title: Efflux-mediated resistance identified among norfloxacin resistant clinical strains of group B Streptococcus from South Korea.
abstract: OBJECTIVE
  Group B Streptococcus (GBS), a common bowel commensal, is a major cause of neonatal sepsis and an emerging cause of infection in immune-compromised adult populations. Fluoroquinolones are used to treat GBS infections in those allergic to beta-lactams, but GBS are increasingly resistant to fluoroquinolones. Fluoroquinolone resistance has been previously attributed to quinolone resistance determining regions (QRDRs) mutations. We demonstrate that some of fluoroquinolone resistance is due to efflux-mediated resistance.
  
  
  METHODS
  We tested 20 GBS strains resistant only to norfloxacin with no mutations in the QRDRs, for the efflux phenotype using norfloxacin and ethidium bromide as substrates in the presence of the efflux inhibitor reserpine. Also tested were 68 GBS strains resistant only to norfloxacin not screened for QRDRs, and 58 GBS strains resistant to ciprofloxacin, levofloxacin or moxifloxacin. Isolates were randomly selected from 221 pregnant women (35-37 weeks of gestation) asymptomatically carrying GBS, and 838 patients with GBS infection identified in South Korea between 2006 and 2008. The VITEK II automatic system (Biomerieux, Durham, NC, USA) was used to determine fluoroquinolone resistance.
  
  
  RESULTS
  The reserpine associated efflux phenotype was found in more than half of GBS strains resistant only to norfloxacin with no QRDR mutations, and half where QRDR mutations were unknown. No evidence of the efflux phenotype was detected in GBS strains that were resistant to moxifloxacin or levofloxacin or both. The reserpine sensitive efflux phenotype resulted in moderate increases in norfloxacin minimum inhibitory concentration (average=3.6 fold, range=>1-16 fold).
  
  
  CONCLUSIONS
  A substantial portion of GBS strains resistant to norfloxacin have an efflux phenotype.
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Trang Nguyen Doan
authors.initials: TN
authors.lastname: Dang
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Usha
authors.initials: U
authors.lastname: Srinivasan
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Zachary
authors.initials: Z
authors.lastname: Britt
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Carl F
authors.initials: CF
authors.lastname: Marrs
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Lixin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cancer Control and Policy, Graduated School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.
authors.forename: Moran
authors.initials: M
authors.lastname: Ki
authors.affiliation: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Betsy
authors.initials: B
authors.lastname: Foxman
keywords: Ciprofloxacin; Efflux; Fluoroquinolones; Levofloxacin; Minimum inhibitory concentration; Moxifloxacin; Mutations; Norfloxacin