Molecular characterization of 8-methoxyfluoroquinolone resistance in a clinical isolate of methicillin-resistant Staphylococcus aureus.
BACKGROUND
Activity of gatifloxacin against clinical isolates of fluoroquinolone-resistant Staphylococcus aureus is more potent than that of other fluoroquinolones such as norfloxacin and levofloxacin. To date, few reports have described high-level resistance to gatifloxacin in clinical isolates of S. aureus, although in vitro studies have shown that mutations in both DNA gyrase and topoisomerase IV were required for gatifloxacin resistance in S. aureus.


METHODS
Minimum inhibitory concentrations were determined for fluoroquinolones and other antimicrobials in a methicillin-resistant S. aureus isolate that was cultured from blood of a patient with septicemia. Fluoroquinolone resistance was characterized by DNA sequencing and microbiologic assay.


RESULTS
The isolate showed high-level resistance to fluoroquinolones including an 8-methoxyfluoroquinolone, gatifloxacin (minimum inhibitory concentration 64 microg/ml). Amino acid mutations of Ser80Tyr and Glu84Lys in GrlA and Ser84Leu and Ser85Pro in GyrA were possibly related to this resistance in methicillin-resistant S. aureus HU2000-062, although efflux may play a minor role in resistance as well.


CONCLUSIONS
GyrA and GrlA mutations mainly conferred to 8-methoxyfluoroquinolone resistance in this isolate.
Horii
Toshinobu
T
Department of Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan. horiihm@hama-med.ac.jp
Suzuki
Yasuhiro
Y
Takeshita
Akihiro
A
Maekawa
Masato
M
D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D024901:Drug Resistance, Multiple, Bacterial; D024841:Fluoroquinolones / Q000627:therapeutic use*; D005798:Genes, Bacterial / Q000235:genetics; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D012772:Shock, Septic / Q000188:drug therapy / Q000401:mortality; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000401:mortality; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C075040:NorA protein, Staphylococcus