[Preclinical evaluation of meropenem, a new parenteral carbapenem]

Meropenem is a new carbapenem antibiotic that is stable to human renal dehydropeptidase-I (DHP-I) and exhibits potent bactericidal activity against almost all clinically significant aerobic and anaerobic bacteria. Activity is achieved through rapid entry into bacteria, resisting hydrolysis by all serine-based beta-lactamases, both of chromosomal or plasmid origin, and high affinity for vital penicillin binding proteins. The antibacterial spectrum of meropenem has been investigated extensively in a world-wide programme of studies. The results from all of these studies are consistent and identify in vitro differences between meropenem and imipenem. Both agents demonstrate high activity against Gram-positive aerobes with meropenem slightly less active than imipenem but significantly more potent than imipenem against Haemophilus influenza, all Enterobacteriaceae and 2-4 fold more active against Pseudomonas aeruginosa and most other pseudomonas. The spectrum of carbapenems is superior to that of all other beta-lactams. This is achieved, in part, by stability to the chromosomal beta-lactamases which hydrolyse ceftazidime, cefotaxime and ceftriaxone and against which newer agents like cefpirome and cefepime are not fully stable. Meropenem is also stable to the new plasmid-mediated enzymes which are responsible for significant elevation of MIC's of all cephalosporins and penicillins. When tested against P. Aeruginosa which have become resistant to imipenem therapy, these strains remained susceptible to meropenem. The activity of meropenem against anaerobes is at least as potent as metronidazole and clindamycin. These impressive in vitro data have been the basis for an extensive clinical evaluation programme in many indications including infections caused by single or multiple pathogens.