory testing (e.g., molecular testing), and can only be determined by a therapeutic trial of Sapropterin.
### Treat All Patients with a Phe-restricted Diet
All patients with PKU who are being treated with Sapropterin should also be treated with a Phe-restricted diet.
# Adverse Reactions
## Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety of Sapropterin was evaluated in 6 clinical studies in patients with PKU (aged 1 month to 50 years).
In Studies1-4 (controlled and uncontrolled studies), 579 patients with PKU aged 4 to 49 years received Sapropterin in doses ranging from 5 to 20 mg/kg per day for lengths of treatment ranging from 1 to 164 weeks. The patient population was evenly distributed in gender, and approximately 95% of patients were Caucasian. The most common adverse reactions (≥4% of patients) were headache, rhinorrhea, pharyngolaryngeal pain, diarrhea, vomiting, cough, and nasal congestion.
The data described in Table 3 reflect exposure of 74 patients with PKU to Sapropterin at doses of 10 to 20 mg/kg per day for 6 to 10 weeks in two double-blind, placebo-controlled clinical trials (Studies 2 and 4).
Table 3 enumerates adverse reactions occurring in at least 4% of patients treated with Sapropterin in the double-blind, placebo-controlled clinical trials described above.
In open-label, uncontrolled clinical trials (Studies 1 and 3) all patients received Sapropterin in doses of 5 to 20 mg/kg per day, adverse reactions were similar in type and frequency to those reported in the double-blind, placebo-controlled clinical trials.
In Study 5, 65 pediatric patients with PKU aged 1 month to 6 years received Sapropterin 20 mg/kg per day for 6 months. Adverse reactions in these patients were similar in frequency and type as those seen in other Sapropterin clinical trials except for an increased incidence of low phe levels. Twenty-five percent (16 out of 65) of patients developed Phe levels below normal for age.
In Study 6, a long term, open-label, extension study of 111 patients aged 4 to 50 years, receiving Sapropterin in doses ranging from 5 to 20 mg/kg per day, adverse reactions were similar in type and frequency to those reported in the previous clinical studies. Fifty-five patients received Sapropterin both as dissolved and intact tablets. There were no notable differences in the incidence or severity of adverse reactions between the two methods of administration. The mean (± SD) exposure to sapropterin for the entire study population was 659 ± 221 days (maximum 953 days).
Approximately 800 healthy volunteers and patients with disorders other than PKU, some of whom had underlying neurologic disorders or cardiovascular disease, have been administered a different formulation of the same active ingredient (sapropterin) in approximately 19 controlled and uncontrolled clinical trials. In these clinical trials, subjects were administered sapropterin at doses ranging from 1 to 100 mg/kg per day for lengths of exposure from 1 day to 2 years. Serious and severe adverse reactions (regardless of causality) during sapropterin administration were convulsions, exacerbation of convulsions, dizziness, gastrointestinal bleeding, post-procedural bleeding, headache, irritability, myocardial infarction, overstimulation, and respiratory failure. Common adverse reactions were headache, peripheral edema, arthralgia, polyuria, agitation, dizziness, nausea, pharyngitis, abdominal pain, upper abdominal pain, and upper respiratory tract infection.
## Postmarketing Experience
The following adverse reactions have been identified during post-approval use of Sapropterin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.
In worldwide marketing experience, the most common adverse reactions due to Sapropterin are oropharyngeal pain, pharyngitis, esophageal pain, gastritis, dyspepsia, abdominal pain, nausea and vomiting. Hypersensitivity reactions including anaphylaxis and rash have been reported. Most hypersensitivity reactions occurred within several days of initiating treatment. Two cases of hyperactivity have been reported, including one case in a patient who received an accidental overdose of Sapropterin.
# Drug Interactions
No drug interaction studies were performed.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): C
A patient registry has been established that collects data on women who are treated with Sapropterin during pregnancy. For more information regarding the registry program call 1-866-906-6100.
Risk Summary
There are no adequate and well-controlled studies with Sapropterin in pregnant women. An embryo-fetal development study with sapropterin dihydrochloride in rats using oral doses up to 3 times the maximum recommended human dose (MRHD) given during the period of organogenesis showed no effects. In a rabbit study using oral administration of sapropterin dihydrochloride during the period of organogenesis, a rare defect, holoprosencephaly, was noted at 10 times the MRHD. Sapropterin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Clinical Considerations
Disease-associated maternal and/or embryofetal risk
Available data from the Maternal Phenylketonuria Collaborative Study on 468 pregnancies and 331 live births in PKU‑affected women demonstrated that uncontrolled Phe levels above 600 µmol/L are associated with a very high incidence of neurological, cardiac, facial dysmorphism, and growth anomalies. Good dietary control of Phe levels during pregnancy is essential to reduce the incidence of Phe-induced teratogenic effects.
Animal Data
No effects on embryo-fetal development were observed in a reproduction study in rats using oral doses of up to 400 mg/kg per day sapropterin dihydrochloride (about 3 times the MRHD of 20 mg/kg per day, based on body surface area) administered during the period of organogenesis. However, in a rabbit reproduction study, oral administration of a maximum dose of 600 mg/kg per day (about 10 times the MRHD, based on body surface area) during the period of organogenesis was associated with a non-statistically significant increase in the incidence of holoprosencephaly in two high dose-treated litters (4 fetuses), compared to one control-treated litter (1 fetus).
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Sapropterin in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Sapropterin during labor and delivery.
### Nursing Mothers
It is not known whether Sapropterin is present in human milk. Sapropterin is present in the milk of intravenously, but not orally, treated lactating rats. The developmental and health benefits of human milk feeding should be considered along with the mother’s clinical need for Sapropterin and any potential adverse effects on the human milk-fed child from the drug or from the underlying maternal condition. Exercise caution when Sapropterin is administered to a nursing woman.
### Pediatric Use
Pediatric patients with PKU, ages 1 month to 16 years, have been treated with Sapropterin in clinical trials.
The efficacy and safety of Sapropterin have not been established in neonates. The safety of Sapropterin has been established in children younger than 4 years in trials of 6 months duration and in children 4 years and older in trials of up to 3 years in length.
In children aged 1 month and older, the efficacy of Sapropterin has been demonstrated in trials of 6 weeks or less in duration.
In a multicenter, open-label, single arm study, 57 patients aged 1 month to 6 years who were defined as Sapropterin responders after 4 weeks of Sapropterin treatment and Phe dietary restriction were treated for 6 months with Sapropterin at 20 mg/kg per day. The effectiveness of Sapropterin alone on reduction of blood Phe levels beyond 4 weeks could not be determined due to concurrent changes in dietary Phe intake during the study. Mean (±SD) blood Phe values over time for patients aged 1 month to <2 years and 2 to <7 years are shown in Figure 1.
### Geriatic Use
Clinical studies of Sapropterin in patients with PKU did not include patients aged 65 years and older. It is not known whether these patients respond differently than younger patients.
### Gender
There is no FDA guidance on the use of Sapropterin with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Sapropterin with respect to specific racial populations.
### Renal Impairment
Patients with renal impairment have not been evaluated in clinical trials. Monitor patients who have renal impairment carefully when they are receiving Sapropterin.
### Hepatic Impairment
There is no FDA guidance on the use of Sapropterin in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Sapropterin in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Sapropterin in patients who are immunocompromised.
# Administration and Monitoring
### Administration
Sapropterin is available as tablets and as powder for oral solution. Sapropterin should be taken orally with a meal to increase absorption, preferably at the same time each day. A missed dose should be taken as soon as possible, but two doses should not be taken on the same day.
Sapropterin tablets may be swallowed either as whole tablets or dissolved in 120 to 240 mL of water or apple juice and taken orally within 15 minutes of dissolution. It may take a few minutes for the tablets to dissolve. To make the tablets dissolve faster, tablets may be stirred or crushed. The tablets may not dissolve completely. Patients may see small pieces floating on top of the water or apple juice. This is normal and safe for patients to swallow. If after drinking the medicine patients still see pieces of the tablet in the container, more water or apple juice can be added to make sure all of the medicine is consumed. Sapropterin tablets may also be crushed and then mixed in a small amount of soft foods such as apple sauce or pudding.
Sapropterin powder for oral solution should be dissolved in 120 to 240 mL of water or apple juice and taken orally within 30 minutes of dissolution. Sapropterin powder for oral solution may also be stirred in a small amount of soft foods such as apple sauce or pudding. Empty the contents of the packet(s) in water, apple juice, or a small amount of soft foods and mix thoroughly. The powder should dissolve completely.
For infants weighing 10 kg or less, Sapropterin can be dissolved in as little as 5 mL of water or apple juice and a portion of this solution corresponding to a 10 mg/kg dose may be administered orally via an oral dosing syringe. Table 1 provides dosing information for infants at the recommended starting dose of 10 mg/kg per day. Refer to Table 2 for dosing information at 20 mg/kg per day if dosage adjustment is needed.
### Monitoring
Patients with liver impairment have not been evaluated in clinical trials with Sapropterin. Monitor liver function tests in patients with liver impairment who are receiving Sapropterin because hepatic damage has been associated with impaired phe metabolism.
Co-administering Sapropterin with drugs known to affect folate metabolism (e.g., methotrexate) and their derivatives may require more frequent monitoring of blood phe levels because these drugs can decrease endogenous BH4 levels by inhibiting the enzyme dihydropteridine reductase (DHPR).
Monitor blood pressure when administering Sapropterin with drugs that affect nitric oxide‑mediated vasorelaxation (e.g., PDE-5 inhibitors such as sildenafil, vardenafil, or tadalafil, because both sapropterin dihydrochloride and PDE-5 inhibitors may induce vasorelaxation. The additive effect of sapropterin and PDE-5 inhibitor co-administration could lead to a reduction in blood pressure; however, the combined use of these medications has not been evaluated in humans. In animal studies, orally administered Sapropterin in combination with a PDE-5 inhibitor had no effect on blood pressure.
Caution should be used with the administration of Sapropterin to patients who are receiving levodopa. In a 10-year post-marketing safety surveillance program for a non-PKU indication using another formulation of the same active ingredient (sapropterin), 3 patients with underlying neurologic disorders experienced convulsions, exacerbation of convulsions, over-stimulation, or irritability during co-administration of levodopa and sapropterin. Monitor for change in neurologic status.
In the post-marketing safety surveillance program for PKU, 2 patients experienced hyperactivity with administration of Sapropterin. Monitor patients for hyperactivity.
# IV Compatibility
There is limited information regarding the compatibility of Sapropterin and IV administrations.
# Overdosage
Two unintentional overdosages with Sapropterin have been reported. One adult patient in a Sapropterin clinical trial received a single Sapropterin dose of 4,500 mg (36 mg/kg) instead of 2,600 mg (20 mg/kg). The patient reported mild headache and mild dizziness immediately after taking the dose; both symptoms resolved within 1 hour with no treatment intervention. There were no associated laboratory test abnormalities. The patient suspended therapy for 24 hours and then restarted Sapropterin with no reports of abnormal signs or symptoms. In postmarketing, one pediatric patient received Sapropterin doses of 45 mg/kg per day instead of 20 mg/kg per day. The patient reported hyperactivity that began at an unspecified time after overdose and resolved after the Sapropterin dose was reduced to 20 mg/kg per day.
In a clinical study to evaluate the effects of Sapropterin on cardiac repolarization, a single supra-therapeutic dose of 100 mg/kg (5 times the maximum recommended dose) was administered to 54 healthy adults. No serious adverse reactions were reported during the study. The only adverse reactions reported in more than 1 subject who received the supra-therapeutic dose were upper abdominal pain (6%) and dizziness (4%). A dose-dependent shortening of the QT interval was observed.
Patients should be advised to notify their physicians in cases of overdose.
# Pharmacology
## Mechanism of Action
Sapropterin is a synthetic form of BH4, the cofactor for the enzyme phenylalanine hydroxylase (PAH). PAH hydroxylates phe through an oxidative reaction to form tyrosine. In patients with PKU, PAH activity is absent or deficient. Treatment with BH4 can activate residual PAH enzyme activity, improve the normal oxidative metabolism of phe, and decrease Phe levels in some patients.
## Structure
Sapropterin dihydrochloride is an orally administered Phenylalanine Hydroxylase activator (or PAH activator). Sapropterin dihydrochloride, the active pharmaceutical ingredient in Sapropterin, is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4). Sapropterin dihydrochloride is an off-white to light yellow crystals or crystalline powder.
The chemical name of sapropterin dihydrochloride is (6R)-2-amino-6--5,6,7,8-tetrahydro-4(1H)-pteridinone dihydrochloride and the molecular formula is C9H15N5O3·2HCl with a molecular weight of 314.17.
Sapropterin dihydrochloride has the following structural formula:
Sapropterin is supplied as tablets and powder for oral solution containing 100 mg of sapropterin dihydrochloride (equivalent to 76.8 mg of sapropterin base).
Tablets are round, off-white to light yellow, mottled, and debossed with “177”. Each tablet contains the following inactive ingredients: ascorbic acid (USP), crospovidone (NF), dibasic calcium phosphate (USP), D-mannitol (USP), riboflavin (USP), and sodium stearyl fumarate (NF).
Sapropterin powder for oral solution is off-white to yellow in color. Each unit dose packet contains the following inactive ingredients: ascorbic acid (USP), D-mannitol (USP), potassium citrate (USP), and sucralose (NF).
## Pharmacodynamics
In PKU patients who are responsive to BH4 treatment, blood phe levels decrease within 24 hours after a single administration of sapropterin dihydrochloride, although maximal effect on Phe level may take up to a month, depending on the patient. A single daily dose of Sapropterin is adequate to maintain stable blood Phe levels over a 24-hour period. Twelve patients with blood Phe levels ranging from 516 to 986 μmol/L (mean 747 ± 153 μmol/L) were assessed with 24‑hour blood Phe level monitoring following a daily morning dose of 10 mg/kg per day. The blood Phe level remained stable during a 24‑hour observation period. No substantial increases in blood Phe levels were observed following food intake throughout the 24-hour period.
Sapropterin dose-response relationship was studied in an open-label, forced titration study at doses of 5 mg/kg per day, then 20 mg/kg per day, and then 10 mg/kg per day (Study 3). Individual blood phe levels were highly variable among patients. The mean blood Phe level observed at the end of each 2-week dosing period decreased as the dose of sapropterin dihydrochloride increased, demonstrating an inverse relationship between the dose of sapropterin dihydrochloride and mean blood Phe levels.
Effects of Sapropterin on the QTc interval
A thorough QTc study was performed in 56 healthy adults. This randomized, placebo and active controlled crossover study was conducted to determine if a single supra-therapeutic (100 mg/kg) of Sapropterin, or a single therapeutic dose (20 mg/kg) of Sapropterin had an effect on cardiac repolarization. In this study, Sapropterin was administered after dissolving tablets in water under fed condition. This study demonstrated a dose-dependent shortening of the QT interval. The maximum placebo-subtracted mean change from baseline of the QTc interval was -3.69 and -8.32 ms (lower bound of 90% CI: -5.3 and -10.6 ms) at 20 and 100 mg/kg, respectively.
## Pharmacokinetics
Studies in healthy volunteers have shown comparable absorption of sapropterin when tablets are dissolved in water or orange juice and taken under fasted conditions. Administration of dissolved tablets after a high-fat/high-calorie meal resulted in mean increases in Cmax of 84% and AUC of 87% (dissolved in water). However, there was extensive variability in individual subject values for Cmax and AUC across the different modes of administration and meal conditions. In the clinical trials of Sapropterin, drug was administered in the morning as a dissolved tablet without regard to meals. The mean elimination half-life in PKU patients was approximately 6.7 hours (range 3.9 to 17 hr), comparable with values seen in healthy subjects (range 3.0 to 5.3 hr).
A study in healthy adults with 10 mg/kg of Sapropterin demonstrated the absorption via intact tablet administration was 40% greater than via dissolved tablet administration under fasted conditions based on AUC0-t. The administration of intact tablets under fed conditions resulted in an approximately 43% increase in the extent of absorption compared to fasted conditions based on AUC0-t.
Population pharmacokinetic analysis of sapropterin including patients from 1 month to 49 years of age showed that body weight is the only covariate substantially affecting clearance or distribution volume (see Table 4). Pharmacokinetics in patients >49 years of age have not been studied.
Metabolism
Sapropterin is a synthetic form of tetrahydrobiopterin (BH4) and is expected to be metabolized and recycled by the same endogenous enzymes. In vivo endogenous BH4 is converted to quinoid dihydrobiopterin and is metabolized to dihydrobiopterin and biopterin. The enzymes dihydrofolate reductase and dihydropteridine reductase are responsible for the metabolism and recycling of BH4.
## Nonclinical Toxicology
## Carcinogenesis, Mutagenesis, Impairment of Fertility
A 2-year carcinogenicity study was conducted in F-344 rats, and a 78-week carcinogenicity study was conducted in CD-1 mice. In the 104-week oral carcinogenicity study in rats, sapropterin dihydrochloride doses of 25, 80, and 250 mg/kg per day (0.2, 0.7, and 2 times the maximum recommended human dose of 20 mg/kg per day, respectively, based on body surface area) were used. In the 78-week oral carcinogenicity study in mice, sapropterin dihydrochloride doses of 25, 80, and 250 mg/kg per day (0.1, 0.3, and 2 times the recommended human dose, respectively, based on body surface area) were used. In the 2‑year rat carcinogenicity study, there was a statistically significant increase in the incidence of benign adrenal pheochromocytoma in male rats treated with the 250 mg/kg per day (about 2 times the maximum recommended human dose, based on body surface area) dose, as compared to vehicle treated rats. The mouse carcinogenicity study showed no evidence of a carcinogenic effect, but the study was not ideal due to its duration of 78 instead of 104 weeks.
Sapropterin dihydrochloride was genotoxic in the in vitro Ames test at concentrations of 625 µg (TA98) and 5000 µg (TA100) per plate, without metabolic activation. However, no genotoxicity was observed in the in vitro Ames test with metabolic activation. Sapropterin dihydrochloride was genotoxic in the in vitro chromosomal aberration assay in Chinese hamster lung cells at concentrations of 0.25 and 0.5 mM. Sapropterin dihydrochloride was not mutagenic in the in vivo micronucleus assay in mice at doses up to 2000 mg/kg per day (about 8 times the maximum recommended human dose of 20 mg/kg per day, based on body surface area). Sapropterin dihydrochloride, at oral doses up to 400 mg/kg per day (about 3 times the maximum recommended human dose, based on body surface area) was found to have no effect on fertility and reproductive function of male and female rats.
# Clinical Studies
The efficacy of Sapropterin was evaluated in five clinical studies in patients with PKU.
Study 1 was a multicenter, open-label, uncontrolled clinical trial of 489 patients with PKU, ages 8 to 48 years (mean 22 years), who had baseline blood phe levels ≥ 450 μmol/L and who were not on Phe-restricted diets. All patients received treatment with Sapropterin 10 mg/kg per day for 8 days. For the purposes of this study, response to Sapropterin treatment was defined as a ≥ 30% decrease in blood Phe from baseline. At Day 8, 96 patients (20%) were identified as responders.
Study 2 was a multicenter, double-blind, placebo-controlled study of 88 patients with PKU who responded to Sapropterin in Study 1. After a washout period from Study 1, patients were randomized equally to either Sapropterin 10 mg/kg per day (N=41) or placebo (N=47) for 6 weeks. Efficacy was assessed by the mean change in blood Phe level from baseline to Week 6 in the Sapropterin-treated group as compared to the mean change in the placebo group.
The results showed that at baseline, the mean (±SD) blood phe level was 843 (±300) μmol/L in the Sapropterin-treated group and 888 (±323) μmol/L in the placebo group. At Week 6, the Sapropterin treated group had a mean (±SD) blood Phe level of 607 (±377) μmol/L, and the placebo group had a mean blood Phe level of 891 (±348) μmol/L. At Week 6, the Sapropterin- and placebo treated groups had mean changes in blood Phe level of –239 and 6 μmol/L, respectively (mean percent changes of –29% (±32) and 3% (±33), respectively). The difference between the groups was statistically significant (p < 0.001) (Table 5).
Study 3 was a multicenter, open-label, extension study in which 80 patients who responded to Sapropterin treatment in Study 1 and completed Study 2 underwent 6 weeks of forced dose-titration with 3 different doses of Sapropterin. Treatments consisted of 3 consecutive 2-week courses of Sapropterin at doses of 5, then 20, and then 10 mg/kg per day. Blood phe level was monitored after 2 weeks of treatment at each dose level. At baseline, mean (±SD) blood Phe was 844 (±398) μmol/L. At the end of treatment with 5, 10, and 20 mg/kg per day, mean (±SD) blood Phe levels were 744 (±384) μmol/L, 640 (±382) μmol/L, and 581 (±399) μmol/L, respectively (Table 6).
Study 4 was a multicenter study of 90 pediatric patients with PKU, ages 4 to 12 years, who were on Phe‑restricted diets and who had blood phe levels ≤480 μmol/L at screening. All patients were treated with open-label Sapropterin 20 mg/kg per day for 8 days. Response to Sapropterin was defined as a ≥30% decrease in blood Phe from baseline at Day 8. At Day 8, 50 patients (56%) had a ≥30% decrease in blood Phe.
Study 5 was an open label, single arm, multicenter trial in 93 pediatric patients with PKU, aged 1 month to 6 years, who had Phe levels greater than or equal to 360 μmol/L at screening. All patients were treated with Sapropterin at 20 mg/kg per day and maintained on a Phe-restricted diet. At Week 4, 57 patients (61%) were identified as responders (defined as ≥ 30% decreased in blood Phe from baseline) (see Figure 1 section 8.4).
# How Supplied
Sapropterin tablets, 100 mg, are round, off-white to light yellow, mottled, and debossed with “177”. The tablets are supplied as follows:
NDC 68135-300-02 Bottle of 120 tablets
Sapropterin powder for oral solution, 100 mg, is an off-white to yellow powder. Sapropterin powder is packaged in unit dose packets as follows:
NDC 68135-301-22 Carton of 30 unit dose packets
NDC 68135-301-11 Single unit dose packet
## Storage
Store Sapropterin tablets at 20ºC to 25ºC (68ºF to 77ºF); excursions allowed between 15ºC to 30ºC (59ºF to 86ºF) . Keep container tightly closed. Protect from moisture.
Store Sapropterin powder for oral solution at 20ºC to 25ºC (68ºF to 77ºF); excursions allowed between 15ºC to 30ºC (59ºF to 86ºF) . Protect from moisture.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
Patients should be advised of the following information before beginning treatment with Kuvan:
- Advise patients that Kuvan may cause low blood Phe levels.
- Advise patients that children younger than 7 years treated with Kuvan doses of 20 mg/kg per day are at increased risk for low levels of blood phe compared with children 7 years and older. Blood phe levels that are too low for prolonged periods of time may be associated with catabolism and protein breakdown.
- Advise patients that Kuvan is to be used in conjunction with a Phe-restricted diet.
- Advise patients that not all patients with PKU respond to treatment with Kuvan and that response to Kuvan can only be determined by a therapeutic trial.
- Advise patients that they must be evaluated for changes in blood Phe after being treated with Kuvan at the recommended dose(s) for age to determine if they are a responder and that blood Phe levels and dietary Phe intake should be measured frequently during the first month.
- Advise patients that they should have frequent blood Phe measurements and nutritional counseling with their physician and other members of the health care team knowledgeable in the management of PKU to ensure maintenance of blood Phe levels in the desirable range.
- Advise patients not to modify their existing dietary Phe intake during the evaluation period in order to get an accurate assessment of the effect of Kuvan on blood Phe levels.
- Advise patients not to continue treatment with Kuvan if they are determined to be a non-responder during the evaluation period.
- Advise patients that reduction of blood Phe levels through dietary control is an important determinant of long-term neurologic outcome in PKU patients. Advise patients that the effect of Kuvan on long-term neurologic function in patients with PKU has not been assessed.
- Advise patients that Kuvan may cause hypersensitivity reactions including anaphylaxis and rash.
- Advise patients to notify their physician for symptoms of severe gastritis.
- Advise patients that blood Phe levels that are too high for prolonged periods of time can result in neurologic impairment.
- Advise patients that adequate blood Phe control needs to be maintained to avoid blood Phe levels that are too high or too low.
- Advise patients that to ensure maintenance of adequate blood Phe control, close monitoring is recommended and that the dose of Kuvan should be adjusted if necessary.
- Advise patients with hepatic impairment , and patients who are taking Kuvan in combination with drugs that inhibit folate metabolism, drugs that affect nitric oxide-mediated vasorelaxation, or levodopa that they may require additional clinical monitoring while taking Kuvan.
- Advise patients that Kuvan may cause hyperactivity.
- Advise patients that BioMarin has a product registry for PKU patients to collect data on women who become pregnant while receiving Kuvan treatment.
# Precautions with Alcohol
Alcohol-Sapropterin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- KUVAN ®
# Look-Alike Drug Names
There is limited information regarding Sapropterin Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Sapropterin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Turky Alkathery, M.D. [2]
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# Overview
Sapropterin is a phenylalanine hydroxylase activator that is FDA approved for the treatment of high blood phenylalanine (Phe) levels in patients with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU). Sapropterin is to be used in conjunction with a Phe-restricted diet.. Common adverse reactions include headache, rhinorrhea, pharyngolaryngeal pain, diarrhea, vomiting, cough, and nasal congestion.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
### Indication
- Sapropterin is indicated to reduce blood phenylalanine (Phe) levels in patients with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU). Sapropterin is to be used in conjunction with a Phe-restricted diet.
### Dosage
- Patients 7 years and older: The recommended starting dose of Sapropterin is 10 to 20 mg/kg taken once daily.
- If a 10 mg/kg per day starting dose is used then response to therapy is determined by change in blood Phe following treatment with Sapropterin at 10 mg/kg per day for a period of up to 1 month. Blood Phe levels should be checked after 1 week of Sapropterin treatment and periodically for up to a month. If blood Phe does not decrease from baseline at 10 mg/kg per day, the dose may be increased to 20 mg/kg per day. Patients whose blood Phe does not decrease after 1 month of treatment at 20 mg/kg per day are non-responders and treatment with Sapropterin should be discontinued in these patients.
- If a 20 mg/kg per day starting dose is used then response to therapy is determined by change in blood Phe following treatment with Sapropterin at 20 mg/kg per day for a period of 1 month. Blood Phe levels should be checked after 1 week of Sapropterin treatment and periodically during the first month. Treatment should be discontinued in patients who do not respond to Sapropterin.
- Once responsiveness to Sapropterin has been established, the dosage may be adjusted within the range of 5 to 20 mg/kg per day according to response to therapy. Periodic blood Phe monitoring is recommended to assess blood Phe control.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Sapropterin in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Sapropterin in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
### Indication
- Sapropterin indicated to reduce blood phenylalanine (Phe) levels in patients with hyperphenylalaninemia (HPA)
### Dosage
- Patients 1 month to 6 years: The recommended starting dose of Sapropterin is 10 mg/kg taken once daily.
- Patients 7 years and older: The recommended starting dose of Sapropterin is 10 to 20 mg/kg taken once daily.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Sapropterin in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Sapropterin in pediatric patients.
# Contraindications
None.
# Warnings
### Hypersensitivity Reactions Including Anaphylaxis
Sapropterin is not recommended in patients with a history of anaphylaxis to Sapropterin. Hypersensitivity reactions, including anaphylaxis and rash, have occurred. Signs of anaphylaxis include wheezing, dyspnea, coughing, hypotension, flushing, nausea, and rash. Discontinue treatment with Sapropterin in patients who experience anaphylaxis and initiate appropriate medical treatment. Continue dietary Phe restrictions in patients who experience anaphylaxis.
### Gastritis
During clinical studies, gastritis was reported as a serious adverse reaction. Monitor patients for signs and symptoms of gastritis.
### Hypophenylalaninemia
In clinical trials, some patients have experienced low blood Phe levels. Children younger than 7 years treated with Sapropterin doses of 20 mg/kg per day are at increased risk for low levels of blood Phe compared with patients 7 years and older.
### Monitor Blood Phe Levels During Treatment
Treatment with Sapropterin should be directed by physicians knowledgeable in the management of PKU. Prolonged elevations in blood phe levels in patients with PKU can result in severe neurologic damage, including severe mental retardation, microcephaly, delayed speech, seizures, and behavioral abnormalities. Conversely, prolonged levels of blood Phe that are too low have been associated with catabolism and protein breakdown. Active management of dietary Phe intake while taking Sapropterin is required to ensure adequate Phe control and nutritional balance. Monitor blood Phe levels during treatment to ensure adequate blood Phe level control. Frequent blood monitoring is recommended in the pediatric population.
### Identify Non-Responders to Sapropterin Treatment
Not all patients with PKU respond to treatment with Sapropterin. In two clinical trials at a dose of 20 mg/kg per day, 56% to 75% of pediatric PKU patients responded to treatment with Sapropterin, and in one clinical trial at a dose of 10 mg/kg per day, 20% of adult and pediatric PKU patients responded to treatment with Sapropterin.
Response to treatment cannot be pre-determined by laboratory testing (e.g., molecular testing), and can only be determined by a therapeutic trial of Sapropterin.
### Treat All Patients with a Phe-restricted Diet
All patients with PKU who are being treated with Sapropterin should also be treated with a Phe-restricted diet.
# Adverse Reactions
## Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety of Sapropterin was evaluated in 6 clinical studies in patients with PKU (aged 1 month to 50 years).
In Studies1-4 (controlled and uncontrolled studies), 579 patients with PKU aged 4 to 49 years received Sapropterin in doses ranging from 5 to 20 mg/kg per day for lengths of treatment ranging from 1 to 164 weeks. The patient population was evenly distributed in gender, and approximately 95% of patients were Caucasian. The most common adverse reactions (≥4% of patients) were headache, rhinorrhea, pharyngolaryngeal pain, diarrhea, vomiting, cough, and nasal congestion.
The data described in Table 3 reflect exposure of 74 patients with PKU to Sapropterin at doses of 10 to 20 mg/kg per day for 6 to 10 weeks in two double-blind, placebo-controlled clinical trials (Studies 2 and 4).
Table 3 enumerates adverse reactions occurring in at least 4% of patients treated with Sapropterin in the double-blind, placebo-controlled clinical trials described above.
In open-label, uncontrolled clinical trials (Studies 1 and 3) all patients received Sapropterin in doses of 5 to 20 mg/kg per day, adverse reactions were similar in type and frequency to those reported in the double-blind, placebo-controlled clinical trials.
In Study 5, 65 pediatric patients with PKU aged 1 month to 6 years received Sapropterin 20 mg/kg per day for 6 months. Adverse reactions in these patients were similar in frequency and type as those seen in other Sapropterin clinical trials except for an increased incidence of low phe levels. Twenty-five percent (16 out of 65) of patients developed Phe levels below normal for age.
In Study 6, a long term, open-label, extension study of 111 patients aged 4 to 50 years, receiving Sapropterin in doses ranging from 5 to 20 mg/kg per day, adverse reactions were similar in type and frequency to those reported in the previous clinical studies. Fifty-five patients received Sapropterin both as dissolved and intact tablets. There were no notable differences in the incidence or severity of adverse reactions between the two methods of administration. The mean (± SD) exposure to sapropterin for the entire study population was 659 ± 221 days (maximum 953 days).
Approximately 800 healthy volunteers and patients with disorders other than PKU, some of whom had underlying neurologic disorders or cardiovascular disease, have been administered a different formulation of the same active ingredient (sapropterin) in approximately 19 controlled and uncontrolled clinical trials. In these clinical trials, subjects were administered sapropterin at doses ranging from 1 to 100 mg/kg per day for lengths of exposure from 1 day to 2 years. Serious and severe adverse reactions (regardless of causality) during sapropterin administration were convulsions, exacerbation of convulsions, dizziness, gastrointestinal bleeding, post-procedural bleeding, headache, irritability, myocardial infarction, overstimulation, and respiratory failure. Common adverse reactions were headache, peripheral edema, arthralgia, polyuria, agitation, dizziness, nausea, pharyngitis, abdominal pain, upper abdominal pain, and upper respiratory tract infection.
## Postmarketing Experience
The following adverse reactions have been identified during post-approval use of Sapropterin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.
In worldwide marketing experience, the most common adverse reactions due to Sapropterin are oropharyngeal pain, pharyngitis, esophageal pain, gastritis, dyspepsia, abdominal pain, nausea and vomiting. Hypersensitivity reactions including anaphylaxis and rash have been reported. Most hypersensitivity reactions occurred within several days of initiating treatment. Two cases of hyperactivity have been reported, including one case in a patient who received an accidental overdose of Sapropterin.
# Drug Interactions
No drug interaction studies were performed.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): C
A patient registry has been established that collects data on women who are treated with Sapropterin during pregnancy. For more information regarding the registry program call 1-866-906-6100.
Risk Summary
There are no adequate and well-controlled studies with Sapropterin in pregnant women. An embryo-fetal development study with sapropterin dihydrochloride in rats using oral doses up to 3 times the maximum recommended human dose (MRHD) given during the period of organogenesis showed no effects. In a rabbit study using oral administration of sapropterin dihydrochloride during the period of organogenesis, a rare defect, holoprosencephaly, was noted at 10 times the MRHD. Sapropterin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Clinical Considerations
Disease-associated maternal and/or embryofetal risk
Available data from the Maternal Phenylketonuria Collaborative Study on 468 pregnancies and 331 live births in PKU‑affected women demonstrated that uncontrolled Phe levels above 600 µmol/L are associated with a very high incidence of neurological, cardiac, facial dysmorphism, and growth anomalies. Good dietary control of Phe levels during pregnancy is essential to reduce the incidence of Phe-induced teratogenic effects.
Animal Data
No effects on embryo-fetal development were observed in a reproduction study in rats using oral doses of up to 400 mg/kg per day sapropterin dihydrochloride (about 3 times the MRHD of 20 mg/kg per day, based on body surface area) administered during the period of organogenesis. However, in a rabbit reproduction study, oral administration of a maximum dose of 600 mg/kg per day (about 10 times the MRHD, based on body surface area) during the period of organogenesis was associated with a non-statistically significant increase in the incidence of holoprosencephaly in two high dose-treated litters (4 fetuses), compared to one control-treated litter (1 fetus).
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Sapropterin in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Sapropterin during labor and delivery.
### Nursing Mothers
It is not known whether Sapropterin is present in human milk. Sapropterin is present in the milk of intravenously, but not orally, treated lactating rats. The developmental and health benefits of human milk feeding should be considered along with the mother’s clinical need for Sapropterin and any potential adverse effects on the human milk-fed child from the drug or from the underlying maternal condition. Exercise caution when Sapropterin is administered to a nursing woman.
### Pediatric Use
Pediatric patients with PKU, ages 1 month to 16 years, have been treated with Sapropterin in clinical trials.
The efficacy and safety of Sapropterin have not been established in neonates. The safety of Sapropterin has been established in children younger than 4 years in trials of 6 months duration and in children 4 years and older in trials of up to 3 years in length.
In children aged 1 month and older, the efficacy of Sapropterin has been demonstrated in trials of 6 weeks or less in duration.
In a multicenter, open-label, single arm study, 57 patients aged 1 month to 6 years who were defined as Sapropterin responders after 4 weeks of Sapropterin treatment and Phe dietary restriction were treated for 6 months with Sapropterin at 20 mg/kg per day. The effectiveness of Sapropterin alone on reduction of blood Phe levels beyond 4 weeks could not be determined due to concurrent changes in dietary Phe intake during the study. Mean (±SD) blood Phe values over time for patients aged 1 month to <2 years and 2 to <7 years are shown in Figure 1.
### Geriatic Use
Clinical studies of Sapropterin in patients with PKU did not include patients aged 65 years and older. It is not known whether these patients respond differently than younger patients.
### Gender
There is no FDA guidance on the use of Sapropterin with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Sapropterin with respect to specific racial populations.
### Renal Impairment
Patients with renal impairment have not been evaluated in clinical trials. Monitor patients who have renal impairment carefully when they are receiving Sapropterin.
### Hepatic Impairment
There is no FDA guidance on the use of Sapropterin in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Sapropterin in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Sapropterin in patients who are immunocompromised.
# Administration and Monitoring
### Administration
Sapropterin is available as tablets and as powder for oral solution. Sapropterin should be taken orally with a meal to increase absorption, preferably at the same time each day. A missed dose should be taken as soon as possible, but two doses should not be taken on the same day.
Sapropterin tablets may be swallowed either as whole tablets or dissolved in 120 to 240 mL of water or apple juice and taken orally within 15 minutes of dissolution. It may take a few minutes for the tablets to dissolve. To make the tablets dissolve faster, tablets may be stirred or crushed. The tablets may not dissolve completely. Patients may see small pieces floating on top of the water or apple juice. This is normal and safe for patients to swallow. If after drinking the medicine patients still see pieces of the tablet in the container, more water or apple juice can be added to make sure all of the medicine is consumed. Sapropterin tablets may also be crushed and then mixed in a small amount of soft foods such as apple sauce or pudding.
Sapropterin powder for oral solution should be dissolved in 120 to 240 mL of water or apple juice and taken orally within 30 minutes of dissolution. Sapropterin powder for oral solution may also be stirred in a small amount of soft foods such as apple sauce or pudding. Empty the contents of the packet(s) in water, apple juice, or a small amount of soft foods and mix thoroughly. The powder should dissolve completely.
For infants weighing 10 kg or less, Sapropterin can be dissolved in as little as 5 mL of water or apple juice and a portion of this solution corresponding to a 10 mg/kg dose may be administered orally via an oral dosing syringe. Table 1 provides dosing information for infants at the recommended starting dose of 10 mg/kg per day. Refer to Table 2 for dosing information at 20 mg/kg per day if dosage adjustment is needed.
### Monitoring
Patients with liver impairment have not been evaluated in clinical trials with Sapropterin. Monitor liver function tests in patients with liver impairment who are receiving Sapropterin because hepatic damage has been associated with impaired phe metabolism.
Co-administering Sapropterin with drugs known to affect folate metabolism (e.g., methotrexate) and their derivatives may require more frequent monitoring of blood phe levels because these drugs can decrease endogenous BH4 levels by inhibiting the enzyme dihydropteridine reductase (DHPR).
Monitor blood pressure when administering Sapropterin with drugs that affect nitric oxide‑mediated vasorelaxation (e.g., PDE-5 inhibitors such as sildenafil, vardenafil, or tadalafil, because both sapropterin dihydrochloride and PDE-5 inhibitors may induce vasorelaxation. The additive effect of sapropterin and PDE-5 inhibitor co-administration could lead to a reduction in blood pressure; however, the combined use of these medications has not been evaluated in humans. In animal studies, orally administered Sapropterin in combination with a PDE-5 inhibitor had no effect on blood pressure.
Caution should be used with the administration of Sapropterin to patients who are receiving levodopa. In a 10-year post-marketing safety surveillance program for a non-PKU indication using another formulation of the same active ingredient (sapropterin), 3 patients with underlying neurologic disorders experienced convulsions, exacerbation of convulsions, over-stimulation, or irritability during co-administration of levodopa and sapropterin. Monitor for change in neurologic status.
In the post-marketing safety surveillance program for PKU, 2 patients experienced hyperactivity with administration of Sapropterin. Monitor patients for hyperactivity.
# IV Compatibility
There is limited information regarding the compatibility of Sapropterin and IV administrations.
# Overdosage
Two unintentional overdosages with Sapropterin have been reported. One adult patient in a Sapropterin clinical trial received a single Sapropterin dose of 4,500 mg (36 mg/kg) instead of 2,600 mg (20 mg/kg). The patient reported mild headache and mild dizziness immediately after taking the dose; both symptoms resolved within 1 hour with no treatment intervention. There were no associated laboratory test abnormalities. The patient suspended therapy for 24 hours and then restarted Sapropterin with no reports of abnormal signs or symptoms. In postmarketing, one pediatric patient received Sapropterin doses of 45 mg/kg per day instead of 20 mg/kg per day. The patient reported hyperactivity that began at an unspecified time after overdose and resolved after the Sapropterin dose was reduced to 20 mg/kg per day.
In a clinical study to evaluate the effects of Sapropterin on cardiac repolarization, a single supra-therapeutic dose of 100 mg/kg (5 times the maximum recommended dose) was administered to 54 healthy adults. No serious adverse reactions were reported during the study. The only adverse reactions reported in more than 1 subject who received the supra-therapeutic dose were upper abdominal pain (6%) and dizziness (4%). A dose-dependent shortening of the QT interval was observed.
Patients should be advised to notify their physicians in cases of overdose.
# Pharmacology
## Mechanism of Action
Sapropterin is a synthetic form of BH4, the cofactor for the enzyme phenylalanine hydroxylase (PAH). PAH hydroxylates phe through an oxidative reaction to form tyrosine. In patients with PKU, PAH activity is absent or deficient. Treatment with BH4 can activate residual PAH enzyme activity, improve the normal oxidative metabolism of phe, and decrease Phe levels in some patients.
## Structure
Sapropterin dihydrochloride is an orally administered Phenylalanine Hydroxylase activator (or PAH activator). Sapropterin dihydrochloride, the active pharmaceutical ingredient in Sapropterin, is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4). Sapropterin dihydrochloride is an off-white to light yellow crystals or crystalline powder.
The chemical name of sapropterin dihydrochloride is (6R)-2-amino-6-[(1R,2S)-1,2-dihydroxypropyl]-5,6,7,8-tetrahydro-4(1H)-pteridinone dihydrochloride and the molecular formula is C9H15N5O3·2HCl with a molecular weight of 314.17.
Sapropterin dihydrochloride has the following structural formula:
Sapropterin is supplied as tablets and powder for oral solution containing 100 mg of sapropterin dihydrochloride (equivalent to 76.8 mg of sapropterin base).
Tablets are round, off-white to light yellow, mottled, and debossed with “177”. Each tablet contains the following inactive ingredients: ascorbic acid (USP), crospovidone (NF), dibasic calcium phosphate (USP), D-mannitol (USP), riboflavin (USP), and sodium stearyl fumarate (NF).
Sapropterin powder for oral solution is off-white to yellow in color. Each unit dose packet contains the following inactive ingredients: ascorbic acid (USP), D-mannitol (USP), potassium citrate (USP), and sucralose (NF).
## Pharmacodynamics
In PKU patients who are responsive to BH4 treatment, blood phe levels decrease within 24 hours after a single administration of sapropterin dihydrochloride, although maximal effect on Phe level may take up to a month, depending on the patient. A single daily dose of Sapropterin is adequate to maintain stable blood Phe levels over a 24-hour period. Twelve patients with blood Phe levels ranging from 516 to 986 μmol/L (mean 747 ± 153 μmol/L) were assessed with 24‑hour blood Phe level monitoring following a daily morning dose of 10 mg/kg per day. The blood Phe level remained stable during a 24‑hour observation period. No substantial increases in blood Phe levels were observed following food intake throughout the 24-hour period.
Sapropterin dose-response relationship was studied in an open-label, forced titration study at doses of 5 mg/kg per day, then 20 mg/kg per day, and then 10 mg/kg per day (Study 3). Individual blood phe levels were highly variable among patients. The mean blood Phe level observed at the end of each 2-week dosing period decreased as the dose of sapropterin dihydrochloride increased, demonstrating an inverse relationship between the dose of sapropterin dihydrochloride and mean blood Phe levels.
Effects of Sapropterin on the QTc interval
A thorough QTc study was performed in 56 healthy adults. This randomized, placebo and active controlled crossover study was conducted to determine if a single supra-therapeutic (100 mg/kg) of Sapropterin, or a single therapeutic dose (20 mg/kg) of Sapropterin had an effect on cardiac repolarization. In this study, Sapropterin was administered after dissolving tablets in water under fed condition. This study demonstrated a dose-dependent shortening of the QT interval. The maximum placebo-subtracted mean change from baseline of the QTc interval was -3.69 and -8.32 ms (lower bound of 90% CI: -5.3 and -10.6 ms) at 20 and 100 mg/kg, respectively.
## Pharmacokinetics
Studies in healthy volunteers have shown comparable absorption of sapropterin when tablets are dissolved in water or orange juice and taken under fasted conditions. Administration of dissolved tablets after a high-fat/high-calorie meal resulted in mean increases in Cmax of 84% and AUC of 87% (dissolved in water). However, there was extensive variability in individual subject values for Cmax and AUC across the different modes of administration and meal conditions. In the clinical trials of Sapropterin, drug was administered in the morning as a dissolved tablet without regard to meals. The mean elimination half-life in PKU patients was approximately 6.7 hours (range 3.9 to 17 hr), comparable with values seen in healthy subjects (range 3.0 to 5.3 hr).
A study in healthy adults with 10 mg/kg of Sapropterin demonstrated the absorption via intact tablet administration was 40% greater than via dissolved tablet administration under fasted conditions based on AUC0-t. The administration of intact tablets under fed conditions resulted in an approximately 43% increase in the extent of absorption compared to fasted conditions based on AUC0-t.
Population pharmacokinetic analysis of sapropterin including patients from 1 month to 49 years of age showed that body weight is the only covariate substantially affecting clearance or distribution volume (see Table 4). Pharmacokinetics in patients >49 years of age have not been studied.
Metabolism
Sapropterin is a synthetic form of tetrahydrobiopterin (BH4) and is expected to be metabolized and recycled by the same endogenous enzymes. In vivo endogenous BH4 is converted to quinoid dihydrobiopterin and is metabolized to dihydrobiopterin and biopterin. The enzymes dihydrofolate reductase and dihydropteridine reductase are responsible for the metabolism and recycling of BH4.
## Nonclinical Toxicology
## Carcinogenesis, Mutagenesis, Impairment of Fertility
A 2-year carcinogenicity study was conducted in F-344 rats, and a 78-week carcinogenicity study was conducted in CD-1 mice. In the 104-week oral carcinogenicity study in rats, sapropterin dihydrochloride doses of 25, 80, and 250 mg/kg per day (0.2, 0.7, and 2 times the maximum recommended human dose of 20 mg/kg per day, respectively, based on body surface area) were used. In the 78-week oral carcinogenicity study in mice, sapropterin dihydrochloride doses of 25, 80, and 250 mg/kg per day (0.1, 0.3, and 2 times the recommended human dose, respectively, based on body surface area) were used. In the 2‑year rat carcinogenicity study, there was a statistically significant increase in the incidence of benign adrenal pheochromocytoma in male rats treated with the 250 mg/kg per day (about 2 times the maximum recommended human dose, based on body surface area) dose, as compared to vehicle treated rats. The mouse carcinogenicity study showed no evidence of a carcinogenic effect, but the study was not ideal due to its duration of 78 instead of 104 weeks.
Sapropterin dihydrochloride was genotoxic in the in vitro Ames test at concentrations of 625 µg (TA98) and 5000 µg (TA100) per plate, without metabolic activation. However, no genotoxicity was observed in the in vitro Ames test with metabolic activation. Sapropterin dihydrochloride was genotoxic in the in vitro chromosomal aberration assay in Chinese hamster lung cells at concentrations of 0.25 and 0.5 mM. Sapropterin dihydrochloride was not mutagenic in the in vivo micronucleus assay in mice at doses up to 2000 mg/kg per day (about 8 times the maximum recommended human dose of 20 mg/kg per day, based on body surface area). Sapropterin dihydrochloride, at oral doses up to 400 mg/kg per day (about 3 times the maximum recommended human dose, based on body surface area) was found to have no effect on fertility and reproductive function of male and female rats.
# Clinical Studies
The efficacy of Sapropterin was evaluated in five clinical studies in patients with PKU.
Study 1 was a multicenter, open-label, uncontrolled clinical trial of 489 patients with PKU, ages 8 to 48 years (mean 22 years), who had baseline blood phe levels ≥ 450 μmol/L and who were not on Phe-restricted diets. All patients received treatment with Sapropterin 10 mg/kg per day for 8 days. For the purposes of this study, response to Sapropterin treatment was defined as a ≥ 30% decrease in blood Phe from baseline. At Day 8, 96 patients (20%) were identified as responders.
Study 2 was a multicenter, double-blind, placebo-controlled study of 88 patients with PKU who responded to Sapropterin in Study 1. After a washout period from Study 1, patients were randomized equally to either Sapropterin 10 mg/kg per day (N=41) or placebo (N=47) for 6 weeks. Efficacy was assessed by the mean change in blood Phe level from baseline to Week 6 in the Sapropterin-treated group as compared to the mean change in the placebo group.
The results showed that at baseline, the mean (±SD) blood phe level was 843 (±300) μmol/L in the Sapropterin-treated group and 888 (±323) μmol/L in the placebo group. At Week 6, the Sapropterin treated group had a mean (±SD) blood Phe level of 607 (±377) μmol/L, and the placebo group had a mean blood Phe level of 891 (±348) μmol/L. At Week 6, the Sapropterin- and placebo treated groups had mean changes in blood Phe level of –239 and 6 μmol/L, respectively (mean percent changes of –29% (±32) and 3% (±33), respectively). The difference between the groups was statistically significant (p < 0.001) (Table 5).
Study 3 was a multicenter, open-label, extension study in which 80 patients who responded to Sapropterin treatment in Study 1 and completed Study 2 underwent 6 weeks of forced dose-titration with 3 different doses of Sapropterin. Treatments consisted of 3 consecutive 2-week courses of Sapropterin at doses of 5, then 20, and then 10 mg/kg per day. Blood phe level was monitored after 2 weeks of treatment at each dose level. At baseline, mean (±SD) blood Phe was 844 (±398) μmol/L. At the end of treatment with 5, 10, and 20 mg/kg per day, mean (±SD) blood Phe levels were 744 (±384) μmol/L, 640 (±382) μmol/L, and 581 (±399) μmol/L, respectively (Table 6).
Study 4 was a multicenter study of 90 pediatric patients with PKU, ages 4 to 12 years, who were on Phe‑restricted diets and who had blood phe levels ≤480 μmol/L at screening. All patients were treated with open-label Sapropterin 20 mg/kg per day for 8 days. Response to Sapropterin was defined as a ≥30% decrease in blood Phe from baseline at Day 8. At Day 8, 50 patients (56%) had a ≥30% decrease in blood Phe.
Study 5 was an open label, single arm, multicenter trial in 93 pediatric patients with PKU, aged 1 month to 6 years, who had Phe levels greater than or equal to 360 μmol/L at screening. All patients were treated with Sapropterin at 20 mg/kg per day and maintained on a Phe-restricted diet. At Week 4, 57 patients (61%) were identified as responders (defined as ≥ 30% decreased in blood Phe from baseline) (see Figure 1 section 8.4).
# How Supplied
Sapropterin tablets, 100 mg, are round, off-white to light yellow, mottled, and debossed with “177”. The tablets are supplied as follows:
NDC 68135-300-02 Bottle of 120 tablets
Sapropterin powder for oral solution, 100 mg, is an off-white to yellow powder. Sapropterin powder is packaged in unit dose packets as follows:
NDC 68135-301-22 Carton of 30 unit dose packets
NDC 68135-301-11 Single unit dose packet
## Storage
Store Sapropterin tablets at 20ºC to 25ºC (68ºF to 77ºF); excursions allowed between 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature]. Keep container tightly closed. Protect from moisture.
Store Sapropterin powder for oral solution at 20ºC to 25ºC (68ºF to 77ºF); excursions allowed between 15ºC to 30ºC (59ºF to 86ºF) [see USP Controlled Room Temperature]. Protect from moisture.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
Patients should be advised of the following information before beginning treatment with Kuvan:
- Advise patients that Kuvan may cause low blood Phe levels.
- Advise patients that children younger than 7 years treated with Kuvan doses of 20 mg/kg per day are at increased risk for low levels of blood phe compared with children 7 years and older. Blood phe levels that are too low for prolonged periods of time may be associated with catabolism and protein breakdown.
- Advise patients that Kuvan is to be used in conjunction with a Phe-restricted diet.
- Advise patients that not all patients with PKU respond to treatment with Kuvan and that response to Kuvan can only be determined by a therapeutic trial.
- Advise patients that they must be evaluated for changes in blood Phe after being treated with Kuvan at the recommended dose(s) for age to determine if they are a responder and that blood Phe levels and dietary Phe intake should be measured frequently during the first month.
- Advise patients that they should have frequent blood Phe measurements and nutritional counseling with their physician and other members of the health care team knowledgeable in the management of PKU to ensure maintenance of blood Phe levels in the desirable range.
- Advise patients not to modify their existing dietary Phe intake during the evaluation period in order to get an accurate assessment of the effect of Kuvan on blood Phe levels.
- Advise patients not to continue treatment with Kuvan if they are determined to be a non-responder during the evaluation period.
- Advise patients that reduction of blood Phe levels through dietary control is an important determinant of long-term neurologic outcome in PKU patients. Advise patients that the effect of Kuvan on long-term neurologic function in patients with PKU has not been assessed.
- Advise patients that Kuvan may cause hypersensitivity reactions including anaphylaxis and rash.
- Advise patients to notify their physician for symptoms of severe gastritis.
- Advise patients that blood Phe levels that are too high for prolonged periods of time can result in neurologic impairment.
- Advise patients that adequate blood Phe control needs to be maintained to avoid blood Phe levels that are too high or too low.
- Advise patients that to ensure maintenance of adequate blood Phe control, close monitoring is recommended and that the dose of Kuvan should be adjusted if necessary.
- Advise patients with hepatic impairment , and patients who are taking Kuvan in combination with drugs that inhibit folate metabolism, drugs that affect nitric oxide-mediated vasorelaxation, or levodopa that they may require additional clinical monitoring while taking Kuvan.
- Advise patients that Kuvan may cause hyperactivity.
- Advise patients that BioMarin has a product registry for PKU patients to collect data on women who become pregnant while receiving Kuvan treatment.
# Precautions with Alcohol
Alcohol-Sapropterin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- KUVAN ®[1]
# Look-Alike Drug Names
There is limited information regarding Sapropterin Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Sapropterin | |
9fe5b01090a585fdc6b8e2e9b530de13d2a30e16 | wikidoc | Sardonicism | Sardonicism
Sardonicism (connected with guffaw) characterizes —as distinct from Sarcasm— not a contumely or bitter, but a ferocious, painful derision.
# Origin
The aborigines of Sardinia Template:Lang-la would kill their elderly and laugh while doing this. This is called sardonic laughter, or the infamous "Risus sardonicus", a convulsive laughing, with which the soul is noninvolved. Template:Lang-it, Template:Lang-fr.
It was already established in the Ancient Greece. They also differentiated between cynic (kynikós "to the world opinion of the cynics"), sardonic (sardánios "the scornful laughter of an angry person, with own pain or own damage") and sarcastic (sarkastikós "derision, hurtful speech"). So Odysseus —after he had at last returned— laughed sardonic to himself when he dodged a foot of a cow, which was thrown by a punter of his wife.
Occasionally, the convulsive laugh is traced back to a bitter Sardinian plant called "sardánion". The Meyers Encyclopedia from 1888 says Sardoniasm was a: .mw-parser-output .templatequote{overflow:hidden;margin:1em 0;padding:0 40px}.mw-parser-output .templatequote .templatequotecite{line-height:1.5em;text-align:left;padding-left:1.6em;margin-top:0}
convulsive, with heavy changing contortion of the face connected, laugh without an exterior cause. The word can be found also in Homer's Odyssee, 20, 302 and should be caused by a Sardinian cabbage (according to Virgil: Sardoa herba), which screws up one's mouth to a laugh. Who eats of it, its face screws up itself to an involuntarily grinning laugh. Also newer works refer the origin of the convulsive laugh to the plant Sardonia.
# Ranunculus
The term sardonic (sardanios) "bitter or scornful laughter", which is often cited as deriving from the Sardinian plant (Ranunculus sardous), known as either Template:Polytonic (sardanē) or σαρδόνιον (sardonion). When eaten, it would cause the eater's face to contort in a look resembling scorn (generally followed by death). It might also be related to σαίρω (sairō) "I grin". | Sardonicism
Template:Search infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Sardonicism (connected with guffaw) characterizes —as distinct from Sarcasm— not a contumely or bitter, but a ferocious, painful derision.
# Origin
The aborigines of Sardinia Template:Lang-la would kill their elderly and laugh while doing this. This is called sardonic laughter, or the infamous "Risus sardonicus", a convulsive laughing, with which the soul is noninvolved. Template:Lang-it, Template:Lang-fr.
It was already established in the Ancient Greece. They also differentiated between cynic (kynikós "to the world opinion of the cynics"), sardonic (sardánios "the scornful laughter of an angry person, with own pain or own damage") and sarcastic (sarkastikós "derision, hurtful speech"). So Odysseus —after he had at last returned— laughed sardonic to himself when he dodged a foot of a cow, which was thrown by a punter of his wife.
Occasionally, the convulsive laugh is traced back to a bitter Sardinian plant called "sardánion". The Meyers Encyclopedia from 1888 says Sardoniasm was a: .mw-parser-output .templatequote{overflow:hidden;margin:1em 0;padding:0 40px}.mw-parser-output .templatequote .templatequotecite{line-height:1.5em;text-align:left;padding-left:1.6em;margin-top:0}
convulsive, with heavy changing contortion of the face connected, laugh without an exterior cause. The word can be found also in Homer's Odyssee, 20, 302 and should be caused by a Sardinian cabbage (according to Virgil: Sardoa herba), which screws up one's mouth to a laugh. Who eats of it, its face screws up itself to an involuntarily grinning laugh. Also newer works refer the origin of the convulsive laugh to the plant Sardonia.
# Ranunculus
The term sardonic (sardanios) "bitter or scornful laughter", which is often cited as deriving from the Sardinian plant (Ranunculus sardous), known as either Template:Polytonic (sardanē) or σαρδόνιον (sardonion). When eaten, it would cause the eater's face to contort in a look resembling scorn (generally followed by death). It might also be related to σαίρω (sairō) "I grin". | https://www.wikidoc.org/index.php/Sardonicism | |
698dd2dd3505e3588d6275bec461a46f125ac137 | wikidoc | Satraplatin | Satraplatin
# Overview
Satraplatin (INN, codenamed JM216) is a platinum-based antineoplastic agent that is under investigation as one treatment of patients with advanced prostate cancer who have failed previous chemotherapy. It has not yet received approval from the U.S. Food and Drug Administration. First mentioned in the medical literature in 1993, satraplatin is the first orally active platinum-based chemotherapeutic drug; other available platinum analogues—cisplatin, carboplatin, and oxaliplatin—must be given intravenously.
It is made available in the United States jointly by Spectrum Pharmaceuticals and GPC Biotech under the name SPERA (SatraPlatin Expanded Rapid Access).
The drug has also been used in the treatment of lung and ovarian cancers. The proposed mode of action is that the compound binds to the DNA of cancer cells rendering them incapable of dividing. | Satraplatin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Satraplatin (INN, codenamed JM216) is a platinum-based antineoplastic agent that is under investigation as one treatment of patients with advanced prostate cancer who have failed previous chemotherapy. It has not yet received approval from the U.S. Food and Drug Administration.[1] First mentioned in the medical literature in 1993,[2] satraplatin is the first orally active platinum-based chemotherapeutic drug;[3] other available platinum analogues—cisplatin, carboplatin, and oxaliplatin—must be given intravenously.
It is made available in the United States jointly by Spectrum Pharmaceuticals and GPC Biotech under the name SPERA (SatraPlatin Expanded Rapid Access).
The drug has also been used in the treatment of lung and ovarian cancers. The proposed mode of action is that the compound binds to the DNA of cancer cells rendering them incapable of dividing.[4] | https://www.wikidoc.org/index.php/Satraplatin | |
c311a548cd315d8c25dff2ce779c7b4b2bdf1687 | wikidoc | Saxagliptin | Saxagliptin
# Disclaimer
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# Overview
Saxagliptin is a Dipeptidyl peptidase-4 inhibitor that is FDA approved for the {{{indicationType}}} of type 2 diabetes mellitus. Common adverse reactions include upper respiratory tract infection, urinary tract infection, and headache.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Monotherapy and Combination Therapy
- ONGLYZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings.
- The recommended dosage of ONGLYZA is 2.5 mg or 5 mg once daily taken regardless of meals.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Saxagliptin in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Saxagliptin in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Saxagliptin in pediatric patients.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Saxagliptin in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Saxagliptin in pediatric patients.
# Contraindications
- ONGLYZA is contraindicated in patients with a history of a serious hypersensitivity reaction to ONGLYZA, such as anaphylaxis, angioedema, or exfoliative skin conditions.
# Warnings
### Precautions
- Pancreatitis
- There have been postmarketing reports of acute pancreatitis in patients taking ONGLYZA. After initiation of ONGLYZA, patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, ONGLYZA should promptly be discontinued and appropriate management should be initiated. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using ONGLYZA.
- Hypoglycemia with Cocomitant Use of Sulfonylurea or Insulin
- When ONGLYZA was used in combination with a sulfonylurea or with insulin, medications known to cause hypoglycemia, the incidence of confirmed hypoglycemia was increased over that of placebo used in combination with a sulfonylurea or with insulin. Therefore, a lower dose of the insulin secretagogue or insulin may be required to minimize the risk of hypoglycemia when used in combination with ONGLYZA.
- Hypersensitivity Reactions
- There have been postmarketing reports of serious hypersensitivity reactions in patients treated with ONGLYZA. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment with ONGLYZA, with some reports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinue ONGLYZA, assess for other potential causes for the event, and institute alternative treatment for diabetes.
- Use caution in a patient with a history of angioedema to another dipeptidyl peptidase-4 (DPP4) inhibitor because it is unknown whether such patients will be predisposed to angioedema with ONGLYZA.
- Macrovascular Outcomes
- There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with ONGLYZA or any other antidiabetic drug.
# Adverse Reactions
## Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- In two placebo-controlled monotherapy trials of 24-weeks duration, patients were treated with ONGLYZA 2.5 mg daily, ONGLYZA 5 mg daily, and placebo. Three 24-week, placebo-controlled, add-on combination therapy trials were also conducted: one with metformin, one with a thiazolidinedione (pioglitazone or rosiglitazone), and one with glyburide. In these three trials, patients were randomized to add-on therapy with ONGLYZA 2.5 mg daily, ONGLYZA 5 mg daily, or placebo. A saxagliptin 10 mg treatment arm was included in one of the monotherapy trials and in the add-on combination trial with metformin. The 10 mg dosage is not an approved dosage.
- In a prespecified pooled analysis of the 24-week data (regardless of glycemic rescue) from the two monotherapy trials, the add-on to metformin trial, the add-on to thiazolidinedione (TZD) trial, and the add-on to glyburide trial, the overall incidence of adverse events in patients treated with ONGLYZA 2.5 mg and ONGLYZA 5 mg was similar to placebo (72% and 72.2% versus 70.6%, respectively). Discontinuation of therapy due to adverse events occurred in 2.2%, 3.3%, and 1.8% of patients receiving ONGLYZA 2.5 mg, ONGLYZA 5 mg, and placebo, respectively. The most common adverse events (reported in at least 2 patients treated with ONGLYZA 2.5 mg or at least 2 patients treated with ONGLYZA 5 mg) associated with premature discontinuation of therapy included lymphopenia (0.1% and 0.5% versus 0%, respectively), rash (0.2% and 0.3% versus 0.3%), blood creatinine increased (0.3% and 0% versus 0%), and blood creatine phosphokinase increased (0.1% and 0.2% versus 0%). The adverse reactions in this pooled analysis reported (regardless of investigator assessment of causality) in ≥5% of patients treated with ONGLYZA 5 mg, and more commonly than in patients treated with placebo are shown in Table 1.
- In patients treated with ONGLYZA 2.5 mg, headache (6.5%) was the only adverse reaction reported at a rate ≥5% and more commonly than in patients treated with placebo.
- In this pooled analysis, adverse reactions that were reported in ≥2% of patients treated with ONGLYZA 2.5 mg or ONGLYZA 5 mg and ≥1% more frequently compared to placebo included: sinusitis (2.9% and 2.6% versus 1.6%, respectively), abdominal pain (2.4% and 1.7% versus 0.5%), gastroenteritis (1.9% and 2.3% versus 0.9%), and vomiting (2.2% and 2.3% versus 1.3%).
- In the add-on to TZD trial, the incidence of peripheral edema was higher for ONGLYZA 5 mg versus placebo (8.1% and 4.3%, respectively). The incidence of peripheral edema for ONGLYZA 2.5 mg was 3.1%. None of the reported adverse reactions of peripheral edema resulted in study drug discontinuation. Rates of peripheral edema for ONGLYZA 2.5 mg and ONGLYZA 5 mg versus placebo were 3.6% and 2% versus 3% given as monotherapy, 2.1% and 2.1% versus 2.2% given as add-on therapy to metformin, and 2.4% and 1.2% versus 2.2% given as add-on therapy to glyburide.
- The incidence rate of fractures was 1.0 and 0.6 per 100 patient-years, respectively, for ONGLYZA (pooled analysis of 2.5 mg, 5 mg, and 10 mg) and placebo. The 10 mg dosage is not an approved dosage. The incidence rate of fracture events in patients who received ONGLYZA did not increase over time. Causality has not been established and nonclinical studies have not demonstrated adverse effects of ONGLYZA on bone.
- An event of thrombocytopenia, consistent with a diagnosis of idiopathic thrombocytopenic purpura, was observed in the clinical program. The relationship of this event to ONGLYZA is not known.
- ONGLYZA 2.5 mg was compared to placebo in a 12-week trial in 170 patients with type 2 diabetes and moderate or severe renal impairment or end-stage renal disease (ESRD). The incidence of adverse events, including serious adverse events and discontinuations due to adverse events, was similar between ONGLYZA and placebo.
- In the add-on to insulin trial, the incidence of adverse events, including serious adverse events and discontinuations due to adverse events, was similar between ONGLYZA and placebo, except for confirmed hypoglycemia.
- Table 2 shows the adverse reactions reported (regardless of investigator assessment of causality) in ≥5% of patients participating in an additional 24-week, active-controlled trial of coadministered ONGLYZA and metformin in treatment-naive patients.
- Adverse reactions of hypoglycemia were based on all reports of hypoglycemia. A concurrent glucose measurement was not required or was normal in some patients. Therefore, it is not possible to conclusively determine that all these reports reflect true hypoglycemia.
- In the add-on to glyburide study, the overall incidence of reported hypoglycemia was higher for ONGLYZA 2.5 mg and ONGLYZA 5 mg (13.3% and 14.6%) versus placebo (10.1%). The incidence of confirmed hypoglycemia in this study, defined as symptoms of hypoglycemia accompanied by a fingerstick glucose value of ≤50 mg/dL, was 2.4% and 0.8% for ONGLYZA 2.5 mg and ONGLYZA 5 mg and 0.7% for placebo. The incidence of reported hypoglycemia for ONGLYZA 2.5 mg and ONGLYZA 5 mg versus placebo given as monotherapy was 4% and 5.6% versus 4.1%, respectively, 7.8% and 5.8% versus 5% given as add-on therapy to metformin, and 4.1% and 2.7% versus 3.8% given as add-on therapy to TZD. The incidence of reported hypoglycemia was 3.4% in treatment-naive patients given ONGLYZA 5 mg plus metformin and 4% in patients given metformin alone.
- In the active-controlled trial comparing add-on therapy with ONGLYZA 5 mg to glipizide in patients inadequately controlled on metformin alone, the incidence of reported hypoglycemia was 3% (19 events in 13 patients) with ONGLYZA 5 mg versus 36.3% (750 events in 156 patients) with glipizide. Confirmed symptomatic hypoglycemia (accompanying fingerstick blood glucose ≤50 mg/dL) was reported in none of the ONGLYZA-treated patients and in 35 glipizide-treated patients (8.1%) (p<0.0001).
- During 12 weeks of treatment in patients with moderate or severe renal impairment or ESRD, the overall incidence of reported hypoglycemia was 20% among patients treated with ONGLYZA 2.5 mg and 22% among patients treated with placebo. Four ONGLYZA-treated patients (4.7%) and three placebo-treated patients (3.5%) reported at least one episode of confirmed symptomatic hypoglycemia (accompanying fingerstick glucose ≤50 mg/dL).
- In the add-on to insulin trial, the overall incidence of reported hypoglycemia was 18.4% for ONGLYZA 5 mg and 19.9% for placebo. However, the incidence of confirmed symptomatic hypoglycemia (accompanying fingerstick blood glucose ≤50 mg/dL) was higher with ONGLYZA 5 mg (5.3%) versus placebo (3.3%).
- In the add-on to metformin plus sulfonylurea trial, the overall incidence of reported hypoglycemia was 10.1% for ONGLYZA 5 mg and 6.3% for placebo. Confirmed hypoglycemia was reported in 1.6% of the ONGLYZA-treated patients and in none of the placebo-treated patients.
- Hypersensitivity-related events, such as urticaria and facial edema in the 5-study pooled analysis up to Week 24 were reported in 1.5%, 1.5%, and 0.4% of patients who received ONGLYZA 2.5 mg, ONGLYZA 5 mg, and placebo, respectively. None of these events in patients who received ONGLYZA required hospitalization or were reported as life-threatening by the investigators. One ONGLYZA-treated patient in this pooled analysis discontinued due to generalized urticaria and facial edema.
- In the unblinded, controlled, clinical trial database for ONGLYZA to date, there have been 6 (0.12%) reports of tuberculosis among the 4959 ONGLYZA-treated patients (1.1 per 1000 patient-years) compared to no reports of tuberculosis among the 2868 comparator-treated patients. Two of these six cases were confirmed with laboratory testing. The remaining cases had limited information or had presumptive diagnoses of tuberculosis. None of the six cases occurred in the United States or in Western Europe. One case occurred in Canada in a patient originally from Indonesia who had recently visited Indonesia. The duration of treatment with ONGLYZA until report of tuberculosis ranged from 144 to 929 days. Post-treatment lymphocyte counts were consistently within the reference range for four cases. One patient had lymphopenia prior to initiation of ONGLYZA that remained stable throughout ONGLYZA treatment. The final patient had an isolated lymphocyte count below normal approximately four months prior to the report of tuberculosis. There have been no spontaneous reports of tuberculosis associated with ONGLYZA use. Causality has not been estimated and there are too few cases to date to determine whether tuberculosis is related to ONGLYZA use.
- There has been one case of a potential opportunistic infection in the unblinded, controlled clinical trial database to date in an ONGLYZA-treated patient who developed suspected foodborne fatal salmonella sepsis after approximately 600 days of ONGLYZA therapy. There have been no spontaneous reports of opportunistic infections associated with ONGLYZA use.
- No clinically meaningful changes in vital signs have been observed in patients treated with ONGLYZA.
- There was a dose-related mean decrease in absolute lymphocyte count observed with ONGLYZA. From a baseline mean absolute lymphocyte count of approximately 2200 cells/microL, mean decreases of approximately 100 and 120 cells/microL with ONGLYZA 5 mg and 10 mg, respectively, relative to placebo were observed at 24 weeks in a pooled analysis of five placebo-controlled clinical studies. Similar effects were observed when ONGLYZA 5 mg was given in initial combination with metformin compared to metformin alone. There was no difference observed for ONGLYZA 2.5 mg relative to placebo. The proportion of patients who were reported to have a lymphocyte count ≤750 cells/microL was 0.5%, 1.5%, 1.4%, and 0.4% in the ONGLYZA 2.5 mg, 5 mg, 10 mg, and placebo groups, respectively. In most patients, recurrence was not observed with repeated exposure to ONGLYZA although some patients had recurrent decreases upon rechallenge that led to discontinuation of ONGLYZA. The decreases in lymphocyte count were not associated with clinically relevant adverse reactions. The 10 mg dosage is not an approved dosage.
- The clinical significance of this decrease in lymphocyte count relative to placebo is not known. When clinically indicated, such as in settings of unusual or prolonged infection, lymphocyte count should be measured. The effect of ONGLYZA on lymphocyte counts in patients with lymphocyte abnormalities (e.g., human immunodeficiency virus) is unknown.
## Postmarketing Experience
- Additional adverse reactions have been identified during postapproval use of ONGLYZA. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Hypersensitivity reactions including anaphylaxis, angioedema, and exfoliative skin conditions.
- Acute pancreatitis.
# Drug Interactions
- Strong Inhibitors of CYP3A4/5 Enzymes
- Ketoconazole significantly increased saxagliptin exposure. Similar significant increases in plasma concentrations of saxagliptin are anticipated with other strong CYP3A4/5 inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin). The dose of ONGLYZA should be limited to 2.5 mg when coadministered with a strong CYP3A4/5 inhibitor.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
- Pregnancy Category B
- There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, ONGLYZA, like other antidiabetic medications, should be used during pregnancy only if clearly needed.
- Saxagliptin was not teratogenic at any dose tested when administered to pregnant rats and rabbits during periods of organogenesis. Incomplete ossification of the pelvis, a form of developmental delay, occurred in rats at a dose of 240 mg/kg, or approximately 1503 and 66 times human exposure to saxagliptin and the active metabolite, respectively, at the maximum recommended human dose (MRHD) of 5 mg. Maternal toxicity and reduced fetal body weights were observed at 7986 and 328 times the human exposure at the MRHD for saxagliptin and the active metabolite, respectively. Minor skeletal variations in rabbits occurred at a maternally toxic dose of 200 mg/kg, or approximately 1432 and 992 times the MRHD.
- Coadministration of saxagliptin and metformin, to pregnant rats and rabbits during the period of organogenesis, was neither embryolethal nor teratogenic in either species when tested at doses yielding systemic exposures (AUC) up to 100 and 10 times the MRHD (saxagliptin 5 mg and metformin 2000 mg), respectively, in rats; and 249 and 1.1 times the MRHDs in rabbits. In rats, minor developmental toxicity was limited to an increased incidence of wavy ribs; associated maternal toxicity was limited to weight decrements of 11% to 17% over the course of the study, and related reductions in maternal food consumption. In rabbits, coadministration was poorly tolerated in a subset of mothers (12 of 30), resulting in death, moribundity, or abortion. However, among surviving mothers with evaluable litters, maternal toxicity was limited to marginal reductions in body weight over the course of gestation days 21 to 29; and associated developmental toxicity in these litters was limited to fetal body weight decrements of 7%, and a low incidence of delayed ossification of the fetal hyoid.
- Saxagliptin administered to female rats from gestation day 6 to lactation day 20 resulted in decreased body weights in male and female offspring only at maternally toxic doses (exposures ≥1629 and 53 times saxagliptin and its active metabolite at the MRHD). No functional or behavioral toxicity was observed in offspring of rats administered saxagliptin at any dose.
- Saxagliptin crosses the placenta into the fetus following dosing in pregnant rats.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Saxagliptin in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Saxagliptin during labor and delivery.
### Nursing Mothers
- Saxagliptin is secreted in the milk of lactating rats at approximately a 1:1 ratio with plasma drug concentrations. It is not known whether saxagliptin is secreted in human milk. Because many drugs are secreted in human milk, caution should be exercised when ONGLYZA is administered to a nursing woman.
### Pediatric Use
- Safety and effectiveness of ONGLYZA in pediatric patients under 18 years of age have not been established. Additionally, studies characterizing the pharmacokinetics of ONGLYZA in pediatric patients have not been performed.
### Geriatic Use
- In the six, double-blind, controlled clinical safety and efficacy trials of ONGLYZA, 634 (15.3%) of the 4148 randomized patients were 65 years and over, and 59 (1.4%) patients were 75 years and over. No overall differences in safety or effectiveness were observed between patients ≥65 years old and the younger patients. While this clinical experience has not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out.
- Saxagliptin and its active metabolite are eliminated in part by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in the elderly based on renal function.
### Gender
There is no FDA guidance on the use of Saxagliptin with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Saxagliptin with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Saxagliptin in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Saxagliptin in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Saxagliptin in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Saxagliptin in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Oral
### Monitoring
There is limited information regarding Monitoring of Saxagliptin in the drug label.
# IV Compatibility
There is limited information regarding IV Compatibility of Saxagliptin in the drug label.
# Overdosage
## Acute Overdose
### Signs and Symptoms
- In a controlled clinical trial, once-daily, orally-administered ONGLYZA in healthy subjects at doses up to 400 mg daily for 2 weeks (80 times the MRHD) had no dose-related clinical adverse reactions and no clinically meaningful effect on QTc interval or heart rate.
### Management
- In the event of an overdose, appropriate supportive treatment should be initiated as dictated by the patient’s clinical status. Saxagliptin and its active metabolite are removed by hemodialysis (23% of dose over 4 hours).
## Chronic Overdose
There is limited information regarding Chronic Overdose of Saxagliptin in the drug label.
# Pharmacology
## Mechanism of Action
- Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the DPP4 enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 diabetes, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved. Saxagliptin is a competitive DPP4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus.
## Structure
- Saxagliptin is an orally-active inhibitor of the DPP4 enzyme.
- Saxagliptin monohydrate is described chemically as (1S,3S,5S)-2-dec-1-yl)acetyl]-2-azabicyclohexane-3-carbonitrile, monohydrate or (1S,3S,5S)-2--2-azabicyclohexane-3-carbonitrile hydrate. The empirical formula is C18H25N3O2H2O and the molecular weight is 333.43. The structural formula is:
- Saxagliptin monohydrate is a white to light yellow or light brown, non-hygroscopic, crystalline powder. It is sparingly soluble in water at 24°C ± 3°C, slightly soluble in ethyl acetate, and soluble in methanol, ethanol, isopropyl alcohol, acetonitrile, acetone, and polyethylene glycol 400 (PEG 400).
- Each film-coated tablet of ONGLYZA for oral use contains either 2.79 mg saxagliptin hydrochloride (anhydrous) equivalent to 2.5 mg saxagliptin or 5.58 mg saxagliptin hydrochloride (anhydrous) equivalent to 5 mg saxagliptin and the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. In addition, the film coating contains the following inactive ingredients: polyvinyl alcohol, polyethylene glycol, titanium dioxide, talc, and iron oxides.
## Pharmacodynamics
- In patients with type 2 diabetes mellitus, administration of ONGLYZA inhibits DPP4 enzyme activity for a 24-hour period. After an oral glucose load or a meal, this DPP4 inhibition resulted in a 2- to 3-fold increase in circulating levels of active GLP-1 and GIP, decreased glucagon concentrations, and increased glucose-dependent insulin secretion from pancreatic beta cells. The rise in insulin and decrease in glucagon were associated with lower fasting glucose concentrations and reduced glucose excursion following an oral glucose load or a meal.
- Cardiac Electrophysiology
- In a randomized, double-blind, placebo-controlled, 4-way crossover, active comparator study using moxifloxacin in 40 healthy subjects, ONGLYZA was not associated with clinically meaningful prolongation of the QTc interval or heart rate at daily doses up to 40 mg (8 times the MRHD).
## Pharmacokinetics
- The pharmacokinetics of saxagliptin and its active metabolite, 5-hydroxy saxagliptin were similar in healthy subjects and in patients with type 2 diabetes mellitus. The Cmax and AUC values of saxagliptin and its active metabolite increased proportionally in the 2.5 to 400 mg dose range. Following a 5 mg single oral dose of saxagliptin to healthy subjects, the mean plasma AUC values for saxagliptin and its active metabolite were 78 ngh/mL and 214 ngh/mL, respectively. The corresponding plasma Cmax values were 24 ng/mL and 47 ng/mL, respectively. The average variability (%CV) for AUC and Cmax for both saxagliptin and its active metabolite was less than 25%.
- No appreciable accumulation of either saxagliptin or its active metabolite was observed with repeated once-daily dosing at any dose level. No dose- and time-dependence were observed in the clearance of saxagliptin and its active metabolite over 14 days of once-daily dosing with saxagliptin at doses ranging from 2.5 to 400 mg.
- Absorption
- The median time to maximum concentration (Tmax) following the 5 mg once daily dose was 2 hours for saxagliptin and 4 hours for its active metabolite. Administration with a high-fat meal resulted in an increase in Tmax of saxagliptin by approximately 20 minutes as compared to fasted conditions. There was a 27% increase in the AUC of saxagliptin when given with a meal as compared to fasted conditions. ONGLYZA may be administered with or without food.
- Distribution
- The in vitro protein binding of saxagliptin and its active metabolite in human serum is negligible. Therefore, changes in blood protein levels in various disease states (e.g., renal or hepatic impairment) are not expected to alter the disposition of saxagliptin.
- Metabolism
- The metabolism of saxagliptin is primarily mediated by cytochrome P450 3A4/5 (CYP3A4/5). The major metabolite of saxagliptin is also a DPP4 inhibitor, which is one-half as potent as saxagliptin. Therefore, strong CYP3A4/5 inhibitors and inducers will alter the pharmacokinetics of saxagliptin and its active metabolite.
- Excretion
- Saxagliptin is eliminated by both renal and hepatic pathways. Following a single 50 mg dose of 14C-saxagliptin, 24%, 36%, and 75% of the dose was excreted in the urine as saxagliptin, its active metabolite, and total radioactivity, respectively. The average renal clearance of saxagliptin (~230 mL/min) was greater than the average estimated glomerular filtration rate (~120 mL/min), suggesting some active renal excretion. A total of 22% of the administered radioactivity was recovered in feces representing the fraction of the saxagliptin dose excreted in bile and/or unabsorbed drug from the gastrointestinal tract. Following a single oral dose of ONGLYZA 5 mg to healthy subjects, the mean plasma terminal half-life (t1/2) for saxagliptin and its active metabolite was 2.5 and 3.1 hours, respectively.
- Specific Populations
- Renal Impairment
- A single-dose, open-label study was conducted to evaluate the pharmacokinetics of saxagliptin (10 mg dose) in subjects with varying degrees of chronic renal impairment (N=8 per group) compared to subjects with normal renal function. The 10 mg dosage is not an approved dosage. The study included patients with renal impairment classified on the basis of creatinine clearance as mild (>50 to ≤80 mL/min), moderate (30 to ≤50 mL/min), and severe (<30 mL/min), as well as patients with end-stage renal disease on hemodialysis. Creatinine clearance was estimated from serum creatinine based on the Cockcroft-Gault formula:
- The degree of renal impairment did not affect the Cmax of saxagliptin or its active metabolite. In subjects with mild renal impairment, the AUC values of saxagliptin and its active metabolite were 20% and 70% higher, respectively, than AUC values in subjects with normal renal function. Because increases of this magnitude are not considered to be clinically relevant, dosage adjustment in patients with mild renal impairment is not recommended. In subjects with moderate or severe renal impairment, the AUC values of saxagliptin and its active metabolite were up to 2.1- and 4.5-fold higher, respectively, than AUC values in subjects with normal renal function. To achieve plasma exposures of saxagliptin and its active metabolite similar to those in patients with normal renal function, the recommended dose is 2.5 mg once daily in patients with moderate and severe renal impairment, as well as in patients with end-stage renal disease requiring hemodialysis. Saxagliptin is removed by hemodialysis.
- Hepatic Impairment
- In subjects with hepatic impairment (Child-Pugh classes A, B, and C), mean Cmax and AUC of saxagliptin were up to 8% and 77% higher, respectively, compared to healthy matched controls following administration of a single 10 mg dose of saxagliptin. The 10 mg dosage is not an approved dosage. The corresponding Cmax and AUC of the active metabolite were up to 59% and 33% lower, respectively, compared to healthy matched controls. These differences are not considered to be clinically meaningful. No dosage adjustment is recommended for patients with hepatic impairment.
- Body Mass Index
- No dosage adjustment is recommended based on body mass index (BMI) which was not identified as a significant covariate on the apparent clearance of saxagliptin or its active metabolite in the population pharmacokinetic analysis.
- Gender
- No dosage adjustment is recommended based on gender. There were no differences observed in saxagliptin pharmacokinetics between males and females. Compared to males, females had approximately 25% higher exposure values for the active metabolite than males, but this difference is unlikely to be of clinical relevance. Gender was not identified as a significant covariate on the apparent clearance of saxagliptin and its active metabolite in the population pharmacokinetic analysis.
- Geriatric
- No dosage adjustment is recommended based on age alone. Elderly subjects (65-80 years) had 23% and 59% higher geometric mean Cmax and geometric mean AUC values, respectively, for saxagliptin than young subjects (18-40 years). Differences in active metabolite pharmacokinetics between elderly and young subjects generally reflected the differences observed in saxagliptin pharmacokinetics. The difference between the pharmacokinetics of saxagliptin and the active metabolite in young and elderly subjects is likely due to multiple factors including declining renal function and metabolic capacity with increasing age. Age was not identified as a significant covariate on the apparent clearance of saxagliptin and its active metabolite in the population pharmacokinetic analysis.
- Race and Ethnicity
- No dosage adjustment is recommended based on race. The population pharmacokinetic analysis compared the pharmacokinetics of saxagliptin and its active metabolite in 309 Caucasian subjects with 105 non-Caucasian subjects (consisting of six racial groups). No significant difference in the pharmacokinetics of saxagliptin and its active metabolite were detected between these two populations.
- Drug Interaction Studies
- In Vitro Assessment of Drug Interactions
- The metabolism of saxagliptin is primarily mediated by CYP3A4/5.
- In in vitro studies, saxagliptin and its active metabolite did not inhibit CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, or 3A4, or induce CYP1A2, 2B6, 2C9, or 3A4. Therefore, saxagliptin is not expected to alter the metabolic clearance of coadministered drugs that are metabolized by these enzymes. Saxagliptin is a P-glycoprotein (P-gp) substrate but is not a significant inhibitor or inducer of P-gp.
## Nonclinical Toxicology
- Carcinogenesis
- Saxagliptin did not induce tumors in either mice (50, 250, and 600 mg/kg) or rats (25, 75, 150, and 300 mg/kg) at the highest doses evaluated. The highest doses evaluated in mice were equivalent to approximately 870 (males) and 1165 (females) times the human exposure at the MRHD of 5 mg/day. In rats, exposures were approximately 355 (males) and 2217 (females) times the MRHD.
- Mutagenesis
- Saxagliptin was not mutagenic or clastogenic with or without metabolic activation in an in vitro Ames bacterial assay, an in vitro cytogenetics assay in primary human lymphocytes, an in vivo oral micronucleus assay in rats, an in vivo oral DNA repair study in rats, and an oral in vivo/in vitro cytogenetics study in rat peripheral blood lymphocytes. The active metabolite was not mutagenic in an in vitro Ames bacterial assay.
- Impairment of Fertility
- In a rat fertility study, males were treated with oral gavage doses for 2 weeks prior to mating, during mating, and up to scheduled termination (approximately 4 weeks total) and females were treated with oral gavage doses for 2 weeks prior to mating through gestation day 7. No adverse effects on fertility were observed at exposures of approximately 603 (males) and 776 (females) times the MRHD. Higher doses that elicited maternal toxicity also increased fetal resorptions (approximately 2069 and 6138 times the MRHD). Additional effects on estrous cycling, fertility, ovulation, and implantation were observed at approximately 6138 times the MRHD.
