Daptomycin Dose Optimization in Pediatric Staphylococcus aureus Bacteremia: A Pharmacokinetic/Pharmacodynamic Investigation.

Autor: Olney KB; Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, KY, USA.; Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY, USA., Howard JI; Department of Pediatrics: Division of Infectious Diseases, University of Kentucky HealthCare, Lexington, KY, USA.; Department of Pediatrics, University of Kentucky College of Medicine, Lexington, KY, USA., Burgess DS; Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY, USA.
Jazyk: angličtina
Zdroj: Journal of clinical pharmacology [J Clin Pharmacol] 2024 Jul; Vol. 64 (7), pp. 860-865. Date of Electronic Publication: 2024 Mar 18.
DOI: 10.1002/jcph.2425
Abstrakt: Daptomycin is an antibiotic with Gram-positive activity, including methicillin-resistant Staphylococcus aureus, for which optimal pediatric dosing is unknown. This study aimed to evaluate daptomycin exposures achieved with package label dosing and to identify dosing regimens necessary to enhance efficacy and minimize toxicity in children with S. aureus bacteremia. Monte Carlo simulations were performed to determine probability of target attainment (PTA) for six pediatric age cohorts. Area under the curve to minimum inhibitory concentration ratio (AUC 0-24 :MIC) ≥666 was used to determine the PTA for efficacy (PTA E ). Minimum concentration (C min ) ≥24.3 mg/L determined the PTA for toxicity (PTA T ). Acceptable dosing regimens were those which achieved the combined target of ≥90% PTA E and ≤5% PTA T . Package label dosing of daptomycin yielded insufficient efficacy with only 26.3% PTA E in children 13-24 months, 39.5% PTA E in children 2-6 years, 30.1% PTA E in children 7-11 years, and 50.1% PTA E in adolescents ≥12 years. To achieve the combined efficacy and safety target, doses of 18-24 mg/kg in children 3-12 months, 20-24 mg/kg in children 13-24 months, 19-24 mg/kg in children 2-6 years, 17-19 mg/kg in children 7-11 years, and 10-14 mg/kg in adolescents ≥12 years are necessary. Package label dosing resulted in suboptimal exposure for the majority of pediatric patients in all age groups evaluated. If targeting validated efficacy and safety endpoints, daily daptomycin doses of at least 20 mg/kg in children ≤6 years, 17 mg/kg in children 7-11 years, and 10 mg/kg in adolescents ≥12 years are necessary. Clinical studies evaluating these higher doses are needed.
(© 2024, The American College of Clinical Pharmacology.)
Databáze: MEDLINE
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