Optimizing antifungal management in immunocompromised paediatric patients: current gaps and future directions

This review examines the critical knowledge gaps limiting optimal management of invasive fungal diseases (IFDs) in immunocompromised paediatric patients and proposes a research agenda to address these deficiencies.

Novel immunomodulatory therapies, including chimeric antigen receptor T-cell therapy, bispecific antibodies, and immune checkpoint inhibitors, are creating new at-risk paediatric populations whose susceptibility to IFDs remains poorly characterized. IFDs in these populations may present differently and beneficial effects from antifungal prophylaxis is not clear. Diagnostic challenges persist due to nonspecific imaging findings, limited performance of fungal biomarkers, and difficult invasive sampling given small sample volumes and procedural risks in children. Therapeutic management still relies on evidence extrapolated from adults, creating uncertainty around optimal antifungal selection, dosing strategies and treatment duration. Age-dependent pharmacokinetic and pharmacodynamic differences add substantial complexity, while newer antifungal agents are only becoming available in a delayed fashion for paediatric use.

Critical research priorities vary from identifying which paediatric populations benefit most from antifungal prophylaxis, to developing more accurate and less invasive diagnostics, defining TDM targets, and developing child-friendly and optimized treatment regimes. Addressing these knowledge gaps through dedicated paediatric research, clinical trials and observational studies is essential for this vulnerable population.