title: Assessment of the combination of doripenem plus a fluoroquinolone against non-susceptible Acinetobacter baumannii isolates from nosocomial pneumonia patients.
abstract: Carbapenem- and fluoroquinolone-non-susceptible Acinetobacter baumannii were obtained from four nosocomial pneumonia patients who were clinically cured following combination therapy with doripenem/levofloxacin or ciprofloxacin. In vitro synergy of doripenem/levofloxacin or ciprofloxacin was evaluated using time-kill analysis. In vivo synergy was tested using a mouse lethal infection model. In time-kill studies, doripenem and levofloxacin were both bactericidal when tested at Cmax; at ½Cmax, the combination showed synergy up to 8 hours. Ciprofloxacin, alone or combined with doripenem, was not bactericidal. For mouse septicemia, doripenem (100 mg/kg) was ≥90% effective in preventing death in all four isolates. Levofloxacin (200 mg/kg) was 73% effective, and ciprofloxacin (35 mg/kg) was ineffective in preventing death. At lower drug concentrations, increased efficacy was observed for doripenem/levofloxacin, but not for doripenem/ciprofloxacin. Overall, the results suggest that a doripenem/levofloxacin combination may have clinical utility in treating some non-susceptible A. baumannii infections.
authors.affiliation: Janssen Research and Development, LLC, Raritan, NJ 08869, USA.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Queenan
authors.forename: Todd A
authors.initials: TA
authors.lastname: Davies
authors.forename: Wenping
authors.initials: W
authors.lastname: He
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Lynch
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy*; D040981:Acinetobacter baumannii / Q000187:drug effects; D000818:Animals; D015780:Carbapenems / Q000008:administration & dosage* / Q000494:pharmacology; D002939:Ciprofloxacin / Q000008:administration & dosage* / Q000494:pharmacology; D000077726:Doripenem; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D064704:Levofloxacin; D051379:Mice; D015242:Ofloxacin / Q000008:administration & dosage* / Q000494:pharmacology; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy*; D011897:Random Allocation; D016019:Survival Analysis
chemical_list: D015780:Carbapenems; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin; D000077726:Doripenem