Daptomycin for Complicated Skin Infections: A Randomized Trial

Pediatrics. 2017 Mar;139(3):e20162477. doi: 10.1542/peds.2016-2477. Epub 2017 Feb 15.

Abstract

Background: Complicated skin and skin structure infections (cSSSI) are common in children. Due to safety and resistance issues with recommended agents, new treatment options would be advantageous.

Methods: Multicenter, evaluator-blinded clinical trial. Patients 1 to 17 years old with cSSSI caused by Gram-positive pathogens were randomized 2:1 to intravenous daptomycin or standard-of-care (SOC) treatment for ≤14 days. Daptomycin was administered once daily with dosing by patient age: 12 to 17 years, 5 mg/kg; 7 to 11 years, 7 mg/kg; 2 to 6 years, 9 mg/kg; 12 to 23 months, 10 mg/kg. The primary objective was to evaluate daptomycin safety. The secondary objective was to assess the efficacy of daptomycin compared with SOC. The intent-to-treat (ITT) population consisted of all randomized patients with any dose of study drug.

Results: The ITT population comprised 257 daptomycin and 132 SOC patients (primarily clindamycin or vancomycin); 35% had confirmed methicillin-resistant Staphylococcus aureus. The most common adverse events were diarrhea (7% daptomycin, 5% SOC) and increased creatine phosphokinase (6% daptomycin, 5% SOC). The proportions of safety population patients with treatment-related adverse events were similar between the daptomycin (14%) and SOC (17%) groups. Clinical success rates (blinded evaluator-assessed complete/partial resolution of cSSSI signs and symptoms 7-14 days after end-of-treatment) in the ITT population were also similar for the daptomycin (91%) and SOC groups.

Conclusions: Once-daily daptomycin was well tolerated, with safety and efficacy comparable to SOC in children/adolescents with cSSSI caused by Gram-positive pathogens, including community-acquired methicillin-resistant S aureus.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Clindamycin / therapeutic use
  • Creatine Kinase / blood
  • Daptomycin / therapeutic use*
  • Diarrhea / chemically induced
  • Drug Administration Schedule
  • Female
  • Fever / chemically induced
  • Gram-Positive Bacterial Infections / drug therapy*
  • Humans
  • Male
  • Methicillin-Resistant Staphylococcus aureus
  • Single-Blind Method
  • Skin Diseases, Bacterial / drug therapy*
  • Vancomycin / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Clindamycin
  • Vancomycin
  • Creatine Kinase
  • Daptomycin