The in vitro antibacterial activity of meropenem and up to nine other antimicrobials was compared in studies at 26 North American centers from 1989 to 1992 with use of standardized and controlled procedures for determining minimal inhibitory concentrations (MICs) against 12,483 recent clinical isolates and additional drug-resistant strains. Overall, carbapenems were the most active drugs. The antibacterial activity of meropenem was consistent against random isolates in all centers; however, inclusion of large proportions of multidrug-resistant gram-negative aerobes by some centers did increase MICs of meropenem and the comparators. Meropenem was 4-64 times more active than imipenem against gram-negatives, including Enterobacteriaceae organisms, Pseudomonas aeruginosa, Burkholderia cepacia, Neisseria meningiditis, and Haemophilus influenzae. Imipenem was up to 2-4 times more active than meropenem against some gram-positive cocci, including Enterococcus faecalis. Carbapenems were similarly active against anaerobes, and resistant strains were rarely encountered. Meropenem, unlike imipenem or ceftazidime, was bactericidal for all strains of Enterobacteriaceae, P. aeruginosa, and gram-positive cocci tested at < or = 8 times the MIC. A lack of antibiotic cross-resistance was frequently observed between comparator-resistant strains and meropenem. These data suggest the potential utility of meropenem as a monotherapeutic agent against a broad range of pathogens.