Systematic review on efficacy and safety of empirical versus pre‐emptive antifungal therapy among children with febrile neutropenia reveals paucity of data

Background Two approaches are used to manage invasive fungal disease (IFD) in febrile neutropenic patients viz. empirical therapy (without attempting to confirm the diagnosis), or pre‐emptive therapy (after screening tests for IFD). Objective This systematic review was undertaken to compare these approaches in children. Methods We searched PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, CINAHL, Clinical Trial Registries and grey literature, for randomized controlled trials (RCT) comparing empirical versus pre‐emptive antifungal therapy in children with FN suspected to have IFD. We used the Cochrane Risk of bias 2 tool for quality assessment, and evaluated the certainty of evidence using the GRADE approach. Results We identified 7989 citations. Stepwise screening identified only one relevant RCT that administered empirical ( n = 73) or pre‐emptive ( n = 76) antifungal therapy. There were no significant differences in all‐cause mortality (RR 1.56, 95% CI: 0.46, 5.31), IFD mortality (RR 1.04, 95% CI:0.15, 7.20) and other clinically important outcomes such as duration of fever, duration of hospitalization and proportion requiring ICU admission. There were no safety data reported. The number of days of antifungal therapy was significantly lower in the pre‐emptive therapy arm. The certainty of evidence for all outcomes was ‘moderate’. Conclusions This systematic review highlighted the paucity of data, comparing empirical versus pre‐emptive antifungal therapy in children with febrile neutropenia having suspected invasive fungal disease. Data from a single included trial suggests that both approaches may be comparable in research settings. Robust trials are warranted to address the gap in existing knowledge about the optimal approach in clinical practice.