title: Are fluoroquinolone-susceptible isolates of Streptococcus pneumoniae really susceptible? A comparison of resistance mechanisms in Canadian isolates from 1997 and 2003.
abstract: OBJECTIVE
  To assess the prevalence of efflux and amino acid substitutions in ParC and GyrA in Canadian clinical isolates of fluoroquinolone-susceptible Streptococcus pneumoniae with levofloxacin MICs of 1 mg/L collected before the introduction of the respiratory fluoroquinolones (1995-1997) and after 7 years of use (2003).
  
  
  METHODS
  Quinolone resistance determining regions of parC and gyrA were sequenced for 111 clinical isolates collected from 1995 to 1997 and 665 isolates collected in 2003. Efflux was assessed using a reserpine agar dilution method.
  
  
  RESULTS
  No isolates exhibited efflux. No significant increase in isolates harbouring amino acid substitutions was observed over time (0.9% in 1995-1997 to 2.1% in 2003, P = 0.32). However, the proportion of isolates with a ciprofloxacin MIC = 2 mg/L and a levofloxacin MIC = 1 mg/L versus ciprofloxacin MIC = 1 mg/L and a levofloxacin MIC = 1 mg/L increased over time (3.6% to 6.5%, P = 0.0021).
  
  
  CONCLUSIONS
  No increase in prevalence of first-step parC mutations was observed among all fluoroquinolone-susceptible clinical isolates of S. pneumoniae with levofloxacin MICs of 1 mg/L after the introduction of the respiratory fluoroquinolones; however, fluoroquinolones appear to be selecting for isolates with elevated ciprofloxacin MICs.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, 5th Floor, Basic Medical Sciences Building, 730 William Avenue, Winnipeg, Manitoba, R3E 0W3, Canada. kris_schurek@yahoo.com
authors.forename: Kristen N
authors.initials: KN
authors.lastname: Schurek
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Adam
authors.forename: Christine G
authors.initials: CG
authors.lastname: Siemens
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Hoban
authors.forename: Daryl J
authors.initials: DJ
authors.lastname: Hoban
authors.forename: George G
authors.initials: GG
authors.lastname: Zhanel
mesh_terms: D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002170:Canada / Q000453:epidemiology; D027081:DNA Gyrase / Q000235:genetics*; D027101:DNA Topoisomerase IV / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase