Antifungal treatment strategies in intensive care unit patients

Background: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among critically ill patients. In the intensive care unit (ICU), invasive candidiasis (IC), invasive pulmonary aspergillosis (IPA), and Pneumocystis jirovecii pneumonia (PjP) represent the most prevalent and clinically relevant fungal diseases. Their diagnosis is often hampered by nonspecific clinical and radiological findings, delayed or negative cultures, and suboptimal performance of fungal biomarkers in this population. As a result, antifungal treatment strategies in the ICU must balance the need for early initiation with the risk of overtreatment and resistance. Methods: This review summarizes current therapeutic approaches, evidence-based recommendations, and recent advances for the treatment of IC, IPA, and PjP in critically ill patients. Pharmacokinetic/pharmacodynamic (PK/PD) considerations, therapeutic drug monitoring, and emerging antifungal agents are also discussed. Results: For IC, echinocandins remain the cornerstone of therapy, while biomarker-guided strategies appear more useful for treatment discontinuation than initiation. In IPA, voriconazole and isavuconazole are first-line agents, with liposomal amphotericin B as an alternative in case of azole resistance or intolerance; the role of combination therapy remains uncertain. For PjP, trimethoprim–sulfamethoxazole is the treatment of choice, while adjunctive corticosteroids are recommended mainly for people with HIV and severe disease. Emerging antifungal agents, including rezafungin, fosmanogepix, and olorofim, may enhance future treatment options. Conclusions: Optimizing antifungal stewardship through individualized therapy and early diagnosis remains essential to improve outcomes in this high-risk population.