Innovation in antifungal therapy.

With a steady increase in the number of at-risk patients, invasive fungal infections now represent a significant public health problem. These infections, caused by major pathogens such as Aspergillus, Candida, Cryptococcus, and Pneumocystis, affect increasingly diverse patient profiles, primarily immunocompromised individuals, with mortality rates often exceeding 50%. Managing these patients remains challenging, as very few systemic antifungals are currently available, compounded by major resistance issues related to the overuse and misuse of these drugs in clinical practice and agriculture. Fortunately, the field of medical mycology has benefited in recent years from major advances in pathogen-directed therapies, including new compounds, repurposing, new formulations, and the identification of new specific fungal targets. Although most immunomodulatory strategies are far from being implemented in clinical practice, recent breakthroughs in translational research have provided unprecedented hope in developing host-directed approaches leveraging cellular aspects and humoral mediators of immunopathogenesis.