MK0787 (N-formimidoyl thienamycin): evaluation of in vitro and in vivo activities.
The practical application of thienamycin, a novel beta-lactam antibiotic with a broad activity spectrum, was compromised by problems of instability. MK0787, N-formimidoyl thienamycin, does not have this liability. As reported, bacterial species resistant to most beta-lactam antibiotics, such as Pseudomonas aeurginosa, Serratis, Enterobacter, Enterococcus, and Bacteroides spp., are uniformly susceptible to MK0787, usually at one-half the inhibitory level of thienamycin. Bactericidal activity usually occurs at the minimal inhibitory concentration endpoint. Activity was reduced only at the highest inoculum densities tested and by a lessor factor than was observed with reference beta-lactam antibiotic active against P. aeruginosa and beta-lactamase-bearing strains. MK0787 exhibits a broad spectrum of in vivo activity when evaluated parenterally for efficacy against systemic infections in mice. The order of potency in vivo, 0.03 to 0.06 mg/kg for gram-positive species and 0.65 to 3.8 mg/kg for gram-negative infections including Pseudomonas, exceeded that of thienamycin and was at least 10-fold superior to reference beta-lactam antibiotics including two recently developed agents with antipseudomonal activity, cefotaxime and LY127935.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy; D004352:Drug Resistance, Microbial; D005260:Female; D015378:Imipenem; D007769:Lactams / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008826:Microbial Sensitivity Tests
D000900:Anti-Bacterial Agents; D007769:Lactams; D015378:Imipenem