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

Clin Infect Dis. 2015 Sep 15;61(6):871-8. doi: 10.1093/cid/civ444. Epub 2015 Jun 10.

Abstract

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.

Keywords: Enterococcus; bloodstream infection; daptomycin; linezolid; vancomycin-resistant Enterococcus.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use*
  • Bacteremia / drug therapy*
  • Bacteremia / microbiology
  • Cohort Studies
  • Daptomycin / adverse effects
  • Daptomycin / therapeutic use*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Female
  • Gram-Positive Bacterial Infections / drug therapy*
  • Gram-Positive Bacterial Infections / microbiology
  • Humans
  • Linezolid / adverse effects
  • Linezolid / therapeutic use*
  • Male
  • Middle Aged
  • Recurrence
  • Retrospective Studies
  • Survival Analysis
  • Treatment Failure
  • Vancomycin-Resistant Enterococci / isolation & purification*
  • Veterans

Substances

  • Anti-Bacterial Agents
  • Linezolid
  • Daptomycin