Clinical Experience With Daptomycin for the Treatment of Gram-Positive Infections in Children and Adolescents

Vassiliki Syriopoulou, MD; Zoe Dailiana, MD; Nisichenko Dmitriy, MD; Riccardo Utili, MD; Rashidkhan Pathan, MSc; Kamal Hamed, MD, MPH


Pediatr Infect Dis J. 2016;35(5):511-516. 

In This Article

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.[1] 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.[1]

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.[11]

Daptomycin is not approved for the treatment of pediatric patients,[12] and limited data are currently available regarding its use in the treatment of Gram-positive infections in this population.[1] 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.