Improved bactericidal activity of Q-35 against quinolone-resistant staphylococci.
The bactericidal effects of Q-35, sparfloxacin, tosufloxacin, and ofloxacin on 18 strains of methicillin-resistant Staphylococcus aureus (MRSA) and 3 strains of Staphylococcus epidermidis were studied by a viable-count method. Staphylococci as used in this study were clearly divided into two groups with respect to their susceptibilities to sparfloxacin. MICs of Q-35 and tosufloxacin were 0.05 to 0.78 microgram/ml for sparfloxacin-susceptible strains (MICs, 0.05 to 0.2 microgram/ml) and 1.56 to 12.5 micrograms/ml for sparfloxacin-resistant strains (6.25 to 25 micrograms/ml). All the sparfloxacin-resistant strains of MRSA tested contained the gyrA mutation at codon 84. Time-kill studies showed that Q-35 decreased the viable counts from approximately 10(7) CFU/ml to 10(3) to 10(5) CFU/ml within 3 h at concentrations greater than the MICs against both sparfloxacin-susceptible and -resistant strains. In contrast, sparfloxacin, tosufloxacin, and ofloxacin produced bacteriostatic effects at 3 h after exposure against sparfloxacin-resistant strains at concentrations which were greater than the respective MICs, whereas these quinolones were bactericidal against sparfloxacin-susceptible strains. The rapid bactericidal activities of Q-35 against sparfloxacin-resistant MRSA were reduced when the methoxy group of Q-35 at the 8 position was substituted with fluorine or hydrogen. Thus, our data suggest that the introduction of a methoxy group into the 8 position of quinolones contributes to the bactericidal activities of fluoroquinolones against quinolone-resistant staphylococci.
D000890:Anti-Infective Agents / Q000494:pharmacology*; D001483:Base Sequence; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D024841:Fluoroquinolones; D016106:Methicillin Resistance / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D015363:Quinolones / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000235:genetics
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II; C077155:balofloxacin