• Kalisvar Marimuthu, Oon Tek Ng, Benjamin Pei Zhi Cherng, Raymond Kok Choon Fong, Surinder Kaur Pada, Partha Pratim De, Say Tat Ooi, Nares Smitasin, Koh Cheng Thoon, Prabha Unny Krishnan, Michelle Lay Teng Ang, Douglas Su Gin Chan, Andrea Lay Hoon Kwa, Rama Narayana Deepak, Yu Kit Chan, Yvonne Fu Zi Chan, Xiaowei Huan, Zaw LinnKyawKNational Centre for Infectious Diseases, Singapore., TeeNancy Wen SimNWSDepartment of Laboratory Medicine, National University Hospital, Singapore., Thean Yen Tan, Tse Hsien Koh, LinRaymond Tzer PinRTPNational Public Health Laboratory, National Centre for Infectious Diseases, Singapore.Department of Laboratory Medicine, National University Hospital, Singapore.Department of Microbiology and Immunology, National University of Singap, Li Yang Hsu, Sharmila Sengupta, David L Paterson, Eli Perencevich, Stephan Harbarth, Jeanette Teo, Indumathi Venkatachalam, and CaPES Study Group.
• Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore kalisvar_marimuthu@ttsh.com.sg.
• Antimicrob. Agents Chemother. 2019 Oct 1; 63 (10).

AbstractCarbapenem-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 bla NDM (42.8%), bla KPC (38.4%), and bla OXA-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 (bla NDM and bla KPC). 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.Copyright © 2019 American Society for Microbiology.

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