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. 2017 Mar 1;64(5):605-613.
doi: 10.1093/cid/ciw815.

Comparative Effectiveness and Safety of Standard-, Medium-, and High-Dose Daptomycin Strategies for the Treatment of Vancomycin-Resistant Enterococcal Bacteremia Among Veterans Affairs Patients

Nicholas S Britt  1   2 , Emily M Potter  3 , Nimish Patel  4 , Molly E Steed  2   5
Affiliations

Comparative Effectiveness and Safety of Standard-, Medium-, and High-Dose Daptomycin Strategies for the Treatment of Vancomycin-Resistant Enterococcal Bacteremia Among Veterans Affairs Patients

Nicholas S Britt et al. Clin Infect Dis. .

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: High-dose daptomycin was associated with improved survival and microbiological clearance in VRE-BSI.

Keywords: bloodstream infection; daptomycin; high-dose daptomycin; vancomycin resistance; vancomycin-resistant Enterococcus.

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Comment in

  • High-Dose Daptomycin and Mortality: The Case Is Not Yet Closed.
    Chanderraj R, Banerjee M, Rao K. Chanderraj R, et al. Clin Infect Dis. 2017 Oct 15;65(8):1426-1427. doi: 10.1093/cid/cix551. Clin Infect Dis. 2017. PMID: 29017242 No abstract available.
  • Reply to Chanderraj et al.
    Britt NS, Potter EM, Patel N, Steed ME. Britt NS, et al. Clin Infect Dis. 2017 Oct 15;65(8):1427-1428. doi: 10.1093/cid/cix553. Clin Infect Dis. 2017. PMID: 29017243 No abstract available.

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