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  • Title: Improved bactericidal activity of Q-35 against quinolone-resistant staphylococci.
    Author: Ito T, Matsumoto M, Nishino T.
    Journal: Antimicrob Agents Chemother; 1995 Jul; 39(7):1522-5. PubMed ID: 7492097.
    Abstract:
    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.
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