Adjunctive Daptomycin in the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Randomized Controlled Trial

Abstract

Background

Bloodstream infections (BSI) with methicillin-susceptible Staphylococcus aureus (MSSA) are associated with significant morbidity and mortality. The objective of our study was to determine the efficacy of synergistic treatment of daptomycin when given with either cefazolin or cloxacillin for the treatment of MSSA BSI.

Methods

A randomized, double blind, placebo-controlled trial was performed at two academic hospitals in Montreal, Canada. Patients ≥ 18 years of age with MSSA BSI receiving either cefazolin or cloxacillin monotherapy were considered for inclusion. In addition to the standard of care treatment, participants received a 5-day course of adjunctive daptomycin or placebo. The primary outcome was the duration of MSSA BSI in days.

Results

Of 318 participants screened, 115 were enrolled and 104 were included in the intention to treat analysis (median age 67 years; 34.5% female). The median duration of bacteremia was 2.04 days among patients who received daptomycin versus 1.65 days in those who received placebo (absolute difference 0.39 days, p=0.40). A modified intention to treat analysis involving participants who remained bacteremic at the time of enrollment found a median duration of bacteremia of 3.06 days among patients who received daptomycin versus 3.0 days in those who received placebo (absolute difference 0.06 days, p=0.77). Ninety-day mortality in the daptomycin arm was 18.9% vs. 17.7% in the placebo arm (p=1.0).

Conclusion

Among patients with MSSA bloodstream infections, the administration of adjunctive daptomycin therapy to standard of care treatment did not shorten the duration of bacteremia and should not be routinely considered.