Bacterial eradication by clinafloxacin, CI-990, and ciprofloxacin employing MBC test, in-vitro time-kill and in-vivo time-kill studies.
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.
Cohen
M A
MA
Parke-Davis Pharmaceutical Research, Ann Arbor, MI 48105, USA.
Huband
M D
MD
Yoder
S L
SL
Gage
J W
JW
Roland
G E
GE
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D001424:Bacterial Infections / Q000188:drug therapy; D002939:Ciprofloxacin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D024841:Fluoroquinolones; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D051379:Mice; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; C092809:PD 131112; D015363:Quinolones; D002939:Ciprofloxacin; C057477:clinafloxacin