INVITRO ANTIBACTERIAL ACTIVITIES OF THE FLUOROQUINOLONES PD-117596, PD-124816, AND PD-127391

Three new aminopyrrolidine-substituted fluorocyclopropyl quinolones-PD 117596, PD 124816, and PD 127391-were tested for in vitro antibacterial activity against 349 bacterial strains, which are primarily clinical isolates. The minimum inhibitory concentrations (MIC) in mu-g/ml required for greater-than-or-equal-to 90% of strains were 0.03-0.06 for staphylococci (26 strains); 0.06-0.25 for Streptocococcus pyogenes, S. agalactiae, S. pneumoniae, and Enterococcus faecalis (80); less-than-or-equal-to 0.015 for Branhamella catarrhalis, Haemophilus influenzae, and Neisseria gonorrhoeae (42); 0.06 for Enterobacteriaceae (97); 0.125-0.25 for Acinetobacter spp. (14); 0.5 for Pseudomonas aeruginosa (20); 0.125-1.0 for Bacteroides fragilis (13); and 0.25-0.5 for anaerobic cocci (11). These activities were generally superior to that of ciprofloxacin, imipenem, ampicillin, penicillin G, oxacillin, cefazolin, ceftazidime, cefoxitin, cefsulodin, aztreonam, piperacillin, amikacin, spectinomycin, doxycycline, erythomycin, clindamycin, metronidazole, and vancomycin. The activities of the new quinolones were generally unchanged with light, 50% human serum, aerobic/anaerobic atmosphere, 5% sodium cholate, cation supplementation, and 100-fold increased or decreased inoculum; as with other quinolones, potency was measurably diminished with decreasing pH (pH less-than-or-equal-to 6.0) and in 100% urine.