IN-VITRO ACTIVITY OF BMS-181139, A NEW CARBAPENEM WITH POTENT ANTIPSEUDOMONAL ACTIVITY

The in vitro activities of the carbapenem BMS-181139 were determined i n comparison with those of imipenem, meropenem, ciprofloxacin, ceftria xone, and vancomycin, BMS-181139 was the most active against species o f Pseudomonas and related genera Alteromonas and Burkholderia, with MI Cs for 147 of 149 isolates of <4 mu g/ml. Of 22 imipenem-resistant (MI C > 8 mu g/ml) P. aeruginosa strains, only 1 required an MIC of BMS-18 1139 of >4 mu g/ml, compared with 14 requiring the same meropenem MIC. BMS-181139 was the most active carbapenem against the majority of oth er gram-negative species except members of the tribe Proteeae, against which meropenem was more active. Although imipenem was more active ag ainst gram-positive species, BMS-18139 MICs at which 90% of strain tes ted were inhibited were <1 mu g/ml for these species, BMS-181139 was g enerally active against isolates resistant to ciprofloxacin or broad-s pectrum cephalosporins, including those containing plasmid-encoded bet a-lactamases or high levels of chromosome-encoded beta-lactamases, as well as anaerobes except Clostridium difficile. Inoculum effects were noted for all three carbapenems against Klebsiella pneumoniae, Enterob acter cloacae, and Serratia marcescens but not Escherichia coli, Pseud omonas aeruginosa, or Staphylococcus aureus, BMS-181139's inoculum eff ect tended to be more marked, BMS-181139 exhibited bactericidal activi ty at the MIC for some strains and up to four to eight times the MIC f or others, The postantibiotic effect of BMS-181139 was equal to or les s than that of imipenem and, like meropenem, exhibited intraspecies va riability. BMS-181139 was 30-fold more stable than imipenem and 7-fold more stable than meropenem to hydrolysis by hog kidney dehydropeptida se.