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. 2019 Mar;93(3):250-257.
doi: 10.1016/j.diagmicrobio.2018.10.004. Epub 2018 Oct 13.

Diversity of resistance mechanisms in carbapenem-resistant Enterobacteriaceae at a health care system in Northern California, from 2013 to 2016

Fiona Senchyna  1 , Rajiv L Gaur  1 , Johanna Sandlund  1 , Cynthia Truong  1 , Guillaume Tremintin  2 , Dietmar Kültz  3 , Carlos A Gomez  4 , Fiona B Tamburini  5 , Tessa Andermann  6 , Ami Bhatt  5 , Isabella Tickler  7 , Nancy Watz  8 , Indre Budvytiene  8 , Gongyi Shi  2 , Fred C Tenover  7 , Niaz Banaei  9
Affiliations

Diversity of resistance mechanisms in carbapenem-resistant Enterobacteriaceae at a health care system in Northern California, from 2013 to 2016

Fiona Senchyna et al. Diagn Microbiol Infect Dis. 2019 Mar.

Abstract

The mechanism of resistance in carbapenem-resistant Enterobacteriaceae (CRE) has therapeutic implications. We comprehensively characterized emerging mechanisms of resistance in CRE between 2013 and 2016 at a health system in Northern California. A total of 38.7% (24/62) of CRE isolates were carbapenemase gene-positive, comprising 25.0% (6/24) blaOXA-48 like, 20.8% (5/24) blaKPC, 20.8% (5/24) blaNDM, 20.8% (5/24) blaSME, 8.3% (2/24) blaIMP, and 4.2% (1/24) blaVIM. Between carbapenemases and porin loss, the resistance mechanism was identified in 95.2% (59/62) of CRE isolates. Isolates expressing blaKPC were 100% susceptible to ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam; blaOXA-48 like-positive isolates were 100% susceptible to ceftazidime-avibactam; and metallo β-lactamase-positive isolates were nearly all nonsusceptible to above antibiotics. Carbapenemase gene-negative CRE were 100% (38/38), 92.1% (35/38), 89.5% (34/38), and 31.6% (12/38) susceptible to ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, and ceftolozane-tazobactam, respectively. None of the CRE strains were identical by whole genome sequencing. At this health system, CRE were mediated by diverse mechanisms with predictable susceptibility to newer β-lactamase inhibitors.

Keywords: Avibactam; Carbapenem-resistant Enterobacteriaceae; Carbapenemase; Porin; Relebactam; Vaborbactam.

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Conflict of interest statement

Declarations of interest: none.

Figures

Fig. 1.
Fig. 1.
Carbapenemase genes detected in CRE isolates annually from 2013 to 2016. Carbapenemase genes tested include blaKPC, blaNDM, blaIMP, blaVIM, blaOXA-48 like, blaSME, blaSIM, blaSPM, blaGES, blaIMI, blaNMC-A, and blaGIM.
Fig. 2.
Fig. 2.
Porin protein and mRNA levels in CRE isolates with and without a carbapenemase gene. Bars show percentage of carbapenemase gene-positive (CARBase gene +) and gene-negative (CARBase gene−) CRE isolates with relative protein (A) and porin mRNA (B) down 2-fold or more compared with susceptible isolates.
Fig. 3.
Fig. 3.
Susceptibility of CRE isolates to imipenem–relebactam, meropenem–vaborbactam, ceftazidime–avibactam, and ceftolozane–tazobactam. Bars show percent susceptibility of carbapenemase gene-positive (CARBase gene +) and gene-negative (CARBase gene−) CRE to (A) imipenem–relebactam, (C) meropenem–vaborbactam, (E) ceftazidime–avibactam, and (G) ceftolozane–tazobactam. Graphs on the right (B, D, F, H) show fraction of carbapenemase genes detected in carbapenemase gene-positive isolates that are susceptible, intermediate, or resistant to the respective antibiotic combination.
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