Safety and Efficacy of Daptomycin as First-Line Treatment for Complicated Skin and Soft Tissue Infections in Elderly Patients: An Open-Label, Multicentre, Randomized Phase IIIb Trial

Background Daptomycin has proven efficacy in patients with Gram-positive complicated skin and soft tissue infections (cSSTIs), including those caused by Staphylococcus aureus, regardless of methicillin susceptibility. Objective This study was undertaken to evaluate the efficacy and safety of daptomycin in elderly patients. Study design This was an open-label, multicentre, randomized phase IIIb study conducted in hospitalized patients Patients aged >= 65 years with a diagnosis of Gram-positive cSSTIs with or without bacteraemia were included. In addition, infections were required to be of sufficient severity to require inpatient hospitalization and treatment with parenteral antibiotics for at least 96 h. The main exclusion criterion was the presence of a non-complicated SSTI that could heal by itself or be cured by surgical removal of the site of infection. Intervention Patients were randomized (2:1) to intravenous daptomycin or pooled intravenous standard therapies (semi-synthetic penicillin or vancomycin, referred to as the 'comparator'). Duration of treatment was between 5 and 14 days for cSSTIs without bacteraemia and between 10 and 28 days for cSSTIs with bacteraemia. Main Outcome Measure The primary objective was descriptive comparison of clinical success in clinically evaluable patients at test of cure, 7-14 days post treatment. Secondary objectives were microbiological outcome, duration of treatment and safety. Results In total, 120 patients were randomized (81 to daptomycin; 39 to the comparator) and 102 patients completed the study. Baseline characteristics were similar between the two groups. Common infections included cellulitis, ulcers and abscesses; six patients had bacteraemia [five documented (daptomycin, n = 3; comparator, n = 2); and one suspected (daptomycin, n = 1)]. Test-of-cure clinical success rates were numerically higher for daptomycin than for the comparator [89.0 % (65/73) vs. 83.3 % (25/30); odds ratio 1.65 (95 % confidence interval 0.49-5.54)]. For patients with S. aureus infections, cure rates were 89.7 % (35/39) versus 69.2 % (9/13), respectively; percentage points difference, 20.5 (95 % confidence interval -12.2 to 50.9)]. Rates of adverse events (AEs) and serious AEs were similar in both treatment arms; however, discontinuation rates for AEs/serious AEs were lower for daptomycin than for the comparator (3.8 % vs. 10.0 %). Three serious AEs were considered to be related to the study drug: one case each of pancytopenia (semi-synthetic penicillin), renal failure (vancomycin) and asymptomatic increase in creatine phosphokinase concentrations (daptomycin). Conclusion In elderly patients, for whom data were previously limited, the efficacy and safety of daptomycin have been confirmed, including for infections caused by S. aureus, regardless of methicillin susceptibility.