Matthew P Cheng1, Alexander Lawandi2, Guillaume Butler-Laporte2, Samuel De l'Étoile-Morel2, Katryn Paquette3, Todd C Lee2,4,5. 1. Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 2. Division of Infectious Diseases, Department of Medicine, McGill University, Montreal, Quebec, Canada. 3. Division of Neonatology, Montreal Children's Hospital, McGill University, Montreal, Quebec, Canada. 4. Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada. 5. Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montreal, Quebec, Canada.
Abstract
BACKGROUND: Bloodstream infections (BSIs) with methicillin-susceptible Staphylococcus aureus (MSSA) are associated with significant morbidity and mortality. Our objective in this study was to determine the efficacy of synergistic treatment with 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 2 academic hospitals in Montreal, Canada. Patients aged ≥18 years with MSSA BSI receiving eithercefazolin 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 vs 1.65 days in those who received placebo (absolute difference, 0.39 days; P = .40). In a modified intention-to-treat analysis that involved participants who remained bacteremic at the time of enrollment, we found a median duration of bacteremia of 3.06 days among patients who received daptomycin vs 3.0 days in those who received placebo (absolute difference, 0.06 days; P = .77). Ninety-day mortality in the daptomycin arm was 18.9% vs 17.7% in the placebo arm (P = 1.0). CONCLUSIONS: Among patients with MSSA BSIs, the administration of adjunctive daptomycin therapy to standard-of-care treatment did not shorten the duration of bacteremia and should not be routinely considered. CLINICAL TRIALS REGISTRATION: NCT02972983.
RCT Entities:
BACKGROUND: Bloodstream infections (BSIs) with methicillin-susceptible Staphylococcus aureus (MSSA) are associated with significant morbidity and mortality. Our objective in this study was to determine the efficacy of synergistic treatment with 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 2 academic hospitals in Montreal, Canada. Patients aged ≥18 years 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 vs 1.65 days in those who received placebo (absolute difference, 0.39 days; P = .40). In a modified intention-to-treat analysis that involved participants who remained bacteremic at the time of enrollment, we found a median duration of bacteremia of 3.06 days among patients who received daptomycin vs 3.0 days in those who received placebo (absolute difference, 0.06 days; P = .77). Ninety-day mortality in the daptomycin arm was 18.9% vs 17.7% in the placebo arm (P = 1.0). CONCLUSIONS: Among patients with MSSA BSIs, the administration of adjunctive daptomycin therapy to standard-of-care treatment did not shorten the duration of bacteremia and should not be routinely considered. CLINICAL TRIALS REGISTRATION: NCT02972983.
Authors: Guillaume Butler-Laporte; Matthew P Cheng; Daniel J G Thirion; Samuel De L'Étoile-Morel; Charles Frenette; Katryn Paquette; Alexander Lawandi; Emily G McDonald; Todd C Lee Journal: Open Forum Infect Dis Date: 2020-09-24 Impact factor: 3.835
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