Colistin: the re-emerging antibiotic for multidrug-resistant Gram-negative bacterial infections.
Li J,
Nation RL,
Turnidge JD,
Milne RW,
Coulthard K,
Rayner CR,
Paterson DL.
Facility for Anti-infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia.
Increasing multidrug resistance in Gram-negative bacteria, in particular Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae, presents a critical problem. Limited therapeutic options have forced infectious disease clinicians and microbiologists to reappraise the clinical application of colistin, a polymyxin antibiotic discovered more than 50 years ago.
We summarise recent progress in understanding the complex chemistry, pharmacokinetics, and pharmacodynamics of colistin, the interplay between these three aspects, and their effect on the clinical use of this important antibiotic. Recent clinical findings are reviewed, focusing on evaluation of efficacy, emerging resistance, potential toxicities, and combination therapy.
In the battle against rapidly emerging bacterial resistance we can no longer rely entirely on the discovery of new antibiotics; we must also pursue rational approaches to the use of older antibiotics such as colistin.
PMID: 16931410 [PubMed - in process]
Related Articles
Evaluation of colistin as an agent against multi-resistant Gram-negative bacteria.
Saturday, August 26, 2006
Sunday, August 20, 2006
Efficacy and safety of Sultamicillin and Amoxicillin/Clavulanic Acid in the treatment of upper respiratory tract infections
[Efficacy and safety of Sultamicillin (Ampicillin/Sulbactan) and Amoxicillin/Clavulanic Acid in the treatment of upper respiratory tract infections in adults: an open-label, multicentric, randomized trial.]
Feb 2006
Ferreira JB,
Rapoport PB,
Sakano E,
Kos AO,
Piltcher OB,
Pignatari SS,
Pinheiro SD,
Mocellin M.
Servico de Otorrinolaringologia, Depto. de Cirurgia, Faculdade de Medicina, UFG.
Upper respiratory tract infections are the most common causes of medical visits in children and adults, demanding massive use of antibiotics. Bacterial resistance caused by beta-lactamase is one of the most serious problems in this matter. Sultamicillin, a double pro-drug of Ampicillin/Sulbactan, is a potent beta-lactamase inhibitor which can face this challenge. AIM: evaluate efficacy, safety and tolerability of Ampicillin/Sulbactan compared to Amoxicillin/Clavulanate in upper respiratory tract infections in adults.
METHODS:
102 patients were enrolled and randomized to receive Ampicillin/Sulbactan or Amoxicillin/Clavulanate during 10 days. They were evaluated 10 and 30 days after treatment to learn about the therapeutic response.
RESULTS:
There were no differences between the two groups respecting cure at the end of treatment (visit 2) or at the end of the study (visit 3). Cure ratio was 61.7% and 93.2% (visits 2 and 3) in the Amoxicillin/Clavulanate group compared to 64.4% and 97.4%, respectively, in Ampicillin/Sulbactan group. The adverse events ratio for the two groups was the same (p=0.940). The number of patients with diarrhea was greater in the group of patients receiving Amoxicillin/Clavulanate (70.6%) than in the group receiving Ampicillin/Sulbactan (29.4%) (p=0.0164).
CONCLUSIONS:
Ampicillin/Sulbactan is as safe and efficient as Amoxicillin/Clavulanate in the empiric treatment of upper respiratory infections in adults. The low occurrence of diarrhea in the group receiving Ampicillin/Sulbactan needs confirmation in other studies.
PMID: 16917560 [PubMed - in process]
Monday, August 14, 2006
Antibiotics / anti-inflammatories for reducing acute inflammatory episodes in lymphoedema of the limbs.
Antibiotics / anti-inflammatories for reducing acute inflammatory episodes in lymphoedema of the limbs.
Badger C,
Seers K,
Preston N,
Mortimer P.
BACKGROUND: Lymphoedema is a chronic and progressive condition and current debate revolves around the best course of management for infective/inflammatory episodes.
OBJECTIVES: To determine whether antibiotic/anti-inflammatory drugs given prophylactically reduce the number and severity of infective/inflammatory episodes in patients with lymphoedema.
SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group register in September 2003, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), CINAHL, MEDLINE, PASCAL, SIGLE, UnCover, reference lists produced by The British Lymphology Society, the National Research Register (NRR) and the International Society of Lymphology congress proceedings.
SELECTION CRITERIA: Types of studies considered for review were randomised controlled trials testing an antibiotic or anti-inflammatory drug against placebo (with or without physical therapies). DATA
COLLECTION AND ANALYSIS: Eligibility for inclusion was confirmed by two blinded reviewers who screened the papers independently using a checklist of criteria relating to the randomisation and blinding of a trial. Both reviewers extracted data from the eligible studies using a data extraction form.
MAIN RESULTS: Overall, four studies (364 randomised patients) were included. Two of these studied the effects of intensive physical treatment plus selenium or placebo in preventing AIE, and two studied the effects of Ivermectin, Diethylcarbamazine (DEC) (anti-filarial agents) and penicillin as prophylactic treatment for adeno lymphangitis(ADL) versus placebo.Both selenium trials reported no inflammatory episodes during the trial period in the treated group but one case of infection in the two placebo groups respectively during the first three weeks of each trial. Seven additional cases of infection in trial one and 14 cases in trial two required treatment in the three month follow up period.One anti filarial trial reported a total of 127 ADL episodes for all groups during the treatment year (compared with 684 episodes reported for the same participants during the pre-treatment year). Another 228 ADL episodes were reported during the trial follow-up year but no significant differences were found between the three groups. No apparent link was found between the grade of oedema and the frequency of ADL episodes. However, there was a significant link between increased episodes and the rainy season. In the penicillin group the mean number of inflammatory episodes was reduced from 4.6 to 0.5 after treatment and increased to 1.9 at the end of the follow-up year.
REVIEWERS' CONCLUSIONS: The effectiveness of selenium in preventing AIE in lymphoedema remains inconclusive in the absence of properly conducted randomised controlled trials. Anti-filarials (DEC and Ivermectin) do not appear to reduce ADL episodes in filarial lymphoedema. Foot care may be important in reducing ADL episodes, and penicillin appears to contribute to a significant reduction in ADL, when combined with foot-care. It seems reasonable to emphasise the importance of foot-care to patients and practitioners in preventing infection and this may also apply to care of the arm in women who develop lymphoedema following breast cancer treatment. However, properly conducted trials are needed to demonstrate any efficacy of these interventions.
PMID: 15106193 [PubMed - indexed for MEDLINE]
Badger C,
Seers K,
Preston N,
Mortimer P.
BACKGROUND: Lymphoedema is a chronic and progressive condition and current debate revolves around the best course of management for infective/inflammatory episodes.
OBJECTIVES: To determine whether antibiotic/anti-inflammatory drugs given prophylactically reduce the number and severity of infective/inflammatory episodes in patients with lymphoedema.
SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group register in September 2003, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), CINAHL, MEDLINE, PASCAL, SIGLE, UnCover, reference lists produced by The British Lymphology Society, the National Research Register (NRR) and the International Society of Lymphology congress proceedings.
SELECTION CRITERIA: Types of studies considered for review were randomised controlled trials testing an antibiotic or anti-inflammatory drug against placebo (with or without physical therapies). DATA
COLLECTION AND ANALYSIS: Eligibility for inclusion was confirmed by two blinded reviewers who screened the papers independently using a checklist of criteria relating to the randomisation and blinding of a trial. Both reviewers extracted data from the eligible studies using a data extraction form.
MAIN RESULTS: Overall, four studies (364 randomised patients) were included. Two of these studied the effects of intensive physical treatment plus selenium or placebo in preventing AIE, and two studied the effects of Ivermectin, Diethylcarbamazine (DEC) (anti-filarial agents) and penicillin as prophylactic treatment for adeno lymphangitis(ADL) versus placebo.Both selenium trials reported no inflammatory episodes during the trial period in the treated group but one case of infection in the two placebo groups respectively during the first three weeks of each trial. Seven additional cases of infection in trial one and 14 cases in trial two required treatment in the three month follow up period.One anti filarial trial reported a total of 127 ADL episodes for all groups during the treatment year (compared with 684 episodes reported for the same participants during the pre-treatment year). Another 228 ADL episodes were reported during the trial follow-up year but no significant differences were found between the three groups. No apparent link was found between the grade of oedema and the frequency of ADL episodes. However, there was a significant link between increased episodes and the rainy season. In the penicillin group the mean number of inflammatory episodes was reduced from 4.6 to 0.5 after treatment and increased to 1.9 at the end of the follow-up year.
