title: In vitro and in vivo antibacterial activities of AM-1155, a new 6-fluoro-8-methoxy quinolone.
abstract: AM-1155 is a new quinolone with a wide spectrum of antibacterial activity against various bacteria including anaerobes and Mycoplasma pneumoniae. AM-1155 was 2- to 16-fold more active than ciprofloxacin and ofloxacin against Staphylococcus aureus including methicillin-resistant strains, Staphylococcus epidermidis, Streptococcus pneumoniae, and Enterococcus faecalis; its MICs for 90% of strains tested were 0.10 to 0.78 micrograms/ml. The activity of AM-1155 was comparable to that of ciprofloxacin against members of the family Enterobacteriaceae, Branhamella catarrhalis, Haemophilus influenzae, and Neisseria gonorrhoeae, but was fourfold less than that of ciprofloxacin against Pseudomonas aeruginosa. Against Xanthomonas maltophilia, Acinetobacter calcoaceticus, and Campylobacter jejuni, AM-1155 was two- to fourfold more active than ciprofloxacin. At a concentration of 1.56 micrograms/ml, AM-1155 inhibited 90% of Bacteroides fragilis strains tested; its activity was 8- to 10-fold higher than those of ofloxacin and ciprofloxacin. Development of resistance to AM-1155 in S. aureus and S. epidermidis occurred at a lower frequency than did that to ciprofloxacin after eight transfers in the presence of drug. In the oral treatment of mouse systemic infections, AM-1155 was four- to eightfold more effective than ciprofloxacin against gram-positive cocci and was as active as ciprofloxacin against gram-negative rods. The efficacy of an oral or a subcutaneous dose of AM-1155 was two- to fivefold greater than that of ofloxacin. Against experimental pneumonia with Klebsiella pneumoniae and P. aeruginosa, AM-1155 was two- to fourfold more active than ciprofloxacin and ofloxacin. AM-1155 also had good efficacy against mouse ascending urinary tract infections with Escherichia coli and P. aeruginosa. These results suggest that AM-1155 may be a potent antibacterial agent applicable to various infections.
authors.affiliation: Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd., Tochigi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Hosaka
authors.forename: T
authors.initials: T
authors.lastname: Yasue
authors.forename: H
authors.initials: H
authors.lastname: Fukuda
authors.forename: H
authors.initials: H
authors.lastname: Tomizawa
authors.forename: H
authors.initials: H
authors.lastname: Aoyama
authors.forename: K
authors.initials: K
authors.lastname: Hirai
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001424:Bacterial Infections / Q000188:drug therapy*; D002939:Ciprofloxacin / Q000494:pharmacology; D004250:DNA Topoisomerases, Type II / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D024841:Fluoroquinolones; D000077734:Gatifloxacin; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008826:Microbial Sensitivity Tests; D009643:Norfloxacin / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D010879:Piperazines / Q000493:pharmacokinetics / Q000494:pharmacology*; D015363:Quinolones / Q000493:pharmacokinetics / Q000494:pharmacology*; D014018:Tissue Distribution
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D010879:Piperazines; D015363:Quinolones; D002939:Ciprofloxacin; D015242:Ofloxacin; D004250:DNA Topoisomerases, Type II; D000077734:Gatifloxacin; D009643:Norfloxacin