- Animal Toxicology and/or Pharmacology
- Saxagliptin produced adverse skin changes in the extremities of cynomolgus monkeys (scabs and/or ulceration of tail, digits, scrotum, and/or nose). Skin lesions were reversible at ≥20 times the MRHD but in some cases were irreversible and necrotizing at higher exposures. Adverse skin changes were not observed at exposures similar to (1 to 3 times) the MRHD of 5 mg. Clinical correlates to skin lesions in monkeys have not been observed in human clinical trials of saxagliptin.
# Clinical Studies
- ONGLYZA has been studied as monotherapy and in combination with metformin, glyburide, and thiazolidinedione (pioglitazone and rosiglitazone) therapy.
- A total of 4148 patients with type 2 diabetes mellitus were randomized in six, double-blind, controlled clinical trials conducted to evaluate the safety and glycemic efficacy of ONGLYZA. A total of 3021 patients in these trials were treated with ONGLYZA. In these trials, the mean age was 54 years, and 71% of patients were Caucasian, 16% were Asian, 4% were black, and 9% were of other racial groups. An additional 423 patients, including 315 who received ONGLYZA, participated in a placebo-controlled, dose-ranging study of 6 to 12 weeks in duration.
- In these six, double-blind trials, ONGLYZA was evaluated at doses of 2.5 mg and 5 mg once daily. Three of these trials also evaluated a saxagliptin dose of 10 mg daily. The 10 mg daily dose of saxagliptin did not provide greater efficacy than the 5 mg daily dose. The 10 mg dosage is not an approved dosage. Treatment with ONGLYZA 5 mg and 2.5 mg doses produced clinically relevant and statistically significant improvements in hemoglobin A1c (A1C), fasting plasma glucose (FPG), and 2-hour postprandial glucose (PPG) following a standard oral glucose tolerance test (OGTT), compared to control. Reductions in A1C were seen across subgroups including gender, age, race, and baseline BMI.
- ONGLYZA was not associated with significant changes from baseline in body weight or fasting serum lipids compared to placebo.
- ONGLYZA has also been evaluated in four additional trials in patients with type 2 diabetes: an active-controlled trial comparing add-on therapy with ONGLYZA to glipizide in 858 patients inadequately controlled on metformin alone, a trial comparing ONGLYZA to placebo in 455 patients inadequately controlled on insulin alone or on insulin in combination with metformin, a trial comparing ONGLYZA to placebo in 257 patients inadequately controlled on metformin plus a sulfonylurea, and a trial comparing ONGLYZA to placebo in 170 patients with type 2 diabetes and moderate or severe renal impairment or ESRD.
- A total of 766 patients with type 2 diabetes inadequately controlled on diet and exercise (A1C ≥7% to ≤10%) participated in two 24-week, double-blind, placebo-controlled trials evaluating the efficacy and safety of ONGLYZA monotherapy.
- In the first trial, following a 2-week single-blind diet, exercise, and placebo lead-in period, 401 patients were randomized to 2.5 mg, 5 mg, or 10 mg of ONGLYZA or placebo. The 10 mg dosage is not an approved dosage. Patients who failed to meet specific glycemic goals during the study were treated with metformin rescue therapy, added on to placebo or ONGLYZA. Efficacy was evaluated at the last measurement prior to rescue therapy for patients needing rescue. Dose titration of ONGLYZA was not permitted.
- Treatment with ONGLYZA 2.5 mg and 5 mg daily provided significant improvements in A1C, FPG, and PPG compared to placebo (Table 5). The percentage of patients who discontinued for lack of glycemic control or who were rescued for meeting prespecified glycemic criteria was 16% in the ONGLYZA 2.5 mg treatment group, 20% in the ONGLYZA 5 mg treatment group, and 26% in the placebo group.
- A second 24-week monotherapy trial was conducted to assess a range of dosing regimens for ONGLYZA. Treatment-naive patients with inadequately controlled diabetes (A1C ≥7% to ≤10%) underwent a 2-week, single-blind diet, exercise, and placebo lead-in period. A total of 365 patients were randomized to 2.5 mg every morning, 5 mg every morning, 2.5 mg with possible titration to 5 mg every morning, or 5 mg every evening of ONGLYZA, or placebo. Patients who failed to meet specific glycemic goals during the study were treated with metformin rescue therapy added on to placebo or ONGLYZA; the number of patients randomized per treatment group ranged from 71 to 74.
- Treatment with either ONGLYZA 5 mg every morning or 5 mg every evening provided significant improvements in A1C versus placebo (mean placebo-corrected reductions of −0.4% and −0.3%, respectively). Treatment with ONGLYZA 2.5 mg every morning also provided significant improvement in A1C versus placebo (mean placebo-corrected reduction of −0.4%).
- Add-On Combination Therapy with Metformin
- A total of 743 patients with type 2 diabetes participated in this 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of ONGLYZA in combination with metformin in patients with inadequate glycemic control (A1C ≥7% and ≤10%) on metformin alone. To qualify for enrollment, patients were required to be on a stable dose of metformin (1500-2550 mg daily) for at least 8 weeks.
- Patients who met eligibility criteria were enrolled in a single-blind, 2-week, dietary and exercise placebo lead-in period during which patients received metformin at their pre-study dose, up to 2500 mg daily. Following the lead-in period, eligible patients were randomized to 2.5 mg, 5 mg, or 10 mg of ONGLYZA or placebo in addition to their current dose of open-label metformin. The 10 mg dosage is not an approved dosage. Patients who failed to meet specific glycemic goals during the study were treated with pioglitazone rescue therapy, added on to existing study medications. Dose titrations of ONGLYZA and metformin were not permitted.
- ONGLYZA 2.5 mg and 5 mg add-on to metformin provided significant improvements in A1C, FPG, and PPG compared with placebo add-on to metformin (Table 6). Mean changes from baseline for A1C over time and at endpoint are shown in Figure 1. The proportion of patients who discontinued for lack of glycemic control or who were rescued for meeting prespecified glycemic criteria was 15% in the ONGLYZA 2.5 mg add-on to metformin group, 13% in the ONGLYZA 5 mg add-on to metformin group, and 27% in the placebo add-on to metformin group.
- Add-On Combination Therapy with a Thiazolidinedione
- A total of 565 patients with type 2 diabetes participated in this 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of ONGLYZA in combination with a thiazolidinedione (TZD) in patients with inadequate glycemic control (A1C ≥7% to ≤10.5%) on TZD alone. To qualify for enrollment, patients were required to be on a stable dose of pioglitazone (30-45 mg once daily) or rosiglitazone (4 mg once daily or 8 mg either once daily or in two divided doses of 4 mg) for at least 12 weeks.
- Patients who met eligibility criteria were enrolled in a single-blind, 2-week, dietary and exercise placebo lead-in period during which patients received TZD at their pre-study dose. Following the lead-in period, eligible patients were randomized to 2.5 mg or 5 mg of ONGLYZA or placebo in addition to their current dose of TZD. Patients who failed to meet specific glycemic goals during the study were treated with metformin rescue, added on to existing study medications. Dose titration of ONGLYZA or TZD was not permitted during the study. A change in TZD regimen from rosiglitazone to pioglitazone at specified, equivalent therapeutic doses was permitted at the investigator’s discretion if believed to be medically appropriate.
- ONGLYZA 2.5 mg and 5 mg add-on to TZD provided significant improvements in A1C, FPG, and PPG compared with placebo add-on to TZD (Table 7). The proportion of patients who discontinued for lack of glycemic control or who were rescued for meeting prespecified glycemic criteria was 10% in the ONGLYZA 2.5 mg add-on to TZD group, 6% for the ONGLYZA 5 mg add-on to TZD group, and 10% in the placebo add-on to TZD group.
- Add-On Combination Therapy with Glyburide
- A total of 768 patients with type 2 diabetes participated in this 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of ONGLYZA in combination with a sulfonylurea (SU) in patients with inadequate glycemic control at enrollment (A1C ≥7.5% to ≤10%) on a submaximal dose of SU alone. To qualify for enrollment, patients were required to be on a submaximal dose of SU for 2 months or greater. In this study, ONGLYZA in combination with a fixed, intermediate dose of SU was compared to titration to a higher dose of SU.
- Patients who met eligibility criteria were enrolled in a single-blind, 4-week, dietary and exercise lead-in period, and placed on glyburide 7.5 mg once daily. Following the lead-in period, eligible patients with A1C ≥7% to ≤10% were randomized to either 2.5 mg or 5 mg of ONGLYZA add-on to 7.5 mg glyburide or to placebo plus a 10 mg total daily dose of glyburide. Patients who received placebo were eligible to have glyburide up-titrated to a total daily dose of 15 mg. Up-titration of glyburide was not permitted in patients who received ONGLYZA 2.5 mg or 5 mg. Glyburide could be down-titrated in any treatment group once during the 24-week study period due to hypoglycemia as deemed necessary by the investigator. Approximately 92% of patients in the placebo plus glyburide group were up-titrated to a final total daily dose of 15 mg during the first 4 weeks of the study period. Patients who failed to meet specific glycemic goals during the study were treated with metformin rescue, added on to existing study medication. Dose titration of ONGLYZA was not permitted during the study.
- In combination with glyburide, ONGLYZA 2.5 mg and 5 mg provided significant improvements in A1C, FPG, and PPG compared with the placebo plus up-titrated glyburide group (Table 8). The proportion of patients who discontinued for lack of glycemic control or who were rescued for meeting prespecified glycemic criteria was 18% in the ONGLYZA 2.5 mg add-on to glyburide group, 17% in the ONGLYZA 5 mg add-on to glyburide group, and 30% in the placebo plus up-titrated glyburide group.
- Coadministration with Metformin in Treatment-Naive Patients
- A total of 1306 treatment-naive patients with type 2 diabetes mellitus participated in this 24-week, randomized, double-blind, active-controlled trial to evaluate the efficacy and safety of ONGLYZA coadministered with metformin in patients with inadequate glycemic control (A1C ≥8% to ≤12%) on diet and exercise alone. Patients were required to be treatment-naive to be enrolled in this study.
- Patients who met eligibility criteria were enrolled in a single-blind, 1-week, dietary and exercise placebo lead-in period. Patients were randomized to one of four treatment arms: ONGLYZA 5 mg + metformin 500 mg, saxagliptin 10 mg + metformin 500 mg, saxagliptin 10 mg + placebo, or metformin 500 mg + placebo. The 10 mg dosage is not an approved dosage. ONGLYZA was dosed once daily. In the 3 treatment groups using metformin, the metformin dose was up-titrated weekly in 500 mg per day increments, as tolerated, to a maximum of 2000 mg per day based on FPG. Patients who failed to meet specific glycemic goals during the studies were treated with pioglitazone rescue as add-on therapy.
- Coadministration of ONGLYZA 5 mg plus metformin provided significant improvements in A1C, FPG, and PPG compared with placebo plus metformin (Table 9).
- Add-On Combination Therapy with Metformin versus Glipizide Add-On Combination Therapy with Metformin
- In this 52-week, active-controlled trial, a total of 858 patients with type 2 diabetes and inadequate glycemic control (A1C >6.5% and ≤10%) on metformin alone were randomized to double-blind add-on therapy with ONGLYZA or glipizide. Patients were required to be on a stable dose of metformin (at least 1500 mg daily) for at least 8 weeks prior to enrollment.
- Patients who met eligibility criteria were enrolled in a single-blind, 2-week, dietary and exercise placebo lead-in period during which patients received metformin (1500-3000 mg based on their pre-study dose). Following the lead-in period, eligible patients were randomized to 5 mg of ONGLYZA or 5 mg of glipizide in addition to their current dose of open-label metformin. Patients in the glipizide plus metformin group underwent blinded titration of the glipizide dose during the first 18 weeks of the trial up to a maximum glipizide dose of 20 mg per day. Titration was based on a goal FPG ≤110 mg/dL or the highest tolerable glipizide dose. Fifty percent (50%) of the glipizide-treated patients were titrated to the 20-mg daily dose; 21% of the glipizide-treated patients had a final daily glipizide dose of 5 mg or less. The mean final daily dose of glipizide was 15 mg.
- After 52 weeks of treatment, ONGLYZA and glipizide resulted in similar mean reductions from baseline in A1C when added to metformin therapy (Table 10). This conclusion may be limited to patients with baseline A1C comparable to those in the trial (91% of patients had baseline A1C <9%).
- From a baseline mean body weight of 89 kg, there was a statistically significant mean reduction of 1.1 kg in patients treated with ONGLYZA compared to a mean weight gain of 1.1 kg in patients treated with glipizide (p<0.0001).
- Add-On Combination Therapy with Insulin (with or without metformin)
- A total of 455 patients with type 2 diabetes participated in this 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of ONGLYZA in combination with insulin in patients with inadequate glycemic control (A1C ≥7.5% and ≤11%) on insulin alone (N=141) or on insulin in combination with a stable dose of metformin (N=314). Patients were required to be on a stable dose of insulin (≥30 units to ≤150 units daily) with ≤20% variation in total daily dose for ≥8 weeks prior to screening. Patients entered the trial on intermediate- or long-acting (basal) insulin or premixed insulin. Patients using short-acting insulins were excluded unless the short-acting insulin was administered as part of a premixed insulin.
- Patients who met eligibility criteria were enrolled in a single-blind, four-week, dietary and exercise placebo lead-in period during which patients received insulin (and metformin if applicable) at their pretrial dose(s). Following the lead-in period, eligible patients were randomized to add-on therapy with either ONGLYZA 5 mg or placebo. Doses of the antidiabetic therapies were to remain stable but patients were rescued and allowed to adjust the insulin regimen if specific glycemic goals were not met or if the investigator learned that the patient had self-increased the insulin dose by >20%. Data after rescue were excluded from the primary efficacy analyses.
- Add-on therapy with ONGLYZA 5 mg provided significant improvements from baseline to Week 24 in A1C and PPG compared with add-on placebo (Table 11). Similar mean reductions in A1C versus placebo were observed for patients using ONGLYZA 5 mg add-on to insulin alone and ONGLYZA 5 mg add-on to insulin in combination with metformin (−0.4% and −0.4%, respectively). The percentage of patients who discontinued for lack of glycemic control or who were rescued was 23% in the ONGLYZA group and 32% in the placebo group.
- The mean daily insulin dose at baseline was 53 units in patients treated with ONGLYZA 5 mg and 55 units in patients treated with placebo. The mean change from baseline in daily dose of insulin was 2 units for the ONGLYZA 5 mg group and 5 units for the placebo group.
- The change in fasting plasma glucose from baseline to Week 24 was also tested, but was not statistically significant. The percent of patients achieving an A1C <7% was 17% (52/300) with ONGLYZA in combination with insulin compared to 7% (10/149) with placebo. Significance was not tested.
- Add-On Combination Therapy with Metformin plus Sulfonylurea
- A total of 257 patients with type 2 diabetes participated in this 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of ONGLYZA in combination with metformin plus a sulfonylurea in patients with inadequate glycemic control (A1C ≥7% and ≤10%). Patients were to be on a stable combined dose of metformin extended-release or immediate-release (at maximum tolerated dose, with minimum dose for enrollment being 1500 mg) and a sulfonylurea (at maximum tolerated dose, with minimum dose for enrollment being ≥50% of the maximum recommended dose) for ≥8 weeks prior to enrollment.
- Patients who met eligibility criteria were entered in a 2-week enrollment period to allow assessment of inclusion/exclusion criteria. Following the 2-week enrollment period, eligible patients were randomized to either double-blind ONGLYZA (5 mg once daily) or double-blind matching placebo for 24 weeks. During the 24-week double-blind treatment period, patients were to receive metformin and a sulfonylurea at the same constant dose ascertained during enrollment. Sulfonylurea dose could be down titrated once in the case of a major hypoglycemic event or recurring minor hypoglycemic events. In the absence of hypoglycemia, titration (up or down) of study medication during the treatment period was prohibited.
- ONGLYZA in combination with metformin plus a sulfonylurea provided significant improvements in A1C and PPG compared with placebo in combination with metformin plus a sulfonylurea (Table 12). The percentage of patients who discontinued for a lack of glycemic control was 6% in the ONGLYZA group and 5% in the placebo group.
- The change in fasting plasma glucose from baseline to Week 24 was also tested, but was not statistically significant. The percent of patients achieving an A1C <7% was 31% (39/127) with ONGLYZA in combination with metformin plus a sulfonylurea compared to 9% (12/127) with placebo. Significance was not tested.
- Renal Impairment
- A total of 170 patients participated in a 12-week, randomized, double-blind, placebo-controlled trial conducted to evaluate the efficacy and safety of ONGLYZA 2.5 mg once daily compared with placebo in patients with type 2 diabetes and moderate (n=90) or severe (n=41) renal impairment or ESRD (n=39). In this trial, 98% of the patients were using background antidiabetic medications (75% were using insulin and 31% were using oral antidiabetic medications, mostly sulfonylureas).
- After 12 weeks of treatment, ONGLYZA 2.5 mg provided significant improvement in A1C compared to placebo (Table 13). In the subgroup of patients with ESRD, ONGLYZA and placebo resulted in comparable reductions in A1C from baseline to Week 12. This finding is inconclusive because the trial was not adequately powered to show efficacy within specific subgroups of renal impairment.
- After 12 weeks of treatment, the mean change in FPG was −12 mg/dL with ONGLYZA 2.5 mg and −13 mg/dL with placebo. Compared to placebo, the mean change in FPG with ONGLYZA was −12 mg/dL in the subgroup of patients with moderate renal impairment, −4 mg/dL in the subgroup of patients with severe renal impairment, and +44 mg/dL in the subgroup of patients with ESRD. These findings are inconclusive because the trial was not adequately powered to show efficacy within specific subgroups of renal impairment.
# How Supplied
- ONGLYZA® (saxagliptin) tablets have markings on both sides and are available in the strengths and packages listed in Table 14.
- Storage and Handling
- Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) .
## Storage
There is limited information regarding Saxagliptin Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
- Healthcare providers should instruct their patients to read the Medication Guide before starting ONGLYZA therapy and to reread it each time the prescription is renewed. Patients should be instructed to inform their healthcare provider if they develop any unusual symptom or if any existing symptom persists or worsens.
- Patients should be informed of the potential risks and benefits of ONGLYZA and of alternative modes of therapy. Patients should also be informed about the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and A1C testing, recognition and management of hypoglycemia and hyperglycemia, and assessment of diabetes complications. During periods of stress such as fever, trauma, infection, or surgery, medication requirements may change and patients should be advised to seek medical advice promptly.
- Pancreatitis
- Patients should be informed that acute pancreatitis has been reported during postmarketing use of ONGLYZA. Before initiating ONGLYZA, patients should be questioned about other risk factors for pancreatitis, such as a history of pancreatitis, alcoholism, gallstones, or hypertriglyceridemia. Patients should also be informed that persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting, is the hallmark symptom of acute pancreatitis. Patients should be instructed to promptly discontinue ONGLYZA and contact their healthcare provider if persistent severe abdominal pain occurs.
- Hypersensitivity Reactions
- Patients should be informed that serious allergic (hypersensitivity) reactions, such as angioedema, anaphylaxis, and exfoliative skin conditions, have been reported during postmarketing use of ONGLYZA. If symptoms of these allergic reactions (such as rash, skin flaking or peeling, urticaria, swelling of the skin, or swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing) occur, patients must stop taking ONGLYZA and seek medical advice promptly.
- Missed Dose
- Patients should be informed that if they miss a dose of ONGLYZA they should take the next dose as prescribed, unless otherwise instructed by their healthcare provider. Patients should be instructed not to take an extra dose the next day.
- Administration Instructions
- Patients should be informed that ONGLYZA tablets must not be split or cut.
- Laboratory Tests
- Patients should be informed that response to all diabetic therapies should be monitored by periodic measurements of blood glucose and A1C, with a goal of decreasing these levels toward the normal range. A1C is especially useful for evaluating long-term glycemic control. Patients should be informed of the potential need to adjust their dose based on changes in renal function tests over time.
# Precautions with Alcohol
- Alcohol-Saxagliptin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- ONGLYZA®
# Look-Alike Drug Names
There is limited information regarding Saxagliptin Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Saxagliptin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vignesh Ponnusamy, M.B.B.S. [2]
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# Overview
Saxagliptin is a Dipeptidyl peptidase-4 inhibitor that is FDA approved for the {{{indicationType}}} of type 2 diabetes mellitus. Common adverse reactions include upper respiratory tract infection, urinary tract infection, and headache.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Monotherapy and Combination Therapy
- ONGLYZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings.
- The recommended dosage of ONGLYZA is 2.5 mg or 5 mg once daily taken regardless of meals.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Saxagliptin in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Saxagliptin in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Saxagliptin in pediatric patients.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Saxagliptin in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Saxagliptin in pediatric patients.
# Contraindications
- ONGLYZA is contraindicated in patients with a history of a serious hypersensitivity reaction to ONGLYZA, such as anaphylaxis, angioedema, or exfoliative skin conditions.
# Warnings
### Precautions
- Pancreatitis
- There have been postmarketing reports of acute pancreatitis in patients taking ONGLYZA. After initiation of ONGLYZA, patients should be observed carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, ONGLYZA should promptly be discontinued and appropriate management should be initiated. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using ONGLYZA.
- Hypoglycemia with Cocomitant Use of Sulfonylurea or Insulin
- When ONGLYZA was used in combination with a sulfonylurea or with insulin, medications known to cause hypoglycemia, the incidence of confirmed hypoglycemia was increased over that of placebo used in combination with a sulfonylurea or with insulin. Therefore, a lower dose of the insulin secretagogue or insulin may be required to minimize the risk of hypoglycemia when used in combination with ONGLYZA.
- Hypersensitivity Reactions
- There have been postmarketing reports of serious hypersensitivity reactions in patients treated with ONGLYZA. These reactions include anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment with ONGLYZA, with some reports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinue ONGLYZA, assess for other potential causes for the event, and institute alternative treatment for diabetes.
- Use caution in a patient with a history of angioedema to another dipeptidyl peptidase-4 (DPP4) inhibitor because it is unknown whether such patients will be predisposed to angioedema with ONGLYZA.
- Macrovascular Outcomes
- There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with ONGLYZA or any other antidiabetic drug.
# Adverse Reactions
## Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- In two placebo-controlled monotherapy trials of 24-weeks duration, patients were treated with ONGLYZA 2.5 mg daily, ONGLYZA 5 mg daily, and placebo. Three 24-week, placebo-controlled, add-on combination therapy trials were also conducted: one with metformin, one with a thiazolidinedione (pioglitazone or rosiglitazone), and one with glyburide. In these three trials, patients were randomized to add-on therapy with ONGLYZA 2.5 mg daily, ONGLYZA 5 mg daily, or placebo. A saxagliptin 10 mg treatment arm was included in one of the monotherapy trials and in the add-on combination trial with metformin. The 10 mg dosage is not an approved dosage.
- In a prespecified pooled analysis of the 24-week data (regardless of glycemic rescue) from the two monotherapy trials, the add-on to metformin trial, the add-on to thiazolidinedione (TZD) trial, and the add-on to glyburide trial, the overall incidence of adverse events in patients treated with ONGLYZA 2.5 mg and ONGLYZA 5 mg was similar to placebo (72% and 72.2% versus 70.6%, respectively). Discontinuation of therapy due to adverse events occurred in 2.2%, 3.3%, and 1.8% of patients receiving ONGLYZA 2.5 mg, ONGLYZA 5 mg, and placebo, respectively. The most common adverse events (reported in at least 2 patients treated with ONGLYZA 2.5 mg or at least 2 patients treated with ONGLYZA 5 mg) associated with premature discontinuation of therapy included lymphopenia (0.1% and 0.5% versus 0%, respectively), rash (0.2% and 0.3% versus 0.3%), blood creatinine increased (0.3% and 0% versus 0%), and blood creatine phosphokinase increased (0.1% and 0.2% versus 0%). The adverse reactions in this pooled analysis reported (regardless of investigator assessment of causality) in ≥5% of patients treated with ONGLYZA 5 mg, and more commonly than in patients treated with placebo are shown in Table 1.
- In patients treated with ONGLYZA 2.5 mg, headache (6.5%) was the only adverse reaction reported at a rate ≥5% and more commonly than in patients treated with placebo.
- In this pooled analysis, adverse reactions that were reported in ≥2% of patients treated with ONGLYZA 2.5 mg or ONGLYZA 5 mg and ≥1% more frequently compared to placebo included: sinusitis (2.9% and 2.6% versus 1.6%, respectively), abdominal pain (2.4% and 1.7% versus 0.5%), gastroenteritis (1.9% and 2.3% versus 0.9%), and vomiting (2.2% and 2.3% versus 1.3%).
- In the add-on to TZD trial, the incidence of peripheral edema was higher for ONGLYZA 5 mg versus placebo (8.1% and 4.3%, respectively). The incidence of peripheral edema for ONGLYZA 2.5 mg was 3.1%. None of the reported adverse reactions of peripheral edema resulted in study drug discontinuation. Rates of peripheral edema for ONGLYZA 2.5 mg and ONGLYZA 5 mg versus placebo were 3.6% and 2% versus 3% given as monotherapy, 2.1% and 2.1% versus 2.2% given as add-on therapy to metformin, and 2.4% and 1.2% versus 2.2% given as add-on therapy to glyburide.
- The incidence rate of fractures was 1.0 and 0.6 per 100 patient-years, respectively, for ONGLYZA (pooled analysis of 2.5 mg, 5 mg, and 10 mg) and placebo. The 10 mg dosage is not an approved dosage. The incidence rate of fracture events in patients who received ONGLYZA did not increase over time. Causality has not been established and nonclinical studies have not demonstrated adverse effects of ONGLYZA on bone.
- An event of thrombocytopenia, consistent with a diagnosis of idiopathic thrombocytopenic purpura, was observed in the clinical program. The relationship of this event to ONGLYZA is not known.
- ONGLYZA 2.5 mg was compared to placebo in a 12-week trial in 170 patients with type 2 diabetes and moderate or severe renal impairment or end-stage renal disease (ESRD). The incidence of adverse events, including serious adverse events and discontinuations due to adverse events, was similar between ONGLYZA and placebo.
- In the add-on to insulin trial, the incidence of adverse events, including serious adverse events and discontinuations due to adverse events, was similar between ONGLYZA and placebo, except for confirmed hypoglycemia.
- Table 2 shows the adverse reactions reported (regardless of investigator assessment of causality) in ≥5% of patients participating in an additional 24-week, active-controlled trial of coadministered ONGLYZA and metformin in treatment-naive patients.
- Adverse reactions of hypoglycemia were based on all reports of hypoglycemia. A concurrent glucose measurement was not required or was normal in some patients. Therefore, it is not possible to conclusively determine that all these reports reflect true hypoglycemia.
- In the add-on to glyburide study, the overall incidence of reported hypoglycemia was higher for ONGLYZA 2.5 mg and ONGLYZA 5 mg (13.3% and 14.6%) versus placebo (10.1%). The incidence of confirmed hypoglycemia in this study, defined as symptoms of hypoglycemia accompanied by a fingerstick glucose value of ≤50 mg/dL, was 2.4% and 0.8% for ONGLYZA 2.5 mg and ONGLYZA 5 mg and 0.7% for placebo. The incidence of reported hypoglycemia for ONGLYZA 2.5 mg and ONGLYZA 5 mg versus placebo given as monotherapy was 4% and 5.6% versus 4.1%, respectively, 7.8% and 5.8% versus 5% given as add-on therapy to metformin, and 4.1% and 2.7% versus 3.8% given as add-on therapy to TZD. The incidence of reported hypoglycemia was 3.4% in treatment-naive patients given ONGLYZA 5 mg plus metformin and 4% in patients given metformin alone.
- In the active-controlled trial comparing add-on therapy with ONGLYZA 5 mg to glipizide in patients inadequately controlled on metformin alone, the incidence of reported hypoglycemia was 3% (19 events in 13 patients) with ONGLYZA 5 mg versus 36.3% (750 events in 156 patients) with glipizide. Confirmed symptomatic hypoglycemia (accompanying fingerstick blood glucose ≤50 mg/dL) was reported in none of the ONGLYZA-treated patients and in 35 glipizide-treated patients (8.1%) (p<0.0001).
- During 12 weeks of treatment in patients with moderate or severe renal impairment or ESRD, the overall incidence of reported hypoglycemia was 20% among patients treated with ONGLYZA 2.5 mg and 22% among patients treated with placebo. Four ONGLYZA-treated patients (4.7%) and three placebo-treated patients (3.5%) reported at least one episode of confirmed symptomatic hypoglycemia (accompanying fingerstick glucose ≤50 mg/dL).
- In the add-on to insulin trial, the overall incidence of reported hypoglycemia was 18.4% for ONGLYZA 5 mg and 19.9% for placebo. However, the incidence of confirmed symptomatic hypoglycemia (accompanying fingerstick blood glucose ≤50 mg/dL) was higher with ONGLYZA 5 mg (5.3%) versus placebo (3.3%).
- In the add-on to metformin plus sulfonylurea trial, the overall incidence of reported hypoglycemia was 10.1% for ONGLYZA 5 mg and 6.3% for placebo. Confirmed hypoglycemia was reported in 1.6% of the ONGLYZA-treated patients and in none of the placebo-treated patients.
- Hypersensitivity-related events, such as urticaria and facial edema in the 5-study pooled analysis up to Week 24 were reported in 1.5%, 1.5%, and 0.4% of patients who received ONGLYZA 2.5 mg, ONGLYZA 5 mg, and placebo, respectively. None of these events in patients who received ONGLYZA required hospitalization or were reported as life-threatening by the investigators. One ONGLYZA-treated patient in this pooled analysis discontinued due to generalized urticaria and facial edema.
- In the unblinded, controlled, clinical trial database for ONGLYZA to date, there have been 6 (0.12%) reports of tuberculosis among the 4959 ONGLYZA-treated patients (1.1 per 1000 patient-years) compared to no reports of tuberculosis among the 2868 comparator-treated patients. Two of these six cases were confirmed with laboratory testing. The remaining cases had limited information or had presumptive diagnoses of tuberculosis. None of the six cases occurred in the United States or in Western Europe. One case occurred in Canada in a patient originally from Indonesia who had recently visited Indonesia. The duration of treatment with ONGLYZA until report of tuberculosis ranged from 144 to 929 days. Post-treatment lymphocyte counts were consistently within the reference range for four cases. One patient had lymphopenia prior to initiation of ONGLYZA that remained stable throughout ONGLYZA treatment. The final patient had an isolated lymphocyte count below normal approximately four months prior to the report of tuberculosis. There have been no spontaneous reports of tuberculosis associated with ONGLYZA use. Causality has not been estimated and there are too few cases to date to determine whether tuberculosis is related to ONGLYZA use.
- There has been one case of a potential opportunistic infection in the unblinded, controlled clinical trial database to date in an ONGLYZA-treated patient who developed suspected foodborne fatal salmonella sepsis after approximately 600 days of ONGLYZA therapy. There have been no spontaneous reports of opportunistic infections associated with ONGLYZA use.
- No clinically meaningful changes in vital signs have been observed in patients treated with ONGLYZA.
- There was a dose-related mean decrease in absolute lymphocyte count observed with ONGLYZA. From a baseline mean absolute lymphocyte count of approximately 2200 cells/microL, mean decreases of approximately 100 and 120 cells/microL with ONGLYZA 5 mg and 10 mg, respectively, relative to placebo were observed at 24 weeks in a pooled analysis of five placebo-controlled clinical studies. Similar effects were observed when ONGLYZA 5 mg was given in initial combination with metformin compared to metformin alone. There was no difference observed for ONGLYZA 2.5 mg relative to placebo. The proportion of patients who were reported to have a lymphocyte count ≤750 cells/microL was 0.5%, 1.5%, 1.4%, and 0.4% in the ONGLYZA 2.5 mg, 5 mg, 10 mg, and placebo groups, respectively. In most patients, recurrence was not observed with repeated exposure to ONGLYZA although some patients had recurrent decreases upon rechallenge that led to discontinuation of ONGLYZA. The decreases in lymphocyte count were not associated with clinically relevant adverse reactions. The 10 mg dosage is not an approved dosage.
- The clinical significance of this decrease in lymphocyte count relative to placebo is not known. When clinically indicated, such as in settings of unusual or prolonged infection, lymphocyte count should be measured. The effect of ONGLYZA on lymphocyte counts in patients with lymphocyte abnormalities (e.g., human immunodeficiency virus) is unknown.
## Postmarketing Experience
- Additional adverse reactions have been identified during postapproval use of ONGLYZA. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Hypersensitivity reactions including anaphylaxis, angioedema, and exfoliative skin conditions.
- Acute pancreatitis.
# Drug Interactions
- Strong Inhibitors of CYP3A4/5 Enzymes
- Ketoconazole significantly increased saxagliptin exposure. Similar significant increases in plasma concentrations of saxagliptin are anticipated with other strong CYP3A4/5 inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin). The dose of ONGLYZA should be limited to 2.5 mg when coadministered with a strong CYP3A4/5 inhibitor.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
- Pregnancy Category B
- There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, ONGLYZA, like other antidiabetic medications, should be used during pregnancy only if clearly needed.
- Saxagliptin was not teratogenic at any dose tested when administered to pregnant rats and rabbits during periods of organogenesis. Incomplete ossification of the pelvis, a form of developmental delay, occurred in rats at a dose of 240 mg/kg, or approximately 1503 and 66 times human exposure to saxagliptin and the active metabolite, respectively, at the maximum recommended human dose (MRHD) of 5 mg. Maternal toxicity and reduced fetal body weights were observed at 7986 and 328 times the human exposure at the MRHD for saxagliptin and the active metabolite, respectively. Minor skeletal variations in rabbits occurred at a maternally toxic dose of 200 mg/kg, or approximately 1432 and 992 times the MRHD.
- Coadministration of saxagliptin and metformin, to pregnant rats and rabbits during the period of organogenesis, was neither embryolethal nor teratogenic in either species when tested at doses yielding systemic exposures (AUC) up to 100 and 10 times the MRHD (saxagliptin 5 mg and metformin 2000 mg), respectively, in rats; and 249 and 1.1 times the MRHDs in rabbits. In rats, minor developmental toxicity was limited to an increased incidence of wavy ribs; associated maternal toxicity was limited to weight decrements of 11% to 17% over the course of the study, and related reductions in maternal food consumption. In rabbits, coadministration was poorly tolerated in a subset of mothers (12 of 30), resulting in death, moribundity, or abortion. However, among surviving mothers with evaluable litters, maternal toxicity was limited to marginal reductions in body weight over the course of gestation days 21 to 29; and associated developmental toxicity in these litters was limited to fetal body weight decrements of 7%, and a low incidence of delayed ossification of the fetal hyoid.
- Saxagliptin administered to female rats from gestation day 6 to lactation day 20 resulted in decreased body weights in male and female offspring only at maternally toxic doses (exposures ≥1629 and 53 times saxagliptin and its active metabolite at the MRHD). No functional or behavioral toxicity was observed in offspring of rats administered saxagliptin at any dose.
- Saxagliptin crosses the placenta into the fetus following dosing in pregnant rats.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Saxagliptin in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Saxagliptin during labor and delivery.
### Nursing Mothers
- Saxagliptin is secreted in the milk of lactating rats at approximately a 1:1 ratio with plasma drug concentrations. It is not known whether saxagliptin is secreted in human milk. Because many drugs are secreted in human milk, caution should be exercised when ONGLYZA is administered to a nursing woman.
### Pediatric Use
- Safety and effectiveness of ONGLYZA in pediatric patients under 18 years of age have not been established. Additionally, studies characterizing the pharmacokinetics of ONGLYZA in pediatric patients have not been performed.
### Geriatic Use
- In the six, double-blind, controlled clinical safety and efficacy trials of ONGLYZA, 634 (15.3%) of the 4148 randomized patients were 65 years and over, and 59 (1.4%) patients were 75 years and over. No overall differences in safety or effectiveness were observed between patients ≥65 years old and the younger patients. While this clinical experience has not identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out.
- Saxagliptin and its active metabolite are eliminated in part by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in the elderly based on renal function.
### Gender
There is no FDA guidance on the use of Saxagliptin with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Saxagliptin with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Saxagliptin in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Saxagliptin in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Saxagliptin in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Saxagliptin in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Oral
### Monitoring
There is limited information regarding Monitoring of Saxagliptin in the drug label.
# IV Compatibility
There is limited information regarding IV Compatibility of Saxagliptin in the drug label.
# Overdosage
## Acute Overdose
### Signs and Symptoms
- In a controlled clinical trial, once-daily, orally-administered ONGLYZA in healthy subjects at doses up to 400 mg daily for 2 weeks (80 times the MRHD) had no dose-related clinical adverse reactions and no clinically meaningful effect on QTc interval or heart rate.
### Management
- In the event of an overdose, appropriate supportive treatment should be initiated as dictated by the patient’s clinical status. Saxagliptin and its active metabolite are removed by hemodialysis (23% of dose over 4 hours).
## Chronic Overdose
There is limited information regarding Chronic Overdose of Saxagliptin in the drug label.
# Pharmacology
## Mechanism of Action
- Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the DPP4 enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 diabetes, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved. Saxagliptin is a competitive DPP4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus.
## Structure
- Saxagliptin is an orally-active inhibitor of the DPP4 enzyme.
- Saxagliptin monohydrate is described chemically as (1S,3S,5S)-2-[(2S)-2-Amino-2-(3-hydroxytricyclo[3.3.1.13,7]dec-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile, monohydrate or (1S,3S,5S)-2-[(2S)-2-Amino-2-(3-hydroxyadamantan-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile hydrate. The empirical formula is C18H25N3O2•H2O and the molecular weight is 333.43. The structural formula is:
- Saxagliptin monohydrate is a white to light yellow or light brown, non-hygroscopic, crystalline powder. It is sparingly soluble in water at 24°C ± 3°C, slightly soluble in ethyl acetate, and soluble in methanol, ethanol, isopropyl alcohol, acetonitrile, acetone, and polyethylene glycol 400 (PEG 400).
- Each film-coated tablet of ONGLYZA for oral use contains either 2.79 mg saxagliptin hydrochloride (anhydrous) equivalent to 2.5 mg saxagliptin or 5.58 mg saxagliptin hydrochloride (anhydrous) equivalent to 5 mg saxagliptin and the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, and magnesium stearate. In addition, the film coating contains the following inactive ingredients: polyvinyl alcohol, polyethylene glycol, titanium dioxide, talc, and iron oxides.
## Pharmacodynamics
- In patients with type 2 diabetes mellitus, administration of ONGLYZA inhibits DPP4 enzyme activity for a 24-hour period. After an oral glucose load or a meal, this DPP4 inhibition resulted in a 2- to 3-fold increase in circulating levels of active GLP-1 and GIP, decreased glucagon concentrations, and increased glucose-dependent insulin secretion from pancreatic beta cells. The rise in insulin and decrease in glucagon were associated with lower fasting glucose concentrations and reduced glucose excursion following an oral glucose load or a meal.
- Cardiac Electrophysiology
- In a randomized, double-blind, placebo-controlled, 4-way crossover, active comparator study using moxifloxacin in 40 healthy subjects, ONGLYZA was not associated with clinically meaningful prolongation of the QTc interval or heart rate at daily doses up to 40 mg (8 times the MRHD).
## Pharmacokinetics
- The pharmacokinetics of saxagliptin and its active metabolite, 5-hydroxy saxagliptin were similar in healthy subjects and in patients with type 2 diabetes mellitus. The Cmax and AUC values of saxagliptin and its active metabolite increased proportionally in the 2.5 to 400 mg dose range. Following a 5 mg single oral dose of saxagliptin to healthy subjects, the mean plasma AUC values for saxagliptin and its active metabolite were 78 ng•h/mL and 214 ng•h/mL, respectively. The corresponding plasma Cmax values were 24 ng/mL and 47 ng/mL, respectively. The average variability (%CV) for AUC and Cmax for both saxagliptin and its active metabolite was less than 25%.
- No appreciable accumulation of either saxagliptin or its active metabolite was observed with repeated once-daily dosing at any dose level. No dose- and time-dependence were observed in the clearance of saxagliptin and its active metabolite over 14 days of once-daily dosing with saxagliptin at doses ranging from 2.5 to 400 mg.
- Absorption
- The median time to maximum concentration (Tmax) following the 5 mg once daily dose was 2 hours for saxagliptin and 4 hours for its active metabolite. Administration with a high-fat meal resulted in an increase in Tmax of saxagliptin by approximately 20 minutes as compared to fasted conditions. There was a 27% increase in the AUC of saxagliptin when given with a meal as compared to fasted conditions. ONGLYZA may be administered with or without food.
- Distribution
- The in vitro protein binding of saxagliptin and its active metabolite in human serum is negligible. Therefore, changes in blood protein levels in various disease states (e.g., renal or hepatic impairment) are not expected to alter the disposition of saxagliptin.
- Metabolism
- The metabolism of saxagliptin is primarily mediated by cytochrome P450 3A4/5 (CYP3A4/5). The major metabolite of saxagliptin is also a DPP4 inhibitor, which is one-half as potent as saxagliptin. Therefore, strong CYP3A4/5 inhibitors and inducers will alter the pharmacokinetics of saxagliptin and its active metabolite.
- Excretion
- Saxagliptin is eliminated by both renal and hepatic pathways. Following a single 50 mg dose of 14C-saxagliptin, 24%, 36%, and 75% of the dose was excreted in the urine as saxagliptin, its active metabolite, and total radioactivity, respectively. The average renal clearance of saxagliptin (~230 mL/min) was greater than the average estimated glomerular filtration rate (~120 mL/min), suggesting some active renal excretion. A total of 22% of the administered radioactivity was recovered in feces representing the fraction of the saxagliptin dose excreted in bile and/or unabsorbed drug from the gastrointestinal tract. Following a single oral dose of ONGLYZA 5 mg to healthy subjects, the mean plasma terminal half-life (t1/2) for saxagliptin and its active metabolite was 2.5 and 3.1 hours, respectively.
- Specific Populations
- Renal Impairment
- A single-dose, open-label study was conducted to evaluate the pharmacokinetics of saxagliptin (10 mg dose) in subjects with varying degrees of chronic renal impairment (N=8 per group) compared to subjects with normal renal function. The 10 mg dosage is not an approved dosage. The study included patients with renal impairment classified on the basis of creatinine clearance as mild (>50 to ≤80 mL/min), moderate (30 to ≤50 mL/min), and severe (<30 mL/min), as well as patients with end-stage renal disease on hemodialysis. Creatinine clearance was estimated from serum creatinine based on the Cockcroft-Gault formula:
- The degree of renal impairment did not affect the Cmax of saxagliptin or its active metabolite. In subjects with mild renal impairment, the AUC values of saxagliptin and its active metabolite were 20% and 70% higher, respectively, than AUC values in subjects with normal renal function. Because increases of this magnitude are not considered to be clinically relevant, dosage adjustment in patients with mild renal impairment is not recommended. In subjects with moderate or severe renal impairment, the AUC values of saxagliptin and its active metabolite were up to 2.1- and 4.5-fold higher, respectively, than AUC values in subjects with normal renal function. To achieve plasma exposures of saxagliptin and its active metabolite similar to those in patients with normal renal function, the recommended dose is 2.5 mg once daily in patients with moderate and severe renal impairment, as well as in patients with end-stage renal disease requiring hemodialysis. Saxagliptin is removed by hemodialysis.
- Hepatic Impairment
- In subjects with hepatic impairment (Child-Pugh classes A, B, and C), mean Cmax and AUC of saxagliptin were up to 8% and 77% higher, respectively, compared to healthy matched controls following administration of a single 10 mg dose of saxagliptin. The 10 mg dosage is not an approved dosage. The corresponding Cmax and AUC of the active metabolite were up to 59% and 33% lower, respectively, compared to healthy matched controls. These differences are not considered to be clinically meaningful. No dosage adjustment is recommended for patients with hepatic impairment.
- Body Mass Index
- No dosage adjustment is recommended based on body mass index (BMI) which was not identified as a significant covariate on the apparent clearance of saxagliptin or its active metabolite in the population pharmacokinetic analysis.
- Gender
- No dosage adjustment is recommended based on gender. There were no differences observed in saxagliptin pharmacokinetics between males and females. Compared to males, females had approximately 25% higher exposure values for the active metabolite than males, but this difference is unlikely to be of clinical relevance. Gender was not identified as a significant covariate on the apparent clearance of saxagliptin and its active metabolite in the population pharmacokinetic analysis.
- Geriatric
- No dosage adjustment is recommended based on age alone. Elderly subjects (65-80 years) had 23% and 59% higher geometric mean Cmax and geometric mean AUC values, respectively, for saxagliptin than young subjects (18-40 years). Differences in active metabolite pharmacokinetics between elderly and young subjects generally reflected the differences observed in saxagliptin pharmacokinetics. The difference between the pharmacokinetics of saxagliptin and the active metabolite in young and elderly subjects is likely due to multiple factors including declining renal function and metabolic capacity with increasing age. Age was not identified as a significant covariate on the apparent clearance of saxagliptin and its active metabolite in the population pharmacokinetic analysis.
- Race and Ethnicity
- No dosage adjustment is recommended based on race. The population pharmacokinetic analysis compared the pharmacokinetics of saxagliptin and its active metabolite in 309 Caucasian subjects with 105 non-Caucasian subjects (consisting of six racial groups). No significant difference in the pharmacokinetics of saxagliptin and its active metabolite were detected between these two populations.
- Drug Interaction Studies
- In Vitro Assessment of Drug Interactions
- The metabolism of saxagliptin is primarily mediated by CYP3A4/5.
- In in vitro studies, saxagliptin and its active metabolite did not inhibit CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, or 3A4, or induce CYP1A2, 2B6, 2C9, or 3A4. Therefore, saxagliptin is not expected to alter the metabolic clearance of coadministered drugs that are metabolized by these enzymes. Saxagliptin is a P-glycoprotein (P-gp) substrate but is not a significant inhibitor or inducer of P-gp.
## Nonclinical Toxicology
- Carcinogenesis
- Saxagliptin did not induce tumors in either mice (50, 250, and 600 mg/kg) or rats (25, 75, 150, and 300 mg/kg) at the highest doses evaluated. The highest doses evaluated in mice were equivalent to approximately 870 (males) and 1165 (females) times the human exposure at the MRHD of 5 mg/day. In rats, exposures were approximately 355 (males) and 2217 (females) times the MRHD.
- Mutagenesis
- Saxagliptin was not mutagenic or clastogenic with or without metabolic activation in an in vitro Ames bacterial assay, an in vitro cytogenetics assay in primary human lymphocytes, an in vivo oral micronucleus assay in rats, an in vivo oral DNA repair study in rats, and an oral in vivo/in vitro cytogenetics study in rat peripheral blood lymphocytes. The active metabolite was not mutagenic in an in vitro Ames bacterial assay.
- Impairment of Fertility
- In a rat fertility study, males were treated with oral gavage doses for 2 weeks prior to mating, during mating, and up to scheduled termination (approximately 4 weeks total) and females were treated with oral gavage doses for 2 weeks prior to mating through gestation day 7. No adverse effects on fertility were observed at exposures of approximately 603 (males) and 776 (females) times the MRHD. Higher doses that elicited maternal toxicity also increased fetal resorptions (approximately 2069 and 6138 times the MRHD). Additional effects on estrous cycling, fertility, ovulation, and implantation were observed at approximately 6138 times the MRHD.
- Animal Toxicology and/or Pharmacology
- Saxagliptin produced adverse skin changes in the extremities of cynomolgus monkeys (scabs and/or ulceration of tail, digits, scrotum, and/or nose). Skin lesions were reversible at ≥20 times the MRHD but in some cases were irreversible and necrotizing at higher exposures. Adverse skin changes were not observed at exposures similar to (1 to 3 times) the MRHD of 5 mg. Clinical correlates to skin lesions in monkeys have not been observed in human clinical trials of saxagliptin.
# Clinical Studies
- ONGLYZA has been studied as monotherapy and in combination with metformin, glyburide, and thiazolidinedione (pioglitazone and rosiglitazone) therapy.
- A total of 4148 patients with type 2 diabetes mellitus were randomized in six, double-blind, controlled clinical trials conducted to evaluate the safety and glycemic efficacy of ONGLYZA. A total of 3021 patients in these trials were treated with ONGLYZA. In these trials, the mean age was 54 years, and 71% of patients were Caucasian, 16% were Asian, 4% were black, and 9% were of other racial groups. An additional 423 patients, including 315 who received ONGLYZA, participated in a placebo-controlled, dose-ranging study of 6 to 12 weeks in duration.
- In these six, double-blind trials, ONGLYZA was evaluated at doses of 2.5 mg and 5 mg once daily. Three of these trials also evaluated a saxagliptin dose of 10 mg daily. The 10 mg daily dose of saxagliptin did not provide greater efficacy than the 5 mg daily dose. The 10 mg dosage is not an approved dosage. Treatment with ONGLYZA 5 mg and 2.5 mg doses produced clinically relevant and statistically significant improvements in hemoglobin A1c (A1C), fasting plasma glucose (FPG), and 2-hour postprandial glucose (PPG) following a standard oral glucose tolerance test (OGTT), compared to control. Reductions in A1C were seen across subgroups including gender, age, race, and baseline BMI.
- ONGLYZA was not associated with significant changes from baseline in body weight or fasting serum lipids compared to placebo.
- ONGLYZA has also been evaluated in four additional trials in patients with type 2 diabetes: an active-controlled trial comparing add-on therapy with ONGLYZA to glipizide in 858 patients inadequately controlled on metformin alone, a trial comparing ONGLYZA to placebo in 455 patients inadequately controlled on insulin alone or on insulin in combination with metformin, a trial comparing ONGLYZA to placebo in 257 patients inadequately controlled on metformin plus a sulfonylurea, and a trial comparing ONGLYZA to placebo in 170 patients with type 2 diabetes and moderate or severe renal impairment or ESRD.
- A total of 766 patients with type 2 diabetes inadequately controlled on diet and exercise (A1C ≥7% to ≤10%) participated in two 24-week, double-blind, placebo-controlled trials evaluating the efficacy and safety of ONGLYZA monotherapy.
- In the first trial, following a 2-week single-blind diet, exercise, and placebo lead-in period, 401 patients were randomized to 2.5 mg, 5 mg, or 10 mg of ONGLYZA or placebo. The 10 mg dosage is not an approved dosage. Patients who failed to meet specific glycemic goals during the study were treated with metformin rescue therapy, added on to placebo or ONGLYZA. Efficacy was evaluated at the last measurement prior to rescue therapy for patients needing rescue. Dose titration of ONGLYZA was not permitted.
- Treatment with ONGLYZA 2.5 mg and 5 mg daily provided significant improvements in A1C, FPG, and PPG compared to placebo (Table 5). The percentage of patients who discontinued for lack of glycemic control or who were rescued for meeting prespecified glycemic criteria was 16% in the ONGLYZA 2.5 mg treatment group, 20% in the ONGLYZA 5 mg treatment group, and 26% in the placebo group.
- A second 24-week monotherapy trial was conducted to assess a range of dosing regimens for ONGLYZA. Treatment-naive patients with inadequately controlled diabetes (A1C ≥7% to ≤10%) underwent a 2-week, single-blind diet, exercise, and placebo lead-in period. A total of 365 patients were randomized to 2.5 mg every morning, 5 mg every morning, 2.5 mg with possible titration to 5 mg every morning, or 5 mg every evening of ONGLYZA, or placebo. Patients who failed to meet specific glycemic goals during the study were treated with metformin rescue therapy added on to placebo or ONGLYZA; the number of patients randomized per treatment group ranged from 71 to 74.
- Treatment with either ONGLYZA 5 mg every morning or 5 mg every evening provided significant improvements in A1C versus placebo (mean placebo-corrected reductions of −0.4% and −0.3%, respectively). Treatment with ONGLYZA 2.5 mg every morning also provided significant improvement in A1C versus placebo (mean placebo-corrected reduction of −0.4%).
- Add-On Combination Therapy with Metformin
- A total of 743 patients with type 2 diabetes participated in this 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of ONGLYZA in combination with metformin in patients with inadequate glycemic control (A1C ≥7% and ≤10%) on metformin alone. To qualify for enrollment, patients were required to be on a stable dose of metformin (1500-2550 mg daily) for at least 8 weeks.
- Patients who met eligibility criteria were enrolled in a single-blind, 2-week, dietary and exercise placebo lead-in period during which patients received metformin at their pre-study dose, up to 2500 mg daily. Following the lead-in period, eligible patients were randomized to 2.5 mg, 5 mg, or 10 mg of ONGLYZA or placebo in addition to their current dose of open-label metformin. The 10 mg dosage is not an approved dosage. Patients who failed to meet specific glycemic goals during the study were treated with pioglitazone rescue therapy, added on to existing study medications. Dose titrations of ONGLYZA and metformin were not permitted.
- ONGLYZA 2.5 mg and 5 mg add-on to metformin provided significant improvements in A1C, FPG, and PPG compared with placebo add-on to metformin (Table 6). Mean changes from baseline for A1C over time and at endpoint are shown in Figure 1. The proportion of patients who discontinued for lack of glycemic control or who were rescued for meeting prespecified glycemic criteria was 15% in the ONGLYZA 2.5 mg add-on to metformin group, 13% in the ONGLYZA 5 mg add-on to metformin group, and 27% in the placebo add-on to metformin group.
- Add-On Combination Therapy with a Thiazolidinedione
- A total of 565 patients with type 2 diabetes participated in this 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of ONGLYZA in combination with a thiazolidinedione (TZD) in patients with inadequate glycemic control (A1C ≥7% to ≤10.5%) on TZD alone. To qualify for enrollment, patients were required to be on a stable dose of pioglitazone (30-45 mg once daily) or rosiglitazone (4 mg once daily or 8 mg either once daily or in two divided doses of 4 mg) for at least 12 weeks.
- Patients who met eligibility criteria were enrolled in a single-blind, 2-week, dietary and exercise placebo lead-in period during which patients received TZD at their pre-study dose. Following the lead-in period, eligible patients were randomized to 2.5 mg or 5 mg of ONGLYZA or placebo in addition to their current dose of TZD. Patients who failed to meet specific glycemic goals during the study were treated with metformin rescue, added on to existing study medications. Dose titration of ONGLYZA or TZD was not permitted during the study. A change in TZD regimen from rosiglitazone to pioglitazone at specified, equivalent therapeutic doses was permitted at the investigator’s discretion if believed to be medically appropriate.
- ONGLYZA 2.5 mg and 5 mg add-on to TZD provided significant improvements in A1C, FPG, and PPG compared with placebo add-on to TZD (Table 7). The proportion of patients who discontinued for lack of glycemic control or who were rescued for meeting prespecified glycemic criteria was 10% in the ONGLYZA 2.5 mg add-on to TZD group, 6% for the ONGLYZA 5 mg add-on to TZD group, and 10% in the placebo add-on to TZD group.
- Add-On Combination Therapy with Glyburide
- A total of 768 patients with type 2 diabetes participated in this 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of ONGLYZA in combination with a sulfonylurea (SU) in patients with inadequate glycemic control at enrollment (A1C ≥7.5% to ≤10%) on a submaximal dose of SU alone. To qualify for enrollment, patients were required to be on a submaximal dose of SU for 2 months or greater. In this study, ONGLYZA in combination with a fixed, intermediate dose of SU was compared to titration to a higher dose of SU.
- Patients who met eligibility criteria were enrolled in a single-blind, 4-week, dietary and exercise lead-in period, and placed on glyburide 7.5 mg once daily. Following the lead-in period, eligible patients with A1C ≥7% to ≤10% were randomized to either 2.5 mg or 5 mg of ONGLYZA add-on to 7.5 mg glyburide or to placebo plus a 10 mg total daily dose of glyburide. Patients who received placebo were eligible to have glyburide up-titrated to a total daily dose of 15 mg. Up-titration of glyburide was not permitted in patients who received ONGLYZA 2.5 mg or 5 mg. Glyburide could be down-titrated in any treatment group once during the 24-week study period due to hypoglycemia as deemed necessary by the investigator. Approximately 92% of patients in the placebo plus glyburide group were up-titrated to a final total daily dose of 15 mg during the first 4 weeks of the study period. Patients who failed to meet specific glycemic goals during the study were treated with metformin rescue, added on to existing study medication. Dose titration of ONGLYZA was not permitted during the study.
- In combination with glyburide, ONGLYZA 2.5 mg and 5 mg provided significant improvements in A1C, FPG, and PPG compared with the placebo plus up-titrated glyburide group (Table 8). The proportion of patients who discontinued for lack of glycemic control or who were rescued for meeting prespecified glycemic criteria was 18% in the ONGLYZA 2.5 mg add-on to glyburide group, 17% in the ONGLYZA 5 mg add-on to glyburide group, and 30% in the placebo plus up-titrated glyburide group.
- Coadministration with Metformin in Treatment-Naive Patients
- A total of 1306 treatment-naive patients with type 2 diabetes mellitus participated in this 24-week, randomized, double-blind, active-controlled trial to evaluate the efficacy and safety of ONGLYZA coadministered with metformin in patients with inadequate glycemic control (A1C ≥8% to ≤12%) on diet and exercise alone. Patients were required to be treatment-naive to be enrolled in this study.
- Patients who met eligibility criteria were enrolled in a single-blind, 1-week, dietary and exercise placebo lead-in period. Patients were randomized to one of four treatment arms: ONGLYZA 5 mg + metformin 500 mg, saxagliptin 10 mg + metformin 500 mg, saxagliptin 10 mg + placebo, or metformin 500 mg + placebo. The 10 mg dosage is not an approved dosage. ONGLYZA was dosed once daily. In the 3 treatment groups using metformin, the metformin dose was up-titrated weekly in 500 mg per day increments, as tolerated, to a maximum of 2000 mg per day based on FPG. Patients who failed to meet specific glycemic goals during the studies were treated with pioglitazone rescue as add-on therapy.
- Coadministration of ONGLYZA 5 mg plus metformin provided significant improvements in A1C, FPG, and PPG compared with placebo plus metformin (Table 9).
- Add-On Combination Therapy with Metformin versus Glipizide Add-On Combination Therapy with Metformin
- In this 52-week, active-controlled trial, a total of 858 patients with type 2 diabetes and inadequate glycemic control (A1C >6.5% and ≤10%) on metformin alone were randomized to double-blind add-on therapy with ONGLYZA or glipizide. Patients were required to be on a stable dose of metformin (at least 1500 mg daily) for at least 8 weeks prior to enrollment.
- Patients who met eligibility criteria were enrolled in a single-blind, 2-week, dietary and exercise placebo lead-in period during which patients received metformin (1500-3000 mg based on their pre-study dose). Following the lead-in period, eligible patients were randomized to 5 mg of ONGLYZA or 5 mg of glipizide in addition to their current dose of open-label metformin. Patients in the glipizide plus metformin group underwent blinded titration of the glipizide dose during the first 18 weeks of the trial up to a maximum glipizide dose of 20 mg per day. Titration was based on a goal FPG ≤110 mg/dL or the highest tolerable glipizide dose. Fifty percent (50%) of the glipizide-treated patients were titrated to the 20-mg daily dose; 21% of the glipizide-treated patients had a final daily glipizide dose of 5 mg or less. The mean final daily dose of glipizide was 15 mg.
- After 52 weeks of treatment, ONGLYZA and glipizide resulted in similar mean reductions from baseline in A1C when added to metformin therapy (Table 10). This conclusion may be limited to patients with baseline A1C comparable to those in the trial (91% of patients had baseline A1C <9%).
- From a baseline mean body weight of 89 kg, there was a statistically significant mean reduction of 1.1 kg in patients treated with ONGLYZA compared to a mean weight gain of 1.1 kg in patients treated with glipizide (p<0.0001).
- Add-On Combination Therapy with Insulin (with or without metformin)
- A total of 455 patients with type 2 diabetes participated in this 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of ONGLYZA in combination with insulin in patients with inadequate glycemic control (A1C ≥7.5% and ≤11%) on insulin alone (N=141) or on insulin in combination with a stable dose of metformin (N=314). Patients were required to be on a stable dose of insulin (≥30 units to ≤150 units daily) with ≤20% variation in total daily dose for ≥8 weeks prior to screening. Patients entered the trial on intermediate- or long-acting (basal) insulin or premixed insulin. Patients using short-acting insulins were excluded unless the short-acting insulin was administered as part of a premixed insulin.
- Patients who met eligibility criteria were enrolled in a single-blind, four-week, dietary and exercise placebo lead-in period during which patients received insulin (and metformin if applicable) at their pretrial dose(s). Following the lead-in period, eligible patients were randomized to add-on therapy with either ONGLYZA 5 mg or placebo. Doses of the antidiabetic therapies were to remain stable but patients were rescued and allowed to adjust the insulin regimen if specific glycemic goals were not met or if the investigator learned that the patient had self-increased the insulin dose by >20%. Data after rescue were excluded from the primary efficacy analyses.
- Add-on therapy with ONGLYZA 5 mg provided significant improvements from baseline to Week 24 in A1C and PPG compared with add-on placebo (Table 11). Similar mean reductions in A1C versus placebo were observed for patients using ONGLYZA 5 mg add-on to insulin alone and ONGLYZA 5 mg add-on to insulin in combination with metformin (−0.4% and −0.4%, respectively). The percentage of patients who discontinued for lack of glycemic control or who were rescued was 23% in the ONGLYZA group and 32% in the placebo group.
- The mean daily insulin dose at baseline was 53 units in patients treated with ONGLYZA 5 mg and 55 units in patients treated with placebo. The mean change from baseline in daily dose of insulin was 2 units for the ONGLYZA 5 mg group and 5 units for the placebo group.
- The change in fasting plasma glucose from baseline to Week 24 was also tested, but was not statistically significant. The percent of patients achieving an A1C <7% was 17% (52/300) with ONGLYZA in combination with insulin compared to 7% (10/149) with placebo. Significance was not tested.
- Add-On Combination Therapy with Metformin plus Sulfonylurea
- A total of 257 patients with type 2 diabetes participated in this 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of ONGLYZA in combination with metformin plus a sulfonylurea in patients with inadequate glycemic control (A1C ≥7% and ≤10%). Patients were to be on a stable combined dose of metformin extended-release or immediate-release (at maximum tolerated dose, with minimum dose for enrollment being 1500 mg) and a sulfonylurea (at maximum tolerated dose, with minimum dose for enrollment being ≥50% of the maximum recommended dose) for ≥8 weeks prior to enrollment.
- Patients who met eligibility criteria were entered in a 2-week enrollment period to allow assessment of inclusion/exclusion criteria. Following the 2-week enrollment period, eligible patients were randomized to either double-blind ONGLYZA (5 mg once daily) or double-blind matching placebo for 24 weeks. During the 24-week double-blind treatment period, patients were to receive metformin and a sulfonylurea at the same constant dose ascertained during enrollment. Sulfonylurea dose could be down titrated once in the case of a major hypoglycemic event or recurring minor hypoglycemic events. In the absence of hypoglycemia, titration (up or down) of study medication during the treatment period was prohibited.
- ONGLYZA in combination with metformin plus a sulfonylurea provided significant improvements in A1C and PPG compared with placebo in combination with metformin plus a sulfonylurea (Table 12). The percentage of patients who discontinued for a lack of glycemic control was 6% in the ONGLYZA group and 5% in the placebo group.
- The change in fasting plasma glucose from baseline to Week 24 was also tested, but was not statistically significant. The percent of patients achieving an A1C <7% was 31% (39/127) with ONGLYZA in combination with metformin plus a sulfonylurea compared to 9% (12/127) with placebo. Significance was not tested.
- Renal Impairment
- A total of 170 patients participated in a 12-week, randomized, double-blind, placebo-controlled trial conducted to evaluate the efficacy and safety of ONGLYZA 2.5 mg once daily compared with placebo in patients with type 2 diabetes and moderate (n=90) or severe (n=41) renal impairment or ESRD (n=39). In this trial, 98% of the patients were using background antidiabetic medications (75% were using insulin and 31% were using oral antidiabetic medications, mostly sulfonylureas).
- After 12 weeks of treatment, ONGLYZA 2.5 mg provided significant improvement in A1C compared to placebo (Table 13). In the subgroup of patients with ESRD, ONGLYZA and placebo resulted in comparable reductions in A1C from baseline to Week 12. This finding is inconclusive because the trial was not adequately powered to show efficacy within specific subgroups of renal impairment.
- After 12 weeks of treatment, the mean change in FPG was −12 mg/dL with ONGLYZA 2.5 mg and −13 mg/dL with placebo. Compared to placebo, the mean change in FPG with ONGLYZA was −12 mg/dL in the subgroup of patients with moderate renal impairment, −4 mg/dL in the subgroup of patients with severe renal impairment, and +44 mg/dL in the subgroup of patients with ESRD. These findings are inconclusive because the trial was not adequately powered to show efficacy within specific subgroups of renal impairment.
# How Supplied
- ONGLYZA® (saxagliptin) tablets have markings on both sides and are available in the strengths and packages listed in Table 14.
- Storage and Handling
- Store at 20°-25°C (68°-77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature].
## Storage
There is limited information regarding Saxagliptin Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
- Healthcare providers should instruct their patients to read the Medication Guide before starting ONGLYZA therapy and to reread it each time the prescription is renewed. Patients should be instructed to inform their healthcare provider if they develop any unusual symptom or if any existing symptom persists or worsens.
- Patients should be informed of the potential risks and benefits of ONGLYZA and of alternative modes of therapy. Patients should also be informed about the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and A1C testing, recognition and management of hypoglycemia and hyperglycemia, and assessment of diabetes complications. During periods of stress such as fever, trauma, infection, or surgery, medication requirements may change and patients should be advised to seek medical advice promptly.
- Pancreatitis
- Patients should be informed that acute pancreatitis has been reported during postmarketing use of ONGLYZA. Before initiating ONGLYZA, patients should be questioned about other risk factors for pancreatitis, such as a history of pancreatitis, alcoholism, gallstones, or hypertriglyceridemia. Patients should also be informed that persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting, is the hallmark symptom of acute pancreatitis. Patients should be instructed to promptly discontinue ONGLYZA and contact their healthcare provider if persistent severe abdominal pain occurs.
- Hypersensitivity Reactions
- Patients should be informed that serious allergic (hypersensitivity) reactions, such as angioedema, anaphylaxis, and exfoliative skin conditions, have been reported during postmarketing use of ONGLYZA. If symptoms of these allergic reactions (such as rash, skin flaking or peeling, urticaria, swelling of the skin, or swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing) occur, patients must stop taking ONGLYZA and seek medical advice promptly.
- Missed Dose
- Patients should be informed that if they miss a dose of ONGLYZA they should take the next dose as prescribed, unless otherwise instructed by their healthcare provider. Patients should be instructed not to take an extra dose the next day.
- Administration Instructions
- Patients should be informed that ONGLYZA tablets must not be split or cut.
- Laboratory Tests
- Patients should be informed that response to all diabetic therapies should be monitored by periodic measurements of blood glucose and A1C, with a goal of decreasing these levels toward the normal range. A1C is especially useful for evaluating long-term glycemic control. Patients should be informed of the potential need to adjust their dose based on changes in renal function tests over time.
# Precautions with Alcohol
- Alcohol-Saxagliptin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- ONGLYZA®[1]
# Look-Alike Drug Names
There is limited information regarding Saxagliptin Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Saxagliptin | |
e42a6bd9792362fe1131f11783ed57fa0613b7ca | wikidoc | Sea anemone | Sea anemone
Sea anemones are a group of water dwelling, predatory animals of the order Actiniaria; they are named after the anemone, a terrestrial flower. As cnidarians, sea anemones are closely related to corals, jellyfish, tube-dwelling anemones and Hydra.
# Anatomy
A sea anemone is a small sac, attached to the bottom by an adhesive foot, with a column shaped body ending in an oral disc. The mouth is in the middle of the oral disc, surrounded by tentacles armed with many cnidocytes, which are cells that function as a defense and as a means to capture prey. Cnidocytes contain cnidae, capsule-like organelles capable of everting, giving phylum Cnidaria its name . The cnidae that sting are called nematocysts. Each nematocyst contains a small vesicle filled with toxins—actinoporins—an inner filament and an external sensory hair. When the hair is touched, it mechanically triggers the cell explosion, a harpoon-like structure which attaches to organisms that trigger it, and injects a dose of poison in the flesh of the aggressor or prey. This gives the anemone its characteristic sticky feeling.
The poison is a mix of toxins, including neurotoxins, which paralyze and capture the prey, which is then moved by the tentacles to the mouth/anus for digestion inside the gastrovascular cavity. Actinoporins have been reported as highly toxic to fish and crustaceans, which may be the natural prey of sea anemones. In addition to their role in predation, it has been suggested that actinoporins could act, when released in water, as repellents against potential predators. Clownfish are immune to an anemone's sting.
The internal anatomy of anemones is simple. There is a gastrovascular cavity (which functions as a stomach) with a single opening to the outside which functions as both a mouth and an anus: waste and undigested matter is excreted through the mouth/anus. A primitive nervous system, without centralization, coordinates the processes involved in maintaining homeostasis as well as biochemical and physical responses to various stimuli. Anemones range in size from less than 1¼ cm (½ in) to nearly 2 m (6 ft) in diameter. They can have a range of 10 tentacles to hundreds.
The muscles and nerves in anemones are much simpler than those of other animals. Cells in the outer layer (epidermis) and the inner layer (gastrodermis) have microfilaments grouped together into contractile fibers. These are not true muscles because they are not freely suspended in the body cavity as they are in more developed animals. Since the anemone lacks a skeleton, the contractile cells pull against the gastrovascular cavity, which acts as a hydrostatic skeleton. The stability for this hydrostatic skeleton is caused by the anemone shutting its mouth, which keeps the gastrovascular cavity at a constant volume, making it more rigid.
# Life cycle
Unlike other cnidarians, anemones (and other anthozoans) entirely lack the free-swimming medusa stage of the life cycle: the polyp produces eggs and sperm, and the fertilized egg develops into a planula that develops directly into another polyp.
A few anemones are parasitic to marine organisms. Anemones tend to stay in the same spot until conditions become unsuitable (prolonged dryness, for example), or a predator is attacking them. In the case of an attack, anemones can release themselves from the substrate and swim away to a new location using flexing motions.
The sexes in sea anemones are separate for some species while some are hermaphroditic. Both sexual and asexual reproduction may occur. In sexual reproduction males release sperm which stimulates females to release eggs, and fertilization occurs. The eggs or sperm are ejected through the mouth. The fertilized egg develops into a planula, which finally settles down and grows into a single anemone. They can also reproduce asexually by budding, binary fission, which involves pulling apart into two halves, and pedal laceration, in which small pieces of the pedal disc break off and regenerate into small anemones.
# Ecology
The sea anemone has a foot which in most species attaches itself to rocks or anchors in the sand. Some species attach to kelp and others are free-swimming. Although not plants and therefore incapable of photosynthesis themselves, many sea anemones form an important facultative symbiotic relationship with certain single-celled green algae species which reside in the animals' gastrodermal cells. These algae may be either zooxanthellae, zoochlorellae or both. The sea anemone benefits from the products of the algae's photosynthesis, namely oxygen and food in the form of glycerol, glucose and alanine; the algae in turn are assured a reliable exposure to sunlight and protection from micro-feeders, which the anemones actively maintain. The algae also benefit by being protected due to the presence of stinging cells called nematacysts, reducing the likelihood of being eaten by herbivores. Most species inhabit tropical reefs, although there are species adapted to relatively cold waters, intertidal reefs, and sand/kelp environments.
# Conservation
Marine aquarists with reef aquariums often seek to acquire anemone and clownfish for their home aquarium. To fulfill the demand, suppliers harvest anemones directly from coral reefs. Anemones reproduce extremely slowly, and are unlikely to replenish themselves in the regions where they have been over-harvested. Their removal can also negatively impact any creatures which share a symbiotic relationship with it, such as clownfish, anemone shrimp, and anemone crabs. For those aquarists who simply desire clownfish, it should be noted that clownfish can live in captivity without anemones.
# Fossil record
Most Actiniaria do not form hard parts that can be recognized as fossils but a few fossils do exist; Mackenzia, from the Middle Cambrian Burgess Shale of Canada, is the oldest fossil identified as a sea anemone.
# Gallery
- Sea anemones
Sea anemones
- A closed sea anemone
A closed sea anemone
- Deep–sea anemone
Deep–sea anemone
- Sea anemones in a "mini-reef" marine aquarium
Sea anemones in a "mini-reef" marine aquarium
- Venus flytrap sea anemone
Venus flytrap sea anemone
- A shrimp living with a Beaded sea anemone
A shrimp living with a Beaded sea anemone
- Actinia fragacea (Strawberry anemone)
Actinia fragacea (Strawberry anemone)
- Clown fish
Clown fish
- File:Sea anemone in tidepools.jpg | Sea anemone
Sea anemones are a group of water dwelling, predatory animals of the order Actiniaria; they are named after the anemone, a terrestrial flower. As cnidarians, sea anemones are closely related to corals, jellyfish, tube-dwelling anemones and Hydra.
# Anatomy
A sea anemone is a small sac, attached to the bottom by an adhesive foot, with a column shaped body ending in an oral disc. The mouth is in the middle of the oral disc, surrounded by tentacles armed with many cnidocytes, which are cells that function as a defense and as a means to capture prey. Cnidocytes contain cnidae, capsule-like organelles capable of everting, giving phylum Cnidaria its name [1]. The cnidae that sting are called nematocysts. Each nematocyst contains a small vesicle filled with toxins—actinoporins—an inner filament and an external sensory hair. When the hair is touched, it mechanically triggers the cell explosion, a harpoon-like structure which attaches to organisms that trigger it, and injects a dose of poison in the flesh of the aggressor or prey. This gives the anemone its characteristic sticky feeling.
The poison is a mix of toxins, including neurotoxins, which paralyze and capture the prey, which is then moved by the tentacles to the mouth/anus for digestion inside the gastrovascular cavity. Actinoporins have been reported as highly toxic to fish and crustaceans, which may be the natural prey of sea anemones. In addition to their role in predation, it has been suggested that actinoporins could act, when released in water, as repellents against potential predators. Clownfish are immune to an anemone's sting.
The internal anatomy of anemones is simple. There is a gastrovascular cavity (which functions as a stomach) with a single opening to the outside which functions as both a mouth and an anus: waste and undigested matter is excreted through the mouth/anus. A primitive nervous system, without centralization, coordinates the processes involved in maintaining homeostasis as well as biochemical and physical responses to various stimuli. Anemones range in size from less than 1¼ cm (½ in) to nearly 2 m (6 ft) in diameter.[citation needed] They can have a range of 10 tentacles to hundreds.
The muscles and nerves in anemones are much simpler than those of other animals. Cells in the outer layer (epidermis) and the inner layer (gastrodermis) have microfilaments grouped together into contractile fibers. These are not true muscles because they are not freely suspended in the body cavity as they are in more developed animals. Since the anemone lacks a skeleton, the contractile cells pull against the gastrovascular cavity, which acts as a hydrostatic skeleton. The stability for this hydrostatic skeleton is caused by the anemone shutting its mouth, which keeps the gastrovascular cavity at a constant volume, making it more rigid.
# Life cycle
Unlike other cnidarians, anemones (and other anthozoans) entirely lack the free-swimming medusa stage of the life cycle: the polyp produces eggs and sperm, and the fertilized egg develops into a planula that develops directly into another polyp.
A few anemones are parasitic to marine organisms. Anemones tend to stay in the same spot until conditions become unsuitable (prolonged dryness, for example), or a predator is attacking them. In the case of an attack, anemones can release themselves from the substrate and swim away to a new location using flexing motions.
The sexes in sea anemones are separate for some species while some are hermaphroditic. Both sexual and asexual reproduction may occur. In sexual reproduction males release sperm which stimulates females to release eggs, and fertilization occurs. The eggs or sperm are ejected through the mouth. The fertilized egg develops into a planula, which finally settles down and grows into a single anemone. They can also reproduce asexually by budding, binary fission, which involves pulling apart into two halves, and pedal laceration, in which small pieces of the pedal disc break off and regenerate into small anemones.
# Ecology
The sea anemone has a foot which in most species attaches itself to rocks or anchors in the sand. Some species attach to kelp and others are free-swimming. Although not plants and therefore incapable of photosynthesis themselves, many sea anemones form an important facultative symbiotic relationship with certain single-celled green algae species which reside in the animals' gastrodermal cells. These algae may be either zooxanthellae, zoochlorellae or both. The sea anemone benefits from the products of the algae's photosynthesis, namely oxygen and food in the form of glycerol, glucose and alanine; the algae in turn are assured a reliable exposure to sunlight and protection from micro-feeders, which the anemones actively maintain. The algae also benefit by being protected due to the presence of stinging cells called nematacysts, reducing the likelihood of being eaten by herbivores. Most species inhabit tropical reefs, although there are species adapted to relatively cold waters, intertidal reefs, and sand/kelp environments.
# Conservation
Template:Inappropriate tone
Marine aquarists with reef aquariums often seek to acquire anemone and clownfish for their home aquarium. To fulfill the demand, suppliers harvest anemones directly from coral reefs. Anemones reproduce extremely slowly, and are unlikely to replenish themselves in the regions where they have been over-harvested. Their removal can also negatively impact any creatures which share a symbiotic relationship with it, such as clownfish, anemone shrimp, and anemone crabs. For those aquarists who simply desire clownfish, it should be noted that clownfish can live in captivity without anemones. [2]
# Fossil record
Most Actiniaria do not form hard parts that can be recognized as fossils but a few fossils do exist; Mackenzia, from the Middle Cambrian Burgess Shale of Canada, is the oldest fossil identified as a sea anemone.
# Gallery
- Sea anemones
Sea anemones
- A closed sea anemone
A closed sea anemone
- Deep–sea anemone
Deep–sea anemone
- Sea anemones in a "mini-reef" marine aquarium
Sea anemones in a "mini-reef" marine aquarium
- Venus flytrap sea anemone
Venus flytrap sea anemone
- A shrimp living with a Beaded sea anemone
A shrimp living with a Beaded sea anemone
- Actinia fragacea (Strawberry anemone)
Actinia fragacea (Strawberry anemone)
- Clown fish
Clown fish
- File:Sea anemone in tidepools.jpg | https://www.wikidoc.org/index.php/Sea_anemone | |
b7a5a079d02932825564c3b9f5db8ec1baa8df88 | wikidoc | Seal finger | Seal finger
Seal finger, also known as sealer's finger and spekk-finger (from the Norwegian for "blubber"), is an infection that afflicts the fingers of sealers and other people who handle pinnipeds, as a result of bites or contact with exposed seal bones; it has also been contracted by exposure to untreated seal pelts. It can cause cellulitis, debilitating joint inflammation, and edema of the bone marrow; historically, seal finger was treated by amputation of the afflicted digits once they became unusable.
The precise nature of the organism responsible for seal finger is unknown, as it has resisted culturing; however, as seal finger can be treated with tetracycline or similar antibiotics, the causative organism is most likely bacterial, or possibly fungal; in 1998, Baker, Ruoff, and Madoff showed that the organism is most likely a species of Mycoplasma called Mycoplasma phocacerebrale. This mycoplasma was isolated in an epidemic of seal disease occurring in the Baltic Sea.
# Notes
- ↑ Baker AS, Ruoff KL, Madoff S.; November, 1998. "Isolation of Mycoplasma species from a patient with seal finger." Clinical Infectious Diseases | Seal finger
Seal finger, also known as sealer's finger and spekk-finger (from the Norwegian for "blubber"), is an infection that afflicts the fingers of sealers and other people who handle pinnipeds, as a result of bites or contact with exposed seal bones; it has also been contracted by exposure to untreated seal pelts. It can cause cellulitis, debilitating joint inflammation, and edema of the bone marrow; historically, seal finger was treated by amputation of the afflicted digits once they became unusable.
The precise nature of the organism responsible for seal finger is unknown, as it has resisted culturing; however, as seal finger can be treated with tetracycline or similar antibiotics, the causative organism is most likely bacterial, or possibly fungal; in 1998, Baker, Ruoff, and Madoff showed that the organism is most likely a species of Mycoplasma called Mycoplasma phocacerebrale. This mycoplasma was isolated in an epidemic of seal disease occurring in the Baltic Sea.
[1]
# Notes
- ↑ Baker AS, Ruoff KL, Madoff S.; November, 1998. "Isolation of Mycoplasma species from a patient with seal finger." Clinical Infectious Diseases
# External links
- State of Alaska Epidemiology Bulletin from 1983
- Alaska Science Forum from 1979
- NOAA document on zoonoses, including seal finger (requires Acrobat Reader)
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Seal_finger | |
8e58c06da4e4094b5d361ed619fb65d6fa8ca67e | wikidoc | Secnidazole | Secnidazole
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Secnidazole is a nitroimidazole antimicrobial that is FDA approved for the treatment of bacterial vaginosis in adult women. Common adverse reactions include vulvo-vaginal candidiasis, headache, nausea, dysgeusia, vomiting, diarrhea, abdominal pain, and vulvovaginal pruritus.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Secnidazole is indicated for the treatment of bacterial vaginosis in adult women.
- The recommended dosage of Secnidazole is a single 2-gram packet of granules taken once orally, without regard to the timing of meals.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Secnidazole Off-Label Guideline-Supported Use and Dosage (Adult) in the drug label.
### Non–Guideline-Supported Use
There is limited information regarding Secnidazole Off-Label Non-Guideline-Supported Use and Dosage (Adult) in the drug label.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Secnidazole FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Secnidazole Off-Label Guideline-Supported Use and Dosage (Pediatric) in the drug label.
### Non–Guideline-Supported Use
There is limited information regarding Secnidazole Off-Label Non-Guideline-Supported Use and Dosage (Pediatric) in the drug label.
# Contraindications
Hypersensitivity
- Secnidazole is contraindicated in patients who have shown hypersensitivity to Secnidazole, other ingredients of the formulation, or other nitroimidazole derivatives.
# Warnings
- The use of Secnidazole may result in vulvo-vaginal candidiasis. In controlled clinical trials of non-pregnant women with bacterial vaginosis, vulvo-vaginal candidiasis developed in 19/197 (9.6%) of subjects who received 2 g Secnidazole and 4/136 (2.9%) subjects who received placebo. Symptomatic vulvo-vaginal candidiasis may require treatment with an antifungal agent.
- Carcinogenicity has been seen in mice and rats treated chronically with nitroimidazole derivatives which are structurally related to Secnidazole. It is unclear if the positive tumor findings in lifetime rodent studies of these nitroimidazoles indicate a risk to patients taking a single dose of Secnidazole to treat bacterial vaginosis. Avoid chronic use of Secnidazole.
- Prescribing Secnidazole in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
# Adverse Reactions
## Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- The safety data described below reflect exposure to 589 patients, of whom 518 received a 2 g dose of Secnidazole. Secnidazole was evaluated in three clinical trials of patients diagnosed with bacterial vaginosis: two placebo-controlled trials (Trial 1 n=215, Trial 2 n=189) and one uncontrolled safety trial (Trial 3 n=321).
- All patients received a single oral dose of study medication or placebo. Trial 1 evaluated a 1 g (this dose is not approved) dose (n=71) and a 2 g dose (n=72) of Secnidazole. Trial 2 evaluated a 2 g dose (n=125). The population was female, aged 15 to 54 years. Patients in the placebo- controlled trials were primarily Black or African American (54%) or Caucasian (41%).
- There were no deaths in the trials. Two patients in Trial 3 discontinued due to vulvovaginal candidiasis in the Secnidazole-treated arm.
Most Common Adverse Reactions
- Among 197 patients treated with a single 2 g dose of Secnidazole in the two placebo-controlled trials, Trial 1 and 2, adverse reactions were reported by approximately 29% of patients. Table 1 displays the most common adverse reactions (≥ 2 % in Secnidazole-treated patients) in these two trials.
- Among the 321 patients in an uncontrolled trial, Trial 3, adverse reactions were reported in 30% of patients. Vulvovaginal candidiasis (8.4%), nausea (5.3%), vomiting (2.5%) and dysgeusia (3.4%) were the most common adverse reactions reported in this trial.
## Postmarketing Experience
- The following adverse reactions have been reported during use of other formulations of Secnidazole 2 g outside of the United States. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Reported adverse reactions were nausea, dysgeusia, abdominal pain, headache, and vomiting.
# Drug Interactions
- Oral Contraceptives
- There was no clinically significant drug interaction between Secnidazole and the combination oral contraceptive, ethinyl estradiol plus norethindrone. Secnidazole can be co-administered with combination oral contraceptives (e.g., ethinyl estradiol plus norethindrone).
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
Risk Summary
- Limited available data with Secnidazole use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. In animal reproduction studies, there were no adverse developmental outcomes when Secnidazole was administered orally to pregnant rats and rabbits during organogenesis at doses up to 4 times the clinical dose.
- The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data (Animal)
- In animal reproduction studies, pregnant rats were dosed orally with Secnidazole during organogenesis (gestational days 6-17) at 100, 300 and 1000 mg/kg/day, up to 4 times the clinical dose based on AUC comparisons. Animals showed no evidence of adverse developmental outcomes, but maternal toxicity (including reduced body weight gain) was observed at and above 300 mg/kg/day. In rabbits, no evidence of adverse developmental outcomes was observed when oral doses of Secnidazole were administered to dams during organogenesis (gestational days 7-20) at doses up to 100 mg/kg/day (about 0.1 times the clinical dose, based on AUC comparisons). Secnidazole was associated with maternal toxicity (reduced food consumption and markedly reduced body weight gain) in dams at 100 mg/kg/day.
- In a peri- and post-natal development study in rats, Secnidazole was administered at 30, 100 and 300 mg/kg/day from Day 6 of gestation through Day 20 of lactation. Secnidazole was not associated with any adverse effects on gestation, parturition, lactation or on subsequent development of first generation (F1) and second generation (F2) offspring at these doses, equivalent to up to 1.4 times the clinical dose based on AUC comparisons. Maternal toxicity (reduced gestational body weight gain) was evident at doses of 100 mg/kg and above (about 0.3 times the clinical dose based on AUC comparisons).
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Secnidazole in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Secnidazole during labor and delivery.
### Nursing Mothers
Risk Summary
- There is no information on the presence of Secnidazole in human milk, the effects on the breast- fed child, or the effects on milk production. Other nitroimidazole derivatives are present in human milk. Because of the potential for serious adverse reactions, including tumorigenicity, advise patients that breastfeeding is not recommended during treatment with Secnidazole and for 96 hours (based on half-life) after administration of Secnidazole.
