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In vitro and in vivo antibacterial activities of T-3761, a new quinolone derivative.

Abstract
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.
AuthorsY Fukuoka, Y Ikeda, Y Yamashiro, M Takahata, Y Todo, H Narita
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 37 Issue 3 Pg. 384-92 (Mar 1993) ISSN: 0066-4804 [Print] United States
PMID8460909 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Anti-Infective Agents
  • Fluoroquinolones
  • Naphthyridines
  • Oxazines
  • pazufloxacin
  • Ciprofloxacin
  • Ofloxacin
  • tosufloxacin
  • Norfloxacin
Topics
  • Animals
  • Anti-Infective Agents (pharmacology, therapeutic use)
  • Bacterial Infections (drug therapy, microbiology)
  • Ciprofloxacin (pharmacology)
  • Fluoroquinolones
  • Lung Diseases (drug therapy, microbiology)
  • Male
  • Mice
  • Mice, Inbred ICR
  • Microbial Sensitivity Tests
  • Naphthyridines (pharmacology)
  • Norfloxacin (pharmacology)
  • Ofloxacin (pharmacology)
  • Oxazines (pharmacology, therapeutic use)
  • Urinary Tract Infections (drug therapy, microbiology)

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