In vitro antibacterial activity of BMY-28142, a new extended-spectrum cephalosporin

Abstract

The in vitro activity of BMY-28142 was compared with that of cefotaxime, ceftazidime, moxalactam, and imipenem against 639 clinical isolates and a number of in vitro-selected resistant mutants. BMY-28142 was the most potent compound against the members of the family Enterobacteriaceae with a MIC for 90% of the strains of 0.12 micrograms/ml. The activity against Pseudomonas aeruginosa was comparable to that of ceftazidime and imipenem. Strains of staphylococci were moderately susceptible to BMY-28142 (MIC required to inhibit 90% of strains, 4 micrograms/ml), but Streptococcus faecalis isolates were resistant. The activity of the five compounds was inoculum dependent for several gram-negative species. By a single-step selection procedure, resistant mutants were selected from strains of Citrobacter freundii, Enterobacter cloacae, and P. aeruginosa. The mutant frequencies with the cephalosporins, including BMY-28142, ranged between 10(-6) and 10(-8). BMY-28142 was the most active cephalosporin against these resistant organisms, most of them strong beta-lactamase producers. It inhibited all mutants of C. freundii and E. cloacae at 2 micrograms/ml and all mutants of P. aeruginosa at 32 micrograms/ml. Imipenem on the other hand was as active on all of these resistant organisms as on the parent strains.