Meropenem: evaluation of a new generation carbapenem.
Meropenem is a new beta-lactam antibiotic belonging to the carbapenem class. It differs structurally from imipenem, the first carbapenem to be marketed, by possessing a 1-beta-methyl group on the carbapenem moiety and a substituted 2' side chain. Meropenem is relatively stable to human dehydropeptidase-I (DHP-I), and therefore, unlike imipenem, it does not need to be administered with a DHP-I inhibitor such as cilastatin. Meropenem has an ultra-broad spectrum of antibacterial activity which encompasses Gram-positive and Gram-negative aerobes and anaerobes, including many strains resistant to other antibacterials. Compared to imipenem, meropenem is more active against Enterobacteriaceae and Pseudomonas aeruginosa and a little less active against some Gram-positive cocci. Meropenem is susceptible to few clinically important beta-lactamases. Meropenem exhibits a linear pharmacokinetic profile which shows predictable age and disease-related changes. Elimination is primarily renal with a half-life of approximately 1 h after intravenous (IV) administration. Meropenem monotherapy has proved efficacious in the treatment of a variety of infections in adults and children and can be administered by bolus IV injection, as well as IV infusion and intramuscular (IM) injection. Prospective, randomised clinical trials have shown it to be as efficacious as comparator regimens in the treatment of lower respiratory tract, intra-abdominal, urinary tract and skin and soft tissue infections, meningitis and septicaemia. Furthermore, meropenem monotherapy has demonstrated efficacy in the empirical treatment of febrile neutropenic cancer patients. Meropenem is well tolerated by the CNS in clinical studies, which reflects animal data, suggesting a low propensity to cause seizures. Thus, meropenem is an important new antibacterial which should prove particularly useful in severe and polymicrobial infections and those caused by organisms resistant to other agents.
Blumer
J L
JL
Division of Pediatric Pharmacology and Critical Care, Rainbow Babies and Childrens Hospital, University Hospitals of Cleveland, 11 100 Euclid Avenue, Cleveland, OH 44106-6010, USA.