New and emerging drugs for the treatment of invasive fungal infections.

Introduction: The prevalence of invasive fungal infections (IFI) is increasing globally, with approximately 6,500,000 cases of IFI per year and 3,800,000 deaths. Most IFI deaths are attributable to opportunistic mycoses, such as Aspergillus and Candida. However, changes in climate and travel are leading to rising rates of endemic mycoses. Compounding this burden is the rise of antifungal drug resistance, requiring the development of new agents.

Areas covered: Data were identified using PubMed searches for the terms 'antifungal,' 'olorofim,' 'SUBA-itraconazole,' 'ibrexafungerp,' 'rezafungin,' 'fosmanogepix,' and 'encochleated amphotericin B.' Approved agents include ibrexafungerp, an oral triterpenoid inhibitor of 1,3-β-D-glucan synthase; rezafungin, a long-acting echinocandin with weekly dosing; and SUBA-itraconazole, a reformulation of itraconazole with more consistent absorption. Other investigational agents include: olorofim, an inhibitor of dihydroorotate dehydrogenase with activity against invasive molds and Coccidioides; fosmanogepix, an inhibitor of mannoprotein cell wall attachment, with broad activity against yeasts and molds; encochleated amphotericin B, an oral formulation of the long-established intravenous agent; and nikkomycin Z, a chitin synthase inhibitor under development since 1992.

Expert opinion: Despite improvements, gaps remain in treatments for severe IFI, particularly given increasing resistance. These agents represent significant advances, but further research is needed to define their use in patient management.