Antibacterial activity of imipenem: the first thienamycin antibiotic

Abstract

Imipenem (N-formimidoyl thienamycin) is the first representative of a new class of beta-lactam antibiotics--the carbapenems. Imipenem has an unusually broad spectrum, high potency, and no cross-resistance with other beta-lactam antibiotics. Susceptible gram-negative species include Pseudomonas aeruginosa, Serratia, and Enterobacter. Activity is high against Staphylococcus aureus, most group D streptococci, and Staphylococcus epidermidis but is variable against methicillin-resistant S. aureus. Imipenem is more active against Bacteroides than are other beta-lactam agents, chloramphenicol, metronidazole, and clindamycin. The minimal inhibitory concentrations (MICs) for 98% of 30,655 isolates--excluding those of the three resistant species (Pseudomonas maltophilia, Pseudomonas cepacia, and Streptococcus faecium)--were less than 8 micrograms/ml, the susceptibility breakpoint adopted for clinical trials. Imipenem is bactericidal (minimal bactericidal concentrations (MBCs] less than twice the MICs). For P. aeruginosa, MBCs of imipenem are less influenced by high inoculum density rather than are MBCs of antipseudomonal penicillins and cephalosporins. Stability of imipenem to diverse classes of plasmid-mediated and chromosomal beta-lactamases accounts for its lack of cross-resistance with other beta-lactam antibiotics. Imipenem is also active against P. aeruginosa with non-lactamase-mediated resistance to classical beta-lactam agents. Efficacy of imipenem was shown in animal models, including septicemia in normal and neutropenic rodents and P. aeruginosa pneumonia. Imipenem also has a unique postantibiotic effect against P. aeruginosa in vivo.