Meropenem: laboratory and clinical data.
The usefulness of many beta-lactams, including the third-generation cephalosporins, has been threatened in recent years by the dissemination of beta-lactamase-mediated resistance. The carbapenems, meropenem and imipenem/cilastatin, demonstrate ultra-broad spectra of antibacterial activity which encompass the majority of clinically significant Gram-positive and Gram-negative aerobic and anaerobic pathogens. Due to the unique arrangement of the moieties around the carbapenem beta-lactam ring, these agents possess unrivaled stability to almost all serine beta-lactamases, including the mutant extended-spectrum types produced by Enterobacteriaceae which hydrolyze third-generation cephalosporins. Meropenem has a number of additional structural features which confer advantages over imipenem, notably stability to metabolism by dehydropeptidase-I and enhanced activity against Gram-negative organisms, including Pseudomonas aeruginosa. In the treatment of nosocomial respiratory tract infections, meropenem monotherapy has compared favorably with ceftazidime plus aminoglycoside combination regimens or imipenem/cilastatin, producing rates of clinical efficacy of > 75%. Likewise, in patients with intra-abdominal infections, meropenem has proved to be as efficacious as clindamycin plus tobramycin, cefotaxime plus metronidazole and equivalent dosages of imipenem/cilastatin. Meropenem is well tolerated by the central nervous system and, unlike imipenem/cilastatin, is approved for the treatment of meningitis.
Drusano
George
G
Division of Clinical Pharmacology, Department of Medicine, Albany Medical College, Albany, New York, USA.