Risk Factors and Outcomes Associated With Acquisition of Daptomycin and Linezolid–Nonsusceptible Vancomycin-Resistant Enterococcus

BACKGROUND: Vancomycin-resistant enterococcus (VRE) causes substantial health care–associated infection with increasing reports of resistance to daptomycin or linezolid. We conducted a case–control study reporting 81 cases of daptomycin and linezolid–nonsusceptible VRE (DLVRE), a resistance pattern not previously reported. METHODS: We reviewed VRE isolates from June 2010 through June 2015 for nonsusceptibility to both daptomycin (minimum inhibitory concentration [MIC] > 4) and linezolid (MIC ≥ 4). We matched cases by year to control patients with VRE susceptible to both daptomycin and linezolid and performed retrospective chart review to gather risk factor and outcome data. RESULTS: We identified 81 DLVRE cases. Resistance to both daptomycin and linezolid was more common than resistance to either agent individually. Compared with susceptible VRE, DLVRE was more likely to present as bacteremia without focus (P < 0.01), with DLVRE patients more likely to be immune suppressed (P = .04), to be neutropenic (P = .03), or to have had an invasive procedure in the prior 30 days (P = .04). Any antibiotic exposure over the prior 30 days conferred a 4-fold increased risk for DLVRE (odds ratio [OR], 4.25; 95% confidence interval [CI], 1.43−12.63; P = .01); multivariate analysis implicated daptomycin days of therapy (DOT) over the past year as a specific risk factor (OR, 1.10; 95% CI, 1.01−1.19; P = .03). DLVRE cases had longer hospitalizations (P = .04) but no increased risk for in-hospital death. CONCLUSIONS: DLVRE is an emerging multidrug-resistant pathogen associated with immune suppression, neutropenia, and recent invasive procedure. Prior antibiotic exposure, specifically daptomycin exposure, confers risk for acquisition of DLVRE.