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. 2019 Sep 23;63(10):e00845-19.
doi: 10.1128/AAC.00845-19. Print 2019 Oct.

Antecedent Carbapenem Exposure as a Risk Factor for Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenemase-Producing Enterobacteriaceae

Kalisvar Marimuthu  1   2   3 , Oon Tek Ng  4   2   5 , Benjamin Pei Zhi Cherng  3   6   7 , Raymond Kok Choon Fong  8 , Surinder Kaur Pada  9 , Partha Pratim De  10 , Say Tat Ooi  11 , Nares Smitasin  3   12 , Koh Cheng Thoon  3   5   7   13 , Prabha Unny Krishnan  5   10   14 , Michelle Lay Teng Ang  14 , Douglas Su Gin Chan  15 , Andrea Lay Hoon Kwa  7   16 , Rama Narayana Deepak  17 , Yu Kit Chan  4   2 , Yvonne Fu Zi Chan  6 , Xiaowei Huan  2 , Kyaw Zaw Linn  2 , Nancy Wen Sim Tee  18 , Thean Yen Tan  19 , Tse Hsien Koh  7   20 , Raymond Tzer Pin Lin  14   18   21 , Li Yang Hsu  4   2   22 , Sharmila Sengupta  2 , David L Paterson  23 , Eli Perencevich  24 , Stephan Harbarth  25 , Jeanette Teo  18 , Indumathi Venkatachalam  6 ; CaPES Study Group
Collaborators, Affiliations

Antecedent Carbapenem Exposure as a Risk Factor for Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenemase-Producing Enterobacteriaceae

Kalisvar Marimuthu et al. Antimicrob Agents Chemother. .

Abstract

Carbapenem-resistant Enterobacteriaceae (CRE) can be mechanistically classified into carbapenemase-producing Enterobacteriaceae (CPE) and non-carbapenemase-producing carbapenem nonsusceptible Enterobacteriaceae (NCPCRE). We sought to investigate the effect of antecedent carbapenem exposure as a risk factor for NCPCRE versus CPE. Among all patients with CRE colonization and infection, we conducted a case-control study comparing patients with NCPCRE (cases) and patients with CPE (controls). The presence of carbapenemases was investigated with phenotypic tests followed by PCR for predominant carbapenemase genes. We included 843 unique patients with first-episode CRE, including 387 (45.9%) NCPCRE and 456 (54.1%) CPE. The resistance genes detected in CPEs were blaNDM (42.8%), blaKPC (38.4%), and blaOXA-48-like (12.1%). After adjusting for confounders and clustering at the institutional level, the odds of prior 30-day carbapenem exposure was three times higher among NCPCRE than CPE patients (adjusted odds ratio [aOR], 3.48; 95% confidence interval [CI], 2.39 to 5.09; P < 0.001). The odds of prior carbapenem exposure and NCPCRE detection persisted in stratified analyses by Enterobacteriaceae species (Klebsiella pneumoniae and Escherichia coli) and carbapenemase gene (blaNDM and blaKPC). CPE was associated with male gender (aOR, 1.45; 95% CI, 1.07 to 1.97; P = 0.02), intensive care unit stay (aOR, 1.84; 95% CI, 1.24 to 2.74; P = 0.003), and hospitalization in the preceding 1 year (aOR, 1.42; 95% CI, 1.01 to 2.02; P = 0.05). In a large nationwide study, antecedent carbapenem exposure was a significant risk factor for NCPCRE versus CPE, suggesting a differential effect of antibiotic selection pressure.

Keywords: carbapenem resistance; carbapenem-resistant Enterobacteriaceae; carbapenemase-producing Enterobacteriaceae; risk factors.

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