IN-VITRO AND IN-VIVO EVALUATION OF BO-2727 AGAINST IMIPENEM-RESISTANTAND OR MEROPENEM-RESISTANT PSEUDOMONAS-AERUGINOSA/

The in vitro and in vivo activity of BO-2727, a carbapenem antibiotic, against resistant clinical isolates of Pseudomonas aeruginosa was stu died. The geometric mean MICs against three groups of clinical isolate s resistant to imipenem, meropenem and both carbapenems were 4.28, 4.0 8 and 5.44 mu g/ml, respectively. BO-2727 also inhibited multiply anti biotic resistant isolates and laboratory mutants including a nalB-type mutant, which showed resistance to antibiotics such as imipenem, mero penem, ceftazidime, and/or ciprofloxacin, at less than 1.56 mu g/ml. O verall, BO-2727 was 4-fold more active than biapenem, meropenem, panip enem and imipenem with an MIC(90) of less than 6.25 mu g/ml. The prese nce of basic amino acids in minimal medium less affected the antipseud omonal activity to a minimal extent, suggesting that BO-2727 has diver se penetration routes through the outer membrane other than OprD chann el, which facilitates the diffusion of basic amino acids and carbapene ms. The in vitro activity of BO-2727 reflected well in its therapeutic efficacy in experimental systemic infection in mice. These results su ggest a possibility for the development of antipseudomonal carbapenems having activity against imipenem- and/or meropenem-resistant P. aerug inosa as well as a broad spectrum encompassing Gram-positive and -nega tive bacteria.