**Background:** The COVID-19 pandemic has been associated with a surge in opportunistic invasive fungal infections (IFIs), including COVID-19-associated candidemia (CAC), pulmonary aspergillosis (CAPA), and mucormycosis (CAM). These infections contribute to poor outcomes, with a retrospective multicenter French cohort reporting a mortality rate of 50.6% in critically ill COVID-19 patients with IFIs versus 22.6% in those without. Diagnostic challenges—such as non-specific radiological findings, limited sensitivity of serum biomarkers (e.g., serum galactomannan positive in <15% of CAPA patients), and difficulty distinguishing colonization from invasive disease—have led to overprescribing of antifungal agents. This overuse increases drug toxicity, drug-drug interactions, costs, and antifungal resistance, including echinocandin-resistant Candida glabrata, multidrug-resistant Candida auris, and triazole-resistant Aspergillus fumigatus. The Mycoses Study Group Education and Research Consortium (MSGERC) has recently adapted core antimicrobial stewardship elements to antifungal stewardship (AFS), but integration into hospital protocols remains incomplete.
**Methods:** This is a narrative review focusing on AFS in the context of COVID-19. The authors discuss predominant fungal pathogens, diagnostic strategies, treatment principles, infection control measures, and quality improvement frameworks. They synthesize evidence from published studies, guidelines, and expert consensus, including data from multicenter observational studies, case series, systematic reviews, and Delphi surveys.
**Key Results:** Blood culture remains the cornerstone for diagnosing yeast bloodstream infections, but (1,3)-β-D-glucan (BDG) testing may enhance detection. For CAPA, bronchoalveolar lavage (BAL) with culture, galactomannan (GM), and Aspergillus PCR is recommended, though positive results do not confirm invasive disease. The Aspergillus Lateral Flow Assay (LFA) shows good diagnostic performance: at a 1.0 cutoff, sensitivity for CAPA was 52%, 80%, and 81% for BAL fluid, non-directed BAL, and tracheal aspiration, respectively, with specificity of 98%, 88%, and 67%. Serum LFA sensitivity is limited (20% at 0.5 cutoff, 9% at 1.0 cutoff). Serum GM positivity is a marker of angioinvasion and advanced disease, with one study reporting 86% mortality in serum GM-positive CAPA patients and 90% in serum BDG-positive patients versus 38% in biomarker-negative patients. Mucorales PCR of serum was positive in 14 of 17 (82%) CAM patients in a French study. Treatment recommendations include echinocandins as first-line for candidiasis, voriconazole or isavuconazole for aspergillosis, and lipid formulations of amphotericin B for mucormycosis. Therapeutic drug monitoring (TDM) is recommended for voriconazole (target trough 1–5.5 mg/L, with higher 2–6 mg/L for severe infections), posaconazole (target >0.7 mg/L for prophylaxis, >1 mg/L for treatment), and itraconazole, but not routinely for isavuconazole, polyenes, or echinocandins. Antifungal prophylaxis for CAPA reduced incidence in three of six studies but did not influence survival in the two reporting survival data. Infection control measures include central line-associated bloodstream infection prevention bundles, screening for C. auris (axilla and groin sites), negative pressure room considerations (one French study found negative pressure increased airborne mold risk), and environmental cleaning with chlorine-based products. A systematic review of 13 AFS studies in the US found improved appropriate antifungal choice and reduced consumption but no detectable improvement in clinical outcomes. A pharmacist-led candidemia bundle in India increased appropriate prescribing from 30% to 65% and reduced in-hospital mortality from 40% to 36% (P=0.26). A Greek AFS program with educational intervention showed a large immediate decline in improper prescriptions and acquisition costs but no difference in mortality or length of stay.
**Clinical Implications:** The COVID-19 pandemic has highlighted critical gaps in fungal diagnostics and antifungal prescribing practices. AFS programs should be multidisciplinary, involving intensivists, pulmonologists, infection specialists, and clinical pharmacists. Key strategies include: (1) using biomarkers (BDG, GM, PCR) to guide therapy and reduce empirical overuse; (2) implementing TDM for azoles to optimize efficacy and minimize toxicity; (3) adhering to evidence-based treatment durations (e.g., 2 weeks for uncomplicated candidemia after first negative culture, 6–12 weeks for pulmonary aspergillosis); (4) enforcing infection control bundles including catheter removal, environmental cleaning, and targeted screening for resistant organisms like C. auris; and (5) regularly auditing antifungal use against process, outcome, and structural measures. The authors emphasize that AFS must be integrated into a continuous quality improvement cycle, and that a One Health approach—linking clinical, environmental, and agricultural antifungal use data—is essential to combat the growing threat of antifungal resistance.