Decision-Rule Architecture in Fungal Biomarker-Guided Antifungal Stewardship for Critically Ill Adults: A Systematic Review and Candida-Focused Randomised Meta-Analysis
In brief
Candida biomarker rule-in strategies doubled antifungal use without demonstrated patient benefit
Across five randomized Candida trials, rule-in strategies increased antifungal treatment, while no patient benefit was demonstrated. In rule-out trials, mortality was similar between groups, but only 16 invasive Candida infections informed safety estimates, leaving the risk of stopping treatment uncertain. Biomarkers can support risk-based reassessment, but neither isolated positivity nor a negative result should dictate treatment alone.
- Journal
- Journal of fungi (Basel, Switzerland) (Q2)
- Published
- 10 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Giuseppe Neri, Giuseppe Mazza, Jessica Ielapi, Alessandro Russo, Francesca Serapide, Helenia Mastrangelo, et al.
- PMID
- 42783976
- DOI
- 10.3390/jof12090681
Why clinicians should know about it
- Picked for Biochemistry (medical) (top studies of the week, 27 September 2026).
- Picked for Microbiology (medical) (top studies of the week, 27 September 2026).
Abstract
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.