title: Effect of low-level resistance on subsequent enrichment of fluoroquinolone-resistant Streptococcus pneumoniae in rabbits.
abstract: BACKGROUND
  We measured the effect of low-level fluoroquinolone resistance in Streptococcus pneumoniae on the development of high-level resistance within the context of the mutant selection window.
  
  
  METHODS
  Rabbits infected with S. pneumoniae were treated with ciprofloxacin or moxifloxacin concentrations that simulated pharmacokinetics in treated humans; bacteria obtained from lungs were examined for fluoroquinolone susceptibility.
  
  
  RESULTS
  Ciprofloxacin enriched resistant mutants from a wild-type strain; moxifloxacin did not. However, moxifloxacin enriched resistant mutants from a parC mutant; the drug concentration at the top of the selection window was determined.
  
  
  CONCLUSIONS
  A parC resistance mutation facilitates the enrichment of high-level resistance, as was predicted by in vitro measurements.
authors.affiliation: Service des Maladies Infectieuses, Hopital du Bocage, Dijon, France.
authors.forename: Manuel
authors.initials: M
authors.lastname: Etienne
authors.forename: Delphine
authors.initials: D
authors.lastname: Croisier
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Charles
authors.forename: Catherine
authors.initials: C
authors.lastname: Lequeu
authors.forename: Lionel
authors.initials: L
authors.lastname: Piroth
authors.forename: Henri
authors.initials: H
authors.lastname: Portier
authors.forename: Karl
authors.initials: K
authors.lastname: Drlica
authors.forename: Pascal
authors.initials: P
authors.lastname: Chavanet
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001372:Aza Compounds / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000627:therapeutic use; D027101:DNA Topoisomerase IV / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D024841:Fluoroquinolones / Q000494:pharmacology*; D008168:Lung / Q000382:microbiology; D000077266:Moxifloxacin; D009154:Mutation; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D011804:Quinolines / Q000627:therapeutic use; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
chemical_list: D000890:Anti-Infective Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D002939:Ciprofloxacin; D027101:DNA Topoisomerase IV; D000077266:Moxifloxacin