Clinical Considerations
- A nursing mother may choose to pump and discard her milk during treatment with Secnidazole and for 96 hours after administration of Secnidazole and feed her infant stored human milk or formula.
### Pediatric Use
- The safety and effectiveness of Secnidazole in pediatric patients below the age of 18 years have not been established.
### Geriatic Use
- Clinical studies with Secnidazole did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
### Gender
There is no FDA guidance on the use of Secnidazole with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Secnidazole with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Secnidazole in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Secnidazole in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Secnidazole in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Secnidazole in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Administer without regard to meals.
- Sprinkle entire contents of packet onto applesauce, yogurt, or pudding and consume within 30 minutes without chewing or crunching the granules.
- To aid swallowing the mixture, take a glass of water after administration.
- Granules are not intended to dissolve in liquid.
### Monitoring
- Improvement in the signs and symptoms of bacterial vaginosis may indicate efficacy.
# IV Compatibility
There is limited information regarding the compatibility of Secnidazole and IV administrations.
# Overdosage
There is limited information regarding Secnidazole overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
# Pharmacology
## Mechanism of Action
- Secnidazole is a nitroimidazole antimicrobial drug.
## Structure
## Pharmacodynamics
- Secnidazole exposure-response relationships and the time course of pharmacodynamic response are unknown.
Cardiac Electrophysiology
- The effect of Secnidazole on the QTc interval was evaluated in a Phase 1 randomized, double blind, placebo- and positive-controlled four-period crossover thorough QTc study in 52 healthy adult subjects following single oral granule doses of 2 g and 6 g (3-times the recommended dose). Although there was a positive relationship of the QTc interval with Secnidazole concentrations, there was no clinically relevant increase in the QTc interval following either dose.
## Pharmacokinetics
- A single oral dose of 2 g of Secnidazole in healthy adult female subjects, following an overnight fast and admixed with (4 oz) of applesauce, resulted in a mean (SD) Secnidazole peak plasma concentration (Cmax) of 45.4 (7.64) mcg/mL and mean (SD) systemic exposure (AUC0-inf) of 1331.6 (230.16) mcghr/mL. Median (range) time to peak concentration (Tmax) was 4.0 (3.0-4.0) hours. Following administration of the 2 g dose, mean Secnidazole plasma concentrations decreased to 22.1 mcg/mL at 24 hours, 9.2 mcg/mL at 48 hours, 3.8 mcg/mL at 72 hours, and 1.4 mcg/mL at 96 hours.
Absorption
Effect of Food
- Administration of 2 g of Secnidazole admixed with applesauce followed by ingestion of a high-fat meal (approximately 150 protein calories, 250 carbohydrate calories, and 500-600 fat calories) resulted in no significant change in the rate (Cmax) and extent (AUC) of Secnidazole exposure as compared to administration when admixed with applesauce and taken under fasted conditions. There was no effect of admixing Secnidazole with pudding and yogurt as compared to admixing with applesauce (TABLE 2).
Distribution
- The apparent volume of distribution of Secnidazole is approximately 42 L. The plasma protein binding of Secnidazole is <5%.
Elimination
- The total body clearance of Secnidazole is approximately 25 mL/min. The renal clearance of Secnidazole is approximately 3.9 mL/min.
- The plasma elimination half-life for Secnidazole is approximately 17 hours.
Metabolism
- Secnidazole is metabolized in vitro via oxidation by human hepatic CYP450 enzyme system with ≤ 1% conversion to metabolites.
Excretion
- Approximately 15% of a 2 g oral dose of Secnidazole is excreted as unchanged Secnidazole in the urine.
Drug Interactions
Oral Contraceptives
- Concomitant administration of 2 g of Secnidazole with the combination oral contraceptive (OC), ethinyl estradiol (EE) plus norethindrone (NE), to healthy adult female subjects resulted in a decrease in mean Cmax of EE of 29%, and no significant effect on the mean AUC of EE. Administration of 2 g of Secnidazole 1 day before combination OC administration resulted in no significant effect on mean Cmax or AUC of EE.
- Concomitant administration of 2 g of Secnidazole with the combination OC resulted in no significant effect on mean Cmax and AUC of NE (increases of 13% and 16%, respectively). Administration of 2 g of Secnidazole 1 day before combination OC administration also resulted in no significant effect on mean Cmax and AUC of NE.
Ethanol Metabolism
- In vitro studies showed that Secnidazole had no effect on aldehyde dehydrogenase activity.
## Nonclinical Toxicology
- Nitroimidazoles, which have similar chemical structures to Secnidazole, have been associated with tumors affecting the liver, lungs, mammary, and lymphatic tissues in animals after lifetime exposures. It is unclear if these positive tumor findings in lifetime rodent studies of these nitroimidazoles indicate a risk to patients taking a single dose of Secnidazole to treat bacterial vaginosis.
- Secnidazole was positive in the bacterial reverse mutation assay, but was negative for the rat micronucleus test and mouse lymphoma test.
- In a rat fertility study, females were dosed for two weeks prior to mating until Day 7 of gestation with males that were dosed for a minimum of 28 days before cohabitation. No parental toxicity or adverse effects on mating performance, estrous cycles, fertility or conception was observed at doses of up to the maximum tolerated dose (300 mg/kg/day, approximately 1.4 times the recommended dose based on AUC comparisons).
# Clinical Studies
- Two randomized placebo-controlled clinical trials (Trial 1 and Trial 2) with similar designs were conducted to evaluate the efficacy of Secnidazole 2 gram for the treatment of bacterial vaginosis. A diagnosis of bacterial vaginosis was defined as all of (a) the presence of an off-white (milky or gray), thin, homogeneous vaginal discharge; (b) a vaginal pH ≥ 4.7; (c) the presence of Clue cells ≥ 20% of the total epithelial cells on a microscopic examination of the vaginal saline wet mount; (d) a positive "whiff" test (detection of amine odor on addition of 10% KOH solution to a sample of the vaginal discharge); and (e) a Nugent score ≥ 4.
- Trial 1 enrolled 144 non-pregnant female patients aged 19 to 54 years and Trial 2 enrolled 189 non-pregnant females aged 18 to 54 years. Black or African American subjects in both trials were 54%. Efficacy was assessed by clinical outcome evaluated 21 to 30 days following a single dose of Secnidazole. A clinical responder was defined as "normal" vaginal discharge, negative "whiff" test, and clue cells <20%. Additional endpoints included Nugent score cure (Nugent score of 0-3) and therapeutic outcome. A therapeutic responder was defined as a clinical responder with a Nugent score cure. In Trial 2, the endpoints were also assessed at Day 7-14.
- In both trials, a statistically significantly greater percentage of patients experienced clinical response, Nugent score cure, and therapeutic response at 21 to 30 days following a single dose of Secnidazole compared to placebo. Statistically significant results for the endpoints were also achieved at Day 7-14 in Trial 2.
- The percentage of patients with clinical response was also consistently higher in both trials in the Secnidazole arm compared to placebo among all subsets of patients: number of prior episodes of bacterial vaginosis (≤ 3 episodes and ≥ 4 episodes) in past 12 months, baseline Nugent score (score 4-6 and score 7-10), and race (Black/African American and White). TABLES 3 and 4 describe the efficacy of Secnidazole in the treatment of bacterial vaginosis.
# How Supplied
- Secnidazole Oral Granules, 2 g, consists of off-white to slightly yellowish granules containing Secnidazole. Secnidazole is supplied in a unit-of-use package containing one packet of granules in an individual carton. Each packet contains 4.8 g of granules containing 2 g Secnidazole. Secnidazole is supplied as follows:
- NDC 27437-051-01 carton containing one unit-of-use 2 g packet.
## Storage
- Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
Administration Instructions
- Instruct the patient:
- To sprinkle the entire contents of the packet of Secnidazole onto applesauce, yogurt or pudding and take all the mixture within 30 minutes without chewing or crunching the granules.
- That after consuming the mixture, they may take a glass of water to aid in swallowing.
- That Secnidazole is not intended to be dissolved in any liquid.
- Advise the patient that Secnidazole may be taken without regard to the timing of meals.
Lactation
- Advise women not to breastfeed during treatment with Secnidazole and to discontinue breastfeeding for 96 hours following the administration of Secnidazole. Also, advise a nursing mother that she may choose to pump and discard her milk for 96 hours after administration of Secnidazole and feed her infant stored human milk or formula.
Vulvo-Vaginal Candidiasis
- Advise the patient that use of Secnidazole may result in vulvo-vaginal candidiasis that may require treatment with an antifungal agent.
Drug Resistance
- Patients should be counseled that antibacterial drugs including Secnidazole should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Secnidazole is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Secnidazole or other antibacterial drugs in the future.
# Precautions with Alcohol
Alcohol-Secnidazole interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
# Brand Names
- Solosec
# Look-Alike Drug Names
There is limited information regarding Secnidazole Look-Alike Drug Names in the drug label.
# Drug Shortage Status
Drug Shortage
# Price | Secnidazole
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yashasvi Aryaputra[2];
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Secnidazole is a nitroimidazole antimicrobial that is FDA approved for the treatment of bacterial vaginosis in adult women. Common adverse reactions include vulvo-vaginal candidiasis, headache, nausea, dysgeusia, vomiting, diarrhea, abdominal pain, and vulvovaginal pruritus.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Secnidazole is indicated for the treatment of bacterial vaginosis in adult women.
- The recommended dosage of Secnidazole is a single 2-gram packet of granules taken once orally, without regard to the timing of meals.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Secnidazole Off-Label Guideline-Supported Use and Dosage (Adult) in the drug label.
### Non–Guideline-Supported Use
There is limited information regarding Secnidazole Off-Label Non-Guideline-Supported Use and Dosage (Adult) in the drug label.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Secnidazole FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Secnidazole Off-Label Guideline-Supported Use and Dosage (Pediatric) in the drug label.
### Non–Guideline-Supported Use
There is limited information regarding Secnidazole Off-Label Non-Guideline-Supported Use and Dosage (Pediatric) in the drug label.
# Contraindications
Hypersensitivity
- Secnidazole is contraindicated in patients who have shown hypersensitivity to Secnidazole, other ingredients of the formulation, or other nitroimidazole derivatives.
# Warnings
- The use of Secnidazole may result in vulvo-vaginal candidiasis. In controlled clinical trials of non-pregnant women with bacterial vaginosis, vulvo-vaginal candidiasis developed in 19/197 (9.6%) of subjects who received 2 g Secnidazole and 4/136 (2.9%) subjects who received placebo. Symptomatic vulvo-vaginal candidiasis may require treatment with an antifungal agent.
- Carcinogenicity has been seen in mice and rats treated chronically with nitroimidazole derivatives which are structurally related to Secnidazole. It is unclear if the positive tumor findings in lifetime rodent studies of these nitroimidazoles indicate a risk to patients taking a single dose of Secnidazole to treat bacterial vaginosis. Avoid chronic use of Secnidazole.
- Prescribing Secnidazole in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
# Adverse Reactions
## Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- The safety data described below reflect exposure to 589 patients, of whom 518 received a 2 g dose of Secnidazole. Secnidazole was evaluated in three clinical trials of patients diagnosed with bacterial vaginosis: two placebo-controlled trials (Trial 1 n=215, Trial 2 n=189) and one uncontrolled safety trial (Trial 3 n=321).
- All patients received a single oral dose of study medication or placebo. Trial 1 evaluated a 1 g (this dose is not approved) dose (n=71) and a 2 g dose (n=72) of Secnidazole. Trial 2 evaluated a 2 g dose (n=125). The population was female, aged 15 to 54 years. Patients in the placebo- controlled trials were primarily Black or African American (54%) or Caucasian (41%).
- There were no deaths in the trials. Two patients in Trial 3 discontinued due to vulvovaginal candidiasis in the Secnidazole-treated arm.
Most Common Adverse Reactions
- Among 197 patients treated with a single 2 g dose of Secnidazole in the two placebo-controlled trials, Trial 1 and 2, adverse reactions were reported by approximately 29% of patients. Table 1 displays the most common adverse reactions (≥ 2 % in Secnidazole-treated patients) in these two trials.
- Among the 321 patients in an uncontrolled trial, Trial 3, adverse reactions were reported in 30% of patients. Vulvovaginal candidiasis (8.4%), nausea (5.3%), vomiting (2.5%) and dysgeusia (3.4%) were the most common adverse reactions reported in this trial.
## Postmarketing Experience
- The following adverse reactions have been reported during use of other formulations of Secnidazole 2 g outside of the United States. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Reported adverse reactions were nausea, dysgeusia, abdominal pain, headache, and vomiting.
# Drug Interactions
- Oral Contraceptives
- There was no clinically significant drug interaction between Secnidazole and the combination oral contraceptive, ethinyl estradiol plus norethindrone. Secnidazole can be co-administered with combination oral contraceptives (e.g., ethinyl estradiol plus norethindrone).
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
Risk Summary
- Limited available data with Secnidazole use in pregnant women are insufficient to inform a drug associated risk of adverse developmental outcomes. In animal reproduction studies, there were no adverse developmental outcomes when Secnidazole was administered orally to pregnant rats and rabbits during organogenesis at doses up to 4 times the clinical dose.
- The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data (Animal)
- In animal reproduction studies, pregnant rats were dosed orally with Secnidazole during organogenesis (gestational days 6-17) at 100, 300 and 1000 mg/kg/day, up to 4 times the clinical dose based on AUC comparisons. Animals showed no evidence of adverse developmental outcomes, but maternal toxicity (including reduced body weight gain) was observed at and above 300 mg/kg/day. In rabbits, no evidence of adverse developmental outcomes was observed when oral doses of Secnidazole were administered to dams during organogenesis (gestational days 7-20) at doses up to 100 mg/kg/day (about 0.1 times the clinical dose, based on AUC comparisons). Secnidazole was associated with maternal toxicity (reduced food consumption and markedly reduced body weight gain) in dams at 100 mg/kg/day.
- In a peri- and post-natal development study in rats, Secnidazole was administered at 30, 100 and 300 mg/kg/day from Day 6 of gestation through Day 20 of lactation. Secnidazole was not associated with any adverse effects on gestation, parturition, lactation or on subsequent development of first generation (F1) and second generation (F2) offspring at these doses, equivalent to up to 1.4 times the clinical dose based on AUC comparisons. Maternal toxicity (reduced gestational body weight gain) was evident at doses of 100 mg/kg and above (about 0.3 times the clinical dose based on AUC comparisons).
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Secnidazole in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Secnidazole during labor and delivery.
### Nursing Mothers
Risk Summary
- There is no information on the presence of Secnidazole in human milk, the effects on the breast- fed child, or the effects on milk production. Other nitroimidazole derivatives are present in human milk. Because of the potential for serious adverse reactions, including tumorigenicity, advise patients that breastfeeding is not recommended during treatment with Secnidazole and for 96 hours (based on half-life) after administration of Secnidazole.
Clinical Considerations
- A nursing mother may choose to pump and discard her milk during treatment with Secnidazole and for 96 hours after administration of Secnidazole and feed her infant stored human milk or formula.
### Pediatric Use
- The safety and effectiveness of Secnidazole in pediatric patients below the age of 18 years have not been established.
### Geriatic Use
- Clinical studies with Secnidazole did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
### Gender
There is no FDA guidance on the use of Secnidazole with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Secnidazole with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Secnidazole in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Secnidazole in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Secnidazole in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Secnidazole in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Administer without regard to meals.
- Sprinkle entire contents of packet onto applesauce, yogurt, or pudding and consume within 30 minutes without chewing or crunching the granules.
- To aid swallowing the mixture, take a glass of water after administration.
- Granules are not intended to dissolve in liquid.
### Monitoring
- Improvement in the signs and symptoms of bacterial vaginosis may indicate efficacy.
# IV Compatibility
There is limited information regarding the compatibility of Secnidazole and IV administrations.
# Overdosage
There is limited information regarding Secnidazole overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
# Pharmacology
## Mechanism of Action
- Secnidazole is a nitroimidazole antimicrobial drug.
## Structure
## Pharmacodynamics
- Secnidazole exposure-response relationships and the time course of pharmacodynamic response are unknown.
Cardiac Electrophysiology
- The effect of Secnidazole on the QTc interval was evaluated in a Phase 1 randomized, double blind, placebo- and positive-controlled four-period crossover thorough QTc study in 52 healthy adult subjects following single oral granule doses of 2 g and 6 g (3-times the recommended dose). Although there was a positive relationship of the QTc interval with Secnidazole concentrations, there was no clinically relevant increase in the QTc interval following either dose.
## Pharmacokinetics
- A single oral dose of 2 g of Secnidazole in healthy adult female subjects, following an overnight fast and admixed with (4 oz) of applesauce, resulted in a mean (SD) Secnidazole peak plasma concentration (Cmax) of 45.4 (7.64) mcg/mL and mean (SD) systemic exposure (AUC0-inf) of 1331.6 (230.16) mcg•hr/mL. Median (range) time to peak concentration (Tmax) was 4.0 (3.0-4.0) hours. Following administration of the 2 g dose, mean Secnidazole plasma concentrations decreased to 22.1 mcg/mL at 24 hours, 9.2 mcg/mL at 48 hours, 3.8 mcg/mL at 72 hours, and 1.4 mcg/mL at 96 hours.
Absorption
Effect of Food
- Administration of 2 g of Secnidazole admixed with applesauce followed by ingestion of a high-fat meal (approximately 150 protein calories, 250 carbohydrate calories, and 500-600 fat calories) resulted in no significant change in the rate (Cmax) and extent (AUC) of Secnidazole exposure as compared to administration when admixed with applesauce and taken under fasted conditions. There was no effect of admixing Secnidazole with pudding and yogurt as compared to admixing with applesauce (TABLE 2).
Distribution
- The apparent volume of distribution of Secnidazole is approximately 42 L. The plasma protein binding of Secnidazole is <5%.
Elimination
- The total body clearance of Secnidazole is approximately 25 mL/min. The renal clearance of Secnidazole is approximately 3.9 mL/min.
- The plasma elimination half-life for Secnidazole is approximately 17 hours.
Metabolism
- Secnidazole is metabolized in vitro via oxidation by human hepatic CYP450 enzyme system with ≤ 1% conversion to metabolites.
Excretion
- Approximately 15% of a 2 g oral dose of Secnidazole is excreted as unchanged Secnidazole in the urine.
Drug Interactions
Oral Contraceptives
- Concomitant administration of 2 g of Secnidazole with the combination oral contraceptive (OC), ethinyl estradiol (EE) plus norethindrone (NE), to healthy adult female subjects resulted in a decrease in mean Cmax of EE of 29%, and no significant effect on the mean AUC of EE. Administration of 2 g of Secnidazole 1 day before combination OC administration resulted in no significant effect on mean Cmax or AUC of EE.
- Concomitant administration of 2 g of Secnidazole with the combination OC resulted in no significant effect on mean Cmax and AUC of NE (increases of 13% and 16%, respectively). Administration of 2 g of Secnidazole 1 day before combination OC administration also resulted in no significant effect on mean Cmax and AUC of NE.
Ethanol Metabolism
- In vitro studies showed that Secnidazole had no effect on aldehyde dehydrogenase activity.
## Nonclinical Toxicology
- Nitroimidazoles, which have similar chemical structures to Secnidazole, have been associated with tumors affecting the liver, lungs, mammary, and lymphatic tissues in animals after lifetime exposures. It is unclear if these positive tumor findings in lifetime rodent studies of these nitroimidazoles indicate a risk to patients taking a single dose of Secnidazole to treat bacterial vaginosis.
- Secnidazole was positive in the bacterial reverse mutation assay, but was negative for the rat micronucleus test and mouse lymphoma test.
- In a rat fertility study, females were dosed for two weeks prior to mating until Day 7 of gestation with males that were dosed for a minimum of 28 days before cohabitation. No parental toxicity or adverse effects on mating performance, estrous cycles, fertility or conception was observed at doses of up to the maximum tolerated dose (300 mg/kg/day, approximately 1.4 times the recommended dose based on AUC comparisons).
# Clinical Studies
- Two randomized placebo-controlled clinical trials (Trial 1 and Trial 2) with similar designs were conducted to evaluate the efficacy of Secnidazole 2 gram for the treatment of bacterial vaginosis. A diagnosis of bacterial vaginosis was defined as all of (a) the presence of an off-white (milky or gray), thin, homogeneous vaginal discharge; (b) a vaginal pH ≥ 4.7; (c) the presence of Clue cells ≥ 20% of the total epithelial cells on a microscopic examination of the vaginal saline wet mount; (d) a positive "whiff" test (detection of amine odor on addition of 10% KOH solution to a sample of the vaginal discharge); and (e) a Nugent score ≥ 4.
- Trial 1 enrolled 144 non-pregnant female patients aged 19 to 54 years and Trial 2 enrolled 189 non-pregnant females aged 18 to 54 years. Black or African American subjects in both trials were 54%. Efficacy was assessed by clinical outcome evaluated 21 to 30 days following a single dose of Secnidazole. A clinical responder was defined as "normal" vaginal discharge, negative "whiff" test, and clue cells <20%. Additional endpoints included Nugent score cure (Nugent score of 0-3) and therapeutic outcome. A therapeutic responder was defined as a clinical responder with a Nugent score cure. In Trial 2, the endpoints were also assessed at Day 7-14.
- In both trials, a statistically significantly greater percentage of patients experienced clinical response, Nugent score cure, and therapeutic response at 21 to 30 days following a single dose of Secnidazole compared to placebo. Statistically significant results for the endpoints were also achieved at Day 7-14 in Trial 2.
- The percentage of patients with clinical response was also consistently higher in both trials in the Secnidazole arm compared to placebo among all subsets of patients: number of prior episodes of bacterial vaginosis (≤ 3 episodes and ≥ 4 episodes) in past 12 months, baseline Nugent score (score 4-6 and score 7-10), and race (Black/African American and White). TABLES 3 and 4 describe the efficacy of Secnidazole in the treatment of bacterial vaginosis.
# How Supplied
- Secnidazole Oral Granules, 2 g, consists of off-white to slightly yellowish granules containing Secnidazole. Secnidazole is supplied in a unit-of-use package containing one packet of granules in an individual carton. Each packet contains 4.8 g of granules containing 2 g Secnidazole. Secnidazole is supplied as follows:
- NDC 27437-051-01 carton containing one unit-of-use 2 g packet.
## Storage
- Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
Administration Instructions
- Instruct the patient:
- To sprinkle the entire contents of the packet of Secnidazole onto applesauce, yogurt or pudding and take all the mixture within 30 minutes without chewing or crunching the granules.
- That after consuming the mixture, they may take a glass of water to aid in swallowing.
- That Secnidazole is not intended to be dissolved in any liquid.
- Advise the patient that Secnidazole may be taken without regard to the timing of meals.
Lactation
- Advise women not to breastfeed during treatment with Secnidazole and to discontinue breastfeeding for 96 hours following the administration of Secnidazole. Also, advise a nursing mother that she may choose to pump and discard her milk for 96 hours after administration of Secnidazole and feed her infant stored human milk or formula.
Vulvo-Vaginal Candidiasis
- Advise the patient that use of Secnidazole may result in vulvo-vaginal candidiasis that may require treatment with an antifungal agent.
Drug Resistance
- Patients should be counseled that antibacterial drugs including Secnidazole should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Secnidazole is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Secnidazole or other antibacterial drugs in the future.
# Precautions with Alcohol
Alcohol-Secnidazole interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
# Brand Names
- Solosec
# Look-Alike Drug Names
There is limited information regarding Secnidazole Look-Alike Drug Names in the drug label.
# Drug Shortage Status
Drug Shortage
# Price | https://www.wikidoc.org/index.php/Secnidazole | |
61bd786f522fae5b5046d5fcddd184597dfcc5ba | wikidoc | Secukinumab | Secukinumab
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Secukinumab is a human interleukin-17A antagonist that is FDA approved for the treatment of moderate to severe plaque psoriasis in adult patients. Common adverse reactions include nasopharyngitis, diarrhea, and upper respiratory tract infection.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
### Indications
- COSENTYXTM is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.
### Recommended Dosage
- The recommended dose is 300 mg by subcutaneous injection at Weeks 0, 1, 2, 3, and 4 followed by 300 mg every 4 weeks. Each 300 mg dose is given as 2 subcutaneous injections of 150 mg.
- For some patients, a dose of 150 mg may be acceptable.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Secukinumab in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Secukinumab in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Secukinumab in pediatric patients.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Secukinumab in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Secukinumab in pediatric patients.
# Contraindications
- COSENTYX is contraindicated in patients with a previous serious hypersensitivity reaction to secukinumab or to any of the excipients
# Warnings
- COSENTYX may increase the risk of infections. In clinical trials, a higher rate of infections was observed in COSENTYX-treated subjects compared to placebo-treated subjects. In placebo-controlled clinical trials, higher rates of common infections such as nasopharyngitis (11.4% versus 8.6%), upper respiratory tract infection (2.5% versus 0.7%) and mucocutaneous infections with candida (1.2% versus 0.3%) were observed with COSENTYX compared with placebo. The incidence of some types of infections appeared to be dose-dependent in clinical studies.
- Exercise caution when considering the use of COSENTYX in patients with a chronic infection or a history of recurrent infection.
- Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur. If a patient develops a serious infection, the patient should be closely monitored and COSENTYX should be discontinued until the infection resolves.
- Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with COSENTYX. Do not administer COSENTYX to patients with active TB infection. Initiate treatment of latent TB prior to administering COSENTYX. Consider anti-TB therapy prior to initiation of COSENTYX in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving COSENTYX should be monitored closely for signs and symptoms of active TB during and after treatment.
- Exercise caution when prescribing COSENTYX to patients with active Crohn’s disease, as exacerbations of Crohn’s disease, in some cases serious, were observed in COSENTYX-treated patients during clinical trials. Patients who are treated with COSENTYX and have active Crohn’s disease should be monitored closely.
- Anaphylaxis and cases of urticaria occurred in COSENTYX-treated patients in the clinical trials. If an anaphylactic or other serious allergic reaction occurs, administration of COSENTYX should be discontinued immediately and appropriate therapy initiated.
- The removable cap of the COSENTYX Sensoready pen and the COSENTYX prefilled syringe contains natural rubber latex which may cause an allergic reaction in latex-sensitive individuals. The safe use of COSENTYX Sensoready pen or prefilled syringe in latex-sensitive individuals has not been studied.
- Prior to initiating therapy with COSENTYX, consider completion of all age appropriate immunizations according to current immunization guidelines. Patients treated with COSENTYX should not receive live vaccines.
- Non-live vaccinations received during a course of COSENTYX may not elicit an immune response sufficient to prevent disease.
# Adverse Reactions
## Clinical Trials Experience
### Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- A total of 3430 plaque psoriasis subjects were treated with COSENTYX in controlled and uncontrolled clinical trials. Of these, 1641 subjects were exposed for at least 1 year.
- Four placebo-controlled phase 3 trials in plaque psoriasis subjects were pooled to evaluate the safety of COSENTYX in comparison to placebo up to 12 weeks after treatment initiation, in Trials 1, 2, 3, and 4. In total, 2077 subjects were evaluated (691 to COSENTYX 300 mg group, 692 to COSENTYX 150 mg group, and 694 to placebo group).
- Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the COSENTYX groups than the placebo group during the 12-week placebo-controlled period of the placebo-controlled trials.
- Adverse reactions that occurred at rates less than 1% in the placebo-controlled period of Trials 1, 2, 3, and 4 through Week 12 included: sinusitis, tinea pedis, conjunctivitis, tonsillitis, oral candidiasis, impetigo, otitis media, otitis externa, inflammatory bowel disease, increased liver transaminases and neutropenia.
- In the placebo-controlled period of the clinical trials in plaque psoriasis (a total of 1382 subjects treated with COSENTYX and 694 subjects treated with placebo up to 12 weeks), infections were reported in 28.7% of subjects treated with COSENTYX compared with 18.9% of subjects treated with placebo. Serious infections occurred in 0.14% of patients treated with COSENTYX and in 0.3% of patients treated with placebo.
- Over the entire treatment period (a total of 3430 plaque psoriasis subjects treated with COSENTYX for up to 52 weeks for the majority of subjects), infections were reported in 47.5% of subjects treated with COSENTYX (0.9 per patient-year of follow-up). Serious infections were reported in 1.2% of subjects treated with COSENTYX (0.015 per patient-year of follow-up).
- Phase 3 data showed an increasing trend for some types of infection with increasing serum concentration of secukinumab. Candida infections, herpes viral infections, staphylococcal skin infections, and infections requiring treatment increased as serum concentration of secukinumab increased.
- Neutropenia was observed in clinical trials. Most cases of secukinumab-associated neutropenia were transient and reversible. No serious infections were associated with cases of neutropenia.
- Exacerbation of Crohn’s Disease
- Exacerbations of Crohn’s disease, in some cases serious, were observed in clinical trials in both COSENTYX and placebo treated patients. In the psoriasis program, with 3430 patients exposed to COSENTYX there were 3 cases of exacerbation of Crohn’s disease .
- Anaphylaxis and cases of urticaria occurred in COSENTYX-treated patients in clinical trials.
- As with all therapeutic proteins, there is the potential for immunogenicity. The immunogenicity of COSENTYX was evaluated using an electrochemiluminescence-based bridging immunoassay. Less than 1% of subjects treated with COSENTYX developed antibodies to secukinumab in up to 52 weeks of treatment. However, this assay has limitations in detecting anti-secukinumab antibodies in the presence of secukinumab; therefore the incidence of antibody development might not have been reliably determined. Of the subjects who developed antidrug antibodies, approximately one-half had antibodies that were classified as neutralizing. Neutralizing antibodies were not associated with loss of efficacy.
- The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to COSENTYX with the incidences of antibodies to other products may be misleading.
## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Secukinumab in the drug label.
# Drug Interactions
- Drug interaction trials have not been conducted with COSENTYX.
- Patients treated with COSENTYX may not receive live vaccinations .
- Patients treated with COSENTYX may receive non-live vaccinations. Healthy individuals who received a single 150 mg dose of COSENTYX 2 weeks prior to vaccination with a non-U.S. approved group C meningococcal polysaccharide conjugate vaccine and a non-U.S. approved inactivated seasonal influenza vaccine had similar antibody responses compared to individuals who did not receive COSENTYX prior to vaccination. The clinical effectiveness of meningococcal and influenza vaccines has not been assessed in patients undergoing treatment with COSENTYX.
- A role for IL-17A in the regulation of CYP450 enzymes has not been reported. The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFα, IFN) during chronic inflammation. Thus, COSENTYX, an antagonist of IL-17A, could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of COSENTYX in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect (e.g., for warfarin) or drug concentration (e.g., for cyclosporine) and consider dosage modification of the CYP450 substrate.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): B
- There are no adequate and well controlled trials of COSENTYX in pregnant women. Developmental toxicity studies conducted with monkeys found no evidence of harm to the fetus due to secukinumab. COSENTYX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- An embryofetal development study was performed in cynomolgus monkeys with secukinumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys that were administered secukinumab weekly by the subcutaneous route during the period of organogenesis at doses up to 30 times the maximum recommended human dose (MRHD; on a mg/kg basis at a maternal dose of 150 mg/kg).
- A pre- and postnatal development toxicity study was performed in mice with a murine analog of secukinumab. No treatment related effects on functional, morphological or immunological development were observed in fetuses from pregnant mice that were administered the murine analog of secukinumab on gestation days 6, 11, and 17 and on postpartum days 4, 10, and 16 at doses up to 150 mg/kg/dose.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Secukinumab in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Secukinumab during labor and delivery.
### Nursing Mothers
- It is not known whether secukinumab is excreted in human milk or absorbed systemically after ingestion. Because many drugs are excreted in human milk, caution should be exercised when COSENTYX is administered to a nursing woman.
### Pediatric Use
- Safety and effectiveness of COSENTYX in pediatric patients have not been evaluated.
### Geriatic Use
- Of the 3430 plaque psoriasis subjects exposed to COSENTYX in clinical trials, a total of 230 were 65 years or older, and 32 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 years and older was not sufficient to determine whether they responded differently from younger subjects.
### Gender
There is no FDA guidance on the use of Secukinumab with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Secukinumab with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Secukinumab in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Secukinumab in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Secukinumab in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Secukinumab in patients who are immunocompromised.
# Administration and Monitoring
### Administration
### Important Administration Instructions
- There are three presentations for COSENTYX (i.e., Sensoready pen, prefilled syringe, and lyophilized powder in vial for reconstitution). The COSENTYX “Instructions for Use” for each presentation contains more detailed instructions on the preparation and administration of COSENTYX.
- COSENTYX is intended for use under the guidance and supervision of a physician. Patients may self-inject after proper training in subcutaneous injection technique using the Sensoready pen or prefilled syringe and when deemed appropriate. The lyophilized powder for reconstitution is for healthcare provider use only. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, erythematous, indurated or affected by psoriasis. Administration of COSENTYX in the upper, outer arm may be performed by a caregiver or healthcare provider.
- Before injection, remove COSENTYX Sensoready pen or COSENTYX prefilled syringe from the refrigerator and allow COSENTYX to reach room temperature (15 to 30 minutes) without removing the needle cap.
- The removable cap of the COSENTYX Sensoready pen and the COSENTYX prefilled syringe contains natural rubber latex and should not be handled by latex-sensitive individuals.
- Inspect COSENTYX visually for particulate matter and discoloration prior to administration. COSENTYX injection is a clear to slightly opalescent, colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy. COSENTYX does not contain preservatives; therefore, administer the Sensoready pen or prefilled syringe within 1 hour after removal from the refrigerator. Discard any unused product remaining in the Sensoready pen or prefilled syringe.
- COSENTYX lyophilized powder should be prepared and reconstituted with Sterile Water for Injection by a trained healthcare provider using aseptic technique and without interruption. The preparation time from piercing the stopper until end of reconstitution on average takes 20 minutes and should not exceed 90 minutes.
- Remove the vial of COSENTYX lyophilized powder from the refrigerator and allow to stand for 15 to 30 minutes to reach room temperature. Ensure the Sterile Water for Injection is at room temperature.
- Slowly inject 1 mL of Sterile Water for Injection into the vial containing COSENTYX lyophilized powder and direct the stream of Sterile Water for Injection onto the lyophilized powder.
- Tilt the vial at an angle of approximately 45 degrees and gently rotate between the fingertips for approximately 1 minute. Do not shake or invert the vial.
- Allow the vial to stand for about 10 minutes at room temperature to allow for dissolution. Note that foaming may occur.
- Tilt the vial at an angle of approximately 45 degrees and gently rotate between the fingertips for approximately 1 minute. Do not shake or invert the vial.
- Allow the vial to stand undisturbed at room temperature for approximately 5 minutes. The reconstituted COSENTYX solution should be essentially free of visible particles, clear to opalescent, and colorless to slightly yellow. Do not use if the lyophilized powder has not fully dissolved or if the liquid contains visible particles, is cloudy or discolored.
- Prepare the required number of vials (1 vial for the 150 mg dose or 2 vials for the 300 mg dose).
- The COSENTYX reconstituted solution contains 150 mg of secukinumab in 1 mL of solution. After reconstitution, use the solution immediately or store in the refrigerator at 2ºC to 8ºC (36ºF to 46ºF) for up to 24 hours. Do not freeze.
- If stored at 2ºC to 8ºC (36ºF to 46ºF), allow the reconstituted COSENTYX solution to reach room temperature (15 to 30 minutes) before administration. COSENTYX does not contain preservatives; therefore, administer within 1 hour after removal from 2ºC to 8ºC (36ºF to 46ºF) storage.
### Monitoring
There is limited information regarding Monitoring of Secukinumab in the drug label.
# IV Compatibility
There is limited information regarding IV Compatibility of Secukinumab in the drug label.
# Overdosage
- Doses up to 30 mg/kg intravenously (i.e., approximately 2000 to 3000 mg) have been administered in clinical trials without dose-limiting toxicity. In the event of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted immediately.
# Pharmacology
## Mechanism of Action
- Secukinumab is a human IgG1 monoclonal antibody that selectively binds to the interleukin-17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Secukinumab inhibits the release of proinflammatory cytokines and chemokines.
## Structure
- Secukinumab is a recombinant human monoclonal IgG1/κ antibody that binds specifically to IL-17A. It is expressed in a recombinant Chinese Hamster Ovary (CHO) cell line. Secukinumab has a molecular mass of approximately 151 kDa; both heavy chains of secukinumab contain oligosaccharide chains.
- COSENTYX injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution. COSENTYX is supplied in a single-use Sensoready pen with a 27 gauge fixed ½ inch needle, or a single-use prefilled syringe with a 27 gauge fixed ½ inch needle. The removable cap of the COSENTYX Sensoready pen or prefilled syringe contains natural rubber latex.
- Each COSENTYX Sensoready pen or prefilled syringe contains 150 mg of secukinumab formulated in: L-histidine/histidine hydrochloride monohydrate (3.103 mg), L-methionine (0.746 mg), polysorbate 80 (0.2 mg), trehalose dihydrate (75.67 mg), and Sterile Water for Injection, USP, at pH of 5.8.
- COSENTYX for injection is supplied as a sterile, preservative free, white to slightly yellow, lyophilized powder in single-use vials. Each COSENTYX vial contains 150 mg of secukinumab formulated in L-histidine/L-histidine hydrochloride monohydrate (4.656 mg), polysorbate 80 (0.6 mg), and sucrose (92.43 mg). Following reconstitution with 1 mL Sterile Water for Injection, USP, the resulting pH is approximately 5.8.
## Pharmacodynamics
- Elevated levels of IL-17A are found in psoriatic plaques. Treatment with COSENTYX may reduce epidermal neutrophils and IL-17A levels in psoriatic plaques. Serum levels of total IL-17A (free and secukinumab-bound IL-17A) measured at Week 4 and Week 12 were increased following secukinumab treatment. These pharmacodynamic activities are based on small exploratory studies. The relationship between these pharmacodynamic activities and the mechanism(s) by which secukinumab exerts its clinical effects is unknown.
## Pharmacokinetics
- Following a single subcutaneous dose of either 150 mg (one-half the recommended dose) or 300 mg in plaque psoriasis patients, secukinumab reached peak mean (± SD) serum concentrations (Cmax) of 13.7 ± 4.8 mcg/mL and 27.3 ± 9.5 mcg/mL, respectively, by approximately 6 days post dose.
- Following multiple subcutaneous doses of secukinumab, the mean (± SD) serum trough concentrations of secukinumab ranged from 22.8 ± 10.2 mcg/mL (150 mg) to 45.4 ± 21.2 mcg/mL (300 mg) at Week 12. At the 300 mg dose at Week 4 and Week 12, the mean trough concentrations resulted from the Sensoready pen were 23% to 30% higher than those from the lyophilized powder and 23% to 26% higher than those from the prefilled syringe based on cross-study comparisons.
- Steady-state concentrations of secukinumab were achieved by Week 24 following the every 4 week dosing regimens. The mean (± SD) steady-state trough concentrations ranged from 16.7 ± 8.2 mcg/mL (150 mg) to 34.4 ± 16.6 mcg/mL (300 mg).
- In healthy subjects and subjects with plaque psoriasis, secukinumab bioavailability ranged from 55% to 77% following subcutaneous dose of 150 mg (one-half the recommended dose) or 300 mg.
- The mean volume of distribution during the terminal phase (Vz) following a single intravenous administration ranged from 7.10 to 8.60 L in plaque psoriasis patients. Intravenous use is not recommended .
- Secukinumab concentrations in interstitial fluid in lesional and non-lesional skin of plaque psoriasis patients ranged from 27% to 40% of those in serum at 1 and 2 weeks after a single subcutaneous dose of secukinumab 300 mg.
- The metabolic pathway of secukinumab has not been characterized. As a human IgG1κ monoclonal antibody secukinumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.
- The mean systemic clearance (CL) ranged from 0.14 L/day to 0.22 L/day and the mean half-life ranged from 22 to 31 days in plaque psoriasis subjects following intravenous and subcutaneous administration across all psoriasis trials. Intravenous use is not recommended .
- Secukinumab exhibited dose-proportional pharmacokinetics in subjects with psoriasis over a dose range from 25 mg (approximately 0.083 times the recommended dose) to 300 mg following subcutaneous administrations.
- Secukinumab clearance and volume of distribution increase as body weight increases.
- No formal trial of the effect of hepatic or renal impairment on the pharmacokinetics of secukinumab was conducted.
- Geriatric Population:
- Population pharmacokinetic analysis indicated that the clearance of secukinumab was not significantly influenced by age in adult subjects with plaque psoriasis. Subjects who are 65 years or older had apparent clearance of secukinumab similar to subjects less than 65 years old.
## Nonclinical Toxicology
- Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of COSENTYX. Some published literature suggests that IL-17A directly promotes cancer cell invasion in vitro, whereas other reports indicate IL-17A promotes T-cell mediated tumor rejection. Depletion of IL-17A with a neutralizing antibody inhibited tumor development in mice. The relevance of experimental findings in mouse models for malignancy risk in humans is unknown.
- No effects on fertility were observed in male and female mice that were administered a murine analog of secukinumab at subcutaneous doses up to 150 mg/kg once weekly prior to and during the mating period.
# Clinical Studies
- Four multicenter, randomized, double-blind, placebo-controlled trials (Trials 1, 2, 3, and 4) enrolled 2403 subjects (691 randomized to COSENTYX 300 mg, 692 to COSENTYX 150 mg, 694 to placebo, and 323 to a biologic active control) 18 years of age and older with plaque psoriasis who had a minimum body surface area involvement of 10%, and Psoriasis Area and Severity Index (PASI) score greater than or equal to 12, and who were candidates for phototherapy or systemic therapy.
- Trial 1 enrolled 738 subjects (245 randomized to COSENTYX 300 mg, 245 to COSENTYX 150 mg, and 248 to placebo). Subjects received subcutaneous treatment at Weeks 0, 1, 2, 3, and 4 followed by dosing every 4 weeks. Subjects randomized to COSENTYX received 300 mg or 150 mg doses at Weeks 0, 1, 2, 3, and 4 followed by the same dose every 4 weeks. Subjects randomized to receive placebo that were non-responders at Week 12 were then crossed over to receive COSENTYX (either 300 mg or 150 mg) at Weeks 12, 13, 14, 15, and 16 followed by the same dose every 4 weeks. All subjects were followed for up to 52 weeks following first administration of study treatment.
- Trial 2 enrolled 1306 subjects (327 randomized to COSENTYX 300 mg, 327 to COSENTYX 150 mg, 326 to placebo and 323 to a biologic active control). COSENTYX and placebo data are described. Subjects received subcutaneous treatment at Weeks 0, 1, 2, 3, and 4 followed by dosing every 4 weeks. Subjects randomized to COSENTYX received 300 mg or 150 mg doses at Weeks 0, 1, 2, 3, and 4 followed by the same dose every 4 weeks. Subjects randomized to receive placebo that were non-responders at Week 12 then crossed over to receive COSENTYX (either 300 mg or 150 mg) at Weeks 12, 13, 14, 15, and 16 followed by the same dose every 4 weeks. All subjects were followed for up to 52 weeks following first administration of study treatment.
- Trial 3 enrolled 177 subjects (59 randomized to COSENTYX 300 mg, 59 to COSENTYX 150 mg, and 59 to placebo) and assessed safety, tolerability, and usability of COSENTYX self-administration via prefilled syringe for 12 weeks. Subjects received subcutaneous treatment at Weeks 0, 1, 2, 3, and 4, followed by the same dose every 4 weeks for up to 12 weeks total.
- Trial 4 enrolled 182 subjects (60 randomized to COSENTYX 300 mg, 61 to COSENTYX 150 mg, and 61 to placebo) and assessed safety, tolerability, and usability of COSENTYX self-administration via Sensoready pen for 12 weeks. Subjects received subcutaneous treatment at Weeks 0, 1, 2, 3, and 4, followed by the same dose every 4 weeks for up to 12 weeks total.
Endpoints
- In all trials, the endpoints were the proportion of subjects who achieved a reduction in PASI score of at least 75% (PASI 75) from baseline to Week 12 and treatment success (clear or almost clear) on the Investigator’s Global Assessment modified 2011 (IGA). Other evaluated outcomes included the proportion of subjects who achieved a reduction in PASI score of at least 90% (PASI 90) from baseline at Week 12, maintenance of efficacy to Week 52, and improvements in itching, pain and scaling at Week 12 based on the Psoriasis Symptom Diary©.
- The PASI is a composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of psoriatic changes within the affected regions (induration, erythema and scaling). The IGA is a 5-category scale including “0 = clear” “1 = almost clear”, “2 = mild”, “3 = moderate” or “4 = severe” indicating the physician’s overall assessment of the psoriasis severity focusing on induration, erythema and scaling. Treatment success of “clear” or “almost clear” consisted of no signs of psoriasis or normal to pink coloration of lesions, no thickening of the plaque and none to minimal focal scaling.
- Across all treatment groups the baseline PASI score ranged from 11 to 72 with a median of 20 and the baseline IGA score ranged from “moderate” (62%) to “severe” (38%). Of the 2077 plaque psoriasis subjects who were included in the placebo-controlled trials, 79% were biologic-naïve (have never received a prior treatment with biologics) and 45% were non-biologic failures (failed to respond to a prior treatment with non-biologics therapies). Of the patients who received a prior treatment with biologics, over one-third were biologic failures. Approximately 15% to 25% of trial subjects had a history of psoriatic arthritis.
- The results of Trials 1 and 2 are presented in Table 2.
- Examination of age, gender, and race subgroups did not identify differences in response to COSENTYX among these subgroups. Based on post-hoc sub-group analyses in patients with moderate to severe psoriasis, patients with lower body weight and lower disease severity may achieve an acceptable response with COSENTYX 150 mg.
- PASI 90 response at Week 12 was achieved with COSENTYX 300 mg and 150 mg compared to placebo in 59% (145/245) and 39% (95/245) versus 1% (3/248) of subjects, respectively (Trial 1) and 54% (175/327) and 42% (137/327) versus 2% (5/326) of subjects, respectively (Trial 2). Similar results were seen in Trials 3 and 4.
- With continued treatment over 52 weeks, subjects in Trial 1 who were PASI 75 responders at Week 12 maintained their responses in 81% (161/200) of the subjects treated with COSENTYX 300 mg and in 72% (126/174) of subjects treated with COSENTYX 150 mg. Trial 1 subjects who were clear or almost clear on the IGA at Week 12 also maintained their responses in 74% (119/160) of subjects treated with COSENTYX 300 mg and in 59% (74/125) of subjects treated with COSENTYX 150 mg. Similarly in Trial 2, PASI 75 responders maintained their responses in 84% (210/249) of subjects treated with COSENTYX 300 mg and in 82% (180/219) of subjects treated with COSENTYX 150 mg. Trial 2 subjects who were clear or almost clear on the IGA also maintained their responses in 80% (161/202) of subjects treated with COSENTYX 300 mg and in 68% (113/167) of subjects treated with COSENTYX 150 mg.
- Among the subjects who chose to participate (39%) in assessments of patient reported outcomes, improvements in signs and symptoms related to itching, pain, and scaling, at Week 12 compared to placebo (Trials 1 and 2) were observed using the Psoriasis Symptom Diary©.
# How Supplied
- COSENTYX Sensoready pen:
- COSENTYX prefilled syringe:
- The removable cap of the COSENTYX Sensoready pen and prefilled syringe contains natural rubber latex. Each Sensoready pen and prefilled syringe is equipped with a needle safety guard.
- COSENTYX vial (for healthcare professional use only):
## Storage
- COSENTYX Sensoready pens, prefilled syringes and vials must be refrigerated at 2ºC to 8ºC (36ºF to 46ºF). Keep the product in the original carton to protect from light until the time of use. Do not freeze. To avoid foaming do not shake. COSENTYX does not contain a preservative; discard any unused portion.
# Images
## Drug Images
## Package and Label Display Panel
### PRINCIPAL DISPLAY PANEL
COSENTYXTM
(secukinumab)
Injection
150 mg/mL
1 Prefilled Syringe
NDC 0078-0639-97
Single-use Prefilled Syringe
ATTENTION: Dispense with enclosed Medication Guide
For Subcutaneous Use Only
Sterile Solution - Contains No Preservative
Caution: Contains Natural Rubber Latex Which May Cause Allergic Reaction.
Rx only
### Ingredients and Appearance
# Patient Counseling Information
- Advise the patient to read FDA-approved patient labeling .
- Instruct patients to read the Medication Guide before starting COSENTYX therapy and to reread the Medication Guide each time the prescription is renewed.
- Advise patients of the potential benefits and risks of COSENTYX.
- Inform patients that COSENTYX may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to the doctor and contacting their doctor if they develop any symptoms of infection .
- Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions .
- Perform the first self-injection under the supervision of a qualified healthcare professional. If a patient or caregiver is to administer COSENTYX, instruct him/her in injection techniques and assess their ability to inject subcutaneously to ensure the proper administration of COSENTYX .
- Instruct patients or caregivers in the technique of proper syringe and needle disposal, and advise them not to reuse these items. Instruct patients to inject the full amount of COSENTYX (1 or 2 subcutaneous injections of 150 mg) according to the directions provided in the Medication Guide and Instructions for Use. Dispose of needles, syringes and pens in a puncture-resistant container.
### MEDICATION GUIDE
- COSENTYX is a medicine that affects your immune system. COSENTYX may increase your risk of having serious side effects such as:
- Infections. COSENTYX may lower the ability of your immune system to fight infections and may increase your risk of infections.
- Your healthcare provider should check you for tuberculosis (TB) before starting treatment with COSENTYX.
- If your healthcare provider feels that you are at risk for TB, you may be treated with medicine for TB before you begin treatment with COSENTYX and during treatment with COSENTYX.
- Your healthcare provider should watch you closely for signs and symptoms of TB during treatment with COSENTYX. Do not take COSENTYX if you have an active TB infection.
- are being treated for an infection
- have an infection that does not go away or that keeps coming back
- have TB or have been in close contact with someone with TB
- think you have an infection or have symptoms of an infection such as:
- fever, sweats, or chills
- muscle aches
- cough
- shortness of breath
- blood in your phlegm
- weight loss
- warm, red, or painful skin or sores on your body
- diarrhea or stomach pain
- burning when you urinate or urinate more often than normal
- After starting COSENTYX, call your healthcare provider right away if you have any of the signs of infection listed above. Do not use COSENTYX if you have any signs of infection unless you are instructed to by your healthcare provider.
- See “What are the possible side effects of COSENTYX?” for more information about side effects.
- COSENTYX is a prescription medicine used to treat adults:
- with moderate to severe plaque psoriasis that involves large areas or many areas of the body, and
- who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet or UV light alone or with systemic therapy)
- COSENTYX may improve your psoriasis but it may also lower the ability of your immune system to fight infections.
- It is not known if COSENTYX is safe and effective in children.
- Do not use COSENTYX if you have had a severe allergic reaction to secukinumab or any of the other ingredients in COSENTYX. See the end of this Medication Guide for a complete list of ingredients in COSENTYX.
- Before starting COSENTYX, tell your healthcare provider if you:
- have any of the conditions or symptoms listed in the section “What is the most important information I should know about COSENTYX?”
- have Crohn’s disease
- are allergic to latex. The needle cap on the COSENTYX Sensoready® pen and prefilled syringe contains latex.
- have recently received or are scheduled to receive an immunization (vaccine). People who take COSENTYX should not receive live vaccines.
- have any other medical conditions
- are pregnant or plan to become pregnant. It is not known if COSENTYX can harm your unborn baby. You and your healthcare provider should decide if you will use COSENTYX.
- are breastfeeding or plan to breastfeed. It is not known if COSENTYX passes into your breast milk.
- Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
- Know the medicines you take. Keep a list of your medicines to show your healthcare provider and pharmacist when you get a new medicine.
- See the detailed “Instructions for Use” that comes with your COSENTYX for information on how to prepare and inject a dose of COSENTYX, and how to properly throw away (dispose of) used COSENTYX Sensoready pens and prefilled syringes.
- Use COSENTYX exactly as prescribed by your healthcare provider.
- If your healthcare provider decides that you or a caregiver may give your injections of COSENTYX at home, you should receive training on the right way to prepare and inject COSENTYX. Do not try to inject COSENTYX yourself, until you or your caregiver has been shown how to inject COSENTYX by your healthcare provider.
- COSENTYX comes in a Sensoready pen or prefilled syringe that you or your caregiver may use at home to give injections. Your healthcare provider will decide which type of COSENTYX is best for you to use at home.
- Your healthcare provider will prescribe the dose of COSENTYX that is right for you.
- If your prescribed dose of COSENTYX is 150 mg, you must give 1 injection of COSENTYX for each dose.
- If your prescribed dose of COSENTYX is 300 mg, you must give 2 injections for each dose.
- COSENTYX is given as an injection under your skin (subcutaneous injection), in your upper legs (thighs) or stomach-area (abdomen) by you or a caregiver. A caregiver may also give you an injection of COSENTYX in your upper outer arm.
- Do not give an injection in an area of the skin that is tender, bruised, red or hard, or in an area of skin that is affected by psoriasis.
- Each injection should be given at a different site. Do not use the 2 inch area around your navel (belly button).
- If you inject more COSENTYX than prescribed, call your healthcare provider or go to the nearest emergency room right away.
- COSENTYX may cause serious side effects, including:
- See “What is the most important information I should know about COSENTYX?”
- Crohn’s disease “flare-ups” (worsening Crohn’s disease). Crohn’s disease “flare-ups” can happen with COSENTYX, and can sometimes be serious. If you have Crohn’s disease, tell your healthcare provider if you have worsening Crohn’s disease symptoms during treatment with COSENTYX.
- Serious allergic reactions. Get emergency medical help right away if you get any of the following symptoms of a serious allergic reaction:
- feel faint
- swelling of your face, eyelids, lips, mouth, tongue, or throat
- trouble breathing or throat tightness
- chest tightness
- skin rash
- If you have a severe allergic reaction, do not give another injection of COSENTYX.
- The most common side effects of COSENTYX include:
- cold symptoms
- diarrhea
- upper respiratory infections
- These are not all of the possible side effects of COSENTYX. Tell your healthcare provider about any side effect that bothers you or that does not go away. For more information, ask your healthcare provider or pharmacist.
- Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
- Store COSENTYX in a refrigerator, between 36°F to 46°F (2°C to 8°C).
- Keep COSENTYX in the original carton until ready for use to protect from light.
- Do not freeze COSENTYX.
- Do not shake COSENTYX.
- Keep COSENTYX and all medicines out of the reach of children.
- Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use COSENTYX for a condition for which it was not prescribed. Do not give COSENTYX to other people, even if they have the same symptoms you have. It may harm them.
- If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about COSENTYX that is written for health professionals.
- For more information, call 1-888-669-6682 or go to www.COSENTYX.com.
- Active ingredient: secukinumab
- Inactive ingredients:
- Sensoready pen and prefilled syringe: L-histidine/histidine hydrochloride monohydrate, L-methionine, polysorbate 80, trehalose dihydrate, and sterile water for injection.
- Vial: L-histidine/histidine hydrochloride monohydrate, polysorbate 80, and sucrose.
- This Medication Guide has been approved by the U.S. Food and Drug Administration.
### INSTRUCTIONS FOR USE
INSTRUCTIONS FOR USE
COSENTYXTM (koe-sen’-tix)
(secukinumab)
For Injection
The following information is intended for medical or healthcare professionals only.
IMPORTANT:
- The single-use vial contains 150 mg of COSENTYX for reconstitution with Sterile Water for Injection (SWFI). Do not use the vial after the expiry date shown on the outer box or vial. If it has expired, return the entire pack to the pharmacy.
- The preparation of the solution for subcutaneous injection shall be done without interruption ensuring that aseptic technique is used. The preparation time from piercing the stopper until end of reconstitution on average takes 20 minutes and should not exceed 90 minutes.
- Throw away (dispose of) the used syringe right away after use. Do not re-use a syringe. See “How should I dispose of a used syringe?” at the end of this Instructions for Use.
- Store the vial of COSENTYX in the refrigerator between 2°C to 8°C (36°F to 46°F).
- To prepare COSENTYX 150 mg for injection, please adhere to the following instructions:
- Instructions for reconstitution of COSENTYX 150 mg for injection:
INSTRUCTIONS FOR USE
COSENTYXTM (koe-sen’-tix)
(secukinumab)
Injection
Prefilled Syringe
- Be sure that you read, understand, and follow this Instructions for Use before injecting COSENTYX. Your healthcare provider should show you how to prepare and inject COSENTYX properly using the prefilled syringe before you use it for the first time. Talk to your healthcare provider if you have any questions.
Important:
- Do not use the COSENTYX prefilled syringe if either the seal on the outside carton or the seal of the blister are broken. Keep the COSENTYX prefilled syringe in the sealed carton until you are ready to use it.
- Inject COSENTYX within 1 hour after taking it out of the refrigerator.
- Do not shake the COSENTYX prefilled syringe.
- The needle caps of the prefilled syringes contain latex. Do not handle the prefilled syringes if you are sensitive to latex.
- The prefilled syringe has a needle guard that will be activated to cover the needle after the injection is finished. The needle guard will help to prevent needle stick injuries to anyone who handles the prefilled syringe.
- Do not remove the needle cap until just before you give the injection.
- Avoid touching the syringe guard wings before use. Touching them may cause the syringe guard to be activated too early.
- Throw away (dispose of) the used COSENTYX prefilled syringe right away after use. Do not re-use a COSENTYX prefilled syringe. See “How should I dispose of used COSENTYX prefilled syringes?” at the end of this Instructions for Use.
- Store your carton of COSENTYX prefilled syringes in a refrigerator, between 36°F to 46°F (2°C to 8°C).
- Keep COSENTYX prefilled syringes in the original carton until ready to use to protect from light.
- Do not freeze COSENTYX prefilled syringes.
Keep COSENTYX and all medicines out of the reach of children.
INSTRUCTIONS FOR USE
COSENTYXTM (koe-sen’-tix)
(secukinumab)
Injection
Sensoready® Pen
Be sure that you read, understand, and follow this Instructions for Use before injecting COSENTYX. Your healthcare provider should show you how to prepare and inject COSENTYX properly using the Sensoready Pen before you use it for the first time. Talk to your healthcare provider if you have any questions.
Important:
- Do not use the COSENTYX Sensoready Pen if either the seal on the outer carton or the seal on the pen is broken. Keep the COSENTYX Sensoready Pen in the sealed outer carton until you are ready to use it.
- Inject COSENTYX within 1 hour after taking it out of the refrigerator.
- Do not shake the COSENTYX Sensoready Pen.
- The caps of the Sensoready Pens contain latex. Do not handle the Sensoready Pens if you are sensitive to latex.
- If you drop your COSENTYX Sensoready Pen, do not use it if the Sensoready Pen looks damaged, or if you dropped it with the cap removed.
- Throw away (dispose of) the used COSENTYX Sensoready Pen right away after use. Do not re-use a COSENTYX Sensoready Pen. See “How should I dispose of used COSENTYX Sensoready Pens?” at the end of this Instructions for Use.
How should I store COSENTYX?
- Store your carton of COSENTYX Sensoready Pen in a refrigerator, between 36°F to 46°F (2°C to 8°C).
- Keep COSENTYX Sensoready Pen in the original carton until ready to use to protect from light.
- Do not freeze COSENTYX Sensoready Pen.
- Keep COSENTYX and all medicines out of the reach of children.
# Precautions with Alcohol
- Alcohol-Secukinumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- COSENTYX ®
# Look-Alike Drug Names
There is limited information regarding Secukinumab Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Secukinumab
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rabin Bista, M.B.B.S. [2]
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Secukinumab is a human interleukin-17A antagonist that is FDA approved for the treatment of moderate to severe plaque psoriasis in adult patients. Common adverse reactions include nasopharyngitis, diarrhea, and upper respiratory tract infection.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
### Indications
- COSENTYXTM is indicated for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.
### Recommended Dosage
- The recommended dose is 300 mg by subcutaneous injection at Weeks 0, 1, 2, 3, and 4 followed by 300 mg every 4 weeks. Each 300 mg dose is given as 2 subcutaneous injections of 150 mg.
- For some patients, a dose of 150 mg may be acceptable.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Secukinumab in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Secukinumab in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Secukinumab in pediatric patients.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Secukinumab in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Secukinumab in pediatric patients.
# Contraindications
- COSENTYX is contraindicated in patients with a previous serious hypersensitivity reaction to secukinumab or to any of the excipients
# Warnings
- COSENTYX may increase the risk of infections. In clinical trials, a higher rate of infections was observed in COSENTYX-treated subjects compared to placebo-treated subjects. In placebo-controlled clinical trials, higher rates of common infections such as nasopharyngitis (11.4% versus 8.6%), upper respiratory tract infection (2.5% versus 0.7%) and mucocutaneous infections with candida (1.2% versus 0.3%) were observed with COSENTYX compared with placebo. The incidence of some types of infections appeared to be dose-dependent in clinical studies.
- Exercise caution when considering the use of COSENTYX in patients with a chronic infection or a history of recurrent infection.
- Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur. If a patient develops a serious infection, the patient should be closely monitored and COSENTYX should be discontinued until the infection resolves.
- Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with COSENTYX. Do not administer COSENTYX to patients with active TB infection. Initiate treatment of latent TB prior to administering COSENTYX. Consider anti-TB therapy prior to initiation of COSENTYX in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving COSENTYX should be monitored closely for signs and symptoms of active TB during and after treatment.
- Exercise caution when prescribing COSENTYX to patients with active Crohn’s disease, as exacerbations of Crohn’s disease, in some cases serious, were observed in COSENTYX-treated patients during clinical trials. Patients who are treated with COSENTYX and have active Crohn’s disease should be monitored closely.
- Anaphylaxis and cases of urticaria occurred in COSENTYX-treated patients in the clinical trials. If an anaphylactic or other serious allergic reaction occurs, administration of COSENTYX should be discontinued immediately and appropriate therapy initiated.
- The removable cap of the COSENTYX Sensoready pen and the COSENTYX prefilled syringe contains natural rubber latex which may cause an allergic reaction in latex-sensitive individuals. The safe use of COSENTYX Sensoready pen or prefilled syringe in latex-sensitive individuals has not been studied.
- Prior to initiating therapy with COSENTYX, consider completion of all age appropriate immunizations according to current immunization guidelines. Patients treated with COSENTYX should not receive live vaccines.
- Non-live vaccinations received during a course of COSENTYX may not elicit an immune response sufficient to prevent disease.
# Adverse Reactions
## Clinical Trials Experience
### Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- A total of 3430 plaque psoriasis subjects were treated with COSENTYX in controlled and uncontrolled clinical trials. Of these, 1641 subjects were exposed for at least 1 year.
- Four placebo-controlled phase 3 trials in plaque psoriasis subjects were pooled to evaluate the safety of COSENTYX in comparison to placebo up to 12 weeks after treatment initiation, in Trials 1, 2, 3, and 4. In total, 2077 subjects were evaluated (691 to COSENTYX 300 mg group, 692 to COSENTYX 150 mg group, and 694 to placebo group).
- Table 1 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the COSENTYX groups than the placebo group during the 12-week placebo-controlled period of the placebo-controlled trials.
- Adverse reactions that occurred at rates less than 1% in the placebo-controlled period of Trials 1, 2, 3, and 4 through Week 12 included: sinusitis, tinea pedis, conjunctivitis, tonsillitis, oral candidiasis, impetigo, otitis media, otitis externa, inflammatory bowel disease, increased liver transaminases and neutropenia.
- In the placebo-controlled period of the clinical trials in plaque psoriasis (a total of 1382 subjects treated with COSENTYX and 694 subjects treated with placebo up to 12 weeks), infections were reported in 28.7% of subjects treated with COSENTYX compared with 18.9% of subjects treated with placebo. Serious infections occurred in 0.14% of patients treated with COSENTYX and in 0.3% of patients treated with placebo.
- Over the entire treatment period (a total of 3430 plaque psoriasis subjects treated with COSENTYX for up to 52 weeks for the majority of subjects), infections were reported in 47.5% of subjects treated with COSENTYX (0.9 per patient-year of follow-up). Serious infections were reported in 1.2% of subjects treated with COSENTYX (0.015 per patient-year of follow-up).
- Phase 3 data showed an increasing trend for some types of infection with increasing serum concentration of secukinumab. Candida infections, herpes viral infections, staphylococcal skin infections, and infections requiring treatment increased as serum concentration of secukinumab increased.
- Neutropenia was observed in clinical trials. Most cases of secukinumab-associated neutropenia were transient and reversible. No serious infections were associated with cases of neutropenia.
- Exacerbation of Crohn’s Disease
- Exacerbations of Crohn’s disease, in some cases serious, were observed in clinical trials in both COSENTYX and placebo treated patients. In the psoriasis program, with 3430 patients exposed to COSENTYX there were 3 cases of exacerbation of Crohn’s disease .
- Anaphylaxis and cases of urticaria occurred in COSENTYX-treated patients in clinical trials.
- As with all therapeutic proteins, there is the potential for immunogenicity. The immunogenicity of COSENTYX was evaluated using an electrochemiluminescence-based bridging immunoassay. Less than 1% of subjects treated with COSENTYX developed antibodies to secukinumab in up to 52 weeks of treatment. However, this assay has limitations in detecting anti-secukinumab antibodies in the presence of secukinumab; therefore the incidence of antibody development might not have been reliably determined. Of the subjects who developed antidrug antibodies, approximately one-half had antibodies that were classified as neutralizing. Neutralizing antibodies were not associated with loss of efficacy.
- The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to COSENTYX with the incidences of antibodies to other products may be misleading.
## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Secukinumab in the drug label.
# Drug Interactions
- Drug interaction trials have not been conducted with COSENTYX.
- Patients treated with COSENTYX may not receive live vaccinations [see Warnings and Precautions (5.6)].
- Patients treated with COSENTYX may receive non-live vaccinations. Healthy individuals who received a single 150 mg dose of COSENTYX 2 weeks prior to vaccination with a non-U.S. approved group C meningococcal polysaccharide conjugate vaccine and a non-U.S. approved inactivated seasonal influenza vaccine had similar antibody responses compared to individuals who did not receive COSENTYX prior to vaccination. The clinical effectiveness of meningococcal and influenza vaccines has not been assessed in patients undergoing treatment with COSENTYX.
- A role for IL-17A in the regulation of CYP450 enzymes has not been reported. The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNFα, IFN) during chronic inflammation. Thus, COSENTYX, an antagonist of IL-17A, could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of COSENTYX in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect (e.g., for warfarin) or drug concentration (e.g., for cyclosporine) and consider dosage modification of the CYP450 substrate.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): B
- There are no adequate and well controlled trials of COSENTYX in pregnant women. Developmental toxicity studies conducted with monkeys found no evidence of harm to the fetus due to secukinumab. COSENTYX should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- An embryofetal development study was performed in cynomolgus monkeys with secukinumab. No malformations or embryofetal toxicity were observed in fetuses from pregnant monkeys that were administered secukinumab weekly by the subcutaneous route during the period of organogenesis at doses up to 30 times the maximum recommended human dose (MRHD; on a mg/kg basis at a maternal dose of 150 mg/kg).
- A pre- and postnatal development toxicity study was performed in mice with a murine analog of secukinumab. No treatment related effects on functional, morphological or immunological development were observed in fetuses from pregnant mice that were administered the murine analog of secukinumab on gestation days 6, 11, and 17 and on postpartum days 4, 10, and 16 at doses up to 150 mg/kg/dose.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Secukinumab in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Secukinumab during labor and delivery.
### Nursing Mothers
- It is not known whether secukinumab is excreted in human milk or absorbed systemically after ingestion. Because many drugs are excreted in human milk, caution should be exercised when COSENTYX is administered to a nursing woman.
### Pediatric Use
- Safety and effectiveness of COSENTYX in pediatric patients have not been evaluated.
### Geriatic Use
- Of the 3430 plaque psoriasis subjects exposed to COSENTYX in clinical trials, a total of 230 were 65 years or older, and 32 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 years and older was not sufficient to determine whether they responded differently from younger subjects.
### Gender
There is no FDA guidance on the use of Secukinumab with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Secukinumab with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Secukinumab in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Secukinumab in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Secukinumab in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Secukinumab in patients who are immunocompromised.
# Administration and Monitoring
### Administration
### Important Administration Instructions
- There are three presentations for COSENTYX (i.e., Sensoready pen, prefilled syringe, and lyophilized powder in vial for reconstitution). The COSENTYX “Instructions for Use” for each presentation contains more detailed instructions on the preparation and administration of COSENTYX.
- COSENTYX is intended for use under the guidance and supervision of a physician. Patients may self-inject after proper training in subcutaneous injection technique using the Sensoready pen or prefilled syringe and when deemed appropriate. The lyophilized powder for reconstitution is for healthcare provider use only. Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, erythematous, indurated or affected by psoriasis. Administration of COSENTYX in the upper, outer arm may be performed by a caregiver or healthcare provider.
- Before injection, remove COSENTYX Sensoready pen or COSENTYX prefilled syringe from the refrigerator and allow COSENTYX to reach room temperature (15 to 30 minutes) without removing the needle cap.
- The removable cap of the COSENTYX Sensoready pen and the COSENTYX prefilled syringe contains natural rubber latex and should not be handled by latex-sensitive individuals.
- Inspect COSENTYX visually for particulate matter and discoloration prior to administration. COSENTYX injection is a clear to slightly opalescent, colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy. COSENTYX does not contain preservatives; therefore, administer the Sensoready pen or prefilled syringe within 1 hour after removal from the refrigerator. Discard any unused product remaining in the Sensoready pen or prefilled syringe.
- COSENTYX lyophilized powder should be prepared and reconstituted with Sterile Water for Injection by a trained healthcare provider using aseptic technique and without interruption. The preparation time from piercing the stopper until end of reconstitution on average takes 20 minutes and should not exceed 90 minutes.
- Remove the vial of COSENTYX lyophilized powder from the refrigerator and allow to stand for 15 to 30 minutes to reach room temperature. Ensure the Sterile Water for Injection is at room temperature.
- Slowly inject 1 mL of Sterile Water for Injection into the vial containing COSENTYX lyophilized powder and direct the stream of Sterile Water for Injection onto the lyophilized powder.
- Tilt the vial at an angle of approximately 45 degrees and gently rotate between the fingertips for approximately 1 minute. Do not shake or invert the vial.
- Allow the vial to stand for about 10 minutes at room temperature to allow for dissolution. Note that foaming may occur.
- Tilt the vial at an angle of approximately 45 degrees and gently rotate between the fingertips for approximately 1 minute. Do not shake or invert the vial.
- Allow the vial to stand undisturbed at room temperature for approximately 5 minutes. The reconstituted COSENTYX solution should be essentially free of visible particles, clear to opalescent, and colorless to slightly yellow. Do not use if the lyophilized powder has not fully dissolved or if the liquid contains visible particles, is cloudy or discolored.
- Prepare the required number of vials (1 vial for the 150 mg dose or 2 vials for the 300 mg dose).
- The COSENTYX reconstituted solution contains 150 mg of secukinumab in 1 mL of solution. After reconstitution, use the solution immediately or store in the refrigerator at 2ºC to 8ºC (36ºF to 46ºF) for up to 24 hours. Do not freeze.
- If stored at 2ºC to 8ºC (36ºF to 46ºF), allow the reconstituted COSENTYX solution to reach room temperature (15 to 30 minutes) before administration. COSENTYX does not contain preservatives; therefore, administer within 1 hour after removal from 2ºC to 8ºC (36ºF to 46ºF) storage.
### Monitoring
There is limited information regarding Monitoring of Secukinumab in the drug label.
# IV Compatibility
There is limited information regarding IV Compatibility of Secukinumab in the drug label.
# Overdosage
- Doses up to 30 mg/kg intravenously (i.e., approximately 2000 to 3000 mg) have been administered in clinical trials without dose-limiting toxicity. In the event of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted immediately.
# Pharmacology
## Mechanism of Action
- Secukinumab is a human IgG1 monoclonal antibody that selectively binds to the interleukin-17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Secukinumab inhibits the release of proinflammatory cytokines and chemokines.
## Structure
- Secukinumab is a recombinant human monoclonal IgG1/κ antibody that binds specifically to IL-17A. It is expressed in a recombinant Chinese Hamster Ovary (CHO) cell line. Secukinumab has a molecular mass of approximately 151 kDa; both heavy chains of secukinumab contain oligosaccharide chains.
- COSENTYX injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution. COSENTYX is supplied in a single-use Sensoready pen with a 27 gauge fixed ½ inch needle, or a single-use prefilled syringe with a 27 gauge fixed ½ inch needle. The removable cap of the COSENTYX Sensoready pen or prefilled syringe contains natural rubber latex.
- Each COSENTYX Sensoready pen or prefilled syringe contains 150 mg of secukinumab formulated in: L-histidine/histidine hydrochloride monohydrate (3.103 mg), L-methionine (0.746 mg), polysorbate 80 (0.2 mg), trehalose dihydrate (75.67 mg), and Sterile Water for Injection, USP, at pH of 5.8.
- COSENTYX for injection is supplied as a sterile, preservative free, white to slightly yellow, lyophilized powder in single-use vials. Each COSENTYX vial contains 150 mg of secukinumab formulated in L-histidine/L-histidine hydrochloride monohydrate (4.656 mg), polysorbate 80 (0.6 mg), and sucrose (92.43 mg). Following reconstitution with 1 mL Sterile Water for Injection, USP, the resulting pH is approximately 5.8.
## Pharmacodynamics
- Elevated levels of IL-17A are found in psoriatic plaques. Treatment with COSENTYX may reduce epidermal neutrophils and IL-17A levels in psoriatic plaques. Serum levels of total IL-17A (free and secukinumab-bound IL-17A) measured at Week 4 and Week 12 were increased following secukinumab treatment. These pharmacodynamic activities are based on small exploratory studies. The relationship between these pharmacodynamic activities and the mechanism(s) by which secukinumab exerts its clinical effects is unknown.
## Pharmacokinetics
- Following a single subcutaneous dose of either 150 mg (one-half the recommended dose) or 300 mg in plaque psoriasis patients, secukinumab reached peak mean (± SD) serum concentrations (Cmax) of 13.7 ± 4.8 mcg/mL and 27.3 ± 9.5 mcg/mL, respectively, by approximately 6 days post dose.
- Following multiple subcutaneous doses of secukinumab, the mean (± SD) serum trough concentrations of secukinumab ranged from 22.8 ± 10.2 mcg/mL (150 mg) to 45.4 ± 21.2 mcg/mL (300 mg) at Week 12. At the 300 mg dose at Week 4 and Week 12, the mean trough concentrations resulted from the Sensoready pen were 23% to 30% higher than those from the lyophilized powder and 23% to 26% higher than those from the prefilled syringe based on cross-study comparisons.
- Steady-state concentrations of secukinumab were achieved by Week 24 following the every 4 week dosing regimens. The mean (± SD) steady-state trough concentrations ranged from 16.7 ± 8.2 mcg/mL (150 mg) to 34.4 ± 16.6 mcg/mL (300 mg).
- In healthy subjects and subjects with plaque psoriasis, secukinumab bioavailability ranged from 55% to 77% following subcutaneous dose of 150 mg (one-half the recommended dose) or 300 mg.
- The mean volume of distribution during the terminal phase (Vz) following a single intravenous administration ranged from 7.10 to 8.60 L in plaque psoriasis patients. Intravenous use is not recommended [see Dosage and Administration (2)].
- Secukinumab concentrations in interstitial fluid in lesional and non-lesional skin of plaque psoriasis patients ranged from 27% to 40% of those in serum at 1 and 2 weeks after a single subcutaneous dose of secukinumab 300 mg.
- The metabolic pathway of secukinumab has not been characterized. As a human IgG1κ monoclonal antibody secukinumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.
- The mean systemic clearance (CL) ranged from 0.14 L/day to 0.22 L/day and the mean half-life ranged from 22 to 31 days in plaque psoriasis subjects following intravenous and subcutaneous administration across all psoriasis trials. Intravenous use is not recommended [see Dosage and Administration (2)].
- Secukinumab exhibited dose-proportional pharmacokinetics in subjects with psoriasis over a dose range from 25 mg (approximately 0.083 times the recommended dose) to 300 mg following subcutaneous administrations.
- Secukinumab clearance and volume of distribution increase as body weight increases.
- No formal trial of the effect of hepatic or renal impairment on the pharmacokinetics of secukinumab was conducted.
- Geriatric Population:
- Population pharmacokinetic analysis indicated that the clearance of secukinumab was not significantly influenced by age in adult subjects with plaque psoriasis. Subjects who are 65 years or older had apparent clearance of secukinumab similar to subjects less than 65 years old.
## Nonclinical Toxicology
- Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of COSENTYX. Some published literature suggests that IL-17A directly promotes cancer cell invasion in vitro, whereas other reports indicate IL-17A promotes T-cell mediated tumor rejection. Depletion of IL-17A with a neutralizing antibody inhibited tumor development in mice. The relevance of experimental findings in mouse models for malignancy risk in humans is unknown.
- No effects on fertility were observed in male and female mice that were administered a murine analog of secukinumab at subcutaneous doses up to 150 mg/kg once weekly prior to and during the mating period.
# Clinical Studies
- Four multicenter, randomized, double-blind, placebo-controlled trials (Trials 1, 2, 3, and 4) enrolled 2403 subjects (691 randomized to COSENTYX 300 mg, 692 to COSENTYX 150 mg, 694 to placebo, and 323 to a biologic active control) 18 years of age and older with plaque psoriasis who had a minimum body surface area involvement of 10%, and Psoriasis Area and Severity Index (PASI) score greater than or equal to 12, and who were candidates for phototherapy or systemic therapy.
- Trial 1 enrolled 738 subjects (245 randomized to COSENTYX 300 mg, 245 to COSENTYX 150 mg, and 248 to placebo). Subjects received subcutaneous treatment at Weeks 0, 1, 2, 3, and 4 followed by dosing every 4 weeks. Subjects randomized to COSENTYX received 300 mg or 150 mg doses at Weeks 0, 1, 2, 3, and 4 followed by the same dose every 4 weeks. Subjects randomized to receive placebo that were non-responders at Week 12 were then crossed over to receive COSENTYX (either 300 mg or 150 mg) at Weeks 12, 13, 14, 15, and 16 followed by the same dose every 4 weeks. All subjects were followed for up to 52 weeks following first administration of study treatment.
- Trial 2 enrolled 1306 subjects (327 randomized to COSENTYX 300 mg, 327 to COSENTYX 150 mg, 326 to placebo and 323 to a biologic active control). COSENTYX and placebo data are described. Subjects received subcutaneous treatment at Weeks 0, 1, 2, 3, and 4 followed by dosing every 4 weeks. Subjects randomized to COSENTYX received 300 mg or 150 mg doses at Weeks 0, 1, 2, 3, and 4 followed by the same dose every 4 weeks. Subjects randomized to receive placebo that were non-responders at Week 12 then crossed over to receive COSENTYX (either 300 mg or 150 mg) at Weeks 12, 13, 14, 15, and 16 followed by the same dose every 4 weeks. All subjects were followed for up to 52 weeks following first administration of study treatment.
- Trial 3 enrolled 177 subjects (59 randomized to COSENTYX 300 mg, 59 to COSENTYX 150 mg, and 59 to placebo) and assessed safety, tolerability, and usability of COSENTYX self-administration via prefilled syringe for 12 weeks. Subjects received subcutaneous treatment at Weeks 0, 1, 2, 3, and 4, followed by the same dose every 4 weeks for up to 12 weeks total.
- Trial 4 enrolled 182 subjects (60 randomized to COSENTYX 300 mg, 61 to COSENTYX 150 mg, and 61 to placebo) and assessed safety, tolerability, and usability of COSENTYX self-administration via Sensoready pen for 12 weeks. Subjects received subcutaneous treatment at Weeks 0, 1, 2, 3, and 4, followed by the same dose every 4 weeks for up to 12 weeks total.
Endpoints
- In all trials, the endpoints were the proportion of subjects who achieved a reduction in PASI score of at least 75% (PASI 75) from baseline to Week 12 and treatment success (clear or almost clear) on the Investigator’s Global Assessment modified 2011 (IGA). Other evaluated outcomes included the proportion of subjects who achieved a reduction in PASI score of at least 90% (PASI 90) from baseline at Week 12, maintenance of efficacy to Week 52, and improvements in itching, pain and scaling at Week 12 based on the Psoriasis Symptom Diary©.
- The PASI is a composite score that takes into consideration both the percentage of body surface area affected and the nature and severity of psoriatic changes within the affected regions (induration, erythema and scaling). The IGA is a 5-category scale including “0 = clear” “1 = almost clear”, “2 = mild”, “3 = moderate” or “4 = severe” indicating the physician’s overall assessment of the psoriasis severity focusing on induration, erythema and scaling. Treatment success of “clear” or “almost clear” consisted of no signs of psoriasis or normal to pink coloration of lesions, no thickening of the plaque and none to minimal focal scaling.
- Across all treatment groups the baseline PASI score ranged from 11 to 72 with a median of 20 and the baseline IGA score ranged from “moderate” (62%) to “severe” (38%). Of the 2077 plaque psoriasis subjects who were included in the placebo-controlled trials, 79% were biologic-naïve (have never received a prior treatment with biologics) and 45% were non-biologic failures (failed to respond to a prior treatment with non-biologics therapies). Of the patients who received a prior treatment with biologics, over one-third were biologic failures. Approximately 15% to 25% of trial subjects had a history of psoriatic arthritis.
- The results of Trials 1 and 2 are presented in Table 2.
- Examination of age, gender, and race subgroups did not identify differences in response to COSENTYX among these subgroups. Based on post-hoc sub-group analyses in patients with moderate to severe psoriasis, patients with lower body weight and lower disease severity may achieve an acceptable response with COSENTYX 150 mg.
- PASI 90 response at Week 12 was achieved with COSENTYX 300 mg and 150 mg compared to placebo in 59% (145/245) and 39% (95/245) versus 1% (3/248) of subjects, respectively (Trial 1) and 54% (175/327) and 42% (137/327) versus 2% (5/326) of subjects, respectively (Trial 2). Similar results were seen in Trials 3 and 4.
- With continued treatment over 52 weeks, subjects in Trial 1 who were PASI 75 responders at Week 12 maintained their responses in 81% (161/200) of the subjects treated with COSENTYX 300 mg and in 72% (126/174) of subjects treated with COSENTYX 150 mg. Trial 1 subjects who were clear or almost clear on the IGA at Week 12 also maintained their responses in 74% (119/160) of subjects treated with COSENTYX 300 mg and in 59% (74/125) of subjects treated with COSENTYX 150 mg. Similarly in Trial 2, PASI 75 responders maintained their responses in 84% (210/249) of subjects treated with COSENTYX 300 mg and in 82% (180/219) of subjects treated with COSENTYX 150 mg. Trial 2 subjects who were clear or almost clear on the IGA also maintained their responses in 80% (161/202) of subjects treated with COSENTYX 300 mg and in 68% (113/167) of subjects treated with COSENTYX 150 mg.
- Among the subjects who chose to participate (39%) in assessments of patient reported outcomes, improvements in signs and symptoms related to itching, pain, and scaling, at Week 12 compared to placebo (Trials 1 and 2) were observed using the Psoriasis Symptom Diary©.
# How Supplied
- COSENTYX Sensoready pen:
- COSENTYX prefilled syringe:
- The removable cap of the COSENTYX Sensoready pen and prefilled syringe contains natural rubber latex. Each Sensoready pen and prefilled syringe is equipped with a needle safety guard.
- COSENTYX vial (for healthcare professional use only):
## Storage
- COSENTYX Sensoready pens, prefilled syringes and vials must be refrigerated at 2ºC to 8ºC (36ºF to 46ºF). Keep the product in the original carton to protect from light until the time of use. Do not freeze. To avoid foaming do not shake. COSENTYX does not contain a preservative; discard any unused portion.
# Images
## Drug Images
## Package and Label Display Panel
### PRINCIPAL DISPLAY PANEL
COSENTYXTM
(secukinumab)
Injection
150 mg/mL
1 Prefilled Syringe
NDC 0078-0639-97
Single-use Prefilled Syringe
ATTENTION: Dispense with enclosed Medication Guide
For Subcutaneous Use Only
Sterile Solution - Contains No Preservative
Caution: Contains Natural Rubber Latex Which May Cause Allergic Reaction.
Rx only
### Ingredients and Appearance
# Patient Counseling Information
- Advise the patient to read FDA-approved patient labeling [Medication Guide and Instructions for Use].
- Instruct patients to read the Medication Guide before starting COSENTYX therapy and to reread the Medication Guide each time the prescription is renewed.
- Advise patients of the potential benefits and risks of COSENTYX.
- Inform patients that COSENTYX may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to the doctor and contacting their doctor if they develop any symptoms of infection [see Warnings and Precautions (5.1)].
- Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions (5.4)].
- Perform the first self-injection under the supervision of a qualified healthcare professional. If a patient or caregiver is to administer COSENTYX, instruct him/her in injection techniques and assess their ability to inject subcutaneously to ensure the proper administration of COSENTYX [see Medication Guide and Instructions for Use].
- Instruct patients or caregivers in the technique of proper syringe and needle disposal, and advise them not to reuse these items. Instruct patients to inject the full amount of COSENTYX (1 or 2 subcutaneous injections of 150 mg) according to the directions provided in the Medication Guide and Instructions for Use. Dispose of needles, syringes and pens in a puncture-resistant container.
### MEDICATION GUIDE
- COSENTYX is a medicine that affects your immune system. COSENTYX may increase your risk of having serious side effects such as:
- Infections. COSENTYX may lower the ability of your immune system to fight infections and may increase your risk of infections.
- Your healthcare provider should check you for tuberculosis (TB) before starting treatment with COSENTYX.
- If your healthcare provider feels that you are at risk for TB, you may be treated with medicine for TB before you begin treatment with COSENTYX and during treatment with COSENTYX.
- Your healthcare provider should watch you closely for signs and symptoms of TB during treatment with COSENTYX. Do not take COSENTYX if you have an active TB infection.
- are being treated for an infection
- have an infection that does not go away or that keeps coming back
- have TB or have been in close contact with someone with TB
- think you have an infection or have symptoms of an infection such as:
- fever, sweats, or chills
- muscle aches
- cough
- shortness of breath
- blood in your phlegm
- weight loss
- warm, red, or painful skin or sores on your body
- diarrhea or stomach pain
- burning when you urinate or urinate more often than normal
- After starting COSENTYX, call your healthcare provider right away if you have any of the signs of infection listed above. Do not use COSENTYX if you have any signs of infection unless you are instructed to by your healthcare provider.
- See “What are the possible side effects of COSENTYX?” for more information about side effects.
