title: Comparative Effectiveness and Safety of Standard-, Medium-, and High-Dose Daptomycin Strategies for the Treatment of Vancomycin-Resistant Enterococcal Bacteremia Among Veterans Affairs Patients.
abstract: Vancomycin-resistant Enterococcus bloodstream infections (VRE-BSIs) are associated with significant mortality. Daptomycin exhibits concentration-dependent activity vs VRE in vitro, yet the clinical impact of higher-dose strategies remains unclear.
  
  
  
  We performed a national retrospective cohort study of hospitalized Veterans Affairs patients treated with standard-dose (6 mg/kg total body weight), medium-dose (8 mg/kg total body weight), or high-dose (≥10 mg/kg total body weight) daptomycin for VRE-BSI. Patient-related, microbiological, and outcomes data were abstracted from clinical databases. The primary outcome was overall survival, evaluated by Cox regression. Secondary outcomes included 30-day mortality, time to microbiological clearance, and creatine phosphokinase (CPK) elevation.
  
  
  
  A total of 911 patients were included (standard dose, n = 709; medium dose, n = 142; high dose, n = 60). Compared to high-dose daptomycin, both standard-dose (hazard ratio [HR], 2.68; 95% confidence interval; [CI], 1.33-3.06; P = .002) and medium-dose (HR, 2.66; 95% CI, 1.33-3.92; P = .003) daptomycin were associated with poorer survival. After adjusting for confounders, the relationship between poorer survival and standard-dose (adjusted HR [aHR], 2.58; 95% CI, 1.27-4.88; P = .004) and medium-dose (aHR, 2.52; 95% CI, 1.27-5.00; P = .008) daptomycin persisted. Thirty-day mortality was significantly lower among high-dose daptomycin-treated patients compared with other dosing strategies (risk ratio, 0.83; 95% CI, .74-.94; P = .015). Compared with standard-dose daptomycin, both medium-dose (HR, 0.78; 95% CI, .55-.90; P = .012) and high-dose daptomycin (HR, 0.70; 95% CI, .41-.84; P = .006) were associated with significantly improved microbiological clearance. No difference in the risk of CPK elevation was observed between the treatment groups (P = .504).
  
  
  
  High-dose daptomycin was associated with improved survival and microbiological clearance in VRE-BSI.
authors.affiliation: Department of Pharmacy, Barnes-Jewish Hospital, St Louis, Missouri, USA.|Research Department, Dwight D. Eisenhower Veterans Affairs Medical Center, Leavenworth, Kansas, USA.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Britt
authors.affiliation: Pharmacy Service, Dwight D. Eisenhower Veterans Affairs Medical Center, Leavenworth, Kansas, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Potter
authors.affiliation: Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
authors.forename: Nimish
authors.initials: N
authors.lastname: Patel
authors.affiliation: Research Department, Dwight D. Eisenhower Veterans Affairs Medical Center, Leavenworth, Kansas, USA.|Department of Pharmacy Practice, University of Kansas School of Pharmacy, Lawrence, KS, USA.
authors.forename: Molly E
authors.initials: ME
authors.lastname: Steed
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D016470:Bacteremia / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology* / Q000635:transmission; D015897:Comorbidity; D017576:Daptomycin / Q000008:administration & dosage* / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D016984:Enterococcus faecium; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome; D020713:Vancomycin Resistance; D065507:Vancomycin-Resistant Enterococci / Q000187:drug effects*; D014728:Veterans
chemical_list: D000900:Anti-Bacterial Agents; D017576:Daptomycin
keywords: bloodstream infection; daptomycin; high-dose daptomycin; vancomycin resistance; vancomycin-resistant Enterococcus