Activity of meropenem, against gram-positive bacteria

Abstract

A new carbapenem antibiotic, meropenem, was shown to be active against a large number of Gram-positive bacteria. The drug inhibited penicillinase-positive and -negative, methicillin-susceptible staphylococci equally well. Among the comparative antimicrobials examined, only N-formimidoyl-thienamycin (imipenem) was two to four times more active than meropenem. Compared with vancomycin or methicillin, meropenem was 10-20 times more active. Strains of 11 species of streptococci were highly susceptible to meropenem; the geometric mean MICs of the drug for these species ranged from 0.01 to 0.04 mg/l. The agent, however, only had moderate activity against Enterococcus faecalis (mean MIC 5 mg/l) and Ent. faecium (mean MIC 11.6 mg/l). Among Corynebacterium jeikeium, strains were encountered that showed susceptibility to meropenem but resistance to imipenem and other beta-lactams. Strains of other corynebacteria, Rhodococcus equi, Erysopelothrix rhusiopathiae, Listeria monocytogenes, and Bacillus spp. all were highly susceptible to meropenem (mean MICs 0.04-0.17 mg/l). Although methicillin-resistant staphylococci were inhibited by concentrations of 1-2 mg/l of meropenem in agar dilution tests, such strains showed heteroresistance in population studies, as is typical for all beta-lactam antibiotics. In addition, the biochemical correlate of methicillin-resistance, penicillin-binding protein 2', showed low affinity for meropenem, similar to that for imipenem. Meropenem was as bactericidal as imipenem and comparative bactericidal antimicrobials in killing-curve experiments. Strains of Ent. faecium, C. jeikeium, and L. monocytogenes were killed at a slower rate than streptococci or staphylococci.