- COSENTYX is a prescription medicine used to treat adults:
- with moderate to severe plaque psoriasis that involves large areas or many areas of the body, and
- who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet or UV light alone or with systemic therapy)
- COSENTYX may improve your psoriasis but it may also lower the ability of your immune system to fight infections.
- It is not known if COSENTYX is safe and effective in children.
- Do not use COSENTYX if you have had a severe allergic reaction to secukinumab or any of the other ingredients in COSENTYX. See the end of this Medication Guide for a complete list of ingredients in COSENTYX.
- Before starting COSENTYX, tell your healthcare provider if you:
- have any of the conditions or symptoms listed in the section “What is the most important information I should know about COSENTYX?”
- have Crohn’s disease
- are allergic to latex. The needle cap on the COSENTYX Sensoready® pen and prefilled syringe contains latex.
- have recently received or are scheduled to receive an immunization (vaccine). People who take COSENTYX should not receive live vaccines.
- have any other medical conditions
- are pregnant or plan to become pregnant. It is not known if COSENTYX can harm your unborn baby. You and your healthcare provider should decide if you will use COSENTYX.
- are breastfeeding or plan to breastfeed. It is not known if COSENTYX passes into your breast milk.
- Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
- Know the medicines you take. Keep a list of your medicines to show your healthcare provider and pharmacist when you get a new medicine.
- See the detailed “Instructions for Use” that comes with your COSENTYX for information on how to prepare and inject a dose of COSENTYX, and how to properly throw away (dispose of) used COSENTYX Sensoready pens and prefilled syringes.
- Use COSENTYX exactly as prescribed by your healthcare provider.
- If your healthcare provider decides that you or a caregiver may give your injections of COSENTYX at home, you should receive training on the right way to prepare and inject COSENTYX. Do not try to inject COSENTYX yourself, until you or your caregiver has been shown how to inject COSENTYX by your healthcare provider.
- COSENTYX comes in a Sensoready pen or prefilled syringe that you or your caregiver may use at home to give injections. Your healthcare provider will decide which type of COSENTYX is best for you to use at home.
- Your healthcare provider will prescribe the dose of COSENTYX that is right for you.
- If your prescribed dose of COSENTYX is 150 mg, you must give 1 injection of COSENTYX for each dose.
- If your prescribed dose of COSENTYX is 300 mg, you must give 2 injections for each dose.
- COSENTYX is given as an injection under your skin (subcutaneous injection), in your upper legs (thighs) or stomach-area (abdomen) by you or a caregiver. A caregiver may also give you an injection of COSENTYX in your upper outer arm.
- Do not give an injection in an area of the skin that is tender, bruised, red or hard, or in an area of skin that is affected by psoriasis.
- Each injection should be given at a different site. Do not use the 2 inch area around your navel (belly button).
- If you inject more COSENTYX than prescribed, call your healthcare provider or go to the nearest emergency room right away.
- COSENTYX may cause serious side effects, including:
- See “What is the most important information I should know about COSENTYX?”
- Crohn’s disease “flare-ups” (worsening Crohn’s disease). Crohn’s disease “flare-ups” can happen with COSENTYX, and can sometimes be serious. If you have Crohn’s disease, tell your healthcare provider if you have worsening Crohn’s disease symptoms during treatment with COSENTYX.
- Serious allergic reactions. Get emergency medical help right away if you get any of the following symptoms of a serious allergic reaction:
- feel faint
- swelling of your face, eyelids, lips, mouth, tongue, or throat
- trouble breathing or throat tightness
- chest tightness
- skin rash
- If you have a severe allergic reaction, do not give another injection of COSENTYX.
- The most common side effects of COSENTYX include:
- cold symptoms
- diarrhea
- upper respiratory infections
- These are not all of the possible side effects of COSENTYX. Tell your healthcare provider about any side effect that bothers you or that does not go away. For more information, ask your healthcare provider or pharmacist.
- Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
- Store COSENTYX in a refrigerator, between 36°F to 46°F (2°C to 8°C).
- Keep COSENTYX in the original carton until ready for use to protect from light.
- Do not freeze COSENTYX.
- Do not shake COSENTYX.
- Keep COSENTYX and all medicines out of the reach of children.
- Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use COSENTYX for a condition for which it was not prescribed. Do not give COSENTYX to other people, even if they have the same symptoms you have. It may harm them.
- If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about COSENTYX that is written for health professionals.
- For more information, call 1-888-669-6682 or go to www.COSENTYX.com.
- Active ingredient: secukinumab
- Inactive ingredients:
- Sensoready pen and prefilled syringe: L-histidine/histidine hydrochloride monohydrate, L-methionine, polysorbate 80, trehalose dihydrate, and sterile water for injection.
- Vial: L-histidine/histidine hydrochloride monohydrate, polysorbate 80, and sucrose.
- This Medication Guide has been approved by the U.S. Food and Drug Administration.
### INSTRUCTIONS FOR USE
INSTRUCTIONS FOR USE
COSENTYXTM (koe-sen’-tix)
(secukinumab)
For Injection
The following information is intended for medical or healthcare professionals only.
IMPORTANT:
- The single-use vial contains 150 mg of COSENTYX for reconstitution with Sterile Water for Injection (SWFI). Do not use the vial after the expiry date shown on the outer box or vial. If it has expired, return the entire pack to the pharmacy.
- The preparation of the solution for subcutaneous injection shall be done without interruption ensuring that aseptic technique is used. The preparation time from piercing the stopper until end of reconstitution on average takes 20 minutes and should not exceed 90 minutes.
- Throw away (dispose of) the used syringe right away after use. Do not re-use a syringe. See “How should I dispose of a used syringe?” at the end of this Instructions for Use.
- Store the vial of COSENTYX in the refrigerator between 2°C to 8°C (36°F to 46°F).
- To prepare COSENTYX 150 mg for injection, please adhere to the following instructions:
- Instructions for reconstitution of COSENTYX 150 mg for injection:
INSTRUCTIONS FOR USE
COSENTYXTM (koe-sen’-tix)
(secukinumab)
Injection
Prefilled Syringe
- Be sure that you read, understand, and follow this Instructions for Use before injecting COSENTYX. Your healthcare provider should show you how to prepare and inject COSENTYX properly using the prefilled syringe before you use it for the first time. Talk to your healthcare provider if you have any questions.
Important:
- Do not use the COSENTYX prefilled syringe if either the seal on the outside carton or the seal of the blister are broken. Keep the COSENTYX prefilled syringe in the sealed carton until you are ready to use it.
- Inject COSENTYX within 1 hour after taking it out of the refrigerator.
- Do not shake the COSENTYX prefilled syringe.
- The needle caps of the prefilled syringes contain latex. Do not handle the prefilled syringes if you are sensitive to latex.
- The prefilled syringe has a needle guard that will be activated to cover the needle after the injection is finished. The needle guard will help to prevent needle stick injuries to anyone who handles the prefilled syringe.
- Do not remove the needle cap until just before you give the injection.
- Avoid touching the syringe guard wings before use. Touching them may cause the syringe guard to be activated too early.
- Throw away (dispose of) the used COSENTYX prefilled syringe right away after use. Do not re-use a COSENTYX prefilled syringe. See “How should I dispose of used COSENTYX prefilled syringes?” at the end of this Instructions for Use.
- Store your carton of COSENTYX prefilled syringes in a refrigerator, between 36°F to 46°F (2°C to 8°C).
- Keep COSENTYX prefilled syringes in the original carton until ready to use to protect from light.
- Do not freeze COSENTYX prefilled syringes.
Keep COSENTYX and all medicines out of the reach of children.
INSTRUCTIONS FOR USE
COSENTYXTM (koe-sen’-tix)
(secukinumab)
Injection
Sensoready® Pen
Be sure that you read, understand, and follow this Instructions for Use before injecting COSENTYX. Your healthcare provider should show you how to prepare and inject COSENTYX properly using the Sensoready Pen before you use it for the first time. Talk to your healthcare provider if you have any questions.
Important:
- Do not use the COSENTYX Sensoready Pen if either the seal on the outer carton or the seal on the pen is broken. Keep the COSENTYX Sensoready Pen in the sealed outer carton until you are ready to use it.
- Inject COSENTYX within 1 hour after taking it out of the refrigerator.
- Do not shake the COSENTYX Sensoready Pen.
- The caps of the Sensoready Pens contain latex. Do not handle the Sensoready Pens if you are sensitive to latex.
- If you drop your COSENTYX Sensoready Pen, do not use it if the Sensoready Pen looks damaged, or if you dropped it with the cap removed.
- Throw away (dispose of) the used COSENTYX Sensoready Pen right away after use. Do not re-use a COSENTYX Sensoready Pen. See “How should I dispose of used COSENTYX Sensoready Pens?” at the end of this Instructions for Use.
How should I store COSENTYX?
- Store your carton of COSENTYX Sensoready Pen in a refrigerator, between 36°F to 46°F (2°C to 8°C).
- Keep COSENTYX Sensoready Pen in the original carton until ready to use to protect from light.
- Do not freeze COSENTYX Sensoready Pen.
- Keep COSENTYX and all medicines out of the reach of children.
# Precautions with Alcohol
- Alcohol-Secukinumab interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- COSENTYX ®[1]
# Look-Alike Drug Names
There is limited information regarding Secukinumab Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Secukinumab | |
f9d60d28318702d40540c7f5692eb8c0a05c7967 | wikidoc | Seidel test | Seidel test
# Overview
Seidel’s test is a test used to assess the presence of anterior chamber leakage in the cornea. It is used as a screening test for many corneal disorders including post corneal trauma, corneal perforation and corneal degeneration.
# Name
Seidel’s test is named after the German Ophthalmologist Erich Seidel.
# Procedure
A fluorescein strip containing 10% fluorescein is applied topically to the affected area and is looked at with a cobalt blue filter. At this point, the fluorescein appears dark orange in color. Any changes in color of the fluorescein strip indicate presence corneal deformities.
# Results of the test
If the fluorescein strip turns pale upon application to the corneal surface, the person tests positive for corneal deformity he/ she is being tested for. The change in the color of the fluorescein strip is due to dilution of fluorescein caused by the aqueous leakage in the cornea.
# Precautions
Do not apply pressure on the eye during test. There is risk of tissue extrusion in doing so. | Seidel test
# Overview
Seidel’s test is a test used to assess the presence of anterior chamber leakage in the cornea. It is used as a screening test for many corneal disorders including post corneal trauma, corneal perforation and corneal degeneration.
# Name
Seidel’s test is named after the German Ophthalmologist Erich Seidel.
# Procedure
A fluorescein strip containing 10% fluorescein is applied topically to the affected area and is looked at with a cobalt blue filter. At this point, the fluorescein appears dark orange in color. Any changes in color of the fluorescein strip indicate presence corneal deformities.
# Results of the test
If the fluorescein strip turns pale upon application to the corneal surface, the person tests positive for corneal deformity he/ she is being tested for. The change in the color of the fluorescein strip is due to dilution of fluorescein caused by the aqueous leakage in the cornea.
# Precautions
Do not apply pressure on the eye during test. There is risk of tissue extrusion in doing so. | https://www.wikidoc.org/index.php/Seidel_test | |
4d375ca563951455d3b311ab0f6e480025793284 | wikidoc | Terfenadine | Terfenadine
# Overview
Terfenadine is an antihistamine formerly used for the treatment of allergic conditions. It was brought to market by Hoechst Marion Roussel (now Sanofi-Aventis) and marketed under various brand names, including Seldane in the United States, Triludan in the United Kingdom, and Teldane in Australia. According to its manufacturer, terfenadine had been used by over 100 million patients worldwide as of 1990.It was superseded by fexofenadine in the 1990s due to the risk of a particular type of disruption of the electrical rhythms of the heart (specifically cardiac arrhythmia caused by QT interval prolongation).
Terfenadine is a prodrug, generally completely metabolized to the active form fexofenadine in the liver by the enzyme cytochrome P450 CYP3A4 isoform.
Due to its near complete metabolism by the liver immediately after leaving the gut, terfenadine normally is not measurable in the plasma.
Terfenadine itself, however, is cardiotoxic at higher doses, while its major active metabolite is not. Terfenadine, in addition to its antihistamine effects, also acts as a potassium channel blocker (Kv11.1 encoded by the gene hERG). Since its active metabolite is not a potassium channel blocker, no cardiotoxicity is associated with fexofenadine.Toxicity is possible after years of continued use with no previous problems as a result of an interaction with other medications such as erythromycin, or foods such as grapefruit. The addition of, or dosage change in, these CYP3A4 inhibitors makes it harder for the body to metabolize and remove terfenadine. In larger plasma concentrations, it may lead to toxic effects on the heart's rhythm (e.g. ventricular tachycardia and torsades de pointes).
# History
In the United States, Seldane was brought to market in 1985 as the first nonsedating antihistamine for the treatment of allergic rhinitis.In June 1990, evidence of serious ventricular arrhythmias among those taking Seldane prompted the FDA to issue a report on the risk factors associated with concomitant use of the drug with macrolide antibiotics and ketoconazole.Two months later, the FDA required the manufacturer to send a letter to all physicians, alerting them to the problem; in July 1992, the existing precautions were elevated to a black box warningand the issue attracted mass media attention in reports that people with liver disease or who took ketoconazole, an antifungal agent, or the antibiotic erythromycin, could suffer cardiac arrhythmia if they also took Seldane.
In January 1997, the same month when the U.S. Food and Drug Administration (FDA) had earlier approved a generic version of Seldane made by IVAX Corporation of Miami, the FDA recommended terfenadine-containing drugs be removed from the market and physicians consider alternative medications for their patients.Seldane (and Seldane-D, terfenadine combined with the decongestant pseudoephedrine) were removed from the U.S. market by their manufacturer in late 1997 after the FDA approval of Allegra-D (fexofenadine/pseudoephedrine). >"FDA Approves Allegra-D, Manufacturer To Withdraw Seldane From Marketplace". Food and Drug Administration. Archived from Terfenadine-containing drugs were subsequently removed from the Canadian market in 1999, | Terfenadine
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Terfenadine is an antihistamine formerly used for the treatment of allergic conditions. It was brought to market by Hoechst Marion Roussel (now Sanofi-Aventis) and marketed under various brand names, including Seldane in the United States, Triludan in the United Kingdom, and Teldane in Australia. According to its manufacturer, terfenadine had been used by over 100 million patients worldwide as of 1990.It was superseded by fexofenadine in the 1990s due to the risk of a particular type of disruption of the electrical rhythms of the heart (specifically cardiac arrhythmia caused by QT interval prolongation).
Terfenadine is a prodrug, generally completely metabolized to the active form fexofenadine in the liver by the enzyme cytochrome P450 CYP3A4 isoform.
Due to its near complete metabolism by the liver immediately after leaving the gut, terfenadine normally is not measurable in the plasma.
Terfenadine itself, however, is cardiotoxic at higher doses, while its major active metabolite is not. Terfenadine, in addition to its antihistamine effects, also acts as a potassium channel blocker (Kv11.1 encoded by the gene hERG). Since its active metabolite is not a potassium channel blocker, no cardiotoxicity is associated with fexofenadine.Toxicity is possible after years of continued use with no previous problems as a result of an interaction with other medications such as erythromycin, or foods such as grapefruit. The addition of, or dosage change in, these CYP3A4 inhibitors makes it harder for the body to metabolize and remove terfenadine. In larger plasma concentrations, it may lead to toxic effects on the heart's rhythm (e.g. ventricular tachycardia and torsades de pointes).
# History
In the United States, Seldane was brought to market in 1985 as the first nonsedating antihistamine for the treatment of allergic rhinitis.In June 1990, evidence of serious ventricular arrhythmias among those taking Seldane prompted the FDA to issue a report on the risk factors associated with concomitant use of the drug with macrolide antibiotics and ketoconazole.Two months later, the FDA required the manufacturer to send a letter to all physicians, alerting them to the problem; in July 1992, the existing precautions were elevated to a black box warningand the issue attracted mass media attention in reports that people with liver disease or who took ketoconazole, an antifungal agent, or the antibiotic erythromycin, could suffer cardiac arrhythmia if they also took Seldane.
In January 1997, the same month when the U.S. Food and Drug Administration (FDA) had earlier approved a generic version of Seldane made by IVAX Corporation of Miami, the FDA recommended terfenadine-containing drugs be removed from the market and physicians consider alternative medications for their patients.Seldane (and Seldane-D, terfenadine combined with the decongestant pseudoephedrine) were removed from the U.S. market by their manufacturer in late 1997 after the FDA approval of Allegra-D (fexofenadine/pseudoephedrine). >"FDA Approves Allegra-D, Manufacturer To Withdraw Seldane From Marketplace". Food and Drug Administration. Archived from <refs/topics/ANSWERS/ANS00843.html the original on 2008-02-23. Retrieved 2010-11-11..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}</ref> Terfenadine-containing drugs were subsequently removed from the Canadian market in 1999,[1] | https://www.wikidoc.org/index.php/Seldane | |
88ae708d791f7819cf26ab7af9fe06fcd97c153a | wikidoc | Self-injury | Self-injury
# Background
Self-injury (SI) or self-harm (SH) is deliberate injury inflicted by a person upon their own body without suicidal intent. Some scholars use more technical definitions related to specific aspects of this behavior. These acts may be aimed at relieving otherwise unbearable emotions, sensations of unreality and numbness. It is listed in the DSM-IV-TR as a symptom of borderline personality disorder and depressive disorders, it is sometimes associated with mental illness, a history of trauma and abuse including emotional abuse, sexual abuse, eating disorders, or mental traits such as low self-esteem or perfectionism. Self harmers are often mistaken for being suicidal, but the majority of the time this is not the case. Non-fatal self-harm is common in young people worldwide and due to this prevailance the term self-harm is increasingly used to denote any non-fatal acts of deliberate self-harm, irrespective of the intention.
# Definition
Self-injury, sometimes referred to as self-harm (SH), self-inflicted violence (SIV) or self-injurious behavior (SIB), refers to a spectrum of behaviors where demonstrable injury is self-inflicted. The term self-mutilation is also sometimes used, although this phrase evokes connotations that some find worrisome, inaccurate, or offensive. A broader definition of self-injury might also include those who inflict harm on their bodies by means of disordered eating, as well as tattooing or body piercing that goes beyond the limits of culturally accepted body modification.
A common belief regarding self-injury is that it is an attention-seeking behavior; however, in most cases, this is untrue. Most self-injurers are very self-conscious of both their wounds and scars, and go to great lengths to conceal their behavior from others. They may offer alternative explanations for their injuries, or conceal their scars with clothing. Self-injury in such individuals is not associated with suicidal or para-suicidal behavior. The person who self-injures is not usually seeking to end his or her own life; it has been suggested instead that he or she is using self-injury as a coping mechanism to relieve emotional pain or discomfort. However, studies of individuals with developmental disabilities (such as mental retardation) have shown self-injury being dependent on environmental factors such as obtaining attention or escape from demands. Though this is not always the case, some individuals suffer from disassociation and they harbor a desire to feel real and/or to fit in to society's rules.
## Methods of injury
A common form of self-injury involves making cuts in the skin of the arms, legs, abdomen, inner thighs, etc. This is colloquially referred to as "cutting"; a person who routinely does this may be colloquially called a "cutter". The number of self-injury methods are only limited by an individual's creativity. The bodily locations of self-injury are often areas that are easily hidden and concealed from the detection of others.
Examples of self-injury other than cutting include:
- Punching, hitting and scratching
- Choking or constriction of the airway
- Biting of own body parts including the tongue, lips, hands or arms
- Picking at or re-opening wounds (dermatillomania), ulceration, or sutures
- Hair-pulling (trichotillomania)
- Burning by self-incediarism, stubbing out cigarettes on skin, friction or chemical burns
- Stabbing self with wire, pins, needles, nails, staples, pens or hair accessories
- Pinching or clamping using, for example, clothes pins or paper clips
- Ingesting corrosive chemicals, batteries, or pins
- Self-poisoning; for example by over-dosing on medication and/or alcohol, without suicidal intent
- Self-injury among individuals with developmental disabilities often involves relatively simple actions, such as banging one's head against a hard surface, punching hard surfaces, biting oneself (usually hands or arms), or picking wounds. It may also include pica, the swallowing of nonfood items, which can be extremely dangerous and sometimes fatal.
- Constriction of the blood circulation via the use of rubber bands over a long period of time.
- Self-inflicted starvation.
## Other definitions
Strictly speaking, self-harm is a general term for self-damaging activities (which could include such activities as alcohol abuse or bulimia). Self-injury refers more specifically to the practice of cutting, bruising, poisoning, over-dosing (without suicidal intent), burning, or otherwise directly injuring the body. Many people, including health-care workers, define self-harm based around the act of damaging one's own body. It may be more accurate to define self-harm based around the intent, and the emotional distress that the person wishes to deal with. An example of this form of definition is provided by the self-injury awareness voluntary organisation, LifeSIGNS.
Neither the DSM-IV-TR nor the ICD-10 provide diagnostic criteria for self-injury. It is often seen as only a symptom of an underlying disorder, though many people who self-injure would like this to be addressed.
Self-inflicted wounds is a specific term associated with soldiers, where they inflicted harm on themselves (commonly a shot in the foot or hand) in order to obtain early dismissal from combat.This differs from the common definition of self-injury as the damage is inflicted for a specific secondary purpose.
# Life style
Many teenagers who suffer from depression self harm, this can be from being emotionaly hurt or just a cry for attention. Teenagers who self harm are labled "Emo's" which is short for emotional.
# Risk factors
A number of social or psychological factors can be seen to have a positive statistical correlation with self-injury or its repetition.
People experiencing various forms of mental ill-health can be considered to be at higher risk of self-injuring. Key issues are depression, phobias, and conduct disorders. Substance abuse is also considered a risk factor as are some personal characteristics such as poor problem resolution skills, impulsivity, hopelessness and aggression. Emotionally invalidating environments where parents punish children for expressing sadness or hurt can attribute to a lack of trust in oneself and difficulty experiencing intense emotions. Abuse during childhood is accepted as a primary social factor, also losing a parent or loved one, along with troubled parental or partner relationships. Factors such as war, poverty, and unemployment may also contribute.
In addition, some individuals with pervasive developmental disabilities, more popularly known as autism, engage in self-injury, while is debated whether it is a form of self-stimulation or for the purpose of harming one's self. However, some people who self-injure do not experience these factors.
# Demographics
Accurate statistics on self-injury are hard to come by since most self-injurers conceal their injuries. Recorded figures can be based on three sources: psychiatric samples, hospital admissions and general population surveys. Studies based only on hospital admissions may hide the larger group of self-injurers who do not need or seek hospital treatment for their injuries. Many of these statistics show that more women seem to self-injure than men, and that it is more common among young people. This most likely explains the female bias that the media seems to portray in its attitude to self-injury, despite research in 2006 by Marchetto which suggests no gender differences were observed among skin-cutters.
The Mental Health Foundation estimates the rate in the UK to be 0.77%, and that the majority of people who self-harm are aged between 11 and 25 years, with between 1 in 12 and 1 in 15 young people self-harming. Many adolescents who present to general hospitals with deliberate self-harm report previous episodes for which they did not receive medical attention. A study of homeless youth (age 16 to 19) found that 69% practiced self-injury on at least one occasion with 12% receiving medical attention for the self-inflicted wounds. There was no significant difference in frequency between gender (72% of males vs. 66% females), however gender correlations may be made between the methods of self-injury with the exception of cutting being most common for both.
About 10% of admissions to medical wards in the UK are as a result of self-harm, the majority of which are drug overdoses. The WHO/EURO Multicentre Study of Suicide estimated that the average European rate of self-injury for persons over 15 years is 0.14% for males and 0.193% for females. For each age group the female rate exceeded that of the males, with the highest rate among females in the 15-24 age group and the highest rate among males in the 12-34 age group. Recently, however, it has been found that the female to male ratio, previously thought to be around 2:1, is diminishing – in Ireland it has been close to unity for a number of years.. In a study of psychiatric morbidity carried out in the UK an overall lifetime prevalence of 2.4% was found, 2.0% of which were male and 2.7% of female.
In a study of undergraduate students in the United States, 9.8% of the students surveyed indicated that they had purposefully cut or burned themselves on at least one occasion in the past. When the definition of self-injury was expanded to include head-banging, scratching oneself, and hitting oneself along with cutting and burning, 32% of the sample said they had done this. This suggests that this problem is not associated only with severely disturbed psychiatric patients but is not uncommon among young adults.
## Gender differences
A discourse analysis of self-injury research demonstrates methodological and sampling errors that explain the disproportional representation of females that practice self-injury. Brickman argues "Medical discourse has again pathologised the female" and the profiling of self-injurers as female is the unsubstantiated result of social biases.
There does not appear to be a difference in motivation for self-harm in adolescent males and females. For example, for both genders there is an incremental increase in deliberate self-harm associated with an increase in consumption of cigarettes, drugs and alcohol. Triggering factors such as low self-esteem and having friends and family members who self-harm are also common between both males and females. However, females who self-cut are more likely than males to explain their self-harm episode by saying that they had wanted to punish themselves.
The most common methods of self-injury reported by both male and female subjects were scratching or pinching with fingernails or other objects to the point that bleeding occurred or marks remained on the skin (51.6%), banging or punching objects to the point of bruising or bleeding (37.6%), cutting (33.7%), and punching or banging oneself to the point of bruising or bleeding (24.5%). Female subjects were 2.3 times more likely to scratch or pinch and 2.4 times more likely to cut. Male subjects were 2.8 times more likely than female subjects to punch an object with the intention of injuring themselves. Male subjects were 1.8 times more likely to injure their hands, whereas female subjects were 2.3 times more likely to injure their wrists and 2.4 times more likely to injure their thighs. Self-injury is popularly assumed to represent a female phenomenon, and although there is some disputed support to this claim, the authors of the study believe that the popular association of self-injury with cutting may account for this belief.
In New Zealand, more females are hospitalised for intentional self-harm than males. Females more commonly choose methods such as self-poisoning that generally are not fatal, but still serious enough to require hospitalisation.
## Self-harm in the elderly
In a study of a district general hospital in the UK, 5.4% of all the hospital's self-harm cases were aged over 65. The male to female ratio was 2:3 although the self-harm rates for males and females over 65 in the local population were identical. Over 90% had depressive conditions, and 63% had significant physical illness. Under 10% of the patients gave a history of earlier self-harm, while both the repetition and suicide rates were very low which could be explained due to the absence of factors known to be associated with repetition such as personality disorder and alcohol abuse.
## Self-harm in the developing world
Only recently have attempts to improve health in the developing world concentrated on not only physical illness, but mental health also. Deliberate self-harm is common in the developing world. For example, Sri Lanka has a high incidence of suicide and self poisoning with agricultural pesticides or natural poisons is an important cause of mortality in many rural areas. Many people admitted for deliberate self-poisoning during a study by Eddleston et al. were young and few expressed a desire to die, but death was relatively common in the young in these cases. The improvement of medical management of acute poisoning in the developing world is poor and improvements are required in order to reduce mortality.
Some of the causes of deliberate self-poisoning in Sri Lankan adolescents included bereavement and harsh discipline by parents. The coping mechanisms are being spread in local communities as people are surrounded by others who have previously deliberately harmed themselves or attempted suicide. One way of reducing self-harm would be to limit access to poisons; however many cases involve pesticides or yellow oleander seeds, and the reduction of access to these agents would be difficult. Great potential for the reduction of self-harm lies in education and prevention, but limited resources in the developing world make these methods challenging.
# Psychology
File:Self-injury.svg
Attempts to understand self-injury fall broadly into either attempts to interpret motives, or application of psychological models.
Motives for self-injury are often personal, often do not fit into medicalised models of behaviour and may seem incomprehensible to others, as demonstrated by this quote:
Motives for self-injury can be different. Some feel as if they are not good enough and they might not want to take it out on the person who harmed them. It's often difficult for them to open up and tell about their "secret shame". Often when the sufferer does tell somebody there is a lack of understanding or knowledge of how to help.
Assessment of motives in a medical setting is usually based on precursors to the incident, circumstances and information from the patient however the limited studies comparing professional and personal assessments show that these differ with professionals suggesting more manipulative or punitive motives.
The UK ONS study reported only two motives: “to draw attention” and “because of anger”.
Many people who self-injure state that it allows them to "go away" or dissociate, separating the mind from feelings that are causing anguish. This may be achieved by tricking the mind into believing the pain felt at the time is caused by self-injury instead of the issues they were facing before: the physical pain therefore acts as a distraction from emotional pain. To complement this theory, one can consider the need to 'stop' feeling emotional pain and mental agitation. "A person may be hyper-sensitive and overwhelmed; a great many thoughts may be revolving within their mind, and they may either become triggered or could make a decision to stop the overwhelming feelings." The sexual organs may be deliberately hurt as a way to deal with unwanted feelings of sexuality, or as a means of punishing sexual organs that may be perceived as having responded in contravention to the person's wellbeing. (e.g., responses to childhood sexual abuse).
Alternatively self-injury may be a means of feeling something, even if the sensation is unpleasant and painful. Those who self-injure sometimes describe feelings of emptiness or numbness (anhedonia), and physical pain may be a relief from these feelings. "A person may be detached from himself or herself, detached from life, numb and unfeeling. They may then recognise the need to function more, or have a desire to feel real again, and a decision is made to create sensation and ‘wake up’." A flow diagram of these two theories accompanies this section.
It is also important to note that many self-injurers report feeling very little to no pain while self-harming.
Those who engage in self-injury face the contradictory reality of harming themselves whilst at the same time obtaining relief from this act. It may even be hard for some to actually initiate cutting, but they often do because they know the relief that will follow. For some self-injurers this relief is primarily psychological whilst for others this feeling of relief comes from the beta endorphins released in the brain (the same chemicals that are thought to be responsible for the "runner's high"). These act to reduce tension and emotional distress and may lead to a feeling of calm.
As a coping mechanism, self-injury can become psychologically addictive because, to the self-injurer, it works; it enables him/her to deal with intense stress in the current moment. The patterns sometimes created by it, such as specific time intervals between acts of self-injury, can also create a behavioral pattern that can result in a wanting or craving to fulfill thoughts of self-injury.
Another possible source of self-injury can be self-loathing, often as a means of punishment for having strong feelings that they were expected to suppress when they were children, or because they feel bad and undeserving, having previously been physically or emotionally abused and feeling that they were deserving of the abuse.
# Motives
Self-injury is not typically suicidal behavior, although there is the possibility that a self-inflicted injury may result in life-threatening damage. Although the person may not recognise the connection, self-injury often occurs when facing what seem like overwhelming or distressing feelings. The motivations for self-injury vary as it may be used to fulfill a number of different functions. These functions include self-injury being used as a coping mechanism which provides temporary relief of intense feelings such as anxiety, depression, stress, emotional numbness and a sense of failure or self-loathing. There is a positive statistical correlation between self-injury and emotional abuse. Intense pain can lead to the release of endorphins and so deliberate self-harm may become a means of seeking pleasure, although in many cases self-injury becomes a means to manage pain, in contrast to the pain that may have been experience through abuse earlier in the sufferers life of which they had no control over. For some people harming oneself can be a way to draw attention to the need for help and to ask for assistance in an indirect way but may also be an attempt to affect others and to manipulate them in some way emotionally. However, those with chronic, repetitive self injury often do not want attention and hide their scars carefully.
# Self-injury awareness
There are many movements among the general self-injury community to make self-injury itself and treatment better known to mental health professionals as well as the general public. Self Injury Awareness Day (SIAD), which is set for March 1 of every year, is one such movement. On this day, some people choose to be more open about their own self-injury, and awareness organisations make special efforts to raise awareness about self-injury. Some people wear ribbons to show awareness; commonly orange ribbons are used for this. Sometimes a red and black ribbon is also used, generally signifying a person who self-injures. Sometimes orange is used to represent those who self-injure, white for those who don't injure but show support, and white and orange together show someone who is trying to stop or has stopped self-injury. A single white bead on an orange bracelet may sometimes be used for those who want to stop and several mixed white and orange beads is for those who have stopped.
# Treatment
There is considerable uncertainty about which forms of psychosocial and physical treatments of patients who harm themselves are most effective and as such further clinical studies are required. Psychiatric and personality disorders are common in individuals who self-harm and as a result self-injury may be an indicator of depression and/or other psychological problems. Many people who self-harm suffer from moderate or severe clinical depression and therefore treatment with antidepressant drugs may often be indicated for these patients. Cognitive Behavioral Therapy may also be used (where the resources are available) to assist those with axis 1 diagnoses, such as depression, schizophrenia, and bipolar disorder. DBT, or Dialectical behavioral therapy can be very successful for those individuals exhibiting a personality disorder, and could potentially be used for those with other mental illnesses who exhibit self-injurious behavior. Diagnosis and treatment of the causes of self-harm is thought by many to be the best approach to self-injury.Template:Who But in some cases, particularly in clients with a personality disorder, this is not very effective, so more clinicians are starting to take a DBT approach in order to reduce the behavior itself. People who self-injure may be advised to use coping skills, such as journaling or taking a walk, when they have the urge to harm themselves. They may also be told to avoid having the objects they use to harm themselves within easy reach. People who rely on habitual self-injury are sometimes psychiatrically hospitalised, based on their stability, and their ability and especially their willingness to get help.
In individuals with developmental disabilities, occurrence of self-injury is often demonstrated to be related to its effects on the environment, such as obtaining attention or desired materials or escaping demands. As developmentally disabled individuals often have communication or social deficits, self-injury may be their way of obtaining these things which they are otherwise unable to obtain in a socially appropriate way (such as by asking). One approach for treating self-injury thus is to teach an alternative, appropriate response which obtains the same result as the self-injury. | Self-injury
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Background
Self-injury (SI) or self-harm (SH) is deliberate injury inflicted by a person upon their own body without suicidal intent. Some scholars use more technical definitions related to specific aspects of this behavior. These acts may be aimed at relieving otherwise unbearable emotions, sensations of unreality and numbness. It is listed in the DSM-IV-TR as a symptom of borderline personality disorder and depressive disorders, it is sometimes associated with mental illness, a history of trauma and abuse including emotional abuse, sexual abuse, eating disorders, or mental traits such as low self-esteem or perfectionism. Self harmers are often mistaken for being suicidal, but the majority of the time this is not the case.[1] Non-fatal self-harm is common in young people worldwide[2] and due to this prevailance the term self-harm is increasingly used to denote any non-fatal acts of deliberate self-harm, irrespective of the intention.[3]
# Definition
Self-injury, sometimes referred to as self-harm (SH), self-inflicted violence (SIV) or self-injurious behavior (SIB), refers to a spectrum of behaviors where demonstrable injury is self-inflicted.[4] The term self-mutilation is also sometimes used, although this phrase evokes connotations that some find worrisome, inaccurate, or offensive.[4] A broader definition of self-injury might also include those who inflict harm on their bodies by means of disordered eating, as well as tattooing or body piercing that goes beyond the limits of culturally accepted body modification.
A common belief regarding self-injury is that it is an attention-seeking behavior; however, in most cases, this is untrue. Most self-injurers are very self-conscious of both their wounds and scars, and go to great lengths to conceal their behavior from others. They may offer alternative explanations for their injuries, or conceal their scars with clothing.[5][6] Self-injury in such individuals is not associated with suicidal or para-suicidal behavior. The person who self-injures is not usually seeking to end his or her own life; it has been suggested instead that he or she is using self-injury as a coping mechanism to relieve emotional pain or discomfort.[7] However, studies of individuals with developmental disabilities (such as mental retardation) have shown self-injury being dependent on environmental factors such as obtaining attention or escape from demands.[8] Though this is not always the case, some individuals suffer from disassociation and they harbor a desire to feel real and/or to fit in to society's rules.
## Methods of injury
A common form of self-injury involves making cuts in the skin of the arms, legs, abdomen, inner thighs, etc. This is colloquially referred to as "cutting"; a person who routinely does this may be colloquially called a "cutter".[9] The number of self-injury methods are only limited by an individual's creativity. The bodily locations of self-injury are often areas that are easily hidden and concealed from the detection of others.[10]
Examples of self-injury other than cutting include:
- Punching, hitting and scratching
- Choking or constriction of the airway
- Biting of own body parts including the tongue, lips, hands or arms
- Picking at or re-opening wounds (dermatillomania), ulceration, or sutures
- Hair-pulling (trichotillomania)
- Burning by self-incediarism, stubbing out cigarettes on skin, friction or chemical burns
- Stabbing self with wire, pins, needles, nails, staples, pens or hair accessories
- Pinching or clamping using, for example, clothes pins or paper clips
- Ingesting corrosive chemicals, batteries, or pins[11]
- Self-poisoning; for example by over-dosing on medication and/or alcohol, without suicidal intent[5]
- Self-injury among individuals with developmental disabilities often involves relatively simple actions, such as banging one's head against a hard surface, punching hard surfaces, biting oneself (usually hands or arms), or picking wounds. It may also include pica, the swallowing of nonfood items, which can be extremely dangerous and sometimes fatal.
- Constriction of the blood circulation via the use of rubber bands over a long period of time.
- Self-inflicted starvation.
## Other definitions
Strictly speaking, self-harm is a general term for self-damaging activities (which could include such activities as alcohol abuse or bulimia). Self-injury refers more specifically to the practice of cutting, bruising, poisoning, over-dosing (without suicidal intent), burning, or otherwise directly injuring the body.[12] Many people, including health-care workers, define self-harm based around the act of damaging one's own body. It may be more accurate to define self-harm based around the intent, and the emotional distress that the person wishes to deal with. An example of this form of definition is provided by the self-injury awareness voluntary organisation, LifeSIGNS.[13]
Neither the DSM-IV-TR nor the ICD-10 provide diagnostic criteria for self-injury. It is often seen as only a symptom of an underlying disorder,[7] though many people who self-injure would like this to be addressed.[6]
Self-inflicted wounds is a specific term associated with soldiers, where they inflicted harm on themselves (commonly a shot in the foot or hand) in order to obtain early dismissal from combat.[14][15]This differs from the common definition of self-injury as the damage is inflicted for a specific secondary purpose.
# Life style
Many teenagers who suffer from depression self harm, this can be from being emotionaly hurt or just a cry for attention. Teenagers who self harm are labled "Emo's" which is short for emotional.
# Risk factors
A number of social or psychological factors can be seen to have a positive statistical correlation with self-injury or its repetition.
People experiencing various forms of mental ill-health can be considered to be at higher risk of self-injuring. Key issues are depression,[16][17] phobias,[16] and conduct disorders.[18] Substance abuse is also considered a risk factor[7] as are some personal characteristics such as poor problem resolution skills, impulsivity, hopelessness and aggression.[7] Emotionally invalidating environments where parents punish children for expressing sadness or hurt can attribute to a lack of trust in oneself and difficulty experiencing intense emotions.[19] Abuse during childhood is accepted as a primary social factor,[20] also losing a parent or loved one,[21] along with troubled parental or partner relationships.[7][22] Factors such as war, poverty, and unemployment may also contribute.[16][23][24]
In addition, some individuals with pervasive developmental disabilities, more popularly known as autism, engage in self-injury, while is debated whether it is a form of self-stimulation or for the purpose of harming one's self. [25] However, some people who self-injure do not experience these factors.[5]
# Demographics
Accurate statistics on self-injury are hard to come by since most self-injurers conceal their injuries. Recorded figures can be based on three sources: psychiatric samples, hospital admissions and general population surveys.[3] Studies based only on hospital admissions may hide the larger group of self-injurers who do not need or seek hospital treatment for their injuries.[7] Many of these statistics show that more women seem to self-injure than men, and that it is more common among young people. This most likely explains the female bias that the media seems to portray in its attitude to self-injury, despite research in 2006 by Marchetto[26] which suggests no gender differences were observed among skin-cutters.
The Mental Health Foundation estimates the rate in the UK to be 0.77%,[21] and that the majority of people who self-harm are aged between 11 and 25 years, with between 1 in 12 and 1 in 15 young people self-harming. Many adolescents who present to general hospitals with deliberate self-harm report previous episodes for which they did not receive medical attention.[3] A study of homeless youth (age 16 to 19) found that 69% practiced self-injury on at least one occasion with 12% receiving medical attention for the self-inflicted wounds. There was no significant difference in frequency between gender (72% of males vs. 66% females), however gender correlations may be made between the methods of self-injury with the exception of cutting being most common for both.[27]
About 10% of admissions to medical wards in the UK are as a result of self-harm, the majority of which are drug overdoses. [21] The WHO/EURO Multicentre Study of Suicide estimated that the average European rate of self-injury for persons over 15 years is 0.14% for males and 0.193% for females. For each age group the female rate exceeded that of the males, with the highest rate among females in the 15-24 age group and the highest rate among males in the 12-34 age group. Recently, however, it has been found that the female to male ratio, previously thought to be around 2:1, is diminishing – in Ireland it has been close to unity for a number of years.[28]. In a study of psychiatric morbidity carried out in the UK an overall lifetime prevalence of 2.4% was found, 2.0% of which were male and 2.7% of female.[16]
In a study of undergraduate students in the United States, 9.8% of the students surveyed indicated that they had purposefully cut or burned themselves on at least one occasion in the past. When the definition of self-injury was expanded to include head-banging, scratching oneself, and hitting oneself along with cutting and burning, 32% of the sample said they had done this. This suggests that this problem is not associated only with severely disturbed psychiatric patients but is not uncommon among young adults.[29]
## Gender differences
A discourse analysis of self-injury research demonstrates methodological and sampling errors that explain the disproportional representation of females that practice self-injury. Brickman argues "Medical discourse has again pathologised the female" and the profiling of self-injurers as female is the unsubstantiated result of social biases.[30]
There does not appear to be a difference in motivation for self-harm in adolescent males and females. For example, for both genders there is an incremental increase in deliberate self-harm associated with an increase in consumption of cigarettes, drugs and alcohol. Triggering factors such as low self-esteem and having friends and family members who self-harm are also common between both males and females. [3] However, females who self-cut are more likely than males to explain their self-harm episode by saying that they had wanted to punish themselves.
The most common methods of self-injury reported by both male and female subjects were scratching or pinching with fingernails or other objects to the point that bleeding occurred or marks remained on the skin (51.6%), banging or punching objects to the point of bruising or bleeding (37.6%), cutting (33.7%), and punching or banging oneself to the point of bruising or bleeding (24.5%).[31] Female subjects were 2.3 times more likely to scratch or pinch and 2.4 times more likely to cut. Male subjects were 2.8 times more likely than female subjects to punch an object with the intention of injuring themselves. Male subjects were 1.8 times more likely to injure their hands, whereas female subjects were 2.3 times more likely to injure their wrists and 2.4 times more likely to injure their thighs. Self-injury is popularly assumed to represent a female phenomenon, and although there is some disputed support to this claim, the authors of the study believe that the popular association of self-injury with cutting may account for this belief.
In New Zealand, more females are hospitalised for intentional self-harm than males. Females more commonly choose methods such as self-poisoning that generally are not fatal, but still serious enough to require hospitalisation.[32]
## Self-harm in the elderly
In a study of a district general hospital in the UK, 5.4% of all the hospital's self-harm cases were aged over 65. The male to female ratio was 2:3 although the self-harm rates for males and females over 65 in the local population were identical. Over 90% had depressive conditions, and 63% had significant physical illness. Under 10% of the patients gave a history of earlier self-harm, while both the repetition and suicide rates were very low which could be explained due to the absence of factors known to be associated with repetition such as personality disorder and alcohol abuse.[33]
## Self-harm in the developing world
Only recently have attempts to improve health in the developing world concentrated on not only physical illness, but mental health also.[34] Deliberate self-harm is common in the developing world. For example, Sri Lanka has a high incidence of suicide[35] and self poisoning with agricultural pesticides or natural poisons is an important cause of mortality in many rural areas. Many people admitted for deliberate self-poisoning during a study by Eddleston et al. [34] were young and few expressed a desire to die, but death was relatively common in the young in these cases. The improvement of medical management of acute poisoning in the developing world is poor and improvements are required in order to reduce mortality.
Some of the causes of deliberate self-poisoning in Sri Lankan adolescents included bereavement and harsh discipline by parents. The coping mechanisms are being spread in local communities as people are surrounded by others who have previously deliberately harmed themselves or attempted suicide.[34] One way of reducing self-harm would be to limit access to poisons;[36] however many cases involve pesticides or yellow oleander seeds, and the reduction of access to these agents would be difficult. Great potential for the reduction of self-harm lies in education and prevention, but limited resources in the developing world make these methods challenging.
# Psychology
File:Self-injury.svg
Attempts to understand self-injury fall broadly into either attempts to interpret motives, or application of psychological models.
Motives for self-injury are often personal, often do not fit into medicalised models of behaviour and may seem incomprehensible to others, as demonstrated by this quote:
Motives for self-injury can be different. Some feel as if they are not good enough and they might not want to take it out on the person who harmed them. It's often difficult for them to open up and tell about their "secret shame". Often when the sufferer does tell somebody there is a lack of understanding or knowledge of how to help.
Assessment of motives in a medical setting is usually based on precursors to the incident, circumstances and information from the patient[7] however the limited studies comparing professional and personal assessments show that these differ with professionals suggesting more manipulative or punitive motives.[38]
The UK ONS study reported only two motives: “to draw attention” and “because of anger”.[16]
Many people who self-injure state that it allows them to "go away" or dissociate, separating the mind from feelings that are causing anguish. This may be achieved by tricking the mind into believing the pain felt at the time is caused by self-injury instead of the issues they were facing before: the physical pain therefore acts as a distraction from emotional pain.[5] To complement this theory, one can consider the need to 'stop' feeling emotional pain and mental agitation. "A person may be hyper-sensitive and overwhelmed; a great many thoughts may be revolving within their mind, and they may either become triggered or could make a decision to stop the overwhelming feelings."[4] The sexual organs may be deliberately hurt as a way to deal with unwanted feelings of sexuality, or as a means of punishing sexual organs that may be perceived as having responded in contravention to the person's wellbeing. (e.g., responses to childhood sexual abuse).
Alternatively self-injury may be a means of feeling something, even if the sensation is unpleasant and painful. Those who self-injure sometimes describe feelings of emptiness or numbness (anhedonia), and physical pain may be a relief from these feelings. "A person may be detached from himself or herself, detached from life, numb and unfeeling. They may then recognise the need to function more, or have a desire to feel real again, and a decision is made to create sensation and ‘wake up’."[4] A flow diagram of these two theories accompanies this section.
It is also important to note that many self-injurers report feeling very little to no pain while self-harming.[20]
Those who engage in self-injury face the contradictory reality of harming themselves whilst at the same time obtaining relief from this act. It may even be hard for some to actually initiate cutting, but they often do because they know the relief that will follow. For some self-injurers this relief is primarily psychological whilst for others this feeling of relief comes from the beta endorphins released in the brain (the same chemicals that are thought to be responsible for the "runner's high"). These act to reduce tension and emotional distress and may lead to a feeling of calm.
As a coping mechanism, self-injury can become psychologically addictive because, to the self-injurer, it works; it enables him/her to deal with intense stress in the current moment. The patterns sometimes created by it, such as specific time intervals between acts of self-injury, can also create a behavioral pattern that can result in a wanting or craving to fulfill thoughts of self-injury.
Another possible source of self-injury can be self-loathing, often as a means of punishment for having strong feelings that they were expected to suppress when they were children, or because they feel bad and undeserving, having previously been physically or emotionally abused and feeling that they were deserving of the abuse.[39]
# Motives
Self-injury is not typically suicidal behavior, although there is the possibility that a self-inflicted injury may result in life-threatening damage. [1] Although the person may not recognise the connection, self-injury often occurs when facing what seem like overwhelming or distressing feelings. The motivations for self-injury vary as it may be used to fulfill a number of different functions.[40] These functions include self-injury being used as a coping mechanism which provides temporary relief of intense feelings such as anxiety, depression, stress, emotional numbness and a sense of failure or self-loathing. There is a positive statistical correlation between self-injury and emotional abuse.[16][22] Intense pain can lead to the release of endorphins [40] and so deliberate self-harm may become a means of seeking pleasure, although in many cases self-injury becomes a means to manage pain, in contrast to the pain that may have been experience through abuse earlier in the sufferers life of which they had no control over.[1] For some people harming oneself can be a way to draw attention to the need for help and to ask for assistance in an indirect way but may also be an attempt to affect others and to manipulate them in some way emotionally.[1] [40] However, those with chronic, repetitive self injury often do not want attention and hide their scars carefully.[41]
# Self-injury awareness
There are many movements among the general self-injury community to make self-injury itself and treatment better known to mental health professionals as well as the general public. Self Injury Awareness Day (SIAD), which is set for March 1 of every year, is one such movement. On this day, some people choose to be more open about their own self-injury, and awareness organisations make special efforts to raise awareness about self-injury. Some people wear ribbons to show awareness; commonly orange ribbons are used for this. Sometimes a red and black ribbon is also used, generally signifying a person who self-injures.[42] Sometimes orange is used to represent those who self-injure, white for those who don't injure but show support, and white and orange together show someone who is trying to stop or has stopped self-injury.[43] A single white bead on an orange bracelet may sometimes be used for those who want to stop and several mixed white and orange beads is for those who have stopped.[44]
# Treatment
There is considerable uncertainty about which forms of psychosocial and physical treatments of patients who harm themselves are most effective and as such further clinical studies are required.[45] Psychiatric and personality disorders are common in individuals who self-harm and as a result self-injury may be an indicator of depression and/or other psychological problems.[46] Many people who self-harm suffer from moderate or severe clinical depression and therefore treatment with antidepressant drugs may often be indicated for these patients.[46] Cognitive Behavioral Therapy may also be used (where the resources are available) to assist those with axis 1 diagnoses, such as depression, schizophrenia, and bipolar disorder. DBT, or Dialectical behavioral therapy can be very successful for those individuals exhibiting a personality disorder, and could potentially be used for those with other mental illnesses who exhibit self-injurious behavior. Diagnosis and treatment of the causes of self-harm is thought by many to be the best approach to self-injury.Template:Who But in some cases, particularly in clients with a personality disorder, this is not very effective, so more clinicians are starting to take a DBT approach in order to reduce the behavior itself. People who self-injure may be advised to use coping skills, such as journaling or taking a walk, when they have the urge to harm themselves. They may also be told to avoid having the objects they use to harm themselves within easy reach. People who rely on habitual self-injury are sometimes psychiatrically hospitalised, based on their stability, and their ability and especially their willingness to get help.[47]
In individuals with developmental disabilities, occurrence of self-injury is often demonstrated to be related to its effects on the environment, such as obtaining attention or desired materials or escaping demands. As developmentally disabled individuals often have communication or social deficits, self-injury may be their way of obtaining these things which they are otherwise unable to obtain in a socially appropriate way (such as by asking). One approach for treating self-injury thus is to teach an alternative, appropriate response which obtains the same result as the self-injury.[48][49][50] | https://www.wikidoc.org/index.php/Self-harm | |
6b355367e65fe5a81892fa64c0cd254c6c6f86bf | wikidoc | Self-hatred | Self-hatred
Self-hatred, self-loathing, also sometimes autophobia refers to an extreme dislike of oneself, or being angry at oneself. The term is also used to designate a dislike or hatred of a group to which one belongs. For instance, 'ethnic self-hatred' is the extreme dislike of one's ethnic group. Accusations of self-hatred are often used as an ad hominem attack.
The term 'self-hatred' is used infrequently by psychologists and psychiatrists, who would usually describe people who hate themselves as 'persons with low self-esteem'. Some people think that self-hatred and shame are important factors in some or many mental disorders, especially disorders that involve a perceived defect of oneself (e.g. body dysmorphic disorder). "Ethnic self-hatred" is considered by some people as being a cultural issue, to which psychological theories have limited relevance.
# Types of self-hatred
The term self-hatred can refer to either a strong dislike for oneself, one's actions, or a strong dislike or hatred of one's own race, gender, nationality, sexual orientation et cetera. When used in the latter context it is generally defined as hatred of one's identity based on the demographic in question, as well as a desire to distance oneself from this identity.
## Personal self-hatred
Personal self-hatred and self-loathing can result from an inferiority complex. Some sociology theorists such as Jerry Mander see television programming as being deliberately designed to induce self-hatred, negative body image, and depression, with the advertising then being used to suggest the cure . See also the arguments related to the Kill your television phenomenon.
## Self-injury as self-hatred
Self-harm is a psychological disorder, which may involve self-hatred, where the subject feels compelled to physically injure themselves. | Self-hatred
Template:Search infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Self-hatred, self-loathing, also sometimes autophobia refers to an extreme dislike of oneself, or being angry at oneself. The term is also used to designate a dislike or hatred of a group to which one belongs. For instance, 'ethnic self-hatred' is the extreme dislike of one's ethnic group. Accusations of self-hatred are often used as an ad hominem attack. [1] [2]
The term 'self-hatred' is used infrequently by psychologists and psychiatrists, who would usually describe people who hate themselves as 'persons with low self-esteem'. Some people think that self-hatred and shame are important factors in some or many mental disorders, especially disorders that involve a perceived defect of oneself (e.g. body dysmorphic disorder). "Ethnic self-hatred" is considered by some people as being a cultural issue, to which psychological theories have limited relevance.
# Types of self-hatred
The term self-hatred can refer to either a strong dislike for oneself, one's actions, or a strong dislike or hatred of one's own race, gender, nationality, sexual orientation et cetera. When used in the latter context it is generally defined as hatred of one's identity based on the demographic in question, as well as a desire to distance oneself from this identity.
## Personal self-hatred
Personal self-hatred and self-loathing can result from an inferiority complex. Some sociology theorists such as Jerry Mander see television programming as being deliberately designed to induce self-hatred, negative body image, and depression, with the advertising then being used to suggest the cure [2]. See also the arguments related to the Kill your television phenomenon.
## Self-injury as self-hatred
Self-harm is a psychological disorder, which may involve self-hatred, where the subject feels compelled to physically injure themselves. | https://www.wikidoc.org/index.php/Self-hatred | |
336c763a62d0d437051e971058a9ff90cd8146b2 | wikidoc | Self injury | Self injury
Synonyms and keywords: Self-mutilation.
# Overview
Self-injury (SI) or self-harm (SH) is deliberate injury inflicted by a person upon their own body without suicidal intent. Some scholars use more technical definitions related to specific aspects of this behavior. These acts may be aimed at relieving otherwise unbearable emotions, sensations of unreality and numbness. It is listed in the DSM-IV-TR as a symptom of borderline personality disorder and depressive disorders, it is sometimes associated with mental illness, a history of trauma and abuse including emotional abuse, sexual abuse, eating disorders, or mental traits such as low self-esteem or perfectionism. Self harmers are often mistaken for being suicidal, but the majority of the time this is not the case. Non-fatal self-harm is common in young people worldwide and due to this prevailance the term self-harm is increasingly used to denote any non-fatal acts of deliberate self-harm, irrespective of the intention.
# Definition
Self-injury, sometimes referred to as self-harm (SH), self-inflicted violence (SIV) or self-injurious behavior (SIB), refers to a spectrum of behaviors where demonstrable injury is self-inflicted. The term self-mutilation is also sometimes used, although this phrase evokes connotations that some find worrisome, inaccurate, or offensive. A broader definition of self-injury might also include those who inflict harm on their bodies by means of disordered eating, as well as tattooing or body piercing that goes beyond the limits of culturally accepted body modification.
A common belief regarding self-injury is that it is an attention-seeking behavior; however, in most cases, this is untrue. Most self-injurers are very self-conscious of both their wounds and scars, and go to great lengths to conceal their behavior from others. They may offer alternative explanations for their injuries, or conceal their scars with clothing. Self-injury in such individuals is not associated with suicidal or para-suicidal behavior. The person who self-injures is not usually seeking to end his or her own life; it has been suggested instead that he or she is using self-injury as a coping mechanism to relieve emotional pain or discomfort. However, studies of individuals with developmental disabilities (such as mental retardation) have shown self-injury being dependent on environmental factors such as obtaining attention or escape from demands. Though this is not always the case, some individuals suffer from disassociation and they harbor a desire to feel real and/or to fit in to society's rules.
## Methods of injury
A common form of self-injury involves making cuts in the skin of the arms, legs, abdomen, inner thighs, etc. This is colloquially referred to as "cutting"; a person who routinely does this may be colloquially called a "cutter". The number of self-injury methods are only limited by an individual's creativity. The bodily locations of self-injury are often areas that are easily hidden and concealed from the detection of others.
Examples of self-injury other than cutting include:
- Punching, hitting and scratching
- Choking, constricting of the airway
- Self-biting of hands, limbs, tongue, lips, or arms
- Picking at or re-opening wounds (dermatillomania), ulceration, or sutures
- Hair-pulling (trichotillomania)
- Burning, including cigarette burns, and self-incendiarism (as well as eraser burns, chemical burns )
- Stabbing self with wire, pins, needles, nails, staples, pens, or hair accessories
- Pinching or clamping, as with clothes pins, paper clips, etc.
- Ingesting corrosive chemicals, batteries, or pins
- Self-poisoning; for example by over-dosing on medication and/or alcohol, without suicidal intent
- Self-injury among individuals with developmental disabilities often involves relatively simple actions, such as banging one's head against a hard surface, punching hard surfaces, biting oneself (usually hands or arms), or picking wounds. It may also include pica, the swallowing of nonfood items, which can be extremely dangerous and sometimes fatal.
- Constriction of the blood circulation via the use of rubber bands over a long period of time.
- Self-inflicted starvation.
## Other definitions
Strictly speaking, self-harm is a general term for self-damaging activities (which could include such activities as alcohol abuse or bulimia). Self-injury refers more specifically to the practice of cutting, bruising, poisoning, over-dosing (without suicidal intent), burning, or otherwise directly injuring the body. Many people, including health-care workers, define self-harm based around the act of damaging one's own body. It may be more accurate to define self-harm based around the intent, and the emotional distress that the person wishes to deal with. An example of this form of definition is provided by the self-injury awareness voluntary organisation, LifeSIGNS.
Neither the DSM-IV-TR nor the ICD-10 provide diagnostic criteria for self-injury. It is often seen as only a symptom of an underlying disorder, though many people who self-injure would like this to be addressed.
Self-inflicted wounds is a specific term associated with soldiers, where they inflicted harm on themselves (commonly a shot in the foot or hand) in order to obtain early dismissal from combat.This differs from the common definition of self-injury as the damage is inflicted for a specific secondary purpose.
# Risk factors
A number of social or psychological factors can be seen to have a positive statistical correlation with self-injury or its repetition.
People experiencing various forms of mental ill-health can be considered to be at higher risk of self-injuring. Key issues are depression, phobias, and conduct disorders. Substance abuse is also considered a risk factor as are some personal characteristics such as poor problem resolution skills, impulsivity, hopelessness and aggression. Emotionally invalidating environments where parents punish children for expressing sadness or hurt can attribute to a lack of trust in oneself and difficulty experiencing intense emotions. Abuse during childhood is accepted as a primary social factor, also losing a parent or loved one, along with troubled parental or partner relationships. Factors such as war, poverty, and unemployment may also contribute.
In addition, some individuals with pervasive developmental disabilities, more popularly known as autism, engage in self-injury, while is debated whether it is a form of self-stimulation or for the purpose of harming one's self. However, some people who self-injure do not experience these factors.
# Demographics
Accurate statistics on self-injury are hard to come by since most self-injurers conceal their injuries. Recorded figures can be based on three sources: psychiatric samples, hospital admissions and general population surveys. Studies based only on hospital admissions may hide the larger group of self-injurers who do not need or seek hospital treatment for their injuries. Many of these statistics show that more women seem to self-injure than men, and that it is more common among young people. This most likely explains the female bias that the media seems to portray in its attitude to self-injury, despite research in 2006 by Marchetto which suggests no gender differences were observed among skin-cutters.
The Mental Health Foundation estimates the rate in the UK to be 0.77%, and that the majority of people who self-harm are aged between 11 and 25 years, with between 1 in 12 and 1 in 15 young people self-harming. Many adolescents who present to general hospitals with deliberate self-harm report previous episodes for which they did not receive medical attention. A study of homeless youth (age 16 to 19) found that 69% practiced self-injury on at least one occasion with 12% receiving medical attention for the self-inflicted wounds. There was no significant difference in frequency between gender (72% of males vs. 66% females), however gender correlations may be made between the methods of self-injury with the exception of cutting being most common for both.
About 10% of admissions to medical wards in the UK are as a result of self-harm, the majority of which are drug overdoses. The WHO/EURO Multicentre Study of Suicide estimated that the average European rate of self-injury for persons over 15 years is 0.14% for males and 0.193% for females. For each age group the female rate exceeded that of the males, with the highest rate among females in the 15-24 age group and the highest rate among males in the 12-34 age group. Recently, however, it has been found that the female to male ratio, previously thought to be around 2:1, is diminishing – in Ireland it has been close to unity for a number of years.. In a study of psychiatric morbidity carried out in the UK an overall lifetime prevalence of 2.4% was found, 2.0% of which were male and 2.7% of female.
In a study of undergraduate students in the United States, 9.8% of the students surveyed indicated that they had purposefully cut or burned themselves on at least one occasion in the past. When the definition of self-injury was expanded to include head-banging, scratching oneself, and hitting oneself along with cutting and burning, 32% of the sample said they had done this. This suggests that this problem is not associated only with severely disturbed psychiatric patients but is not uncommon among young adults.
## Gender differences
A discourse analysis of self-injury research demonstrates methodological and sampling errors that explain the disproportional representation of females that practice self-injury. Brickman argues "Medical discourse has again pathologized the female" and the profiling of self-injurers as female is the unsubstantiated result of social biases.
There does not appear to be a difference in motivation for self-harm in adolescent males and females. For example, for both genders there is an incremental increase in deliberate self-harm associated with an increase in consumption of cigarettes, drugs and alcohol. Triggering factors such as low self-esteem and having friends and family members who self-harm are also common between both males and females. However, females who self-cut are more likely than males to explain their self-harm episode by saying that they had wanted to punish themselves.
The most common methods of self-injury reported by both male and female subjects were scratching or pinching with fingernails or other objects to the point that bleeding occurred or marks remained on the skin (51.6%), banging or punching objects to the point of bruising or bleeding (37.6%), cutting (33.7%), and punching or banging oneself to the point of bruising or bleeding (24.5%). Female subjects were 2.3 times more likely to scratch or pinch and 2.4 times more likely to cut. Male subjects were 2.8 times more likely than female subjects to punch an object with the intention of injuring themselves. Male subjects were 1.8 times more likely to injure their hands, whereas female subjects were 2.3 times more likely to injure their wrists and 2.4 times more likely to injure their thighs. Self-injury is popularly assumed to represent a female phenomenon, and although there is some disputed support to this claim, the authors of the study believe that the popular association of self-injury with cutting may account for this belief.
In New Zealand, more females are hospitalised for intentional self-harm than males. Females more commonly choose methods such as self-poisoning that generally are not fatal, but still serious enough to require hospitalization.
## Self-harm in the elderly
In a study of a district general hospital in the UK, 5.4% of all the hospital's self-harm cases were aged over 65. The male to female ratio was 2:3 although the self-harm rates for males and females over 65 in the local population were identical. Over 90% had depressive conditions, and 63% had significant physical illness. Under 10% of the patients gave a history of earlier self-harm, while both the repetition and suicide rates were very low which could be explained due to the absence of factors known to be associated with repetition such as personality disorder and alcohol abuse.
## Self-harm in the developing world
Only recently have attempts to improve health in the developing world concentrated on not only physical illness, but mental health also. Deliberate self-harm is common in the developing world. For example, Sri Lanka has a high incidence of suicide and self poisoning with agricultural pesticides or natural poisons is an important cause of mortality in many rural areas. Many people admitted for deliberate self-poisoning during a study by Eddleston et al. were young and few expressed a desire to die, but death was relatively common in the young in these cases. The improvement of medical management of acute poisoning in the developing world is poor and improvements are required in order to reduce mortality.
Some of the causes of deliberate self-poisoning in Sri Lankan adolescents included bereavement and harsh discipline by parents. The coping mechanisms are being spread in local communities as people are surrounded by others who have previously deliberately harmed themselves or attempted suicide. One way of reducing self-harm would be to limit access to poisons; however many cases involve pesticides or yellow oleander seeds, and the reduction of access to these agents would be difficult. Great potential for the reduction of self-harm lies in education and prevention, but limited resources in the developing world make these methods challenging.
# Psychology
File:Self-injury.svg
Attempts to understand self-injury fall broadly into either attempts to interpret motives, or application of psychological models.
Motives for self-injury are often personal, often do not fit into medicalised models of behaviour and may seem incomprehensible to others, as demonstrated by this quote:
Motives for self-injury can be different. Some feel as if they are not good enough and they might not want to take it out on the person who harmed them. It's often difficult for them to open up and tell about their "secret shame". Often when the sufferer does tell somebody there is a lack of understanding or knowledge of how to help.
Assessment of motives in a medical setting is usually based on precursors to the incident, circumstances and information from the patient however the limited studies comparing professional and personal assessments show that these differ with professionals suggesting more manipulative or punitive motives.
The UK ONS study reported only two motives: “to draw attention” and “because of anger”.
Many people who self-injure state that it allows them to "go away" or dissociate, separating the mind from feelings that are causing anguish. This may be achieved by tricking the mind into believing the pain felt at the time is caused by self-injury instead of the issues they were facing before: the physical pain therefore acts as a distraction from emotional pain. To complement this theory, one can consider the need to 'stop' feeling emotional pain and mental agitation. "A person may be hyper-sensitive and overwhelmed; a great many thoughts may be revolving within their mind, and they may either become triggered or could make a decision to stop the overwhelming feelings." The sexual organs may be deliberately hurt as a way to deal with unwanted feelings of sexuality, or as a means of punishing sexual organs that may be perceived as having responded in contravention to the person's wellbeing. (e.g., responses to childhood sexual abuse).
Alternatively self-injury may be a means of feeling something, even if the sensation is unpleasant and painful. Those who self-injure sometimes describe feelings of emptiness or numbness (anhedonia), and physical pain may be a relief from these feelings. "A person may be detached from himself or herself, detached from life, numb and unfeeling. They may then recognise the need to function more, or have a desire to feel real again, and a decision is made to create sensation and ‘wake up’." A flow diagram of these two theories accompanies this section.
It is also important to note that many self-injurers report feeling very little to no pain while self-harming.
Those who engage in self-injury face the contradictory reality of harming themselves whilst at the same time obtaining relief from this act. It may even be hard for some to actually initiate cutting, but they often do because they know the relief that will follow. For some self-injurers this relief is primarily psychological whilst for others this feeling of relief comes from the beta endorphins released in the brain (the same chemicals that are thought to be responsible for the "runner's high"). These act to reduce tension and emotional distress and may lead to a feeling of calm.
As a coping mechanism, self-injury can become psychologically addictive because, to the self-injurer, it works; it enables him/her to deal with intense stress in the current moment. The patterns sometimes created by it, such as specific time intervals between acts of self-injury, can also create a behavioral pattern that can result in a wanting or craving to fulfill thoughts of self-injury.
Another possible source of self-injury can be self-loathing, often as a means of punishment for having strong feelings that they were expected to suppress when they were children, or because they feel bad and undeserving, having previously been physically or emotionally abused and feeling that they were deserving of the abuse.
# Motives
Self-injury is not typically suicidal behavior, although there is the possibility that a self-inflicted injury may result in life-threatening damage. Although the person may not recognise the connection, self-injury often occurs when facing what seem like overwhelming or distressing feelings. The motivations for self-injury vary as it may be used to fulfill a number of different functions. These functions include self-injury being used as a coping mechanism which provides temporary relief of intense feelings such as anxiety, depression, stress, emotional numbness and a sense of failure or self-loathing. There is a positive statistical correlation between self-injury and emotional abuse. Intense pain can lead to the release of endorphins and so deliberate self-harm may become a means of seeking pleasure, although in many cases self-injury becomes a means to manage pain, in contrast to the pain that may have been experience through abuse earlier in the sufferers life of which they had no control over. For some people harming oneself can be a way to draw attention to the need for help and to ask for assistance in an indirect way but may also be an attempt to affect others and to manipulate them in some way emotionally. However, those with chronic, repetitive self injury often do not want attention and hide their scars carefully.
# Self-injury awareness
There are many movements among the general self-injury community to make self-injury itself and treatment better known to mental health professionals as well as the general public. Self Injury Awareness Day (SIAD), which is set for March 1 of every year, is one such movement. On this day, some people choose to be more open about their own self-injury, and awareness organisations make special efforts to raise awareness about self-injury. Some people wear ribbons to show awareness; commonly orange ribbons are used for this. Sometimes a red and black ribbon is also used, generally signifying a person who self-injures. Sometimes orange is used to represent those who self-injure, white for those who don't injure but show support, and white and orange together show someone who is trying to stop or has stopped self-injury. A single white bead on an orange bracelet may sometimes be used for those who want to stop and several mixed white and orange beads is for those who have stopped.
# Treatment
There is considerable uncertainty about which forms of psychosocial and physical treatments of patients who harm themselves are most effective and as such further clinical studies are required. Psychiatric and personality disorders are common in individuals who self-harm and as a result self-injury may be an indicator of depression and/or other psychological problems. Many people who self-harm suffer from moderate or severe clinical depression and therefore treatment with antidepressant drugs may often be indicated for these patients. Cognitive Behavioral Therapy may also be used (where the resources are available) to assist those with axis 1 diagnoses, such as depression, schizophrenia, and bipolar disorder. DBT, or Dialectical behavioral therapy can be very successful for those individuals exhibiting a personality disorder, and could potentially be used for those with other mental illnesses who exhibit self-injurious behavior. Diagnosis and treatment of the causes of self-harm is thought by many to be the best approach to self-injury.Template:Who But in some cases, particularly in clients with a personality disorder, this is not very effective, so more clinicians are starting to take a DBT approach in order to reduce the behavior itself. People who self-injure may be advised to use coping skills, such as journaling or taking a walk, when they have the urge to harm themselves. They may also be told to avoid having the objects they use to harm themselves within easy reach. People who rely on habitual self-injury are sometimes psychiatrically hospitalised, based on their stability, and their ability and especially their willingness to get help.
In individuals with developmental disabilities, occurrence of self-injury is often demonstrated to be related to its effects on the environment, such as obtaining attention or desired materials or escaping demands. As developmentally disabled individuals often have communication or social deficits, self-injury may be their way of obtaining these things which they are otherwise unable to obtain in a socially appropriate way (such as by asking). One approach for treating self-injury thus is to teach an alternative, appropriate response which obtains the same result as the self-injury. | Self injury
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Self-mutilation.
# Overview
Self-injury (SI) or self-harm (SH) is deliberate injury inflicted by a person upon their own body without suicidal intent. Some scholars use more technical definitions related to specific aspects of this behavior. These acts may be aimed at relieving otherwise unbearable emotions, sensations of unreality and numbness. It is listed in the DSM-IV-TR as a symptom of borderline personality disorder and depressive disorders, it is sometimes associated with mental illness, a history of trauma and abuse including emotional abuse, sexual abuse, eating disorders, or mental traits such as low self-esteem or perfectionism. Self harmers are often mistaken for being suicidal, but the majority of the time this is not the case.[1] Non-fatal self-harm is common in young people worldwide[2] and due to this prevailance the term self-harm is increasingly used to denote any non-fatal acts of deliberate self-harm, irrespective of the intention.[3]
# Definition
Self-injury, sometimes referred to as self-harm (SH), self-inflicted violence (SIV) or self-injurious behavior (SIB), refers to a spectrum of behaviors where demonstrable injury is self-inflicted.[4] The term self-mutilation is also sometimes used, although this phrase evokes connotations that some find worrisome, inaccurate, or offensive.[4] A broader definition of self-injury might also include those who inflict harm on their bodies by means of disordered eating, as well as tattooing or body piercing that goes beyond the limits of culturally accepted body modification.
A common belief regarding self-injury is that it is an attention-seeking behavior; however, in most cases, this is untrue. Most self-injurers are very self-conscious of both their wounds and scars, and go to great lengths to conceal their behavior from others. They may offer alternative explanations for their injuries, or conceal their scars with clothing.[5][6] Self-injury in such individuals is not associated with suicidal or para-suicidal behavior. The person who self-injures is not usually seeking to end his or her own life; it has been suggested instead that he or she is using self-injury as a coping mechanism to relieve emotional pain or discomfort.[7] However, studies of individuals with developmental disabilities (such as mental retardation) have shown self-injury being dependent on environmental factors such as obtaining attention or escape from demands.[8] Though this is not always the case, some individuals suffer from disassociation and they harbor a desire to feel real and/or to fit in to society's rules.
## Methods of injury
A common form of self-injury involves making cuts in the skin of the arms, legs, abdomen, inner thighs, etc. This is colloquially referred to as "cutting"; a person who routinely does this may be colloquially called a "cutter".[9] The number of self-injury methods are only limited by an individual's creativity. The bodily locations of self-injury are often areas that are easily hidden and concealed from the detection of others.[10]
Examples of self-injury other than cutting include:
- Punching, hitting and scratching
- Choking, constricting of the airway
- Self-biting of hands, limbs, tongue, lips, or arms
- Picking at or re-opening wounds (dermatillomania), ulceration, or sutures
- Hair-pulling (trichotillomania)
- Burning, including cigarette burns, and self-incendiarism (as well as eraser burns, chemical burns [example; salt and ice burns])
- Stabbing self with wire, pins, needles, nails, staples, pens, or hair accessories
- Pinching or clamping, as with clothes pins, paper clips, etc.
- Ingesting corrosive chemicals, batteries, or pins[11]
- Self-poisoning; for example by over-dosing on medication and/or alcohol, without suicidal intent[5]
- Self-injury among individuals with developmental disabilities often involves relatively simple actions, such as banging one's head against a hard surface, punching hard surfaces, biting oneself (usually hands or arms), or picking wounds. It may also include pica, the swallowing of nonfood items, which can be extremely dangerous and sometimes fatal.
- Constriction of the blood circulation via the use of rubber bands over a long period of time.
- Self-inflicted starvation.
## Other definitions
Strictly speaking, self-harm is a general term for self-damaging activities (which could include such activities as alcohol abuse or bulimia). Self-injury refers more specifically to the practice of cutting, bruising, poisoning, over-dosing (without suicidal intent), burning, or otherwise directly injuring the body.[12] Many people, including health-care workers, define self-harm based around the act of damaging one's own body. It may be more accurate to define self-harm based around the intent, and the emotional distress that the person wishes to deal with. An example of this form of definition is provided by the self-injury awareness voluntary organisation, LifeSIGNS.[13]
Neither the DSM-IV-TR nor the ICD-10 provide diagnostic criteria for self-injury. It is often seen as only a symptom of an underlying disorder,[7] though many people who self-injure would like this to be addressed.[6]
Self-inflicted wounds is a specific term associated with soldiers, where they inflicted harm on themselves (commonly a shot in the foot or hand) in order to obtain early dismissal from combat.[14][15]This differs from the common definition of self-injury as the damage is inflicted for a specific secondary purpose.
# Risk factors
A number of social or psychological factors can be seen to have a positive statistical correlation with self-injury or its repetition.
People experiencing various forms of mental ill-health can be considered to be at higher risk of self-injuring. Key issues are depression,[16][17] phobias,[16] and conduct disorders.[18] Substance abuse is also considered a risk factor[7] as are some personal characteristics such as poor problem resolution skills, impulsivity, hopelessness and aggression.[7] Emotionally invalidating environments where parents punish children for expressing sadness or hurt can attribute to a lack of trust in oneself and difficulty experiencing intense emotions.[19] Abuse during childhood is accepted as a primary social factor,[20] also losing a parent or loved one,[21] along with troubled parental or partner relationships.[7][22] Factors such as war, poverty, and unemployment may also contribute.[16][23][24]
In addition, some individuals with pervasive developmental disabilities, more popularly known as autism, engage in self-injury, while is debated whether it is a form of self-stimulation or for the purpose of harming one's self. [25] However, some people who self-injure do not experience these factors.[5]
# Demographics
Accurate statistics on self-injury are hard to come by since most self-injurers conceal their injuries. Recorded figures can be based on three sources: psychiatric samples, hospital admissions and general population surveys.[3] Studies based only on hospital admissions may hide the larger group of self-injurers who do not need or seek hospital treatment for their injuries.[7] Many of these statistics show that more women seem to self-injure than men, and that it is more common among young people. This most likely explains the female bias that the media seems to portray in its attitude to self-injury, despite research in 2006 by Marchetto[26] which suggests no gender differences were observed among skin-cutters.
The Mental Health Foundation estimates the rate in the UK to be 0.77%,[21] and that the majority of people who self-harm are aged between 11 and 25 years, with between 1 in 12 and 1 in 15 young people self-harming. Many adolescents who present to general hospitals with deliberate self-harm report previous episodes for which they did not receive medical attention.[3] A study of homeless youth (age 16 to 19) found that 69% practiced self-injury on at least one occasion with 12% receiving medical attention for the self-inflicted wounds. There was no significant difference in frequency between gender (72% of males vs. 66% females), however gender correlations may be made between the methods of self-injury with the exception of cutting being most common for both.[27]
About 10% of admissions to medical wards in the UK are as a result of self-harm, the majority of which are drug overdoses. [21] The WHO/EURO Multicentre Study of Suicide estimated that the average European rate of self-injury for persons over 15 years is 0.14% for males and 0.193% for females. For each age group the female rate exceeded that of the males, with the highest rate among females in the 15-24 age group and the highest rate among males in the 12-34 age group. Recently, however, it has been found that the female to male ratio, previously thought to be around 2:1, is diminishing – in Ireland it has been close to unity for a number of years.[28]. In a study of psychiatric morbidity carried out in the UK an overall lifetime prevalence of 2.4% was found, 2.0% of which were male and 2.7% of female.[16]
In a study of undergraduate students in the United States, 9.8% of the students surveyed indicated that they had purposefully cut or burned themselves on at least one occasion in the past. When the definition of self-injury was expanded to include head-banging, scratching oneself, and hitting oneself along with cutting and burning, 32% of the sample said they had done this. This suggests that this problem is not associated only with severely disturbed psychiatric patients but is not uncommon among young adults.[29]
## Gender differences
A discourse analysis of self-injury research demonstrates methodological and sampling errors that explain the disproportional representation of females that practice self-injury. Brickman argues "Medical discourse has again pathologized the female" and the profiling of self-injurers as female is the unsubstantiated result of social biases.[30]
There does not appear to be a difference in motivation for self-harm in adolescent males and females. For example, for both genders there is an incremental increase in deliberate self-harm associated with an increase in consumption of cigarettes, drugs and alcohol. Triggering factors such as low self-esteem and having friends and family members who self-harm are also common between both males and females. [3] However, females who self-cut are more likely than males to explain their self-harm episode by saying that they had wanted to punish themselves.
The most common methods of self-injury reported by both male and female subjects were scratching or pinching with fingernails or other objects to the point that bleeding occurred or marks remained on the skin (51.6%), banging or punching objects to the point of bruising or bleeding (37.6%), cutting (33.7%), and punching or banging oneself to the point of bruising or bleeding (24.5%).[31] Female subjects were 2.3 times more likely to scratch or pinch and 2.4 times more likely to cut. Male subjects were 2.8 times more likely than female subjects to punch an object with the intention of injuring themselves. Male subjects were 1.8 times more likely to injure their hands, whereas female subjects were 2.3 times more likely to injure their wrists and 2.4 times more likely to injure their thighs. Self-injury is popularly assumed to represent a female phenomenon, and although there is some disputed support to this claim, the authors of the study believe that the popular association of self-injury with cutting may account for this belief.
In New Zealand, more females are hospitalised for intentional self-harm than males. Females more commonly choose methods such as self-poisoning that generally are not fatal, but still serious enough to require hospitalization.[32]
## Self-harm in the elderly
In a study of a district general hospital in the UK, 5.4% of all the hospital's self-harm cases were aged over 65. The male to female ratio was 2:3 although the self-harm rates for males and females over 65 in the local population were identical. Over 90% had depressive conditions, and 63% had significant physical illness. Under 10% of the patients gave a history of earlier self-harm, while both the repetition and suicide rates were very low which could be explained due to the absence of factors known to be associated with repetition such as personality disorder and alcohol abuse.[33]
## Self-harm in the developing world
Only recently have attempts to improve health in the developing world concentrated on not only physical illness, but mental health also.[34] Deliberate self-harm is common in the developing world. For example, Sri Lanka has a high incidence of suicide[35] and self poisoning with agricultural pesticides or natural poisons is an important cause of mortality in many rural areas. Many people admitted for deliberate self-poisoning during a study by Eddleston et al. [34] were young and few expressed a desire to die, but death was relatively common in the young in these cases. The improvement of medical management of acute poisoning in the developing world is poor and improvements are required in order to reduce mortality.
Some of the causes of deliberate self-poisoning in Sri Lankan adolescents included bereavement and harsh discipline by parents. The coping mechanisms are being spread in local communities as people are surrounded by others who have previously deliberately harmed themselves or attempted suicide.[34] One way of reducing self-harm would be to limit access to poisons;[36] however many cases involve pesticides or yellow oleander seeds, and the reduction of access to these agents would be difficult. Great potential for the reduction of self-harm lies in education and prevention, but limited resources in the developing world make these methods challenging.
# Psychology
File:Self-injury.svg
Attempts to understand self-injury fall broadly into either attempts to interpret motives, or application of psychological models.
Motives for self-injury are often personal, often do not fit into medicalised models of behaviour and may seem incomprehensible to others, as demonstrated by this quote:
Motives for self-injury can be different. Some feel as if they are not good enough and they might not want to take it out on the person who harmed them. It's often difficult for them to open up and tell about their "secret shame". Often when the sufferer does tell somebody there is a lack of understanding or knowledge of how to help.
Assessment of motives in a medical setting is usually based on precursors to the incident, circumstances and information from the patient[7] however the limited studies comparing professional and personal assessments show that these differ with professionals suggesting more manipulative or punitive motives.[38]
The UK ONS study reported only two motives: “to draw attention” and “because of anger”.[16]
Many people who self-injure state that it allows them to "go away" or dissociate, separating the mind from feelings that are causing anguish. This may be achieved by tricking the mind into believing the pain felt at the time is caused by self-injury instead of the issues they were facing before: the physical pain therefore acts as a distraction from emotional pain.[5] To complement this theory, one can consider the need to 'stop' feeling emotional pain and mental agitation. "A person may be hyper-sensitive and overwhelmed; a great many thoughts may be revolving within their mind, and they may either become triggered or could make a decision to stop the overwhelming feelings."[4] The sexual organs may be deliberately hurt as a way to deal with unwanted feelings of sexuality, or as a means of punishing sexual organs that may be perceived as having responded in contravention to the person's wellbeing. (e.g., responses to childhood sexual abuse).[citation needed]
Alternatively self-injury may be a means of feeling something, even if the sensation is unpleasant and painful. Those who self-injure sometimes describe feelings of emptiness or numbness (anhedonia), and physical pain may be a relief from these feelings. "A person may be detached from himself or herself, detached from life, numb and unfeeling. They may then recognise the need to function more, or have a desire to feel real again, and a decision is made to create sensation and ‘wake up’."[4] A flow diagram of these two theories accompanies this section.
It is also important to note that many self-injurers report feeling very little to no pain while self-harming.[20]
Those who engage in self-injury face the contradictory reality of harming themselves whilst at the same time obtaining relief from this act. It may even be hard for some to actually initiate cutting, but they often do because they know the relief that will follow. For some self-injurers this relief is primarily psychological whilst for others this feeling of relief comes from the beta endorphins released in the brain (the same chemicals that are thought to be responsible for the "runner's high"). These act to reduce tension and emotional distress and may lead to a feeling of calm.
As a coping mechanism, self-injury can become psychologically addictive because, to the self-injurer, it works; it enables him/her to deal with intense stress in the current moment. The patterns sometimes created by it, such as specific time intervals between acts of self-injury, can also create a behavioral pattern that can result in a wanting or craving to fulfill thoughts of self-injury.
Another possible source of self-injury can be self-loathing, often as a means of punishment for having strong feelings that they were expected to suppress when they were children, or because they feel bad and undeserving, having previously been physically or emotionally abused and feeling that they were deserving of the abuse.[39]
# Motives
Self-injury is not typically suicidal behavior, although there is the possibility that a self-inflicted injury may result in life-threatening damage. [1] Although the person may not recognise the connection, self-injury often occurs when facing what seem like overwhelming or distressing feelings. The motivations for self-injury vary as it may be used to fulfill a number of different functions.[40] These functions include self-injury being used as a coping mechanism which provides temporary relief of intense feelings such as anxiety, depression, stress, emotional numbness and a sense of failure or self-loathing. There is a positive statistical correlation between self-injury and emotional abuse.[16][22] Intense pain can lead to the release of endorphins [40] and so deliberate self-harm may become a means of seeking pleasure, although in many cases self-injury becomes a means to manage pain, in contrast to the pain that may have been experience through abuse earlier in the sufferers life of which they had no control over.[1] For some people harming oneself can be a way to draw attention to the need for help and to ask for assistance in an indirect way but may also be an attempt to affect others and to manipulate them in some way emotionally.[1] [40] However, those with chronic, repetitive self injury often do not want attention and hide their scars carefully.[41]
# Self-injury awareness
There are many movements among the general self-injury community to make self-injury itself and treatment better known to mental health professionals as well as the general public. Self Injury Awareness Day (SIAD), which is set for March 1 of every year, is one such movement. On this day, some people choose to be more open about their own self-injury, and awareness organisations make special efforts to raise awareness about self-injury. Some people wear ribbons to show awareness; commonly orange ribbons are used for this. Sometimes a red and black ribbon is also used, generally signifying a person who self-injures.[42] Sometimes orange is used to represent those who self-injure, white for those who don't injure but show support, and white and orange together show someone who is trying to stop or has stopped self-injury.[43] A single white bead on an orange bracelet may sometimes be used for those who want to stop and several mixed white and orange beads is for those who have stopped.[44]
# Treatment
There is considerable uncertainty about which forms of psychosocial and physical treatments of patients who harm themselves are most effective and as such further clinical studies are required.[45] Psychiatric and personality disorders are common in individuals who self-harm and as a result self-injury may be an indicator of depression and/or other psychological problems.[46] Many people who self-harm suffer from moderate or severe clinical depression and therefore treatment with antidepressant drugs may often be indicated for these patients.[46] Cognitive Behavioral Therapy may also be used (where the resources are available) to assist those with axis 1 diagnoses, such as depression, schizophrenia, and bipolar disorder. DBT, or Dialectical behavioral therapy can be very successful for those individuals exhibiting a personality disorder, and could potentially be used for those with other mental illnesses who exhibit self-injurious behavior. Diagnosis and treatment of the causes of self-harm is thought by many to be the best approach to self-injury.Template:Who But in some cases, particularly in clients with a personality disorder, this is not very effective, so more clinicians are starting to take a DBT approach in order to reduce the behavior itself. People who self-injure may be advised to use coping skills, such as journaling or taking a walk, when they have the urge to harm themselves. They may also be told to avoid having the objects they use to harm themselves within easy reach. People who rely on habitual self-injury are sometimes psychiatrically hospitalised, based on their stability, and their ability and especially their willingness to get help.[47]
In individuals with developmental disabilities, occurrence of self-injury is often demonstrated to be related to its effects on the environment, such as obtaining attention or desired materials or escaping demands. As developmentally disabled individuals often have communication or social deficits, self-injury may be their way of obtaining these things which they are otherwise unable to obtain in a socially appropriate way (such as by asking). One approach for treating self-injury thus is to teach an alternative, appropriate response which obtains the same result as the self-injury.[48][49][50] | https://www.wikidoc.org/index.php/Self_injury | |
8327b6657bfc7e958f692b0865ad0f032bc4f800 | wikidoc | Semaglutide | Semaglutide
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# Black Box Warning
# Overview
Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist that is FDA approved for the adjunction of diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. There is a Black Box Warning for this drug as shown here. Common adverse reactions include nausea, vomiting, diarrhea, abdominal pain and constipation.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Semaglutide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
- Semaglutide is not recommended as a first-line therapy for patients who have inadequate glycemic control on diet and exercise because of the uncertain relevance of rodent C-cell tumor findings to humans.
