Decision-Rule Architecture in Fungal Biomarker-Guided Antifungal Stewardship for Critically Ill Adults: A Systematic Review and Candida-Focused Randomised Meta-Analysis.

Fungal biomarkers may support antifungal stewardship in critically ill adults, but their clinical effect depends on the decision rule linking test results to treatment. We systematically reviewed ICU or ICU-relevant adult studies in which fungal biomarkers or rapid fungal diagnostics explicitly informed antifungal management. Searches were updated through 24 July 2026 (PROSPERO CRD420261432481), and clinically compatible Candida randomised outcomes were synthesised by rule direction. Twenty-one reports represented 19 independent studies. Five core Candida trials randomised 677 participants (661 analysed). Rule-in assignment increased systemic antifungal receipt (two trials; RR 2.06, 95% CI 1.58-2.67) without demonstrated patient benefit. In three rule-out trials, mortality was 34/126 versus 38/132 (RR 0.94, 95% CI 0.63-1.40), while only 16 post-randomisation invasive Candida events informed highly uncertain fungal-safety estimates (RR 1.85, 95% CI 0.51-6.65). The evidence is therefore insufficient to establish a clinically acceptable fungal-safety margin for biomarker-guided discontinuation. Biomarkers should therefore support, not replace, risk-based reassessment: timely negative results may justify supervised discontinuation, whereas isolated positivity should not be a stand-alone treatment trigger.