In vitro and in vivo antibacterial activities of T-3761, a new quinolone derivative.
T-3761, a new quinolone derivative, showed broad and potent antibacterial activity. Its MICs for 90% of the strains tested were 0.20 to 100 micrograms/ml against gram-positive bacteria, including members of the genera Staphylococcus, Streptococcus, and Enterococcus; 0.025 to 3.13 micrograms/ml against gram-negative bacteria, including members of the family Enterobacteriaceae and the genus Haemophilus; 0.05 to 50 micrograms/ml against glucose nonfermenters, including members of the genera Pseudomonas, Xanthomonas, Acinetobacter, Alcaligenes, and Moraxella; 0.025 micrograms/ml against Legionella spp.; and 6.25 to 25 micrograms/ml against anaerobes, including Bacteroides fragilis, Clostridium difficile, and Peptostreptococcus spp. The in vitro activity of T-3761 against these clinical isolates was comparable to or 2- to 32-fold greater than those of ofloxacin and norfloxacin and 2- to 16-fold less and 1- to 8-fold greater than those of ciprofloxacin and tosulfoxacin, respectively. When administered orally, T-3761 showed good efficacy in mice against systemic, pulmonary, and urinary tract infections with gram-positive and gram-negative bacteria, including quinolone-resistant Serratia marcescens and Pseudomonas aeruginosa. The in vivo activity of T-3761 was comparable to or greater than those of ofloxacin, ciprofloxacin, norfloxacin, and tosufloxacin against most infection models in mice. The activities of T-3761 were lower than those of tosufloxacin against gram-positive bacterial systemic and pulmonary infections in mice but not against infections with methicillin-resistant Staphylococcus aureus. The activities of T-3761 against systemic quinolone-resistant Serratia marcescens and Pseudomonas aeruginosa infections in mice were 2- to 14-fold greater than those of the reference agents.
Fukuoka
Y
Y
Research Laboratories, Toyama Chemical Co., Ltd., Japan.
Ikeda
Y
Y
Yamashiro
Y
Y
Takahata
M
M
Todo
Y
Y
Narita
H
H
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D002939:Ciprofloxacin / Q000494:pharmacology; D024841:Fluoroquinolones; D008171:Lung Diseases / Q000188:drug therapy / Q000382:microbiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000494:pharmacology; D009643:Norfloxacin / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology* / Q000627:therapeutic use; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000382:microbiology
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D010078:Oxazines; C078052:pazufloxacin; D002939:Ciprofloxacin; D015242:Ofloxacin; C055185:tosufloxacin; D009643:Norfloxacin