title: Doripenem, gentamicin, and colistin, alone and in combinations, against gentamicin-susceptible, KPC-producing Klebsiella pneumoniae strains with various ompK36 genotypes.
abstract: Gentamicin doses of 2 and 10 μg/ml were bactericidal against 64% and 100%, respectively, of gentamicin-susceptible KPC-2-producing Klebsiella pneumoniae strains. Treatment with the combination of doripenem (8 μg/ml) plus colistin (2 μg/ml) was inferior to treatment with gentamicin (2 μg/ml), doripenem-gentamicin, gentamicin-colistin, and doripenem-gentamicin-colistin against strains with glycine and aspartic acid insertions in OpmK36 porin at amino acid (aa) positions 134 and 135 (n = 9). Doripenem-colistin was comparable to other 2- or 3-drug regimens and superior to single drugs against wild-type/minor ompK36 mutants (n = 5). An algorithm incorporating ompK36 genotypes and susceptibility to gentamicin and doripenem may predict antimicrobial activity against KPC-producing K. pneumoniae.
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania, USA XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA Pittsburgh VA Healthcare System, Pittsburgh, Pennsylvania, USA.
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Clancy
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania, USA XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Binghua
authors.initials: B
authors.lastname: Hao
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania, USA XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Shields
authors.affiliation: Public Health Research Institute, New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Public Health Research Institute, New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Perlin
authors.affiliation: Public Health Research Institute, New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA.
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
authors.affiliation: University of Pittsburgh, Pittsburgh, Pennsylvania, USA XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA mhn5@pitt.edu.
authors.forename: M Hong
authors.initials: MH
authors.lastname: Nguyen
mesh_terms: D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001224:Aspartic Acid; D001426:Bacterial Proteins / Q000235:genetics; D015780:Carbapenems / Q000494:pharmacology*; D003091:Colistin / Q000494:pharmacology*; D000077726:Doripenem; D004359:Drug Therapy, Combination; D005838:Genotype; D005839:Gentamicins / Q000494:pharmacology*; D005998:Glycine; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D008826:Microbial Sensitivity Tests; D016254:Mutagenesis, Insertional; D018272:Porins / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D005839:Gentamicins; D018272:Porins; D001224:Aspartic Acid; D000077726:Doripenem; D001618:beta-Lactamases; C547585:beta-lactamase KPC-2, Klebsiella pneumoniae; D005998:Glycine; D003091:Colistin