Efficacy of daptomycin in complicated skin and skin-structure infections due to methicillin-sensitive and -resistant Staphylococcus aureus: results from the CORE Registry

Abstract

Objective: To characterize postmarketing clinical experience with daptomycin in treating complicated skin and skin-structure infections (cSSSIs) due to culture-confirmed MRSA and MSSA in real-life prescribing situations.

Research design and methods: The Cubicin Outcomes Registry and Experience 2004 (CORE 2004) is a multicenter observational registry involving 45 separate institutions, designed to characterize infection types, pathogens, and outcomes of patients who were treated with daptomycin. A subset analysis of the CORE 2004 data was conducted to characterize patients with cSSSI due to culture-confirmed MRSA and MSSA, but without bacteremia, endocarditis, osteomyelitis, or other significant infectious processes. Clinical information, including patient demographics, antibiotic treatments, and clinical outcome, was analyzed. Adverse event data were not collected in CORE 2004.

Main outcome measure: Clinical success (cured or improved) or failure was assessed at the end of daptomycin treatment.

Results: A total of 165 patients were identified, including 145 patients (87.9%) with MRSA and 20 patients (12.1%) with MSSA infections. Most patients received daptomycin at a dosage of 4-6 mg/kg intravenously and at a frequency of once every 24 h. Daptomycin dosing frequency was adjusted to once every 48 h or thrice weekly in all seven patients who had received hemodialysis. Prior antibiotic therapy had been administered to 121/163 (74.2%) patients and concomitant antibiotic therapy to 65/165 (39.4%) of patients. Clinical success was achieved with daptomycin in 89.1% of patients overall, including 89.7% and 85.0% of those with MRSA and MSSA, respectively. Among patients with a successful outcome, the total days of daptomycin therapy (median days: MRSA = 13.0, MSSA = 11.0) and the days to clinical response (median days: MRSA = 3.5, MSSA = 2.0) were not significantly different for MRSA and MSSA patients (p = 0.27 and p = 0.15 respectively, median test).

Conclusions: Given the limitations of this registry (which include its retrospective nature; limited numbers of MSSA patients; and lack of specific information on adverse events, type and duration of prior antibiotic therapy, timing and duration of concomitant antibiotic therapy, concomitant surgical interventions, and possible on-therapy dosing adjustments), daptomycin appeared effective in postmarketing clinical practice in the treatment of cSSSI caused by MRSA and MSSA.