title: The combination of doripenem and colistin is bactericidal and synergistic against colistin-resistant, carbapenemase-producing Klebsiella pneumoniae.
abstract: We tested two-drug combinations of doripenem, colistin, gentamicin, and doxycycline against 12 carbapenemase-producing Klebsiella pneumoniae (KPC) isolates by time-kill. The combination of doripenem and colistin reduced the starting inocula by 2 logs for each isolate (range, 2.02 to 6.01 log(10)) and was bactericidal and synergistic against 75 and 50%, respectively. Among colistin- and pan-drug-resistant isolates, synergy was identified in 60 and 67%, respectively. All other combinations were inferior. We are currently evaluating the combination of doripenem and colistin as a frontline therapy for KPC infection.
authors.affiliation: Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Meredith G
authors.initials: MG
authors.lastname: Jernigan
authors.forename: Ellen G
authors.initials: EG
authors.lastname: Press
authors.forename: M Hong
authors.initials: MH
authors.lastname: Nguyen
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Clancy
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Shields
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015780:Carbapenems / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D000077726:Doripenem; D004338:Drug Combinations; D004347:Drug Interactions; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology*; D008826:Microbial Sensitivity Tests; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D004338:Drug Combinations; D000077726:Doripenem; D001618:beta-Lactamases; C063912:carbapenemase; D003091:Colistin