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≃6.25 μg/ml, ciprofloxacin≤1.56 μg/ml) and 4 out of 5 norfloxacin- and ciprofloxacin-moderately resistant strains (MIC : 25 μg/ml≤norfloxacin≤50 μg/ml, 3.13 μg/ml, &l;ciprofloxacin≤12.5 μg/ml) were 0.05 μg/ml. Similar findings were obtained on the quinolone-resistant mutants derived by norfloxacin- or KB-5246-selection from quinolone -susceptible clinical isolates of S. auresu. The uptake of No. 5290 into a quinolone-susceptible strain of S. aureus was 2.47 μg/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.
