Effect of Daptomycin Dose on the Outcome of Vancomycin-Resistant, Daptomycin-Susceptible Enterococcus faecium Bacteremia

Clin Infect Dis. 2017 Apr 15;64(8):1026-1034. doi: 10.1093/cid/cix024.

Abstract

Background: Treatment options for vancomycin-resistant enterococci (VRE) bloodstream infection (BSI) are limited. Daptomycin, although not currently approved for this indication, is frequently used for the treatment of VRE-BSI. Its optimal dose still needs to be determined.

Methods: We conducted a prospective, observational, cohort study during 2010-2015. We included patients who received a daptomycin dose of ≥6 mg/kg for the treatment of VRE-BSI caused by daptomycin-susceptible VRE. The primary endpoint was 14-day mortality, and multivariable logistic regression was performed for outcome analysis.

Results: We included 112 patients treated with daptomycin for VRE-BSI and with evaluable clinical outcomes. The daptomycin minimum inhibitory concentration (MIC) was 4 mg/L in 78 (69.6%) and ≤2 mg/L in 34 (30.4%) isolates. The overall mortality was 40/112 (35.7%). The unadjusted mortality was 18/36 (50.0%) for a daptomycin dose of <7 mg/kg, 17/51 (33.3%) for a dose of 7-9 mg/kg, and 5/25 (20%) for a dose of ≥9 mg/kg (P = .05). The best outcomes were associated with a daptomycin dose of ≥9 mg/kg compared to doses of <7 mg/kg (adjusted odds ratio [aOR], 10.57; 95% confidence interval [CI], 2.25-49.62; P=.003) and 7-9 mg/kg (aOR, 5.01; 95% CI, 1.14-21.98; P=.03). There was no significant difference in mortality with respect to the daptomycin MIC. There was no association between daptomycin dose and elevated creatinine kinase.

Conclusion: Higher daptomycin doses (≥9 mg/kg) were associated with lower mortality in patients with VRE-BSI. Our results suggest that higher daptomycin doses need to be considered for VRE-BSI treatment.

Keywords: bacteremia.; daptomycin; dose; mortality; vancomycin-resistant enterococci.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / administration & dosage*
  • Bacteremia / drug therapy*
  • Bacteremia / microbiology
  • Bacteremia / mortality
  • Daptomycin / administration & dosage*
  • Enterococcus faecium / drug effects
  • Enterococcus faecium / isolation & purification*
  • Female
  • Gram-Positive Bacterial Infections / drug therapy*
  • Gram-Positive Bacterial Infections / microbiology
  • Gram-Positive Bacterial Infections / mortality
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Prospective Studies
  • Survival Analysis
  • Treatment Outcome
  • Vancomycin-Resistant Enterococci / drug effects
  • Vancomycin-Resistant Enterococci / isolation & purification*
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Daptomycin