title: Doripenem MICs and ompK36 porin genotypes of sequence type 258, KPC-producing Klebsiella pneumoniae may predict responses to carbapenem-colistin combination therapy among patients with bacteremia.
abstract: Treatment failures of a carbapenem-colistin regimen among patients with bacteremia due to sequence type 258 (ST258), KPC-2-producing Klebsiella pneumoniae were significantly more likely if both agents were inactive in vitro, as defined by a colistin MIC of >2 μg/ml and the presence of either a major ompK36 porin mutation (guanine and alanine insertions at amino acids 134 and 135 [ins aa 134-135 GD], IS5 promoter insertion [P = 0.007]) or a doripenem MIC of >8 μg/ml (P = 0.01). Major ompK36 mutations among KPC-K. pneumoniae strains are important determinants of carbapenem-colistin responses in vitro and in vivo.
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA Antibiotic Management Program, University of Pittsburgh Medical Center, 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: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA Antibiotic Management Program, University of Pittsburgh Medical Center, 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
authors.affiliation: Antibiotic Management Program, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Potoski
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Ellen G
authors.initials: EG
authors.lastname: Press
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
authors.affiliation: Antibiotic Management Program, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Lloyd G
authors.initials: LG
authors.lastname: Clarke
authors.affiliation: Antibiotic Management Program, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA Department of Pharmacy, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Eschenauer
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA VA Pittsburgh Health System, Pittsburgh, Pennsylvania, USA.
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Clancy
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015780:Carbapenems / Q000627:therapeutic use*; D003091:Colistin / Q000627:therapeutic use*; D000077726:Doripenem; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005838:Genotype; D006801:Humans; D007710:Klebsiella Infections / Q000188:drug therapy / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D018272:Porins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; C092233:OmpK36 protein, Klebsiella pneumoniae; D018272:Porins; D000077726:Doripenem; C491478:beta-lactamase KPC-2; D001618:beta-Lactamases; D003091:Colistin