title: Prevalence of gyrA, gyrB, parC, and parE mutations in clinical isolates of Streptococcus pneumoniae with decreased susceptibilities to different fluoroquinolones and originating from Worldwide Surveillance Studies during the 1997-1998 respiratory season.
abstract: From 8,419 worldwide clinical isolates of Streptococcus pneumoniae obtained during 1997-1998, 69 isolates with reduced susceptibility or resistance to fluoroquinolones (FQs) were molecularly characterized. For the isolates in this prevalence study, only parC (Ser-79-->Tyr) and gyrA (Ser-81-->Phe or Tyr) mutations, especially in combination, were found to contribute significantly to resistance. These mutations influenced the FQ MICs to varying degrees, although the rank order of activity remains independent of mutation type, with ciprofloxacin the least active, followed by levofloxacin, gatifloxacin/grepafloxacin/moxifloxacin/sparfloxaci n/trovafloxacin, and clinafloxacin/sitafloxacin. Efflux likely plays a crucial role in reduced susceptibility for new hydrophilic FQs.
authors.affiliation: MRL Pharmaceutical Services, Utrecht, The Netherlands. mjones@thetsn.com
authors.forename: M E
authors.initials: ME
authors.lastname: Jones
authors.forename: D F
authors.initials: DF
authors.lastname: Sahm
authors.forename: N
authors.initials: N
authors.lastname: Martin
authors.forename: S
authors.initials: S
authors.lastname: Scheuring
authors.forename: P
authors.initials: P
authors.lastname: Heisig
authors.forename: C
authors.initials: C
authors.lastname: Thornsberry
authors.forename: K
authors.initials: K
authors.lastname: Köhrer
authors.forename: F J
authors.initials: FJ
authors.lastname: Schmitz
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D027081:DNA Gyrase; D027101:DNA Topoisomerase IV; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004352:Drug Resistance, Microbial / Q000235:genetics; D024841:Fluoroquinolones; D005787:Gene Frequency; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D012137:Respiratory System / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics*
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D024841:Fluoroquinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; D004250:DNA Topoisomerases, Type II