REVIEWERS' CONCLUSIONS: The effectiveness of selenium in preventing AIE in lymphoedema remains inconclusive in the absence of properly conducted randomised controlled trials. Anti-filarials (DEC and Ivermectin) do not appear to reduce ADL episodes in filarial lymphoedema. Foot care may be important in reducing ADL episodes, and penicillin appears to contribute to a significant reduction in ADL, when combined with foot-care. It seems reasonable to emphasise the importance of foot-care to patients and practitioners in preventing infection and this may also apply to care of the arm in women who develop lymphoedema following breast cancer treatment. However, properly conducted trials are needed to demonstrate any efficacy of these interventions.
PMID: 15106193 [PubMed - indexed for MEDLINE]
Thursday, August 10, 2006
WHO issues guidelines on use of cotrimoxazole prophylaxis
WHO issues guidelines on use of cotrimoxazole prophylaxis
Theo Smart, Thursday, August 10, 2006
Cotrimoxazole prophylaxis should be widely used by people with progressing HIV disease and by all HIV-infected or exposed infants (until it is clear that they are uninfected) according to guidelines issued this week by the World Health Organization (WHO).
In fact, where HIV prevalence is high, infectious diseases common and healthcare infrastructure is limited, governments may want to consider simply giving cotrimoxazole to everyone with HIV and to infants known or suspected of having been exposed to HIV, says WHO.
Background on cotrimoxazole prophylaxis Cotrimoxazole prophylaxis has long been part of the standard care for people living with advanced HIV disease in industrialised countries, where it is primarily used to prevent illnesses such as Pneumocystis jiroveci pneumonia (PCP) and toxoplasmosis. Studies have also shown that cotrimoxazole prophylaxis prevents infections and prolongs life in resource-limited settings. However, even though the treatment is simple, quite inexpensive and potentially life-saving, most countries have been slow to adopt or implement cotrimoxazole prophylaxis as a routine part of their HIV programmes for a number of reasons.
There were several reasons for this. Firstly, PCP and toxoplasmosis are not as common in resource-limited countries — where people with HIV usually first die from other illnesses. Also, there were concerns about fostering resistance to the drug (a widely used antibiotic) and cross-resistance to sulfadoxine/pyrimethamine (used to treat malaria). In fact, in some parts of Africa, there are already high levels of bacterial resistance to cotrimoxazole — until recently, there was little evidence to show that cotrimoxazole prophylaxis would be effective in such settings. Furthermore, clinical studies were needed to answer questions about the safety and practical aspects of using cotrimoxazole in infants or pregnant women.
Finally, although WHO had put out a provisional statement on the use of cotrimoxazole in 2000, it has never previously issued clear technical guidelines on the operational aspects of implementing cotrimoxazole prophylaxis, especially in the context of scaling up HIV care in resource-limited settings. However, over the last several years, the evidence base in support of cotrimoxazole prophylaxis has strengthened considerably. For instance, new studies have shown that PCP, which cotrimoxazole can prevent, is the leading cause of death in infants with HIV in all settings (and the incidence peaks during the first six months of life). Other new evidence has been drawn from recent clinical trials and observational cohort studies in a wide range of populations and settings, even in regions where malaria is endemic and background resistance to cotrimoxazole is common. Consistently, the studies have shown that cotrimoxazole prophylaxis reduces mortality and morbidity in adults, children and infants.
The new WHO guidelines review the clinical evidence as well as essential information needed to use cotrimoxazole safely; with annexes that summarise the criteria for recognising HIV-related clinical events used in the WHO staging system of HIV disease, as well as how to grade the seriousness of adverse events that may occur in persons taking cotrimoxazole.
Recommendations in infants and children It is especially important that infants with, or suspected of having, HIV receive cotrimoxazole during the first six months of their life. Cotrimoxazole prophylaxis is recommended for all HIV-exposed infants starting at 4–6 weeks of age (or at first encounter with the healthcare system) and should be continued until HIV infection can be excluded by HIV antibody testing (beyond 18 months of age) or virological testing (before 18 months of age) at least six weeks after complete cessation of breastfeeding.
Cotrimoxazole prophylaxis is recommended for all HIV-infected infants below one year of age regardless of symptoms or CD4 percentage. Treatment should continue until they are at least five years of age regardless of clinical symptoms or CD4 percentage or whether they have had a good immune response on antiretroviral therapy.
For children between one to four years old, cotrimoxazole prophylaxis is recommended for all children with WHO stage II, III or IV disease, or all children with a CD4 cell% <>
For children aged five or older, see adult recommendations in terms of starting or stopping cotrimoxazole prophylaxis. In settings with limited infrastructure and high child mortality and HIV prevalence — and where HIV screening may not be possible, WHO recommends a universal option: giving cotrimoxazole to all children born to mothers with or suspected of having HIV.
