title: Antimicrobial susceptibility breakpoints and first-step parC mutations in Streptococcus pneumoniae: redefining fluoroquinolone resistance.
abstract: Clinical antimicrobial susceptibility breakpoints are used to predict the clinical outcome of antimicrobial treatment. In contrast, microbiologic breakpoints are used to identify isolates that may be categorized as susceptible when applying clinical breakpoints but harbor resistance mechanisms that result in their reduced susceptibility to the agent being tested. Currently, the National Committee for Clinical Laboratory Standards (NCCLS) guidelines utilize clinical breakpoints to characterize the activity of the fluoroquinolones against Streptococcus pneumoniae. To determine whether levofloxacin breakpoints can identify isolates that harbor recognized resistance mechanisms, we examined 115 S. pneumoniae isolates with a levofloxacin MIC of >2 mg/mL for first-step parC mutations. A total of 48 (59%) of 82 isolates with a levofloxacin MIC of 2 mg/mL, a level considered susceptible by NCCLS criteria, had a first-step mutation in parC. Whether surveillance programs that use levofloxacin data can effectively detect emerging resistance and whether fluoroquinolones can effectively treat infections caused by such isolates should be evaluated.
authors.affiliation: Toronto Medical Laboratories/Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Sue
authors.initials: S
authors.lastname: Lim
authors.forename: Darrin
authors.initials: D
authors.lastname: Bast
authors.forename: Allison
authors.initials: A
authors.lastname: McGeer
authors.forename: Joyce
authors.initials: J
authors.lastname: de Azavedo
authors.forename: Donald E
authors.initials: DE
authors.lastname: Low
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics*; D015242:Ofloxacin / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics*
chemical_list: D000890:Anti-Infective Agents; D064704:Levofloxacin; D015242:Ofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase