LY-127935: a novel beta-lactam antibiotic with unusual antibacterial activity

The in vitro activity of LY-127935, a new beta-lactam antibiotic, was examined by using 370 clinical bacterial strains. In comparison with several other beta-lactam agents, LY-127935 was the most inhibitory against the Enterobacteriaceae. It was remarkably active against multi-drug-resistant strains of Enterobacter spp., Serratia spp., and Pseudomonas aeruginosa. LY-127935 had four- to eightfold greater activity than did cefoxitin against Bacteroides fragilis. Production of beta-lactamase by Enterobacteriaceae did not influence the minimal inhibitory concentration of LY-127935. However, the beta-lactamase-producing strains of B. fragilis and Haemophilus influenzae had generally higher minimal inhibitory concentrations. LY-127935 was the least active agent tested against gram-positive aerobic cocci. Variations in pH, salt content, protein content, or inocula size had little influence on susceptibility to LY-127935. Although combination studies with LY-127935 and gentamicin demonstrated synergy for P. aeruginosa, the rates of killing for the combination and for gentamicin alone were similar.