However, cotrimoxazole should not be given to young children who have (or have a history of) severe adverse reactions (grade 4 reactions) to cotrimoxazole or other sulfa-containing drugs and children with glucose-6-phosphate dehydrogenase (although WHO does not recommend routine screening for glucose-6-phosphate dehydrogenase deficiency in resource limited settings). If a child cannot take cotrimoxazole, dapsone 2 mg/kg once daily should be used. Recommendations in adolescents and adults Where CD4 cell counts are available, WHO recommends that everyone with CD4 cell counts below 350 should take cotrimoxazole prophylaxis whether they have symptoms or not. In addition, those with stage III and IV disease should take cotrimoxazole regardless of their CD4 cell count.
Where CD4 cell counts are not available, cotrimoxazole prophylaxis should be taken by everyone with mild, advanced or severe symptoms of HIV disease (WHO stage II, III or IV disease).
Where infrastructure is even more limited, and HIV prevalence is high, WHO says countries can consider offering cotrimoxazole to everyone who tests HIV-positive.
Cotrimoxazole is recommended to HIV-positive pregnant women, regardless of the stage of pregnancy and should continue while she is breastfeeding. Women with HIV who live in an area where there is malaria, should take cotrimoxazole rather than sulfadoxine/pyrimethamine–based intermittent presumptive therapy for malaria.
For people with HIV who qualify for antiretroviral therapy, WHO recommends that they start cotrimoxazole two weeks before their ART regimen — in case there is rash or any other adverse reaction.
In industrialised countries, it is considered safe to discontinue cotrimoxazole in response to effective antiretroviral treatment (that increases the CD4 cell count to over 200). However, in resource limited settings where the primary causes of mortality are malaria or bacterial infections that strike people down with much higher CD4 cell counts, WHO’s “general recommendation is to continue cotrimoxazole prophylaxis among adults living with HIV indefinitely.” Even so, the guidelines (perhaps prematurely considering the evidence base) discuss the alternatives, such as discontinuing cotrimoxazole once the CD4 cell count has been over 350 for at least six months. Recommended daily dosing: For infants below 6 months or <>30 kgs (800 mg/160 mg)
Cotrimoxazole suspension contains 200 mg/40 mg per 5 ml of syrup. Single strength tablets contain 400 mg/80 mg, double strength tablet twice that. It is possible to divide the tablets for children and infants.
Theo Smart, Thursday, August 10, 2006
Cotrimoxazole prophylaxis should be widely used by people with progressing HIV disease and by all HIV-infected or exposed infants (until it is clear that they are uninfected) according to guidelines issued this week by the World Health Organization (WHO).
In fact, where HIV prevalence is high, infectious diseases common and healthcare infrastructure is limited, governments may want to consider simply giving cotrimoxazole to everyone with HIV and to infants known or suspected of having been exposed to HIV, says WHO.
Background on cotrimoxazole prophylaxis Cotrimoxazole prophylaxis has long been part of the standard care for people living with advanced HIV disease in industrialised countries, where it is primarily used to prevent illnesses such as Pneumocystis jiroveci pneumonia (PCP) and toxoplasmosis. Studies have also shown that cotrimoxazole prophylaxis prevents infections and prolongs life in resource-limited settings. However, even though the treatment is simple, quite inexpensive and potentially life-saving, most countries have been slow to adopt or implement cotrimoxazole prophylaxis as a routine part of their HIV programmes for a number of reasons.
There were several reasons for this. Firstly, PCP and toxoplasmosis are not as common in resource-limited countries — where people with HIV usually first die from other illnesses. Also, there were concerns about fostering resistance to the drug (a widely used antibiotic) and cross-resistance to sulfadoxine/pyrimethamine (used to treat malaria). In fact, in some parts of Africa, there are already high levels of bacterial resistance to cotrimoxazole — until recently, there was little evidence to show that cotrimoxazole prophylaxis would be effective in such settings. Furthermore, clinical studies were needed to answer questions about the safety and practical aspects of using cotrimoxazole in infants or pregnant women.
