ANTIBACTERIAL ACTIVITY OF BMS-180680, A NEW CATECHOL-CONTAINING MONOBACTAM

The in vitro activities of a new catechol-containing monobactam, BMS-1 80680 (SQ 84,100), were compared to those of aztreonam, ceftazidime, i mipenem, piperacillin-tazobactam, ciprofloxacin, amikacin, and trimeth oprim-sulfamethosazole. BMS-180680 was often the most active compound against many species of the family Enterobacteriaceae, with MICs at wh ich 90% of the isolates were inhibited (MIC(90)s) of less than or equa l to 0.5 mu g/ml for Escherichia coli, Klebsiella spp., Citrobacter di versus, Enterobacter aerogenes, Serratia marcescens, Protens spp., and Providencia spp, BMS-180680 had moderate activities (MIC90, of 2 to g mu g/ml) against Citrobacter freundii, Morganella morganii, Shigella spp., and non-E. aerogenes Enterobacter spp. BMS-180680 was the only a ntibiotic evaluated that was active against >90% of the Pseudomonas ae ruginosa (MIC90, 0.25 mu g/ml), Burkholderia cepacia, and Stenotrophom onas maltophilia (MIC(90)s, 1 mu g/ml) strains tested, BMS-180680 was inactive against most strains of Pseudomonas fluorescens, Pseudomonas stutzeri, Pseudomonas diminuta, and Burkholderia pickettii. BMS-180680 was moderately active (MIC(90)s of 4 to 8 mu g/ml) against Alcaligene s spp. and Acinetobacter lwoffii and less active (MIC90, 16 mu g/mL) a gainst Acinetobacter calcoaceticus-Acinctobacter baumanii complex. BMS -180680 lacked activity against gram-positive bacteria and anaerobic b acteria, Both ton2B and cir fiu double mutants of E. coli had greatly decreased susceptibility to BMS-180680. Of the TEM, PSE, and chromosom al-encoded beta-lactamases tested, only the K1 enzyme hydrolyzed BMS-1 80680 to any measurable extent. Like aztreonam, BMS-180680 bound prefe rentially to penicillin-binding protein 3. The MICs of BMS-180680 were not influenced by the presence of hematin or 5% sheep blood in the te st medium or with incubation in an atmosphere containing 5% CO2. BMS-1 80680 MICs obtained under strict anaerobic conditions were significant ly higher than those obtained in ambient air.