Irrational and Inappropriate Use of Antifungals in the NICU: A Narrative Review

Invasive Candida infections in the neonatal intensive care unit (NICU) are associated with significant morbidity and mortality, particularly among extremely preterm neonates. Early treatment with antifungals is critical to improve survival rates and avoid long-term adverse outcomes. Prevention with antifungal prophylaxis in high-risk neonates has been shown to reduce the prevalence of invasive Candida infections effectively. However, the irrational and/or inappropriate use of antifungals has been documented. This narrative review aims to provide an overview of the rationales for the inappropriate use of antifungals in the NICU, the consequences that ensue, and the promising strategy of antifungal stewardship programs to optimize antifungal use. The nonspecific clinical presentation of systemic Candida infections and the lack of rapid, accurate diagnostic techniques for Candida identification and specification in most settings lead to a high rate of empirical treatment in neonates without a proven infection. Moreover, evidence on the optimal dosing of antifungal agents and the treatment duration in the neonatal population is lacking, which may result in excessive or subtherapeutic drug exposure. Antifungal misuse is associated with microbiological consequences, including the emergence of antifungal-resistant Candida strains, and clinical consequences, such as drug toxicities and alterations in the intestinal mycobiome. It is therefore imperative to optimize antifungal use in the NICU. The implementation of antifungal stewardship programs, which, through a multidisciplinary approach, aim to improve diagnosis and guide clinicians on antifungal selection, dosing, and duration for both prevention and treatment according to the local epidemiology, represents a promising strategy for antifungal optimization in the NICU.