Abstract and Introduction
Background: This subgroup analysis of the European Cubicin Outcomes Registry Experience evaluated the safety and effectiveness of daptomycin in children and adolescent patients (<18 years).
Methods: Clinical outcomes at the end of therapy were assessed as success (cured or improved), failure or nonevaluable. Safety was assessed for up to 30 days post treatment.
Results: Eighty-one children and adolescent patients were included in this study. The most common primary infections were bacteremia (19.8%), complicated skin and soft-tissue infection (18.5%), osteomyelitis (13.6%), endocarditis (12.3%), foreign body/prosthetic infection (12.3%), uncomplicated skin and soft-tissue infection (9.9%) and other (13.6%). Daptomycin doses ranged from 4 to >10 mg/kg/day. Median duration of therapy was 12.5 (interquartile range, 7–25; mean, 16.7; standard deviation, 12.8) days. Staphylococcus aureus (46.7%) was the most commonly isolated pathogen (23.8% methicillin-resistant S. aureus). Forty-nine (60.5%) patients completed daptomycin therapy without further antibiotics, 27 (33.3%) switched to another antibiotic, 4 (4.9%) discontinued because of adverse events (AEs) and 1 (1.2%) discontinued because of other reason. Overall, 75 (92.6%; 95% confidence interval: 95.2–100.0%) patients achieved clinical success; 39 of 41 (95.1%) patients receiving daptomycin monotherapy and 36 of 40 (90.0%) patients receiving concomitant antibiotics. Six (7.4%) patients reported AEs, including 1 patient with increased blood creatine phosphokinase. Three (3.7%) patients had serious AEs; 1 (1.2%) had a serious AE possibly related to daptomycin.
Conclusion: Daptomycin, alone or combined with other antibiotics and/or surgery, demonstrated high clinical success rates against a wide variety of infections and was well tolerated in children and adolescents.
Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), are known to be common pathogens in children and adolescents in both healthcare and community-associated infections.[1–3] Treatment of resistant pathogens including MRSA and vancomycin-resistant enterococci remains challenging even with standard antimicrobial protocols.[4–6] Higher mortality has been reported because of MRSA infections than infections caused by methicillin-susceptible S. aureus.[7,8] Several treatment options are available for the management of MRSA infections in adults; however, these options are limited for pediatric patients owing to a lack of sufficient safety and efficacy data. Clindamycin, vancomycin and linezolid are currently the only antibiotics approved by the US Food and Drug Administration for the management of MRSA infections in pediatric patients.
Daptomycin is a cyclic lipopeptide that is active against a wide range of Gram-positive bacteria. Its mechanism of action involves calcium-dependent binding to the bacterial cell membrane, resulting in rapid depolarization of the membrane potential and bacterial cell death, without cell lysis and release of inflammatory mediators.[9,10] Daptomycin is a concentration-dependent bactericidal agent indicated for the treatment of adult patients with complicated skin and soft-tissue infection (cSSTI), right-sided endocarditis caused by S. aureus, and bacteremia associated with cSSTI or right-sided endocarditis.
Daptomycin is not approved for the treatment of pediatric patients, and limited data are currently available regarding its use in the treatment of Gram-positive infections in this population. A few case reports and retrospective studies have described that use of daptomycin is beneficial in treating Gram-positive infections in children.[2,12]
The European Cubicin Outcomes Registry and Experience (EU-CORESM) study was a retrospective, noninterventional registry developed to collect real-world data on the use of daptomycin in the treatment of patients with Gram-positive infections. This subgroup analysis evaluated the safety and effectiveness of daptomycin in children and adolescent patients from the EU-CORE study.
Pediatr Infect Dis J. 2016;35(5):511-516. © 2016 Lippincott Williams & Wilkins