A pilot study of high-dose short duration daptomycin for the treatment of patients with complicated skin and skin structure infections caused by gram-positive bacteria

Background: Methicillin-susceptible and -resistant (MRSA) Staphylococcus aureus are significant causes of complicated skin and skin structure infections (cSSSI). The bactericidal antibiotic daptomycin is approved for gram-positive cSSSI at 4 mg/kg/day for 7-14 days, but the optimal dose level and duration of therapy have not been firmly established. This pilot study evaluated the efficacy and safety of daptomycin at 10 mg/kg every 24 h for 4 days [high-dose short duration (HDSD) regimen] vs. standard of care therapy with vancomycin or semi-synthetic penicillin for the treatment of cSSSI. Methods: This was a semi-single blind, randomised, multicentre, comparative trial. The primary efficacy end-point was the clinical response 7-14 days posttherapy. Results: One hundred patients were randomised; 48 in each arm were treated. The treatment groups were well balanced with respect to demographics, comorbidities and the type of infection (75% because of MRSA). Overall, clinical success rates were 75.0% (36/48) for daptomycin and 87.5% (42/48) for comparator (95% confidence interval for the difference: -27.9, 2.9). The median duration of comparator therapy was 8 days. Two comparator patients and no daptomycin patients experienced treatment-related serious adverse events requiring hospitalisation. Conclusion: We found that the HDSD regimen had a safety profile similar to that seen in previous studies. Although the differences were not statistically significant, clinical success rates for comparator were higher than for daptomycin. In post hoc analyses HDSD daptomycin performed better in some subgroups (e.g. outpatients) than in others (e.g. certain MRSA infections). These observations require confirmation in larger trials.