Ertapenem: a new carbapenem.
Ertapenem is a new 1-beta-methyl carbapenem, stable to dehydropeptidase, which binds preferable to penicillin-binding proteins (PBP) 2 and 3. Ertapenem has a broad antibacterial spectrum with MIC90 values < 0.5 mg/l for penicillin-susceptible Streptococcus pneumoniae, Streptococcus pyogenes, methicillin-sensitive Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Citrobacter spp., Klebsiella spp., Serratia spp., Proteus spp., Clostridium perfringens, Fusobacterium spp. Peptostreptococcus spp. and anaerobic Streptococcus spp. Ertapenem exhibits a bactericidal mode of action as shown by time-killing curves and exhibits a short PAE of 1.4 - 2.6 h against the Gram-positive strains but no PAE against Gram-negative strains. In an infection model in mice, it has been shown that ertapenem and imipenem were highly efficacious at a level of 2 mg/kg in bacterial clearance in comparison to ceftriaxone, cefepime, ceftazidime, cefazolin, cefonicid, cefotaxime and meropenem. In comparison to other available carbapenems, ertapenem has a long half-life of 4.5 h and is developed as a single daily dose carbapenem. The protein binding is dose-dependent and is estimated to 94% at concentrations under 100 mg/l and approximately 85% at 300 mg/l. Cmax after a dose of 1 g in healthy volunteers has been estimated to 190 mg/l. Given the pharmacokinetic/pharmacodynamic data, it may be predicted that ertapenem will have an effect on most Gram-positive and Gram-negative bacteria with the exception of Pseudomonas aeruginosa, Enterococcus spp. and Acinetobacter spp. For pathogens with a MIC of 0.5 mg/l, the estimated T > MIC will be 50% (of 24 h) and for pathogens with a MIC of 1 mg/l 31%. For anaerobic bacteria with MIC values between 1-2 mg/l, the T > MIC may not be sufficient for bacterial eradication. However, clinical trials have to confirm this hypothesis.
Odenholt
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Department of Infectious Diseases, University Hospital MAS, SE-205 02, MalmO, Sweden. inga.odenholt@inf.mas.luse
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D015780:Carbapenems / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D017322:Clinical Trials, Phase II as Topic / Q000379:methods / Q000706:statistics & numerical data; D004341:Drug Evaluation / Q000379:methods; D000077727:Ertapenem; D006088:Gram-Negative Aerobic Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D007769:Lactams; D008826:Microbial Sensitivity Tests / Q000706:statistics & numerical data; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D007769:Lactams; D047090:beta-Lactams; D000077727:Ertapenem