Comparison of the Effectiveness and Safety of Linezolid and Daptomycin in Vancomycin-Resistant Enterococcal Bloodstream Infection: A National Cohort Study of Veterans Affairs Patients

Background. Vancomycin-resistant Enterococcus bloodstream infections (VRE-BSIs) are becoming increasingly common. Linezolid and daptomycin are the primary treatment options for VRE-BSI, but optimal treatment is unclear. Methods. This was a national retrospective cohort study comparing linezolid and daptomycin for the treatment of VRE-BSI among Veterans Affairs Medical Center patients admitted during 2004-2013. The primary outcome was treatment failure, defined as a composite of (1) 30-day all-cause mortality; (2) microbiologic failure; and (3) 60-day VRE-BSI recurrence. Poisson regression was conducted to determine if antimicrobial treatment was independently associated with clinical outcomes. Results. A total of 644 patients were included (linezolid, n = 319; daptomycin, n = 325). Overall, treatment failure was 60.9% (n = 392/644), and 30-day all-cause mortality was 38.2% (n = 246/644). Linezolid was associated with a significantly higher risk of treatment failure compared with daptomycin (risk ratio [RR], 1.37; 95% confidence interval [CI], 1.13-1.67; P = .001). After adjusting for confounding factors in Poisson regression, the relationship between linezolid use and treatment failure persisted (adjusted RR, 1.15; 95% CI, 1.02-1.30; P = .026). Linezolid was also associated with higher 30-day mortality (42.9% vs 33.5%; RR, 1.17; 95% CI, 1.04-1.32;P = .014) and microbiologic failure rates (RR, 1.10; 95% CI, 1.02-1.18; P = .011). No difference in 60-day VRE-BSI recurrence was observed between treatment groups. Conclusions. Treatment with linezolid for VRE-BSI resulted in significantly higher treatment failure in comparison to daptomycin. Linezolid treatment was also associated with greater 30-day all-cause mortality and microbiologic failure in this cohort.