New antifungal agents under development in children and neonates

PURPOSE OF REVIEW: This review focuses on only the newest antifungal agents recently approved or still under development and the available data in pediatric and neonatal patients. The larger body of data in adult patients is used for comparative purposes only in an attempt to understand pediatric implications. RECENT FINDINGS: Pharmacokinetic data suggest differences in dosing for many newer agents in children versus adult patients, but each agent has not been fully evaluated. Voriconazole displays non-linear pharmacokinetics in adults but has linear pharmacokinetics in children, necessitating a higher dose in smaller patients and potential treatment failures using the approved adult dosing schedule. Caspofungin likewise requires higher doses relative to adult patients, and dosing in children is best accomplished on a body surface area scheme and not a body weight dosing platform. Preliminary data suggest posaconazole, an investigational triazole, in children may lead to similar levels as in adults, but very limited efficacy data are available at any dose. Micafungin dosing has been explored in neonatal patients and there is a clear trend toward lower levels obtained in the very smallest infants, highlighting the importance of the neonatal period as a separate entity to even the pediatric age group. SUMMARY: Initial data suggest dosing differences in children with some antifungals, and other newer agents have not been fully tested for the correct dosing. The underlying concern of efficacy in children compared with adult patients has never been answered as there are no randomized, phase III antifungal clinical trials from which pediatric-specific data were obtained.