Role of Prophylactic Antifungal Therapy in Reducing Infections in Critically Ill Patients with Severe Burn and Trauma

Jie Fan

University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.

Siti Nurfatimah Mohd Shahpudin

Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia

Xiangcheng Zhang

zhxc0318@163.com

Department of Critical Care Medicine, Huai'an First People's Hospital, Huai'an, China

Address correspondence to

Xiangcheng Zhang, Department of Critical Care Medicine, Huai'an First People's Hospital, Huai'an, China. Email:zhxc0318@163.com

Open Access

Role of Prophylactic Antifungal Therapy in Reducing Infections in Critically Ill Patients with Severe Burn and Trauma

Jie Fan

University of Pittsburgh, Pittsburgh, Pennsylvania, U.S.

Siti Nurfatimah Mohd Shahpudin

Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia

Xiangcheng Zhang

zhxc0318@163.com

Department of Critical Care Medicine, Huai'an First People's Hospital, Huai'an, China

Address correspondence to

Xiangcheng Zhang, Department of Critical Care Medicine, Huai'an First People's Hospital, Huai'an, China. Email:zhxc0318@163.com

2026 Mar;1(1):40-44

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Abstract

Objective: To evaluate the efficacy and safety of prophylactic antifungal therapy in reducing invasive fungal infections (IFIs) and improving clinical outcomes in critically ill patients with severe burn and trauma. Methods: A multicenter randomized controlled trial was conducted on 426 patients with severe burn (total body surface area [TBSA] ≥ 30%) or polytrauma (Injury Severity Score [ISS] ≥ 25) admitted to 12 Level 1 trauma and burn centers across the United States from January 2022 to March 2025. Patients were randomly assigned to the prophylactic antifungal group (n=213, fluconazole 400 mg/day intravenously for 14 days) and the control group (n=213, placebo). The primary outcome measure was the incidence of proven or probable IFIs within 28 days of admission, diagnosed according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria. Secondary outcomes included 28 day and 90 day all cause mortality, length of intensive care unit (ICU) stay, total hospital stay, and incidence of adverse drug reactions. Results: The incidence of IFIs was significantly lower in the prophylactic antifungal group than in the control group (8.9% vs. 22.1%, P<0.001). The most common IFIs in the control group were candidemia (12.2%) and invasive pulmonary aspergillosis (5.6%). The 28 day mortality rate was 15.5% in the prophylactic antifungal group and 26.3% in the control group (P=0.002), while the 90 day mortality rate was 21.1% and 32.4% respectively (P=0.003). Multivariate logistic regression analysis confirmed that prophylactic antifungal therapy was an independent protective factor for IFIs (OR=0.32, 95% CI=0.17–0.60, P<0.001) and 28 day mortality (OR=0.46, 95% CI=0.27–0.79, P=0.005). The prophylactic antifungal group also had shorter mean ICU stay (22.5 ± 6.8 days vs. 28.7 ± 8.2 days, P<0.001) and total hospital stay (38.2 ± 9.5 days vs. 46.5 ± 11.3 days, P<0.001). The incidence of adverse drug reactions (including hepatotoxicity and electrolyte disturbances) was comparable between the two groups (7.5% vs. 6.1%, P=0.486). Conclusion: Prophylactic antifungal therapy with fluconazole significantly reduces the incidence of IFIs and improves survival in critically ill patients with severe burn and trauma, with a favorable safety profile. This intervention should be considered as a standard component of care for this high risk population.

Keywords: Prophylactic antifungal therapy; Severe burn; Polytrauma; Invasive fungal infections; Mortality

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