Finally, although WHO had put out a provisional statement on the use of cotrimoxazole in 2000, it has never previously issued clear technical guidelines on the operational aspects of implementing cotrimoxazole prophylaxis, especially in the context of scaling up HIV care in resource-limited settings. However, over the last several years, the evidence base in support of cotrimoxazole prophylaxis has strengthened considerably. For instance, new studies have shown that PCP, which cotrimoxazole can prevent, is the leading cause of death in infants with HIV in all settings (and the incidence peaks during the first six months of life). Other new evidence has been drawn from recent clinical trials and observational cohort studies in a wide range of populations and settings, even in regions where malaria is endemic and background resistance to cotrimoxazole is common. Consistently, the studies have shown that cotrimoxazole prophylaxis reduces mortality and morbidity in adults, children and infants.
The new WHO guidelines review the clinical evidence as well as essential information needed to use cotrimoxazole safely; with annexes that summarise the criteria for recognising HIV-related clinical events used in the WHO staging system of HIV disease, as well as how to grade the seriousness of adverse events that may occur in persons taking cotrimoxazole.
Recommendations in infants and children It is especially important that infants with, or suspected of having, HIV receive cotrimoxazole during the first six months of their life. Cotrimoxazole prophylaxis is recommended for all HIV-exposed infants starting at 4–6 weeks of age (or at first encounter with the healthcare system) and should be continued until HIV infection can be excluded by HIV antibody testing (beyond 18 months of age) or virological testing (before 18 months of age) at least six weeks after complete cessation of breastfeeding.
Cotrimoxazole prophylaxis is recommended for all HIV-infected infants below one year of age regardless of symptoms or CD4 percentage. Treatment should continue until they are at least five years of age regardless of clinical symptoms or CD4 percentage or whether they have had a good immune response on antiretroviral therapy.
For children between one to four years old, cotrimoxazole prophylaxis is recommended for all children with WHO stage II, III or IV disease, or all children with a CD4 cell% <>
For children aged five or older, see adult recommendations in terms of starting or stopping cotrimoxazole prophylaxis. In settings with limited infrastructure and high child mortality and HIV prevalence — and where HIV screening may not be possible, WHO recommends a universal option: giving cotrimoxazole to all children born to mothers with or suspected of having HIV.
However, cotrimoxazole should not be given to young children who have (or have a history of) severe adverse reactions (grade 4 reactions) to cotrimoxazole or other sulfa-containing drugs and children with glucose-6-phosphate dehydrogenase (although WHO does not recommend routine screening for glucose-6-phosphate dehydrogenase deficiency in resource limited settings). If a child cannot take cotrimoxazole, dapsone 2 mg/kg once daily should be used. Recommendations in adolescents and adults Where CD4 cell counts are available, WHO recommends that everyone with CD4 cell counts below 350 should take cotrimoxazole prophylaxis whether they have symptoms or not. In addition, those with stage III and IV disease should take cotrimoxazole regardless of their CD4 cell count.
Where CD4 cell counts are not available, cotrimoxazole prophylaxis should be taken by everyone with mild, advanced or severe symptoms of HIV disease (WHO stage II, III or IV disease).
Where infrastructure is even more limited, and HIV prevalence is high, WHO says countries can consider offering cotrimoxazole to everyone who tests HIV-positive.
Cotrimoxazole is recommended to HIV-positive pregnant women, regardless of the stage of pregnancy and should continue while she is breastfeeding. Women with HIV who live in an area where there is malaria, should take cotrimoxazole rather than sulfadoxine/pyrimethamine–based intermittent presumptive therapy for malaria.
For people with HIV who qualify for antiretroviral therapy, WHO recommends that they start cotrimoxazole two weeks before their ART regimen — in case there is rash or any other adverse reaction.
In industrialised countries, it is considered safe to discontinue cotrimoxazole in response to effective antiretroviral treatment (that increases the CD4 cell count to over 200). However, in resource limited settings where the primary causes of mortality are malaria or bacterial infections that strike people down with much higher CD4 cell counts, WHO’s “general recommendation is to continue cotrimoxazole prophylaxis among adults living with HIV indefinitely.” Even so, the guidelines (perhaps prematurely considering the evidence base) discuss the alternatives, such as discontinuing cotrimoxazole once the CD4 cell count has been over 350 for at least six months. Recommended daily dosing: For infants below 6 months or <>30 kgs (800 mg/160 mg)
Cotrimoxazole suspension contains 200 mg/40 mg per 5 ml of syrup. Single strength tablets contain 400 mg/80 mg, double strength tablet twice that. It is possible to divide the tablets for children and infants.
Sunday, August 06, 2006
Carbapenems
Carbapenems
Carbapenems are a class of beta-lactam antibiotics.
