title: Antibacterial properties of BO-2727, a new carbapenem antibiotic.
abstract: BO-2727 is a new injectable carbapenem antibiotic with broad-spectrum, potent antibacterial activity. The in-vitro and in-vivo antibacterial activities of BO-2727 were compared with those of meropenem, imipenem and biapenem. BO-2727 was four- to eight-fold more active in vitro than meropenem, imipenem and biapenem against methicillin-resistant Staphylococcus aureus, inhibiting more than 90% of clinical isolates at a concentration of 12.5 mg/L. BO-2727 also showed superior activity against Pseudomonas aeruginosa, and was two- to four-fold more active than imipenem against imipenem-resistant strains. The antimicrobial activity of BO-2727 was influenced by the pH of the medium and inoculum size, in the same way as meropenem and imipenem. In time-killing kinetic studies, BO-2727 showed dose-dependent bactericidal activity against S. aureus, Escherichia coli and P. aeruginosa. In a morphological study, BO-2727 induced spherical forms in E. coli and bulging forms in P. aeruginosa. The affinity of BO-2727 for E. coli (PBP 2) was about twice that of imipenem. BO-2727 also had high affinities for P. aeruginosa penicillin-binding protein (PBPs) 2 and 3. The prophylactic efficacy of BO-2727 against Gram-positive and Gram-negative bacterial systemic infections was similar to that of imipenem and biapenem.
authors.affiliation: Department of Microbiology, Kyoto Pharmaceutical University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kato
authors.forename: M
authors.initials: M
authors.lastname: Otsuki
authors.forename: T
authors.initials: T
authors.lastname: Nishino
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis; D015780:Carbapenems / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D051379:Mice; D008826:Microbial Sensitivity Tests; D008858:Microscopy, Phase-Contrast; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; C085890:BO 2727