Selection of moxifloxacin-resistant Staphylococcus aureus compared with five other fluoroquinolones.

Article Details

Citation

Copy to clipboard

Griggs DJ, Marona H, Piddock LJ

Selection of moxifloxacin-resistant Staphylococcus aureus compared with five other fluoroquinolones.

J Antimicrob Chemother. 2003 Jun;51(6):1403-7. Epub 2003 Apr 25.

PubMed ID

12716775 [ View in PubMed

]

Abstract

Fluoroquinolone-resistant mutants were selected from Staphylococcus aureus NCTC 8532 (F77), and two GrlA mutants of F77 (F193 and F194) with moxifloxacin, sparfloxacin, ofloxacin, grepafloxacin, levofloxacin and trovafloxacin. For mutants selected from F77, moxifloxacin, grepafloxacin and sparfloxacin selected preferentially for mutations in gyrA (Glu-88-->Lys). Ofloxacin and trovafloxacin selected most commonly for mutations in grlA, conferring substitutions for Ser-80. Three mutants of F77 were shown to have substitutions in both GrlA (Phe-80) and GyrA (Lys-88). Of the mutants selected from F193 (GrlA Phe-80), restriction fragment length polymorphism analysis of gyrA showed that 76/94 had a mutation at codon 84; those analysed in detail all had the substitution Ser-->Leu. Two mutants selected with grepafloxacin contained the substitution Lys-88. One mutant selected with trovafloxacin contained a novel mutation in gyrA substituting Gly-82-->Cys. Of the mutants selected from F194 (GrlA Tyr-80), 6/8 had a mutation in gyrA codon 84; of which three contained Leu. The MICs of most agents for mutants selected from F193 and F194 were similar, irrespective of the mutation selected. No mutants had any changes in grlB, and only one had a mutation in gyrB giving rise to the novel substitution Asp-437-->His. The mutations arising in first-step mutants were influenced by the fluoroquinolone used for selection. The phenotypes and genotypes of second-step mutants, derived from mutants with existing mutations in grlA, were similar, regardless of the selecting antibiotic.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Grepafloxacin	DNA gyrase subunit A	Protein	Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)	Yes	Inhibitor	Details