title: Mutations in the quinolone resistance determining region in Staphylococcus epidermidis recovered from conjunctiva and their association with susceptibility to various fluoroquinolones.
abstract: BACKGROUND
  Staphylococcus epidermidis is one of the prominent pathogens in ocular infection. The prevalence of mutations in the quinolone resistance determining region (QRDR) area in S epidermidis isolated from the ocular surface and its association with fluoroquinolone resistance has not been fully elucidated.
  
  
  METHODS
  Mutations in the QRDR of gyrA, gyrB, parC, and parE genes of 138 isolates of S epidermidis recovered from the human conjunctival flora were analysed. The minimal inhibitory concentrations (MICs) of four fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin and tosufloxacin) against these isolates were also determined using agar dilution methods.
  
  
  RESULTS
  The MIC(90) values of levofloxacin, gatifloxacin, moxifloxacin and tosufloxacin were 3.13, 1.56, 0.78 and 3.13 microg/ml, respectively. The MIC values of all fluoroquinolones showed a bimodal distribution (susceptible strain and less susceptible strain). Mutations with amino acid substitution in the QRDR were present in 70 (50.7%) isolates. 19 different combinations of mutations were detected: 3 isolates (2.2%) had four mutations, 8 (5.8%) had three mutations, 43 (31.2%) had double mutations and 16 (11.6%) had single mutations. Isolates with mutations in the QRDR of both gyrA and parC (n = 53) were less susceptible to fluoroquinolones.
  
  
  CONCLUSIONS
  The present findings show that approximately half the S epidermidis isolates from the normal human conjunctiva have mutation(s) in the QRDR. The presence of mutations in both gyrA and parC is strongly associated with reduced susceptibility to fluoroquinolones.
authors.affiliation: Division for Vision Research, National Institute of Sensory Organs, National Tokyo Medical Center, 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan. yamadamasakazu@kankakuki.go.jp
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: J
authors.initials: J
authors.lastname: Yoshida
authors.forename: S
authors.initials: S
authors.lastname: Hatou
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Minagawa
mesh_terms: D001372:Aza Compounds / Q000494:pharmacology; D003228:Conjunctiva / Q000382:microbiology*; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology; D000077734:Gatifloxacin; D019450:Genes, MDR; D006801:Humans; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D000077266:Moxifloxacin; D009154:Mutation; D009287:Naphthyridines / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D015363:Quinolones; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000235:genetics*
chemical_list: D001372:Aza Compounds; D024841:Fluoroquinolones; D009287:Naphthyridines; D011804:Quinolines; D015363:Quinolones; D064704:Levofloxacin; D015242:Ofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; C055185:tosufloxacin; D000077734:Gatifloxacin; D000077266:Moxifloxacin