title: Clonal spread of fluoroquinolone non-susceptible Streptococcus pyogenes.
abstract: BACKGROUND
  Fluoroquinolones are an important group of antibiotics widely used in adults, and, despite the absence of official approval, these drugs are also used in children. So far, resistance to fluoroquinolones in Streptococcus pyogenes is very rare.
  
  
  METHODS
  During a national surveillance programme in Belgium from 1999 to 2002, 2793 non-duplicate S. pyogenes recovered from tonsillopharyngitis patients were screened for fluoroquinolone resistance. Mutations in topoisomerase genes and the presence of any efflux pump activity were investigated to elucidate the fluoroquinolone resistance mechanisms. Clonality was assessed by pulsed-field gel electrophoresis (PFGE) and emm typing.
  
  
  RESULTS
  Non-susceptibility to fluoroquinolones, defined as ciprofloxacin MIC > or = 2 mg/L, was identified in 152 (5.4%) of 2793 S. pyogenes. Fifty-five (36%) fluoroquinolone non-susceptible isolates were investigated for known resistance mechanisms; all showed mutations in parC, and 29 (19%) isolates also in parE; antibiotic efflux was not noted. Two major PFGE types comprised 88% of fluoroquinolone non-susceptible S. pyogenes and belonged to serotypes emm6 and emm75. Overall, emm6 and emm75 constituted >90% of all fluoroquinolone non-susceptible isolates and showed a significant temporal and geographical shift within Belgian provinces. Although fluoroquinolone-susceptible S. pyogenes also showed fluctuations in the predominant S. pyogenes serotypes, emm6 or emm75 were under-represented in this population. Approx. 55% of the fluoroquinolone non-susceptible isolates were recovered from children ( < or =16 years).
  
  
  CONCLUSIONS
  We show here, for the first time, a multi-clonal spread of fluoroquinolone non-susceptible S. pyogenes exhibiting a known resistance mechanism. Non-susceptibility to fluoroquinolones in paediatric isolates is of concern.
authors.affiliation: Belgian Reference Centre for Group A Streptococcus, University of Antwerp, Campus Drie Eiken, S3, Universiteitsplein 1, B-2610 Wilrijk, Antwerp, Belgium. surbhi.malhotra@ua.ac.be
authors.forename: Surbhi
authors.initials: S
authors.lastname: Malhotra-Kumar
authors.forename: Christine
authors.initials: C
authors.lastname: Lammens
authors.forename: Sabine
authors.initials: S
authors.lastname: Chapelle
authors.forename: Cecile
authors.initials: C
authors.lastname: Mallentjer
authors.forename: Joost
authors.initials: J
authors.lastname: Weyler
authors.forename: Herman
authors.initials: H
authors.lastname: Goossens
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008826:Microbial Sensitivity Tests; D013297:Streptococcus pyogenes / Q000187:drug effects*
chemical_list: D024841:Fluoroquinolones