title: In VitroSelection of Meropenem Resistance among Ceftazidime-Avibactam-Resistant, Meropenem-Susceptible Klebsiella pneumoniae Isolates with Variant KPC-3 Carbapenemases.
abstract: Ceftazidime-avibactam resistance is mediated byblaKPC-3mutations, which restore carbapenem susceptibility. We subjectedKlebsiella pneumoniaeisolates with differentblaKPC-3mutations (n= 5) or wild-typeblaKPC-3(n= 2) to serial passages with meropenem. The meropenem MIC against each isolate increased. Mutations in theompK36porin gene evolved in 5 isolates. Among isolates with D179Y substitutions in KPC-3,blaKPC-3mutations reverted to wild type, were replaced by new mutations, or were retained. Carbapenem treatment of ceftazidime-avibactam-resistantK. pneumoniaeinfections may select for carbapenem resistance.
authors.affiliation: Department of Medicine, 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: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA mhn5@pitt.edu.|XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: M Hong
authors.initials: MH
authors.lastname: Nguyen
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 Tuberculosis Center, 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 Tuberculosis Center, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.|XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.|VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, USA.
authors.forename: Cornelius J
authors.initials: CJ
authors.lastname: Clancy
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics*; D000073182:Carbapenem-Resistant Enterobacteriaceae / Q000235:genetics; D002442:Ceftazidime / Q000494:pharmacology*; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D018272:Porins / Q000235:genetics; D012641:Selection, Genetic / Q000235:genetics; D013845:Thienamycins / Q000494:pharmacology*; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D001426:Bacterial Proteins; D004338:Drug Combinations; C092233:OmpK36 protein, Klebsiella pneumoniae; D018272:Porins; D013845:Thienamycins; C000595613:avibactam, ceftazidime drug combination; D002442:Ceftazidime; D001618:beta-Lactamases; C495220:beta-lactamase KPC-3, Klebsiella pneumoniae; C063912:carbapenemase; D000077731:Meropenem
keywords: KPC mutations; Klebsiella pneumoniae carbapenemase; carbapenem-resistant Enterobacteriaceae; ceftazidime-avibactam resistance; sequence type 258 Klebsiella pneumoniae