In Vitro selection of meropenem resistance among ceftazidime-avibactam-resistant, meropenem-susceptible Klebsiella pneumoniae isolates with variant KPC-3 carbapenemases

Ryan K. Shields; M. Hong Nguyen; Ellen G. Press; Liang Chen; Barry N. Kreiswirth; Cornelius J. Clancy

doi:10.1128/AAC.00079-17

In Vitro selection of meropenem resistance among ceftazidime-avibactam-resistant, meropenem-susceptible Klebsiella pneumoniae isolates with variant KPC-3 carbapenemases

Ryan K. Shields
, M. Hong Nguyen
, Ellen G. Press
, Liang Chen
, Barry N. Kreiswirth
, Cornelius J. Clancy

Center for Discovery and Innovation

University of Pittsburgh
Rutgers - The State University of New Jersey, Newark
VA Medical Center

Research output: Contribution to journal › Article › peer-review

103 Scopus citations

Abstract

Ceftazidime-avibactam resistance is mediated by bla_KPC-3 mutations, which restore carbapenem susceptibility. We subjected Klebsiella pneumoniae isolates with different bla_KPC-3 mutations (n = 5) or wild-type bla_KPC-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, bla_KPC-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.

Original language	English
Article number	e00079
Journal	Antimicrobial Agents and Chemotherapy
Volume	61
Issue number	5
DOIs	https://doi.org/10.1128/AAC.00079-17
State	Published - May 2017

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Carbapenem-resistant Enterobacteriaceae
Ceftazidime-avibactam resistance
Klebsiella pneumoniae carbapenemase
KPC mutations
Sequence type 258 Klebsiella pneumonia

Access to Document

10.1128/AAC.00079-17

Cite this

@article{6bd1ea48293c4ff6978361c6f50b1462,

title = "In Vitro selection of meropenem resistance among ceftazidime-avibactam-resistant, meropenem-susceptible Klebsiella pneumoniae isolates with variant KPC-3 carbapenemases",

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.",

keywords = "Carbapenem-resistant Enterobacteriaceae, Ceftazidime-avibactam resistance, Klebsiella pneumoniae carbapenemase, KPC mutations, Sequence type 258 Klebsiella pneumonia",

author = "Shields, \{Ryan K.\} and Nguyen, \{M. Hong\} and Press, \{Ellen G.\} and Liang Chen and Kreiswirth, \{Barry N.\} and Clancy, \{Cornelius J.\}",

year = "2017",

month = may,

doi = "10.1128/AAC.00079-17",

language = "English",

volume = "61",

journal = "Antimicrobial Agents and Chemotherapy",

issn = "0066-4804",

publisher = "American Society for Microbiology",

number = "5",

}

In Vitro selection of meropenem resistance among ceftazidime-avibactam-resistant, meropenem-susceptible Klebsiella pneumoniae isolates with variant KPC-3 carbapenemases. / Shields, Ryan K.; Nguyen, M. Hong; Press, Ellen G. et al.
In: Antimicrobial Agents and Chemotherapy, Vol. 61, No. 5, e00079, 05.2017.

Research output: Contribution to journal › Article › peer-review

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.

PY - 2017/5

Y1 - 2017/5

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.

AB - 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.

KW - Carbapenem-resistant Enterobacteriaceae

KW - Ceftazidime-avibactam resistance

KW - Klebsiella pneumoniae carbapenemase

KW - KPC mutations

KW - Sequence type 258 Klebsiella pneumonia

UR - https://www.scopus.com/pages/publications/85018185416

U2 - 10.1128/AAC.00079-17

DO - 10.1128/AAC.00079-17

M3 - Article

C2 - 28242667

AN - SCOPUS:85018185416

SN - 0066-4804

VL - 61

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

IS - 5

M1 - e00079

ER -

In Vitro selection of meropenem resistance among ceftazidime-avibactam-resistant, meropenem-susceptible Klebsiella pneumoniae isolates with variant KPC-3 carbapenemases

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Cite this