Randomized Multicenter Study Comparing Safety and Efficacy of Daptomycin Versus Standard of Care in Pediatric Patients with Staphylococcal Bacteremia.

Background:Staphylococcus aureus, including community-associated methicillin-resistant S. aureus, is an important cause of pediatric bacteremia. Daptomycin is a well-established treatment option for Gram-positive bacteremia in adults, but its safety and efficacy in children require confirmation. Methods: This was a randomized (2:1), evaluator-blinded, multicenter, phase 4 clinical trial comparing intravenous daptomycin with standard-of-care (SOC) for treatment of S. aureus bacteremia in 1- to 17-year-old patients (Clinicaltrials.gov: NCT01728376). Total treatment duration (intravenous followed by oral step-down therapy) was 5-42 days. Daptomycin was dosed once daily by patient age: 12-17 years, 7mg/kg; 7-11 years, 9mg/kg and 1-6 years, 12mg/kg. The primary objective was to evaluate daptomycin safety in children who received 1 dose; secondary objectives included comparing daptomycin efficacy with SOC (the trial was not designed to confirm noninferiority) and pharmacokinetic analysis. Results: Fifty-five children were randomized to daptomycin and 27 to SOC (primarily vancomycin or cefazolin); 90% had S. aureus. In both groups, 15% of patients had drug-related adverse events, primarily diarrhea (4% daptomycin, 8% SOC) and increased creatine phosphokinase (4% daptomycin, 0% SOC). Clinical success (blinded evaluator-assessed complete/partial resolution of bacteremia signs and symptoms 7-14 days after end-of-treatment) rates were similar for daptomycin (88%) and SOC (77%; 95% confidence interval for difference: -9% to 31%). Daptomycin plasma levels across age groups were comparable with those in adults receiving daptomycin at 6mg/kg. Conclusions: Once-daily, age-appropriate daptomycin was well tolerated in children with staphylococcal bacteremia; efficacy was comparable with SOC. Daptomycin in age-adjusted doses is a safe treatment alternative in this setting.