- Semaglutide has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.
- Semaglutide is not a substitute for insulin. Semaglutide is not indicated for use in patients with type 1 diabetes mellitus or for the treatment of patients with diabetic ketoacidosis, as it would not be effective in these settings.
- Start semaglutide with a 0.25 mg subcutaneous injection once weekly for 4 weeks. The 0.25 mg dose is intended for treatment initiation and is not effective for glycemic control.
- After 4 weeks on the 0.25 mg dose, increase the dosage to 0.5 mg once weekly.
- If additional glycemic control is needed after at least 4 weeks on the 0.5 mg dose, the dosage may be increased to 1 mg once weekly. The maximum recommended dosage is 1 mg once weekly.
- Administer semaglutide once weekly, on the same day each week, at any time of the day, with or without meals.
- The day of weekly administration can be changed if necessary as long as the time between two doses is at least 2 days (>48 hours).
- If a dose is missed, administer semaglutide as soon as possible within 5 days after the missed dose. If more than 5 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule.
- Injection: 2 mg/1.5 mL (1.34 mg/mL) of semaglutide as a clear, colorless solution available in:
- Pre-filled, disposable, single-patient-use pen that delivers 0.25 mg (for treatment initiation) or 0.5 mg (for maintenance treatment) per injection.
- Pre-filled, disposable, single-patient-use pen that delivers 1 mg (for maintenance treatment) per injection.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding semaglutide Off-Label Guideline-Supported Use and Dosage (Adult) in the drug label.
### Non–Guideline-Supported Use
There is limited information regarding semaglutide Off-Label Non-Guideline-Supported Use and Dosage (Adult) in the drug label.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Semaglutide FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding semaglutide Off-Label Guideline-Supported Use and Dosage (Pediatric) in the drug label.
### Non–Guideline-Supported Use
There is limited information regarding semaglutide Off-Label Non-Guideline-Supported Use and Dosage (Pediatric) in the drug label.
# Contraindications
- Semaglutide is contraindicated in patients with:
- A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- Known hypersensitivity to semaglutide or to any of the product components.
# Warnings
- In mice and rats, semaglutide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure at clinically relevant plasma exposures. It is unknown whether semaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined.
- Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist use in humans.
- Semaglutide is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of semaglutide and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness).
- Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with semaglutide. Such monitoring may increase the risk of unnecessary procedures, due to the low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin value may indicate MTC and patients with MTC usually have calcitonin values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.
- In glycemic control trials, acute pancreatitis was confirmed by adjudication in 7 semaglutide-treated patients (0.3 cases per 100 patient years) versus 3 in comparator-treated patients (0.2 cases per 100 patient years). One case of chronic pancreatitis was confirmed in an semaglutide-treated patient. In a 2-year trial, acute pancreatitis was confirmed by adjudication in 8 semaglutide-treated patients (0.27 cases per 100 patient years) and 10 placebo-treated patients (0.33 cases per 100 patient years), both on a background of standard of care.
- After initiation of semaglutide, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, semaglutide should be discontinued and appropriate management initiated; if confirmed, semaglutide should not be restarted.
- In a 2-year trial involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with semaglutide (3.0%) compared to placebo (1.8%). The absolute risk increase for diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy at baseline (semaglutide 8.2%, placebo 5.2%) than among patients without a known history of diabetic retinopathy (semaglutide 0.7%, placebo 0.4%).
- Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. The effect of long-term glycemic control with semaglutide on diabetic retinopathy complications has not been studied. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy.
- Semaglutide pens must never be shared between patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens.
- The risk of hypoglycemia is increased when semaglutide is used in combination with insulin secretagogues (e.g., sulfonylureas) or insulin. Patients may require a lower dose of the secretagogue or insulin to reduce the risk of hypoglycemia in this setting.
- There have been postmarketing reports of acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis, in patients treated with GLP-1 receptor agonists. Some of these events have been reported in patients without known underlying renal disease. A majority of the reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. Monitor renal function when initiating or escalating doses of semaglutide in patients reporting severe adverse gastrointestinal reactions.
- Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported with GLP-1 receptor agonists. If hypersensitivity reactions occur, discontinue use of semaglutide; treat promptly per standard of care, and monitor until signs and symptoms resolve. Do not use in patients with a previous hypersensitivity to semaglutide.
- Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to anaphylaxis with semaglutide.
- There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with semaglutide.
# Adverse Reactions
## Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- The data in Table 1 are derived from 2 placebo-controlled trials (1 monotherapy trial and 1 trial in combination with basal insulin) in patients with type 2 diabetes. These data reflect exposure of 521 patients to semaglutide and a mean duration of exposure to semaglutide of 32.9 weeks. Across the treatment arms, the mean age of patients was 56 years, 3.4% were 75 years or older and 55% were male. In these trials 71% were White, 7% were Black or African American, and 19% were Asian; 21% identified as Hispanic or Latino ethnicity. At baseline, patients had type 2 diabetes for an average of 8.8 years and had a mean HbA1c of 8.2%. At baseline, 8.9% of the population reported retinopathy. Baseline estimated renal function was normal (eGFR ≥90 mL/min/1.73m2) in 57.2%, mildly impaired (eGFR 60 to 90 mL/min/1.73m2) in 35.9% and moderately impaired (eGFR 30 to 60 mL/min/1.73m2) in 6.9% of patients.
- The occurrence of adverse reactions was also evaluated in a larger pool of patients with type 2 diabetes participating in 7 placebo- and active-controlled glycemic control trials including two trials in Japanese patients evaluating the use of semaglutide as monotherapy and add-on therapy to oral medications or insulin. In this pool, a total of 3150 patients with type 2 diabetes were treated with semaglutide for a mean duration of 44.9 weeks. Across the treatment arms, the mean age of patients was 57 years, 3.2% were 75 years or older and 57% were male. In these trials, 60% were White, 6% were Black or African American, and 31% were Asian; 16% identified as Hispanic or Latino ethnicity. At baseline, patients had type 2 diabetes for an average of 8.2 years and had a mean HbA1c of 8.2%. At baseline, 7.8% of the population reported retinopathy. Baseline estimated renal function was normal (eGFR ≥90 mL/min/1.73m2) in 63.1%, mildly impaired (eGFR 60 to 90 mL/min/1.73m2) in 34.3%, and moderately impaired (eGFR 30 to 60 mL/min/1.73m2) in 2.5% of the patients.
- Table 1 shows common adverse reactions, excluding hypoglycemia, associated with the use of semaglutide in the pool of placebo-controlled trials. These adverse reactions occurred more commonly on semaglutide than on placebo, and occurred in at least 5% of patients treated with semaglutide.
- In the pool of placebo- and active-controlled trials and in the 2-year cardiovascular outcomes trial, the types and frequency of common adverse reactions, excluding hypoglycemia, were similar to those listed in Table 1.
Gastrointestinal Adverse Reactions
- In the pool of placebo-controlled trials, gastrointestinal adverse reactions occurred more frequently among patients receiving semaglutide than placebo (placebo 15.3%, semaglutide 0.5 mg 32.7%, semaglutide 1 mg 36.4%). The majority of reports of nausea, vomiting, and/or diarrhea occurred during dose escalation. More patients receiving semaglutide 0.5 mg (3.1%) and semaglutide 1 mg (3.8%) discontinued treatment due to gastrointestinal adverse reactions than patients receiving placebo (0.4%).
- In addition to the reactions in Table 1, the following gastrointestinal adverse reactions with a frequency of <5% were associated with semaglutide (frequencies listed, respectively, as: placebo; 0.5 mg; 1 mg): dyspepsia (1.9%, 3.5%, 2.7%), eructation (0%, 2.7%, 1.1%), flatulence (0.8%, 0.4%, 1.5%), gastroesophageal reflux disease (0%, 1.9%, 1.5%), and gastritis (0.8%, 0.8%, 0.4%).
Hypoglycemia
- Table 2 summarizes the incidence of events related to hypoglycemia by various definitions in the placebo-controlled trials.
- Hypoglycemia was more frequent when semaglutide was used in combination with a sulfonylurea. Severe hypoglycemia occurred in 0.8% and 1.2% of patients when semaglutide 0.5 mg and 1 mg, respectively, was co-administered with a sulfonylurea. Documented symptomatic hypoglycemia occurred in 17.3% and 24.4% of patients when semaglutide 0.5 mg and 1 mg, respectively, was co-administered with a sulfonylurea. Severe or blood glucose confirmed symptomatic hypoglycemia occurred in 6.5% and 10.4% of patients when semaglutide 0.5 mg and 1 mg, respectively, was co-administered with a sulfonylurea.
- In placebo-controlled trials, injection site reactions (e.g., injection-site discomfort, erythema) were reported in 0.2% of semaglutide-treated patients.
- In placebo-controlled trials, patients exposed to semaglutide had a mean increase from baseline in amylase of 13% and lipase of 22%. These changes were not observed in placebo-treated patients.
- In placebo-controlled trials, cholelithiasis was reported in 1.5% and 0.4% of patients-treated with semaglutide 0.5 mg and 1 mg, respectively. Cholelithiasis was not reported in placebo-treated patients.
- In placebo-controlled trials, semaglutide 0.5 mg and 1 mg resulted in a mean increase in heart rate of 2 to 3 beats per minute. There was a mean decrease in heart rate of 0.3 beats per minute in placebo-treated patients.
- Other adverse reactions with a frequency of >0.4% were associated with semaglutide include fatigue, dysgeusia and dizziness.
## Postmarketing Experience
There is limited information regarding Semaglutide Postmarketing Experience in the drug label.
# Drug Interactions
- Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin
- Oral Medications
- The risk of hypoglycemia is increased when semaglutide is used in combination with insulin secretagogues (e.g., sulfonylureas) or insulin. The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin.
- Semaglutide causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, semaglutide did not affect the absorption of orally administered medications to any clinically relevant degree. Nonetheless, caution should be exercised when oral medications are concomitantly administered with semaglutide.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
- There are limited data with semaglutide use in pregnant women to inform a drug-associated risk for adverse developmental outcomes. There are clinical considerations regarding the risks of poorly controlled diabetes in pregnancy. Based on animal reproduction studies, there may be potential risks to the fetus from exposure to semaglutide during pregnancy. Semaglutide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- In pregnant rats administered semaglutide during organogenesis, embryofetal mortality, structural abnormalities and alterations to growth occurred at maternal exposures below the maximum recommended human dose (MRHD) based on AUC. In rabbits and cynomolgus monkeys administered semaglutide during organogenesis, early pregnancy losses and structural abnormalities were observed at below the MRHD (rabbit) and ≥5-fold the MRHD (monkey). These findings coincided with a marked maternal body weight loss in both animal species.
- The estimated background risk of major birth defects is 6–10% in women with pre-gestational diabetes with an HbA1c >7 and has been reported to be as high as 20–25% in women with a HbA1c >10. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Disease Associated Maternal and Fetal Risk
- Poorly controlled diabetes during pregnancy increases the maternal risk for diabetic ketoacidosis, pre- eclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.
- In a combined fertility and embryofetal development study in rats, subcutaneous doses of 0.01, 0.03 and 0.09 mg/kg/day (0.1-, 0.4-, and 1.1-fold the MRHD) were administered to males for 4 weeks prior to and throughout mating and to females for 2 weeks prior to mating, and throughout organogenesis to Gestation Day 17. In parental animals, pharmacologically mediated reductions in body weight gain and food consumption were observed at all dose levels. In the offspring, reduced growth and fetuses with visceral (heart blood vessels) and skeletal (cranial bones, vertebra, ribs) abnormalities were observed at the human exposure.
- In an embryofetal development study in pregnant rabbits, subcutaneous doses of 0.0010, 0.0025 or 0.0075 mg/kg/day (0.03-, 0.3-, and 2.3-fold the MRHD) were administered throughout organogenesis from Gestation Day 6 to 19. Pharmacologically mediated reductions in maternal body weight gain and food consumption were observed at all dose levels. Early pregnancy losses and increased incidences of minor visceral (kidney, liver) and skeletal (sternebra) fetal abnormalities were observed at ≥0.0025 mg/kg/day, at clinically relevant exposures.
- In an embryofetal development study in pregnant cynomolgus monkeys, subcutaneous doses of 0.015, 0.075, and 0.15 mg/kg twice weekly (1.0-, 5.2-, and 14.9-fold the MRHD) were administered throughout organogenesis, from Gestation Day 16 to 50. Pharmacologically mediated, marked initial maternal body weight loss and reductions in body weight gain and food consumption coincided with the occurrence of sporadic abnormalities (vertebra, sternebra, ribs) at ≥0.075 mg/kg twice weekly (>5X human exposure).
- In a pre- and postnatal development study in pregnant cynomolgus monkeys, subcutaneous doses of 0.015, 0.075, and 0.15 mg/kg twice weekly (0.7-, 3.3-, and 7.2-fold the MRHD) were administered from Gestation Day 16 to 140. Pharmacologically mediated marked initial maternal body weight loss and reductions in body weight gain and food consumption coincided with an increase in early pregnancy losses and led to delivery of slightly smaller offspring at ≥0.075 mg/kg twice weekly (>3X human exposure).
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Semaglutide in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Semaglutide during labor and delivery.
### Nursing Mothers
- There are no data on the presence of semaglutide in human milk, the effects on the breastfed infant, or the effects on milk production. Semaglutide was present in the milk of lactating rats, however, due to species-specific differences in lactation physiology, the clinical relevance of these data are not clear. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for semaglutide and any potential adverse effects on the breastfed infant from semaglutide or from the underlying maternal condition.
- In lactating rats, semaglutide was detected in milk at levels 3-12 fold lower than in maternal plasma.
### Pediatric Use
- Safety and efficacy of semaglutide have not been established in pediatric patients (younger than 18 years).
### Geriatic Use
- In the pool of placebo- and active-controlled glycemic control trials, 744 (23.6%) semaglutide-treated patients were 65 years of age and over and 102 semaglutide-treated patients (3.2%) patients were 75 years of age and over. In SUSTAIN 6, the cardiovascular outcome trial, 788 (48.0%) semaglutide-treated patients were 65 years of age and over and 157 semaglutide-treated patients (9.6%) patients were 75 years of age and over.
- No overall differences in safety or efficacy were detected between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
### Gender
There is no FDA guidance on the use of Semaglutide with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Semaglutide with respect to specific racial populations.
### Renal Impairment
- No dose adjustment of semaglutide is recommended for patients with renal impairment. In subjects with renal impairment including end-stage renal disease (ESRD), no clinically relevant change in semaglutide pharmacokinetics (PK) was observed.
### Hepatic Impairment
- No dose adjustment of semaglutide is recommended for patients with hepatic impairment. In a study in subjects with different degrees of hepatic impairment, no clinically relevant change in semaglutide pharmacokinetics (PK) was observed.
### Females of Reproductive Potential and Males
- Discontinue semaglutide in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide.
### Immunocompromised Patients
There is no FDA guidance one the use of Semaglutide in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Administer semaglutide subcutaneously to the abdomen, thigh, or upper arm. Instruct patients to use a different injection site each week when injecting in the same body region.
- Inspect semaglutide visually before use. It should appear clear and colorless. Do not use semaglutide if particulate matter and coloration is seen.
- When using semaglutide with insulin, instruct patients to administer as separate injections and to never mix the products. It is acceptable to inject semaglutide and insulin in the same body region but the injections should not be adjacent to each other.
### Monitoring
- Achieving glycemic control, including meeting HbA1c goal is indicative of efficacy.
- HbA1c: Twice yearly in patients who are meeting treatment goals; every 3 months in patients whose therapy has changed and/or who are not meeting glycemic goals; more frequently as clinically warranted.
- Renal function: When initiating or escalating doses and in patients reporting severe adverse reactions, especially in patients with renal impairment.
- Progression of diabetic retinopathy: In patients with a history of disease.
- Signs and symptoms of pancreatitis, including persistent severe abdominal pain, sometimes radiating to the back with or without vomiting.
# IV Compatibility
There is limited information regarding the compatibility of Semaglutide and IV administrations.
# Overdosage
- In the event of overdose, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms. A prolonged period of observation and treatment for these symptoms may be necessary, taking into account the long half-life of semaglutide of approximately 1 week.
# Pharmacology
## Mechanism of Action
- Semaglutide is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1.
- GLP-1 is a physiological hormone that has multiple actions on glucose, mediated by the GLP-1 receptors.
- The principal mechanism of protraction resulting in the long half-life of semaglutide is albumin binding, which results in decreased renal clearance and protection from metabolic degradation. Furthermore, semaglutide is stabilized against degradation by the DPP-4 enzyme.
- Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Thus, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase.
## Structure
## Pharmacodynamics
- Semaglutide lowers fasting and postprandial blood glucose and reduces body weight. All pharmacodynamic evaluations were performed after 12 weeks of treatment (including dose escalation) at steady state with semaglutide 1 mg.
- Semaglutide reduces fasting and postprandial glucose concentrations. In patients with type 2 diabetes, treatment with semaglutide 1 mg resulted in reductions in glucose in terms of absolute change from baseline and relative reduction compared to placebo of 29 mg/dL (22%) for fasting glucose, 74 mg/dL (36%) for 2 hour postprandial glucose, and 30 mg/dL (22%) for mean 24 hour glucose concentration (see Figure 1).
- Both first-and second-phase insulin secretion are increased in patients with type 2 diabetes treated with semaglutide compared with placebo.
- Semaglutide lowers the fasting and postprandial glucagon concentrations. In patients with type 2 diabetes, treatment with semaglutide resulted in the following relative reductions in glucagon compared to placebo, fasting glucagon (8%), postprandial glucagon response (14-15%), and mean 24 hour glucagon concentration (12%).
- Semaglutide lowers high blood glucose concentrations by stimulating insulin secretion and lowering glucagon secretion in a glucose-dependent manner. With semaglutide, the insulin secretion rate in patients with type 2 diabetes was similar to that of healthy subjects (see Figure 2).
- During induced hypoglycemia, semaglutide did not alter the counter regulatory responses of increased glucagon compared to placebo, and did not impair the decrease of C-peptide in patients with type 2 diabetes.
- Semaglutide causes a delay of early postprandial gastric emptying, thereby reducing the rate at which glucose appears in the circulation postprandially.
- The effect of semaglutide on cardiac repolarization was tested in a thorough QTc trial. At a dose 1.5 times the maximum recommended dose, semaglutide does not prolong QTc intervals to any clinically relevant extent.
## Pharmacokinetics
- Absolute bioavailability of semaglutide is 89%. Maximum concentration of semaglutide is reached 1 to 3 days post dose.
- Similar exposure is achieved with subcutaneous administration of semaglutide in the abdomen, thigh, or upper arm.
- In patients with type 2 diabetes, semaglutide exposure increases in a dose-proportional manner for once-weekly doses of 0.5 mg and 1 mg. Steady-state exposure is achieved following 4-5 weeks of once-weekly administration. In patients with type 2 diabetes, the mean population-PK estimated steady-state concentrations following once weekly subcutaneous administration of 0.5 mg and 1 mg semaglutide were approximately 65.0 ng/mL and 123.0 ng/mL, respectively.
- The mean apparent volume of distribution of semaglutide following subcutaneous administration in patients with type 2 diabetes is approximately 12.5 L. Semaglutide is extensively bound to plasma albumin (>99%).
- The apparent clearance of semaglutide in patients with type 2 diabetes is approximately 0.05 L/h. With an elimination half-life of approximately 1 week, semaglutide will be present in the circulation for about 5 weeks after the last dose.
Metabolism
- The primary route of elimination for semaglutide is metabolism following proteolytic cleavage of the peptide backbone and sequential beta-oxidation of the fatty acid sidechain.
Excretion
- The primary excretion routes of semaglutide-related material is via the urine and feces. Approximately 3% of the dose is excreted in the urine as intact semaglutide.
- Based on a population pharmacokinetic analysis, age, sex, race, and ethnicity, and renal impairment do not have a clinically meaningful effect on the pharmacokinetics of semaglutide. The exposure of semaglutide decreases with an increase in body weight. However, semaglutide doses of 0.5 mg and 1 mg provide adequate systemic exposure over the body weight range of 40-198 kg evaluated in the clinical trials. The effects of intrinsic factors on the pharmacokinetics of semaglutide are shown in Figure 3.
Patients with Renal Impairment
- Renal impairment does not impact the pharmacokinetics of semaglutide in a clinically relevant manner. This was shown in a study with a single dose of 0.5 mg semaglutide in patients with different degrees of renal impairment (mild, moderate, severe, ESRD) compared with subjects with normal renal function. This was also shown for subjects with both type 2 diabetes and renal impairment based on data from clinical studies (Figure 3).
Patients with Hepatic Impairment
- Hepatic impairment does not have any impact on the exposure of semaglutide. The pharmacokinetics of semaglutide were evaluated in patients with different degrees of hepatic impairment (mild, moderate, severe) compared with subjects with normal hepatic function in a study with a single-dose of 0.5 mg semaglutide.
Pediatric Patients
- Semaglutide has not been studied in pediatric patients.
- In vitro studies have shown very low potential for semaglutide to inhibit or induce CYP enzymes, and to inhibit drug transporters.
- The delay of gastric emptying with semaglutide may influence the absorption of concomitantly administered oral medicinal products. The potential effect of semaglutide on the absorption of co-administered oral medications was studied in trials at semaglutide 1 mg steady-state exposure.
- No clinically relevant drug-drug interaction with semaglutide (Figure 4) was observed based on the evaluated medications; therefore, no dose adjustment is required when co-administered with semaglutide.
- Relative exposure in terms of AUC and Cmax for each medication when given with semaglutide compared to without semaglutide. Metformin and oral contraceptive drug (ethinylestradiol/levonorgestrel) were assessed at steady state. Warfarin (S-warfarin/R-warfarin), digoxin and atorvastatin were assessed after a single dose.
- Abbreviations: AUC: area under the curve. Cmax: maximum concentration. CI: confidence interval.
## Nonclinical Toxicology
- In a 2-year carcinogenicity study in CD-1 mice, subcutaneous doses of 0.3, 1 and 3 mg/kg/day were administered to the males, and 0.1, 0.3 and 1 mg/kg/day (2-, 5-, and 17-fold MRHD) were administered to the females. A statistically significant increase in thyroid C-cell adenomas and a numerical increase in C-cell carcinomas were observed in males and females at all dose levels (>2X human exposure).
- In a 2-year carcinogenicity study in Sprague Dawley rats, subcutaneous doses of 0.0025, 0.01, 0.025 and 0.1 mg/kg/day were administered (below quantification, 0.4-, 1-, and 6-fold the exposure at the MRHD). A statistically significant increase in thyroid C-cell adenomas was observed in males and females at all dose levels, and a statistically significant increase in thyroid C-cell carcinomas was observed in males at ≥0.01 mg/kg/day, at clinically relevant exposures.
- Human relevance of thyroid C-cell tumors in rats is unknown and could not be determined by clinical studies or nonclinical studies.
- Semaglutide was not mutagenic or clastogenic in a standard battery of genotoxicity tests (bacterial mutagenicity (Ames), human lymphocyte chromosome aberration, rat bone marrow micronucleus).
- In a combined fertility and embryo-fetal development study in rats, subcutaneous doses of 0.01, 0.03 and 0.09 mg/kg/day (0.1-, 0.4-, and 1.1-fold the MRHD) were administered to male and female rats. Males were dosed for 4 weeks prior to mating, and females were dosed for 2 weeks prior to mating and throughout organogenesis until Gestation Day 17. No effects were observed on male fertility. In females, an increase in oestrus cycle length was observed at all dose levels, together with a small reduction in numbers of corpora lutea at ≥0.03 mg/kg/day. These effects were likely an adaptive response secondary to the pharmacological effect of semaglutide on food consumption and body weight.
# Clinical Studies
- Semaglutide has been studied as monotherapy and in combination with metformin, metformin and sulfonylureas, metformin and/or thiazolidinedione, and basal insulin in patients with type 2 diabetes mellitus. The efficacy of semaglutide was compared with placebo, sitagliptin, exenatide extended-release (ER), and insulin glargine.
- Most trials evaluated the use of semaglutide 0.5 mg, and 1 mg, with the exception of the trial comparing semaglutide and exenatide ER where only the 1 mg dose was studied.
- In patients with type 2 diabetes mellitus, semaglutide produced clinically relevant reduction from baseline in HbA1c compared with placebo.
- The efficacy of semaglutide was not impacted by age, gender, race, ethnicity, BMI at baseline, body weight (kg) at baseline, diabetes duration and level of renal function impairment.
- In a 30-week double-blind trial (NCT02054897), 388 patients with type 2 diabetes mellitus inadequately controlled with diet and exercise were randomized to semaglutide 0.5 mg or semaglutide 1 mg once weekly or placebo. Patients had a mean age of 54 years and 54% were men. The mean duration of type 2 diabetes was 4.2 years, and the mean BMI was 33 kg/m2. Overall, 64% were White, 8% were Black or African American, and 21% were Asian; 30% identified as Hispanic or Latino ethnicity.
- Monotherapy with semaglutide 0.5 mg and 1 mg once weekly for 30 weeks resulted in a statistically significant reduction in HbA1c compared with placebo (see Table 3).
- In a 56-week, double-blind trial (NCT01930188), 1231 patients with type 2 diabetes mellitus were randomized to semaglutide 0.5 mg once weekly, semaglutide 1 mg once weekly, or sitagliptin 100 mg once daily, all in combination with metformin (94%) and/or thiazolidinediones (6%). Patients had a mean age of 55 years and 51% were men. The mean duration of type 2 diabetes was 6.6 years, and the mean BMI was 32 kg/m2. Overall, 68% were White, 5% were Black or African American, and 25% were Asian; 17% identified as Hispanic or Latino ethnicity.
- Treatment with semaglutide 0.5 mg and 1 mg once weekly for 56 weeks resulted in a statistically significant reduction in HbA1c compared to sitagliptin (see Table 4 and Figure 5).
- In a 56-week, open-label trial (NCT01885208), 813 patients with type 2 diabetes mellitus on metformin alone (49%), metformin with sulfonylurea (45%), or other (6%) were randomized to semaglutide 1 mg once weekly or exenatide 2 mg once weekly. Patients had a mean age of 57 years and 55% were men. The mean duration of type 2 diabetes was 9 years, and the mean BMI was 34 kg/m2. Overall, 84% were White, 7% were Black or African American, and 2% were Asian; 24% identified as Hispanic or Latino ethnicity.
- Treatment with semaglutide 1 mg once weekly for 56 weeks resulted in a statistically significant reduction in HbA1c compared to exenatide 2 mg once weekly (see Table 5).
- In a 30-week, open-label trial (NCT02128932), 1089 patients with type 2 diabetes mellitus were randomized to semaglutide 0.5 mg once weekly, semaglutide 1 mg once weekly, or insulin glargine once daily on a background of metformin (48%) or metformin and sulfonylurea (51%). Patients had a mean age of 57 years and 53% were men. The mean duration of type 2 diabetes was 8.6 years, and the mean BMI was 33 kg/m2. Overall, 77% were White, 9% were Black or African American, and 11% were Asian; 20% identified as Hispanic or Latino ethnicity.
- Patients assigned to insulin glargine had a baseline mean HbA1c of 8.1% and were started on a dose of 10 U once daily. Insulin glargine dose adjustments occurred throughout the trial period based on self-measured fasting plasma glucose before breakfast, targeting 71 to <100 mg/dL. In addition, investigators could titrate insulin glargine at their discretion between study visits. Only 26% of patients had been titrated to goal by the primary endpoint at week 30, at which time the mean daily insulin dose was 29 U per day.
- Treatment with semaglutide 0.5 mg and 1 mg once weekly for 30 weeks resulted in a statistically significant reduction in HbA1c compared with the insulin glargine titration implemented in this study protocol (see Table 6).
- In a 30-week, double-blind trial (NCT02305381), 397 patients with type 2 diabetes mellitus inadequately controlled with basal insulin, with or without metformin, were randomized to semaglutide 0.5 mg once weekly, semaglutide 1 mg once weekly, or placebo. Patients with HbA1c ≤ 8.0% at screening reduced their insulin dose by 20% at start of the trial to reduce the risk of hypoglycemia. Patients had a mean age of 59 years and 56% were men. The mean duration of type 2 diabetes was 13 years, and the mean BMI was 32 kg/m2. Overall, 78% were White, 5% were Black or African American, and 17% were Asian; 12% identified as Hispanic or Latino ethnicity.
- Treatment with semaglutide resulted in a statistically significant reduction in HbA1c after 30 weeks of treatment compared to placebo (see Table 7).
- SUSTAIN 6 (NCT01720446) was a 104-week, double-blind trial in which 3,297 patients with type 2 diabetes and high risk of cardiovascular events were randomized to semaglutide 0.5 mg once weekly, semaglutide 1 mg once weekly, or placebo in addition to standard-of-care. In total, 2,735 (83%) of the patients had a history of cardiovascular disease and 562 (17%) were at high risk but without known cardiovascular disease. The mean age at baseline was 65 years, and 61% were men. The mean duration of diabetes was 13.9 years, and mean BMI was 33 kg/m2. Overall, 83% were White, 7% were Black or African American, and 8% were Asian; 16% identified as Hispanic or Latino ethnicity. Concomitant diseases of patients in this trial included, but were not limited to, heart failure (24%), hypertension (93%), history of ischemic stroke (12%) and history of a myocardial infarction (33%).
- In total, 98.0% of the patients completed the trial and the vital status was known at the end of the trial for 99.6%. The primary composite endpoint was the time from randomization to first occurrence of a major adverse cardiovascular event (MACE): cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. The secondary endpoint was time from randomization to first occurrence of an expanded composite cardiovascular outcome, defined as MACE, revascularization (coronary and peripheral), unstable angina requiring hospitalization or hospitalization for heart failure. The total number of primary component MACE endpoints was 254 (108 with semaglutide and 146 with placebo). No increased risk for MACE was observed with semaglutide.
# How Supplied
- Semaglutide injection is supplied as a clear, colorless solution that contains 2 mg of semaglutide in a 1.5 mL (1.34 mg/mL) pre-filled, disposable, single-patient-use pen injector in the following packaging configurations:
- Pen delivers doses of 0.25 mg or 0.5 mg per injection.
- 6 NovoFine ® Plus needles.
- Intended for treatment initiation at the 0.25 mg dose and maintenance treatment at the 0.5 mg dose.
- Pen delivers doses of 1 mg per injection.
- 4 NovoFine ® Plus needles.
- Intended for maintenance treatment at the 1 mg dose only.
- Each semaglutide pen is for use by a single patient. An semaglutide pen must never be shared between patients, even if the needle is changed.
## Storage
- Prior to first use, semaglutide should be stored in a refrigerator between 36ºF to 46ºF (2ºC to 8ºC) (Table 8). Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze semaglutide and do not use semaglutide if it has been frozen.
- After first use of the semaglutide pen, the pen can be stored for 56 days at controlled room temperature (59°F to 86°F; 15°C to 30°C) or in a refrigerator (36°F to 46°F; 2°C to 8°C). Do not freeze. Keep the pen cap on when not in use. Semaglutide should be protected from excessive heat and sunlight.
- Always remove and safely discard the needle after each injection and store the semaglutide pen without an injection needle attached. Always use a new needle for each injection.
- The storage conditions are summarized in Table 8:
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
- Advise the patient to read the FDA-approved patient labeling.
- Inform patients that semaglutide causes thyroid C-cell tumors in rodents and that the human relevance of this finding has not been determined. Counsel patients to report symptoms of thyroid tumors (e.g., a lump in the neck, hoarseness, dysphagia, or dyspnea) to their physician.
- Inform patients of the potential risk for pancreatitis. Instruct patients to discontinue semaglutide promptly and contact their physician if pancreatitis is suspected (severe abdominal pain that may radiate to the back, and which may or may not be accompanied by vomiting).
- Inform patients to contact their physician if changes in vision are experienced during treatment with semaglutide.
- Advise patients that they must never share an semaglutide pen with another person, even if the needle is changed, because doing so carries a risk for transmission of blood-borne pathogens.
- Advise patients treated with semaglutide of the potential risk of dehydration due to gastrointestinal adverse reactions and take precautions to avoid fluid depletion. Inform patients of the potential risk for worsening renal function and explain the associated signs and symptoms of renal impairment, as well as the possibility of dialysis as a medical intervention if renal failure occurs.
- Inform patients to stop taking semaglutide and seek medical advice promptly if symptoms of hypersensitivity reactions occur.
- Advise a pregnant woman of the potential risk to a fetus. Advise women to inform their healthcare provider if they are pregnant or intend to become pregnant.
- Inform patients of the potential risks and benefits of semaglutide and of alternative modes of therapy. Inform patients about the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and A1c testing, recognition and management of hypoglycemia and hyperglycemia, and assessment for diabetes complications. Advise patients to seek medical advice promptly during periods of stress such as fever, trauma, infection, or surgery as medication requirements may change.
- Advise patients that the most common side effects of semaglutide are nausea, vomiting, diarrhea, abdominal pain and constipation. Inform patients that nausea, vomiting and diarrhea are most common when first starting semaglutide, but decreases over time in the majority of patients.
- Instruct patients to reread the Medication Guide each time the prescription is renewed.
- Inform patients if a dose is missed, it should be administered as soon as possible within 5 days after the missed dose. If more than 5 days have passed, the missed dose should be skipped and the next dose should be administered on the regularly scheduled day. In each case, inform patients to resume their regular once weekly dosing schedule.
- Semaglutide (oh-ZEM-pick)
- (Semaglutide)
- Injection, for subcutaneous use
- Do not share your semaglutide pen with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them.
- Read this Medication Guide before you start using semaglutide and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
- What is the most important information I should know about semaglutide?
- Semaglutide may cause serious side effects, including:
- Possible thyroid tumors, including cancer. Tell your healthcare provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. In studies with rodents, semaglutide and medicines that work like semaglutide caused thyroid tumors, including thyroid cancer. It is not known if semaglutide will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people.
- Do not use semaglutide if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC), or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- What is semaglutide?
- Semaglutide is an injectable prescription medicine for adults with type 2 diabetes mellitus that:
- Along with diet and exercise may improve blood sugar (glucose).
- Semaglutide is not recommended as the first choice of medicine for treating diabetes.
- It is not known if semaglutide can be used in people who have had pancreatitis.
- Semaglutide is not a substitute for insulin and is not for use in people with type 1 diabetes or people with diabetic ketoacidosis.
- It is not known if semaglutide is safe and effective for use in children under 18 years of age.
- Do not use semaglutide if:
- You or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC) or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- You are allergic to semaglutide or any of the ingredients in semaglutide. See the end of this Medication Guide for a complete list of ingredients in semaglutide.
- Before using semaglutide, tell your healthcare provider if you have any other medical conditions, including if you:
- Have or have had problems with your pancreas or kidneys.
- Have a history of diabetic retinopathy.
- Are pregnant or plan to become pregnant. It is not known if semaglutide will harm your unborn baby. You should stop using semaglutide 2 months before you plan to become pregnant. Talk to your healthcare provider about the best way to control your blood sugar if you plan to become pregnant or while you are pregnant.
- Are breastfeeding or plan to breastfeed. It is not known if semaglutide passes into your breast milk. You should talk with your healthcare provider about the best way to feed your baby while using semaglutide.
- Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Semaglutide may affect the way some medicines work and some medicines may affect the way semaglutide works.
- Before using semaglutide, talk to your healthcare provider about low blood sugar and how to manage it. Tell your healthcare provider if you are taking other medicines to treat diabetes, including insulin or sulfonylureas.
- Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
- How should I use semaglutide?
- Read the Instructions for Use that comes with semaglutide.
- Use semaglutide exactly as your healthcare provider tells you to.
- Your healthcare provider should show you how to use semaglutide before you use it for the first time.
- Semaglutide is injected under the skin (subcutaneously) of your stomach (abdomen), thigh, or upper arm. Do not inject semaglutide into a muscle (intramuscularly) or vein (intravenously).
- Use semaglutide 1 time each week, on the same day each week, at any time of the day.
- You may change the day of the week you use semaglutide as long as your last dose was given 2 or more days before.
- If you miss a dose of semaglutide, take the missed dose as soon as possible within 5 days after the missed dose. If more than 5 days have passed, skip the missed dose and take your next dose on the regularly scheduled day.
- Semaglutide may be taken with or without food.
- Do not mix insulin and semaglutide together in the same injection.
- You may give an injection of semaglutide and insulin in the same body area (such as your stomach area), but not right next to each other.
- Change (rotate) your injection site with each injection. Do not use the same site for each injection.
- Check your blood sugar as your healthcare provider tells you to.
- Stay on your prescribed diet and exercise program while using semaglutide.
- Talk to your healthcare provider about how to prevent, recognize and manage low blood sugar (hypoglycemia), high blood sugar (hyperglycemia), and problems you have because of your diabetes.
- Your healthcare provider will check your diabetes with regular blood tests, including your blood sugar levels and your hemoglobin A1C.
- Do not share your semaglutide pen with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them.
- Your dose of semaglutide and other diabetes medicines may need to change because of:
- Change in level of physical activity or exercise, weight gain or loss, increased stress, illness, change in diet, fever, trauma, infection, surgery or because of other medicines you take.
- What are the possible side effects of semaglutide?
- Semaglutide may cause serious side effects, including:
- See “What is the most important information I should know about semaglutide?”
- Inflammation of your pancreas (pancreatitis). Stop using semaglutide and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back.
- Changes in vision. Tell your healthcare provider if you have changes in vision during treatment with semaglutide.
- Low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use semaglutide with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin. Signs and symptoms of low blood sugar may include:
- Dizziness or light-headedness
- Blurred vision
- Anxiety, irritability, or mood changes
- Sweating
- Slurred speech
- Hunger
- Confusion or drowsiness
- Shakiness
- Weakness
- Headache
- Fast heartbeat
- Feeling jittery
- Kidney problems (kidney failure). In people who have kidney problems, diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration) which may cause kidney problems to get worse. It is important for you to drink fluids to help reduce your chance of dehydration.
- Serious allergic reactions. Stop using semaglutide and get medical help right away, if you have any symptoms of a serious allergic reaction including itching, rash, or difficulty breathing.
- The most common side effects of semaglutide may include nausea, vomiting, diarrhea, stomach (abdominal) pain and constipation.
- Talk to your healthcare provider about any side effect that bothers you or does not go away. These are not all the possible side effects of semaglutide.
- Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800‑FDA‑1088.
- General information about the safe and effective use of semaglutide.
- Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use semaglutide for a condition for which it was not prescribed. Do not give semaglutide to other people, even if they have the same symptoms that you have. It may harm them.
- You can ask your pharmacist or healthcare provider for information about semaglutide that is written for health professionals.
- For more information, go to OZEMPIC.com or call 1-888-693-6742.
- What are the ingredients in OZEMPIC?
- Active Ingredient: semaglutide.
- Inactive Ingredients: disodium phosphate dihydrate, propylene glycol, phenol and water for injection.
# Precautions with Alcohol
Alcohol-Semaglutide interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
# Brand Names
- Ozempic
# Look-Alike Drug Names
There is limited information regarding Semaglutide Look-Alike Drug Names in the drug label.
# Drug Shortage Status
Drug Shortage
# Price | Semaglutide
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sonya Gelfand
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# Black Box Warning
# Overview
Semaglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist that is FDA approved for the adjunction of diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. There is a Black Box Warning for this drug as shown here. Common adverse reactions include nausea, vomiting, diarrhea, abdominal pain and constipation.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Semaglutide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
- Semaglutide is not recommended as a first-line therapy for patients who have inadequate glycemic control on diet and exercise because of the uncertain relevance of rodent C-cell tumor findings to humans.
- Semaglutide has not been studied in patients with a history of pancreatitis. Consider other antidiabetic therapies in patients with a history of pancreatitis.
- Semaglutide is not a substitute for insulin. Semaglutide is not indicated for use in patients with type 1 diabetes mellitus or for the treatment of patients with diabetic ketoacidosis, as it would not be effective in these settings.
- Start semaglutide with a 0.25 mg subcutaneous injection once weekly for 4 weeks. The 0.25 mg dose is intended for treatment initiation and is not effective for glycemic control.
- After 4 weeks on the 0.25 mg dose, increase the dosage to 0.5 mg once weekly.
- If additional glycemic control is needed after at least 4 weeks on the 0.5 mg dose, the dosage may be increased to 1 mg once weekly. The maximum recommended dosage is 1 mg once weekly.
- Administer semaglutide once weekly, on the same day each week, at any time of the day, with or without meals.
- The day of weekly administration can be changed if necessary as long as the time between two doses is at least 2 days (>48 hours).
- If a dose is missed, administer semaglutide as soon as possible within 5 days after the missed dose. If more than 5 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule.
- Injection: 2 mg/1.5 mL (1.34 mg/mL) of semaglutide as a clear, colorless solution available in:
- Pre-filled, disposable, single-patient-use pen that delivers 0.25 mg (for treatment initiation) or 0.5 mg (for maintenance treatment) per injection.
- Pre-filled, disposable, single-patient-use pen that delivers 1 mg (for maintenance treatment) per injection.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding semaglutide Off-Label Guideline-Supported Use and Dosage (Adult) in the drug label.
### Non–Guideline-Supported Use
There is limited information regarding semaglutide Off-Label Non-Guideline-Supported Use and Dosage (Adult) in the drug label.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Semaglutide FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding semaglutide Off-Label Guideline-Supported Use and Dosage (Pediatric) in the drug label.
### Non–Guideline-Supported Use
There is limited information regarding semaglutide Off-Label Non-Guideline-Supported Use and Dosage (Pediatric) in the drug label.
# Contraindications
- Semaglutide is contraindicated in patients with:
- A personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- Known hypersensitivity to semaglutide or to any of the product components.
# Warnings
- In mice and rats, semaglutide caused a dose-dependent and treatment-duration-dependent increase in the incidence of thyroid C-cell tumors (adenomas and carcinomas) after lifetime exposure at clinically relevant plasma exposures. It is unknown whether semaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined.
- Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist use in humans.
- Semaglutide is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2. Counsel patients regarding the potential risk for MTC with the use of semaglutide and inform them of symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea, persistent hoarseness).
- Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with semaglutide. Such monitoring may increase the risk of unnecessary procedures, due to the low test specificity for serum calcitonin and a high background incidence of thyroid disease. Significantly elevated serum calcitonin value may indicate MTC and patients with MTC usually have calcitonin values >50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be further evaluated.
- In glycemic control trials, acute pancreatitis was confirmed by adjudication in 7 semaglutide-treated patients (0.3 cases per 100 patient years) versus 3 in comparator-treated patients (0.2 cases per 100 patient years). One case of chronic pancreatitis was confirmed in an semaglutide-treated patient. In a 2-year trial, acute pancreatitis was confirmed by adjudication in 8 semaglutide-treated patients (0.27 cases per 100 patient years) and 10 placebo-treated patients (0.33 cases per 100 patient years), both on a background of standard of care.
- After initiation of semaglutide, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, semaglutide should be discontinued and appropriate management initiated; if confirmed, semaglutide should not be restarted.
- In a 2-year trial involving patients with type 2 diabetes and high cardiovascular risk, more events of diabetic retinopathy complications occurred in patients treated with semaglutide (3.0%) compared to placebo (1.8%). The absolute risk increase for diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy at baseline (semaglutide 8.2%, placebo 5.2%) than among patients without a known history of diabetic retinopathy (semaglutide 0.7%, placebo 0.4%).
- Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. The effect of long-term glycemic control with semaglutide on diabetic retinopathy complications has not been studied. Patients with a history of diabetic retinopathy should be monitored for progression of diabetic retinopathy.
- Semaglutide pens must never be shared between patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens.
- The risk of hypoglycemia is increased when semaglutide is used in combination with insulin secretagogues (e.g., sulfonylureas) or insulin. Patients may require a lower dose of the secretagogue or insulin to reduce the risk of hypoglycemia in this setting.
- There have been postmarketing reports of acute kidney injury and worsening of chronic renal failure, which may sometimes require hemodialysis, in patients treated with GLP-1 receptor agonists. Some of these events have been reported in patients without known underlying renal disease. A majority of the reported events occurred in patients who had experienced nausea, vomiting, diarrhea, or dehydration. Monitor renal function when initiating or escalating doses of semaglutide in patients reporting severe adverse gastrointestinal reactions.
- Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported with GLP-1 receptor agonists. If hypersensitivity reactions occur, discontinue use of semaglutide; treat promptly per standard of care, and monitor until signs and symptoms resolve. Do not use in patients with a previous hypersensitivity to semaglutide.
- Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists. Use caution in a patient with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist because it is unknown whether such patients will be predisposed to anaphylaxis with semaglutide.
- There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with semaglutide.
# Adverse Reactions
## Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- The data in Table 1 are derived from 2 placebo-controlled trials (1 monotherapy trial and 1 trial in combination with basal insulin) in patients with type 2 diabetes. These data reflect exposure of 521 patients to semaglutide and a mean duration of exposure to semaglutide of 32.9 weeks. Across the treatment arms, the mean age of patients was 56 years, 3.4% were 75 years or older and 55% were male. In these trials 71% were White, 7% were Black or African American, and 19% were Asian; 21% identified as Hispanic or Latino ethnicity. At baseline, patients had type 2 diabetes for an average of 8.8 years and had a mean HbA1c of 8.2%. At baseline, 8.9% of the population reported retinopathy. Baseline estimated renal function was normal (eGFR ≥90 mL/min/1.73m2) in 57.2%, mildly impaired (eGFR 60 to 90 mL/min/1.73m2) in 35.9% and moderately impaired (eGFR 30 to 60 mL/min/1.73m2) in 6.9% of patients.
- The occurrence of adverse reactions was also evaluated in a larger pool of patients with type 2 diabetes participating in 7 placebo- and active-controlled glycemic control trials including two trials in Japanese patients evaluating the use of semaglutide as monotherapy and add-on therapy to oral medications or insulin. In this pool, a total of 3150 patients with type 2 diabetes were treated with semaglutide for a mean duration of 44.9 weeks. Across the treatment arms, the mean age of patients was 57 years, 3.2% were 75 years or older and 57% were male. In these trials, 60% were White, 6% were Black or African American, and 31% were Asian; 16% identified as Hispanic or Latino ethnicity. At baseline, patients had type 2 diabetes for an average of 8.2 years and had a mean HbA1c of 8.2%. At baseline, 7.8% of the population reported retinopathy. Baseline estimated renal function was normal (eGFR ≥90 mL/min/1.73m2) in 63.1%, mildly impaired (eGFR 60 to 90 mL/min/1.73m2) in 34.3%, and moderately impaired (eGFR 30 to 60 mL/min/1.73m2) in 2.5% of the patients.
- Table 1 shows common adverse reactions, excluding hypoglycemia, associated with the use of semaglutide in the pool of placebo-controlled trials. These adverse reactions occurred more commonly on semaglutide than on placebo, and occurred in at least 5% of patients treated with semaglutide.
- In the pool of placebo- and active-controlled trials and in the 2-year cardiovascular outcomes trial, the types and frequency of common adverse reactions, excluding hypoglycemia, were similar to those listed in Table 1.
Gastrointestinal Adverse Reactions
- In the pool of placebo-controlled trials, gastrointestinal adverse reactions occurred more frequently among patients receiving semaglutide than placebo (placebo 15.3%, semaglutide 0.5 mg 32.7%, semaglutide 1 mg 36.4%). The majority of reports of nausea, vomiting, and/or diarrhea occurred during dose escalation. More patients receiving semaglutide 0.5 mg (3.1%) and semaglutide 1 mg (3.8%) discontinued treatment due to gastrointestinal adverse reactions than patients receiving placebo (0.4%).
- In addition to the reactions in Table 1, the following gastrointestinal adverse reactions with a frequency of <5% were associated with semaglutide (frequencies listed, respectively, as: placebo; 0.5 mg; 1 mg): dyspepsia (1.9%, 3.5%, 2.7%), eructation (0%, 2.7%, 1.1%), flatulence (0.8%, 0.4%, 1.5%), gastroesophageal reflux disease (0%, 1.9%, 1.5%), and gastritis (0.8%, 0.8%, 0.4%).
Hypoglycemia
- Table 2 summarizes the incidence of events related to hypoglycemia by various definitions in the placebo-controlled trials.
- Hypoglycemia was more frequent when semaglutide was used in combination with a sulfonylurea. Severe hypoglycemia occurred in 0.8% and 1.2% of patients when semaglutide 0.5 mg and 1 mg, respectively, was co-administered with a sulfonylurea. Documented symptomatic hypoglycemia occurred in 17.3% and 24.4% of patients when semaglutide 0.5 mg and 1 mg, respectively, was co-administered with a sulfonylurea. Severe or blood glucose confirmed symptomatic hypoglycemia occurred in 6.5% and 10.4% of patients when semaglutide 0.5 mg and 1 mg, respectively, was co-administered with a sulfonylurea.
- In placebo-controlled trials, injection site reactions (e.g., injection-site discomfort, erythema) were reported in 0.2% of semaglutide-treated patients.
- In placebo-controlled trials, patients exposed to semaglutide had a mean increase from baseline in amylase of 13% and lipase of 22%. These changes were not observed in placebo-treated patients.
- In placebo-controlled trials, cholelithiasis was reported in 1.5% and 0.4% of patients-treated with semaglutide 0.5 mg and 1 mg, respectively. Cholelithiasis was not reported in placebo-treated patients.
- In placebo-controlled trials, semaglutide 0.5 mg and 1 mg resulted in a mean increase in heart rate of 2 to 3 beats per minute. There was a mean decrease in heart rate of 0.3 beats per minute in placebo-treated patients.
- Other adverse reactions with a frequency of >0.4% were associated with semaglutide include fatigue, dysgeusia and dizziness.
## Postmarketing Experience
There is limited information regarding Semaglutide Postmarketing Experience in the drug label.
# Drug Interactions
- Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin
- Oral Medications
- The risk of hypoglycemia is increased when semaglutide is used in combination with insulin secretagogues (e.g., sulfonylureas) or insulin. The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogues) or insulin.
- Semaglutide causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, semaglutide did not affect the absorption of orally administered medications to any clinically relevant degree. Nonetheless, caution should be exercised when oral medications are concomitantly administered with semaglutide.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
- There are limited data with semaglutide use in pregnant women to inform a drug-associated risk for adverse developmental outcomes. There are clinical considerations regarding the risks of poorly controlled diabetes in pregnancy. Based on animal reproduction studies, there may be potential risks to the fetus from exposure to semaglutide during pregnancy. Semaglutide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
- In pregnant rats administered semaglutide during organogenesis, embryofetal mortality, structural abnormalities and alterations to growth occurred at maternal exposures below the maximum recommended human dose (MRHD) based on AUC. In rabbits and cynomolgus monkeys administered semaglutide during organogenesis, early pregnancy losses and structural abnormalities were observed at below the MRHD (rabbit) and ≥5-fold the MRHD (monkey). These findings coincided with a marked maternal body weight loss in both animal species.
- The estimated background risk of major birth defects is 6–10% in women with pre-gestational diabetes with an HbA1c >7 and has been reported to be as high as 20–25% in women with a HbA1c >10. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Disease Associated Maternal and Fetal Risk
- Poorly controlled diabetes during pregnancy increases the maternal risk for diabetic ketoacidosis, pre- eclampsia, spontaneous abortions, preterm delivery, stillbirth and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.
- In a combined fertility and embryofetal development study in rats, subcutaneous doses of 0.01, 0.03 and 0.09 mg/kg/day (0.1-, 0.4-, and 1.1-fold the MRHD) were administered to males for 4 weeks prior to and throughout mating and to females for 2 weeks prior to mating, and throughout organogenesis to Gestation Day 17. In parental animals, pharmacologically mediated reductions in body weight gain and food consumption were observed at all dose levels. In the offspring, reduced growth and fetuses with visceral (heart blood vessels) and skeletal (cranial bones, vertebra, ribs) abnormalities were observed at the human exposure.
- In an embryofetal development study in pregnant rabbits, subcutaneous doses of 0.0010, 0.0025 or 0.0075 mg/kg/day (0.03-, 0.3-, and 2.3-fold the MRHD) were administered throughout organogenesis from Gestation Day 6 to 19. Pharmacologically mediated reductions in maternal body weight gain and food consumption were observed at all dose levels. Early pregnancy losses and increased incidences of minor visceral (kidney, liver) and skeletal (sternebra) fetal abnormalities were observed at ≥0.0025 mg/kg/day, at clinically relevant exposures.
- In an embryofetal development study in pregnant cynomolgus monkeys, subcutaneous doses of 0.015, 0.075, and 0.15 mg/kg twice weekly (1.0-, 5.2-, and 14.9-fold the MRHD) were administered throughout organogenesis, from Gestation Day 16 to 50. Pharmacologically mediated, marked initial maternal body weight loss and reductions in body weight gain and food consumption coincided with the occurrence of sporadic abnormalities (vertebra, sternebra, ribs) at ≥0.075 mg/kg twice weekly (>5X human exposure).
- In a pre- and postnatal development study in pregnant cynomolgus monkeys, subcutaneous doses of 0.015, 0.075, and 0.15 mg/kg twice weekly (0.7-, 3.3-, and 7.2-fold the MRHD) were administered from Gestation Day 16 to 140. Pharmacologically mediated marked initial maternal body weight loss and reductions in body weight gain and food consumption coincided with an increase in early pregnancy losses and led to delivery of slightly smaller offspring at ≥0.075 mg/kg twice weekly (>3X human exposure).
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Semaglutide in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Semaglutide during labor and delivery.
### Nursing Mothers
- There are no data on the presence of semaglutide in human milk, the effects on the breastfed infant, or the effects on milk production. Semaglutide was present in the milk of lactating rats, however, due to species-specific differences in lactation physiology, the clinical relevance of these data are not clear. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for semaglutide and any potential adverse effects on the breastfed infant from semaglutide or from the underlying maternal condition.
- In lactating rats, semaglutide was detected in milk at levels 3-12 fold lower than in maternal plasma.
### Pediatric Use
- Safety and efficacy of semaglutide have not been established in pediatric patients (younger than 18 years).
### Geriatic Use
- In the pool of placebo- and active-controlled glycemic control trials, 744 (23.6%) semaglutide-treated patients were 65 years of age and over and 102 semaglutide-treated patients (3.2%) patients were 75 years of age and over. In SUSTAIN 6, the cardiovascular outcome trial, 788 (48.0%) semaglutide-treated patients were 65 years of age and over and 157 semaglutide-treated patients (9.6%) patients were 75 years of age and over.
- No overall differences in safety or efficacy were detected between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
### Gender
There is no FDA guidance on the use of Semaglutide with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Semaglutide with respect to specific racial populations.
### Renal Impairment
- No dose adjustment of semaglutide is recommended for patients with renal impairment. In subjects with renal impairment including end-stage renal disease (ESRD), no clinically relevant change in semaglutide pharmacokinetics (PK) was observed.
### Hepatic Impairment
- No dose adjustment of semaglutide is recommended for patients with hepatic impairment. In a study in subjects with different degrees of hepatic impairment, no clinically relevant change in semaglutide pharmacokinetics (PK) was observed.
### Females of Reproductive Potential and Males
- Discontinue semaglutide in women at least 2 months before a planned pregnancy due to the long washout period for semaglutide.
### Immunocompromised Patients
There is no FDA guidance one the use of Semaglutide in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Administer semaglutide subcutaneously to the abdomen, thigh, or upper arm. Instruct patients to use a different injection site each week when injecting in the same body region.
- Inspect semaglutide visually before use. It should appear clear and colorless. Do not use semaglutide if particulate matter and coloration is seen.
- When using semaglutide with insulin, instruct patients to administer as separate injections and to never mix the products. It is acceptable to inject semaglutide and insulin in the same body region but the injections should not be adjacent to each other.
### Monitoring
- Achieving glycemic control, including meeting HbA1c goal is indicative of efficacy.
- HbA1c: Twice yearly in patients who are meeting treatment goals; every 3 months in patients whose therapy has changed and/or who are not meeting glycemic goals; more frequently as clinically warranted.
- Renal function: When initiating or escalating doses and in patients reporting severe adverse reactions, especially in patients with renal impairment.
- Progression of diabetic retinopathy: In patients with a history of disease.
- Signs and symptoms of pancreatitis, including persistent severe abdominal pain, sometimes radiating to the back with or without vomiting.
# IV Compatibility
There is limited information regarding the compatibility of Semaglutide and IV administrations.
# Overdosage
- In the event of overdose, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms. A prolonged period of observation and treatment for these symptoms may be necessary, taking into account the long half-life of semaglutide of approximately 1 week.
# Pharmacology
## Mechanism of Action
- Semaglutide is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1.
- GLP-1 is a physiological hormone that has multiple actions on glucose, mediated by the GLP-1 receptors.
- The principal mechanism of protraction resulting in the long half-life of semaglutide is albumin binding, which results in decreased renal clearance and protection from metabolic degradation. Furthermore, semaglutide is stabilized against degradation by the DPP-4 enzyme.
- Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Thus, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase.
## Structure
## Pharmacodynamics
- Semaglutide lowers fasting and postprandial blood glucose and reduces body weight. All pharmacodynamic evaluations were performed after 12 weeks of treatment (including dose escalation) at steady state with semaglutide 1 mg.
- Semaglutide reduces fasting and postprandial glucose concentrations. In patients with type 2 diabetes, treatment with semaglutide 1 mg resulted in reductions in glucose in terms of absolute change from baseline and relative reduction compared to placebo of 29 mg/dL (22%) for fasting glucose, 74 mg/dL (36%) for 2 hour postprandial glucose, and 30 mg/dL (22%) for mean 24 hour glucose concentration (see Figure 1).
- Both first-and second-phase insulin secretion are increased in patients with type 2 diabetes treated with semaglutide compared with placebo.
- Semaglutide lowers the fasting and postprandial glucagon concentrations. In patients with type 2 diabetes, treatment with semaglutide resulted in the following relative reductions in glucagon compared to placebo, fasting glucagon (8%), postprandial glucagon response (14-15%), and mean 24 hour glucagon concentration (12%).
- Semaglutide lowers high blood glucose concentrations by stimulating insulin secretion and lowering glucagon secretion in a glucose-dependent manner. With semaglutide, the insulin secretion rate in patients with type 2 diabetes was similar to that of healthy subjects (see Figure 2).
- During induced hypoglycemia, semaglutide did not alter the counter regulatory responses of increased glucagon compared to placebo, and did not impair the decrease of C-peptide in patients with type 2 diabetes.
- Semaglutide causes a delay of early postprandial gastric emptying, thereby reducing the rate at which glucose appears in the circulation postprandially.
- The effect of semaglutide on cardiac repolarization was tested in a thorough QTc trial. At a dose 1.5 times the maximum recommended dose, semaglutide does not prolong QTc intervals to any clinically relevant extent.
## Pharmacokinetics
- Absolute bioavailability of semaglutide is 89%. Maximum concentration of semaglutide is reached 1 to 3 days post dose.
- Similar exposure is achieved with subcutaneous administration of semaglutide in the abdomen, thigh, or upper arm.
- In patients with type 2 diabetes, semaglutide exposure increases in a dose-proportional manner for once-weekly doses of 0.5 mg and 1 mg. Steady-state exposure is achieved following 4-5 weeks of once-weekly administration. In patients with type 2 diabetes, the mean population-PK estimated steady-state concentrations following once weekly subcutaneous administration of 0.5 mg and 1 mg semaglutide were approximately 65.0 ng/mL and 123.0 ng/mL, respectively.
- The mean apparent volume of distribution of semaglutide following subcutaneous administration in patients with type 2 diabetes is approximately 12.5 L. Semaglutide is extensively bound to plasma albumin (>99%).
- The apparent clearance of semaglutide in patients with type 2 diabetes is approximately 0.05 L/h. With an elimination half-life of approximately 1 week, semaglutide will be present in the circulation for about 5 weeks after the last dose.
Metabolism
- The primary route of elimination for semaglutide is metabolism following proteolytic cleavage of the peptide backbone and sequential beta-oxidation of the fatty acid sidechain.
Excretion
- The primary excretion routes of semaglutide-related material is via the urine and feces. Approximately 3% of the dose is excreted in the urine as intact semaglutide.
- Based on a population pharmacokinetic analysis, age, sex, race, and ethnicity, and renal impairment do not have a clinically meaningful effect on the pharmacokinetics of semaglutide. The exposure of semaglutide decreases with an increase in body weight. However, semaglutide doses of 0.5 mg and 1 mg provide adequate systemic exposure over the body weight range of 40-198 kg evaluated in the clinical trials. The effects of intrinsic factors on the pharmacokinetics of semaglutide are shown in Figure 3.
Patients with Renal Impairment
- Renal impairment does not impact the pharmacokinetics of semaglutide in a clinically relevant manner. This was shown in a study with a single dose of 0.5 mg semaglutide in patients with different degrees of renal impairment (mild, moderate, severe, ESRD) compared with subjects with normal renal function. This was also shown for subjects with both type 2 diabetes and renal impairment based on data from clinical studies (Figure 3).
Patients with Hepatic Impairment
- Hepatic impairment does not have any impact on the exposure of semaglutide. The pharmacokinetics of semaglutide were evaluated in patients with different degrees of hepatic impairment (mild, moderate, severe) compared with subjects with normal hepatic function in a study with a single-dose of 0.5 mg semaglutide.
Pediatric Patients
- Semaglutide has not been studied in pediatric patients.
- In vitro studies have shown very low potential for semaglutide to inhibit or induce CYP enzymes, and to inhibit drug transporters.
- The delay of gastric emptying with semaglutide may influence the absorption of concomitantly administered oral medicinal products. The potential effect of semaglutide on the absorption of co-administered oral medications was studied in trials at semaglutide 1 mg steady-state exposure.
- No clinically relevant drug-drug interaction with semaglutide (Figure 4) was observed based on the evaluated medications; therefore, no dose adjustment is required when co-administered with semaglutide.
- Relative exposure in terms of AUC and Cmax for each medication when given with semaglutide compared to without semaglutide. Metformin and oral contraceptive drug (ethinylestradiol/levonorgestrel) were assessed at steady state. Warfarin (S-warfarin/R-warfarin), digoxin and atorvastatin were assessed after a single dose.
- Abbreviations: AUC: area under the curve. Cmax: maximum concentration. CI: confidence interval.
## Nonclinical Toxicology
- In a 2-year carcinogenicity study in CD-1 mice, subcutaneous doses of 0.3, 1 and 3 mg/kg/day [5-, 17-, and 59-fold the maximum recommended human dose (MRHD) of 1 mg/week, based on AUC] were administered to the males, and 0.1, 0.3 and 1 mg/kg/day (2-, 5-, and 17-fold MRHD) were administered to the females. A statistically significant increase in thyroid C-cell adenomas and a numerical increase in C-cell carcinomas were observed in males and females at all dose levels (>2X human exposure).
- In a 2-year carcinogenicity study in Sprague Dawley rats, subcutaneous doses of 0.0025, 0.01, 0.025 and 0.1 mg/kg/day were administered (below quantification, 0.4-, 1-, and 6-fold the exposure at the MRHD). A statistically significant increase in thyroid C-cell adenomas was observed in males and females at all dose levels, and a statistically significant increase in thyroid C-cell carcinomas was observed in males at ≥0.01 mg/kg/day, at clinically relevant exposures.
- Human relevance of thyroid C-cell tumors in rats is unknown and could not be determined by clinical studies or nonclinical studies.
- Semaglutide was not mutagenic or clastogenic in a standard battery of genotoxicity tests (bacterial mutagenicity (Ames), human lymphocyte chromosome aberration, rat bone marrow micronucleus).
- In a combined fertility and embryo-fetal development study in rats, subcutaneous doses of 0.01, 0.03 and 0.09 mg/kg/day (0.1-, 0.4-, and 1.1-fold the MRHD) were administered to male and female rats. Males were dosed for 4 weeks prior to mating, and females were dosed for 2 weeks prior to mating and throughout organogenesis until Gestation Day 17. No effects were observed on male fertility. In females, an increase in oestrus cycle length was observed at all dose levels, together with a small reduction in numbers of corpora lutea at ≥0.03 mg/kg/day. These effects were likely an adaptive response secondary to the pharmacological effect of semaglutide on food consumption and body weight.
# Clinical Studies
- Semaglutide has been studied as monotherapy and in combination with metformin, metformin and sulfonylureas, metformin and/or thiazolidinedione, and basal insulin in patients with type 2 diabetes mellitus. The efficacy of semaglutide was compared with placebo, sitagliptin, exenatide extended-release (ER), and insulin glargine.
- Most trials evaluated the use of semaglutide 0.5 mg, and 1 mg, with the exception of the trial comparing semaglutide and exenatide ER where only the 1 mg dose was studied.
- In patients with type 2 diabetes mellitus, semaglutide produced clinically relevant reduction from baseline in HbA1c compared with placebo.
- The efficacy of semaglutide was not impacted by age, gender, race, ethnicity, BMI at baseline, body weight (kg) at baseline, diabetes duration and level of renal function impairment.
- In a 30-week double-blind trial (NCT02054897), 388 patients with type 2 diabetes mellitus inadequately controlled with diet and exercise were randomized to semaglutide 0.5 mg or semaglutide 1 mg once weekly or placebo. Patients had a mean age of 54 years and 54% were men. The mean duration of type 2 diabetes was 4.2 years, and the mean BMI was 33 kg/m2. Overall, 64% were White, 8% were Black or African American, and 21% were Asian; 30% identified as Hispanic or Latino ethnicity.
- Monotherapy with semaglutide 0.5 mg and 1 mg once weekly for 30 weeks resulted in a statistically significant reduction in HbA1c compared with placebo (see Table 3).
- In a 56-week, double-blind trial (NCT01930188), 1231 patients with type 2 diabetes mellitus were randomized to semaglutide 0.5 mg once weekly, semaglutide 1 mg once weekly, or sitagliptin 100 mg once daily, all in combination with metformin (94%) and/or thiazolidinediones (6%). Patients had a mean age of 55 years and 51% were men. The mean duration of type 2 diabetes was 6.6 years, and the mean BMI was 32 kg/m2. Overall, 68% were White, 5% were Black or African American, and 25% were Asian; 17% identified as Hispanic or Latino ethnicity.
- Treatment with semaglutide 0.5 mg and 1 mg once weekly for 56 weeks resulted in a statistically significant reduction in HbA1c compared to sitagliptin (see Table 4 and Figure 5).
- In a 56-week, open-label trial (NCT01885208), 813 patients with type 2 diabetes mellitus on metformin alone (49%), metformin with sulfonylurea (45%), or other (6%) were randomized to semaglutide 1 mg once weekly or exenatide 2 mg once weekly. Patients had a mean age of 57 years and 55% were men. The mean duration of type 2 diabetes was 9 years, and the mean BMI was 34 kg/m2. Overall, 84% were White, 7% were Black or African American, and 2% were Asian; 24% identified as Hispanic or Latino ethnicity.
- Treatment with semaglutide 1 mg once weekly for 56 weeks resulted in a statistically significant reduction in HbA1c compared to exenatide 2 mg once weekly (see Table 5).
- In a 30-week, open-label trial (NCT02128932), 1089 patients with type 2 diabetes mellitus were randomized to semaglutide 0.5 mg once weekly, semaglutide 1 mg once weekly, or insulin glargine once daily on a background of metformin (48%) or metformin and sulfonylurea (51%). Patients had a mean age of 57 years and 53% were men. The mean duration of type 2 diabetes was 8.6 years, and the mean BMI was 33 kg/m2. Overall, 77% were White, 9% were Black or African American, and 11% were Asian; 20% identified as Hispanic or Latino ethnicity.
- Patients assigned to insulin glargine had a baseline mean HbA1c of 8.1% and were started on a dose of 10 U once daily. Insulin glargine dose adjustments occurred throughout the trial period based on self-measured fasting plasma glucose before breakfast, targeting 71 to <100 mg/dL. In addition, investigators could titrate insulin glargine at their discretion between study visits. Only 26% of patients had been titrated to goal by the primary endpoint at week 30, at which time the mean daily insulin dose was 29 U per day.
- Treatment with semaglutide 0.5 mg and 1 mg once weekly for 30 weeks resulted in a statistically significant reduction in HbA1c compared with the insulin glargine titration implemented in this study protocol (see Table 6).
- In a 30-week, double-blind trial (NCT02305381), 397 patients with type 2 diabetes mellitus inadequately controlled with basal insulin, with or without metformin, were randomized to semaglutide 0.5 mg once weekly, semaglutide 1 mg once weekly, or placebo. Patients with HbA1c ≤ 8.0% at screening reduced their insulin dose by 20% at start of the trial to reduce the risk of hypoglycemia. Patients had a mean age of 59 years and 56% were men. The mean duration of type 2 diabetes was 13 years, and the mean BMI was 32 kg/m2. Overall, 78% were White, 5% were Black or African American, and 17% were Asian; 12% identified as Hispanic or Latino ethnicity.
- Treatment with semaglutide resulted in a statistically significant reduction in HbA1c after 30 weeks of treatment compared to placebo (see Table 7).
- SUSTAIN 6 (NCT01720446) was a 104-week, double-blind trial in which 3,297 patients with type 2 diabetes and high risk of cardiovascular events were randomized to semaglutide 0.5 mg once weekly, semaglutide 1 mg once weekly, or placebo in addition to standard-of-care. In total, 2,735 (83%) of the patients had a history of cardiovascular disease and 562 (17%) were at high risk but without known cardiovascular disease. The mean age at baseline was 65 years, and 61% were men. The mean duration of diabetes was 13.9 years, and mean BMI was 33 kg/m2. Overall, 83% were White, 7% were Black or African American, and 8% were Asian; 16% identified as Hispanic or Latino ethnicity. Concomitant diseases of patients in this trial included, but were not limited to, heart failure (24%), hypertension (93%), history of ischemic stroke (12%) and history of a myocardial infarction (33%).
- In total, 98.0% of the patients completed the trial and the vital status was known at the end of the trial for 99.6%. The primary composite endpoint was the time from randomization to first occurrence of a major adverse cardiovascular event (MACE): cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. The secondary endpoint was time from randomization to first occurrence of an expanded composite cardiovascular outcome, defined as MACE, revascularization (coronary and peripheral), unstable angina requiring hospitalization or hospitalization for heart failure. The total number of primary component MACE endpoints was 254 (108 [6.6%] with semaglutide and 146 [8.9%] with placebo). No increased risk for MACE was observed with semaglutide.
# How Supplied
- Semaglutide injection is supplied as a clear, colorless solution that contains 2 mg of semaglutide in a 1.5 mL (1.34 mg/mL) pre-filled, disposable, single-patient-use pen injector in the following packaging configurations:
- Pen delivers doses of 0.25 mg or 0.5 mg per injection.
- 6 NovoFine ® Plus needles.
- Intended for treatment initiation at the 0.25 mg dose and maintenance treatment at the 0.5 mg dose.
- Pen delivers doses of 1 mg per injection.
- 4 NovoFine ® Plus needles.
- Intended for maintenance treatment at the 1 mg dose only.
- Each semaglutide pen is for use by a single patient. An semaglutide pen must never be shared between patients, even if the needle is changed.
## Storage
- Prior to first use, semaglutide should be stored in a refrigerator between 36ºF to 46ºF (2ºC to 8ºC) (Table 8). Do not store in the freezer or directly adjacent to the refrigerator cooling element. Do not freeze semaglutide and do not use semaglutide if it has been frozen.
- After first use of the semaglutide pen, the pen can be stored for 56 days at controlled room temperature (59°F to 86°F; 15°C to 30°C) or in a refrigerator (36°F to 46°F; 2°C to 8°C). Do not freeze. Keep the pen cap on when not in use. Semaglutide should be protected from excessive heat and sunlight.
- Always remove and safely discard the needle after each injection and store the semaglutide pen without an injection needle attached. Always use a new needle for each injection.
- The storage conditions are summarized in Table 8:
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
- Advise the patient to read the FDA-approved patient labeling.
- Inform patients that semaglutide causes thyroid C-cell tumors in rodents and that the human relevance of this finding has not been determined. Counsel patients to report symptoms of thyroid tumors (e.g., a lump in the neck, hoarseness, dysphagia, or dyspnea) to their physician.
- Inform patients of the potential risk for pancreatitis. Instruct patients to discontinue semaglutide promptly and contact their physician if pancreatitis is suspected (severe abdominal pain that may radiate to the back, and which may or may not be accompanied by vomiting).
- Inform patients to contact their physician if changes in vision are experienced during treatment with semaglutide.
- Advise patients that they must never share an semaglutide pen with another person, even if the needle is changed, because doing so carries a risk for transmission of blood-borne pathogens.
- Advise patients treated with semaglutide of the potential risk of dehydration due to gastrointestinal adverse reactions and take precautions to avoid fluid depletion. Inform patients of the potential risk for worsening renal function and explain the associated signs and symptoms of renal impairment, as well as the possibility of dialysis as a medical intervention if renal failure occurs.
- Inform patients to stop taking semaglutide and seek medical advice promptly if symptoms of hypersensitivity reactions occur.
- Advise a pregnant woman of the potential risk to a fetus. Advise women to inform their healthcare provider if they are pregnant or intend to become pregnant.
- Inform patients of the potential risks and benefits of semaglutide and of alternative modes of therapy. Inform patients about the importance of adherence to dietary instructions, regular physical activity, periodic blood glucose monitoring and A1c testing, recognition and management of hypoglycemia and hyperglycemia, and assessment for diabetes complications. Advise patients to seek medical advice promptly during periods of stress such as fever, trauma, infection, or surgery as medication requirements may change.
- Advise patients that the most common side effects of semaglutide are nausea, vomiting, diarrhea, abdominal pain and constipation. Inform patients that nausea, vomiting and diarrhea are most common when first starting semaglutide, but decreases over time in the majority of patients.
- Instruct patients to reread the Medication Guide each time the prescription is renewed.
- Inform patients if a dose is missed, it should be administered as soon as possible within 5 days after the missed dose. If more than 5 days have passed, the missed dose should be skipped and the next dose should be administered on the regularly scheduled day. In each case, inform patients to resume their regular once weekly dosing schedule.
- Semaglutide (oh-ZEM-pick)
- (Semaglutide)
- Injection, for subcutaneous use
- Do not share your semaglutide pen with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them.
- Read this Medication Guide before you start using semaglutide and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
- What is the most important information I should know about semaglutide?
- Semaglutide may cause serious side effects, including:
- Possible thyroid tumors, including cancer. Tell your healthcare provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. In studies with rodents, semaglutide and medicines that work like semaglutide caused thyroid tumors, including thyroid cancer. It is not known if semaglutide will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people.
- Do not use semaglutide if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC), or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- What is semaglutide?
- Semaglutide is an injectable prescription medicine for adults with type 2 diabetes mellitus that:
- Along with diet and exercise may improve blood sugar (glucose).
- Semaglutide is not recommended as the first choice of medicine for treating diabetes.
- It is not known if semaglutide can be used in people who have had pancreatitis.
- Semaglutide is not a substitute for insulin and is not for use in people with type 1 diabetes or people with diabetic ketoacidosis.
- It is not known if semaglutide is safe and effective for use in children under 18 years of age.
- Do not use semaglutide if:
- You or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC) or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- You are allergic to semaglutide or any of the ingredients in semaglutide. See the end of this Medication Guide for a complete list of ingredients in semaglutide.
- Before using semaglutide, tell your healthcare provider if you have any other medical conditions, including if you:
- Have or have had problems with your pancreas or kidneys.
- Have a history of diabetic retinopathy.
- Are pregnant or plan to become pregnant. It is not known if semaglutide will harm your unborn baby. You should stop using semaglutide 2 months before you plan to become pregnant. Talk to your healthcare provider about the best way to control your blood sugar if you plan to become pregnant or while you are pregnant.
- Are breastfeeding or plan to breastfeed. It is not known if semaglutide passes into your breast milk. You should talk with your healthcare provider about the best way to feed your baby while using semaglutide.
- Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Semaglutide may affect the way some medicines work and some medicines may affect the way semaglutide works.
- Before using semaglutide, talk to your healthcare provider about low blood sugar and how to manage it. Tell your healthcare provider if you are taking other medicines to treat diabetes, including insulin or sulfonylureas.
- Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
- How should I use semaglutide?
- Read the Instructions for Use that comes with semaglutide.
- Use semaglutide exactly as your healthcare provider tells you to.
- Your healthcare provider should show you how to use semaglutide before you use it for the first time.
- Semaglutide is injected under the skin (subcutaneously) of your stomach (abdomen), thigh, or upper arm. Do not inject semaglutide into a muscle (intramuscularly) or vein (intravenously).
- Use semaglutide 1 time each week, on the same day each week, at any time of the day.
- You may change the day of the week you use semaglutide as long as your last dose was given 2 or more days before.
- If you miss a dose of semaglutide, take the missed dose as soon as possible within 5 days after the missed dose. If more than 5 days have passed, skip the missed dose and take your next dose on the regularly scheduled day.
- Semaglutide may be taken with or without food.
- Do not mix insulin and semaglutide together in the same injection.
- You may give an injection of semaglutide and insulin in the same body area (such as your stomach area), but not right next to each other.
- Change (rotate) your injection site with each injection. Do not use the same site for each injection.
- Check your blood sugar as your healthcare provider tells you to.
- Stay on your prescribed diet and exercise program while using semaglutide.
- Talk to your healthcare provider about how to prevent, recognize and manage low blood sugar (hypoglycemia), high blood sugar (hyperglycemia), and problems you have because of your diabetes.
- Your healthcare provider will check your diabetes with regular blood tests, including your blood sugar levels and your hemoglobin A1C.
- Do not share your semaglutide pen with other people, even if the needle has been changed. You may give other people a serious infection, or get a serious infection from them.
- Your dose of semaglutide and other diabetes medicines may need to change because of:
- Change in level of physical activity or exercise, weight gain or loss, increased stress, illness, change in diet, fever, trauma, infection, surgery or because of other medicines you take.
- What are the possible side effects of semaglutide?
- Semaglutide may cause serious side effects, including:
- See “What is the most important information I should know about semaglutide?”
- Inflammation of your pancreas (pancreatitis). Stop using semaglutide and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back.
- Changes in vision. Tell your healthcare provider if you have changes in vision during treatment with semaglutide.
- Low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use semaglutide with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin. Signs and symptoms of low blood sugar may include:
- Dizziness or light-headedness
- Blurred vision
- Anxiety, irritability, or mood changes
- Sweating
- Slurred speech
- Hunger
- Confusion or drowsiness
- Shakiness
- Weakness
- Headache
- Fast heartbeat
- Feeling jittery
- Kidney problems (kidney failure). In people who have kidney problems, diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration) which may cause kidney problems to get worse. It is important for you to drink fluids to help reduce your chance of dehydration.
- Serious allergic reactions. Stop using semaglutide and get medical help right away, if you have any symptoms of a serious allergic reaction including itching, rash, or difficulty breathing.
- The most common side effects of semaglutide may include nausea, vomiting, diarrhea, stomach (abdominal) pain and constipation.
- Talk to your healthcare provider about any side effect that bothers you or does not go away. These are not all the possible side effects of semaglutide.
- Call your doctor for medical advice about side effects. You may report side effects to FDA at 1‑800‑FDA‑1088.
- General information about the safe and effective use of semaglutide.
- Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use semaglutide for a condition for which it was not prescribed. Do not give semaglutide to other people, even if they have the same symptoms that you have. It may harm them.
- You can ask your pharmacist or healthcare provider for information about semaglutide that is written for health professionals.
- For more information, go to OZEMPIC.com or call 1-888-693-6742.
- What are the ingredients in OZEMPIC?
- Active Ingredient: semaglutide.
- Inactive Ingredients: disodium phosphate dihydrate, propylene glycol, phenol and water for injection.
# Precautions with Alcohol
Alcohol-Semaglutide interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
# Brand Names
- Ozempic
# Look-Alike Drug Names
There is limited information regarding Semaglutide Look-Alike Drug Names in the drug label.
# Drug Shortage Status
Drug Shortage
# Price | https://www.wikidoc.org/index.php/Semaglutide | |
3b1403ce73d883126cdeedc3d42efe47e0ae9b7b | wikidoc | Seratrodast | Seratrodast
# Overview
Seratrodast (INN) is a thromboxane A2 (TXA2) receptor (TP receptor) antagonist used primarily in the treatment of asthma. It was the first TP receptor antagonist that was developed as an anti-asthmatic drug and received marketing approval in Japan in 1997.Seratrodast is currently marketed in Japan,and India(approved in Dec 2012) as an add-on controller therapy in the management of asthma.
Unlike thromboxane synthase inhibitors, like Ozagrel, Seratrodast does not affect thrombus formation, time to occlusion and bleeding time.Seratrodast has no effect on prothrombin time and activated partial thromboplastin time, thus ruling out any action on blood coagulation cascade.
# Pharmacodynamics
TXA2 and other bronchoconstrictor prostanoids, like PGD2 and PGF2α, are generated in asthma and participate in acute and chronic inflammatory processes. Seratrodast, being a TP receptor antagonist, inhibits the following pathophysiological processes in asthma:
## Airway smooth muscle contraction
Ligand binding studies on TP receptors have shown the existence of TP receptors on airway smooth muscle. Experimental studies have indicated that the contractile potency of TXA2 is about two times more potent than other prostaglandins.Experiments utilizing several TP receptor antagonists have further supported the view that not only TXA2 but even PGF2α, PGD2 and its metabolite 9α,11β-PGF2 contract airway smooth muscle via direct stimulation of TP receptors, indicating the involvement of TP receptors in airway smooth muscle contractions.In studies, Seratrodast competitively inhibited the contractile response to the TXA2 mimetic (analogue), PGD2, 9α,11β-PGF2 and PGF2α.Other than inhibition of actions of prostanoids, Seratrodast, when given orally, inhibited bronchoconstriction in guinea pigs induced by leukotriene D4 (LTD4) and platelet activating factor (PAF).
## Vascular smooth muscle contraction
Activation of vascular TP receptors has been observed to invariably induce vasoconstriction.The same has been illustrated by in vitro potency and efficacy of TXA2 in inducing constriction of internal mammary arteries.Seratrodast competitively inhibited the contractile response to TXA2 mimetic (analogue) in guinea pig lung parenchymal strips and dog saphenous vein strips.In anesthetized rabbits, Seratrodast abolished the decrease in internal diameter of small pulmonary arteries in response to TXA2 mimetic (analogue), indicating direct role of activation of TP receptors in vascular smooth muscle contraction.
## Plasma extravasation
TXA2 and PGF2α potently induce plasma exudation in airways.Studies have indicated inhibition of PAF- or leukotriene D4 (LTD4)-induced plasma exudation by TP receptor antagonists, suggesting that TXA2 is endogenously released in response to inflammatory mediators other than prostanoids resulting in airway microvascular leakage.
## Neuromodulatory effects
Prostanoids have potent neuromodulatory effects. Experimental studies on isolated arterial preparation have suggested that TXA2 and related prostaglandins may have some vascular effects on adrenergic fibres that have been found to be in close association with bronchial vessels.TXA2 has also been implicated in acting presynaptically to enhance the release or duration of release of acetylcholine, a potent bronchoconstrictor, from cholinergic nerves.
## Mucous secretion
Prostanoids such as PGF2α and PGD2 have been observed to significantly increase mucous glycoprotein release,while TXA2 has been shown to increase tracheal mucous gel layer.Antagonism of TP receptor was not only observed to inhibit the tracheal mucous gel layer response of TXA2, but was also found to attenuate the mucous gel layer response caused by leukotrienes, indicating an indirect link between leukotrienes and TP receptors.
## Smooth muscle proliferation
TXA2 elicits the proliferation of human airway smooth muscle cells as well as vascular smooth muscle cells,thus participating in airway smooth muscle hypertrophy and hyperplasia.
## Airway hyper-responsiveness
The effects of TXA2 and related prostaglandins on plasma exudation, acetylcholine release and smooth muscle proliferation support the potential role of TP receptor stimulation in the pathogenesis of airway hyper-responsiveness. The airway mucosal edema due to plasma exudation and the smooth muscle proliferation contribute to thickening of the airway wall Plasma exudation leads to liquid filling of the airway interstices formed between luminal epithelial projections, which amplify the luminal narrowing due to airway smooth muscle contraction.
In addition to inhibition of actions of prostanoids, TP receptor antagonism has been shown to prevent increased airway reactivity to allergens, PAF, LTC4, D4, and B4, bradykinin, endothelin, endotoxin, and ozone.
# Pharmacokinetics
The pharmacokinetics of Seratrodast have been studied in Japanese and Caucasian, including Indian, healthy volunteers. The plasma concentrations of Seratrodast increase with increasing doses. The absorption of Seratrodast is relatively rapid with maximum plasma concentrations of 4.6-6 µg/ml obtained in 3 to 4 hours. Steady state plasma concentrations of seratrodast are reached within 4–5 days. Seratrodast is slowly cleared, mainly by hepatic biotransformation. The drug shows biexponential decay in plasma profiles with a mean elimination half-life of 22 hours. Approximately 20% of the administered dose is recovered in the urine, with 60% of the urinary recovery being in the form of conjugates
# Dosage and administration
## Recommended dosage
The average recommended dose of Seratrodast is 80 mg once daily. Seratrodast has been well tolerated following repeated once daily oral doses of up to a maximum of 320 mg. In elderly patients it is recommended that the treatment should be started with a lower dose of 40 mg/day.
