Highlighting gaps in paediatric antifungal drugs: a qualitative synthesis of current data from the International Pediatric Association AMR Working Group

Invasive fungal diseases (IFDs) in neonates and the paediatric population pose a global challenge due to the difficult estimation of true burden, under-reported mortality rates, diagnostic difficulties and limited therapeutic options, particularly in resource-limited settings. The current state is further complicated by the rising antifungal resistance (AFR). There is also a lack of inclusivity in paediatric antifungal research trials, often resulting in extrapolation of research data obtained from adult populations, despite differences in pharmacokinetic and pharmacodynamic (PK/PD) parameters. Although this approach is not inherently inappropriate, it is not applicable in the setting of pediatric antifungal medication since disease pathophysiology and exposure–response relationships are not comparable between neonates and adults. This report synthesises the current evidence available for new antifungals in children and neonates, summarising available trial data (including PK/PD and any efficacy signals) and real-world observations to define present gaps and immediate priorities. The search strategy, eligibility criteria and data-extraction approach are set out in the Scope and Methodology section; the records identified were too few and too heterogeneous to pool, and the evidence was therefore synthesised qualitatively rather than by meta-analysis. The International Pediatric Association (IPA) Working Group proposes an urgent adoption of an ‘AMR–AFR paediatric ACCELERATE framework’, a synthesis of existing paediatric drug-development instruments adapted to antifungal agents and given defined implementation steps and measurable indicators, to guide policy, research, and regulatory strategies. This framework recommends improving awareness through the engagement of national and international stakeholders to estimate the true burden of IFD and AFR, prioritise early inclusion of paediatric populations in antifungal development, invest in child-appropriate formulations for antifungals, and increase access to diagnostic testing including resistance detection with the establishment of referral laboratories, real-world data integration, engagement of regulatory and industry stakeholders, prioritising high-burden regions for capacity building and use of modern technologies like artificial intelligence to bridge the gaps in AFR research.