Antifungal combinations in paediatric invasive fungal infections: a protocol for systematic review and meta-analysis

Background Invasive fungal infections (IFIs) significantly impact immunocompromised paediatric patients, contributing to high rates of morbidity and mortality. Despite the evolution of antifungal therapy, the efficacy and safety of combination antifungal therapies in paediatric patients, especially those with haematological malignancies, remain controversial. This systematic review and meta-analysis seeks to critically evaluate the efficacy and safety of antifungal combinations in paediatric IFIs. Methods We will conduct a search in PubMed, ScienceDirect, Cochrane Library, BMJ and Springer databases to include randomised controlled trials and observational studies focused on combination antifungal therapies in paediatric patients under 18 years with IFIs, using COVIDENCE for data management and analysis, ensuring rigorous quality assessment and statistical integrity in synthesising data. The time frame for the search will encompass publications from the inception of each database to the present, ensuring a comprehensive coverage of the literature. The database search will not be restricted by date. The review will assess combined antifungal treatment against placebo or single-antifungal therapy, examining outcomes like response rates, survival, mortality, adverse effects, cost-effectiveness and quality of life. Ethics and dissemination The review will be disseminated to healthcare professionals, community groups and policy-makers via journal publication and conference presentations to help them tailor antifungal prophylaxis treatment and outcomes for paediatric patients with IFIs. The analysis will not include any individual patient data, so ethical approval is not required. PROSPERO registration number CRD42024503620.