## Pregnancy and lactation
There are no adequate and well controlled studies of Seratrodast in pregnant women. The drug should be used in pregnancy only if the potential benefits justify the risk to the fetus. Seratrodast should not be used during lactation.
## Pediatric use
The safety and efficacy of Seratrodast has not been established in children (< 18 years of age).
# Clinical experience
The efficacy and safety of seratrodast has been established through various clinical studies conducted on over 5000 patients in indications like asthma, perennial allergic rhinitis, chronic bronchitis and chronic pulmonary emphysema.
## Asthma
In various clinical studies, seratrodast improved lung function parameters such as FEV1, FVC and PEF, and clinical symptoms of asthma such as wheezing, shortness of breath, cough, expectoration and chest tightness. The improvement in PEF with seratrodast (80 mg o.d. for 28 days) was found to be significantly greater than Montelukast (10 mg o.d. for 28 days). With respect to the levels of various biochemical parameters of sputum, seratrodast showed significant reduction in sputum fucose, eosinophil cationic protein (ECP) and albumin levels. The decrease in sputum ECP and albumin levels with seratrodast was found to be better than Montelukast In a 6-week comparative clinical study with zafirlukast 20 mg, seratrodast was observed to have a better control over asthma compared to zafirlukast (71.68% vs. 62.62%). Seratrodast (80 mg o.d.) administered over 12 weeks was found to decrease airway hyper-responsiveness to acetylcholine with significant improvement in PEF, clinical symptoms of asthma and sputum ECP levels. In a 6-week clinical study with seratrodast (40 mg o.d.), significant decrease in the amount and dynamic viscosity of sputum, and reduction in nasal clearance time of saccharin particle were observed. Long term administration of seratrodast (80 mg o.d.) over 2 years was observed to lessen exacerbation rate of asthma in patient after first 12 months of therapy and reduce the average dose of inhaled beclomethasone dipropionate (iBDP).
## Perennial allergic rhinitis
Seratrodast has been observed to show improvement in nasal obstruction, nasal discharge and sneezing in patients with allergic rhinitis. Improvement rates of nasal obstruction, nasal discharge and sneezing with Seratrodast (80 mg/day) were found to be better than terfenadine (120 mg/day). Concomitant use with Mequitazine was found to have better impact on nasal symptoms than using Mequitazine alone, though there was no significant difference in improvement rate between concomitant group and Seratrodast group. Dose dependent increase in improvement rates of nasal symptoms has been observed with Seratrodast, with equivalent efficacy of 80 mg/day and 120 mg/day dosage of Seratrodast. Seratrodast (80 mg o.d.) administered over 4 weeks was found to significantly improve nasal volume and cross-sectional area. Long term administration of Seratrodast (80 mg o.d.) over 24 weeks was found to be highly effective in treating allergic rhinitis with significant reduction in nasal obstruction, nasal discharge and sneezing.
## Chronic bronchitis
In patients with chronic bronchitis, Seratrodast (80 mg o.d. for 4 weeks) was observed to significantly increase the cough threshold compared to placebo, while pranlukast (112.5 mg o.d. for 4 weeks) did not have any impact on the same.
## COPD
Seratrodast (80 mg o.d.), administered over 8 weeks in patients with chronic pulmonary emphysema, was shown to significantly improve respiratory distress, evaluated on both the Hugh-Jones classification and the Borg scale, with significant improvement in FVC. Plasma levels of 11-dehydro-TXB2 were also observed to decrease significantly by the end of 8 weeks.
## Smoker's cough
There are anecdotal evidences of improvement of cough with once daily dosage of seratrodast. Various experimental studies have been conducted providing fresh evidence for reducing the incidence of smokers cough.
# Safety and tolerability
In post-marketing study conducted in over 4000 patients by the innovator, the most frequently observed (0.1 to 5%) adverse reactions were elevated levels of liver enzymes such as ALT, AST, ALP, LDH and γ-GTP, nausea, loss of appetite, stomach discomfort, abdominal pain, diarrhea, constipation, dry mouth, taste disturbance, drowsiness, headache, dizziness, palpitations and malaise. Less than 0.1% of patients experienced vomiting, thrombocytopenia, epistaxis, bleeding tendency, insomnia, tremor, numbness, hot flushes and edema. All the adverse reactions reported were of mild to moderate severity, and resolved when the drug was discontinued.
In clinical studies with Seratrodast, no significant difference was observed in the incidence of adverse events when compared with Montelukast. Global assessment towards the therapy with Seratrodast was deemed as “satisfactory-to-excellent” by the investigators. No difference in overall drug compliance was observed with Seratrodast when compared with Montelukast (99.02% vs. 98.06%).
# Synthesis
Seratrodast can be prepared in five steps starting from pimelic acid monoester. | Seratrodast
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]
# Overview
Seratrodast (INN) is a thromboxane A2 (TXA2) receptor (TP receptor) antagonist used primarily in the treatment of asthma. It was the first TP receptor antagonist that was developed as an anti-asthmatic drug and received marketing approval in Japan in 1997.Seratrodast is currently marketed in Japan,and India(approved in Dec 2012) as an add-on controller therapy in the management of asthma.
Unlike thromboxane synthase inhibitors, like Ozagrel, Seratrodast does not affect thrombus formation, time to occlusion and bleeding time.Seratrodast has no effect on prothrombin time and activated partial thromboplastin time, thus ruling out any action on blood coagulation cascade.
# Pharmacodynamics
TXA2 and other bronchoconstrictor prostanoids, like PGD2 and PGF2α, are generated in asthma and participate in acute and chronic inflammatory processes. Seratrodast, being a TP receptor antagonist, inhibits the following pathophysiological processes in asthma:
## Airway smooth muscle contraction
Ligand binding studies on TP receptors have shown the existence of TP receptors on airway smooth muscle. Experimental studies have indicated that the contractile potency of TXA2 is about two times more potent than other prostaglandins.Experiments utilizing several TP receptor antagonists have further supported the view that not only TXA2 but even PGF2α, PGD2 and its metabolite 9α,11β-PGF2 contract airway smooth muscle via direct stimulation of TP receptors, indicating the involvement of TP receptors in airway smooth muscle contractions.In studies, Seratrodast competitively inhibited the contractile response to the TXA2 mimetic (analogue), PGD2, 9α,11β-PGF2 and PGF2α.Other than inhibition of actions of prostanoids, Seratrodast, when given orally, inhibited bronchoconstriction in guinea pigs induced by leukotriene D4 (LTD4) and platelet activating factor (PAF).
## Vascular smooth muscle contraction
Activation of vascular TP receptors has been observed to invariably induce vasoconstriction.The same has been illustrated by in vitro potency and efficacy of TXA2 in inducing constriction of internal mammary arteries.Seratrodast competitively inhibited the contractile response to TXA2 mimetic (analogue) in guinea pig lung parenchymal strips and dog saphenous vein strips.In anesthetized rabbits, Seratrodast abolished the decrease in internal diameter of small pulmonary arteries in response to TXA2 mimetic (analogue), indicating direct role of activation of TP receptors in vascular smooth muscle contraction.
## Plasma extravasation
TXA2 and PGF2α potently induce plasma exudation in airways.Studies have indicated inhibition of PAF- or leukotriene D4 (LTD4)-induced plasma exudation by TP receptor antagonists, suggesting that TXA2 is endogenously released in response to inflammatory mediators other than prostanoids resulting in airway microvascular leakage.
## Neuromodulatory effects
Prostanoids have potent neuromodulatory effects. Experimental studies on isolated arterial preparation have suggested that TXA2 and related prostaglandins may have some vascular effects on adrenergic fibres that have been found to be in close association with bronchial vessels.TXA2 has also been implicated in acting presynaptically to enhance the release or duration of release of acetylcholine, a potent bronchoconstrictor, from cholinergic nerves.
## Mucous secretion
Prostanoids such as PGF2α and PGD2 have been observed to significantly increase mucous glycoprotein release,while TXA2 has been shown to increase tracheal mucous gel layer.Antagonism of TP receptor was not only observed to inhibit the tracheal mucous gel layer response of TXA2, but was also found to attenuate the mucous gel layer response caused by leukotrienes, indicating an indirect link between leukotrienes and TP receptors.
## Smooth muscle proliferation
TXA2 elicits the proliferation of human airway smooth muscle cells as well as vascular smooth muscle cells,thus participating in airway smooth muscle hypertrophy and hyperplasia.
## Airway hyper-responsiveness
The effects of TXA2 and related prostaglandins on plasma exudation, acetylcholine release and smooth muscle proliferation support the potential role of TP receptor stimulation in the pathogenesis of airway hyper-responsiveness.[1] The airway mucosal edema due to plasma exudation and the smooth muscle proliferation contribute to thickening of the airway wall [1] Plasma exudation leads to liquid filling of the airway interstices formed between luminal epithelial projections, which amplify the luminal narrowing due to airway smooth muscle contraction.[1]
In addition to inhibition of actions of prostanoids, TP receptor antagonism has been shown to prevent increased airway reactivity to allergens,[2] PAF,[3] LTC4, D4,[4][5] and B4,[6] bradykinin,[7] endothelin,[8] endotoxin,[9] and ozone.[10]
# Pharmacokinetics
The pharmacokinetics of Seratrodast have been studied in Japanese and Caucasian, including Indian, healthy volunteers.[11][12][13][14] The plasma concentrations of Seratrodast increase with increasing doses. The absorption of Seratrodast is relatively rapid with maximum plasma concentrations of 4.6-6 µg/ml obtained in 3 to 4 hours.[11] Steady state plasma concentrations of seratrodast are reached within 4–5 days.[13] Seratrodast is slowly cleared, mainly by hepatic biotransformation. The drug shows biexponential decay in plasma profiles with a mean elimination half-life of 22 hours.[11][13] Approximately 20% of the administered dose is recovered in the urine, with 60% of the urinary recovery being in the form of conjugates [12]
# Dosage and administration
## Recommended dosage
The average recommended dose of Seratrodast is 80 mg once daily.[15] Seratrodast has been well tolerated following repeated once daily oral doses of up to a maximum of 320 mg. In elderly patients it is recommended that the treatment should be started with a lower dose of 40 mg/day.[15]
## Pregnancy and lactation
There are no adequate and well controlled studies of Seratrodast in pregnant women. The drug should be used in pregnancy only if the potential benefits justify the risk to the fetus.[15] Seratrodast should not be used during lactation.[15]
## Pediatric use
The safety and efficacy of Seratrodast has not been established in children (< 18 years of age).[15]
# Clinical experience
The efficacy and safety of seratrodast has been established through various clinical studies conducted on over 5000 patients in indications like asthma, perennial allergic rhinitis, chronic bronchitis and chronic pulmonary emphysema.
## Asthma
In various clinical studies, seratrodast improved lung function parameters such as FEV1, FVC and PEF, and clinical symptoms of asthma such as wheezing, shortness of breath, cough, expectoration and chest tightness.[16][17][18][19][20] The improvement in PEF with seratrodast (80 mg o.d. for 28 days) was found to be significantly greater than Montelukast (10 mg o.d. for 28 days).[16] With respect to the levels of various biochemical parameters of sputum, seratrodast showed significant reduction in sputum fucose,[16][21] eosinophil cationic protein (ECP) [16][22] and albumin levels.[16][21] The decrease in sputum ECP and albumin levels with seratrodast was found to be better than Montelukast [16] In a 6-week comparative clinical study with zafirlukast 20 mg, seratrodast was observed to have a better control over asthma compared to zafirlukast (71.68% vs. 62.62%).[17] Seratrodast (80 mg o.d.) administered over 12 weeks was found to decrease airway hyper-responsiveness to acetylcholine with significant improvement in PEF, clinical symptoms of asthma and sputum ECP levels.[22] In a 6-week clinical study with seratrodast (40 mg o.d.), significant decrease in the amount and dynamic viscosity of sputum, and reduction in nasal clearance time of saccharin particle were observed.[21] Long term administration of seratrodast (80 mg o.d.) over 2 years was observed to lessen exacerbation rate of asthma in patient after first 12 months of therapy and reduce the average dose of inhaled beclomethasone dipropionate (iBDP).[23]
## Perennial allergic rhinitis
Seratrodast has been observed to show improvement in nasal obstruction, nasal discharge and sneezing in patients with allergic rhinitis.[24][25][26][27][28][29][30][31] Improvement rates of nasal obstruction, nasal discharge and sneezing with Seratrodast (80 mg/day) were found to be better than terfenadine (120 mg/day).[24] Concomitant use with Mequitazine was found to have better impact on nasal symptoms than using Mequitazine alone, though there was no significant difference in improvement rate between concomitant group and Seratrodast group.[26] Dose dependent increase in improvement rates of nasal symptoms has been observed with Seratrodast,[27] with equivalent efficacy of 80 mg/day and 120 mg/day dosage of Seratrodast.[28] Seratrodast (80 mg o.d.) administered over 4 weeks was found to significantly improve nasal volume and cross-sectional area.[30] Long term administration of Seratrodast (80 mg o.d.) over 24 weeks was found to be highly effective in treating allergic rhinitis with significant reduction in nasal obstruction, nasal discharge and sneezing.[29]
## Chronic bronchitis
In patients with chronic bronchitis, Seratrodast (80 mg o.d. for 4 weeks) was observed to significantly increase the cough threshold compared to placebo, while pranlukast (112.5 mg o.d. for 4 weeks) did not have any impact on the same.[32]
## COPD
Seratrodast (80 mg o.d.), administered over 8 weeks in patients with chronic pulmonary emphysema, was shown to significantly improve respiratory distress, evaluated on both the Hugh-Jones classification and the Borg scale, with significant improvement in FVC.[33] Plasma levels of 11-dehydro-TXB2 were also observed to decrease significantly by the end of 8 weeks.[33]
## Smoker's cough
There are anecdotal evidences of improvement of cough with once daily dosage of seratrodast. Various experimental studies have been conducted providing fresh evidence for reducing the incidence of smokers cough.[34][35]
# Safety and tolerability
In post-marketing study conducted in over 4000 patients by the innovator, the most frequently observed (0.1 to 5%) adverse reactions were elevated levels of liver enzymes such as ALT, AST, ALP, LDH and γ-GTP, nausea, loss of appetite, stomach discomfort, abdominal pain, diarrhea, constipation, dry mouth, taste disturbance, drowsiness, headache, dizziness, palpitations and malaise.[15] Less than 0.1% of patients experienced vomiting, thrombocytopenia, epistaxis, bleeding tendency, insomnia, tremor, numbness, hot flushes and edema.[15] All the adverse reactions reported were of mild to moderate severity, and resolved when the drug was discontinued.[15]
In clinical studies with Seratrodast, no significant difference was observed in the incidence of adverse events when compared with Montelukast.[16] Global assessment towards the therapy with Seratrodast was deemed as “satisfactory-to-excellent” by the investigators.[16] No difference in overall drug compliance was observed with Seratrodast when compared with Montelukast (99.02% vs. 98.06%).[16]
# Synthesis
Seratrodast can be prepared in five steps starting from pimelic acid monoester.[36] | https://www.wikidoc.org/index.php/Seratrodast | |
1dcafe2059a03a6613afb9b154e17869aabd2548 | wikidoc | Sevoflurane | Sevoflurane
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# Overview
Sevoflurane is a general anesthetic that is FDA approved for the {{{indicationType}}} of general anesthesia. Common adverse reactions include cardiovascular: bradyarrhythmia (3% to 5% ), hypotension (4% to 11% ), gastrointestinal: nausea (25% ), vomiting (18% ), neurologic: somnolence (9% ), psychiatric: agitation (6% to 15%), respiratory: cough (5% to 11% ), interrupted breathing (2% to 6% ), other: shivering (6% ).
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- General anesthesia: 0.5% to 3% concentration with or without concomitant use of nitrous oxide
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information about Off-Label Guideline-Supported Use of Sevoflurane in adult patients.
### Non–Guideline-Supported Use
There is limited information about Off-Label Non–Guideline-Supported Use of Sevoflurane in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- General anesthesia: 0.5% to 3% concentration with or without concomitant use of nitrous oxide
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information about Off-Label Guideline-Supported Use of Sevoflurane in pediatric patients.
### Non–Guideline-Supported Use
There is limited information about Off-Label Non–Guideline-Supported Use of Sevoflurane in pediatric patients.
# Contraindications
- Sevoflurane can cause malignant hyperthermia. It should not be used in patients with known sensitivity to sevoflurane or to other halogenated agents nor in patients with known or suspected susceptibility to malignant hyperthermia.
# Warnings
- Although data from controlled clinical studies at low flow rates are limited, findings taken from patient and animal studies suggest that there is a potential for renal injury which is presumed due to Compound A. Animal and human studies demonstrate that sevoflurane administered for more than 2 MAC·hours and at fresh gas flow rates of < 2 L/min may be associated with proteinuria and glycosuria.
- While a level of Compound A exposure at which clinical nephrotoxicity might be expected to occur has not been established, it is prudent to consider all of the factors leading to Compound A exposure in humans, especially duration of exposure, fresh gas flow rate, and concentration of sevoflurane. During sevoflurane anesthesia the clinician should adjust inspired concentration and fresh gas flow rate to minimize exposure to Compound A. To minimize exposure to Compound A, sevoflurane exposure should not exceed 2 MAC·hours at flow rates of 1 to < 2 L/min. Fresh gas flow rates < 1 L/min are not recommended.
- Because clinical experience in administering sevoflurane to patients with renal insufficiency (creatinine > 1.5 mg/dL) is limited, its safety in these patients has not been established.
- Sevoflurane may be associated with glycosuria and proteinuria when used for long procedures at low flow rates. The safety of low flow sevoflurane on renal function was evaluated in patients with normal preoperative renal function. One study compared sevoflurane (N = 98) to an active control (N = 90) administered for ≥ 2 hours at a fresh gas flow rate of ≤ 1 Liter/minute. Per study defined criteria (Hou et al.) one patient in the sevoflurane group developed elevations of creatinine, in addition to glycosuria and proteinuria. This patient received sevoflurane at fresh gas flow rates of ≤ 800 mL/minute. Using these same criteria, there were no patients in the active control group who developed treatment emergent elevations in serum creatinine.
- Sevoflurane may present an increased risk in patients with known sensitivity to volatile halogenated anesthetic agents. KOH containing CO2 absorbents are not recommended for use with sevoflurane.
- Reports of QT prolongation, associated with torsade de pointes (in exceptional cases, fatal), have been received. Caution should be exercised when administering sevoflurane to susceptible patients (e.g. patients with congenital Long QT Syndrome or patients taking drugs that can prolong the QT interval).
- In susceptible individuals, potent inhalation anesthetic agents, including sevoflurane, may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia. Sevoflurane can induce malignant hyperthermia in genetically susceptible individuals, such as those with certain inherited ryanodine receptor mutations. The clinical syndrome is signaled by hypercapnia, and may include muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias, and/or unstable blood pressure. Some of these nonspecific signs may also appear during light anesthesia, acute hypoxia, hypercapnia, and hypovolemia.
- In clinical trials, one case of malignant hyperthermia was reported. In addition, there have been postmarketing reports of malignant hyperthermia. Some of these cases have been fatal.
- Treatment of malignant hyperthermia includes discontinuation of triggering agents (e.g., sevoflurane), administration of intravenous dantrolene sodium (consult prescribing information for intravenous dantrolene sodium for additional information on patient management), and application of supportive therapy. Supportive therapy may include efforts to restore body temperature, respiratory and circulatory support as indicated, and management of electrolyte-fluid-acid-base abnormalities. Renal failure may appear later, and urine flow should be monitored and sustained if possible.
- Use of inhaled anesthetic agents has been associated with rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in pediatric patients during the postoperative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Concomitant use of succinylcholine has been associated with most, but not all, of these cases. These patients also experienced significant elevations in serum creatine kinase levels and, in some cases, changes in urine consistent with myoglobinuria. Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended; as is subsequent evaluation for latent neuromuscular disease.
# Adverse Reactions
## Clinical Trials Experience
- Adverse events are derived from controlled clinical trials conducted in the United States, Canada, and Europe. The reference drugs were isoflurane, enflurane, and propofol in adults and halothane in pediatric patients. The studies were conducted using a variety of premedications, other anesthetics, and surgical procedures of varying length. Most adverse events reported were mild and transient, and may reflect the surgical procedures, patient characteristics (including disease) and/or medications administered.
- Of the 5182 patients enrolled in the clinical trials, 2906 were exposed to sevoflurane, including 118 adults and 507 pediatric patients who underwent mask induction. Each patient was counted once for each type of adverse event. Adverse events reported in patients in clinical trials and considered to be possibly or probably related to sevoflurane are presented within each body system in order of decreasing frequency in the following listings. One case of malignant hyperthermia was reported in pre-registration clinical trials.
- Adverse Events During the Induction Period (from Onset of Anesthesia by Mask Induction to Surgical Incision) Incidence > 1%
- Adult Patients (N = 118)
- Bradycardia 5%, hypotension 4%, tachycardia 2%
- Agitation 7%
- Laryngospasm 8%, airway obstruction 8%, breathholding 5%, cough increased 5%
### Pediatric Patients (N = 507)
- Tachycardia 6%, hypotension 4%
- Agitation 15%
- Breathholding 5%, cough increased 5%, laryngospasm 3%, apnea 2%
- Increased salivation 2%
### Adverse Events During Maintenance and Emergence Periods, Incidence > 1% (N = 2906)
- Fever 1%, shivering 6%, hypothermia 1%, movement 1%, headache 1%
- Hypotension 11%, hypertension 2%, bradycardia 5%, tachycardia 2%
- Somnolence 9%, agitation 9%, dizziness 4%, increased salivation 4%
- Nausea 25%, vomiting 18%
- Cough increased 11%, Breathholding 2%, Laryngospasm 2%
### Adverse Events, All Patients in Clinical Trials (N = 2906), All Anesthetic Periods, Incidence < 1% (Reported in 3 or More Patients)
- Asthenia, pain
- Arrhythmia, ventricular extrasystoles, supraventricular extrasystoles, complete av block, bigeminy, hemorrhage, inverted t wave, atrial fibrillation, atrial arrhythmia, second degree av block, syncope, s-t depressed
- Crying, nervousness, confusion, hypertonia, dry mouth, insomnia
- Sputum Increased, apnea, hypoxia, wheezing, bronchospasm, hyperventilation, pharyngitis, hiccup, hypoventilation, dyspnea, stridor
- Increases in LDH, AST, ALT, BUN, alkaline phosphatase, creatinine, bilirubinemia, glycosuria, fluorosis, albuminuria, hypophosphatemia, acidosis, hyperglycemia
- Leucocytosis, thrombocytopenia
- Amblyopia, pruritus, taste perversion, rash, conjunctivitis
- Urination impaired, urine abnormality, urinary retention, oliguria
- See Warnings for information regarding malignant hyperthermia.
## Postmarketing Experience
- The following adverse events have been identified during post-approval use of Ultane (sevoflurane USP). Due to the spontaneous nature of these reports, the actual incidence and relationship of Ultane to these events cannot be established with certainty.
- Seizures — Post-marketing reports indicate that sevoflurane use has been associated with seizures. The majority of cases were in children and young adults, most of whom had no medical history of seizures. Several cases reported no concomitant medications, and at least one case was confirmed by EEG. Although many cases were single seizures that resolved spontaneously or after treatment, cases of multiple seizures have also been reported. Seizures have occurred during, or soon after sevoflurane induction, during emergence, and during post-operative recovery up to a day following anesthesia.
- Cardiac arrest
- Cases of mild, moderate and severe post-operative hepatic dysfunction or hepatitis with or without jaundice have been reported. Histological evidence was not provided for any of the reported hepatitis cases. In most of these cases, patients had underlying hepatic conditions or were under treatment with drugs known to cause hepatic dysfunction. Most of the reported events were transient and resolved spontaneously (see Precautions).
- Hepatic necrosis
- Hepatic failure
- Malignant hyperthermia (see Contraindications and Warnings)
- Allergic reactions, such as rash, urticaria, pruritus, bronchospasm, anaphylactic or anaphylactoid reactions (see Contraindications)
- Reports of hypersensitivity (including contact dermatitis, rash, dyspnea, wheezing, chest discomfort, swelling face, or anaphylactic reaction) have been received, particularly in association with long-term occupational exposure to inhaled anesthetic agents, including sevoflurane (see Occupational caution).
- Transient elevations in glucose, liver function tests, and white blood cell count may occur as with use of other anesthetic agents.
# Drug Interactions
- In clinical trials, no significant adverse reactions occurred with other drugs commonly used in the perioperative period, including: central nervous system depressants, autonomic drugs, skeletal muscle relaxants, anti-infective agents, hormones and synthetic substitutes, blood derivatives, and cardiovascular drugs.
- Sevoflurane administration is compatible with barbiturates, propofol, and other commonly used intravenous anesthetics.
- Benzodiazepines and opioids would be expected to decrease the MAC of sevoflurane in the same manner as with other inhalational anesthetics. Sevoflurane administration is compatible with benzodiazepines and opioids as commonly used in surgical practice.
- As with other halogenated volatile anesthetics, the anesthetic requirement for sevoflurane is decreased when administered in combination with nitrous oxide. Using 50% N2O, the MAC equivalent dose requirement is reduced approximately 50% in adults, and approximately 25% in pediatric patients (see Dosage and administration).
- As is the case with other volatile anesthetics, sevoflurane increases both the intensity and duration of neuromuscular blockade induced by nondepolarizing muscle relaxants. When used to supplement alfentanil-N2O anesthesia, sevoflurane and isoflurane equally potentiate neuromuscular block induced with pancuronium, vecuronium or atracurium. Therefore, during sevoflurane anesthesia, the dosage adjustments for these muscle relaxants are similar to those required with isoflurane.
- Potentiation of neuromuscular blocking agents requires equilibration of muscle with delivered partial pressure of sevoflurane. Reduced doses of neuromuscular blocking agents during induction of anesthesia may result in delayed onset of conditions suitable for endotracheal intubation or inadequate muscle relaxation.
- Among available nondepolarizing agents, only vecuronium, pancuronium and atracurium interactions have been studied during sevoflurane anesthesia. In the absence of specific guidelines:
- For endotracheal intubation, do not reduce the dose of nondepolarizing muscle relaxants.
- During maintenance of anesthesia, the required dose of nondepolarizing muscle relaxants is likely to be reduced compared to that during N2O/opioid anesthesia. Administration of supplemental doses of muscle relaxants should be guided by the response to nerve stimulation.
- The effect of sevoflurane on the duration of depolarizing neuromuscular blockade induced by succinylcholine has not been studied.
- Results of evaluations of laboratory parameters (e.g., ALT, AST, alkaline phosphatase, and total bilirubin, etc.), as well as investigator-reported incidence of adverse events relating to liver function, demonstrate that sevoflurane can be administered to patients with normal or mild-to-moderately impaired hepatic function. However, patients with severe hepatic dysfunction were not investigated.
- Occasional cases of transient changes in postoperative hepatic function tests were reported with both sevoflurane and reference agents. Sevoflurane was found to be comparable to isoflurane with regard to these changes in hepatic function.
- Very rare cases of mild, moderate and severe post-operative hepatic dysfunction or hepatitis with or without jaundice have been reported from postmarketing experiences. Clinical judgement should be exercised when sevoflurane is used in patients with underlying hepatic conditions or under treatment with drugs known to cause hepatic dysfunction (see ADVERSE REACTIONS).
- It has been reported that previous exposure to halogenated hydrocarbon anesthetics may increase the potential for hepatic injury.
- An exothermic reaction occurs when sevoflurane is exposed to CO2 absorbents. This reaction is increased when the CO2 absorbent becomes desiccated, such as after an extended period of dry gas flow through the CO2 absorbent canisters. Rare cases of extreme heat, smoke, and/or spontaneous fire in the anesthesia breathing circuit have been reported during sevoflurane use in conjunction with the use of desiccated CO2 absorbent, specifically those containing potassium hydroxide (e.g. Baralyme). KOH containing CO2 absorbents are not recommended for use with sevoflurane. An unusually delayed rise or unexpected decline of inspired sevoflurane concentration compared to the vaporizer setting may be associated with excessive heating of the CO2 absorbent and chemical breakdown of sevoflurane.
- As with other inhalational anesthetics, degradation and production of degradation products can occur when sevoflurane is exposed to desiccated absorbents. When a clinician suspects that the CO2 absorbent may be desiccated, it should be replaced. The color indicator of most CO2 absorbents may not change upon desiccation. Therefore, the lack of significant color change should not be taken as an assurance of adequate hydration. CO2 absorbents should be replaced routinely regardless of the state of the color indicator.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): B
- Reproduction studies have been performed in rats and rabbits at doses up to 1 MAC (minimum alveolar concentration) without CO2 absorbent and have revealed no evidence of impaired fertility or harm to the fetus due to sevoflurane at 0.3 MAC, the highest nontoxic dose. Developmental and reproductive toxicity studies of sevoflurane in animals in the presence of strong alkalies (i.e., degradation of sevoflurane and production of Compound A) have not been conducted. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, sevoflurane should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Sevoflurane in women who are pregnant.
### Labor and Delivery
- Sevoflurane has been used as part of general anesthesia for elective cesarean section in 29 women. There were no untoward effects in mother or neonate (see Pharmacodynamics - Clinical Trials). The safety of sevoflurane in labor and delivery has not been demonstrated.
### Nursing Mothers
- The concentrations of sevoflurane in milk are probably of no clinical importance 24 hours after anesthesia. Because of rapid washout, sevoflurane concentrations in milk are predicted to be below those found with many other volatile anesthetics.
### Pediatric Use
- Induction and maintenance of general anesthesia with sevoflurane have been established in controlled clinical trials in pediatric patients aged 1 to 18 years (see Pharmacodynamics - Clinical Trials and Adverse reactions). Sevoflurane has a nonpungent odor and is suitable for mask induction in pediatric patients.
- The concentration of sevoflurane required for maintenance of general anesthesia is age dependent. When used in combination with nitrous oxide, the MAC equivalent dose of sevoflurane should be reduced in pediatric patients. MAC in premature infants has not been determined (see Precautions - Drug Interactions and Dosage and administration for recommendations in pediatric patients 1 day of age and older).
- The use of sevoflurane has been associated with seizures (see PRECAUTIONS and ADVERSE REACTIONS). The majority of these have occurred in children and young adults starting from 2 months of age, most of whom had no predisposing risk factors. Clinical judgement should be exercised when using sevoflurane in patients who may be at risk for seizures.
### Geriatic Use
- MAC decreases with increasing age. The average concentration of sevoflurane to achieve MAC in an 80 year old is approximately 50% of that required in a 20 year old.
### Gender
There is no FDA guidance on the use of Sevoflurane with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Sevoflurane with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Sevoflurane in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Sevoflurane in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Sevoflurane in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Sevoflurane in patients who are immunocompromised.
# Administration and Monitoring
### Administration
There is limited information regarding Sevoflurane Administration in the drug label.
### Monitoring
There is limited information regarding Sevoflurane Monitoring in the drug label.
# IV Compatibility
There is limited information regarding the compatibility of Sevoflurane and IV administrations.
# Overdosage
- In the event of overdosage, or what may appear to be overdosage, the following action should be taken: discontinue administration of sevoflurane, maintain a patent airway, initiate assisted or controlled ventilation with oxygen, and maintain adequate cardiovascular function.
# Pharmacology
## Mechanism of Action
- Sevoflurane is an inhalational anesthetic agent for use in induction and maintenance of general anesthesia. Minimum alveolar concentration (MAC) of sevoflurane in oxygen for a 40-year-old adult is 2.1%. The MAC of sevoflurane decreases with age (see Dosage and administration for details).
## Structure
- ULTANE (sevoflurane), volatile liquid for inhalation, a nonflammable and nonexplosive liquid administered by vaporization, is a halogenated general inhalation anesthetic drug. Sevoflurane is fluoromethyl 2,2,2,-trifluoro-1-(trifluoromethyl) ethyl ether and its structural formula is:
- Sevoflurane is nonflammable and nonexplosive as defined by the requirements of International Electrotechnical Commission 601-2-13.
- Sevoflurane is a clear, colorless, liquid containing no additives. Sevoflurane is not corrosive to stainless steel, brass, aluminum, nickel-plated brass, chrome-plated brass or copper beryllium. Sevoflurane is nonpungent. It is miscible with ethanol, ether, chloroform, and benzene, and it is slightly soluble in water. Sevoflurane is stable when stored under normal room lighting conditions according to instructions. No discernible degradation of sevoflurane occurs in the presence of strong acids or heat. When in contact with alkaline CO2 absorbents (e.g Baralyme® and to a lesser extent soda lime) within the anesthesia machine, sevoflurane can undergo degradation under certain conditions. Degradation of sevoflurane is minimal, and degradants are either undetectable or present in non-toxic amounts when used as directed with fresh absorbents. Sevoflurane degradation and subsequent degradant formation are enhanced by increasing absorbent temperature increased sevoflurane concentration, decreased fresh gas flow and desiccated CO2 absorbents (especially with potassium hydroxide containing absorbents e.g. Baralyme).
- Sevoflurane alkaline degradation occurs by two pathways. The first results from the loss of hydrogen fluoride with the formation of pentafluoroisopropenyl fluoromethyl ether, (PIFE, C4H2F6O), also known as Compound A, and trace amounts of pentafluoromethoxy isopropyl fluoromethyl ether, (PMFE, C5H6F6O), also known as Compound B. The second pathway for degradation of sevoflurane, which occurs primarily in the presence of desiccated CO2 absorbents, is discussed later.
- In the first pathway, the defluorination pathway, the production of degradants in the anesthesia circuit results from the extraction of the acidic proton in the presence of a strong base (KOH and/or NaOH) forming an alkene (Compound A) from sevoflurane similar to formation of 2-bromo-2-chloro-1,1-difluoro ethylene (BCDFE) from halothane. Laboratory simulations have shown that the concentration of these degradants is inversely correlated with the fresh gas flow rate (See Figure 1).
- Since the reaction of carbon dioxide with absorbents is exothermic, the temperature increase will be determined by quantities of CO2 absorbed, which in turn will depend on fresh gas flow in the anesthesia circle system, metabolic status of the patient, and ventilation. The relationship of temperature produced by varying levels of CO2 and Compound A production is illustrated in the following in vitro simulation where CO2 was added to a circle absorber system.
- Compound A concentration in a circle absorber system increases as a function of increasing CO2 absorbent temperature and composition (Baralyme producing higher levels than soda lime), increased body temperature, and increased minute ventilation, and decreasing fresh gas flow rates. It has been reported that the concentration of Compound A increases significantly with prolonged dehydration of Baralyme. Compound A exposure in patients also has been shown to rise with increased sevoflurane concentrations and duration of anesthesia. In a clinical study in which sevoflurane was administered to patients under low flow conditions for ≥ 2 hours at flow rates of 1 Liter/minute, Compound A levels were measured in an effort to determine the relationship between MAC hours and Compound A levels produced. The relationship between Compound A levels and sevoflurane exposure are shown in Figure 2a.
- Compound A has been shown to be nephrotoxic in rats after exposures that have varied in duration from one to three hours. No histopathologic change was seen at a concentration of up to 270 ppm for one hour. Sporadic single cell necrosis of proximal tubule cells has been reported at a concentration of 114 ppm after a 3-hour exposure to Compound A in rats. The LC50 reported at 1 hour is 1050-1090 ppm (male-female) and, at 3 hours, 350-490 ppm (male-female).
- An experiment was performed comparing sevoflurane plus 75 or 100 ppm Compound A with an active control to evaluate the potential nephrotoxicity of Compound A in non-human primates. A single 8-hour exposure of Sevoflurane in the presence of Compound A produced single-cell renal tubular degeneration and single-cell necrosis in cynomolgus monkeys. These changes are consistent with the increased urinary protein, glucose level and enzymic activity noted on days one and three on the clinical pathology evaluation. This nephrotoxicity produced by Compound A is dose and duration of exposure dependent.
- At a fresh gas flow rate of 1 L/min, mean maximum concentrations of Compound A in the anesthesia circuit in clinical settings are approximately 20 ppm (0.002%) with soda lime and 30 ppm (0.003%) with Baralyme in adult patients; mean maximum concentrations in pediatric patients with soda lime are about half those found in adults. The highest concentration observed in a single patient with Baralyme was 61 ppm (0.0061%) and 32 ppm (0.0032%) with soda lime. The levels of Compound A at which toxicity occurs in humans is not known.
- The second pathway for degradation of sevoflurane occurs primarily in the presence of desiccated CO2 absorbents and leads to the dissociation of sevoflurane into hexafluoroisopropanol (HFIP) and formaldehyde. HFIP is inactive, non-genotoxic, rapidly glucuronidated and cleared by the liver. Formaldehyde is present during normal metabolic processes. Upon exposure to a highly desiccated absorbent, formaldehyde can further degrade into methanol and formate. Formate can contribute to the formation of carbon monoxide in the presence of high temperature that can be associated with desiccated Baralyme®. Methanol can react with Compound A to form the methoxy addition product Compound B. Compound B can undergo further HF elimination to form Compounds C, D, and E.
- Sevoflurane degradants were observed in the respiratory circuit of an experimental anesthesia machine using desiccated CO2 absorbents and maximum sevoflurane concentrations (8%) for extended periods of time (> 2 hours). Concentrations of formaldehyde observed with desiccated soda lime in this experimental anesthesia respiratory circuit were consistent with levels that could potentially result in respiratory irritation. Although KOH containing CO2 absorbents are no longer commercially available, in the laboratory experiments, exposure of sevoflurane to the desiccated KOH containing CO2 absorbent, Baralyme, resulted in the detection of substantially greater degradant levels.
## Pharmacodynamics
- Changes in the depth of sevoflurane anesthesia rapidly follow changes in the inspired concentration.
- In the sevoflurane clinical program, the following recovery variables were evaluated:
- Time to events measured from the end of study drug:
- Time to removal of the endotracheal tube (extubation time)
- Time required for the patient to open his/her eyes on verbal command (emergence time)
- Time to respond to simple command (e.g., squeeze my hand) or demonstrates purposeful movement (response to command time, orientation time)
- Recovery of cognitive function and motor coordination was evaluated based on:
- Psychomotor performance tests (Digit Symbol Substitution Test , Treiger Dot Test)
- The results of subjective (Visual Analog Scale ) and objective (objective pain-discomfort scale ) measurements
- Time to administration of the first post-anesthesia analgesic medication
- Assessments of post-anesthesia patient status
- Other recovery times were:
- Time to achieve an Aldrete Score of ≥ 8
- Time required for the patient to be eligible for discharge from the recovery area, per standard criteria at site
- Time when the patient was eligible for discharge from the hospital
- Time when the patient was able to sit up or stand without dizziness
- Some of these variables are summarized as follows:
- Sevoflurane was studied in 14 healthy volunteers (18-35 years old) comparing sevoflurane-O2 (Sevo/O2) to sevoflurane-N2O/O2 (Sevo/N2O/O2) during 7 hours of anesthesia. During controlled ventilation, hemodynamic parameters measured are shown in Figures 7-10:
- Sevoflurane is a dose-related cardiac depressant. Sevoflurane does not produce increases in heart rate at doses less than 2 MAC.
- A study investigating the epinephrine induced arrhythmogenic effect of sevoflurane versus isoflurane in adult patients undergoing transsphenoidal hypophysectomy demonstrated that the threshold dose of epinephrine (i.e., the dose at which the first sign of arrhythmia was observed) producing multiple ventricular arrhythmias was 5 mcg/kg with both sevoflurane and isoflurane. Consequently, the interaction of sevoflurane with epinephrine appears to be equal to that seen with isoflurane.
## Pharmacokinetics
### Uptake and Distribution
- Because of the low solubility of sevoflurane in blood (blood/gas partition coefficient @ 37°C = 0.63-0.69), a minimal amount of sevoflurane is required to be dissolved in the blood before the alveolar partial pressure is in equilibrium with the arterial partial pressure. Therefore there is a rapid rate of increase in the alveolar (end-tidal) concentration (FA) toward the inspired concentration (FI) during induction.
- In a study in which seven healthy male volunteers were administered 70% N2O/30%O2 for 30 minutes followed by 1.0% sevoflurane and 0.6% isoflurane for another 30 minutes the FA/FI ratio was greater for sevoflurane than isoflurane at all time points. The time for the concentration in the alveoli to reach 50% of the inspired concentration was 4-8 minutes for isoflurane and approximately 1 minute for sevoflurane.
- FA/FI data from this study were compared with FA/FI data of other halogenated anesthetic agents from another study. When all data were normalized to isoflurane, the uptake and distribution of sevoflurane was shown to be faster than isoflurane and halothane, but slower than desflurane. The results are depicted in Figure 3.
- The low solubility of sevoflurane facilitates rapid elimination via the lungs. The rate of elimination is quantified as the rate of change of the alveolar (end-tidal) concentration following termination of anesthesia (FA), relative to the last alveolar concentration (FaO) measured immediately before discontinuance of the anesthetic. In the healthy volunteer study described above, rate of elimination of sevoflurane was similar compared with desflurane, but faster compared with either halothane or isoflurane. These results are depicted in Figure 4.
- Figure 3. Ratio of Concentration of Anesthetic in Alveolar Gas to Inspired Gas
- The effects of sevoflurane on the displacement of drugs from serum and tissue proteins have not been investigated. Other fluorinated volatile anesthetics have been shown to displace drugs from serum and tissue proteins in vitro. The clinical significance of this is unknown. Clinical studies have shown no untoward effects when sevoflurane is administered to patients taking drugs that are highly bound and have a small volume of distribution (e.g., phenytoin).
- Sevoflurane is metabolized by cytochrome P450 2E1, to hexafluoroisopropanol (HFIP) with release of inorganic fluoride and CO2. Once formed HFIP is rapidly conjugated with glucuronic acid and eliminated as a urinary metabolite. No other metabolic pathways for sevoflurane have been identified. In vivo metabolism studies suggest that approximately 5% of the sevoflurane dose may be metabolized.
- Cytochrome P450 2E1 is the principal isoform identified for sevoflurane metabolism and this may be induced by chronic exposure to isoniazid and ethanol. This is similar to the metabolism of isoflurane and enflurane and is distinct from that of methoxyflurane which is metabolized via a variety of cytochrome P450 isoforms. The metabolism of sevoflurane is not inducible by barbiturates. As shown in Figure 5, inorganic fluoride concentrations peak within 2 hours of the end of sevoflurane anesthesia and return to baseline concentrations within 48 hours post-anesthesia in the majority of cases (67%). The rapid and extensive pulmonary elimination of sevoflurane minimizes the amount of anesthetic available for metabolism.
- Figure 5. Serum Inorganic Fluoride Concentrations for Sevoflurane and Other Volatile Anesthetics
- Cousins M.J., Greenstein L.R., Hitt B.A., et al: Metabolism and renal effects of enflurane in man. Anesthesiology 44:44; 1976- and Sevo-93-044+.
- Up to 3.5% of the sevoflurane dose appears in the urine as inorganic fluoride. Studies on fluoride indicate that up to 50% of fluoride clearance is nonrenal (via fluoride being taken up into bone).
- Fluoride ion concentrations are influenced by the duration of anesthesia, the concentration of sevoflurane administered, and the composition of the anesthetic gas mixture. In studies where anesthesia was maintained purely with sevoflurane for periods ranging from 1 to 6 hours, peak fluoride concentrations ranged between 12 µM and 90 µM. As shown in Figure 6, peak concentrations occur within 2 hours of the end of anesthesia and are less than 25 µM (475 ng/mL) for the majority of the population after 10 hours. The half-life is in the range of 15-23 hours.
- It has been reported that following administration of methoxyflurane, serum inorganic fluoride concentrations > 50 µM were correlated with the development of vasopressin-resistant, polyuric, renal failure. In clinical trials with sevoflurane, there were no reports of toxicity associated with elevated fluoride ion levels.
- Figure 6. Fluoride Ion Concentrations Following Administration of Sevoflurane (mean MAC = 1.27, mean duration = 2.06 hr) Mean Fluoride Ion Concentrations (n = 48)
- Fluoride concentrations have been measured after single, extended, and repeat exposure to sevoflurane in normal surgical and special patient populations, and pharmacokinetic parameters were determined.
- Compared with healthy individuals, the fluoride ion half-life was prolonged in patients with renal impairment, but not in the elderly. A study in 8 patients with hepatic impairment suggests a slight prolongation of the half-life. The mean half-life in patients with renal impairment averaged approximately 33 hours (range 21-61 hours) as compared to a mean of approximately 21 hours (range 10-48 hours) in normal healthy individuals. The mean half-life in the elderly (greater than 65 years) approximated 24 hours (range 18-72 hours). The mean half-life in individuals with hepatic impairment was 23 hours (range 16-47 hours). Mean maximal fluoride values (Cmax) determined in individual studies of special populations are displayed below.
## Nonclinical Toxicology
There is limited information regarding Sevoflurane Nonclinical Toxicology in the drug label.
# Clinical Studies
There is limited information regarding Sevoflurane Clinical Studies in the drug label.
# How Supplied
- ULTANE (sevoflurane), Volatile Liquid for Inhalation, is packaged in amber colored bottles containing 250 mL sevoflurane, List 4456, NDC # 0074-4456-04 (plastic).
## Storage
- Store at controlled room temperature, 15° - 30°C (59° - 86°F). See USP.
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# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Sevoflurane Patient Counseling Information in the drug label.
# Precautions with Alcohol
Alcohol-Sevoflurane interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
There is limited information regarding Sevoflurane Brand Names in the drug label.
# Look-Alike Drug Names
There is limited information regarding Sevoflurane Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Sevoflurane
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# Overview
Sevoflurane is a general anesthetic that is FDA approved for the {{{indicationType}}} of general anesthesia. Common adverse reactions include cardiovascular: bradyarrhythmia (3% to 5% ), hypotension (4% to 11% ), gastrointestinal: nausea (25% ), vomiting (18% ), neurologic: somnolence (9% ), psychiatric: agitation (6% to 15%), respiratory: cough (5% to 11% ), interrupted breathing (2% to 6% ), other: shivering (6% ).
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- General anesthesia: 0.5% to 3% concentration with or without concomitant use of nitrous oxide
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information about Off-Label Guideline-Supported Use of Sevoflurane in adult patients.
### Non–Guideline-Supported Use
There is limited information about Off-Label Non–Guideline-Supported Use of Sevoflurane in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- General anesthesia: 0.5% to 3% concentration with or without concomitant use of nitrous oxide
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information about Off-Label Guideline-Supported Use of Sevoflurane in pediatric patients.
### Non–Guideline-Supported Use
There is limited information about Off-Label Non–Guideline-Supported Use of Sevoflurane in pediatric patients.
# Contraindications
- Sevoflurane can cause malignant hyperthermia. It should not be used in patients with known sensitivity to sevoflurane or to other halogenated agents nor in patients with known or suspected susceptibility to malignant hyperthermia.
# Warnings
- Although data from controlled clinical studies at low flow rates are limited, findings taken from patient and animal studies suggest that there is a potential for renal injury which is presumed due to Compound A. Animal and human studies demonstrate that sevoflurane administered for more than 2 MAC·hours and at fresh gas flow rates of < 2 L/min may be associated with proteinuria and glycosuria.
- While a level of Compound A exposure at which clinical nephrotoxicity might be expected to occur has not been established, it is prudent to consider all of the factors leading to Compound A exposure in humans, especially duration of exposure, fresh gas flow rate, and concentration of sevoflurane. During sevoflurane anesthesia the clinician should adjust inspired concentration and fresh gas flow rate to minimize exposure to Compound A. To minimize exposure to Compound A, sevoflurane exposure should not exceed 2 MAC·hours at flow rates of 1 to < 2 L/min. Fresh gas flow rates < 1 L/min are not recommended.
- Because clinical experience in administering sevoflurane to patients with renal insufficiency (creatinine > 1.5 mg/dL) is limited, its safety in these patients has not been established.
- Sevoflurane may be associated with glycosuria and proteinuria when used for long procedures at low flow rates. The safety of low flow sevoflurane on renal function was evaluated in patients with normal preoperative renal function. One study compared sevoflurane (N = 98) to an active control (N = 90) administered for ≥ 2 hours at a fresh gas flow rate of ≤ 1 Liter/minute. Per study defined criteria (Hou et al.) one patient in the sevoflurane group developed elevations of creatinine, in addition to glycosuria and proteinuria. This patient received sevoflurane at fresh gas flow rates of ≤ 800 mL/minute. Using these same criteria, there were no patients in the active control group who developed treatment emergent elevations in serum creatinine.
- Sevoflurane may present an increased risk in patients with known sensitivity to volatile halogenated anesthetic agents. KOH containing CO2 absorbents are not recommended for use with sevoflurane.
- Reports of QT prolongation, associated with torsade de pointes (in exceptional cases, fatal), have been received. Caution should be exercised when administering sevoflurane to susceptible patients (e.g. patients with congenital Long QT Syndrome or patients taking drugs that can prolong the QT interval).
- In susceptible individuals, potent inhalation anesthetic agents, including sevoflurane, may trigger a skeletal muscle hypermetabolic state leading to high oxygen demand and the clinical syndrome known as malignant hyperthermia. Sevoflurane can induce malignant hyperthermia in genetically susceptible individuals, such as those with certain inherited ryanodine receptor mutations. The clinical syndrome is signaled by hypercapnia, and may include muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias, and/or unstable blood pressure. Some of these nonspecific signs may also appear during light anesthesia, acute hypoxia, hypercapnia, and hypovolemia.
- In clinical trials, one case of malignant hyperthermia was reported. In addition, there have been postmarketing reports of malignant hyperthermia. Some of these cases have been fatal.
- Treatment of malignant hyperthermia includes discontinuation of triggering agents (e.g., sevoflurane), administration of intravenous dantrolene sodium (consult prescribing information for intravenous dantrolene sodium for additional information on patient management), and application of supportive therapy. Supportive therapy may include efforts to restore body temperature, respiratory and circulatory support as indicated, and management of electrolyte-fluid-acid-base abnormalities. Renal failure may appear later, and urine flow should be monitored and sustained if possible.
- Use of inhaled anesthetic agents has been associated with rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in pediatric patients during the postoperative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Concomitant use of succinylcholine has been associated with most, but not all, of these cases. These patients also experienced significant elevations in serum creatine kinase levels and, in some cases, changes in urine consistent with myoglobinuria. Despite the similarity in presentation to malignant hyperthermia, none of these patients exhibited signs or symptoms of muscle rigidity or hypermetabolic state. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended; as is subsequent evaluation for latent neuromuscular disease.
# Adverse Reactions
## Clinical Trials Experience
- Adverse events are derived from controlled clinical trials conducted in the United States, Canada, and Europe. The reference drugs were isoflurane, enflurane, and propofol in adults and halothane in pediatric patients. The studies were conducted using a variety of premedications, other anesthetics, and surgical procedures of varying length. Most adverse events reported were mild and transient, and may reflect the surgical procedures, patient characteristics (including disease) and/or medications administered.
- Of the 5182 patients enrolled in the clinical trials, 2906 were exposed to sevoflurane, including 118 adults and 507 pediatric patients who underwent mask induction. Each patient was counted once for each type of adverse event. Adverse events reported in patients in clinical trials and considered to be possibly or probably related to sevoflurane are presented within each body system in order of decreasing frequency in the following listings. One case of malignant hyperthermia was reported in pre-registration clinical trials.
- Adverse Events During the Induction Period (from Onset of Anesthesia by Mask Induction to Surgical Incision) Incidence > 1%
- Adult Patients (N = 118)
- Bradycardia 5%, hypotension 4%, tachycardia 2%
- Agitation 7%
- Laryngospasm 8%, airway obstruction 8%, breathholding 5%, cough increased 5%
### Pediatric Patients (N = 507)
- Tachycardia 6%, hypotension 4%
- Agitation 15%
- Breathholding 5%, cough increased 5%, laryngospasm 3%, apnea 2%
- Increased salivation 2%
### Adverse Events During Maintenance and Emergence Periods, Incidence > 1% (N = 2906)
- Fever 1%, shivering 6%, hypothermia 1%, movement 1%, headache 1%
- Hypotension 11%, hypertension 2%, bradycardia 5%, tachycardia 2%
- Somnolence 9%, agitation 9%, dizziness 4%, increased salivation 4%
- Nausea 25%, vomiting 18%
- Cough increased 11%, Breathholding 2%, Laryngospasm 2%
### Adverse Events, All Patients in Clinical Trials (N = 2906), All Anesthetic Periods, Incidence < 1% (Reported in 3 or More Patients)
- Asthenia, pain
- Arrhythmia, ventricular extrasystoles, supraventricular extrasystoles, complete av block, bigeminy, hemorrhage, inverted t wave, atrial fibrillation, atrial arrhythmia, second degree av block, syncope, s-t depressed
- Crying, nervousness, confusion, hypertonia, dry mouth, insomnia
- Sputum Increased, apnea, hypoxia, wheezing, bronchospasm, hyperventilation, pharyngitis, hiccup, hypoventilation, dyspnea, stridor
- Increases in LDH, AST, ALT, BUN, alkaline phosphatase, creatinine, bilirubinemia, glycosuria, fluorosis, albuminuria, hypophosphatemia, acidosis, hyperglycemia
- Leucocytosis, thrombocytopenia
- Amblyopia, pruritus, taste perversion, rash, conjunctivitis
- Urination impaired, urine abnormality, urinary retention, oliguria
- See Warnings for information regarding malignant hyperthermia.
## Postmarketing Experience
- The following adverse events have been identified during post-approval use of Ultane (sevoflurane USP). Due to the spontaneous nature of these reports, the actual incidence and relationship of Ultane to these events cannot be established with certainty.
- Seizures — Post-marketing reports indicate that sevoflurane use has been associated with seizures. The majority of cases were in children and young adults, most of whom had no medical history of seizures. Several cases reported no concomitant medications, and at least one case was confirmed by EEG. Although many cases were single seizures that resolved spontaneously or after treatment, cases of multiple seizures have also been reported. Seizures have occurred during, or soon after sevoflurane induction, during emergence, and during post-operative recovery up to a day following anesthesia.
- Cardiac arrest
- Cases of mild, moderate and severe post-operative hepatic dysfunction or hepatitis with or without jaundice have been reported. Histological evidence was not provided for any of the reported hepatitis cases. In most of these cases, patients had underlying hepatic conditions or were under treatment with drugs known to cause hepatic dysfunction. Most of the reported events were transient and resolved spontaneously (see Precautions).
- Hepatic necrosis
- Hepatic failure
- Malignant hyperthermia (see Contraindications and Warnings)
- Allergic reactions, such as rash, urticaria, pruritus, bronchospasm, anaphylactic or anaphylactoid reactions (see Contraindications)
- Reports of hypersensitivity (including contact dermatitis, rash, dyspnea, wheezing, chest discomfort, swelling face, or anaphylactic reaction) have been received, particularly in association with long-term occupational exposure to inhaled anesthetic agents, including sevoflurane (see Occupational caution).
- Transient elevations in glucose, liver function tests, and white blood cell count may occur as with use of other anesthetic agents.
# Drug Interactions
- In clinical trials, no significant adverse reactions occurred with other drugs commonly used in the perioperative period, including: central nervous system depressants, autonomic drugs, skeletal muscle relaxants, anti-infective agents, hormones and synthetic substitutes, blood derivatives, and cardiovascular drugs.
- Sevoflurane administration is compatible with barbiturates, propofol, and other commonly used intravenous anesthetics.
- Benzodiazepines and opioids would be expected to decrease the MAC of sevoflurane in the same manner as with other inhalational anesthetics. Sevoflurane administration is compatible with benzodiazepines and opioids as commonly used in surgical practice.
- As with other halogenated volatile anesthetics, the anesthetic requirement for sevoflurane is decreased when administered in combination with nitrous oxide. Using 50% N2O, the MAC equivalent dose requirement is reduced approximately 50% in adults, and approximately 25% in pediatric patients (see Dosage and administration).
- As is the case with other volatile anesthetics, sevoflurane increases both the intensity and duration of neuromuscular blockade induced by nondepolarizing muscle relaxants. When used to supplement alfentanil-N2O anesthesia, sevoflurane and isoflurane equally potentiate neuromuscular block induced with pancuronium, vecuronium or atracurium. Therefore, during sevoflurane anesthesia, the dosage adjustments for these muscle relaxants are similar to those required with isoflurane.
- Potentiation of neuromuscular blocking agents requires equilibration of muscle with delivered partial pressure of sevoflurane. Reduced doses of neuromuscular blocking agents during induction of anesthesia may result in delayed onset of conditions suitable for endotracheal intubation or inadequate muscle relaxation.
- Among available nondepolarizing agents, only vecuronium, pancuronium and atracurium interactions have been studied during sevoflurane anesthesia. In the absence of specific guidelines:
- For endotracheal intubation, do not reduce the dose of nondepolarizing muscle relaxants.
- During maintenance of anesthesia, the required dose of nondepolarizing muscle relaxants is likely to be reduced compared to that during N2O/opioid anesthesia. Administration of supplemental doses of muscle relaxants should be guided by the response to nerve stimulation.
- The effect of sevoflurane on the duration of depolarizing neuromuscular blockade induced by succinylcholine has not been studied.
- Results of evaluations of laboratory parameters (e.g., ALT, AST, alkaline phosphatase, and total bilirubin, etc.), as well as investigator-reported incidence of adverse events relating to liver function, demonstrate that sevoflurane can be administered to patients with normal or mild-to-moderately impaired hepatic function. However, patients with severe hepatic dysfunction were not investigated.
- Occasional cases of transient changes in postoperative hepatic function tests were reported with both sevoflurane and reference agents. Sevoflurane was found to be comparable to isoflurane with regard to these changes in hepatic function.
- Very rare cases of mild, moderate and severe post-operative hepatic dysfunction or hepatitis with or without jaundice have been reported from postmarketing experiences. Clinical judgement should be exercised when sevoflurane is used in patients with underlying hepatic conditions or under treatment with drugs known to cause hepatic dysfunction (see ADVERSE REACTIONS).
- It has been reported that previous exposure to halogenated hydrocarbon anesthetics may increase the potential for hepatic injury.
- An exothermic reaction occurs when sevoflurane is exposed to CO2 absorbents. This reaction is increased when the CO2 absorbent becomes desiccated, such as after an extended period of dry gas flow through the CO2 absorbent canisters. Rare cases of extreme heat, smoke, and/or spontaneous fire in the anesthesia breathing circuit have been reported during sevoflurane use in conjunction with the use of desiccated CO2 absorbent, specifically those containing potassium hydroxide (e.g. Baralyme). KOH containing CO2 absorbents are not recommended for use with sevoflurane. An unusually delayed rise or unexpected decline of inspired sevoflurane concentration compared to the vaporizer setting may be associated with excessive heating of the CO2 absorbent and chemical breakdown of sevoflurane.
- As with other inhalational anesthetics, degradation and production of degradation products can occur when sevoflurane is exposed to desiccated absorbents. When a clinician suspects that the CO2 absorbent may be desiccated, it should be replaced. The color indicator of most CO2 absorbents may not change upon desiccation. Therefore, the lack of significant color change should not be taken as an assurance of adequate hydration. CO2 absorbents should be replaced routinely regardless of the state of the color indicator.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): B
- Reproduction studies have been performed in rats and rabbits at doses up to 1 MAC (minimum alveolar concentration) without CO2 absorbent and have revealed no evidence of impaired fertility or harm to the fetus due to sevoflurane at 0.3 MAC, the highest nontoxic dose. Developmental and reproductive toxicity studies of sevoflurane in animals in the presence of strong alkalies (i.e., degradation of sevoflurane and production of Compound A) have not been conducted. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, sevoflurane should be used during pregnancy only if clearly needed.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Sevoflurane in women who are pregnant.
### Labor and Delivery
- Sevoflurane has been used as part of general anesthesia for elective cesarean section in 29 women. There were no untoward effects in mother or neonate (see Pharmacodynamics - Clinical Trials). The safety of sevoflurane in labor and delivery has not been demonstrated.
### Nursing Mothers
- The concentrations of sevoflurane in milk are probably of no clinical importance 24 hours after anesthesia. Because of rapid washout, sevoflurane concentrations in milk are predicted to be below those found with many other volatile anesthetics.
### Pediatric Use
- Induction and maintenance of general anesthesia with sevoflurane have been established in controlled clinical trials in pediatric patients aged 1 to 18 years (see Pharmacodynamics - Clinical Trials and Adverse reactions). Sevoflurane has a nonpungent odor and is suitable for mask induction in pediatric patients.
- The concentration of sevoflurane required for maintenance of general anesthesia is age dependent. When used in combination with nitrous oxide, the MAC equivalent dose of sevoflurane should be reduced in pediatric patients. MAC in premature infants has not been determined (see Precautions - Drug Interactions and Dosage and administration for recommendations in pediatric patients 1 day of age and older).
- The use of sevoflurane has been associated with seizures (see PRECAUTIONS and ADVERSE REACTIONS). The majority of these have occurred in children and young adults starting from 2 months of age, most of whom had no predisposing risk factors. Clinical judgement should be exercised when using sevoflurane in patients who may be at risk for seizures.
### Geriatic Use
- MAC decreases with increasing age. The average concentration of sevoflurane to achieve MAC in an 80 year old is approximately 50% of that required in a 20 year old.
### Gender
There is no FDA guidance on the use of Sevoflurane with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Sevoflurane with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Sevoflurane in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Sevoflurane in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Sevoflurane in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Sevoflurane in patients who are immunocompromised.
# Administration and Monitoring
### Administration
There is limited information regarding Sevoflurane Administration in the drug label.
### Monitoring
There is limited information regarding Sevoflurane Monitoring in the drug label.
# IV Compatibility
There is limited information regarding the compatibility of Sevoflurane and IV administrations.
# Overdosage
- In the event of overdosage, or what may appear to be overdosage, the following action should be taken: discontinue administration of sevoflurane, maintain a patent airway, initiate assisted or controlled ventilation with oxygen, and maintain adequate cardiovascular function.
# Pharmacology
## Mechanism of Action
- Sevoflurane is an inhalational anesthetic agent for use in induction and maintenance of general anesthesia. Minimum alveolar concentration (MAC) of sevoflurane in oxygen for a 40-year-old adult is 2.1%. The MAC of sevoflurane decreases with age (see Dosage and administration for details).
## Structure
- ULTANE (sevoflurane), volatile liquid for inhalation, a nonflammable and nonexplosive liquid administered by vaporization, is a halogenated general inhalation anesthetic drug. Sevoflurane is fluoromethyl 2,2,2,-trifluoro-1-(trifluoromethyl) ethyl ether and its structural formula is:
- Sevoflurane is nonflammable and nonexplosive as defined by the requirements of International Electrotechnical Commission 601-2-13.
- Sevoflurane is a clear, colorless, liquid containing no additives. Sevoflurane is not corrosive to stainless steel, brass, aluminum, nickel-plated brass, chrome-plated brass or copper beryllium. Sevoflurane is nonpungent. It is miscible with ethanol, ether, chloroform, and benzene, and it is slightly soluble in water. Sevoflurane is stable when stored under normal room lighting conditions according to instructions. No discernible degradation of sevoflurane occurs in the presence of strong acids or heat. When in contact with alkaline CO2 absorbents (e.g Baralyme® and to a lesser extent soda lime) within the anesthesia machine, sevoflurane can undergo degradation under certain conditions. Degradation of sevoflurane is minimal, and degradants are either undetectable or present in non-toxic amounts when used as directed with fresh absorbents. Sevoflurane degradation and subsequent degradant formation are enhanced by increasing absorbent temperature increased sevoflurane concentration, decreased fresh gas flow and desiccated CO2 absorbents (especially with potassium hydroxide containing absorbents e.g. Baralyme).
- Sevoflurane alkaline degradation occurs by two pathways. The first results from the loss of hydrogen fluoride with the formation of pentafluoroisopropenyl fluoromethyl ether, (PIFE, C4H2F6O), also known as Compound A, and trace amounts of pentafluoromethoxy isopropyl fluoromethyl ether, (PMFE, C5H6F6O), also known as Compound B. The second pathway for degradation of sevoflurane, which occurs primarily in the presence of desiccated CO2 absorbents, is discussed later.
- In the first pathway, the defluorination pathway, the production of degradants in the anesthesia circuit results from the extraction of the acidic proton in the presence of a strong base (KOH and/or NaOH) forming an alkene (Compound A) from sevoflurane similar to formation of 2-bromo-2-chloro-1,1-difluoro ethylene (BCDFE) from halothane. Laboratory simulations have shown that the concentration of these degradants is inversely correlated with the fresh gas flow rate (See Figure 1).
- Since the reaction of carbon dioxide with absorbents is exothermic, the temperature increase will be determined by quantities of CO2 absorbed, which in turn will depend on fresh gas flow in the anesthesia circle system, metabolic status of the patient, and ventilation. The relationship of temperature produced by varying levels of CO2 and Compound A production is illustrated in the following in vitro simulation where CO2 was added to a circle absorber system.
- Compound A concentration in a circle absorber system increases as a function of increasing CO2 absorbent temperature and composition (Baralyme producing higher levels than soda lime), increased body temperature, and increased minute ventilation, and decreasing fresh gas flow rates. It has been reported that the concentration of Compound A increases significantly with prolonged dehydration of Baralyme. Compound A exposure in patients also has been shown to rise with increased sevoflurane concentrations and duration of anesthesia. In a clinical study in which sevoflurane was administered to patients under low flow conditions for ≥ 2 hours at flow rates of 1 Liter/minute, Compound A levels were measured in an effort to determine the relationship between MAC hours and Compound A levels produced. The relationship between Compound A levels and sevoflurane exposure are shown in Figure 2a.
- Compound A has been shown to be nephrotoxic in rats after exposures that have varied in duration from one to three hours. No histopathologic change was seen at a concentration of up to 270 ppm for one hour. Sporadic single cell necrosis of proximal tubule cells has been reported at a concentration of 114 ppm after a 3-hour exposure to Compound A in rats. The LC50 reported at 1 hour is 1050-1090 ppm (male-female) and, at 3 hours, 350-490 ppm (male-female).
- An experiment was performed comparing sevoflurane plus 75 or 100 ppm Compound A with an active control to evaluate the potential nephrotoxicity of Compound A in non-human primates. A single 8-hour exposure of Sevoflurane in the presence of Compound A produced single-cell renal tubular degeneration and single-cell necrosis in cynomolgus monkeys. These changes are consistent with the increased urinary protein, glucose level and enzymic activity noted on days one and three on the clinical pathology evaluation. This nephrotoxicity produced by Compound A is dose and duration of exposure dependent.
- At a fresh gas flow rate of 1 L/min, mean maximum concentrations of Compound A in the anesthesia circuit in clinical settings are approximately 20 ppm (0.002%) with soda lime and 30 ppm (0.003%) with Baralyme in adult patients; mean maximum concentrations in pediatric patients with soda lime are about half those found in adults. The highest concentration observed in a single patient with Baralyme was 61 ppm (0.0061%) and 32 ppm (0.0032%) with soda lime. The levels of Compound A at which toxicity occurs in humans is not known.
- The second pathway for degradation of sevoflurane occurs primarily in the presence of desiccated CO2 absorbents and leads to the dissociation of sevoflurane into hexafluoroisopropanol (HFIP) and formaldehyde. HFIP is inactive, non-genotoxic, rapidly glucuronidated and cleared by the liver. Formaldehyde is present during normal metabolic processes. Upon exposure to a highly desiccated absorbent, formaldehyde can further degrade into methanol and formate. Formate can contribute to the formation of carbon monoxide in the presence of high temperature that can be associated with desiccated Baralyme®. Methanol can react with Compound A to form the methoxy addition product Compound B. Compound B can undergo further HF elimination to form Compounds C, D, and E.
- Sevoflurane degradants were observed in the respiratory circuit of an experimental anesthesia machine using desiccated CO2 absorbents and maximum sevoflurane concentrations (8%) for extended periods of time (> 2 hours). Concentrations of formaldehyde observed with desiccated soda lime in this experimental anesthesia respiratory circuit were consistent with levels that could potentially result in respiratory irritation. Although KOH containing CO2 absorbents are no longer commercially available, in the laboratory experiments, exposure of sevoflurane to the desiccated KOH containing CO2 absorbent, Baralyme, resulted in the detection of substantially greater degradant levels.
## Pharmacodynamics
- Changes in the depth of sevoflurane anesthesia rapidly follow changes in the inspired concentration.
- In the sevoflurane clinical program, the following recovery variables were evaluated:
- Time to events measured from the end of study drug:
- Time to removal of the endotracheal tube (extubation time)
- Time required for the patient to open his/her eyes on verbal command (emergence time)
- Time to respond to simple command (e.g., squeeze my hand) or demonstrates purposeful movement (response to command time, orientation time)
- Recovery of cognitive function and motor coordination was evaluated based on:
- Psychomotor performance tests (Digit Symbol Substitution Test [DSST], Treiger Dot Test)
- The results of subjective (Visual Analog Scale [VAS]) and objective (objective pain-discomfort scale [OPDS]) measurements
- Time to administration of the first post-anesthesia analgesic medication
- Assessments of post-anesthesia patient status
- Other recovery times were:
- Time to achieve an Aldrete Score of ≥ 8
- Time required for the patient to be eligible for discharge from the recovery area, per standard criteria at site
- Time when the patient was eligible for discharge from the hospital
- Time when the patient was able to sit up or stand without dizziness
- Some of these variables are summarized as follows:
- Sevoflurane was studied in 14 healthy volunteers (18-35 years old) comparing sevoflurane-O2 (Sevo/O2) to sevoflurane-N2O/O2 (Sevo/N2O/O2) during 7 hours of anesthesia. During controlled ventilation, hemodynamic parameters measured are shown in Figures 7-10:
- Sevoflurane is a dose-related cardiac depressant. Sevoflurane does not produce increases in heart rate at doses less than 2 MAC.
- A study investigating the epinephrine induced arrhythmogenic effect of sevoflurane versus isoflurane in adult patients undergoing transsphenoidal hypophysectomy demonstrated that the threshold dose of epinephrine (i.e., the dose at which the first sign of arrhythmia was observed) producing multiple ventricular arrhythmias was 5 mcg/kg with both sevoflurane and isoflurane. Consequently, the interaction of sevoflurane with epinephrine appears to be equal to that seen with isoflurane.
## Pharmacokinetics
### Uptake and Distribution
- Because of the low solubility of sevoflurane in blood (blood/gas partition coefficient @ 37°C = 0.63-0.69), a minimal amount of sevoflurane is required to be dissolved in the blood before the alveolar partial pressure is in equilibrium with the arterial partial pressure. Therefore there is a rapid rate of increase in the alveolar (end-tidal) concentration (FA) toward the inspired concentration (FI) during induction.
- In a study in which seven healthy male volunteers were administered 70% N2O/30%O2 for 30 minutes followed by 1.0% sevoflurane and 0.6% isoflurane for another 30 minutes the FA/FI ratio was greater for sevoflurane than isoflurane at all time points. The time for the concentration in the alveoli to reach 50% of the inspired concentration was 4-8 minutes for isoflurane and approximately 1 minute for sevoflurane.
- FA/FI data from this study were compared with FA/FI data of other halogenated anesthetic agents from another study. When all data were normalized to isoflurane, the uptake and distribution of sevoflurane was shown to be faster than isoflurane and halothane, but slower than desflurane. The results are depicted in Figure 3.
- The low solubility of sevoflurane facilitates rapid elimination via the lungs. The rate of elimination is quantified as the rate of change of the alveolar (end-tidal) concentration following termination of anesthesia (FA), relative to the last alveolar concentration (FaO) measured immediately before discontinuance of the anesthetic. In the healthy volunteer study described above, rate of elimination of sevoflurane was similar compared with desflurane, but faster compared with either halothane or isoflurane. These results are depicted in Figure 4.
- Figure 3. Ratio of Concentration of Anesthetic in Alveolar Gas to Inspired Gas
- The effects of sevoflurane on the displacement of drugs from serum and tissue proteins have not been investigated. Other fluorinated volatile anesthetics have been shown to displace drugs from serum and tissue proteins in vitro. The clinical significance of this is unknown. Clinical studies have shown no untoward effects when sevoflurane is administered to patients taking drugs that are highly bound and have a small volume of distribution (e.g., phenytoin).
- Sevoflurane is metabolized by cytochrome P450 2E1, to hexafluoroisopropanol (HFIP) with release of inorganic fluoride and CO2. Once formed HFIP is rapidly conjugated with glucuronic acid and eliminated as a urinary metabolite. No other metabolic pathways for sevoflurane have been identified. In vivo metabolism studies suggest that approximately 5% of the sevoflurane dose may be metabolized.
- Cytochrome P450 2E1 is the principal isoform identified for sevoflurane metabolism and this may be induced by chronic exposure to isoniazid and ethanol. This is similar to the metabolism of isoflurane and enflurane and is distinct from that of methoxyflurane which is metabolized via a variety of cytochrome P450 isoforms. The metabolism of sevoflurane is not inducible by barbiturates. As shown in Figure 5, inorganic fluoride concentrations peak within 2 hours of the end of sevoflurane anesthesia and return to baseline concentrations within 48 hours post-anesthesia in the majority of cases (67%). The rapid and extensive pulmonary elimination of sevoflurane minimizes the amount of anesthetic available for metabolism.
- Figure 5. Serum Inorganic Fluoride Concentrations for Sevoflurane and Other Volatile Anesthetics
- Cousins M.J., Greenstein L.R., Hitt B.A., et al: Metabolism and renal effects of enflurane in man. Anesthesiology 44:44; 1976* and Sevo-93-044+.
- Up to 3.5% of the sevoflurane dose appears in the urine as inorganic fluoride. Studies on fluoride indicate that up to 50% of fluoride clearance is nonrenal (via fluoride being taken up into bone).
- Fluoride ion concentrations are influenced by the duration of anesthesia, the concentration of sevoflurane administered, and the composition of the anesthetic gas mixture. In studies where anesthesia was maintained purely with sevoflurane for periods ranging from 1 to 6 hours, peak fluoride concentrations ranged between 12 µM and 90 µM. As shown in Figure 6, peak concentrations occur within 2 hours of the end of anesthesia and are less than 25 µM (475 ng/mL) for the majority of the population after 10 hours. The half-life is in the range of 15-23 hours.
- It has been reported that following administration of methoxyflurane, serum inorganic fluoride concentrations > 50 µM were correlated with the development of vasopressin-resistant, polyuric, renal failure. In clinical trials with sevoflurane, there were no reports of toxicity associated with elevated fluoride ion levels.
- Figure 6. Fluoride Ion Concentrations Following Administration of Sevoflurane (mean MAC = 1.27, mean duration = 2.06 hr) Mean Fluoride Ion Concentrations (n = 48)
- Fluoride concentrations have been measured after single, extended, and repeat exposure to sevoflurane in normal surgical and special patient populations, and pharmacokinetic parameters were determined.
- Compared with healthy individuals, the fluoride ion half-life was prolonged in patients with renal impairment, but not in the elderly. A study in 8 patients with hepatic impairment suggests a slight prolongation of the half-life. The mean half-life in patients with renal impairment averaged approximately 33 hours (range 21-61 hours) as compared to a mean of approximately 21 hours (range 10-48 hours) in normal healthy individuals. The mean half-life in the elderly (greater than 65 years) approximated 24 hours (range 18-72 hours). The mean half-life in individuals with hepatic impairment was 23 hours (range 16-47 hours). Mean maximal fluoride values (Cmax) determined in individual studies of special populations are displayed below.
## Nonclinical Toxicology
There is limited information regarding Sevoflurane Nonclinical Toxicology in the drug label.
# Clinical Studies
There is limited information regarding Sevoflurane Clinical Studies in the drug label.
# How Supplied
- ULTANE (sevoflurane), Volatile Liquid for Inhalation, is packaged in amber colored bottles containing 250 mL sevoflurane, List 4456, NDC # 0074-4456-04 (plastic).
## Storage
- Store at controlled room temperature, 15° - 30°C (59° - 86°F). See USP.
abbvie
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
There is limited information regarding Sevoflurane Patient Counseling Information in the drug label.
# Precautions with Alcohol
Alcohol-Sevoflurane interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
There is limited information regarding Sevoflurane Brand Names in the drug label.
# Look-Alike Drug Names
There is limited information regarding Sevoflurane Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Sevoflurane | |
deeb671e6df3eec6d762978c3ada32023e5c405b | wikidoc | Sex linkage | Sex linkage
# Overview
Sex linkage is the phenotypic expression of an allele that is related to the chromosomal sex of the individual. This mode of inheritance is in contrast to the inheritance of traits on autosomal chromosomes, where both sexes have the same probability of expressing the trait. Since, in humans, there are many more genes on the X than there are on the Y, there are many more X-linked traits than there are Y-linked traits.
In mammals, the female is the homogametic sex, having two X chromosomes (XX), while the male is heterogametic, having one X and one Y chromosome (XY). Genes that are present on the X or Y chromosome are called sex linked genes.
X-linked recessive traits are expressed in all heterogametics, but only in those homogametics that are homozygous for the recessive allele. For example, an X-linked recessive allele in humans causes haemophilia. Haemophilia is much more common in males than females because males are hemizygous - they only have one copy of the gene in question - and therefore express the trait when they inherit one mutant allele. In contrast, a female must inherit two mutant alleles, a less frequent event since the mutant allele is rare in the population.
The incidence of recessive X-linked phenotypes in females is the square of that in males (squaring a proportion less than one gives an outcome closer to 0 than the original). If 1 in 20 males in a human population are green color blind, then 1 in 400 females in the population are expected to be color blind (1/20)*(1/20).
X-linked traits are maternally inherited from carrier mothers. Each son born to a carrier mother has a 50% probability of inheriting the X-chromosome carrying the mutant allele. There are a few Y-linked traits; these are inherited from the father.
In classical genetics, a reciprocal cross is performed to test if a trait is sex-linked.
## X-linked recessive
X-linked inherited diseases occur far more frequently in males because they only have one X chromosome. Females must receive a copy of the gene from both parents to have such a recessive disease. However, they will still be carriers if they receive one copy of the gene. Recessive genes on the X chromosome that cause serious diseases are usually passed from female carriers to their ill sons and carrier daughters. This is because males, who always have the disease and are not just carriers, would have to father a daughter to pass on the gene. This is unlikely because severe genetic diseases often cause death in childhood or early adulthood. Even those males who survive childhood are unlikely to father children because a sickly male will be less likely to find a mate. However, if the disease shows up late in life, or is not severe, he will pass the gene to all of his daughters. He can not pass it to his sons because a male receives his X chromosome from his mother. A mother with one copy of the gene has a 50% chance of passing it to her children of both sexes, but her daughters will just be carriers of the gene unless their father has it too.
Diseases well known for their X-linked recessive inheritance are hemophilia (types A and B), and color blindness.
## X-linked dominant
There are few examples of X-linked dominant diseases; the best known in this category is vitamin D resistant rickets. Other examples are:
- Incontinentia pigmenti
- Coffin-Lowry syndrome
## Y-linked
- Various failures in the SRY genes
cs:Dědičnost znaků a pohlaví
it:Caratteri legati al sesso
sr:Наслеђивање везано за X хромозом | Sex linkage
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Sex linkage is the phenotypic expression of an allele that is related to the chromosomal sex of the individual. This mode of inheritance is in contrast to the inheritance of traits on autosomal chromosomes, where both sexes have the same probability of expressing the trait. Since, in humans, there are many more genes on the X than there are on the Y, there are many more X-linked traits than there are Y-linked traits.
In mammals, the female is the homogametic sex, having two X chromosomes (XX), while the male is heterogametic, having one X and one Y chromosome (XY). Genes that are present on the X or Y chromosome are called sex linked genes.
X-linked recessive traits are expressed in all heterogametics, but only in those homogametics that are homozygous for the recessive allele. For example, an X-linked recessive allele in humans causes haemophilia. Haemophilia is much more common in males than females because males are hemizygous - they only have one copy of the gene in question - and therefore express the trait when they inherit one mutant allele. In contrast, a female must inherit two mutant alleles, a less frequent event since the mutant allele is rare in the population.
The incidence of recessive X-linked phenotypes in females is the square of that in males (squaring a proportion less than one gives an outcome closer to 0 than the original). If 1 in 20 males in a human population are green color blind, then 1 in 400 females in the population are expected to be color blind (1/20)*(1/20).
X-linked traits are maternally inherited from carrier mothers. Each son born to a carrier mother has a 50% probability of inheriting the X-chromosome carrying the mutant allele. There are a few Y-linked traits; these are inherited from the father.
In classical genetics, a reciprocal cross is performed to test if a trait is sex-linked.
## X-linked recessive
X-linked inherited diseases occur far more frequently in males because they only have one X chromosome. Females must receive a copy of the gene from both parents to have such a recessive disease. However, they will still be carriers if they receive one copy of the gene. Recessive genes on the X chromosome that cause serious diseases are usually passed from female carriers to their ill sons and carrier daughters. This is because males, who always have the disease and are not just carriers, would have to father a daughter to pass on the gene. This is unlikely because severe genetic diseases often cause death in childhood or early adulthood. Even those males who survive childhood are unlikely to father children because a sickly male will be less likely to find a mate. However, if the disease shows up late in life, or is not severe, he will pass the gene to all of his daughters. He can not pass it to his sons because a male receives his X chromosome from his mother. A mother with one copy of the gene has a 50% chance of passing it to her children of both sexes, but her daughters will just be carriers of the gene unless their father has it too.
Diseases well known for their X-linked recessive inheritance are hemophilia (types A and B), and color blindness.
## X-linked dominant
There are few examples of X-linked dominant diseases; the best known in this category is vitamin D resistant rickets. Other examples are:
- Incontinentia pigmenti
- Coffin-Lowry syndrome
## Y-linked
- Various failures in the SRY genes
cs:Dědičnost znaků a pohlaví
it:Caratteri legati al sesso
sr:Наслеђивање везано за X хромозом
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Sex-linked | |
adf2a3815bcdd4405c66bb04f78a4084af4c8c1c | wikidoc | Shaker gene | Shaker gene
The shaker (Sh) gene, when mutated, causes a variety of atypical behaviors in the fruit fly, Drosophila melanogaster. Under ether anesthesia, the fly’s legs will shake (hence the name); even when the fly is unanaesthetized, it will exhibit aberrant movements. Sh-mutant flies have a shorter lifespan than regular flies; in their larvae, the repetitive firing of action potentials as well as prolonged exposure to neurotransmitters at neuromuscular junctions occurs.
In Drosophila, the shaker gene is located on the X chromosome. The closest human homolog is KCNA3.
# Function
The Sh gene plays a part in the operation of potassium ion channels, which are integral membrane proteins and are essential to the correct functioning of the cell. A working Shaker channel is voltage-dependent and has four subunits, which form a pore through which ions flow, carrying type-A potassium current (IA). A mutation in the Sh gene reduces the conductance of charge across the neuron since the channels do not work, causing the severe phenotypical aberrations mentioned above. These types of ion channels are responsible for the repolarization of the cell.
The ‘Shaker K’ channel is a homo tetrameric protein complex. When confronted with a stimulus, the tetramers undergo conformational changes; some of these changes are cooperative. The final step involved in the opening of the channel is highly synchronized.
Recently, the Shaker gene has also been identified as a gene that helps determine an organism's amount of sleep. The phenotype of the flies that need less sleep is called minisleep (mns).
# Blockers
The ‘Shaker K’ channel is affected by various toxins, which effectively slow the opening of the channel, or reversibly block its functioning.
Toxins that affect the Shaker K channel include:
- Agitoxin
- Charybdotoxin
- Iberiotoxin
- Pandinotoxin
- 6-bromo-2-mercaptotryptamine (BrMT)
BrMT can be seen working in the K channel to prevent the early activation of the channel – before the cooperation has begun. Though its exact mechanism remains unknown, it is expected to work by forcing a conformational change in the pore domain of the channel. This part of the channel is expected to be altered instead of the voltage-sensing domain because of its connections to other subunits. When the conformational change is enacted, the BrMT sites on adjacent subunits are also affected, resulting in a widespread delayed activation of the K channel. | Shaker gene
The shaker (Sh) gene, when mutated, causes a variety of atypical behaviors in the fruit fly, Drosophila melanogaster.[1][2][3][4] Under ether anesthesia, the fly’s legs will shake (hence the name); even when the fly is unanaesthetized, it will exhibit aberrant movements. Sh-mutant flies have a shorter lifespan than regular flies; in their larvae, the repetitive firing of action potentials as well as prolonged exposure to neurotransmitters at neuromuscular junctions occurs.
In Drosophila, the shaker gene is located on the X chromosome. The closest human homolog is KCNA3.[5]
# Function
The Sh gene plays a part in the operation of potassium ion channels, which are integral membrane proteins and are essential to the correct functioning of the cell. A working Shaker channel is voltage-dependent and has four subunits, which form a pore through which ions flow, carrying type-A potassium current (IA). A mutation in the Sh gene reduces the conductance of charge across the neuron since the channels do not work, causing the severe phenotypical aberrations mentioned above. These types of ion channels are responsible for the repolarization of the cell.
The ‘Shaker K’ channel is a homo tetrameric protein complex.[6] When confronted with a stimulus, the tetramers undergo conformational changes; some of these changes are cooperative. The final step involved in the opening of the channel is highly synchronized.[7][8][9]
Recently, the Shaker gene has also been identified as a gene that helps determine an organism's amount of sleep. The phenotype of the flies that need less sleep is called minisleep (mns).[10]
# Blockers
The ‘Shaker K’ channel is affected by various toxins, which effectively slow the opening of the channel, or reversibly block its functioning.[11][12]
Toxins that affect the Shaker K channel include:
- Agitoxin
- Charybdotoxin
- Iberiotoxin
- Pandinotoxin
- 6-bromo-2-mercaptotryptamine (BrMT)
BrMT can be seen working in the K channel to prevent the early activation of the channel – before the cooperation has begun.[11] Though its exact mechanism remains unknown, it is expected to work by forcing a conformational change in the pore domain of the channel. This part of the channel is expected to be altered instead of the voltage-sensing domain because of its connections to other subunits. When the conformational change is enacted, the BrMT sites on adjacent subunits are also affected, resulting in a widespread delayed activation of the K channel.[11] | https://www.wikidoc.org/index.php/Shaker_gene | |
63efc7c68596e26b651e438d88b080f8e3e7d3af | wikidoc | Shea butter | Shea butter
Shea nut butter is a slightly yellowish or ivory-colored natural fat extracted from fruit of the shea tree by crushing and boiling. Shea butter is widely used in cosmetics as a moisturizer and an emollient. Shea butter is also edible. It is used as a cooking oil in West Africa, as well as sometimes being used in the chocolate industry as a substitute for cocoa butter.