The following drugs belong to the carbapenem class:
Imipenem (often given as part of Imipenem/cilastatin)
Meropenem
Ertapenem
Faropenem
Doripenem
External Links
Structure Activity Relationships "Antibacterial Agents; Structure Activity Relationships," André Bryskier MD; beginning at pp131
Carbapenems
* * * * *
Carbapenems
Imipenem/Cilastatin(Primaxin)
Mechanism of action
Inhibits bacterial cell wall synthesis. Cilastatin blocks metabolism of imipenem.
Spectrum of activity
Gram-negative (including P aeruginosa); Gram-positive (including some enterococci); not MRSA; Anaerobes including Bacteroides fragilis
Half-life
1 h
Metabolism
In kidney by dehydropeptidase. Blocked by cilastatin
Excretion
70% unchanged in urine
Clinical Side effects
GI, phlebitis, neurologic (seizures <>
Laboratory abnormalities
Increased LFTs, other rare events
Mechanism of drug interactions
No CYP-450 interactions. Probenecid increases levels
Other considerations
Significant dosage adjustment in renal insufficincy
Approved indications
Intra-abdominal infection, lower respiratory tract infection, UTI, gynecologic infection, bacterial septicemia, bone, joint, and skin infections, endocarditis, polymicrobic infections
Usual Dose
500 mg q6h, adjusted for renal function
----------
Meropenem(Merrem)
Mechanism of action
Ertapenem(Invanz)
Mechanism of action
Carbapenems are a class of beta-lactam antibiotics.
The following drugs belong to the carbapenem class:
Imipenem (often given as part of Imipenem/cilastatin)
Meropenem
Ertapenem
Faropenem
Doripenem
External Links
Structure Activity Relationships "Antibacterial Agents; Structure Activity Relationships," André Bryskier MD; beginning at pp131
Carbapenems
* * * * *
Carbapenems
Imipenem/Cilastatin(Primaxin)
Mechanism of action
Inhibits bacterial cell wall synthesis. Cilastatin blocks metabolism of imipenem.
Spectrum of activity
Gram-negative (including P aeruginosa); Gram-positive (including some enterococci); not MRSA; Anaerobes including Bacteroides fragilis
Half-life
1 h
Metabolism
In kidney by dehydropeptidase. Blocked by cilastatin
Excretion
70% unchanged in urine
Clinical Side effects
GI, phlebitis, neurologic (seizures <>
Laboratory abnormalities
Increased LFTs, other rare events
Mechanism of drug interactions
No CYP-450 interactions. Probenecid increases levels
Other considerations
Significant dosage adjustment in renal insufficincy
Approved indications
Intra-abdominal infection, lower respiratory tract infection, UTI, gynecologic infection, bacterial septicemia, bone, joint, and skin infections, endocarditis, polymicrobic infections
Usual Dose
500 mg q6h, adjusted for renal function
----------
Meropenem(Merrem)
Mechanism of action
Inhibits bacterial cell wall synthesis
Spectrum of activity
Gram-negative (including P aeruginosa); Gram-positive (including some enterococci); not MRSA; Anaerobes including Bacteriodes fragilis
Half-life
1-1.5 h
Metabolism
Minor hepatic to inactive metabolite
Excretion
75% unchanged in urine
Clinical Side effects
Headache, rash, GI, phlebitis, hypotension
Laboratory abnormalities
Increased LFTs, other rare events
Mechanism of drug interactions
No CYP-450 interactions. Probenecid increases levels
Other considerations
Dose adjustment necessary in renal insufficiency
Approved indications
Intra-abdominal infection, bacterial meningitis
Usual Dose
1 g q8h, adjusted for renal function
----------------Ertapenem(Invanz)
Mechanism of action
Inhibits bacterial cell wall synthesis
Spectrum of activityGram-negative—not P aeruginosa;Gram-positive, not enterococci, not MRSA; Anaerobes including Bacteriodes fragilis
Half-life
4h
Metabolism
Minor hepatic to inactive metabolite
Excretion
38% unchanged in urine; 37% inactive metabolite; 10% feces
Clinical Side effects
Headache, rash, GI, phlebitis, hypotension
Laboratory abnormalities
Increased LFTs, other rare events
Mechanism of drug interactions
No CYP-450 interactions. Probenecid increases levels.
Other considerations
Minor dose adjustment necessary in renal insufficiency
Approved indications
Intra-abdominal infection, skin and skin structure, community-acquired pneumonia, UTI, pelvic infections
Usual Dose
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