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

Ryan K Shields; M Hong Nguyen; Brian A Potoski; Ellen G Press; Liang Chen; Barry N Kreiswirth; Lloyd G Clarke; Gregory A Eschenauer; Cornelius J Clancy

doi:10.1128/AAC.03894-14

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

Antimicrob Agents Chemother. 2015 Mar;59(3):1797-801. doi: 10.1128/AAC.03894-14. Epub 2014 Dec 22.

Authors

Ryan K Shields¹, M Hong Nguyen², Brian A Potoski³, Ellen G Press⁴, Liang Chen⁵, Barry N Kreiswirth⁵, Lloyd G Clarke⁶, Gregory A Eschenauer⁷, Cornelius J Clancy⁸

Affiliations

¹ 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.
² 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 [email protected].
³ Antibiotic Management Program, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
⁴ Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
⁵ Public Health Research Institute, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
⁶ Antibiotic Management Program, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
⁷ Antibiotic Management Program, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA Department of Pharmacy, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
⁸ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Anti-Bacterial Agents / therapeutic use
Bacteremia / drug therapy*
Bacteremia / microbiology
Bacterial Proteins / genetics*
Bacterial Proteins / metabolism
Carbapenems / therapeutic use*
Colistin / therapeutic use*
Doripenem
Drug Therapy, Combination / methods
Female
Genotype
Humans
Klebsiella Infections / drug therapy
Klebsiella Infections / microbiology
Klebsiella pneumoniae / drug effects*
Klebsiella pneumoniae / genetics
Klebsiella pneumoniae / metabolism
Male
Microbial Sensitivity Tests / methods
Middle Aged
Porins / drug effects
Porins / genetics*
Porins / metabolism
Retrospective Studies
beta-Lactamases / metabolism*

Substances

Anti-Bacterial Agents
Bacterial Proteins
Carbapenems
OmpK36 protein, Klebsiella pneumoniae
Porins
Doripenem
beta-lactamase KPC-2
beta-Lactamases
Colistin

Abstract

Publication types

MeSH terms

Substances

Grants and funding