The Safety and Efficacy of Dalbavancin and Active Comparator in Pediatric Patients With Acute Bacterial Skin and Skin Structure Infections

Abstract

Background: Acute bacterial skin and skin structure infections (ABSSSIs) are a significant source of morbidity in children. Dalbavancin, approved for the treatment of adults and children with ABSSSI, has a well-established safety profile in adults. We report safety and descriptive efficacy data for the treatment of ABSSSI in children. Methods: Children with ABSSSI (birth–<18 years old) or sepsis (<3 months old) known/suspected to be caused by susceptible Gram-positive organisms were enrolled in this phase 3, multicenter, open-label, comparator-controlled study (NCT02814916). Children ≥3 months old were randomized 3:3:1 to receive single-dose dalbavancin, 2-dose dalbavancin, or a comparator antibiotic in 4 age cohorts; those <3 months old received single-dose dalbavancin. Clinical response and microbiologic efficacy were evaluated 48–72 hours and 14, 28 and 54 days posttreatment. Bowel flora testing and audiology were collected in a subset of patients at baseline and day 28. Adverse events (AEs) were collected throughout the study. Results: Treatment-emergent AEs occurred in 7.2%, 9.0% and 3.3% of patients in dalbavancin single-dose, dalbavancin 2-dose and comparator arms, respectively. Three serious AEs occurred in the dalbavancin single-dose arm; no treatment-related AEs, serious AEs, or AEs leading to study discontinuation were reported. Favorable clinical response at 48–72 hours was documented in 97.4%, 98.6% and 89.7% of patients. Safety and efficacy were comparable across age cohorts. The microbiologic intent-to-treat population had comparable clinical response for all baseline pathogens, including methicillin-resistant Staphylococcus aureus. Conclusion: The safety profile of dalbavancin was consistent in children and adults with ABSSSI. No new safety signals were identified.

Population Pharmacokinetic and Pharmacokinetic/Pharmacodynamic Target Attainment Analyses for Dalbavancin in Pediatric Patients

“…At test-of-cure, >96% of patients treated with dalbavancin achieved a clinical cure. The rate of favorable clinical response in the microbiological ITT population at all time points in study DUR001-306 was similar regardless of baseline pathogen, including MRSA, 33 the most common cause of purulent skin infection in the United States, and associated with complications, recurrence, and treatment failure that often results in hospitalization. 34 In pediatric patients, particularly younger children, early empiric treatment of MRSA purulent skin infection based on clinical symptoms (pending determination of microbiological origin) is paramount to avoiding serious infection and infant mortality.…”

“…Safety outcomes, efficacy endpoints (clinical response, clinical cure), and microbiological outcomes in this study were consistent across the 5 age cohorts and across all populations evaluated in study DUR001-306. 33 That study, comprising 191 patients, including five in the youngest cohort (birth to <3 months), is the first to report safety and efficacy outcomes in very young children with ABSSSI treated with dalbavancin. The safety profile of dalbavancin in pediatric patients was consistent with that in adults with ABSSSI, with no new clinically relevant safety signals identified.…”

Hygiene Measures and Decolonization of Staphylococcus aureus Made Simple for the Pediatric Practitioner

“…19 The antibiotic regimen will be guided by local microbial ecology and infection severity, and can include beta-lactams, clindamycin, trimethoprim-sulfamethoxazole, linezolid, vancomycin or dalbavancin. 38 The routine addition of rifampin is not recommended for SSTI. 39 Whether the acute treatment of SSTI influences recurrences has been studied poorly.…”

A Narrative Review on the Role of Dalbavancin in the Treatment of Bone and Joint Infections

“…To date, there is no clinical evidence about the efficacy and safety of dalbavancin in the treatment of osteoarticular infections in the pediatric population. However, a phase 3 multicenter, open-label, comparator-controlled study (NCT02814916) was performed in children with acute bacterial skin and skin structure infections (birth-<18 years old) or sepsis (<3 months old) known/suspected to be caused by susceptible Gram-positive organisms [58]. Children ≥3 months old were randomized 3:3:1 to receive single-dose dalbavancin, 2-dose dalbavancin, or a standard-of-care treatment; those <3 months old received single-dose dalbavancin [58].…”

“…However, a phase 3 multicenter, open-label, comparator-controlled study (NCT02814916) was performed in children with acute bacterial skin and skin structure infections (birth-<18 years old) or sepsis (<3 months old) known/suspected to be caused by susceptible Gram-positive organisms [58]. Children ≥3 months old were randomized 3:3:1 to receive single-dose dalbavancin, 2-dose dalbavancin, or a standard-of-care treatment; those <3 months old received single-dose dalbavancin [58]. Dalbavancin was generally safe and well tolerated and resulted in clinical responses of 97.4% and 98.6% at 48-72 h post-randomization in the single-and 2-dose study arms, respectively.…”