The shea or karite tree, formerly Butyrospermum paradoxum, is now called Vitellaria paradoxa. It produces its first fruit (which resemble large plums) when it is about 20 years old and reaches its full production when the tree is about 45 years old. It produces nuts for up to 200 years after reaching maturity. Many vernacular names are used for Vitellaria, which is a reflection of its extensive range of occurrence—nearly 5,000km from Senegal (west) to Uganda (east) across the African continent. The nomenclature history and synonymy of the shea tree followed a very tortuous evolution since the oldest recorded specimen collected by a European—Scottish explorer Mungo Park— dated May 26, 1797. It eventually arrived at the name vitellaria with subspecies paradoxa and nilotica. It usually grows to an average height of about 15m with profuse branches and a thick waxy and deeply fissured bark that makes it fire resistant. The shea tree grows naturally in the wild in the dry savannah belt of West Africa from Senegal in the west to Sudan in the east, and onto the foothills of the Ethiopian highlands. It occurs in 19 countries across the African continent, namely Benin, Burkina Faso, Cameroon, Central African Republic, Chad, Ethiopia, Ghana, Guinea Bissau, Côte d'Ivoire, Mali, Niger, Nigeria, Senegal, Sierra Leone, Sudan, Togo, Uganda, Zaire and Guinea.
In Ghana (FAO, 1988a), it occurs extensively in the Guinea savannah and less abundantly in the Sudan Savannah. The shea tree occurs over almost the entire area of Northern Ghana, over about 77,670 square kilometers in Western Dagomba, Southern Mamprusi, Western Gonja, Lawra, Tumu, Wa and Nanumba with Eastern Gonja having the densest stands. There is sparse shea tree cover found in Brong-Ahafo, Ashanti, and the Eastern and Volta regions in the south of the country.
# Properties
Shea butter is known especially for its cosmetic properties as a moisturizer and emollient. It is also a known anti-inflammatory agent.
Shea butter is marketed as being effective at treating the following conditions: fading scars, eczema, burns, rashes, acne, severely dry skin, blemishes, dark spots, skin discolorations, chapped lips, stretchmarks, wrinkles, and in lessening the irritation of psoriasis. Shea butter provides natural ultraviolet sun protection, although the level of protection is extremely variable, ranging from none at all to approximately SPF 6. Sun-sensitive persons should not rely on shea butter for protection. Shea butter absorbs rapidly into the skin without leaving a greasy feeling.
Shea butter is comparatively richer than other emollients but scarcity of supply results in an erratic market price.
# Uses
Shea butter can be found in many high end moisturizing skin products. Shea butter is known for its skin softening effect. It is also used in hair conditioners to add and maintain moisture in dry brittle hair, in addition to revitalizing and preventing breakage.
Shea butter is used in some indigenous ceremonies. Followers of the Holy Spirit Movement rebel group of Uganda smeared their bodies with shea butter in the belief that it would stop bullets.
Handcrafted shea butter is used in Togo, West Africa for ceremonies among the Fulani ethnic group.
Many carvers of djembe shells and other African drum shells use shea butter to condition the wood. Shea butter is also used to condition the goat or cow skin heads of these drums. | Shea butter
Shea nut butter is a slightly yellowish or ivory-colored natural fat extracted from fruit of the shea tree by crushing and boiling. Shea butter is widely used in cosmetics as a moisturizer and an emollient. Shea butter is also edible. It is used as a cooking oil in West Africa, as well as sometimes being used in the chocolate industry as a substitute for cocoa butter.
The shea or karite tree, formerly Butyrospermum paradoxum, is now called Vitellaria paradoxa. It produces its first fruit (which resemble large plums) when it is about 20 years old and reaches its full production when the tree is about 45 years old. It produces nuts for up to 200 years after reaching maturity. Many vernacular names are used for Vitellaria, which is a reflection of its extensive range of occurrence—nearly 5,000km from Senegal (west) to Uganda (east) across the African continent. The nomenclature history and synonymy of the shea tree followed a very tortuous evolution since the oldest recorded specimen collected by a European—Scottish explorer Mungo Park— dated May 26, 1797. It eventually arrived at the name vitellaria with subspecies paradoxa and nilotica. It usually grows to an average height of about 15m with profuse branches and a thick waxy and deeply fissured bark that makes it fire resistant. The shea tree grows naturally in the wild in the dry savannah belt of West Africa from Senegal in the west to Sudan in the east, and onto the foothills of the Ethiopian highlands. It occurs in 19 countries across the African continent, namely Benin, Burkina Faso, Cameroon, Central African Republic, Chad, Ethiopia, Ghana, Guinea Bissau, Côte d'Ivoire, Mali, Niger, Nigeria, Senegal, Sierra Leone, Sudan, Togo, Uganda, Zaire and Guinea.
In Ghana (FAO, 1988a), it occurs extensively in the Guinea savannah and less abundantly in the Sudan Savannah. The shea tree occurs over almost the entire area of Northern Ghana, over about 77,670 square kilometers in Western Dagomba, Southern Mamprusi, Western Gonja, Lawra, Tumu, Wa and Nanumba with Eastern Gonja having the densest stands. There is sparse shea tree cover found in Brong-Ahafo, Ashanti, and the Eastern and Volta regions in the south of the country.
# Properties
Shea butter is known especially for its cosmetic properties as a moisturizer and emollient. It is also a known anti-inflammatory agent.[1]
Shea butter is marketed as being effective at treating the following conditions: fading scars, eczema, burns, rashes, acne, severely dry skin, blemishes, dark spots, skin discolorations, chapped lips, stretchmarks, wrinkles, and in lessening the irritation of psoriasis.[citation needed] Shea butter provides natural ultraviolet sun protection, although the level of protection is extremely variable, ranging from none at all to approximately SPF 6. Sun-sensitive persons should not rely on shea butter for protection. Shea butter absorbs rapidly into the skin without leaving a greasy feeling.
Shea butter is comparatively richer than other emollients but scarcity of supply results in an erratic market price.[citation needed]
# Uses
Shea butter can be found in many high end moisturizing skin products. Shea butter is known for its skin softening effect. It is also used in hair conditioners to add and maintain moisture in dry brittle hair, in addition to revitalizing and preventing breakage.
Shea butter is used in some indigenous ceremonies. Followers of the Holy Spirit Movement rebel group of Uganda smeared their bodies with shea butter in the belief that it would stop bullets.
Handcrafted shea butter is used in Togo, West Africa for ceremonies among the Fulani ethnic group.
Many carvers of djembe shells and other African drum shells use shea butter to condition the wood. Shea butter is also used to condition the goat or cow skin heads of these drums. | https://www.wikidoc.org/index.php/Shea_butter | |
9b6b0caaaa8f721fbf0b7dc286324dee4be73e1b | wikidoc | Shell model | Shell model
In nuclear physics, the nuclear shell model is a model of the atomic nucleus which uses the Pauli principle to describe the structure of the nucleus in terms of energy levels. The model was developed in 1949 following independent work by several physicists, most notably Eugene Paul Wigner, Maria Goeppert-Mayer and J. Hans D. Jensen, who shared the 1963 Nobel Prize in Physics for their contributions.
The shell model is partly analogous to the atomic shell model which describes the arrangement of electrons in an atom, in that a filled shell results in greater stability. When adding nucleons (protons or neutrons) to a nucleus, there are certain points where the binding energy of the next nucleon is significantly less than the last one. This observation, that there are certain magic numbers of nucleons: 2, 8, 20, 28, 50, 82, 126 which are more tightly bound than the next higher number, is the origin of the shell model.
Note that the shells exist for both protons and neutrons individually, so that we can speak of "magic nuclei" where one nucleon type is at a magic number, and "doubly magic nuclei", where both are. Due to some variations in orbital filling, the upper magic numbers are 126 and, speculatively, 184 for neutrons but only 114 for protons. This has a relevant role in the search of the so-called island of stability. Besides, there have been found some semimagic numbers, noticeably Z=40.
In order to get these numbers, the nuclear shell model starts from an average potential with a shape something between the square well and the harmonic oscillator. To this potential a relativistic spin orbit term is added. Even so, the total perturbation does not coincide with experiment, and an empirical spin orbit coupling, named Nilsson Term, must be added with at least two or three different values of its coupling constant, depending on the nuclei being studied.
Nevertheless, the magic numbers of nucleons, as well as other properties, can be arrived at by approximating the model with a three-dimensional harmonic oscillator plus a spin-orbit interaction. A more realistic but also complicated potential is known as Woods Saxon potential.
# Deformed harmonic oscillator approximated model
Consider a three-dimensional harmonic oscillator. This would give, for example, in the first two levels
We can imagine ourselves building a nucleus by adding protons and neutrons. These will always fill the lowest available level. Thus the first two protons fill level zero, the next six protons fill level one, and so on. As with electrons in the periodic table, protons in the outermost shell will be relatively loosely bound to the nucleus if there are only few protons in that shell, because they are farthest from the center of the nucleus. Therefore nuclei which have a full outer proton shell will have a higher binding energy than other nuclei with a similar total number of protons. All this is true for neutrons as well.
This means that the magic numbers are expected to be those in which all occupied shells are full. We see that for the first two numbers we get 2 (level 0 full) and 8 (levels 0 and 1 full), in accord with experiment. However the full set of magic numbers does not turn out correctly. These can be computed as follows:
In particular, the first six shells are:
- level 0: 2 states (l = 0) = 2.
- level 1: 6 states (l = 1) = 6.
- level 2: 2 states (l = 0) + 10 states (l = 2) = 12.
- level 3: 6 states (l = 1) + 14 states (l = 3) = 20.
- level 4: 2 states (l = 0) + 10 states (l = 2) + 18 states (l = 4) = 30.
- level 5: 6 states (l = 1) + 14 states (l = 3) + 22 states (l = 5) = 42.
where for every l there are 2l+1 different values of ml and 2 values of ms, giving a total of 4l+2 states for every specific level.
## Including a spin-orbit interaction
We next include a spin-orbit interaction. First we have to describe the system by the quantum numbers j, mj and parity instead of l, ml and ms, as in the Hydrogen-like atom. Since every even level includes only even values of l, it includes only states of even (positive) parity; Similarly every odd level includes only states of odd (negative) parity. Thus we can ignore parity in counting states. The first six shells, described by the new quantum numbers, are
- level 0 (n=0): 2 states (j = 1/2). Even parity.
- level 1 (n=1): 4 states (j = 3/2) + 2 states (j = 1/2) = 6. Odd parity.
- level 2 (n=2): 6 states (j = 5/2) + 4 states (j = 3/2) + 2 states (j = 1/2) = 12. Even parity.
- level 3 (n=3): 8 states (j = 7/2) + 6 states (j = 5/2) + 4 states (j = 3/2) + 2 states (j = 1/2) = 20. Odd parity.
- level 4 (n=4): 10 states (j = 9/2) + 8 states (j = 7/2) + 6 states (j = 5/2) + 4 states (j = 3/2) + 2 states (j = 1/2) = 30. Even parity.
- level 5 (n=5): 12 states (j = 11/2) + 10 states (j = 9/2) + 8 states (j = 7/2) + 6 states (j = 5/2) + 4 states (j = 3/2) + 2 states (j = 1/2) = 42. Odd parity.
where for every j there are 2j+1 different states from different values of mj.
Due to the spin-orbit interaction the energies of states of the same level but with different j will no longer be identical. This is because in the original quantum numbers, when \vec{s} is parallel to \vec{l}, the interaction energy is negative; and in this case j = l + s = l + 1/2. When \vec{s} is anti-parallel to \vec{l} (i.e. aligned oppositely), the interaction energy is positive, and in this case j = l - s = l - 1/2. Furthermore, the strength of the interaction is roughly proportional to l.
For example, consider the states at level 4:
- The 10 states with j = 9/2 come from l = 4 and s parallel to l. Thus they have a negative spin-orbit interaction energy.
- The 8 states with j = 7/2 came from l = 4 and s anti-parallel to l. Thus they have a positive spin-orbit interaction energy.
- The 6 states with j = 5/2 came from l = 2 and s parallel to l. Thus they have a negative spin-orbit interaction energy. However its magnitude is half compared to the states with j = 9/2.
- The 4 states with j = 3/2 came from l = 2 and s anti-parallel to l. Thus they have a positive spin-orbit interaction energy. However its magnitude is half compared to the states with j = 7/2.
- The 2 states with j = 1/2 came from l = 0 and thus have zero spin-orbit interaction energy.
## Deforming the potential
The harmonic oscillator potential V(r) = \mu \omega^2 r^2 /2 grows infinitely as the distance from the center r goes to infinity. A more realistic potential, such as Woods Saxon potential, would approach a constant at this limit. One main consequence is that the average radius of nucleons orbits would be larger in a realistic potential; This leads to a reduced term \hbar^2 l(l+1)/ 2m r^2 in the Laplacian in the Hamiltonian. Another main difference is that orbits with high average radii, such as those with high n or high l, will have a lower energy than in a harmonic oscillator potential. Both effects lead to a reduction in the energy levels of high l orbits.
## Predicted magic numbers
Together with the spin-orbit interaction, and for appropriate magnitudes of both effects, one is led to the following qualitative picture: At all levels, the highest j states have their energies shifted downwards, especially for high n (where the highest j is high). This is both due to the negative spin-orbit interaction energy and to the reduction in energy resulting from deforming the potential to a more realistic one. The second-to-highest j states, on the contrary, have their energy shifted up by the first effect and down by the second effect, leading to a small overall shift. The shifts in the energy of the highest j states can thus bring the energy of states of one level to be closer to the energy of states of a lower level. The "shells" of the shell model are then no longer identical to the levels denoted by n, and the magic numbers are changed.
We may then suppose that the highest j states for n = 3 have an intermediate energy between the average energies of n = 2 and n = 3, and suppose that the highest j states for larger n (at least up to n = 7) have an energy closer to the average energy of n-1. Then we get the following shells (see the figure)
- 1st Shell: 2 states (n = 0, j = 1/2).
- 2nd Shell: 6 states (n = 1, j = 1/2 or 3/2).
- 3rd shell: 12 states (n = 2, j = 1/2, 3/2 or 5/2).
- 4th shell: 8 states (n = 3, j = 7/2).
- 5th shell: 22 states (n = 3, j = 1/2, 3/2 or 5/2; n = 4, j = 9/2).
- 6th shell: 32 states (n = 4, j = 1/2, 3/2, 5/2 or 7/2; n = 5, j = 11/2).
- 7th shell: 44 states (n = 5, j = 1/2, 3/2, 5/2, 7/2 or 9/2; n = 6, j = 13/2).
- 8th shell: 58 states (n = 6, j = 1/2, 3/2, 5/2, 7/2, 9/2 or 11/2; n = 7, j = 15/2).
and so on.
The magic numbers are then
and so on. This gives all the observed magic numbers, and also predicts a new one, at the value of 184 (for protons, the magic number 126 has not been observed yet, and more complicated theoretical considerations predict the magic number to be 114 instead).
## Other properties of nuclei
This model also predicts or explains with some success other properties of nuclei, in particular spin and parity of nuclei ground states, and to some extent their excited states as well. Take 178O9 as an example - its nucleus has eight protons filling the two first proton shells, eight neutrons filling the two first neutron shells, and one extra neutron. All protons in a complete proton shell have total angular momentum zero, since their angular momenta cancel each other; The same is true for neutrons. All protons in the same level (n) have the same parity (either +1 or -1), and since the parity of a pair of particles is the product of their parities, an even number of protons from the same level (n) will have +1 parity. Thus the total angular momentum of the eight protons and the first eight neutrons is zero, and their total parity is +1. This means that the spin (i.e. angular momentum) of the nucleus, as well as its parity, are fully determined by that of the ninth neutron. This one is in the first (i.e. lowest energy) state of the 3rd shell, and therefore have n = 2, giving it +1 parity, and j = 5/2. Thus the nucleus of 178O9 is expected to have positive parity and spin 5/2, which indeed it has.
For nuclei farther from the magic numbers one must add the assumption that due to the relation between the strong nuclear force and angular momentum, protons or neutrons with the same n tend to form pairs of opposite angular momenta. Therefore a nucleus with an even number of protons and an even number of neutrons has 0 spin and positive parity. A nucleus with an even number of protons and an odd number of neutrons (or vice versa) has the parity of the last neutron (or proton), and the spin equal to the total angular momentum of this neutron (or proton). By "last" we mean the properties coming from the highest energy level.
In the case of a nucleus with an odd number of protons and an odd number of neutrons, one must consider the total angular momentum and parity of both the last neutron and the last proton. The nucleus parity will be a product of theirs, while the nucleus spin will be one of the possible results of the sum of their total angular momenta (with other possible results being excited states of the nucleus).
The ordering of angular momentum levels within each shell is according to the principles described above - due to spin-orbit interaction, with high angular momentum states having their energies shifted downwards due to the deformation of the potential (i.e. moving form a harmonic oscillator potential to a more realistic one). For nucleon pairs, however, it is often energetically favorable to be at high angular momentum, even if its energy level for a single nucleon would be higher. This is due to the relation between angular momentum and the strong nuclear force.
Nuclear magnetic moment is partly predicted by this simple version of the shell model. The magnetic moment is calculated through j, l and s of the "last" nucleon, but nuclei are not in states of well defined l and s. Furthermore, for odd-odd nuclei, one has to consider the two "last" nucleons, as in deuterium. Therefore one gets several possible answers for the nuclear magnetic moment, one for each possible combined l and s state, and the real state of the nucleus is a superposition of them. Thus the real (measured) nuclear magnetic moment is somewhere in between the possible answers.
The electric dipole of a nucleus is always zero, because its ground state has a definite parity, so its matter density (\psi^2, where \psi is the wavefunction) is always invariant under parity. This is usually the situations with the atomic electric dipole as well.
Higher electric and magnetic multipole moments cannot be predicted by this simple version of the shell model, for the reasons similar to those in the case of the deuterium. | Shell model
In nuclear physics, the nuclear shell model is a model of the atomic nucleus which uses the Pauli principle to describe the structure of the nucleus in terms of energy levels. The model was developed in 1949 following independent work by several physicists, most notably Eugene Paul Wigner, Maria Goeppert-Mayer and J. Hans D. Jensen, who shared the 1963 Nobel Prize in Physics for their contributions.
The shell model is partly analogous to the atomic shell model which describes the arrangement of electrons in an atom, in that a filled shell results in greater stability. When adding nucleons (protons or neutrons) to a nucleus, there are certain points where the binding energy of the next nucleon is significantly less than the last one. This observation, that there are certain magic numbers of nucleons: 2, 8, 20, 28, 50, 82, 126 which are more tightly bound than the next higher number, is the origin of the shell model.
Note that the shells exist for both protons and neutrons individually, so that we can speak of "magic nuclei" where one nucleon type is at a magic number, and "doubly magic nuclei", where both are. Due to some variations in orbital filling, the upper magic numbers are 126 and, speculatively, 184 for neutrons but only 114 for protons. This has a relevant role in the search of the so-called island of stability. Besides, there have been found some semimagic numbers, noticeably Z=40.
In order to get these numbers, the nuclear shell model starts from an average potential with a shape something between the square well and the harmonic oscillator. To this potential a relativistic spin orbit term is added. Even so, the total perturbation does not coincide with experiment, and an empirical spin orbit coupling, named Nilsson Term, must be added with at least two or three different values of its coupling constant, depending on the nuclei being studied.
Nevertheless, the magic numbers of nucleons, as well as other properties, can be arrived at by approximating the model with a three-dimensional harmonic oscillator plus a spin-orbit interaction. A more realistic but also complicated potential is known as Woods Saxon potential.
# Deformed harmonic oscillator approximated model
Consider a three-dimensional harmonic oscillator. This would give, for example, in the first two levels
We can imagine ourselves building a nucleus by adding protons and neutrons. These will always fill the lowest available level. Thus the first two protons fill level zero, the next six protons fill level one, and so on. As with electrons in the periodic table, protons in the outermost shell will be relatively loosely bound to the nucleus if there are only few protons in that shell, because they are farthest from the center of the nucleus. Therefore nuclei which have a full outer proton shell will have a higher binding energy than other nuclei with a similar total number of protons. All this is true for neutrons as well.
This means that the magic numbers are expected to be those in which all occupied shells are full. We see that for the first two numbers we get 2 (level 0 full) and 8 (levels 0 and 1 full), in accord with experiment. However the full set of magic numbers does not turn out correctly. These can be computed as follows:
In particular, the first six shells are:
- level 0: 2 states (l = 0) = 2.
- level 1: 6 states (l = 1) = 6.
- level 2: 2 states (l = 0) + 10 states (l = 2) = 12.
- level 3: 6 states (l = 1) + 14 states (l = 3) = 20.
- level 4: 2 states (l = 0) + 10 states (l = 2) + 18 states (l = 4) = 30.
- level 5: 6 states (l = 1) + 14 states (l = 3) + 22 states (l = 5) = 42.
where for every l there are 2l+1 different values of ml and 2 values of ms, giving a total of 4l+2 states for every specific level.
## Including a spin-orbit interaction
We next include a spin-orbit interaction. First we have to describe the system by the quantum numbers j, mj and parity instead of l, ml and ms, as in the Hydrogen-like atom. Since every even level includes only even values of l, it includes only states of even (positive) parity; Similarly every odd level includes only states of odd (negative) parity. Thus we can ignore parity in counting states. The first six shells, described by the new quantum numbers, are
- level 0 (n=0): 2 states (j = 1/2). Even parity.
- level 1 (n=1): 4 states (j = 3/2) + 2 states (j = 1/2) = 6. Odd parity.
- level 2 (n=2): 6 states (j = 5/2) + 4 states (j = 3/2) + 2 states (j = 1/2) = 12. Even parity.
- level 3 (n=3): 8 states (j = 7/2) + 6 states (j = 5/2) + 4 states (j = 3/2) + 2 states (j = 1/2) = 20. Odd parity.
- level 4 (n=4): 10 states (j = 9/2) + 8 states (j = 7/2) + 6 states (j = 5/2) + 4 states (j = 3/2) + 2 states (j = 1/2) = 30. Even parity.
- level 5 (n=5): 12 states (j = 11/2) + 10 states (j = 9/2) + 8 states (j = 7/2) + 6 states (j = 5/2) + 4 states (j = 3/2) + 2 states (j = 1/2) = 42. Odd parity.
where for every j there are 2j+1 different states from different values of mj.
Due to the spin-orbit interaction the energies of states of the same level but with different j will no longer be identical. This is because in the original quantum numbers, when <math>\vec{s}</math> is parallel to <math>\vec{l}</math>, the interaction energy is negative; and in this case j = l + s = l + 1/2. When <math>\vec{s}</math> is anti-parallel to <math>\vec{l}</math> (i.e. aligned oppositely), the interaction energy is positive, and in this case j = l - s = l - 1/2. Furthermore, the strength of the interaction is roughly proportional to l.
For example, consider the states at level 4:
- The 10 states with j = 9/2 come from l = 4 and s parallel to l. Thus they have a negative spin-orbit interaction energy.
- The 8 states with j = 7/2 came from l = 4 and s anti-parallel to l. Thus they have a positive spin-orbit interaction energy.
- The 6 states with j = 5/2 came from l = 2 and s parallel to l. Thus they have a negative spin-orbit interaction energy. However its magnitude is half compared to the states with j = 9/2.
- The 4 states with j = 3/2 came from l = 2 and s anti-parallel to l. Thus they have a positive spin-orbit interaction energy. However its magnitude is half compared to the states with j = 7/2.
- The 2 states with j = 1/2 came from l = 0 and thus have zero spin-orbit interaction energy.
## Deforming the potential
The harmonic oscillator potential <math>V(r) = \mu \omega^2 r^2 /2</math> grows infinitely as the distance from the center r goes to infinity. A more realistic potential, such as Woods Saxon potential, would approach a constant at this limit. One main consequence is that the average radius of nucleons orbits would be larger in a realistic potential; This leads to a reduced term <math>\hbar^2 l(l+1)/ 2m r^2</math> in the Laplacian in the Hamiltonian. Another main difference is that orbits with high average radii, such as those with high n or high l, will have a lower energy than in a harmonic oscillator potential. Both effects lead to a reduction in the energy levels of high l orbits.
## Predicted magic numbers
Together with the spin-orbit interaction, and for appropriate magnitudes of both effects, one is led to the following qualitative picture: At all levels, the highest j states have their energies shifted downwards, especially for high n (where the highest j is high). This is both due to the negative spin-orbit interaction energy and to the reduction in energy resulting from deforming the potential to a more realistic one. The second-to-highest j states, on the contrary, have their energy shifted up by the first effect and down by the second effect, leading to a small overall shift. The shifts in the energy of the highest j states can thus bring the energy of states of one level to be closer to the energy of states of a lower level. The "shells" of the shell model are then no longer identical to the levels denoted by n, and the magic numbers are changed.
We may then suppose that the highest j states for n = 3 have an intermediate energy between the average energies of n = 2 and n = 3, and suppose that the highest j states for larger n (at least up to n = 7) have an energy closer to the average energy of n-1. Then we get the following shells (see the figure)
- 1st Shell: 2 states (n = 0, j = 1/2).
- 2nd Shell: 6 states (n = 1, j = 1/2 or 3/2).
- 3rd shell: 12 states (n = 2, j = 1/2, 3/2 or 5/2).
- 4th shell: 8 states (n = 3, j = 7/2).
- 5th shell: 22 states (n = 3, j = 1/2, 3/2 or 5/2; n = 4, j = 9/2).
- 6th shell: 32 states (n = 4, j = 1/2, 3/2, 5/2 or 7/2; n = 5, j = 11/2).
- 7th shell: 44 states (n = 5, j = 1/2, 3/2, 5/2, 7/2 or 9/2; n = 6, j = 13/2).
- 8th shell: 58 states (n = 6, j = 1/2, 3/2, 5/2, 7/2, 9/2 or 11/2; n = 7, j = 15/2).
and so on.
The magic numbers are then
- 2
- 8 = 2+6
- 20 = 2+6+12
- 28 = 2+6+12+8
- 50 = 2+6+12+8+22
- 82 = 2+6+12+8+22+32
- 126 = 2+6+12+8+22+32+44
- 184 = 2+6+12+8+22+32+44+58
and so on. This gives all the observed magic numbers, and also predicts a new one, at the value of 184 (for protons, the magic number 126 has not been observed yet, and more complicated theoretical considerations predict the magic number to be 114 instead).
## Other properties of nuclei
This model also predicts or explains with some success other properties of nuclei, in particular spin and parity of nuclei ground states, and to some extent their excited states as well. Take 178O9 as an example - its nucleus has eight protons filling the two first proton shells, eight neutrons filling the two first neutron shells, and one extra neutron. All protons in a complete proton shell have total angular momentum zero, since their angular momenta cancel each other; The same is true for neutrons. All protons in the same level (n) have the same parity (either +1 or -1), and since the parity of a pair of particles is the product of their parities, an even number of protons from the same level (n) will have +1 parity. Thus the total angular momentum of the eight protons and the first eight neutrons is zero, and their total parity is +1. This means that the spin (i.e. angular momentum) of the nucleus, as well as its parity, are fully determined by that of the ninth neutron. This one is in the first (i.e. lowest energy) state of the 3rd shell, and therefore have n = 2, giving it +1 parity, and j = 5/2. Thus the nucleus of 178O9 is expected to have positive parity and spin 5/2, which indeed it has.
For nuclei farther from the magic numbers one must add the assumption that due to the relation between the strong nuclear force and angular momentum, protons or neutrons with the same n tend to form pairs of opposite angular momenta. Therefore a nucleus with an even number of protons and an even number of neutrons has 0 spin and positive parity. A nucleus with an even number of protons and an odd number of neutrons (or vice versa) has the parity of the last neutron (or proton), and the spin equal to the total angular momentum of this neutron (or proton). By "last" we mean the properties coming from the highest energy level.
In the case of a nucleus with an odd number of protons and an odd number of neutrons, one must consider the total angular momentum and parity of both the last neutron and the last proton. The nucleus parity will be a product of theirs, while the nucleus spin will be one of the possible results of the sum of their total angular momenta (with other possible results being excited states of the nucleus).
The ordering of angular momentum levels within each shell is according to the principles described above - due to spin-orbit interaction, with high angular momentum states having their energies shifted downwards due to the deformation of the potential (i.e. moving form a harmonic oscillator potential to a more realistic one). For nucleon pairs, however, it is often energetically favorable to be at high angular momentum, even if its energy level for a single nucleon would be higher. This is due to the relation between angular momentum and the strong nuclear force.
Nuclear magnetic moment is partly predicted by this simple version of the shell model. The magnetic moment is calculated through j, l and s of the "last" nucleon, but nuclei are not in states of well defined l and s. Furthermore, for odd-odd nuclei, one has to consider the two "last" nucleons, as in deuterium. Therefore one gets several possible answers for the nuclear magnetic moment, one for each possible combined l and s state, and the real state of the nucleus is a superposition of them. Thus the real (measured) nuclear magnetic moment is somewhere in between the possible answers.
The electric dipole of a nucleus is always zero, because its ground state has a definite parity, so its matter density (<math>\psi^2</math>, where <math>\psi</math> is the wavefunction) is always invariant under parity. This is usually the situations with the atomic electric dipole as well.
Higher electric and magnetic multipole moments cannot be predicted by this simple version of the shell model, for the reasons similar to those in the case of the deuterium. | https://www.wikidoc.org/index.php/Shell_model | |
44b4a59daf0c516cc9763a1b275617bfb3d914e4 | wikidoc | Side stitch | Side stitch
Synonyms and keywords: Side cramp
# Overview
When exercising, a side stitch is an intense stabbing pain under the lower edge of the ribcage. It is also referred to as exercise related transient abdominal pain (ETAP). This pain is caused by the internal organs (like the liver and stomach) pulling downwards on the diaphragm. It is therefore more likely to occur in sports involving up and down actions - like running, jumping and horse riding.
# Causes
## Possible Causes
There are more theories regarding ETAP than merely stretching of the visceral ligaments due to repeated vertical translation and jolting. Other theories include:
- Diaphragmatic ischemia
- Imbalances of the thoracic spine
- Irritation of the parietal peritoneum
The reasons for these theories include, in particular, the prevalence of ETAP during swimming.
Most of the time, side stitches occur on the right side of the body. This is due to the largest organ in the abdominal cavity, the liver, being on that side. Certain athletes also report a pain in the tip of their shoulder blade. This is believed to be because this is a referred site of pain for the diaphragm via the phrenic nerve.
# Treatment
Possible treatments for side stitches include:
- Stop exercising. With your fingers, push into your abdomen on the right side, and up under the rib cage. At the same time, forcefully let out a deep exhale while holding your lips closely together.
- Stop exercising until the pain goes away.
- Try belly breathing; Inhale while pushing out your abdomen, and on the exhale, relax your abdominal muscles.
- Stop exercising and touch your toes with your fingers, moving your liver away from your diaphragm.
- Breathe on different steps
- Reduce the frequency of breathing (e.g. in jogging, inhale for four steps and exhale for four steps)
- Lie down on your back and lift the knee on the side with the stitch up to your chest.
# Primary Prevention
- Improve fitness.
- Strengthen the diaphragm by using exercises such as those that aid respiratory rehabilitation.
- Strengthen core muscles (abdominals, lower back, obliques).
- Limit consumption of food and drink two to three hours before exercising (in particular, drinks of high carbohydrate content and osmolality (reconstituted fruit juices)).
- Drink water beforehand to prevent muscle cramps.
- Warm up properly.
- Gradually increase exercise intensity.
- When running:
Exhale when the left foot hits the ground, and inhale when the right foot hits the ground.
Run on soft surfaces.
- Exhale when the left foot hits the ground, and inhale when the right foot hits the ground.
- Run on soft surfaces. | Side stitch
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Side cramp
# Overview
When exercising, a side stitch is an intense stabbing pain under the lower edge of the ribcage. It is also referred to as exercise related transient abdominal pain (ETAP). This pain is caused by the internal organs (like the liver and stomach) pulling downwards on the diaphragm. It is therefore more likely to occur in sports involving up and down actions - like running, jumping and horse riding.
# Causes
## Possible Causes
There are more theories regarding ETAP than merely stretching of the visceral ligaments due to repeated vertical translation and jolting. Other theories include:
- Diaphragmatic ischemia
- Imbalances of the thoracic spine
- Irritation of the parietal peritoneum
The reasons for these theories include, in particular, the prevalence of ETAP during swimming.
Most of the time, side stitches occur on the right side of the body. This is due to the largest organ in the abdominal cavity, the liver, being on that side. Certain athletes also report a pain in the tip of their shoulder blade. This is believed to be because this is a referred site of pain for the diaphragm via the phrenic nerve.
# Treatment
Possible treatments for side stitches include:
- Stop exercising. With your fingers, push into your abdomen on the right side, and up under the rib cage. At the same time, forcefully let out a deep exhale while holding your lips closely together.
- Stop exercising until the pain goes away.
- Try belly breathing; Inhale while pushing out your abdomen, and on the exhale, relax your abdominal muscles.
- Stop exercising and touch your toes with your fingers, moving your liver away from your diaphragm.
- Breathe on different steps
- Reduce the frequency of breathing (e.g. in jogging, inhale for four steps and exhale for four steps)
- Lie down on your back and lift the knee on the side with the stitch up to your chest.
# Primary Prevention
- Improve fitness.
- Strengthen the diaphragm by using exercises such as those that aid respiratory rehabilitation.[1]
- Strengthen core muscles (abdominals, lower back, obliques).
- Limit consumption of food and drink two to three hours before exercising (in particular, drinks of high carbohydrate content and osmolality (reconstituted fruit juices)).
- Drink water beforehand to prevent muscle cramps.
- Warm up properly.
- Gradually increase exercise intensity.
- When running:
Exhale when the left foot hits the ground, and inhale when the right foot hits the ground.[2]
Run on soft surfaces.
- Exhale when the left foot hits the ground, and inhale when the right foot hits the ground.[2]
- Run on soft surfaces. | https://www.wikidoc.org/index.php/Side_Stitch | |
5c0deef514473984a789d05ae4680b4950a6edad | wikidoc | Silyl ether | Silyl ether
Silyl ethers are a group of chemical compounds which contain a silicon atom covalently bonded to an alkoxy group. The general structure is R1R2R3Si−O−R4 where R4 is an alkyl group or an aryl group. Silyl ethers are usually used as protecting groups in organic synthesis. Common silyl ethers are: trimethylsilyl (TMS), tert-butyldiphenylsilyl (TBDPS), tert-butyldimethylsilyl (TBS/TBDMS) and triisopropylsilyl (TIPS). They are particularly useful because they can installed and removed very selectively under mild conditions.
# Formation
Although many methods are available for forming silyl ethers, there are two common strategies: reaction of the alcohol with a silyl chloride with an amine base at room temperature and reaction of the alcohol with a silyl triflate with a hindered amine base at low temperature. Silyl triflates are more reactive than their corresponding chlorides, so they can be used to install silyl groups onto hindered positions. One extremely reliable and rapid procedure is the Corey protocol in which the alcohol is reacted with a silyl chloride and imidazole at high concentration in DMF. If DMF is replaced by dichloromethane, the reaction is somewhat slower, but the purification of the compound is simplified. A common hindered base for use with silyl triflates is 2,6-lutidine. Primary alcohols can be proteced in less than one hour while some hindered alcohols may require days of reaction time.
When using a silyl chloride, no special precautions are usually required, except for the exclusion of large amounts of water. An excess of silyl chloride can be employed but is not necessary. If excess reagent is used, the product will require flash chromatography to remove excess silanol and siloxane. Silyl triflates are water sensitive and must be run under inert atmosphere conditions. Purification involves the addition of an aqueous acid such as saturated ammonium chloride solution. This quenches remaining silyl reagent and protonates amine bases, removing them from the reaction mixture. Following extraction, the product can be purified by flash chromatography.
Silyl triflate is more reactive and also converts ketones to silyl enol ethers.
# Removal of silyl ether protecting groups
Reaction with acids or fluorides such as tetra-n-butylammonium fluoride remove the silyl group when protection is no longer needed. Larger substituents increase resistance to hydrolysis, but also make introduction of the silyl group more difficult.
In acidic media, the relative stability is:
In basic media, the relative stability is:
# Monoprotection of symmetrical diols
It is possible to monosilylate a symmetrical diol, although this is known to be problematic occasionally. For example, the following monosilylation was reported:
However, it turns out that this reaction is hard to repeat. Statistically, if the dianion is of similar reactivity to the monoanion, then a corresponding statistical mixture of 1:2:1 disilylated:monosilylated:unsilylated diol will result. With sodium hydride, even allowing several hours for equilibration, poor results are usually obtained. Superior results are obtained with butyllithium:
Alternatively, an excess (4 eq) of the relatively cheap diol can be used, forcing the reaction toward monoprotection.
# Selective deprotection
Selective deprotection of silyl groups is possible in many instances. For example:
Silyl ethers are mainly differentiated on the basis of sterics or electronics. In general, acidic deprotections deprotect less hindered silyl groups faster, with the steric bulk on silicon being more significant than the steric bulk on oxygen. Fluoride-based deprotections deprotect electron-poor silyl groups faster than electron-rich silyl groups. There is some evidence that some silyl deprotections proceed via hypervalent silicon species.
The selective deprotection of silyl ethers has been extensively reviewed. Although selective deprotections have been achieved under many different conditions, some procedures, outlined below, are more reliable. A selective deprotection will likely be successful if there is a substantial difference in sterics (e.g., primary TBS vs. secondary TBS or primary TES vs primary TBS) or electronics (e.g. primary TBDPS vs. primary TBS). Unfortunately, some optimization is inevitably required and it is often necessary to run deprotections partway and recycle material.
Some Common Acidic Conditions:
- 100 mol% 10-CSA in MeOH, room temperature; a "blast" of acid, deprotects primary TBS groups within ten minutes.
- 10 mol% 10-CSA, 1:1 MeOH:DCM, −20 or 0 °C; deprotects a primary TBS group within two hours at 0; if CSA is replaced by PPTS, the rate is approximately ten times slower; with pTsOH, approximately ten times faster; solvent mixture is crucial.
- 4:1:1 v/v/v AcOH:THF:water, room temp.; this is very slow, but can be very selective.
Some Common Basic Conditions:
- HF-pyridine, 10:1 THF:pyridine, 0 °C; an excellent deprotection; removes primary TBS groups within eight hours; reactions using HF must be run in plastic containers.
- TBAF, THF or 1:1 TBAF/AcOH, THF; TBDPS and TBS groups can be deprotected in the presence of one another under different conditions. | Silyl ether
Silyl ethers are a group of chemical compounds which contain a silicon atom covalently bonded to an alkoxy group. The general structure is R1R2R3Si−O−R4 where R4 is an alkyl group or an aryl group. Silyl ethers are usually used as protecting groups in organic synthesis. Common silyl ethers are: trimethylsilyl (TMS), tert-butyldiphenylsilyl (TBDPS), tert-butyldimethylsilyl (TBS/TBDMS) and triisopropylsilyl (TIPS). They are particularly useful because they can installed and removed very selectively under mild conditions.
# Formation
Although many methods are available for forming silyl ethers, there are two common strategies: reaction of the alcohol with a silyl chloride with an amine base at room temperature and reaction of the alcohol with a silyl triflate with a hindered amine base at low temperature. Silyl triflates are more reactive than their corresponding chlorides, so they can be used to install silyl groups onto hindered positions. One extremely reliable and rapid procedure is the Corey protocol in which the alcohol is reacted with a silyl chloride and imidazole at high concentration in DMF.[1] If DMF is replaced by dichloromethane, the reaction is somewhat slower, but the purification of the compound is simplified. A common hindered base for use with silyl triflates is 2,6-lutidine.[2] Primary alcohols can be proteced in less than one hour while some hindered alcohols may require days of reaction time.
When using a silyl chloride, no special precautions are usually required, except for the exclusion of large amounts of water. An excess of silyl chloride can be employed but is not necessary. If excess reagent is used, the product will require flash chromatography to remove excess silanol and siloxane. Silyl triflates are water sensitive and must be run under inert atmosphere conditions. Purification involves the addition of an aqueous acid such as saturated ammonium chloride solution. This quenches remaining silyl reagent and protonates amine bases, removing them from the reaction mixture. Following extraction, the product can be purified by flash chromatography.
Silyl triflate is more reactive and also converts ketones to silyl enol ethers.
# Removal of silyl ether protecting groups
Reaction with acids or fluorides such as tetra-n-butylammonium fluoride remove the silyl group when protection is no longer needed. Larger substituents increase resistance to hydrolysis, but also make introduction of the silyl group more difficult.
In acidic media, the relative stability is:
In basic media, the relative stability is:
# Monoprotection of symmetrical diols
It is possible to monosilylate a symmetrical diol, although this is known to be problematic occasionally. For example, the following monosilylation was reported:[3]
However, it turns out that this reaction is hard to repeat. Statistically, if the dianion is of similar reactivity to the monoanion, then a corresponding statistical mixture of 1:2:1 disilylated:monosilylated:unsilylated diol will result. With sodium hydride, even allowing several hours for equilibration, poor results are usually obtained. Superior results are obtained with butyllithium:[citation needed]
Alternatively, an excess (4 eq) of the relatively cheap diol can be used, forcing the reaction toward monoprotection.
# Selective deprotection
Selective deprotection of silyl groups is possible in many instances. For example:[4]
Silyl ethers are mainly differentiated on the basis of sterics or electronics. In general, acidic deprotections deprotect less hindered silyl groups faster, with the steric bulk on silicon being more significant than the steric bulk on oxygen. Fluoride-based deprotections deprotect electron-poor silyl groups faster than electron-rich silyl groups. There is some evidence that some silyl deprotections proceed via hypervalent silicon species.
The selective deprotection of silyl ethers has been extensively reviewed.[5][6] Although selective deprotections have been achieved under many different conditions, some procedures, outlined below, are more reliable. A selective deprotection will likely be successful if there is a substantial difference in sterics (e.g., primary TBS vs. secondary TBS or primary TES vs primary TBS) or electronics (e.g. primary TBDPS vs. primary TBS). Unfortunately, some optimization is inevitably required and it is often necessary to run deprotections partway and recycle material.
Some Common Acidic Conditions:
- 100 mol% 10-CSA in MeOH, room temperature; a "blast" of acid, deprotects primary TBS groups within ten minutes.
- 10 mol% 10-CSA, 1:1 MeOH:DCM, −20 or 0 °C; deprotects a primary TBS group within two hours at 0; if CSA is replaced by PPTS, the rate is approximately ten times slower; with pTsOH, approximately ten times faster; solvent mixture is crucial.
- 4:1:1 v/v/v AcOH:THF:water, room temp.; this is very slow, but can be very selective.
Some Common Basic Conditions:
- HF-pyridine, 10:1 THF:pyridine, 0 °C; an excellent deprotection; removes primary TBS groups within eight hours; reactions using HF must be run in plastic containers.
- TBAF, THF or 1:1 TBAF/AcOH, THF; TBDPS and TBS groups can be deprotected in the presence of one another under different conditions.[7] | https://www.wikidoc.org/index.php/Silyl_ether | |
9e50a796b95366b0f46fdb2cf438c88f4b361ddc | wikidoc | Simethicone | Simethicone
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
NOTE: Most over the counter (OTC) are not reviewed and approved by the FDA. However, they may be marketed if they comply with applicable regulations and policies. FDA has not evaluated whether this product complies.
# Overview
Simethicone is a antiflatulent, diagnostic and gastrointestinal agent that is FDA approved for the treatment of excessive upper gastrointestinal gas. Common adverse reactions include darrhea, nausea, regurgitation and vomiting.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Relieves pressure and bloating commonly referred to as gas.
- Ultrasonography
### Dosing Information
- Chew 2 to 4 tablets thoroughly as needed after meals and at bedtime. Do not exceed 6 tablets per day unless directed by a physician.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Simethicone in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Simethicone in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Simethicone FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Simethicone in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Simethicone in pediatric patients.
# Contraindications
There is limited information regarding Contraindication of Simethicone
# Warnings
- When using this product - do not take more than directed, except under the advice of a doctor
- If pregnant or breast feeding, ask a health professional before use.
- Tamper Evident: Do not use if imprinted seal under cap is missing or broken.
- Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away.
# Adverse Reactions
## Clinical Trials Experience
There is limited information regarding Adverse Reactions of Simethicone.
## Postmarketing Experience
There is limited information regarding Adverse Reactions reported from Post Experience of Simethicone.
# Drug Interactions
There is limited information regarding Drug Interactions of Simethicone.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Simethicone in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Simethicone in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Simethicone during labor and delivery.
### Nursing Mothers
There is no FDA guidance on the use of Simethicone in women who are nursing.
### Pediatric Use
There is no FDA guidance on the use of Simethicone in pediatric settings.
### Geriatic Use
There is no FDA guidance on the use of Simethicone in geriatric settings.
### Gender
There is no FDA guidance on the use of Simethicone with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Simethicone with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Simethicone in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Simethicone in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Simethicone in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Simethicone in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Oral
### Monitoring
There is limited information regarding Simethicone Monitoring in the drug label.
# IV Compatibility
There is limited information regarding the compatibility of Simethicone and IV administrations.
# Overdosage
There is limited information regarding Simethicone overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
# Pharmacology
## Mechanism of Action
There is limited information regarding Simethicone Mechanism of Action in the drug label.
## Structure
There is limited information regarding Simethicone Structure in the drug label.
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Simethicone
## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Simethicone
## Nonclinical Toxicology
There is limited information regarding nonclinical toxicology of Simethicone
# Clinical Studies
There is limited information regarding clinical studies of Simethicone
# How Supplied
There is limited information regarding Simethicone How Supplied in the drug label.
## Storage
- Store at room temperature, 15°C - 30°C (59˚F - 86˚F)
- Package not child resistant
# Images
## Drug Images
## Package and Label Display Panel
### PACKAGE LABEL
GERICARE
NDC 57896-791-01
CHEWABLE
SIMETHICONE
TABLETS USP, 80mg
FOR GAS DISTRESS
MINT FLAVOR
100 Tablets
80 mg each
# Patient Counseling Information
There is limited information regarding Simethicone Patient Counseling Information in the drug label.
# Precautions with Alcohol
Alcohol-Simethicone interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Mylicon
- Gas-X
- Maalox Anti-Gas
- Mylanta Gas
- Genasyme
- Mytab Gas
- Phazyme
- Alka-Seltzer Anti-Gas
# Look-Alike Drug Names
There is limited information regarding Simethicone Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Simethicone
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Adeel Jamil, M.D. [2]
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
NOTE: Most over the counter (OTC) are not reviewed and approved by the FDA. However, they may be marketed if they comply with applicable regulations and policies. FDA has not evaluated whether this product complies.
# Overview
Simethicone is a antiflatulent, diagnostic and gastrointestinal agent that is FDA approved for the treatment of excessive upper gastrointestinal gas. Common adverse reactions include darrhea, nausea, regurgitation and vomiting.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- Relieves pressure and bloating commonly referred to as gas.
- Ultrasonography
### Dosing Information
- Chew 2 to 4 tablets thoroughly as needed after meals and at bedtime. Do not exceed 6 tablets per day unless directed by a physician.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Simethicone in adult patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Simethicone in adult patients.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Simethicone FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Simethicone in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Simethicone in pediatric patients.
# Contraindications
There is limited information regarding Contraindication of Simethicone
# Warnings
- When using this product • do not take more than directed, except under the advice of a doctor
- If pregnant or breast feeding, ask a health professional before use.
- Tamper Evident: Do not use if imprinted seal under cap is missing or broken.
- Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center right away.
# Adverse Reactions
## Clinical Trials Experience
There is limited information regarding Adverse Reactions of Simethicone.
## Postmarketing Experience
There is limited information regarding Adverse Reactions reported from Post Experience of Simethicone.
# Drug Interactions
There is limited information regarding Drug Interactions of Simethicone.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Simethicone in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Simethicone in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Simethicone during labor and delivery.
### Nursing Mothers
There is no FDA guidance on the use of Simethicone in women who are nursing.
### Pediatric Use
There is no FDA guidance on the use of Simethicone in pediatric settings.
### Geriatic Use
There is no FDA guidance on the use of Simethicone in geriatric settings.
### Gender
There is no FDA guidance on the use of Simethicone with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Simethicone with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Simethicone in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Simethicone in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Simethicone in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Simethicone in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Oral
### Monitoring
There is limited information regarding Simethicone Monitoring in the drug label.
# IV Compatibility
There is limited information regarding the compatibility of Simethicone and IV administrations.
# Overdosage
There is limited information regarding Simethicone overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
# Pharmacology
## Mechanism of Action
There is limited information regarding Simethicone Mechanism of Action in the drug label.
## Structure
There is limited information regarding Simethicone Structure in the drug label.
## Pharmacodynamics
There is limited information regarding Pharmacodynamics of Simethicone
## Pharmacokinetics
There is limited information regarding Pharmacokinetics of Simethicone
## Nonclinical Toxicology
There is limited information regarding nonclinical toxicology of Simethicone
# Clinical Studies
There is limited information regarding clinical studies of Simethicone
# How Supplied
There is limited information regarding Simethicone How Supplied in the drug label.
## Storage
- Store at room temperature, 15°C - 30°C (59˚F - 86˚F)
- Package not child resistant
# Images
## Drug Images
## Package and Label Display Panel
### PACKAGE LABEL
GERICARE
NDC 57896-791-01
CHEWABLE
SIMETHICONE
TABLETS USP, 80mg
FOR GAS DISTRESS
MINT FLAVOR
100 Tablets
80 mg each
# Patient Counseling Information
There is limited information regarding Simethicone Patient Counseling Information in the drug label.
# Precautions with Alcohol
Alcohol-Simethicone interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Mylicon
- Gas-X
- Maalox Anti-Gas
- Mylanta Gas
- Genasyme
- Mytab Gas
- Phazyme
- Alka-Seltzer Anti-Gas
# Look-Alike Drug Names
There is limited information regarding Simethicone Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Simethicone | |
68be4f05f0a5dfcba5c9f7386bc176abb2a5f91f | wikidoc | Simvastatin | Simvastatin
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Simvastatin is a HMG-CoA Reductase Inhibitor that is FDA approved for the {{{indicationType}}} of reductions in risk of CHD mortality and cardiovascular events, hyperlipidemia, adolescent patients with heterozygous familial hypercholesterolemia (HeFH). Common adverse reactions include abdominal pain, constipation, nausea, headache, upper respiratory infection.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
The usual dosage range is 5 to 40 mg/day. In patients with CHD or at high risk of CHD, simvastatin can be started simultaneously with diet. The recommended usual starting dose is 10 or 20 mg once a day in the evening. For patients at high risk for a CHD event due to existing CHD, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, the recommended starting dose is 40 mg/day. Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter.
Due to the increased risk of myopathy, including rhabdomyolysis, particularly during the first year of treatment, use of the 80-mg dose of simvastatin should be restricted to patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity.
Patients who are currently tolerating the 80-mg dose of simvastatin who need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to an alternative statin with less potential for the drug-drug interaction.
Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 80-mg dose of simvastatin, patients unable to achieve their LDL-C goal utilizing the 40-mg dose of simvastatin should not be titrated to the 80-mg dose, but should be placed on alternative LDL-C-lowering treatment(s) that provides greater LDL-C lowering.
Patients taking Verapamil, Diltiazem, or Dronedarone
The dose of simvastatin should not exceed 10 mg/day.
Patients taking Amiodarone, Amlodipine or Ranolazine
The dose of simvastatin should not exceed 20 mg/day.
The recommended dosage is 40 mg/day in the evening. simvastatin should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.
Simvastatin exposure is approximately doubled with concomitant use of lomitapide; therefore, the dose of simvastatin should be reduced by 50% if initiating lomitapide. simvastatin dosage should not exceed 20 mg/day (or 40 mg/day for patients who have previously taken simvastatin 80 mg/day chronically, e.g., for 12 months or more, without evidence of muscle toxicity) while taking lomitapide.
Because simvastatin does not undergo significant renal excretion, modification of dosage should not be necessary in patients with mild to moderate renal impairment. However, caution should be exercised when simvastatin is administered to patients with severe renal impairment; such patients should be started at 5 mg/day and be closely monitored.
Because of an increased risk for myopathy in Chinese patients taking simvastatin 40 mg coadministered with lipid-modifying doses (≥1 g/day niacin) of niacin-containing products, caution should be used when treating Chinese patients with simvastatin doses exceeding 20 mg/day coadministered with lipid-modifying doses of niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive simvastatin 80 mg coadministered with lipid-modifying doses of niacin-containing products. The cause of the increased risk of myopathy is not known. It is also unknown if the risk for myopathy with coadministration of simvastatin with lipid-modifying doses of niacin-containing products observed in Chinese patients applies to other Asian patients.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Simvastatin detailed information in adult patients.
### Non–Guideline-Supported Use
- Dosing Information
- 40 mg/day for 1 month followed by 80 mg/day thereafter
- Dosing Information
- 40 mg
- Dosing Information
- 10 to 20 mg/day
- Dosing Information
- 5 mg
- Dosing information
- 80 mg/day
- Dosing information
- 20 mg twice daily
- Dosing information
- 80 mg/day
- Dosing information
- 80 mg/day
- Dosing information
- 20 mg daily
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- Dosing Information
- The recommended usual starting dose is 10 mg once a day in the evening. The recommended dosing range is 10 to 40 mg/day; the maximum recommended dose is 40 mg/day. Doses should be individualized according to the recommended goal of therapy. Adjustments should be made at intervals of 4 weeks or more.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Simvastatin detailed information in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Simvastatin detailed information in pediatric patients.
# Contraindications
- Concomitant administration of strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, and cobicistat-containing products).
- Concomitant administration of gemfibrozil, cyclosporine, or danazol.
- Hypersensitivity to any component of this medication.
- Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels.
- Women who are pregnant or may become pregnant
- Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Because HMG-CoA reductase inhibitors (statins) decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, simvastatin may cause fetal harm when administered to a pregnant woman. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. There are no adequate and well-controlled studies of use with simvastatin during pregnancy; however, in rare reports congenital anomalies were observed following intrauterine exposure to statins. In rat and rabbit animal reproduction studies, simvastatin revealed no evidence of teratogenicity. Simvastatin should be administered to women of childbearing age only when such patients are highly unlikely to conceive. If the patient becomes pregnant while taking this drug, simvastatin should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus.
- Nursing mothers
- It is not known whether simvastatin is excreted into human milk; however, a small amount of another drug in this class does pass into breast milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require treatment with simvastatin should not breastfeed their infants.
# Warnings
Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of statin activity in plasma. Predisposing factors for myopathy include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment.
The risk of myopathy, including rhabdomyolysis, is dose related. In a clinical trial database in which 41,413 patients were treated with simvastatin, 24,747 (approximately 60%) of whom were enrolled in studies with a median follow-up of at least 4 years, the incidence of myopathy was approximately 0.03% and 0.08% at 20 and 40 mg/day, respectively. The incidence of myopathy with 80 mg (0.61%) was disproportionately higher than that observed at the lower doses. In these trials, patients were carefully monitored and some interacting medicinal products were excluded.
In a clinical trial in which 12,064 patients with a history of myocardial infarction were treated with simvastatin (mean follow-up 6.7 years), the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum creatine kinase >10 times upper limit of normal ) in patients on 80 mg/day was approximately 0.9% compared with 0.02% for patients on 20 mg/day. The incidence of rhabdomyolysis (defined as myopathy with a CK >40 times ULN) in patients on 80 mg/day was approximately 0.4% compared with 0% for patients on 20 mg/day. The incidence of myopathy, including rhabdomyolysis, was highest during the first year and then notably decreased during the subsequent years of treatment. In this trial, patients were carefully monitored and some interacting medicinal products were excluded.
The risk of myopathy, including rhabdomyolysis, is greater in patients on simvastatin 80 mg compared with other statin therapies with similar or greater LDL-C-lowering efficacy and compared with lower doses of simvastatin. Therefore, the 80-mg dose of simvastatin should be used only in patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity. If, however, a patient who is currently tolerating the 80-mg dose of simvastatin needs to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin, that patient should be switched to an alternative statin with less potential for the drug-drug interaction. Patients should be advised of the increased risk of myopathy, including rhabdomyolysis, and to report promptly any unexplained muscle pain, tenderness or weakness. If symptoms occur, treatment should be discontinued immediately.
There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents.
All patients starting therapy with simvastatin, or whose dose of simvastatin is being increased, should be advised of the risk of myopathy, including rhabdomyolysis, and told to report promptly any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing simvastatin. simvastatin therapy should be discontinued immediately if myopathy is diagnosed or suspected. In most cases, muscle symptoms and CK increases resolved when treatment was promptly discontinued. Periodic CK determinations may be considered in patients starting therapy with simvastatin or whose dose is being increased, but there is no assurance that such monitoring will prevent myopathy.
Many of the patients who have developed rhabdomyolysis on therapy with simvastatin have had complicated medical histories, including renal insufficiency usually as a consequence of long-standing diabetes mellitus. Such patients merit closer monitoring. simvastatin therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. simvastatin therapy should also be temporarily withheld in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis, e.g., sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy.
Drug Interactions
The risk of myopathy and rhabdomyolysis is increased by high levels of statin activity in plasma. Simvastatin is metabolized by the cytochrome P450 isoform 3A4. Certain drugs which inhibit this metabolic pathway can raise the plasma levels of simvastatin and may increase the risk of myopathy. These include itraconazole, ketoconazole, posaconazole, voriconazole, the macrolide antibiotics erythromycin and clarithromycin, and the ketolide antibiotic telithromycin, HIV protease inhibitors, boceprevir, telaprevir, the antidepressant nefazodone, or grapefruit juice. Combination of these drugs with simvastatin is contraindicated. If short-term treatment with strong CYP3A4 inhibitors is unavoidable, therapy with simvastatin must be suspended during the course of treatment.
The combined use of simvastatin with gemfibrozil, cyclosporine, or danazol is contraindicated.
Caution should be used when prescribing other fibrates with simvastatin, as these agents can cause myopathy when given alone and the risk is increased when they are co-administered.
Cases of myopathy, including rhabdomyolysis, have been reported with simvastatin coadministered with colchicine, and caution should be exercised when prescribing simvastatin with colchicine.
The benefits of the combined use of simvastatin with the following drugs should be carefully weighed against the potential risks of combinations: other lipid-lowering drugs (other fibrates, ≥1 g/day of niacin, or, for patients with HoFH, lomitapide), amiodarone, dronedarone, verapamil, diltiazem, amlodipine, or ranolazine.
Cases of myopathy, including rhabdomyolysis, have been observed with simvastatin coadministered with lipid-modifying doses (≥1 g/day niacin) of niacin-containing products. In an ongoing, double-blind, randomized cardiovascular outcomes trial, an independent safety monitoring committee identified that the incidence of myopathy is higher in Chinese compared with non-Chinese patients taking simvastatin 40 mg coadministered with lipid-modifying doses of a niacin-containing product. Caution should be used when treating Chinese patients with simvastatin in doses exceeding 20 mg/day coadministered with lipid-modifying doses of niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive simvastatin 80 mg coadministered with lipid-modifying doses of niacin-containing products. It is unknown if the risk for myopathy with coadministration of simvastatin with lipid-modifying doses of niacin-containing products observed in Chinese patients applies to other Asian patients.
Prescribing recommendations for interacting agents are summarized in the table below.
Persistent increases (to more than 3X the ULN) in serum transaminases have occurred in approximately 1% of patients who received simvastatin in clinical studies. When drug treatment was interrupted or discontinued in these patients, the transaminase levels usually fell slowly to pretreatment levels. The increases were not associated with jaundice or other clinical signs or symptoms. There was no evidence of hypersensitivity.
In the Scandinavian Simvastatin Survival Study (4S), the number of patients with more than one transaminase elevation to >3X ULN, over the course of the study, was not significantly different between the simvastatin and placebo groups (14 vs. 12 ). Elevated transaminases resulted in the discontinuation of 8 patients from therapy in the simvastatin group (n=2,221) and 5 in the placebo group (n=2,223). Of the 1,986 simvastatin treated patients in 4S with normal liver function tests (LFTs) at baseline, 8 (0.4%) developed consecutive LFT elevations to >3X ULN and/or were discontinued due to transaminase elevations during the 5.4 years (median follow-up) of the study. Among these 8 patients, 5 initially developed these abnormalities within the first year. All of the patients in this study received a starting dose of 20 mg of simvastatin; 37% were titrated to 40 mg.
In 2 controlled clinical studies in 1,105 patients, the 12-month incidence of persistent hepatic transaminase elevation without regard to drug relationship was 0.9% and 2.1% at the 40- and 80-mg dose, respectively. No patients developed persistent liver function abnormalities following the initial 6 months of treatment at a given dose.
It is recommended that liver function tests be performed before the initiation of treatment, and thereafter when clinically indicated. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including simvastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with simvastatin, promptly interrupt therapy. If an alternate etiology is not found do not restart simvastatin. Note that ALT may emanate from muscle, therefore ALT rising with CK may indicate myopathy.
The drug should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease. Active liver diseases or unexplained transaminase elevations are contraindications to the use of simvastatin.
As with other lipid-lowering agents, moderate (less than 3X ULN) elevations of serum transaminases have been reported following therapy with simvastatin. These changes appeared soon after initiation of therapy with simvastatin, were often transient, were not accompanied by any symptoms and did not require interruption of treatment.
Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including simvastatin.
# Adverse Reactions
## Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
In the pre-marketing controlled clinical studies and their open extensions (2,423 patients with median duration of follow-up of approximately 18 months), 1.4% of patients were discontinued due to adverse reactions. The most common adverse reactions that led to treatment discontinuation were: gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia(0.1%). The most commonly reported adverse reactions (incidence ≥5%) in simvastatin controlled clinical trials were: upper respiratory infections (9.0%), headache (7.4%), abdominal pain (7.3%), constipation (6.6%), and nausea (5.4%).
Scandinavian Simvastatin Survival Study
In 4S involving 4,444 (age range 35-71 years, 19% women, 100% Caucasians) treated with 20-40 mg/day of simvastatin (n=2,221) or placebo (n=2,223) over a median of 5.4 years, adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 2.
Heart Protection Study
In the Heart Protection Study (HPS), involving 20,536 patients (age range 40-80 years, 25% women, 97% Caucasians, 3% other races) treated with simvastatin 40 mg/day (n=10,269) or placebo (n=10,267) over a mean of 5 years, only serious adverse reactions and discontinuations due to any adverse reactions were recorded. Discontinuation rates due to adverse reactions were 4.8% in patients treated with simvastatin compared with 5.1% in patients treated with placebo. The incidence of myopathy/rhabdomyolysis was <0.1% in patients treated with simvastatin.
Other Clinical Studies
In a clinical trial in which 12,064 patients with a history of myocardial infarction were treated with simvastatin (mean follow-up 6.7 years), the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum creatine kinase >10 times upper limit of normal ) in patients on 80 mg/day was approximately 0.9% compared with 0.02% for patients on 20 mg/day. The incidence of rhabdomyolysis (defined as myopathy with a CK >40 times ULN) in patients on 80 mg/day was approximately 0.4% compared with 0% for patients on 20 mg/day. The incidence of myopathy, including rhabdomyolysis, was highest during the first year and then notably decreased during the subsequent years of treatment. In this trial, patients were carefully monitored and some interacting medicinal products were excluded.
Other adverse reactions reported in clinical trials were: diarrhea, rash, dyspepsia, flatulence, and asthenia.
Laboratory Tests
Marked persistent increases of hepatic transaminases have been noted. Elevated alkaline phosphatase and γ-glutamyl transpeptidase have also been reported. About 5% of patients had elevations of CK levels of 3 or more times the normal value on one or more occasions. This was attributable to the noncardiac fraction of CK.
Adolescent Patients (ages 10-17 years)
In a 48-week, controlled study in adolescent boys and girls who were at least 1 year post-menarche, 10-17 years of age (43.4% female, 97.7% Caucasians, 1.7% Hispanics, 0.6% Multiracial) with heterozygous familial hypercholesterolemia (n=175), treated with placebo or simvastatin(10-40 mg daily), the most common adverse reactions observed in both groups were upper respiratory infection, headache, abdominal pain, and nausea.
## Postmarketing Experience
Because the below reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following additional adverse reactions have been identified during postapproval use of simvastatin: pruritus, alopecia, a variety of skin changes (e.g., nodules, discoloration, dryness of skin/mucous membranes, changes to hair/nails), dizziness, muscle cramps, myalgia, pancreatitis, paresthesia, peripheral neuropathy, vomiting, anemia, erectile dysfunction, interstitial lung disease, rhabdomyolysis, hepatitis/jaundice, fatal and non-fatal hepatic failure, and depression.
There have been rare reports of immune-mediated necrotizing myopathy associated with statin use .
An apparent hypersensitivity syndrome has been reported rarely which has included some of the following features: anaphylaxis, angioedema, lupus erythematous-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, chills, flushing, malaise, dyspnea, toxic epidermal necrolysis, erythema multiforme, including Stevens-Johnson syndrome.
There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).
# Drug Interactions
Strong CYP3A4 inhibitors: Simvastatin, like several other inhibitors of HMG-CoA reductase, is a substrate of CYP3A4. Simvastatin is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4.
Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated . If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.
Cyclosporine or Danazol: The risk of myopathy, including rhabdomyolysis is increased by concomitant administration of cyclosporine or danazol. Therefore, concomitant use of these drugs is contraindicated.
- Gemfibrozil: Contraindicated with simvastatin.
- Other fibrates: Caution should be used when prescribing with simvastatin.
The risk of myopathy, including rhabdomyolysis, is increased by concomitant administration of amiodarone, dronedarone, ranolazine, or calcium channel blockers such as verapamil, diltiazem, or amlodipine.
Cases of myopathy/rhabdomyolysis have been observed with simvastatin coadministered with lipid-modifying doses (≥1 g/day Niacin) of Niacin-containing products. In particular, caution should be used when treating Chinese patients with simvastatin doses exceeding 20 mg/day coadministered with lipid-modifying doses of Niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive simvastatin 80 mg coadministered with lipid-modifying doses of Niacin-containing products.
## Digoxin
In one study, concomitant administration of digoxin with simvastatin resulted in a slight elevation in digoxin concentrations in plasma. Patients taking digoxin should be monitored appropriately when simvastatin is initiated.
## Coumarin Anticoagulants
In two clinical studies, one in normal volunteers and the other in hypercholesterolemic patients, simvastatin 20-40 mg/day modestly potentiated the effect of coumarin anticoagulants: the prothrombin time, reported as International Normalized Ratio (INR), increased from a baseline of 1.7 to 1.8 and from 2.6 to 3.4 in the volunteer and patient studies, respectively. With other statins, clinically evident bleeding and/or increased prothrombin time has been reported in a few patients taking coumarin anticoagulants concomitantly. In such patients, prothrombin time should be determined before starting simvastatin and frequently enough during early therapy to ensure that no significant alteration of prothrombin time occurs. Once a stable prothrombin time has been documented, prothrombin times can be monitored at the intervals usually recommended for patients on coumarin anticoagulants. If the dose of simvastatin is changed or discontinued, the same procedure should be repeated. Simvastatin therapy has not been associated with bleeding or with changes in prothrombin time in patients not taking anticoagulants.
## Colchicine
Cases of myopathy, including rhabdomyolysis, have been reported with simvastatin coadministered with colchicine, and caution should be exercised when prescribing simvastatin with colchicine.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): X
simvastatin is contraindicated in women who are or may become pregnant. Lipid lowering drugs offer no benefit during pregnancy, because cholesterol and cholesterol derivatives are needed for normal fetal development. Atherosclerosis is a chronic process, and discontinuation of lipid-lowering drugs during pregnancy should have little impact on long-term outcomes of primary hypercholesterolemia therapy. There are no adequate and well-controlled studies of use with simvastatin during pregnancy; however, there are rare reports of congenital anomalies in infants exposed to statins in utero. Animal reproduction studies of simvastatin in rats and rabbits showed no evidence of teratogenicity. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Because statins decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, simvastatin may cause fetal harm when administered to a pregnant woman. If simvastatin is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
There are rare reports of congenital anomalies following intrauterine exposure to statins. In a review3 of approximately 100 prospectively followed pregnancies in women exposed to simvastatin or another structurally related statin, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed those expected in the general population. However, the study was only able to exclude a 3- to 4-fold increased risk of congenital anomalies over the background rate. In 89% of these cases, drug treatment was initiated prior to pregnancy and was discontinued during the first trimester when pregnancy was identified.
Simvastatin was not teratogenic in rats or rabbits at doses (25, 10 mg/kg/day, respectively) that resulted in 3 times the human exposure based on mg/m2 surface area. However, in studies with another structurally-related statin, skeletal malformations were observed in rats and mice.
Women of childbearing potential, who require treatment with simvastatin for a lipid disorder, should be advised to use effective contraception. For women trying to conceive, discontinuation of simvastatin should be considered. If pregnancy occurs, simvastatin should be immediately discontinued.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Simvastatin in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Simvastatin during labor and delivery.
### Nursing Mothers
It is not known whether simvastatin is excreted in human milk. Because a small amount of another drug in this class is excreted in human milk and because of the potential for serious adverse reactions in nursing infants, women taking simvastatin should not nurse their infants. A decision should be made whether to discontinue nursing or discontinue drug, taking into account the importance of the drug to the mother
### Pediatric Use
Safety and effectiveness of simvastatin in patients 10-17 years of age with heterozygous familial hypercholesterolemia have been evaluated in a controlled clinical trial in adolescent boys and in girls who were at least 1 year post-menarche. Patients treated with simvastatin had an adverse reaction profile similar to that of patients treated with placebo. Doses greater than 40 mg have not been studied in this population. In this limited controlled study, there was no significant effect on growth or sexual maturation in the adolescent boys or girls, or on menstrual cycle length in girls. Adolescent females should be counseled on appropriate contraceptive methods while on simvastatin therapy. Simvastatin has not been studied in patients younger than 10 years of age, nor in pre-menarchal girls.
### Geriatic Use
Of the 2,423 patients who received simvastatin in Phase III clinical studies and the 10,269 patients in the Heart Protection Study who received simvastatin, 363 (15%) and 5,366 (52%), respectively were ≥65 years old. In HPS, 615 (6%) were ≥75 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Since advanced age (≥65 years) is a predisposing factor for myopathy, simvastatin should be prescribed with caution in the elderly.
A pharmacokinetic study with simvastatin showed the mean plasma level of statin activity to be approximately 45% higher in elderly patients between 70-78 years of age compared with patients between 18-30 years of age. In 4S, 1,021 (23%) of 4,444 patients were 65 or older. Lipid-lowering efficacy was at least as great in elderly patients compared with younger patients, and simvastatin significantly reduced total mortality and CHD mortality in elderly patients with a history of CHD. In HPS, 52% of patients were elderly (4,891 patients 65-69 years and 5,806 patients 70 years or older). he relative risk reductions of CHD death, non-fatal MI, coronary and non-coronary revascularization procedures, and stroke were similar in older and younger patients. In HPS, among 32,145 patients entering the active run-in period, there were 2 cases of myopathy/rhabdomyolysis; these patients were aged 67 and 73. Of the 7 cases of myopathy/rhabdomyolysis among 10,269 patients allocated to simvastatin, 4 were aged 65 or more (at baseline), of whom one was over 75. There were no overall differences in safety between older and younger patients in either 4S or HPS.
Because advanced age (≥65 years) is a predisposing factor for myopathy, including rhabdomyolysis, simvastatin should be prescribed with caution in the elderly. In a clinical trial of patients treated with simvastatin 80 mg/day, patients ≥65 years of age had an increased risk of myopathy, including rhabdomyolysis, compared to patients <65 years of age.
### Gender
There is no FDA guidance on the use of Simvastatin with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Simvastatin with respect to specific racial populations.
### Renal Impairment
Caution should be exercised when simvastatin is administered to patients with severe renal impairment
### Hepatic Impairment
Simvastatin is contraindicated in patients with active liver disease which may include unexplained persistent elevations in hepatic transaminase levels
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Simvastatin in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Simvastatin in patients who are immunocompromised.
# Administration and Monitoring
### Administration
Oral
### Monitoring
There is limited information regarding motoring of Simvastatin in the drug label.
# IV Compatibility
There is limited information regarding the compatibility of Simvastatin and IV administrations.
# Overdosage
Significant lethality was observed in mice after a single oral dose of 9 g/m2. No evidence of lethality was observed in rats or dogs treated with doses of 30 and 100 g/m2, respectively. No specific diagnostic signs were observed in rodents. At these doses the only signs seen in dogs were emesis and mucoid stools.
A few cases of overdosage with simvastatinhave been reported; the maximum dose taken was 3.6 g. All patients recovered without sequelae. Supportive measures should be taken in the event of an overdose. The dialyzability of simvastatin and its metabolites in man is not known at present
# Pharmacology
## Mechanism of Action
Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin is a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting step in the biosynthetic pathway for cholesterol. In addition, simvastatin reduces VLDL and TG and increases HDL-C.
## Structure
Simvastatin is a lipid-lowering agent that is derived synthetically from a fermentation product of Aspergillus terreus. After oral ingestion, simvastatin, which is an inactive lactone, is hydrolyzed to the corresponding β-hydroxyacid form. This is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate-limiting step in the biosynthesis of cholesterol.
Simvastatin is butanoic acid, 2,2-dimethyl-,1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8--1-naphthalenyl ester, ]. The empirical formula of simvastatin is C25H38O5 and its molecular weight is 418.57. Its structural formula is:
Simvastatin is a white to off-white, nonhygroscopic, crystalline powder that is practically insoluble in water, and freely soluble in chloroform, methanol and ethanol.
Simvastatin talets for oral administration contain either 5 mg, 10 mg, 20 mg, 40 mg or 80 mg of simvastatin and the following inactive ingredients: ascorbic acid, citric acid, hydroxypropyl cellulose, hypromellose, iron oxides, lactose, magnesium stearate, microcrystalline cellulose, starch, talc, and titanium dioxide. Butylated hydroxyanisole is added as a preservative.
## Pharmacodynamics
Epidemiological studies have demonstrated that elevated levels of total-C, LDL-C, as well as decreased levels of HDL-C are associated with the development of atherosclerosis and increased cardiovascular risk. Lowering LDL-C decreases this risk. However, the independent effect of raising HDL-C or lowering TG on the risk of coronary and cardiovascular morbidity and mortality has not been determined.
## Pharmacokinetics
Simvastatin is a lactone that is readily hydrolyzed in vivo to the corresponding β-hydroxyacid, a potent inhibitor of HMG-CoA reductase. Inhibition of HMG-CoA reductase is the basis for an assay in pharmacokinetic studies of the β-hydroxyacid metabolites (active inhibitors) and, following base hydrolysis, active plus latent inhibitors (total inhibitors) in plasma following administration of simvastatin.
Following an oral dose of 14C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces. Plasma concentrations of total radioactivity (simvastatin plus 14C-metabolites) peaked at 4 hours and declined rapidly to about 10% of peak by 12 hours postdose. Since simvastatin undergoes extensive first-pass extraction in the liver, the availability of the drug to the general circulation is low (<5%).
Both simvastatin and its β-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins. Rat studies indicate that when radiolabeled simvastatin was administered, simvastatin-derived radioactivity crossed the blood-brain barrier.
The major active metabolites of simvastatin present in human plasma are the β-hydroxyacid of simvastatin and its 6′-hydroxy, 6′-hydroxymethyl, and 6′-exomethylene derivatives. Peak plasma concentrations of both active and total inhibitors were attained within 1.3 to 2.4 hours postdose. While the recommended therapeutic dose range is 5 to 40 mg/day, there was no substantial deviation from linearity of AUC of inhibitors in the general circulation with an increase in dose to as high as 120 mg. Relative to the fasting state, the plasma profile of inhibitors was not affected when simvastatin was administered immediately before an American Heart Association recommended low-fat meal.
In a study including 16 elderly patients between 70 and 78 years of age who received simvastatin 40 mg/day, the mean plasma level of HMG-CoA reductase inhibitory activity was increased approximately 45% compared with 18 patients between 18-30 years of age. Clinical study experience in the elderly (n=1522), suggests that there were no overall differences in safety between elderly and younger patients .
Kinetic studies with another statin, having a similar principal route of elimination, have suggested that for a given dose level higher systemic exposure may be achieved in patients with severe renal insufficiency (as measured by creatinine clearance).
Although the mechanism is not fully understood, cyclosporine has been shown to increase the AUC of statins. The increase in AUC for simvastatin acid is presumably due, in part, to inhibition of CYP3A4.
The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. Inhibitors of CYP3A4 can raise the plasma levels of HMG-CoA reductase inhibitory activity and increase the risk of myopathy.
In a study of 12 healthy volunteers, simvastatin at the 80-mg dose had no effect on the metabolism of the probe cytochrome P450 isoform 3A4 (CYP3A4) substrates midazolam and erythromycin. This indicates that simvastatin is not an inhibitor of CYP3A4, and, therefore, is not expected to affect the plasma levels of other drugs metabolized by CYP3A4.
Coadministration of simvastatin (40 mg QD for 10 days) resulted in an increase in the maximum mean levels of cardioactive digoxin (given as a single 0.4 mg dose on day 10) by approximately 0.3 ng/mL.
## Nonclinical Toxicology
In a 72-week carcinogenicity study, mice were administered daily doses of simvastatin of 25, 100, and 400 mg/kg body weight, which resulted in mean plasma drug levels approximately 1, 4, and 8 times higher than the mean human plasma drug level, respectively (as total inhibitory activity based on AUC) after an 80-mg oral dose. Liver carcinomas were significantly increased in high-dose females and mid- and high-dose males with a maximum incidence of 90% in males. The incidence of adenomas of the liver was significantly increased in mid- and high-dose females. Drug treatment also significantly increased the incidence of lung adenomas in mid- and high-dose males and females. Adenomas of the Harderian gland (a gland of the eye of rodents) were significantly higher in high-dose mice than in controls. No evidence of a tumorigenic effect was observed at 25 mg/kg/day.
In a separate 92-week carcinogenicity study in mice at doses up to 25 mg/kg/day, no evidence of a tumorigenic effect was observed (mean plasma drug levels were 1 times higher than humans given 80 mg simvastatin as measured by AUC).
In a two-year study in rats at 25 mg/kg/day, there was a statistically significant increase in the incidence of thyroid follicular adenomas in female rats exposed to approximately 11 times higher levels of simvastatin than in humans given 80 mg simvastatin (as measured by AUC).
A second two-year rat carcinogenicity study with doses of 50 and 100 mg/kg/day produced hepatocellular adenomas and carcinomas (in female rats at both doses and in males at 100 mg/kg/day). Thyroid follicular cell adenomas were increased in males and females at both doses; thyroid follicular cell carcinomas were increased in females at 100 mg/kg/day. The increased incidence of thyroid neoplasms appears to be consistent with findings from other statins. These treatment levels represented plasma drug levels (AUC) of approximately 7 and 15 times (males) and 22 and 25 times (females) the mean human plasma drug exposure after an 80 milligram daily dose.
No evidence of mutagenicity was observed in a microbial mutagenicity (Ames) test with or without rat or mouse liver metabolic activation. In addition, no evidence of damage to genetic material was noted in an in vitro alkaline elution assay using rat hepatocytes, a V-79 mammalian cell forward mutation study, an in vitro chromosome aberration study in CHO cells, or an in vivo chromosomal aberration assay in mouse bone marrow.
There was decreased fertility in male rats treated with simvastatin for 34 weeks at 25 mg/kg body weight (4 times the maximum human exposure level, based on AUC, in patients receiving 80 mg/day); however, this effect was not observed during a subsequent fertility study in which simvastatin was administered at this same dose level to male rats for 11 weeks (the entire cycle of spermatogenesis including epididymal maturation). No microscopic changes were observed in the testes of rats from either study. At 180 mg/kg/day, (which produces exposure levels 22 times higher than those in humans taking 80 mg/day based on surface area, mg/m2), seminiferous tubule degeneration (necrosis and loss of spermatogenic epithelium) was observed. In dogs, there was drug-related testicular atrophy, decreased spermatogenesis, spermatocytic degeneration and giant cell formation at 10 mg/kg/day, (approximately 2 times the human exposure, based on AUC, at 80 mg/day). The clinical significance of these findings is unclear.
CNS Toxicity
Optic nerve degeneration was seen in clinically normal dogs treated with simvastatin for 14 weeks at 180 mg/kg/day, a dose that produced mean plasma drug levels about 12 times higher than the mean plasma drug level in humans taking 80 mg/day.
A chemically similar drug in this class also produced optic nerve degeneration (Wallerian degeneration of retinogeniculate fibers) in clinically normal dogs in a dose-dependent fashion starting at 60 mg/kg/day, a dose that produced mean plasma drug levels about 30 times higher than the mean plasma drug level in humans taking the highest recommended dose (as measured by total enzyme inhibitory activity). This same drug also produced vestibulocochlear Wallerian-like degeneration and retinal ganglion cell chromatolysis in dogs treated for 14 weeks at 180 mg/kg/day, a dose that resulted in a mean plasma drug level similar to that seen with the 60 mg/kg/day dose.
CNS vascular lesions, characterized by perivascular hemorrhage and edema, mononuclear cell infiltration of perivascular spaces, perivascular fibrin deposits and necrosis of small vessels were seen in dogs treated with simvastatin at a dose of 360 mg/kg/day, a dose that produced mean plasma drug levels that were about 14 times higher than the mean plasma drug levels in humans taking 80 mg/day. Similar CNS vascular lesions have been observed with several other drugs of this class.
There were cataracts in female rats after two years of treatment with 50 and 100 mg/kg/day (22 and 25 times the human AUC at 80 mg/day, respectively) and in dogs after three months at 90 mg/kg/day (19 times) and at two years at 50 mg/kg/day (5 times).
# Clinical Studies
Reductions in Risk of CHD Mortality and Cardiovascular Events
In 4S, the effect of therapy with simvastatin on total mortality was assessed in 4,444 patients with CHD and baseline total cholesterol 212-309 mg/dL (5.5-8.0 mmol/L). In this multicenter, randomized, double-blind, placebo-controlled study, patients were treated with standard care, including diet, and either simvastatin 20-40 mg/day (n=2,221) or placebo (n=2,223) for a median duration of 5.4 years. Over the course of the study, treatment with simvastatin led to mean reductions in total-C, LDL-C and TG of 25%, 35%, and 10%, respectively, and a mean increase in HDL-C of 8%. simvastatin significantly reduced the risk of mortality by 30% (p=0.0003, 182 deaths in the simvastatin group vs 256 deaths in the placebo group). The risk of CHD mortality was significantly reduced by 42% (p=0.00001, 111 vs 189 deaths). There was no statistically significant difference between groups in non-cardiovascular mortality. simvastatin significantly decreased the risk of having major coronary events (CHD mortality plus hospital-verified and silent non-fatal myocardial infarction MI) by 34% (p<0.00001, 431 vs 622 patients with one or more events). The risk of having a hospital-verified non-fatal MI was reduced by 37%. simvastatin significantly reduced the risk for undergoing myocardial revascularization procedures (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) by 37% (p<0.00001, 252 vs 383 patients). simvastatin significantly reduced the risk of fatal plus non-fatal cerebrovascular events (combined stroke and transient ischemic attacks) by 28% (p=0.033, 75 vs 102 patients). simvastatin reduced the risk of major coronary events to a similar extent across the range of baseline total and LDL cholesterol levels. Because there were only 53 female deaths, the effect of simvastatin on mortality in women could not be adequately assessed. However, simvastatin significantly lessened the risk of having major coronary events by 34% (60 vs 91 women with one or more event). The randomization was stratified by angina alone (21% of each treatment group) or a previous MI. Because there were only 57 deaths among the patients with angina alone at baseline, the effect of simvastatin on mortality in this subgroup could not be adequately assessed. However, trends in reduced coronary mortality, major coronary events and revascularization procedures were consistent between this group and the total study cohort. Additionally, simvastatin resulted in similar decreases in relative risk for total mortality, CHD mortality, and major coronary events in elderly patients (≥65 years), compared with younger patients.
The Heart Protection Study (HPS) was a large, multi-center, placebo-controlled, double-blind study with a mean duration of 5 years conducted in 20,536 patients (10,269 on simvastatin 40 mg and 10,267 on placebo). Patients were allocated to treatment using a covariate adaptive method which took into account the distribution of 10 important baseline characteristics of patients already enrolled and minimized the imbalance of those characteristics across the groups. Patients had a mean age of 64 years (range 40-80 years), were 97% caucasian and were at high risk of developing a major coronary event because of existing CHD (65%), diabetes (Type 2, 26%; Type 1, 3%), history of stroke or other cerebrovascular disease (16%), peripheral vessel disease (33%), or hypertension in males ≥65 years (6%). At baseline, 3,421 patients (17%) had LDL-C levels below 100 mg/dL, of whom 953 (5%) had LDL-C levels below 80 mg/dL; 7,068 patients (34%) had levels between 100 and 130 mg/dL; and 10,047 patients (49%) had levels greater than 130 mg/dL.
The HPS results showed that simvastatin 40 mg/day significantly reduced: total and CHD mortality; non-fatal MI, stroke, and revascularization procedures (coronary and non-coronary), see table below.
Two composite endpoints were defined in order to have sufficient events to assess relative risk reductions across a range of baseline characteristics, see Figure 1. A composite of major coronary events (MCE) was comprised of CHD mortality and non-fatal MI (analyzed by time-to-first event; 898 patients treated with simvastatin had events and 1,212 patients on placebo had events). A composite of major vascular events (MVE) was comprised of MCE, stroke and revascularization procedures including coronary, peripheral and other non-coronary procedures (analyzed by time-to-first event; 2,033 patients treated with simvastatin had events and 2,585 patients on placebo had events). Significant relative risk reductions were observed for both composite endpoints (27% for MCE and 24% for MVE, p<0.0001). Treatment with simvastatin produced significant relative risk reductions for all components of the composite endpoints. The risk reductions produced by simvastatin in both MCE and MVE were evident and consistent regardless of cardiovascular disease related medical history at study entry (i.e., CHD alone; or peripheral vascular disease, cerebrovascular disease, diabetes or treated hypertension, with or without CHD), gender, age, creatinine levels up to the entry limit of 2.3 mg/dL, baseline levels of LDL-C, HDL-C, apolipoprotein B and A-1, baseline concomitant cardiovascular medications (i.e., aspirin, beta blockers, or calcium channel blockers), smoking status, alcohol intake, or obesity. Diabetics showed risk reductions for MCE and MVE due to simvastatin treatment regardless of baseline HbA1c levels or obesity with the greatest effects seen for diabetics without CHD.
