title: Concentration-resistance relationships with Pseudomonas aeruginosa exposed to doripenem and ciprofloxacin in an in vitro model.
abstract: OBJECTIVE
  To compare the abilities of doripenem and ciprofloxacin to restrict the enrichment of resistant Pseudomonas aeruginosa, multiple antibiotic dosing regimens were simulated in an in vitro model at comparable ratios of the 24 h AUC (AUC24) to the MIC.
  
  
  METHODS
  Three clinical isolates of ciprofloxacin-resistant P. aeruginosa (MIC of doripenem 1 mg/L, MIC of ciprofloxacin 4 mg/L) were exposed to thrice-daily doripenem or twice-daily ciprofloxacin for 3 days at AUC24/MIC ratios from 50 to 170 h (doripenem) and from 55 to 180 h (ciprofloxacin).
  
  
  RESULTS
  Doripenem- and ciprofloxacin-resistant mutants were enriched at antibiotic concentrations that fell into the mutant selection window for ≥ 45% and ≥ 60% of the dosing interval, respectively. The anti-mutant effects of doripenem and ciprofloxacin expressed by the area under the bacterial mutant concentration-time curve (AUBCM) depended on the AUC24/MIC ratio, and the AUBCM-log AUC24/MIC relationships were antibiotic specific.
  
  
  CONCLUSIONS
  Based on AUC24/MIC relationships with AUBCM, a greater anti-mutant potential was predicted for doripenem compared with ciprofloxacin.
authors.affiliation: Mount Auburn Hospital, Harvard Medical School, Cambridge, MA, USA.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Zinner
authors.forename: Deborah
authors.initials: D
authors.lastname: Gilbert
authors.forename: Kenneth
authors.initials: K
authors.lastname: Greer
authors.forename: Yury A
authors.initials: YA
authors.lastname: Portnoy
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Firsov
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D000077726:Doripenem; D024881:Drug Resistance, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002939:Ciprofloxacin; D000077726:Doripenem