title: Increase in fluoroquinolone non-susceptibility among clinical Streptococcus pyogenes in Belgium during 2007-10.
abstract: OBJECTIVE
  To study the temporal evolution of fluoroquinolone non-susceptibility among Streptococcus pyogenes during 2007-10 in Belgium.
  
  
  METHODS
  S. pyogenes (n = 4690) recovered from patients with tonsillopharyngitis or skin, wound or invasive infections were screened for fluoroquinolone non-susceptibility. A selection of fluoroquinolone-non-susceptible strains was investigated for resistance mechanisms: reserpine-sensitive efflux and mutations in topoisomerase genes parC and gyrA. Clonality was determined by emm typing.
  
  
  RESULTS
  Fluoroquinolone non-susceptibility (ciprofloxacin MIC ≥2 mg/L) was identified in 535 (11.4%) of 4690 S. pyogenes recovered during 2007-10 in Belgium. The proportion of fluoroquinolone-non-susceptible S. pyogenes increased significantly from 4.3% (2008) to 10.9% (2009) to 21.6% (2010) and coincided with a significant increase in emm6 strains among fluoroquinolone-non-susceptible S. pyogenes. Ciprofloxacin MICs of 2-8 mg/L correlated with first-step ParC substitutions. Two high-level fluoroquinolone-resistant S. pyogenes strains (ciprofloxacin MICs 32 mg/L) showed second-step substitutions in GyrA (Ser-81→Phe or Tyr) in addition to first-step mutations in parC. Reserpine-sensitive efflux was not observed.
  
  
  CONCLUSIONS
  We report an unprecedented increase in fluoroquinolone-non-susceptible S. pyogenes in Belgium, a country with high quinolone use, as well as emergence of two high-level fluoroquinolone-resistant S. pyogenes strains with second-step mutations in gyrA, warning us of the need for more prudent use of fluoroquinolones and for continued resistance surveillance.
authors: National Reference Centre for Group A Streptococcus, Department of Medical Microbiology, Vaccine & Infectious Disease Institute,  Universiteit Antwerpen, Antwerp,  Belgium.
authors: Liesbet
authors: L
authors: Van Heirstraeten
authors: Gert
authors: G
authors: Leten
authors: Christine
authors: C
authors: Lammens
authors: Herman
authors: H
authors: Goossens
authors: Surbhi
authors: S
authors: Malhotra-Kumar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000942:Antigens, Bacterial / Q000235:genetics; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics; D001530:Belgium / Q000453:epidemiology; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D005260:Female; D024841:Fluoroquinolones / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011008:Pneumococcal Infections / Q000453:epidemiology* / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D004269:DNA, Bacterial; D024841:Fluoroquinolones; C014689:streptococcal M protein; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase