In vitro and in vivo antibacterial activity of AT-2266.
AT-2266 [1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine-3-carbo xylic acid] showed a broad spectrum of antibacterial activity against gram-positive and gram-negative microorganisms, including Pseudomonas aeruginosa. The in vitro antibacterial activity of AT-2266 was in general comparable to that of norfloxacin, but much higher than that of pipemidic or nalidixic acid. The 90% minimal inhibitory concentrations (MIC90s) of AT-2266 for P. aeruginosa resistant to gentamicin (MIC range, 25 to greater than 200 microgram/ml) and Enterobacteriaceae resistant to nalidixic acid (25 to greater than 1,600 micrograms/ml) were 3.13 and 12.5 micrograms/ml, respectively. The to nalidixic acid (25 to 1,600 micrograms/ml) were 3.13 and 12.5 micrograms/ml, respectively. The MICs of AT-2266 were only slightly affected by the addition of horse serum or sodium cholate, by the pH of the medium, and by inoculum size. AT-2266 was sodium cholate, by the pH of the medium, and by inoculum size. AT-2266 was bactericidal at concentrations near its MIC value. The 50% effective doses of AT-2266 after oral administration against systemic infections in mice were about 1/2 those of norfloxacin, about 1/10 those of pipemidic acid, and between 1/20 and 1/40 those of nalidixic acid.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy; D004352:Drug Resistance, Microbial; D015365:Enoxacin; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009268:Nalidixic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009287:Naphthyridines / Q000494:pharmacology*; D009643:Norfloxacin; D010876:Pipemidic Acid / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D009287:Naphthyridines; D015365:Enoxacin; D009268:Nalidixic Acid; D010876:Pipemidic Acid; D009643:Norfloxacin