Daptomycin versus Linezolid for the Treatment of Vancomycin-Resistant Enterococcal Bacteremia: Implications of Daptomycin Dose.

Daptomycin versus Linezolid for the Treatment of Vancomycin-Resistant Enterococcal Bacteremia: Implications of Daptomycin Dose.

Clin Microbiol Infect. 2016 Jul 27;

Authors: Chuang YC, Lin HY, Chen PY, Lin CY, Wang JT, Chang SC

Abstract
OBJECTIVES: Treatment options for vancomycin-resistant enterococcus (VRE) bloodstream infection (BSI) are limited. Studies comparing daptomycin or linezolid in treating VRE-BSI have conflicting results and suggest daptomycin underdosing. The responses to different daptomycin doses have not been studied.
METHODS: We conducted a multicenter prospective cohort study to compare linezolid and daptomycin (≥6 mg/kg) for the treatment of VRE-BSI. The primary outcome was 14-day mortality. We used multivariate logistic regression analysis for outcome analysis and a generalized additive model (GAM) for dose-dependent response estimation.
RESULTS: Two hundred twelve patients were included (daptomycin, n = 141; linezolid, n = 71). All-cause 14-day mortality was higher in the daptomycin group (36.9% vs. 21.1%; P = .03). After adjusting for confounders in logistic regression, mortality was lower in the linezolid group (adjusted odds ratio (aOR), 0.45; 95% confidence interval (CI), 0.21-0.96; P = .04). GAM showed that higher-dose daptomycin (≥9 mg/kg) was associated with better survival than lower-dose daptomycin (6-9 mg/kg). Logistic regression showed that linezolid (aOR, 0.36; 95% CI, 0.17-0.79; P = .01) and higher-dose daptomycin (aOR, 0.26; 95% CI, 0.09-0.74; P = .01) independently predicted lower mortality compared with lower-dose daptomycin. Linezolid was not superior to higher-dose daptomycin in terms of mortality (aOR, 1.40; 95% CI, 0.45-4.37; P = .57).
CONCLUSIONS: Higher-dose daptomycin had lower mortality than lower-dose daptomycin. Despite higher mortality for lower-dose daptomycin than linezolid, linezolid conferred no survival benefit compared with higher-dose daptomycin. Our findings suggest that the recommended daptomycin dose is suboptimal for treating VRE bacteremia.

PMID: 27475738 [PubMed - as supplied by publisher]