Daptomycin in paediatrics: current knowledge and the need for future research

Abstract

To overcome the problems stemming from antimicrobial resistance, there have been several attempts to develop new antimicrobials in recent years. Of the highly potent drugs targeting resistant Gram-positive bacteria, daptomycin has a number of attractive characteristics that suggest its possible use in the treatment of serious infections due to these organisms. Although several pharmacokinetic and clinical studies in adults have provided data to determine how this drug should be prescribed to obtain the maximal clinical efficacy without significant risks of severe adverse events, we have not yet solved all of the problems related to the use of this antibiotic in paediatric patients. In this paper, the resolved and lingering problems of daptomycin treatment in newborns and children are reviewed and discussed. Studies have indicated that daptomycin is a promising therapeutic option for the treatment of paediatric diseases caused by MDR Gram-positive bacilli. However, before daptomycin can be licensed for use in newborns and children, further studies are needed to establish the appropriate dosages for paediatric patients of different ages. The data collected in adults can only be transferred to children older than 12 years, and the information available is not sufficient to determine the dosage that will assure the highest antimicrobial efficacy with only marginal risks of adverse events in younger patients. Thus, studies in neonates and younger infants are urgently needed to permit the use of daptomycin in the first months of life, a period in which infections due to MDR Gram-positive pathogens are increasing.

Clinical Experience with Daptomycin for the Treatment of Gram-positive Infections in Children and Adolescents

“…This and its once-daily administration make it an attractive therapeutic option for infections caused by these pathogens. 16 EU-CORE was initiated to capture real-world data regarding the use of daptomycin in the treatment of Gram-positive infections. The results from this analysis showed that children and adolescent patients with a variety of Gram-positive infections treated with daptomycin had a high clinical success rate, whether daptomycin was used as first- or second-line therapy.…”

Vancomycin-resistant Enterococcus bacteremia in a child with acute myeloid leukemia: Successful treatment with daptomycin

“…10 Higher doses may be required in younger patients and the administration of 15 mg/kg/12 h was reported as a maximum dose in the literature in an infant. 2,8 Our patient was treated at a dose of 8 mg/kg/ Serum CPK levels were in normal limits during the treatment. On 3th, 9th and 13th days after completion of daptomycin treatment the blood cultures were persistently negative.…”

“…Moreover, drug dosage, safety and tolerability have not been definitely established in children. 2 We report our experience about treatment of a VRE bacteremia in a 3-yearold boy with acute myeloid leukemia (AML)-M7 and Down syndrome.…”

“…Daptomycin mostly binds a protein in circulation and is eliminated through kidneys. 2 Limited pharmacokinetic studies have manifested faster daptomycin clearance in children and it seems to have a shorter half-life in children aged 2-6 when compared to children aged 12-17. 10 Higher doses may be required in younger patients and the administration of 15 mg/kg/12 h was reported as a maximum dose in the literature in an infant.…”

Daptomycin: an evidence-based review of its role in the treatment of Gram-positive infections

“…Daptomycin is currently not approved for use in the pediatric population, and appropriate dosages for pediatric patients of different ages are yet to be clearly defined. 85 A pharmacokinetic study in 25 children (2–17 years of age) receiving 4 mg/kg/day of daptomycin showed a more rapid clearance in those younger than 6 years. 86 Another study conducted later showed that use of high-dose (8–10 mg/kg/day) daptomycin in children aged 2–6 years provided systemic exposure comparable to that seen in adults treated with the approved daptomycin doses of 4–6 mg/kg/day.…”