Randomized Controlled Noninferiority Trial Comparing Daptomycin to Vancomycin for the Treatment of Complicated Skin and Skin Structure Infections in an Observation Unit.

BACKGROUND: Incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing in complicated skin and skin structure infection (cSSSI) presenting to emergency departments (EDs). Treatment is heterogeneous and can require inpatient admission to an observation unit (OU). Vancomycin is commonly used in the OU for treatment, but increasing MRSA resistance to vancomycin suggests the need for alternatives. Daptomycin is an alternative but it is not known how it compares with vancomycin. OBJECTIVE: This study tested the hypothesis that daptomycin is noninferior to vancomycin for the treatment of cSSSI in an OU, using a relative risk (RR) of 1.3 as the noninferiority limit. METHODS: Subjects admitted to an ED-based OU with a diagnosis of cSSSI were eligible. Consenting subjects were randomized 1:1 to intravenous (i.v.) vancomycin at 15 mg/kg dosing every 12 h or i.v. daptomycin at 4 mg/kg once. Subjects were followed until they met objective criteria for discharge home or hospital admission. Discharged patients were prescribed 10-14 days of oral cephalexin and trimethoprim-sulfamethoxazole, or clindamycin if allergic to either of these medications. The primary endpoint was meeting objective discharge criteria with no change in antibiotic therapy or return to the ED for the same cellulitis within 30 days of OU discharge. RESULTS: There were 100 patients enrolled. RR for satisfying the endpoint was 1.07 (95% confidence interval 0.58-1.98) for daptomycin compared with vancomycin. Hospital admission rates were 36% and 32% for daptomycin and vancomycin treatment, respectively. CONCLUSION: Daptomycin was not inferior to vancomycin in the treatment of cSSSI in an OU.

Duke Scholars

Author Christopher Lindsell Biostatistics & Bioinformatics, Division of Biostatistics