title: Comparison of the Effectiveness and Safety of Linezolid and Daptomycin in Vancomycin-Resistant Enterococcal Bloodstream Infection: A National Cohort Study of Veterans Affairs Patients.
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.
authors.affiliation: Department of Pharmacy Practice, University of Kansas School of Pharmacy, Lawrence Department of Preventive Medicine and Public Health, University of Kansas School of Medicine, Kansas City Pharmacy Service, Dwight D. Eisenhower Veterans Affairs Medical Center, Leavenworth, Kansas.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Britt
authors.affiliation: Pharmacy Service, Dwight D. Eisenhower Veterans Affairs Medical Center, Leavenworth, Kansas.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Potter
authors.affiliation: Albany College of Pharmacy and Health Sciences, New York.
authors.forename: Nimish
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Pharmacy Practice, University of Kansas School of Pharmacy, Lawrence.
authors.forename: Molly E
authors.initials: ME
authors.lastname: Steed
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology; D015331:Cohort Studies; D017576:Daptomycin / Q000009:adverse effects / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D000069349:Linezolid / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D017211:Treatment Failure; D065507:Vancomycin-Resistant Enterococci / Q000302:isolation & purification*; D014728:Veterans
chemical_list: D000900:Anti-Bacterial Agents; D000069349:Linezolid; D017576:Daptomycin
keywords: Enterococcus; bloodstream infection; daptomycin; linezolid; vancomycin-resistant Enterococcus