Daptomycin well tolerated by younger children
Findings from a study of two dosages of daptomycin administered to children for the treatment of gram-positive infections have shown that both were safe and effective, according to a study published online.
Both the 8 mg/kg or 10 mg/kg dosage of daptomycin (Cubicin, Cubist Pharmaceuticals) for young children with suspected or gram-positive infections were well tolerated and yielded similar clearance rates, according to Susan M. Abdel-Rahman, PharmD, of the division of clinical pharmacology and medical toxicology at Children’s Mercy Hospitals and Clinics, in Kansas City, Mo. Richard F. Jacobs, MD, Infectious Diseases in Children Chief Medical Editor, is a co-investigator of the study.
The investigators prospectively looked at 12 children aged younger than 6 years who were stratified to either dose of daptomycin. The patients in group 1 received a single 8-mg/kg dose of daptomycin as a 1-hour infusion, and patients in group 2 were administered 10 mg/kg as a 1-hour infusion. The 1-hour infusion was chosen to minimize possible unknown effects of higher maximum plasma concentration values. Doses were administered in 25 mL of normal saline and infused at a rate of 0.42 mL/minute, according to the researchers.
A previous study reported that although pharmacokinetic variables for adolescents were comparable with those in adults, “[area under the curve] and [terminal half-life] for the same dose were significantly lower, and [plasma clearance] was significantly higher, in subjects 2 to 6 years of age.”
The medication was well tolerated, with no “clinically significant [creatine phosphokinase] elevations or myalgias” reported. The researchers said six patients reported one or more treatment-emergent adverse events while receiving daptomycin; however, only two were judged by investigators to be “possibly related to the study drug.”
The researchers said their data suggest that “a dose of 8 to 10 mg/kg in patients aged 2 to 6 years would provide systemic exposure comparable to that seen in adults treated with US-approved daptomycin doses of 4 to 6 mg/kg.”
Disclosures: The researchers reported that the study was supported by Cubist Pharmaceuticals Inc., and some of the researchers reported that they are employed with Cubist. Another researcher consulted for AstraZeneca, Bristol-Myers Squibb, Johnson & Johnson, and Bayer. Drs. Jacobs and Abdel-Rahman report no relevant financial disclosures.
One of the first axioms taught to pediatric clerkship students is that "children are not little adults." This study, led by Abdel-Rahman and colleagues, highlights this truth for the pharmacokinetics of daptomycin in young children. The authors asked a very straightforward question: in children aged 2-6 years, what is the dose of daptomycin that is required to provide comparable drug levels to adults receiving 4 mg/kg to 6 mg/kg? Not surprisingly, children eliminate daptomycin much more quickly than adults, and doses of 8 mg/kg to 10 mg/kg are needed to provide similar systemic exposures.
The importance of this work is two-fold. First, daptomycin, a cyclic lipopeptide antibiotic, has become a first-line agent for the treatment of bacteremia and native valve infective endocarditis in adults (IDSA Guidelines for Treatment of MRSA in Adults and Children, 2010). For it to be used appropriately in children, however, it is imperative that we understand how to use the drug both safely and effectively. Second, clinical trials aiming to determine best practices in the treatment of pediatric staphylococcal disease should now take into account these higher doses in order to assess the utility of daptomycin.
With the ever-changing landscape of staphylococcal disease in children, it is imperative that our antimicrobial quiver remains full. While it is unknown whether daptomycin holds any advantage over vancomycin in pediatric staphylococcal disease, there may be instances in which its use is necessary; as a result, firm data regarding dosing and tolerability are essential.
— C. Buddy Creech, MD, MPH
Infectious Diseases in Children Editorial Board member
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