Clinical pharmacology of antifungal agents to overcome drug resistance in pediatric patients

Abstract

Introduction: Antifungal resistance is an emerging problem that increases morbidity and mortality in immunosuppressed pediatric patients, who suffer from invasive fungal diseases. Optimal pharmacological management is critical for the successful treatment of invasive fungal infections by resistant strains.

Areas covered: This paper reviews the mechanisms of resistance of different classes of antifungal agents and the current understanding of pediatric antifungal pharmacology for overcoming antifungal resistance in children based on laboratory and clinical studies in the English literature. The therapeutic choices against fungal pathogens with intrinsic or acquired resistance are further reviewed.

Expert opinion: There is a paucity of data in the pediatric population regarding the epidemiology of the resistant organisms to different antifungal agents. It is also unknown if there are more prevalent molecular mechanisms that promote antifungal resistance. Selection and dosages of the most effective antifungal agent for overcoming the antifungal resistance is crucial. However, there are limited studies guiding the optimal dosage and duration of treatment for management of emergent antifungal resistance. Further studies are warranted to elucidate the optimal pharmacology of the current antifungal agents against resistant organisms and to advance the development of new antifungal agents.

Keywords:

• antifungal agents in pediatric population
• antifungal resistance
• invasive aspergillosis
• invasive candidiasis

Acknowledgments

T Walsh is a Scholar of the Henry Schueler Foundation, the Sharp Family Foundation in Pediatric Infectious Diseases, and the Save Our Sick Kids Foundation in Pediatric Infectious Diseases.

Declaration of interest

T Walsh receives research grants for experimental and clinical antimicrobial pharmacotherapeutics from Astellas, Cubist, Theravance, the Medicines Company, Novartis, Merck, ContraFect and Pfizer. He has served as consultant to Astellas, ContraFect, Drais, iCo, Novartis, Pfizer, Methylgene, SigmaTau and Trius. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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