Investigational Agents for the Treatment of Resistant Yeasts and Molds.

This review summarizes the investigational antifungals in clinical development with the potential to address rising drug resistance patterns. The relevant pharmacodynamics, spectrum of activity, preclinical studies, and latest clinical trial data are described. Agricultural and medicinal antifungal use has been selected for inherently drug-resistant fungi and acquired resistance mechanisms. The rates of fungal infections and immunocompromised populations continue to grow as few new antifungals have hit the market. Several agents with the potential to address the emergence of multidrug-resistant (MDR) molds and yeasts are in clinical development. Evolved formulations of echinocandins, polyenes, and triazoles offer less toxicity, convenient dosing, and greater potency, potentially expanding these classes’ indications. Ibrexafungerp, olorofim, oteseconazole, and fosmanogepix possess novel mechanisms of actions with potent activity against MDR fungi. Successful clinical development is neither easy nor guaranteed; thus, perpetual efforts to discover new antifungals are needed.