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In Vitro Selection of Meropenem Resistance among Ceftazidime-Avibactam-Resistant, Meropenem-Susceptible Klebsiella pneumoniae Isolates with Variant KPC-3 Carbapenemases.
Antimicrob Agents Chemother. 2017 05; 61(5)AA

Abstract

Ceftazidime-avibactam resistance is mediated by blaKPC-3 mutations, which restore carbapenem susceptibility. We subjected Klebsiella pneumoniae isolates with different blaKPC-3 mutations (n = 5) or wild-type blaKPC-3 (n = 2) to serial passages with meropenem. The meropenem MIC against each isolate increased. Mutations in the ompK36 porin gene evolved in 5 isolates. Among isolates with D179Y substitutions in KPC-3, blaKPC-3 mutations reverted to wild type, were replaced by new mutations, or were retained. Carbapenem treatment of ceftazidime-avibactam-resistant K. pneumoniae infections may select for carbapenem resistance.

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Authors+Show Affiliations

Shields RK
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Nguyen MH
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA mhn5@pitt.edu. XDR Pathogen Laboratory, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Press EG
Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Chen L
Public Health Research Institute Tuberculosis Center, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
Kreiswirth BN
Public Health Research Institute Tuberculosis Center, New Jersey Medical School, Rutgers University, Newark, New Jersey, USA.
Clancy CJ
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.

MeSH

Anti-Bacterial AgentsAzabicyclo CompoundsBacterial ProteinsCarbapenem-Resistant EnterobacteriaceaeCeftazidimeDrug CombinationsDrug Resistance, Multiple, BacterialHumansKlebsiella pneumoniaeMeropenemMicrobial Sensitivity TestsPorinsSelection, GeneticThienamycinsbeta-Lactamases

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28242667

Citation

Shields, Ryan K., et al. "In Vitro Selection of Meropenem Resistance Among Ceftazidime-Avibactam-Resistant, Meropenem-Susceptible Klebsiella Pneumoniae Isolates With Variant KPC-3 Carbapenemases." Antimicrobial Agents and Chemotherapy, vol. 61, no. 5, 2017.
Shields RK, Nguyen MH, Press EG, et al. In Vitro Selection of Meropenem Resistance among Ceftazidime-Avibactam-Resistant, Meropenem-Susceptible Klebsiella pneumoniae Isolates with Variant KPC-3 Carbapenemases. Antimicrob Agents Chemother. 2017;61(5).
Shields, R. K., Nguyen, M. H., Press, E. G., Chen, L., Kreiswirth, B. N., & Clancy, C. J. (2017). In Vitro Selection of Meropenem Resistance among Ceftazidime-Avibactam-Resistant, Meropenem-Susceptible Klebsiella pneumoniae Isolates with Variant KPC-3 Carbapenemases. Antimicrobial Agents and Chemotherapy, 61(5). https://doi.org/10.1128/AAC.00079-17
Shields RK, et al. In Vitro Selection of Meropenem Resistance Among Ceftazidime-Avibactam-Resistant, Meropenem-Susceptible Klebsiella Pneumoniae Isolates With Variant KPC-3 Carbapenemases. Antimicrob Agents Chemother. 2017;61(5) PubMed PMID: 28242667.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In Vitro Selection of Meropenem Resistance among Ceftazidime-Avibactam-Resistant, Meropenem-Susceptible Klebsiella pneumoniae Isolates with Variant KPC-3 Carbapenemases. AU - Shields,Ryan K, AU - Nguyen,M Hong, AU - Press,Ellen G, AU - Chen,Liang, AU - Kreiswirth,Barry N, AU - Clancy,Cornelius J, Y1 - 2017/04/24/ PY - 2017/01/12/received PY - 2017/02/19/accepted PY - 2017/3/1/pubmed PY - 2017/12/12/medline PY - 2017/3/1/entrez KW - KPC mutations KW - Klebsiella pneumoniae carbapenemase KW - carbapenem-resistant Enterobacteriaceae KW - ceftazidime-avibactam resistance KW - sequence type 258 Klebsiella pneumoniae JF - Antimicrobial agents and chemotherapy JO - Antimicrob Agents Chemother VL - 61 IS - 5 N2 - Ceftazidime-avibactam resistance is mediated by blaKPC-3 mutations, which restore carbapenem susceptibility. We subjected Klebsiella pneumoniae isolates with different blaKPC-3 mutations (n = 5) or wild-type blaKPC-3 (n = 2) to serial passages with meropenem. The meropenem MIC against each isolate increased. Mutations in the ompK36 porin gene evolved in 5 isolates. Among isolates with D179Y substitutions in KPC-3, blaKPC-3 mutations reverted to wild type, were replaced by new mutations, or were retained. Carbapenem treatment of ceftazidime-avibactam-resistant K. pneumoniae infections may select for carbapenem resistance. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/28242667/In_Vitro_Selection_of_Meropenem_Resistance_among_Ceftazidime_Avibactam_Resistant_Meropenem_Susceptible_Klebsiella_pneumoniae_Isolates_with_Variant_KPC_3_Carbapenemases_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=28242667 DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓27 ↑15]

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