title: Comparative in vitro activity of PGE 9262932 and fluoroquinolones against Canadian clinical Streptococcus pneumoniae isolates, including molecularly characterized ciprofloxacin-resistant isolates.
abstract: OBJECTIVE
  The aim of this study was to assess the in vitro activity of the non-fluorinated quinolone PGE 9262932 against Streptococcus pneumoniae isolates with various resistance phenotypes: ciprofloxacin-resistant, macrolide-resistant, penicillin-resistant and trimethoprim/sulfamethoxazole-resistant.
  
  
  METHODS
  The in vitro activity of PGE 9262932 against 2585 recent Canadian S. pneumoniae isolates with various resistance phenotypes was determined and compared with that of gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin. In particular, the activity of PGE 9262932 against ciprofloxacin-resistant isolates with defined parC and gyrA mutations was assessed.
  
  
  RESULTS
  PGE 9262932 MIC90s were < or = 0.015 mg/L for all S. pneumoniae and 0.12 mg/L for the ciprofloxacin-resistant isolates. Resistance to penicillin, macrolides or trimethoprim/sulfamethoxazole had little effect on the PGE 9262932 MICs. The quinolone MIC50/90s were only slightly affected by the presence of one parC or gyrA mutation, but increased 2- to 16-fold in the presence of mutations in both parC and gyrA, depending on the specific quinolone. With each quinolone resistance genotype, the order of activity, based on MIC90, against the ciprofloxacin-resistant isolates was PGE 9262932, gemifloxacin, moxifloxacin, gatifloxacin and levofloxacin.
  
  
  CONCLUSIONS
  PGE 9262932 was the most active quinolone against all S. pneumoniae isolates, regardless of resistance phenotype.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Manitoba 730 William Avenue, Winnipeg, Manitoba, R3E 0W3, Canada. hjadam@gmail.com
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Adam
authors.forename: Kristen N
authors.initials: KN
authors.lastname: Schurek
authors.forename: Melanie R
authors.initials: MR
authors.lastname: Decorby
authors.forename: Barbara
authors.initials: B
authors.lastname: Weshnoweski
authors.forename: Ravinder
authors.initials: R
authors.lastname: Vashisht
authors.forename: Kathy
authors.initials: K
authors.lastname: Karlowsky
authors.forename: Daryl J
authors.initials: DJ
authors.lastname: Hoban
authors.forename: George G
authors.initials: GG
authors.lastname: Zhanel
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002170:Canada; D002939:Ciprofloxacin / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011008:Pneumococcal Infections / Q000453:epidemiology / Q000382:microbiology; D015363:Quinolones / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C466660:PGE 9262932; D015363:Quinolones; D002939:Ciprofloxacin