Review of the in vitro spectrum of activity of imipenem

Abstract

Imipenem ( n-formimidoyl thienamycin, MK0787), a new carbapenem was found to have the widest antimicrobial activity of currently available beta-lactam drugs. Enterobacteriaceae had minimal inhibitory concentrations of imipenem of 8.0 μg/ml or less for 99.8 percent of clinical isolates. Only rare strains of Enterobacter species and Proteus mirabilis have higher imipenem minimal inhibitory concentration results. Hemophilus and Neisseria species were inhibited, but minimal inhibitory concentrations of imipenem were higher than those reported for third-generation cephalosporins. Only Pseudomonas maltophilia and Pseudomonas cepacia strains were imipenem resistant (MIC 50 greater than 32 μg/ml) among the commonly isolated non-enteric gram-negative bacilli. All anaerobes were found susceptible to imipenem with the exception of some strains of Clostridium difficile. Staphylococcus species and nonenterococcal streptococci were very susceptible to imipenem. Streptococcus faecalis had higher minimal inhibitory concentrations of imipenem (MIC 90 3.1 μg/ml) and S. faecium strains were frankly resistant. Methicillin-resistant S. aureus isolates had a MIC 90 of 27.2 μg imipenem/ml. Imipenem was generally bactericidal except for marked minimal inhibitory and minimal bactericidal concentration differences with enterococci, Listeria, methicillin-resistant staphylococci, and some P. aeruginosa strains. The minimal inhibitory and minimal bactericidal concentrations of imipenem were not significantly influenced by organism inoculum size, probably because of its beta-lactamase stability to nearly all commonly encountered bacterial enzymes. Imipenem was found to be an excellent inhibitor of beta-lactamases and a potent enzyme inducer. The induction characteristic seems responsible for the antagonistic interactions of imipenem with some enzyme-labile beta-lactams in combination. Imipenem had limited stability in some in vitro susceptibility test systems. The 10 μg disk test or dry-form broth microdilution systems were preferred, applying the interpretive criteria from the National Committee for Clinical Laboratory Standards (M2-A3). Imipenem-resistant strains were rarely found in clinical practice and bacteria resistant to newer beta-lactams and aminoglycosides were generally very susceptible to this new carbapenem.