title: Antibacterial activity of a new tetracyclic quinolone, No. 5290, against norfloxacin- and ciprofloxacin-resistant strains of Staphylococcus aureus.
abstract: The antibacterial activity of a new tetracyclic quinolone, No. 5290, against 25 strains of Staphylococcus aureus clinically isolated in Japan in 1988-1989 was determined. The minimum inhibitory concentrations (MICs) of No. 5290 against both quinolone-susceptible (MIC: norfloxacin less than or equal to 6.25 micrograms/ml, ciprofloxacin less than or equal to 1.56 micrograms/ml) and 4 out of 5 norfloxacin- and ciprofloxacin-moderately resistant strains (MIC: 25 micrograms/ml less than or equal to norfloxacin less than or equal to 50 micrograms/ml, 3.13 micrograms/ml less than or equal to ciprofloxacin less than or equal to 12.5 micrograms/ml) were 0.05 micrograms/ml. Similar findings were obtained on the quinolone-resistant mutants derived by norfloxacin- or KB-5246-selection from quinolone-susceptible clinical isolates of S. aureus. The uptake of No. 5290 into a quinolone-susceptible strain of S. aureus was 2.47 micrograms/mg dry cell and the uptake in norfloxacin- and ciprofloxacin-moderately resistant strains was comparable to that in the quinolone-susceptible strain. The uptake of No. 5290 in both the quinolone-susceptible strain, and norfloxacin- and ciprofloxacin-moderately resistant, and No. 5290-susceptible strains was only slightly influenced by the treatment of bacteria with carbonyl cyanide m-chlorophenylhydrazone. These findings indicate that: (i) No. 5290 has potent antibacterial activity against quinolone-susceptible strains of S. aureus, and the potent activity might be due to a high uptake caused by an ineffective efflux of No. 5290. (ii) No. 5290 also has potent antibacterial activity against norfloxacin- and ciprofloxacin-moderately resistant strains, the reason for which could not be explained by the efflux.
authors.affiliation: New Drug Research Laboratories, Kanebo, Ltd., Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kotera
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
authors.forename: M
authors.initials: M
authors.lastname: Ohashi
authors.forename: K
authors.initials: K
authors.lastname: Ito
authors.forename: G
authors.initials: G
authors.lastname: Tsukamoto
mesh_terms: D000890:Anti-Infective Agents / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000235:genetics; D024841:Fluoroquinolones; D009154:Mutation; D009643:Norfloxacin / Q000494:pharmacology*; D010879:Piperazines / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D015363:Quinolones / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013844:Thiazoles / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D010879:Piperazines; D015363:Quinolones; D013844:Thiazoles; C074008:tetracyclic quinolone No. 5290; D002939:Ciprofloxacin; D009643:Norfloxacin