Epidemiology and Outcomes of Vancomycin-Resistant Enterococcus Infections in the U.S. Military Health System

Abstract

ABSTRACT Introduction Vancomycin-resistant enterococci (VRE) are classified by the Centers for Diseases Control and Prevention as a serious antibiotic resistance threat. Our study aims to characterize the epidemiology, associated conditions, and outcomes of VRE infections among hospitalized patients in the U.S. military health system (MHS). Materials and Methods We performed a retrospective cohort study of patients with VRE infection using the MHS database. Cases included all patients admitted to a military treatment facility for ≥2 days from October 2008 to September 2015 with a clinical culture growing Enterococcus faecalis, Enterococcus faecium, or Enterococcus species (unspecified), reported as resistant to vancomycin. Co-morbid conditions and procedures associated with VRE infection were identified by multivariable conditional logistic regression. Patient case-mix adjusted outcomes including in-hospital mortality, length of stay, and hospitalization cost were evaluated by high-dimensional propensity score adjustment. Results During the seven-year study period and among 1,161,335 hospitalized patients within the MHS, we identified 577 (0.05%) patients with VRE infection. A majority of VRE infections were urinary tract infections (57.7%), followed by bloodstream (24.7%), other site/device-related (12.9%), respiratory (2.9%), and wound infections (1.8%). Risk factors for VRE infection included invasive gastrointestinal, pulmonary, and urologic procedures, indwelling devices, and exposure to 4th generation cephalosporins, but not to glycopeptides. Patients hospitalized with VRE infection had significantly higher hospitalization costs (attributable difference [AD] $135,534, P<0.001), prolonged hospital stays (AD 20.44 days, P<0.001, and higher in-hospital mortality (case-mix adjusted odds ratio 5.77; 95% confidence interval 4.59-7.25). Conclusions VRE infections carry a considerable burden for hospitalized patients given their impact on length of stay, hospitalization costs, and in-hospital mortality. Active surveillance and infection control efforts should target those identified as high-risk for VRE infection. Antimicrobial stewardship programs should focus on limiting exposure to 4th generation cephalosporins.