Angiographic Studies
In the Multicenter Anti-Atheroma Study, the effect of simvastatin on atherosclerosis was assessed by quantitative coronary angiography in hypercholesterolemic patients with CHD. In this randomized, double-blind, controlled study, patients were treated with simvastatin 20 mg/day or placebo. Angiograms were evaluated at baseline, two and four years. The co-primary study endpoints were mean change per-patient in minimum and mean lumen diameters, indicating focal and diffuse disease, respectively. Simvastatin significantly slowed the progression of lesions as measured in the Year 4 angiogram by both parameters, as well as by change in percent diameter stenosis. In addition, simvastatin significantly decreased the proportion of patients with new lesions and with new total occlusions.
Modifications of Lipid Profiles
- Primary Hyperlipidemia (Fredrickson type lla and llb)
- Simvastatin has been shown to be effective in reducing total-C and LDL-C in heterozygous familial and non-familial forms of hyperlipidemia and in mixed hyperlipidemia. Maximal to near maximal response is generally achieved within 4-6 weeks and maintained during chronic therapy. Simvastatin consistently and significantly decreased total-C, LDL-C, total-C/HDL-C ratio, and LDL-C/HDL-C ratio; simvastatin also decreased TG and increased HDL-C, see table below.
- Hypertriglyceridemia (Fredrickson type IV)
- The results of a subgroup analysis in 74 patients with type lV hyperlipidemia from a 130-patient, double-blind, placebo-controlled, 3-period crossover study are presented in the table below.
- Dysbetalipoproteinemia (Fredrickson type lll)
- The results of a subgroup analysis in 7 patients with type lll hyperlipidemia (dysbetalipoproteinemia) (apo E2/2) (VLDL-C/TG>0.25) from a 130-patient, double-blind, placebo-controlled, 3-period crossover study are presented the table below.
- Homozygous Familial Hypercholesterolemia
- In a controlled clinical study, 12 patients 15-39 years of age with homozygous familial hypercholesterolemia received simvastatin 40 mg/day in a single dose or in 3 divided doses, or 80 mg/day in 3 divided doses. In 11 patients with reductions in LDL-C, the mean LDL-C changes for the 40- and 80-mg doses were 14% (range 8% to 23%, median 12%) and 30% (range 14% to 46%, median 29%), respectively. One patient had an increase of 15% in LDL-C. Another patient with absent LDL-C receptor function had an LDL-C reduction of 41% with the 80-mg dose.
- Endocrine Function
- In clinical studies, simvastatin did not impair adrenal reserve or significantly reduce basal plasma cortisol concentration. Small reductions from baseline in basal plasma testosterone in men were observed in clinical studies with simvastatin, an effect also observed with other statins and the bile acid sequestrant cholestyramine. There was no effect on plasma gonadotropin levels. In a placebo-controlled, 12-week study there was no significant effect of simvastatin 80 mg on the plasma testosterone response to human chorionic gonadotropin. In another 24-week study, simvastatin 20-40 mg had no detectable effect on spermatogenesis. In 4S, in which 4,444 patients were randomized to simvastatin 20-40 mg/day or placebo for a median duration of 5.4 years, the incidence of male sexual adverse events in the two treatment groups was not significantly different. Because of these factors, the small changes in plasma testosterone are unlikely to be clinically significant. The effects, if any, on the pituitary-gonadalaxis in pre-menopausal women are unknown.
In a double-blind, placebo-controlled study, 175 patients (99 adolescent boys and 76 post-menarchal girls) 10-17 years of age (mean age 14.1 years) with heterozygous familial hypercholesterolemia (HeFH) were randomized to simvastatin (n=106) or placebo (n=67) for 24 weeks (base study). Inclusion in the study required a baseline LDL-C level between 160 and 400 mg/dL and at least one parent with an LDL-C level >189 mg/dL. The dosage of simvastatin (once daily in the evening) was 10 mg for the first 8 weeks, 20 mg for the second 8 weeks, and 40 mg thereafter. In a 24-week extension, 144 patients elected to continue therapy with simvastatin 40 mg or placebo.
Simvastatin significantly decreased plasma levels of total-C, LDL-C, and Apo B see table below. Results from the extension at 48 weeks were comparable to those observed in the base study.
After 24 weeks of treatment, the mean achieved LDL-C value was 124.9 mg/dL (range: 64.0-289.0 mg/dL) in the simvastatin 40 mg group compared to 207.8 mg/dL (range: 128.0-334.0 mg/dL) in the placebo group.
The safety and efficacy of doses above 40 mg daily have not been studied in children with HeFH. The long-term efficacy of simvastatin therapy in childhood to reduce morbidity and mortality in adulthood has not been established.
# How Supplied
No. 8360 — Tablets ZOCOR 5 mg are buff, oval, film-coated tablets, coded MSD 726 on one side and ZOCOR 5 on the other. They are supplied as follows:
NDC 0006-0726-31 unit of use bottles of 30.
No. 8146 — Tablets ZOCOR 10 mg are peach, oval, film-coated tablets, coded MSD 735 on one side and plain on the other. They are supplied as follows:
NDC 0006-0735-31 unit of use bottles of 30
NDC 0006-0735-54 unit of use bottles of 90.
No. 8147 — Tablets ZOCOR 20 mg are tan, oval, film-coated tablets, coded MSD 740 on one side and plain on the other. They are supplied as follows:
NDC 0006-0740-31 unit of use bottles of 30
NDC 0006-0740-54 unit of use bottles of 90.
No. 8148 — Tablets ZOCOR 40 mg are brick red, oval, film-coated tablets, coded MSD 749 on one side and plain on the other. They are supplied as follows:
NDC 0006-0749-31 unit of use bottles of 30
NDC 0006-0749-54 unit of use bottles of 90.
No. 6577 — Tablets ZOCOR 80 mg are brick red, capsule-shaped, film-coated tablets, coded 543 on one side and 80 on the other. They are supplied as follows:
NDC 0006-0543-31 unit of use bottles of 30
NDC 0006-0543-54 unit of use bottles of 90.
## Storage
Store between 5-30°C (41-86°F).
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
Patients should be advised to adhere to their National Cholesterol Education Program (NCEP)-recommended diet, a regular exercise program, and periodic testing of a fasting lipid panel.
Patients should be advised about substances they should not take concomitantly with simvastatin. Patients should also be advised to inform other healthcare professionals prescribing a new medication or increasing the dose of an existing medication that they are taking simvastatin.
All patients starting therapy with simvastatin should be advised of the risk of myopathy, including rhabdomyolysis, and told to report promptly any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever or if these muscle signs or symptoms persist after discontinuing simvastatin. Patients using the 80-mg dose should be informed that the risk of myopathy, including rhabdomyolysis, is increased with use of the 80-mg dose. The risk of myopathy, including rhabdomyolysis, occurring with use of simvastatin is increased when taking certain types of medication or consuming grapefruit juice. Patients should discuss all medication, both prescription and over the counter, with their healthcare professional.
It is recommended that liver function tests be performed before the initiation of simvastatin, and thereafter when clinically indicated. All patients treated with simvastatin should be advised to report promptly any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.
Women of childbearing age should be advised to use an effective method of birth control to prevent pregnancy while using simvastatin. Discuss future pregnancy plans with your patients, and discuss when to stop taking simvastatin if they are trying to conceive. Patients should be advised that if they become pregnant they should stop taking simvastatin and call their healthcare professional.
Women who are breastfeeding should not use simvastatin. Patients who have a lipid disorder and are breastfeeding should be advised to discuss the options with their healthcare professional.
# Precautions with Alcohol
Alcohol-Simvastatin detailed information interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Zocor
# Look-Alike Drug Names
- Zocor - Cozaar
- Zocor - ZyrTEC
# Drug Shortage Status
Drug Shortage
# Price | Simvastatin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alonso Alvarado, M.D. [2]
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# Overview
Simvastatin is a HMG-CoA Reductase Inhibitor that is FDA approved for the {{{indicationType}}} of reductions in risk of CHD mortality and cardiovascular events, hyperlipidemia, adolescent patients with heterozygous familial hypercholesterolemia (HeFH). Common adverse reactions include abdominal pain, constipation, nausea, headache, upper respiratory infection.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
The usual dosage range is 5 to 40 mg/day. In patients with CHD or at high risk of CHD, simvastatin can be started simultaneously with diet. The recommended usual starting dose is 10 or 20 mg once a day in the evening. For patients at high risk for a CHD event due to existing CHD, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, the recommended starting dose is 40 mg/day. Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter.
Due to the increased risk of myopathy, including rhabdomyolysis, particularly during the first year of treatment, use of the 80-mg dose of simvastatin should be restricted to patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity.
Patients who are currently tolerating the 80-mg dose of simvastatin who need to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin should be switched to an alternative statin with less potential for the drug-drug interaction.
Due to the increased risk of myopathy, including rhabdomyolysis, associated with the 80-mg dose of simvastatin, patients unable to achieve their LDL-C goal utilizing the 40-mg dose of simvastatin should not be titrated to the 80-mg dose, but should be placed on alternative LDL-C-lowering treatment(s) that provides greater LDL-C lowering.
Patients taking Verapamil, Diltiazem, or Dronedarone
The dose of simvastatin should not exceed 10 mg/day.
Patients taking Amiodarone, Amlodipine or Ranolazine
The dose of simvastatin should not exceed 20 mg/day.
The recommended dosage is 40 mg/day in the evening. simvastatin should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.
Simvastatin exposure is approximately doubled with concomitant use of lomitapide; therefore, the dose of simvastatin should be reduced by 50% if initiating lomitapide. simvastatin dosage should not exceed 20 mg/day (or 40 mg/day for patients who have previously taken simvastatin 80 mg/day chronically, e.g., for 12 months or more, without evidence of muscle toxicity) while taking lomitapide.
Because simvastatin does not undergo significant renal excretion, modification of dosage should not be necessary in patients with mild to moderate renal impairment. However, caution should be exercised when simvastatin is administered to patients with severe renal impairment; such patients should be started at 5 mg/day and be closely monitored.
Because of an increased risk for myopathy in Chinese patients taking simvastatin 40 mg coadministered with lipid-modifying doses (≥1 g/day niacin) of niacin-containing products, caution should be used when treating Chinese patients with simvastatin doses exceeding 20 mg/day coadministered with lipid-modifying doses of niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive simvastatin 80 mg coadministered with lipid-modifying doses of niacin-containing products. The cause of the increased risk of myopathy is not known. It is also unknown if the risk for myopathy with coadministration of simvastatin with lipid-modifying doses of niacin-containing products observed in Chinese patients applies to other Asian patients.[1]
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Simvastatin detailed information in adult patients.
### Non–Guideline-Supported Use
- Dosing Information
- 40 mg/day for 1 month followed by 80 mg/day thereafter
- Dosing Information
- 40 mg
- Dosing Information
- 10 to 20 mg/day
- Dosing Information
- 5 mg[2]
- Dosing information
- 80 mg/day[3]
- Dosing information
- 20 mg twice daily[4]
- Dosing information
- 80 mg/day[5]
- Dosing information
- 80 mg/day[5]
- Dosing information
- 20 mg daily[6]
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- Dosing Information
- The recommended usual starting dose is 10 mg once a day in the evening. The recommended dosing range is 10 to 40 mg/day; the maximum recommended dose is 40 mg/day. Doses should be individualized according to the recommended goal of therapy. Adjustments should be made at intervals of 4 weeks or more.[7]
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Simvastatin detailed information in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Simvastatin detailed information in pediatric patients.
# Contraindications
- Concomitant administration of strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin, nefazodone, and cobicistat-containing products).
- Concomitant administration of gemfibrozil, cyclosporine, or danazol.
- Hypersensitivity to any component of this medication.
- Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels.
- Women who are pregnant or may become pregnant
- Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Because HMG-CoA reductase inhibitors (statins) decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, simvastatin may cause fetal harm when administered to a pregnant woman. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. There are no adequate and well-controlled studies of use with simvastatin during pregnancy; however, in rare reports congenital anomalies were observed following intrauterine exposure to statins. In rat and rabbit animal reproduction studies, simvastatin revealed no evidence of teratogenicity. Simvastatin should be administered to women of childbearing age only when such patients are highly unlikely to conceive. If the patient becomes pregnant while taking this drug, simvastatin should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus.
- Nursing mothers
- It is not known whether simvastatin is excreted into human milk; however, a small amount of another drug in this class does pass into breast milk. Because statins have the potential for serious adverse reactions in nursing infants, women who require treatment with simvastatin should not breastfeed their infants.
# Warnings
Simvastatin occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of statin activity in plasma. Predisposing factors for myopathy include advanced age (≥65 years), female gender, uncontrolled hypothyroidism, and renal impairment.
The risk of myopathy, including rhabdomyolysis, is dose related. In a clinical trial database in which 41,413 patients were treated with simvastatin, 24,747 (approximately 60%) of whom were enrolled in studies with a median follow-up of at least 4 years, the incidence of myopathy was approximately 0.03% and 0.08% at 20 and 40 mg/day, respectively. The incidence of myopathy with 80 mg (0.61%) was disproportionately higher than that observed at the lower doses. In these trials, patients were carefully monitored and some interacting medicinal products were excluded.
In a clinical trial in which 12,064 patients with a history of myocardial infarction were treated with simvastatin (mean follow-up 6.7 years), the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum creatine kinase [CK] >10 times upper limit of normal [ULN]) in patients on 80 mg/day was approximately 0.9% compared with 0.02% for patients on 20 mg/day. The incidence of rhabdomyolysis (defined as myopathy with a CK >40 times ULN) in patients on 80 mg/day was approximately 0.4% compared with 0% for patients on 20 mg/day. The incidence of myopathy, including rhabdomyolysis, was highest during the first year and then notably decreased during the subsequent years of treatment. In this trial, patients were carefully monitored and some interacting medicinal products were excluded.
The risk of myopathy, including rhabdomyolysis, is greater in patients on simvastatin 80 mg compared with other statin therapies with similar or greater LDL-C-lowering efficacy and compared with lower doses of simvastatin. Therefore, the 80-mg dose of simvastatin should be used only in patients who have been taking simvastatin 80 mg chronically (e.g., for 12 months or more) without evidence of muscle toxicity. If, however, a patient who is currently tolerating the 80-mg dose of simvastatin needs to be initiated on an interacting drug that is contraindicated or is associated with a dose cap for simvastatin, that patient should be switched to an alternative statin with less potential for the drug-drug interaction. Patients should be advised of the increased risk of myopathy, including rhabdomyolysis, and to report promptly any unexplained muscle pain, tenderness or weakness. If symptoms occur, treatment should be discontinued immediately.
There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use. IMNM is characterized by: proximal muscle weakness and elevated serum creatine kinase, which persist despite discontinuation of statin treatment; muscle biopsy showing necrotizing myopathy without significant inflammation; improvement with immunosuppressive agents.
All patients starting therapy with simvastatin, or whose dose of simvastatin is being increased, should be advised of the risk of myopathy, including rhabdomyolysis, and told to report promptly any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever or if muscle signs and symptoms persist after discontinuing simvastatin. simvastatin therapy should be discontinued immediately if myopathy is diagnosed or suspected. In most cases, muscle symptoms and CK increases resolved when treatment was promptly discontinued. Periodic CK determinations may be considered in patients starting therapy with simvastatin or whose dose is being increased, but there is no assurance that such monitoring will prevent myopathy.
Many of the patients who have developed rhabdomyolysis on therapy with simvastatin have had complicated medical histories, including renal insufficiency usually as a consequence of long-standing diabetes mellitus. Such patients merit closer monitoring. simvastatin therapy should be discontinued if markedly elevated CPK levels occur or myopathy is diagnosed or suspected. simvastatin therapy should also be temporarily withheld in any patient experiencing an acute or serious condition predisposing to the development of renal failure secondary to rhabdomyolysis, e.g., sepsis; hypotension; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy.
Drug Interactions
The risk of myopathy and rhabdomyolysis is increased by high levels of statin activity in plasma. Simvastatin is metabolized by the cytochrome P450 isoform 3A4. Certain drugs which inhibit this metabolic pathway can raise the plasma levels of simvastatin and may increase the risk of myopathy. These include itraconazole, ketoconazole, posaconazole, voriconazole, the macrolide antibiotics erythromycin and clarithromycin, and the ketolide antibiotic telithromycin, HIV protease inhibitors, boceprevir, telaprevir, the antidepressant nefazodone, or grapefruit juice. Combination of these drugs with simvastatin is contraindicated. If short-term treatment with strong CYP3A4 inhibitors is unavoidable, therapy with simvastatin must be suspended during the course of treatment.
The combined use of simvastatin with gemfibrozil, cyclosporine, or danazol is contraindicated.
Caution should be used when prescribing other fibrates with simvastatin, as these agents can cause myopathy when given alone and the risk is increased when they are co-administered.
Cases of myopathy, including rhabdomyolysis, have been reported with simvastatin coadministered with colchicine, and caution should be exercised when prescribing simvastatin with colchicine.
The benefits of the combined use of simvastatin with the following drugs should be carefully weighed against the potential risks of combinations: other lipid-lowering drugs (other fibrates, ≥1 g/day of niacin, or, for patients with HoFH, lomitapide), amiodarone, dronedarone, verapamil, diltiazem, amlodipine, or ranolazine.
Cases of myopathy, including rhabdomyolysis, have been observed with simvastatin coadministered with lipid-modifying doses (≥1 g/day niacin) of niacin-containing products. In an ongoing, double-blind, randomized cardiovascular outcomes trial, an independent safety monitoring committee identified that the incidence of myopathy is higher in Chinese compared with non-Chinese patients taking simvastatin 40 mg coadministered with lipid-modifying doses of a niacin-containing product. Caution should be used when treating Chinese patients with simvastatin in doses exceeding 20 mg/day coadministered with lipid-modifying doses of niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive simvastatin 80 mg coadministered with lipid-modifying doses of niacin-containing products. It is unknown if the risk for myopathy with coadministration of simvastatin with lipid-modifying doses of niacin-containing products observed in Chinese patients applies to other Asian patients.
Prescribing recommendations for interacting agents are summarized in the table below.
Persistent increases (to more than 3X the ULN) in serum transaminases have occurred in approximately 1% of patients who received simvastatin in clinical studies. When drug treatment was interrupted or discontinued in these patients, the transaminase levels usually fell slowly to pretreatment levels. The increases were not associated with jaundice or other clinical signs or symptoms. There was no evidence of hypersensitivity.
In the Scandinavian Simvastatin Survival Study (4S), the number of patients with more than one transaminase elevation to >3X ULN, over the course of the study, was not significantly different between the simvastatin and placebo groups (14 [0.7%] vs. 12 [0.6%]). Elevated transaminases resulted in the discontinuation of 8 patients from therapy in the simvastatin group (n=2,221) and 5 in the placebo group (n=2,223). Of the 1,986 simvastatin treated patients in 4S with normal liver function tests (LFTs) at baseline, 8 (0.4%) developed consecutive LFT elevations to >3X ULN and/or were discontinued due to transaminase elevations during the 5.4 years (median follow-up) of the study. Among these 8 patients, 5 initially developed these abnormalities within the first year. All of the patients in this study received a starting dose of 20 mg of simvastatin; 37% were titrated to 40 mg.
In 2 controlled clinical studies in 1,105 patients, the 12-month incidence of persistent hepatic transaminase elevation without regard to drug relationship was 0.9% and 2.1% at the 40- and 80-mg dose, respectively. No patients developed persistent liver function abnormalities following the initial 6 months of treatment at a given dose.
It is recommended that liver function tests be performed before the initiation of treatment, and thereafter when clinically indicated. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including simvastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with simvastatin, promptly interrupt therapy. If an alternate etiology is not found do not restart simvastatin. Note that ALT may emanate from muscle, therefore ALT rising with CK may indicate myopathy.
The drug should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease. Active liver diseases or unexplained transaminase elevations are contraindications to the use of simvastatin.
As with other lipid-lowering agents, moderate (less than 3X ULN) elevations of serum transaminases have been reported following therapy with simvastatin. These changes appeared soon after initiation of therapy with simvastatin, were often transient, were not accompanied by any symptoms and did not require interruption of treatment.
Increases in HbA1c and fasting serum glucose levels have been reported with HMG-CoA reductase inhibitors, including simvastatin.[1]
# Adverse Reactions
## Clinical Trials Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
In the pre-marketing controlled clinical studies and their open extensions (2,423 patients with median duration of follow-up of approximately 18 months), 1.4% of patients were discontinued due to adverse reactions. The most common adverse reactions that led to treatment discontinuation were: gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia(0.1%). The most commonly reported adverse reactions (incidence ≥5%) in simvastatin controlled clinical trials were: upper respiratory infections (9.0%), headache (7.4%), abdominal pain (7.3%), constipation (6.6%), and nausea (5.4%).
Scandinavian Simvastatin Survival Study
In 4S involving 4,444 (age range 35-71 years, 19% women, 100% Caucasians) treated with 20-40 mg/day of simvastatin (n=2,221) or placebo (n=2,223) over a median of 5.4 years, adverse reactions reported in ≥2% of patients and at a rate greater than placebo are shown in Table 2.
Heart Protection Study
In the Heart Protection Study (HPS), involving 20,536 patients (age range 40-80 years, 25% women, 97% Caucasians, 3% other races) treated with simvastatin 40 mg/day (n=10,269) or placebo (n=10,267) over a mean of 5 years, only serious adverse reactions and discontinuations due to any adverse reactions were recorded. Discontinuation rates due to adverse reactions were 4.8% in patients treated with simvastatin compared with 5.1% in patients treated with placebo. The incidence of myopathy/rhabdomyolysis was <0.1% in patients treated with simvastatin.
Other Clinical Studies
In a clinical trial in which 12,064 patients with a history of myocardial infarction were treated with simvastatin (mean follow-up 6.7 years), the incidence of myopathy (defined as unexplained muscle weakness or pain with a serum creatine kinase [CK] >10 times upper limit of normal [ULN]) in patients on 80 mg/day was approximately 0.9% compared with 0.02% for patients on 20 mg/day. The incidence of rhabdomyolysis (defined as myopathy with a CK >40 times ULN) in patients on 80 mg/day was approximately 0.4% compared with 0% for patients on 20 mg/day. The incidence of myopathy, including rhabdomyolysis, was highest during the first year and then notably decreased during the subsequent years of treatment. In this trial, patients were carefully monitored and some interacting medicinal products were excluded.
Other adverse reactions reported in clinical trials were: diarrhea, rash, dyspepsia, flatulence, and asthenia.
Laboratory Tests
Marked persistent increases of hepatic transaminases have been noted. Elevated alkaline phosphatase and γ-glutamyl transpeptidase have also been reported. About 5% of patients had elevations of CK levels of 3 or more times the normal value on one or more occasions. This was attributable to the noncardiac fraction of CK.
Adolescent Patients (ages 10-17 years)
In a 48-week, controlled study in adolescent boys and girls who were at least 1 year post-menarche, 10-17 years of age (43.4% female, 97.7% Caucasians, 1.7% Hispanics, 0.6% Multiracial) with heterozygous familial hypercholesterolemia (n=175), treated with placebo or simvastatin(10-40 mg daily), the most common adverse reactions observed in both groups were upper respiratory infection, headache, abdominal pain, and nausea.
## Postmarketing Experience
Because the below reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The following additional adverse reactions have been identified during postapproval use of simvastatin: pruritus, alopecia, a variety of skin changes (e.g., nodules, discoloration, dryness of skin/mucous membranes, changes to hair/nails), dizziness, muscle cramps, myalgia, pancreatitis, paresthesia, peripheral neuropathy, vomiting, anemia, erectile dysfunction, interstitial lung disease, rhabdomyolysis, hepatitis/jaundice, fatal and non-fatal hepatic failure, and depression.
There have been rare reports of immune-mediated necrotizing myopathy associated with statin use [see Warnings and Precautions (5.1)].
An apparent hypersensitivity syndrome has been reported rarely which has included some of the following features: anaphylaxis, angioedema, lupus erythematous-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, chills, flushing, malaise, dyspnea, toxic epidermal necrolysis, erythema multiforme, including Stevens-Johnson syndrome.
There have been rare postmarketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These cognitive issues have been reported for all statins. The reports are generally nonserious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).[1]
# Drug Interactions
Strong CYP3A4 inhibitors: Simvastatin, like several other inhibitors of HMG-CoA reductase, is a substrate of CYP3A4. Simvastatin is metabolized by CYP3A4 but has no CYP3A4 inhibitory activity; therefore it is not expected to affect the plasma concentrations of other drugs metabolized by CYP3A4.
Elevated plasma levels of HMG-CoA reductase inhibitory activity increases the risk of myopathy and rhabdomyolysis, particularly with higher doses of simvastatin. [SeeWarnings and Precautions (5.1) and Clinical Pharmacology (12.3).] Concomitant use of drugs labeled as having a strong inhibitory effect on CYP3A4 is contraindicated [see Contraindications (4)]. If treatment with itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment.
Cyclosporine or Danazol: The risk of myopathy, including rhabdomyolysis is increased by concomitant administration of cyclosporine or danazol. Therefore, concomitant use of these drugs is contraindicated.
- Gemfibrozil: Contraindicated with simvastatin.
- Other fibrates: Caution should be used when prescribing with simvastatin.
The risk of myopathy, including rhabdomyolysis, is increased by concomitant administration of amiodarone, dronedarone, ranolazine, or calcium channel blockers such as verapamil, diltiazem, or amlodipine.
Cases of myopathy/rhabdomyolysis have been observed with simvastatin coadministered with lipid-modifying doses (≥1 g/day Niacin) of Niacin-containing products. In particular, caution should be used when treating Chinese patients with simvastatin doses exceeding 20 mg/day coadministered with lipid-modifying doses of Niacin-containing products. Because the risk for myopathy is dose-related, Chinese patients should not receive simvastatin 80 mg coadministered with lipid-modifying doses of Niacin-containing products.
## Digoxin
In one study, concomitant administration of digoxin with simvastatin resulted in a slight elevation in digoxin concentrations in plasma. Patients taking digoxin should be monitored appropriately when simvastatin is initiated.
## Coumarin Anticoagulants
In two clinical studies, one in normal volunteers and the other in hypercholesterolemic patients, simvastatin 20-40 mg/day modestly potentiated the effect of coumarin anticoagulants: the prothrombin time, reported as International Normalized Ratio (INR), increased from a baseline of 1.7 to 1.8 and from 2.6 to 3.4 in the volunteer and patient studies, respectively. With other statins, clinically evident bleeding and/or increased prothrombin time has been reported in a few patients taking coumarin anticoagulants concomitantly. In such patients, prothrombin time should be determined before starting simvastatin and frequently enough during early therapy to ensure that no significant alteration of prothrombin time occurs. Once a stable prothrombin time has been documented, prothrombin times can be monitored at the intervals usually recommended for patients on coumarin anticoagulants. If the dose of simvastatin is changed or discontinued, the same procedure should be repeated. Simvastatin therapy has not been associated with bleeding or with changes in prothrombin time in patients not taking anticoagulants.
## Colchicine
Cases of myopathy, including rhabdomyolysis, have been reported with simvastatin coadministered with colchicine, and caution should be exercised when prescribing simvastatin with colchicine.[1]
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA): X
simvastatin is contraindicated in women who are or may become pregnant. Lipid lowering drugs offer no benefit during pregnancy, because cholesterol and cholesterol derivatives are needed for normal fetal development. Atherosclerosis is a chronic process, and discontinuation of lipid-lowering drugs during pregnancy should have little impact on long-term outcomes of primary hypercholesterolemia therapy. There are no adequate and well-controlled studies of use with simvastatin during pregnancy; however, there are rare reports of congenital anomalies in infants exposed to statins in utero. Animal reproduction studies of simvastatin in rats and rabbits showed no evidence of teratogenicity. Serum cholesterol and triglycerides increase during normal pregnancy, and cholesterol or cholesterol derivatives are essential for fetal development. Because statins decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol, simvastatin may cause fetal harm when administered to a pregnant woman. If simvastatin is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
There are rare reports of congenital anomalies following intrauterine exposure to statins. In a review3 of approximately 100 prospectively followed pregnancies in women exposed to simvastatin or another structurally related statin, the incidences of congenital anomalies, spontaneous abortions, and fetal deaths/stillbirths did not exceed those expected in the general population. However, the study was only able to exclude a 3- to 4-fold increased risk of congenital anomalies over the background rate. In 89% of these cases, drug treatment was initiated prior to pregnancy and was discontinued during the first trimester when pregnancy was identified.
Simvastatin was not teratogenic in rats or rabbits at doses (25, 10 mg/kg/day, respectively) that resulted in 3 times the human exposure based on mg/m2 surface area. However, in studies with another structurally-related statin, skeletal malformations were observed in rats and mice.
Women of childbearing potential, who require treatment with simvastatin for a lipid disorder, should be advised to use effective contraception. For women trying to conceive, discontinuation of simvastatin should be considered. If pregnancy occurs, simvastatin should be immediately discontinued.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Simvastatin in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Simvastatin during labor and delivery.
### Nursing Mothers
It is not known whether simvastatin is excreted in human milk. Because a small amount of another drug in this class is excreted in human milk and because of the potential for serious adverse reactions in nursing infants, women taking simvastatin should not nurse their infants. A decision should be made whether to discontinue nursing or discontinue drug, taking into account the importance of the drug to the mother
### Pediatric Use
Safety and effectiveness of simvastatin in patients 10-17 years of age with heterozygous familial hypercholesterolemia have been evaluated in a controlled clinical trial in adolescent boys and in girls who were at least 1 year post-menarche. Patients treated with simvastatin had an adverse reaction profile similar to that of patients treated with placebo. Doses greater than 40 mg have not been studied in this population. In this limited controlled study, there was no significant effect on growth or sexual maturation in the adolescent boys or girls, or on menstrual cycle length in girls. Adolescent females should be counseled on appropriate contraceptive methods while on simvastatin therapy. Simvastatin has not been studied in patients younger than 10 years of age, nor in pre-menarchal girls.
### Geriatic Use
Of the 2,423 patients who received simvastatin in Phase III clinical studies and the 10,269 patients in the Heart Protection Study who received simvastatin, 363 (15%) and 5,366 (52%), respectively were ≥65 years old. In HPS, 615 (6%) were ≥75 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Since advanced age (≥65 years) is a predisposing factor for myopathy, simvastatin should be prescribed with caution in the elderly.
A pharmacokinetic study with simvastatin showed the mean plasma level of statin activity to be approximately 45% higher in elderly patients between 70-78 years of age compared with patients between 18-30 years of age. In 4S, 1,021 (23%) of 4,444 patients were 65 or older. Lipid-lowering efficacy was at least as great in elderly patients compared with younger patients, and simvastatin significantly reduced total mortality and CHD mortality in elderly patients with a history of CHD. In HPS, 52% of patients were elderly (4,891 patients 65-69 years and 5,806 patients 70 years or older). he relative risk reductions of CHD death, non-fatal MI, coronary and non-coronary revascularization procedures, and stroke were similar in older and younger patients. In HPS, among 32,145 patients entering the active run-in period, there were 2 cases of myopathy/rhabdomyolysis; these patients were aged 67 and 73. Of the 7 cases of myopathy/rhabdomyolysis among 10,269 patients allocated to simvastatin, 4 were aged 65 or more (at baseline), of whom one was over 75. There were no overall differences in safety between older and younger patients in either 4S or HPS.
Because advanced age (≥65 years) is a predisposing factor for myopathy, including rhabdomyolysis, simvastatin should be prescribed with caution in the elderly. In a clinical trial of patients treated with simvastatin 80 mg/day, patients ≥65 years of age had an increased risk of myopathy, including rhabdomyolysis, compared to patients <65 years of age.
### Gender
There is no FDA guidance on the use of Simvastatin with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Simvastatin with respect to specific racial populations.
### Renal Impairment
Caution should be exercised when simvastatin is administered to patients with severe renal impairment
### Hepatic Impairment
Simvastatin is contraindicated in patients with active liver disease which may include unexplained persistent elevations in hepatic transaminase levels
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Simvastatin in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Simvastatin in patients who are immunocompromised.
# Administration and Monitoring
### Administration
Oral
### Monitoring
There is limited information regarding motoring of Simvastatin in the drug label.
# IV Compatibility
There is limited information regarding the compatibility of Simvastatin and IV administrations.
# Overdosage
Significant lethality was observed in mice after a single oral dose of 9 g/m2. No evidence of lethality was observed in rats or dogs treated with doses of 30 and 100 g/m2, respectively. No specific diagnostic signs were observed in rodents. At these doses the only signs seen in dogs were emesis and mucoid stools.
A few cases of overdosage with simvastatinhave been reported; the maximum dose taken was 3.6 g. All patients recovered without sequelae. Supportive measures should be taken in the event of an overdose. The dialyzability of simvastatin and its metabolites in man is not known at present
# Pharmacology
## Mechanism of Action
Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxyacid form, simvastatin acid, after administration. Simvastatin is a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting step in the biosynthetic pathway for cholesterol. In addition, simvastatin reduces VLDL and TG and increases HDL-C.
## Structure
Simvastatin is a lipid-lowering agent that is derived synthetically from a fermentation product of Aspergillus terreus. After oral ingestion, simvastatin, which is an inactive lactone, is hydrolyzed to the corresponding β-hydroxyacid form. This is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate-limiting step in the biosynthesis of cholesterol.
Simvastatin is butanoic acid, 2,2-dimethyl-,1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)-ethyl]-1-naphthalenyl ester, [1S-[1α,3α,7β,8β(2S*,4S*),-8aβ]]. The empirical formula of simvastatin is C25H38O5 and its molecular weight is 418.57. Its structural formula is:
Simvastatin is a white to off-white, nonhygroscopic, crystalline powder that is practically insoluble in water, and freely soluble in chloroform, methanol and ethanol.
Simvastatin talets for oral administration contain either 5 mg, 10 mg, 20 mg, 40 mg or 80 mg of simvastatin and the following inactive ingredients: ascorbic acid, citric acid, hydroxypropyl cellulose, hypromellose, iron oxides, lactose, magnesium stearate, microcrystalline cellulose, starch, talc, and titanium dioxide. Butylated hydroxyanisole is added as a preservative.
## Pharmacodynamics
Epidemiological studies have demonstrated that elevated levels of total-C, LDL-C, as well as decreased levels of HDL-C are associated with the development of atherosclerosis and increased cardiovascular risk. Lowering LDL-C decreases this risk. However, the independent effect of raising HDL-C or lowering TG on the risk of coronary and cardiovascular morbidity and mortality has not been determined.
## Pharmacokinetics
Simvastatin is a lactone that is readily hydrolyzed in vivo to the corresponding β-hydroxyacid, a potent inhibitor of HMG-CoA reductase. Inhibition of HMG-CoA reductase is the basis for an assay in pharmacokinetic studies of the β-hydroxyacid metabolites (active inhibitors) and, following base hydrolysis, active plus latent inhibitors (total inhibitors) in plasma following administration of simvastatin.
Following an oral dose of 14C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces. Plasma concentrations of total radioactivity (simvastatin plus 14C-metabolites) peaked at 4 hours and declined rapidly to about 10% of peak by 12 hours postdose. Since simvastatin undergoes extensive first-pass extraction in the liver, the availability of the drug to the general circulation is low (<5%).
Both simvastatin and its β-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins. Rat studies indicate that when radiolabeled simvastatin was administered, simvastatin-derived radioactivity crossed the blood-brain barrier.
The major active metabolites of simvastatin present in human plasma are the β-hydroxyacid of simvastatin and its 6′-hydroxy, 6′-hydroxymethyl, and 6′-exomethylene derivatives. Peak plasma concentrations of both active and total inhibitors were attained within 1.3 to 2.4 hours postdose. While the recommended therapeutic dose range is 5 to 40 mg/day, there was no substantial deviation from linearity of AUC of inhibitors in the general circulation with an increase in dose to as high as 120 mg. Relative to the fasting state, the plasma profile of inhibitors was not affected when simvastatin was administered immediately before an American Heart Association recommended low-fat meal.
In a study including 16 elderly patients between 70 and 78 years of age who received simvastatin 40 mg/day, the mean plasma level of HMG-CoA reductase inhibitory activity was increased approximately 45% compared with 18 patients between 18-30 years of age. Clinical study experience in the elderly (n=1522), suggests that there were no overall differences in safety between elderly and younger patients [see Use in Specific Populations (8.5)].
Kinetic studies with another statin, having a similar principal route of elimination, have suggested that for a given dose level higher systemic exposure may be achieved in patients with severe renal insufficiency (as measured by creatinine clearance).
Although the mechanism is not fully understood, cyclosporine has been shown to increase the AUC of statins. The increase in AUC for simvastatin acid is presumably due, in part, to inhibition of CYP3A4.
The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. Inhibitors of CYP3A4 can raise the plasma levels of HMG-CoA reductase inhibitory activity and increase the risk of myopathy.
In a study of 12 healthy volunteers, simvastatin at the 80-mg dose had no effect on the metabolism of the probe cytochrome P450 isoform 3A4 (CYP3A4) substrates midazolam and erythromycin. This indicates that simvastatin is not an inhibitor of CYP3A4, and, therefore, is not expected to affect the plasma levels of other drugs metabolized by CYP3A4.
Coadministration of simvastatin (40 mg QD for 10 days) resulted in an increase in the maximum mean levels of cardioactive digoxin (given as a single 0.4 mg dose on day 10) by approximately 0.3 ng/mL.
## Nonclinical Toxicology
In a 72-week carcinogenicity study, mice were administered daily doses of simvastatin of 25, 100, and 400 mg/kg body weight, which resulted in mean plasma drug levels approximately 1, 4, and 8 times higher than the mean human plasma drug level, respectively (as total inhibitory activity based on AUC) after an 80-mg oral dose. Liver carcinomas were significantly increased in high-dose females and mid- and high-dose males with a maximum incidence of 90% in males. The incidence of adenomas of the liver was significantly increased in mid- and high-dose females. Drug treatment also significantly increased the incidence of lung adenomas in mid- and high-dose males and females. Adenomas of the Harderian gland (a gland of the eye of rodents) were significantly higher in high-dose mice than in controls. No evidence of a tumorigenic effect was observed at 25 mg/kg/day.
In a separate 92-week carcinogenicity study in mice at doses up to 25 mg/kg/day, no evidence of a tumorigenic effect was observed (mean plasma drug levels were 1 times higher than humans given 80 mg simvastatin as measured by AUC).
In a two-year study in rats at 25 mg/kg/day, there was a statistically significant increase in the incidence of thyroid follicular adenomas in female rats exposed to approximately 11 times higher levels of simvastatin than in humans given 80 mg simvastatin (as measured by AUC).
A second two-year rat carcinogenicity study with doses of 50 and 100 mg/kg/day produced hepatocellular adenomas and carcinomas (in female rats at both doses and in males at 100 mg/kg/day). Thyroid follicular cell adenomas were increased in males and females at both doses; thyroid follicular cell carcinomas were increased in females at 100 mg/kg/day. The increased incidence of thyroid neoplasms appears to be consistent with findings from other statins. These treatment levels represented plasma drug levels (AUC) of approximately 7 and 15 times (males) and 22 and 25 times (females) the mean human plasma drug exposure after an 80 milligram daily dose.
No evidence of mutagenicity was observed in a microbial mutagenicity (Ames) test with or without rat or mouse liver metabolic activation. In addition, no evidence of damage to genetic material was noted in an in vitro alkaline elution assay using rat hepatocytes, a V-79 mammalian cell forward mutation study, an in vitro chromosome aberration study in CHO cells, or an in vivo chromosomal aberration assay in mouse bone marrow.
There was decreased fertility in male rats treated with simvastatin for 34 weeks at 25 mg/kg body weight (4 times the maximum human exposure level, based on AUC, in patients receiving 80 mg/day); however, this effect was not observed during a subsequent fertility study in which simvastatin was administered at this same dose level to male rats for 11 weeks (the entire cycle of spermatogenesis including epididymal maturation). No microscopic changes were observed in the testes of rats from either study. At 180 mg/kg/day, (which produces exposure levels 22 times higher than those in humans taking 80 mg/day based on surface area, mg/m2), seminiferous tubule degeneration (necrosis and loss of spermatogenic epithelium) was observed. In dogs, there was drug-related testicular atrophy, decreased spermatogenesis, spermatocytic degeneration and giant cell formation at 10 mg/kg/day, (approximately 2 times the human exposure, based on AUC, at 80 mg/day). The clinical significance of these findings is unclear.
CNS Toxicity
Optic nerve degeneration was seen in clinically normal dogs treated with simvastatin for 14 weeks at 180 mg/kg/day, a dose that produced mean plasma drug levels about 12 times higher than the mean plasma drug level in humans taking 80 mg/day.
A chemically similar drug in this class also produced optic nerve degeneration (Wallerian degeneration of retinogeniculate fibers) in clinically normal dogs in a dose-dependent fashion starting at 60 mg/kg/day, a dose that produced mean plasma drug levels about 30 times higher than the mean plasma drug level in humans taking the highest recommended dose (as measured by total enzyme inhibitory activity). This same drug also produced vestibulocochlear Wallerian-like degeneration and retinal ganglion cell chromatolysis in dogs treated for 14 weeks at 180 mg/kg/day, a dose that resulted in a mean plasma drug level similar to that seen with the 60 mg/kg/day dose.
CNS vascular lesions, characterized by perivascular hemorrhage and edema, mononuclear cell infiltration of perivascular spaces, perivascular fibrin deposits and necrosis of small vessels were seen in dogs treated with simvastatin at a dose of 360 mg/kg/day, a dose that produced mean plasma drug levels that were about 14 times higher than the mean plasma drug levels in humans taking 80 mg/day. Similar CNS vascular lesions have been observed with several other drugs of this class.
There were cataracts in female rats after two years of treatment with 50 and 100 mg/kg/day (22 and 25 times the human AUC at 80 mg/day, respectively) and in dogs after three months at 90 mg/kg/day (19 times) and at two years at 50 mg/kg/day (5 times).
# Clinical Studies
Reductions in Risk of CHD Mortality and Cardiovascular Events
In 4S, the effect of therapy with simvastatin on total mortality was assessed in 4,444 patients with CHD and baseline total cholesterol 212-309 mg/dL (5.5-8.0 mmol/L). In this multicenter, randomized, double-blind, placebo-controlled study, patients were treated with standard care, including diet, and either simvastatin 20-40 mg/day (n=2,221) or placebo (n=2,223) for a median duration of 5.4 years. Over the course of the study, treatment with simvastatin led to mean reductions in total-C, LDL-C and TG of 25%, 35%, and 10%, respectively, and a mean increase in HDL-C of 8%. simvastatin significantly reduced the risk of mortality by 30% (p=0.0003, 182 deaths in the simvastatin group vs 256 deaths in the placebo group). The risk of CHD mortality was significantly reduced by 42% (p=0.00001, 111 vs 189 deaths). There was no statistically significant difference between groups in non-cardiovascular mortality. simvastatin significantly decreased the risk of having major coronary events (CHD mortality plus hospital-verified and silent non-fatal myocardial infarction MI) by 34% (p<0.00001, 431 vs 622 patients with one or more events). The risk of having a hospital-verified non-fatal MI was reduced by 37%. simvastatin significantly reduced the risk for undergoing myocardial revascularization procedures (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) by 37% (p<0.00001, 252 vs 383 patients). simvastatin significantly reduced the risk of fatal plus non-fatal cerebrovascular events (combined stroke and transient ischemic attacks) by 28% (p=0.033, 75 vs 102 patients). simvastatin reduced the risk of major coronary events to a similar extent across the range of baseline total and LDL cholesterol levels. Because there were only 53 female deaths, the effect of simvastatin on mortality in women could not be adequately assessed. However, simvastatin significantly lessened the risk of having major coronary events by 34% (60 vs 91 women with one or more event). The randomization was stratified by angina alone (21% of each treatment group) or a previous MI. Because there were only 57 deaths among the patients with angina alone at baseline, the effect of simvastatin on mortality in this subgroup could not be adequately assessed. However, trends in reduced coronary mortality, major coronary events and revascularization procedures were consistent between this group and the total study cohort. Additionally, simvastatin resulted in similar decreases in relative risk for total mortality, CHD mortality, and major coronary events in elderly patients (≥65 years), compared with younger patients.
The Heart Protection Study (HPS) was a large, multi-center, placebo-controlled, double-blind study with a mean duration of 5 years conducted in 20,536 patients (10,269 on simvastatin 40 mg and 10,267 on placebo). Patients were allocated to treatment using a covariate adaptive method which took into account the distribution of 10 important baseline characteristics of patients already enrolled and minimized the imbalance of those characteristics across the groups. Patients had a mean age of 64 years (range 40-80 years), were 97% caucasian and were at high risk of developing a major coronary event because of existing CHD (65%), diabetes (Type 2, 26%; Type 1, 3%), history of stroke or other cerebrovascular disease (16%), peripheral vessel disease (33%), or hypertension in males ≥65 years (6%). At baseline, 3,421 patients (17%) had LDL-C levels below 100 mg/dL, of whom 953 (5%) had LDL-C levels below 80 mg/dL; 7,068 patients (34%) had levels between 100 and 130 mg/dL; and 10,047 patients (49%) had levels greater than 130 mg/dL.
The HPS results showed that simvastatin 40 mg/day significantly reduced: total and CHD mortality; non-fatal MI, stroke, and revascularization procedures (coronary and non-coronary), see table below.
Two composite endpoints were defined in order to have sufficient events to assess relative risk reductions across a range of baseline characteristics, see Figure 1. A composite of major coronary events (MCE) was comprised of CHD mortality and non-fatal MI (analyzed by time-to-first event; 898 patients treated with simvastatin had events and 1,212 patients on placebo had events). A composite of major vascular events (MVE) was comprised of MCE, stroke and revascularization procedures including coronary, peripheral and other non-coronary procedures (analyzed by time-to-first event; 2,033 patients treated with simvastatin had events and 2,585 patients on placebo had events). Significant relative risk reductions were observed for both composite endpoints (27% for MCE and 24% for MVE, p<0.0001). Treatment with simvastatin produced significant relative risk reductions for all components of the composite endpoints. The risk reductions produced by simvastatin in both MCE and MVE were evident and consistent regardless of cardiovascular disease related medical history at study entry (i.e., CHD alone; or peripheral vascular disease, cerebrovascular disease, diabetes or treated hypertension, with or without CHD), gender, age, creatinine levels up to the entry limit of 2.3 mg/dL, baseline levels of LDL-C, HDL-C, apolipoprotein B and A-1, baseline concomitant cardiovascular medications (i.e., aspirin, beta blockers, or calcium channel blockers), smoking status, alcohol intake, or obesity. Diabetics showed risk reductions for MCE and MVE due to simvastatin treatment regardless of baseline HbA1c levels or obesity with the greatest effects seen for diabetics without CHD.
Angiographic Studies
In the Multicenter Anti-Atheroma Study, the effect of simvastatin on atherosclerosis was assessed by quantitative coronary angiography in hypercholesterolemic patients with CHD. In this randomized, double-blind, controlled study, patients were treated with simvastatin 20 mg/day or placebo. Angiograms were evaluated at baseline, two and four years. The co-primary study endpoints were mean change per-patient in minimum and mean lumen diameters, indicating focal and diffuse disease, respectively. Simvastatin significantly slowed the progression of lesions as measured in the Year 4 angiogram by both parameters, as well as by change in percent diameter stenosis. In addition, simvastatin significantly decreased the proportion of patients with new lesions and with new total occlusions.
Modifications of Lipid Profiles
- Primary Hyperlipidemia (Fredrickson type lla and llb)
- Simvastatin has been shown to be effective in reducing total-C and LDL-C in heterozygous familial and non-familial forms of hyperlipidemia and in mixed hyperlipidemia. Maximal to near maximal response is generally achieved within 4-6 weeks and maintained during chronic therapy. Simvastatin consistently and significantly decreased total-C, LDL-C, total-C/HDL-C ratio, and LDL-C/HDL-C ratio; simvastatin also decreased TG and increased HDL-C, see table below.
- Hypertriglyceridemia (Fredrickson type IV)
- The results of a subgroup analysis in 74 patients with type lV hyperlipidemia from a 130-patient, double-blind, placebo-controlled, 3-period crossover study are presented in the table below.
- Dysbetalipoproteinemia (Fredrickson type lll)
- The results of a subgroup analysis in 7 patients with type lll hyperlipidemia (dysbetalipoproteinemia) (apo E2/2) (VLDL-C/TG>0.25) from a 130-patient, double-blind, placebo-controlled, 3-period crossover study are presented the table below.
- Homozygous Familial Hypercholesterolemia
- In a controlled clinical study, 12 patients 15-39 years of age with homozygous familial hypercholesterolemia received simvastatin 40 mg/day in a single dose or in 3 divided doses, or 80 mg/day in 3 divided doses. In 11 patients with reductions in LDL-C, the mean LDL-C changes for the 40- and 80-mg doses were 14% (range 8% to 23%, median 12%) and 30% (range 14% to 46%, median 29%), respectively. One patient had an increase of 15% in LDL-C. Another patient with absent LDL-C receptor function had an LDL-C reduction of 41% with the 80-mg dose.
- Endocrine Function
- In clinical studies, simvastatin did not impair adrenal reserve or significantly reduce basal plasma cortisol concentration. Small reductions from baseline in basal plasma testosterone in men were observed in clinical studies with simvastatin, an effect also observed with other statins and the bile acid sequestrant cholestyramine. There was no effect on plasma gonadotropin levels. In a placebo-controlled, 12-week study there was no significant effect of simvastatin 80 mg on the plasma testosterone response to human chorionic gonadotropin. In another 24-week study, simvastatin 20-40 mg had no detectable effect on spermatogenesis. In 4S, in which 4,444 patients were randomized to simvastatin 20-40 mg/day or placebo for a median duration of 5.4 years, the incidence of male sexual adverse events in the two treatment groups was not significantly different. Because of these factors, the small changes in plasma testosterone are unlikely to be clinically significant. The effects, if any, on the pituitary-gonadalaxis in pre-menopausal women are unknown.
In a double-blind, placebo-controlled study, 175 patients (99 adolescent boys and 76 post-menarchal girls) 10-17 years of age (mean age 14.1 years) with heterozygous familial hypercholesterolemia (HeFH) were randomized to simvastatin (n=106) or placebo (n=67) for 24 weeks (base study). Inclusion in the study required a baseline LDL-C level between 160 and 400 mg/dL and at least one parent with an LDL-C level >189 mg/dL. The dosage of simvastatin (once daily in the evening) was 10 mg for the first 8 weeks, 20 mg for the second 8 weeks, and 40 mg thereafter. In a 24-week extension, 144 patients elected to continue therapy with simvastatin 40 mg or placebo.
Simvastatin significantly decreased plasma levels of total-C, LDL-C, and Apo B see table below. Results from the extension at 48 weeks were comparable to those observed in the base study.
After 24 weeks of treatment, the mean achieved LDL-C value was 124.9 mg/dL (range: 64.0-289.0 mg/dL) in the simvastatin 40 mg group compared to 207.8 mg/dL (range: 128.0-334.0 mg/dL) in the placebo group.
The safety and efficacy of doses above 40 mg daily have not been studied in children with HeFH. The long-term efficacy of simvastatin therapy in childhood to reduce morbidity and mortality in adulthood has not been established.
# How Supplied
No. 8360 — Tablets ZOCOR 5 mg are buff, oval, film-coated tablets, coded MSD 726 on one side and ZOCOR 5 on the other. They are supplied as follows:
NDC 0006-0726-31 unit of use bottles of 30.
No. 8146 — Tablets ZOCOR 10 mg are peach, oval, film-coated tablets, coded MSD 735 on one side and plain on the other. They are supplied as follows:
NDC 0006-0735-31 unit of use bottles of 30
NDC 0006-0735-54 unit of use bottles of 90.
No. 8147 — Tablets ZOCOR 20 mg are tan, oval, film-coated tablets, coded MSD 740 on one side and plain on the other. They are supplied as follows:
NDC 0006-0740-31 unit of use bottles of 30
NDC 0006-0740-54 unit of use bottles of 90.
No. 8148 — Tablets ZOCOR 40 mg are brick red, oval, film-coated tablets, coded MSD 749 on one side and plain on the other. They are supplied as follows:
NDC 0006-0749-31 unit of use bottles of 30
NDC 0006-0749-54 unit of use bottles of 90.
No. 6577 — Tablets ZOCOR 80 mg are brick red, capsule-shaped, film-coated tablets, coded 543 on one side and 80 on the other. They are supplied as follows:
NDC 0006-0543-31 unit of use bottles of 30
NDC 0006-0543-54 unit of use bottles of 90.
## Storage
Store between 5-30°C (41-86°F).
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
Patients should be advised to adhere to their National Cholesterol Education Program (NCEP)-recommended diet, a regular exercise program, and periodic testing of a fasting lipid panel.
Patients should be advised about substances they should not take concomitantly with simvastatin. Patients should also be advised to inform other healthcare professionals prescribing a new medication or increasing the dose of an existing medication that they are taking simvastatin.
All patients starting therapy with simvastatin should be advised of the risk of myopathy, including rhabdomyolysis, and told to report promptly any unexplained muscle pain, tenderness or weakness particularly if accompanied by malaise or fever or if these muscle signs or symptoms persist after discontinuing simvastatin. Patients using the 80-mg dose should be informed that the risk of myopathy, including rhabdomyolysis, is increased with use of the 80-mg dose. The risk of myopathy, including rhabdomyolysis, occurring with use of simvastatin is increased when taking certain types of medication or consuming grapefruit juice. Patients should discuss all medication, both prescription and over the counter, with their healthcare professional.
It is recommended that liver function tests be performed before the initiation of simvastatin, and thereafter when clinically indicated. All patients treated with simvastatin should be advised to report promptly any symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.
Women of childbearing age should be advised to use an effective method of birth control to prevent pregnancy while using simvastatin. Discuss future pregnancy plans with your patients, and discuss when to stop taking simvastatin if they are trying to conceive. Patients should be advised that if they become pregnant they should stop taking simvastatin and call their healthcare professional.
Women who are breastfeeding should not use simvastatin. Patients who have a lipid disorder and are breastfeeding should be advised to discuss the options with their healthcare professional.
# Precautions with Alcohol
Alcohol-Simvastatin detailed information interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- Zocor
# Look-Alike Drug Names
- Zocor - Cozaar
- Zocor - ZyrTEC
# Drug Shortage Status
Drug Shortage
# Price | https://www.wikidoc.org/index.php/Simvastatin | |
21e2d1423d0f9fabe19a674b27ab18be0500798e | wikidoc | Single Whip | Single Whip
Single Whip (單鞭 dān biān) is a common posture found in most forms of tai chi chuan. Typically at the end of the posture the left hand is in a palm outward push and the right hand held most commonly in the form of a hook or closed fist. Notable exceptions are the Single Whip in Sun style and Wu/Hao style tai chi chuan which finish with both hands open, palms outward.
Single Whip is one of the movements/postures most repeated in the solo training forms. Its first appearance in most forms follows the Grasp Sparrow's Tail sequence (peng, lu, ji, an) and is seen later as a variant renamed Snake Creeps Down. There is also a posture in the Wu style sword form called Single Whip Fusing Throat.
The martial applications of Single Whip are many. There are various strikes, throws, changeups (using one hand to create an opening so that the other can strike) and kicks derived from this posture trained by different schools. | Single Whip
Single Whip (單鞭 dān biān) is a common posture found in most forms of tai chi chuan. Typically at the end of the posture the left hand is in a palm outward push and the right hand held most commonly in the form of a hook or closed fist. Notable exceptions are the Single Whip in Sun style and Wu/Hao style tai chi chuan which finish with both hands open, palms outward.
Single Whip is one of the movements/postures most repeated in the solo training forms. Its first appearance in most forms follows the Grasp Sparrow's Tail sequence (peng, lu, ji, an) and is seen later as a variant renamed Snake Creeps Down. There is also a posture in the Wu style sword form called Single Whip Fusing Throat.
The martial applications of Single Whip are many[1]. There are various strikes, throws, changeups (using one hand to create an opening so that the other can strike) and kicks derived from this posture trained by different schools. | https://www.wikidoc.org/index.php/Single_Whip | |
3cbdd72a035332d7615eb37931ca115dafc84da9 | wikidoc | Sirenomelia | Sirenomelia
# Overview
Sirenomelia or Mermaid Syndrome is a very rare congenital deformity in which the legs are fused together, giving the appearance of a mermaid. This condition is found in approximately one out of every 70,000 live births (about as rare as conjoined twins) and is usually fatal within a day or two of birth because of complications associated with abnormal kidney and bladder development and function. It results from a failure of normal vascular supply from the lower aorta in utero. Sirenomelia is associated with maternal diabetes.
There may be a connection to VACTERL association.
This disorder was formerly thought to be an extreme case of Caudal Regression Syndrome; however, it was reclassified to be considered a separate condition.
# Notable cases
Only a handful of patients who did not have the usual kidney and bladder complications have survived this condition, three of them being:
- Tiffany Yorks of the United States (born 1988) underwent successful surgery to correct her rare congenital defect, in order to separate her legs.
- Milagros Cerrón of Peru (her name meaning "miracles" in Spanish.) Yorks's surgeon, Mutaz Habal, worked in an advisory capacity during Cerrón's operation.
- Shiloh Pepin of Kennebunkport, Maine in the United States | Sirenomelia
# Overview
Sirenomelia or Mermaid Syndrome is a very rare congenital deformity in which the legs are fused together, giving the appearance of a mermaid. This condition is found in approximately one out of every 70,000 live births[1] (about as rare as conjoined twins) and is usually fatal within a day or two of birth because of complications associated with abnormal kidney and bladder development and function. It results from a failure of normal vascular supply from the lower aorta in utero. Sirenomelia is associated with maternal diabetes.
There may be a connection to VACTERL association.
This disorder was formerly thought to be an extreme case of Caudal Regression Syndrome; however, it was reclassified to be considered a separate condition.
# Notable cases
Only a handful of patients who did not have the usual kidney and bladder complications have survived this condition, three of them being:
- Tiffany Yorks of the United States (born 1988) underwent successful surgery to correct her rare congenital defect, in order to separate her legs.
- Milagros Cerrón[2][3][4][5][6] of Peru (her name meaning "miracles" in Spanish.) Yorks's surgeon, Mutaz Habal, worked in an advisory capacity during Cerrón's operation.
- Shiloh Pepin of Kennebunkport, Maine in the United States [7] | https://www.wikidoc.org/index.php/Sirenomelia | |
68eeb2e5f2e63435aacc847576de033151525d46 | wikidoc | Sitaxsentan | Sitaxsentan
Sitaxsentan or sitaxsentan sodium (actual INN: sitaxentan) (marketed as Thelin® by Encysive Pharmaceuticals) is a small molecule sodium salt that blocks the action of endothelin (ET) on the endothelin-A (ETA) receptor selectively (by a factor of 6000 compared to the ETB). It is a sulfonamide class endothelin receptor antagonist (ERA) and is undergoing Food and Drug Administration (FDA) review for treating pulmonary hypertension. The rationale for benefit compared to bosentan, a nonselective ET blocker, is negligible inhibition of the beneficial effects of ETB stimulation, such as nitric oxide production and clearance of ET from circulation. However, in clinical trials, the efficacy of sitaxsentan has been much the same as bosentan, but the liver toxicity has been better. Therefore sitaxsentan is expected to be marketed as a safer drug than bosentan, but not necessarily more effective.
Thelin has been approved for marketing in both the European Union (on 10 August, 2006), in Canada and in Australia (on 7 March, 2007). It is already marketed in Germany, The Netherlands, the United Kingdom, and Ireland. The medication is currently undergoing phase III clinical trials within the United States.
On the Prescription Drug User Fee Act (PDUFA) target action date of 24 March, 2006 the United States' FDA recommended an approvable status to Thelin® but said it would not yet approve the product. On July 24, 2006 Thelin received a second approvable letter stating that efficacy outcome issues raised in the context of the STRIDE-2 study were still unresolved. In July 2007, Encysive commenced a formal dispute resolution process in a preliminary meeting with the FDA.
# Adverse effects
Adverse effects observed with Thelin® are class effects of endothelin receptor antagonists, and include :
- liver enzyme abnormalities (increased ALT and AST)
- headache
- oedema
- constipation
- nasal congestion
- upper respiratory tract infection
- dizziness
- insomnia
- flushing.
Because Thelin® inhibits metabolism of warfarin, a decreased dose of warfarin is needed when co-administered with thelin. This is due to the fact that warfarin acts to prevent blood from clotting, and if it remains unmetabolized, it can continue to thin the blood. | Sitaxsentan
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# For patient information, click here
Sitaxsentan or sitaxsentan sodium (actual INN: sitaxentan) (marketed as Thelin® by Encysive Pharmaceuticals) is a small molecule sodium salt that blocks the action of endothelin (ET) on the endothelin-A (ETA) receptor selectively (by a factor of 6000 compared to the ETB). It is a sulfonamide class endothelin receptor antagonist (ERA) and is undergoing Food and Drug Administration (FDA) review for treating pulmonary hypertension. The rationale for benefit compared to bosentan, a nonselective ET blocker, is negligible inhibition of the beneficial effects of ETB stimulation, such as nitric oxide production and clearance of ET from circulation. However, in clinical trials, the efficacy of sitaxsentan has been much the same as bosentan, but the liver toxicity has been better. Therefore sitaxsentan is expected to be marketed as a safer drug than bosentan, but not necessarily more effective.
Thelin has been approved for marketing in both the European Union (on 10 August, 2006), in Canada[1] and in Australia (on 7 March, 2007). It is already marketed in Germany, The Netherlands, the United Kingdom, and Ireland. The medication is currently undergoing phase III clinical trials within the United States.
On the Prescription Drug User Fee Act (PDUFA) target action date of 24 March, 2006 the United States' FDA recommended an approvable status to Thelin® but said it would not yet approve the product. On July 24, 2006 Thelin received a second approvable letter stating that efficacy outcome issues raised in the context of the STRIDE-2 study were still unresolved. In July 2007, Encysive commenced a formal dispute resolution process in a preliminary meeting with the FDA.
# Adverse effects
Adverse effects observed with Thelin® are class effects of endothelin receptor antagonists, and include :
- liver enzyme abnormalities (increased ALT and AST)
- headache
- oedema
- constipation
- nasal congestion
- upper respiratory tract infection
- dizziness
- insomnia
- flushing.
Because Thelin® inhibits metabolism of warfarin, a decreased dose of warfarin is needed when co-administered with thelin. This is due to the fact that warfarin acts to prevent blood from clotting, and if it remains unmetabolized, it can continue to thin the blood.
# External links
- http://www.drugs.com/nda/thelin_050714.html | https://www.wikidoc.org/index.php/Sitaxsentan | |
8da20ba799c4954989da799a9eaec0e0cd622e8b | wikidoc | Sleepeating | Sleepeating
# Overview
Sleepeating or Nocturnal Eating Syndrome is a parasomnia where people experience recurrent episodes of eating during their sleep, without being aware of it.
Sleep-related eating might occur often enough to result in significant weight gain. Although it can affect all ages and both sexes, it is more common in young women. In Australia, Ambien is marketed as "Stilnox" and the Australian drug agency found sleepdriving, and sleepeating as side effects.
Episodes of sleepeating can on occasion be repeated throughout the night, with the affected individual sometimes eating the same food over and over again, which can occur during many separate visits to the fridge or cupboard until the desired foodstuff is gone. Certain medication and alcohol can make sleepwalking more likely in an individual prone to these episodes. | Sleepeating
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Sleepeating or Nocturnal Eating Syndrome is a parasomnia where people experience recurrent episodes of eating during their sleep, without being aware of it.
Sleep-related eating might occur often enough to result in significant weight gain. Although it can affect all ages and both sexes, it is more common in young women.[1] In Australia, Ambien is marketed as "Stilnox" and the Australian drug agency found sleepdriving, and sleepeating as side effects.[2]
Episodes of sleepeating can on occasion be repeated throughout the night, with the affected individual sometimes eating the same food over and over again, which can occur during many separate visits to the fridge or cupboard until the desired foodstuff is gone. Certain medication and alcohol can make sleepwalking more likely in an individual prone to these episodes. | https://www.wikidoc.org/index.php/Sleepeating | |
f13b32b1704993b78677e1faae55fc079cca0d80 | wikidoc | Slime layer | Slime layer
A slime layer in bacteria is an easily removed, diffuse, unorganised layer of extracellular material that surrounds bacteria cells. Specifically, this consists mostly of exopolysaccharides, glycoproteins, and glycolipids.
The slime layer is not to be confused with the S-layer, a separate and highly organised glycoprotein layer surrounding many bacterial cells.
The function of the slime layer is to protect the bacteria cells from environmental dangers such as antibiotics and desiccation. The slime layer also allows bacteria to adhere to smooth surfaces such as prosthetic medical devices and catheters. It may permit bacterial colonies to survive chemical sterilization with chlorine, iodine, and other chemicals, leaving autoclaving or flushing with boiling water as the only certain methods of decontamination.
A bacterial capsule is similar, but is a well ordered structure that is resistant to washing off. | Slime layer
A slime layer in bacteria is an easily removed, diffuse, unorganised layer of extracellular material that surrounds bacteria cells. Specifically, this consists mostly of exopolysaccharides, glycoproteins, and glycolipids.
The slime layer is not to be confused with the S-layer, a separate and highly organised glycoprotein layer surrounding many bacterial cells.
The function of the slime layer is to protect the bacteria cells from environmental dangers such as antibiotics and desiccation. The slime layer also allows bacteria to adhere to smooth surfaces such as prosthetic medical devices and catheters. It may permit bacterial colonies to survive chemical sterilization with chlorine, iodine, and other chemicals, leaving autoclaving or flushing with boiling water as the only certain methods of decontamination.
A bacterial capsule is similar, but is a well ordered structure that is resistant to washing off.
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Slime_layer | |
a9579c7cd200830bb09dcc597cc0ea33c1462ca5 | wikidoc | Slug (mass) | Slug (mass)
The slug is an English unit of mass. It is a mass that accelerates by 1 ft/s² when a force of one pound-force (lbf) is exerted on it. Therefore a slug has a mass of about 32.17405 pound-mass or 14.5939 kg.
1\ \mbox{slug} =1 \cfrac{\mbox{lbf}\cdot\mbox{s}^2}{\mbox{ft}}
The slug is part of a subset of coherent units known as the gravitational foot-pound-second system (FPS), one of several such specialized systems of mechanical units developed in the late 19th and the 20th century.
The slug was first used in 1902 by Arthur Mason Worthington (1852–1916) in Dynamics of Rotation (OED), but it didn't see any significant use until decades later. A 1928 textbook says: "No name has yet been given to the unit of mass and, in fact, as we have developed the theory of dynamics no name is necessary. Whenever the mass, m, appears in our formulae, we substitute the ratio of the convenient force-acceleration pair (w/g), and measure the mass in lbs. per ft./sec.² or in grams per cm./sec.²".
Another name for this unit in early literature is the geepound.
The unit slinch (derived from the words slug-inch )
is an inch version of the slug. (1 slinch = 1 lbf·s²/in = 12 slugs)
The unit blob (bl) is also an inch version of the slug (1 lbf·s²/in).
Source: | Slug (mass)
The slug is an English unit of mass. It is a mass that accelerates by 1 ft/s² when a force of one pound-force (lbf) is exerted on it. Therefore a slug has a mass of about 32.17405 pound-mass or 14.5939 kg.[1]
<math>
1\ \mbox{slug} =1 \cfrac{\mbox{lbf}\cdot\mbox{s}^2}{\mbox{ft}}
</math>
The slug is part of a subset of coherent units known as the gravitational foot-pound-second system (FPS), one of several such specialized systems of mechanical units developed in the late 19th and the 20th century.
The slug was first used in 1902 by Arthur Mason Worthington (1852–1916) in Dynamics of Rotation (OED), but it didn't see any significant use until decades later. A 1928 textbook says: "No name has yet been given to the unit of mass and, in fact, as we have developed the theory of dynamics no name is necessary. Whenever the mass, m, appears in our formulae, we substitute the ratio of the convenient force-acceleration pair (w/g), and measure the mass in lbs. per ft./sec.² or in grams per cm./sec.²".[2]
Another name for this unit in early literature is the geepound.
The unit slinch (derived from the words slug-inch [3])
is an inch version of the slug. (1 slinch = 1 lbf·s²/in = 12 slugs)[4]
The unit blob (bl) is also an inch version of the slug (1 lbf·s²/in)[5].
Template:GravEngAbs
Source: [6] | https://www.wikidoc.org/index.php/Slug_(mass) | |
0da6f8faf9311408612248b2c12efd3006b90fad | wikidoc | Snell's law | Snell's law
In optics and physics, Snell's law (also known as Descartes' law or the law of diffraction), is a formula used to describe the relationship between the angles of incidence and refraction, when referring to light or other waves, passing through a boundary between two different isotropic media, such as water and glass. The law says that the ratio of the sines of the angles of incidence and of refraction is a constant that depends on the media.
In optics, the law is used in ray tracing to compute the angles of incidence or refraction, and in experimental optics to find the refractive index of a material.
Named after Dutch mathematician Willebrord Snellius, one of its discoverers, Snell's law states that the ratio of the sines of the angles of incidence and refraction is equivalent to the ratio of velocities in the two media, or equivalent to the opposite ratio of the indices of refraction:
-r
Snell's law follows from Fermat's principle of least time, which in turn follows from the propagation of light as waves.
# History
Ptolemy, of ancient Greece, had, through experiment, found a relationship regarding refraction angles, but which was inaccurate for angles that were not small. Ptolemy was confident he had found an accurate empirical law, partially as a result of fudging his data to fit theory (see: confirmation bias).
Snell's law was first described in a formal manuscript in a 984 writing by Ibn Sahl, who used it to work out the shapes of lenses that focus light with no geometric aberrations, known as anaclastic lenses.
It was described again by Thomas Harriot in 1602, who did not publish his work.
In 1621, Willebrord Snellius (Snel) derived a mathematically equivalent form, that remained unpublished during his lifetime. René Descartes independently derived the law using heuristic momentum conservation arguments in terms of sines in his 1637 treatise Discourse on Method, and used it to solve a range of optical problems. Rejecting Descartes' solution, Pierre de Fermat arrived at the same solution based solely on his principle of least time.
According to Dijksterhuis, "In De natura lucis et proprietate (1662) Isaac Vossius said that Descartes had seen Snell's paper and concocted his own proof. We now know this charge to be undeserved but it has been adopted many times since." Both Fermat and Huygens repeated this accusation that Descartes had copied Snell.
In French, Snell's Law is called "la loi de Descartes" or "loi de Snell-Descartes."
In his 1678 Traité de la Lumiere, Christiaan Huygens showed how Snell's law of sines could be explained by, or derived from, the wave nature of light, using what we have come to call the Huygens–Fresnel principle.
Although he spelled his name "Snel", as noted above, it has conventionally been spelled "Snell", apparently by misinterpreting the Latin form of his name, "Snellius".
# Explanation
Snell's law is used to determine the direction of light rays through refractive media with varying indices of refraction. The indices of refraction of the media, labeled n_1,n_2 and so on, are used to represent the factor by which a light ray's speed decreases when traveling through a refractive medium, such as glass or water, as opposed
to its velocity in a vacuum.
As light passes the border between media, depending upon the relative refractive indices of the two media, the light will either be refracted to a lesser angle, or a greater one. These angles are measured with respect to the normal line, represented perpendicular to the boundary. In the case of light traveling from air into water, light would be refracted towards the normal line, because the light is slowed down in water; light traveling from water to air would refract away from the normal line.
Refraction between two surfaces is also referred to as reversible because if all conditions were identical, the angles would be the same for light propagating in the opposite direction.
Snell's law is generally true only for isotropic or specular media (such as glass). In anisotropic media such as some crystals, birefringence may split the refracted ray into two rays, the ordinary or o-ray which follows Snell's law, and the other extraordinary or e-ray which may not be co-planar with the incident ray.
When the light or other wave involved is monochromatic, that is, of a single frequency, Snell's law can also be expressed in terms of a ratio of wavelengths in the two media, λ1 and λ2:
## Total internal reflection and critical angle
When light moves from a dense to a less dense medium, such as from water to air, Snell's law cannot be used to calculate the refracted angle when the resolved sine value is higher than 1. At this point, light is reflected in the incident medium, known as internal reflection. Before the ray totally internally reflects, the light refracts at the critical angle; it travels directly along the surface between the two refractive media, without a change in phases like in other forms of optical phenomena.
As an example, a ray of light is incident at 50^o towards a water–air boundary. If the angle is calculated using Snell's Law, then the resulting sine value will not invert, and thus the refracted angle cannot be calculated by Snell's law, due to the absence of a refracted outgoing ray:
In order to calculate the critical angle, let \theta_2 = 90^o and solve for \theta_\mathrm{crit}:
When θ1 > θcrit, no refracted ray appears, and the incident ray undergoes total internal reflection from the interface medium.
## Derivations
Snell's law may be derived from Fermat's principle, which states that the light travels the path which takes the least time. By taking the derivative of the optical path length, the stationary point is found giving the path taken by the light (though it should be noted that the result does not show light taking the least time path, but rather one that is stationary with respect to small variations as there are cases where light actually takes the greatest time path, as in a spherical mirror). In a classic analogy by Richard Feynman, the area of lower refractive index is replaced by a beach, the area of higher refractive index by the sea, and the fastest way for a rescuer on the beach to get to a drowning person in the sea is to run along a path that follows Snell's law.
Alternatively, Snell's law can be derived using interference of all possible paths of light wave from source to observer—it results in destructive interference everywhere except extrema of phase (where interference is constructive)—which become actual paths.
Another way to derive Snell’s Law involves an application of the general boundary conditions of Maxwell equations for electromagnetic radiation.
# Vector form
Given a normalized light vector l (pointing from the light source toward the surface) and a normalized plane normal vector n, one can work out the normalized reflected and refracted rays:
\frac{n_1}{n_2}\cos\theta_1 - \cos\theta_2\right)\mathbf{n}
Note: \mathbf{n}\cdot(-\mathbf{l}) must be positive. Otherwise, use
Example:
,~\mathbf{v}_{\mathrm{refract}}=\{0.777817, -0.62849\}
The cosines may be recycled and used in the Fresnel equations for working out the intensity of the resulting rays. During total internal reflection an evanescent wave is produced, which rapidly decays from the surface into the second medium. Conservation of energy is maintained by the circulation of energy across the boundary, averaging to zero net energy transmission.
# Dispersion
In many wave-propagation media, wave velocity changes with frequency or wavelength of the waves; this is true of light propagation in most transparent substances other than a vacuum. These media are called dispersive. The result is that the angles determined by Snell's law also depend on frequency or wavelength, so that a ray of mixed wavelengths, such as white light, will spread or disperse. Such dispersion of light in glass or water underlies the origin of rainbows, in which different wavelengths appear as different colors.
In optical instruments, dispersion leads to chromatic aberration, a color-dependent blurring that sometimes is the resolution-limiting effect. This was especially true in refracting telescopes, before the invention of achromatic objective lenses. | Snell's law
In optics and physics, Snell's law (also known as Descartes' law or the law of diffraction), is a formula used to describe the relationship between the angles of incidence and refraction, when referring to light or other waves, passing through a boundary between two different isotropic media, such as water and glass. The law says that the ratio of the sines of the angles of incidence and of refraction is a constant that depends on the media.
In optics, the law is used in ray tracing to compute the angles of incidence or refraction, and in experimental optics to find the refractive index of a material.
Named after Dutch mathematician Willebrord Snellius, one of its discoverers, Snell's law states that the ratio of the sines of the angles of incidence and refraction is equivalent to the ratio of velocities in the two media, or equivalent to the opposite ratio of the indices of refraction:
or
Snell's law follows from Fermat's principle of least time, which in turn follows from the propagation of light as waves.
# History
Ptolemy, of ancient Greece, had, through experiment, found a relationship regarding refraction angles, but which was inaccurate for angles that were not small. Ptolemy was confident he had found an accurate empirical law, partially as a result of fudging his data to fit theory (see: confirmation bias).[1]
Snell's law was first described in a formal manuscript in a 984 writing by Ibn Sahl,[3][4] who used it to work out the shapes of lenses that focus light with no geometric aberrations, known as anaclastic lenses.
It was described again by Thomas Harriot in 1602,[5] who did not publish his work.
In 1621, Willebrord Snellius (Snel) derived a mathematically equivalent form, that remained unpublished during his lifetime. René Descartes independently derived the law using heuristic momentum conservation arguments in terms of sines in his 1637 treatise Discourse on Method, and used it to solve a range of optical problems. Rejecting Descartes' solution, Pierre de Fermat arrived at the same solution based solely on his principle of least time.
According to Dijksterhuis[6], "In De natura lucis et proprietate (1662) Isaac Vossius said that Descartes had seen Snell's paper and concocted his own proof. We now know this charge to be undeserved but it has been adopted many times since." Both Fermat and Huygens repeated this accusation that Descartes had copied Snell.
In French, Snell's Law is called "la loi de Descartes" or "loi de Snell-Descartes."
In his 1678 Traité de la Lumiere, Christiaan Huygens showed how Snell's law of sines could be explained by, or derived from, the wave nature of light, using what we have come to call the Huygens–Fresnel principle.
Although he spelled his name "Snel", as noted above, it has conventionally been spelled "Snell", apparently by misinterpreting the Latin form of his name, "Snellius".[7]
# Explanation
Snell's law is used to determine the direction of light rays through refractive media with varying indices of refraction. The indices of refraction of the media, labeled <math>n_1,n_2</math> and so on, are used to represent the factor by which a light ray's speed decreases when traveling through a refractive medium, such as glass or water, as opposed
[8]
to its velocity in a vacuum.
As light passes the border between media, depending upon the relative refractive indices of the two media, the light will either be refracted to a lesser angle, or a greater one. These angles are measured with respect to the normal line, represented perpendicular to the boundary. In the case of light traveling from air into water, light would be refracted towards the normal line, because the light is slowed down in water; light traveling from water to air would refract away from the normal line.
Refraction between two surfaces is also referred to as reversible because if all conditions were identical, the angles would be the same for light propagating in the opposite direction.
Snell's law is generally true only for isotropic or specular media (such as glass). In anisotropic media such as some crystals, birefringence may split the refracted ray into two rays, the ordinary or o-ray which follows Snell's law, and the other extraordinary or e-ray which may not be co-planar with the incident ray.
When the light or other wave involved is monochromatic, that is, of a single frequency, Snell's law can also be expressed in terms of a ratio of wavelengths in the two media, λ1 and λ2:
## Total internal reflection and critical angle
When light moves from a dense to a less dense medium, such as from water to air, Snell's law cannot be used to calculate the refracted angle when the resolved sine value is higher than 1. At this point, light is reflected in the incident medium, known as internal reflection. Before the ray totally internally reflects, the light refracts at the critical angle; it travels directly along the surface between the two refractive media, without a change in phases like in other forms of optical phenomena.
As an example, a ray of light is incident at <math>50^o</math> towards a water–air boundary. If the angle is calculated using Snell's Law, then the resulting sine value will not invert, and thus the refracted angle cannot be calculated by Snell's law, due to the absence of a refracted outgoing ray:
In order to calculate the critical angle, let <math>\theta_2 = 90^o</math> and solve for <math>\theta_\mathrm{crit}</math>:
When θ1 > θcrit, no refracted ray appears, and the incident ray undergoes total internal reflection from the interface medium.
## Derivations
Snell's law may be derived from Fermat's principle, which states that the light travels the path which takes the least time. By taking the derivative of the optical path length, the stationary point is found giving the path taken by the light (though it should be noted that the result does not show light taking the least time path, but rather one that is stationary with respect to small variations as there are cases where light actually takes the greatest time path, as in a spherical mirror). In a classic analogy by Richard Feynman, the area of lower refractive index is replaced by a beach, the area of higher refractive index by the sea, and the fastest way for a rescuer on the beach to get to a drowning person in the sea is to run along a path that follows Snell's law.
Alternatively, Snell's law can be derived using interference of all possible paths of light wave from source to observer—it results in destructive interference everywhere except extrema of phase (where interference is constructive)—which become actual paths.
Another way to derive Snell’s Law involves an application of the general boundary conditions of Maxwell equations for electromagnetic radiation.
# Vector form
Given a normalized light vector l (pointing from the light source toward the surface) and a normalized plane normal vector n, one can work out the normalized reflected and refracted rays:
\frac{n_1}{n_2}\cos\theta_1 - \cos\theta_2\right)\mathbf{n}</math>
Note: <math>\mathbf{n}\cdot(-\mathbf{l})</math> must be positive. Otherwise, use
Example:
,~\mathbf{v}_{\mathrm{refract}}=\{0.777817, -0.62849\}</math>
The cosines may be recycled and used in the Fresnel equations for working out the intensity of the resulting rays. During total internal reflection an evanescent wave is produced, which rapidly decays from the surface into the second medium. Conservation of energy is maintained by the circulation of energy across the boundary, averaging to zero net energy transmission.
# Dispersion
In many wave-propagation media, wave velocity changes with frequency or wavelength of the waves; this is true of light propagation in most transparent substances other than a vacuum. These media are called dispersive. The result is that the angles determined by Snell's law also depend on frequency or wavelength, so that a ray of mixed wavelengths, such as white light, will spread or disperse. Such dispersion of light in glass or water underlies the origin of rainbows, in which different wavelengths appear as different colors.
In optical instruments, dispersion leads to chromatic aberration, a color-dependent blurring that sometimes is the resolution-limiting effect. This was especially true in refracting telescopes, before the invention of achromatic objective lenses. | https://www.wikidoc.org/index.php/Snell%27s_Law | |
04b30f9c8c436b9bdd32baa960935904c7c3d973 | wikidoc | Sober Coach | Sober Coach
A sober companion or sober coach is an addiction treatment professional who provides one-on-one assistance to newly recovering drug addicts and alcoholics. The therpeutic goal is to help the patient maintain sufficient abstinence from alcohol and drugs to establish healthy routines outside of a residential treatment facility.
A sober companion chaperones a recovering addict to help ensure they do not relapse. They may be be hired to provide round the clock care, be on-call, or to accompany the recovering addict during particular activities. A companion acts as an advocate for the newly recovering person and provides new ways for the client to act in their own living environment. Companions use techniques such as meditation, prayer and affirmation of sober choices, common to other recovery methods like Alcoholics Anonymous and counseling. They may also search for hidden drugs and restrain a client to prevent them from relapsing.
Companions are sometimes used as a replacement for residential addiction treatment or other forms of drug rehabilitation but companions such as Caine and rehabilitation center staff such as Dr. Hunsicker recommend a combined approach, particularly for people at high risk of relapse. They suggest that companions can help a patient successfully transition from a heavily structured, secure environment into the world where he or she previously failed to stay sober.
Despite this some experts like Dr. Jennifer Schneider are skeptical of the companion approach and its dependence on a single individual.
Companion treatment usually last from one to four weeks, with ten to fourteen days being the norm. Ideally, a companion's presence in the patient's life will decrease as the patient proves his or her ability to confront family, work, and legal issues without relapse. Some providers stay with their client for many months, and some offer only transportation services (for instance, to and from treatment facilities or sober living homes).
In keeping with several other forms of drug rehabilitation practitioners do not need to have any formal training. Most companions are recovering addicts who, themselves, have been able to maintain multiple years of sobriety. While some companions will have some training in psychology, sociology, and/or medicine, in addition to a strong personal program of recovery, there are no professional associations or boards to set standards or monitor the state of the field. This lack of oversight and accountability is a concern according to the California Association of Alcoholism and Drug Abuse Counselors.
Sober Companions are sometimes used in cases where an actor or a musicians will not attend treatment, but must remain abstinent to complete a film or recording project. They are also depicted by some media outlets as adult babysitters for actors, musicians, and other celebrities.
While some coaches do work with high-profile clients, most work anonymously with non-celebrities re-entering the world after residential treatment for alcohol and/or drug abuse. | Sober Coach
A sober companion or sober coach is an addiction treatment professional who provides one-on-one assistance to newly recovering drug addicts and alcoholics. The therpeutic goal is to help the patient maintain sufficient abstinence from alcohol and drugs to establish healthy routines outside of a residential treatment facility.
A sober companion chaperones a recovering addict to help ensure they do not relapse. They may be be hired to provide round the clock care, be on-call, or to accompany the recovering addict during particular activities. A companion acts as an advocate for the newly recovering person and provides new ways for the client to act in their own living environment. Companions use techniques such as meditation, prayer and affirmation of sober choices, common to other recovery methods like Alcoholics Anonymous and counseling. They may also search for hidden drugs and restrain a client to prevent them from relapsing.[1][2]
Companions are sometimes used as a replacement for residential addiction treatment or other forms of drug rehabilitation but companions such as Caine and rehabilitation center staff such as Dr. Hunsicker recommend a combined approach, particularly for people at high risk of relapse. They suggest that companions can help a patient successfully transition from a heavily structured, secure environment into the world where he or she previously failed to stay sober.
[3][1] Despite this some experts like Dr. Jennifer Schneider are skeptical of the companion approach and its dependence on a single individual.[3]
Companion treatment usually last from one to four weeks, with ten to fourteen days being the norm. Ideally, a companion's presence in the patient's life will decrease as the patient proves his or her ability to confront family, work, and legal issues without relapse. Some providers stay with their client for many months, and some offer only transportation services (for instance, to and from treatment facilities or sober living homes).
In keeping with several other forms of drug rehabilitation practitioners do not need to have any formal training. Most companions are recovering addicts who, themselves, have been able to maintain multiple years of sobriety. While some companions will have some training in psychology, sociology, and/or medicine, in addition to a strong personal program of recovery, there are no professional associations or boards to set standards or monitor the state of the field. This lack of oversight and accountability is a concern according to the California Association of Alcoholism and Drug Abuse Counselors.[1]
Sober Companions are sometimes used in cases where an actor or a musicians will not attend treatment, but must remain abstinent to complete a film or recording project. They are also depicted by some media outlets as adult babysitters for actors, musicians, and other celebrities.
[2] While some coaches do work with high-profile clients, most work anonymously with non-celebrities re-entering the world after residential treatment for alcohol and/or drug abuse.[3] | https://www.wikidoc.org/index.php/Sober_Coach |
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