Case–case–control study of risk factors for carbapenem-resistant Enterobacterales infections among hospitalized patients

Abstract Objective: To identify important risk factors for carbapenem-resistant Enterobacterales (CRE) infections among hospitalized patients. Design: We utilized a case–case–control design that compared patients with CRE infections to patients with carbapenem-susceptible Enterobacterales (CSE) infections and randomly selected controls during the period from January 2011 through December 2016. Setting: The study population was selected from patients at a large metropolitan tertiary-care and instructional medical center. Patients: Cases of CRE were defined as initial admission of adults diagnosed with a bacterial infection of an Enterobacterales species resistant clinically or through sensitivity testing to carbapenems 48 hours or more after admission. Cases of CSE were selected from the same patient population as the CRE cases within a 30-day window for admission, with diagnostic pathogens identified as susceptible to carbapenems. Controls were defined as adult patients admitted to any service within a 30-day window from a CRE case for >48 hours who did not meet either of the above case definitions during that admission. Results: Antibiotic exposure within 90 days prior to admission and length of hospital stay were both associated with increased odds of CRE and CSE infections compared to controls. Patients with CRE infections had >18 times greater odds of prior antibiotic exposure compared to patients with CSE infections. Conclusions: Antibiotic exposure and increased length of hospital stay may result in increased patient risk of developing an infection resistant to carbapenems and other β-lactams.