Bacterial eradication by clinafloxacin, CI-990, and ciprofloxacin employing MBC test, in-vitro time-kill and in-vivo time-kill studies

Abstract

Bactericidal activities of clinafloxacin, CI-990 and ciprofloxacin were examined and compared for a small collection of Gram-positive and Gram-negative pathogens. In-vitro antimicrobial activities were measured by MIC, MBC and time-kill studies; in-vivo efficacy of each drug was assessed in an acute lethal mouse infection model that monitored median protective dose, eradicative dose and time-kill in blood. In general, for all test methods, activity of clinafloxacin exceeded that of CI-990, which in turn exceeded that of ciprofloxacin. Improvement in clinafloxacin and CI-990 activity over ciprofloxacin was more apparent against Gram-positive cocci; differences were less noticeable against Escherichia coli and Pseudomonas aeruginosa. Clinafloxacin activity was notably high against Staphylococcus aureus and, against ciprofloxacin-resistant strains, this high activity was maintained in vitro and measurable activity was demonstrated in vivo.