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Marimuthu K, Ng OT, Cherng BPZ, Fong RKC, Pada SK, De PP, Ooi ST, Smitasin N, Thoon KC, Krishnan PU, Ang MLT, Chan DSG, Kwa ALH, Deepak RN, Chan YK, Chan YFZ, Huan X, Zaw Linn K, Tee NWS, Tan TY, Koh TH, Lin RTP, Hsu LY, Sengupta S, Paterson DL, Perencevich E, Harbarth S, Teo J, Venkatachalam I, CaPES Study Group. Antecedent Carbapenem Exposure as a Risk Factor for Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae and Carbapenemase-Producing Enterobacteriaceae. Antimicrobial agents and chemotherapy. 2019 Oct 1; 63(10).
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Abstract: Carbapenem-resistant (CRE) can be mechanistically classified into carbapenemase-producing (CPE) and non-carbapenemase-producing carbapenem nonsusceptible (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 (42.8%), (38.4%), and (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; ? < 0.001). The odds of prior carbapenem exposure and NCPCRE detection persisted in stratified analyses by species ( and ) and carbapenemase gene ( and ). CPE was associated with male gender (aOR, 1.45; 95% CI, 1.07 to 1.97; ? = 0.02), intensive care unit stay (aOR, 1.84; 95% CI, 1.24 to 2.74; ? = 0.003), and hospitalization in the preceding 1?year (aOR, 1.42; 95% CI, 1.01 to 2.02; ? = 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.

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