Comparative in vitro activity of WIN 57273, a new fluoroquinolone antimicrobial agent

Abstract

The in vitro activity of WIN 57273, a new fluoroquinolone antimicrobial agent, was evaluated against approximately 600 bacterial isolates. The new drug was 4- to 128-fold more active than ciprofloxacin against a broad range of gram-positive organisms, with the new drug inhibiting 90% of strains of each species except Enterococcus faecium at concentrations of less than or equal to 0.25 microgram/ml. WIN 57273 was four- to eightfold less active than ciprofloxacin against many members of the family Enterobacteriaceae, but the MICs of the new drug for 90% of strains tested (MIC90s) were less than or equal to 8 micrograms/ml (range, 0.25 to 8 micrograms/ml) for all species. Branhamella catarrhalis, Haemophilus influenzae, Neisseria gonorrhoeae, and Legionella spp. were highly susceptible (MIC90s, less than or equal to 0.06 microgram/ml). WIN 57273 demonstrated excellent activity against anaerobes (MIC90s, less than or equal to 0.25 microgram/ml), and the drug was also more active than ciprofloxacin against 30 strains of Mycobacterium avium-M. intracellulare (MIC, 0.1 to 1.0 microgram/ml). The activity of WIN 57273 against gram-positive organisms was minimally affected by pH and increased at low pH (5.4) against gram-negative organisms. The bactericidal activity of WIN 57273 was demonstrated by time-kill techniques against selected organisms. The frequencies of spontaneous resistance to the new agent were low, but resistant colonies could be selected after serial passage of initially susceptible organisms through incremental concentrations of the drug.