Risk Factors for and Mechanisms of listin esistance Among nterobacterales: Getting at the CORE of the Issue.

Background: Despite the recent emergence of plasmid-mediated colistin resistance, the epidemiology and mechanisms of colistin-resistant Enterobacterales (CORE) infections remain poorly understood.

Methods: A case-case-control study was conducted utilizing routine clinical isolates obtained at a single tertiary health system in Ann Arbor, Michigan. Patients with CORE isolates from January 1, 2016, to March 31, 2017, were matched 1:1 with patients with colistin-susceptible Enterobacterales (COSE) and uninfected controls. Multivariable logistic regression was used to compare clinical and microbiologic features of patients with CORE and COSE to controls. A subset of available CORE isolates underwent whole-genome sequencing to identify putative colistin resistance genes.

Results: Of 16 373 tested clinical isolates, 166 (0.99%) were colistin-resistant, representing 103 unique patients. Among 103 CORE isolates, 103 COSE isolates, and 102 uninfected controls, antibiotic exposure in the antecedent 90 days and age >55 years were predictors of both CORE and COSE. Of 33 isolates that underwent whole-genome sequencing, a large variety of mutations associated with colistin resistance were identified, including 4 -1/-1.1 genes and 4 mutations among 9 isolates and 5 and 3 mutations among 8 isolates. Genetic mutations found in species were not associated with known phenotypic colistin resistance.

Conclusions: Increased age and prior antibiotic receipt were associated with increased risk for patients with CORE and for patients with COSE. -1, , and were the predominant colistin resistance-associated mutations identified among and respectively. Mechanisms of colistin resistance among species could not be determined.