Abstract
Invasive fungal diseases due to resistant yeasts and molds are an important and increasing public health threat, likely due to a growing population of immunosuppressed hosts, increases in antifungal resistance, and improvements in laboratory diagnostics. The significant morbidity and mortality associated with these pathogens bespeaks the urgent need for novel safe and effective therapeutics. This review highlights promising investigational antifungal agents in clinical phases of development: fosmanogepix, ibrexafungerp, rezafungin, encochleated amphotericin B, oteseconazole (VT-1161), VT-1598, PC945, and olorofim. We discuss three first-in-class members of three novel antifungal classes, as well as new agents within existing antifungal classes with improved safety and tolerability profiles due to enhanced pharmacokinetic and pharmacodynamic properties.
Highlights
Invasive fungal diseases due to resistant yeasts and molds are an important and increasing public health threat, likely due to a growing population of immunosuppressed hosts, increases in antifungal resistance, and improvements in laboratory diagnostics
Any further responses from the reviewers can be found at the end of the article Introduction Invasive fungal diseases (IFDs) are a growing public health concern in an expanding population of immunocompromised hosts[1]
Despite significant advances in prevention, diagnosis, and management of IFDs over the past several decades, IFDs remain a formidable threat to immunocompromised hosts
Summary
Invasive fungal diseases due to resistant yeasts and molds are an important and increasing public health threat, likely due to a growing population of immunosuppressed hosts, increases in antifungal resistance, and improvements in laboratory diagnostics. Ibrexafungerp (previously MK-3118 and SCY-078; Scynexis, Jersey City, NJ, USA) disrupts fungal cell wall synthesis through inhibition of (1→3)-β-D-glucan synthase with fungicidal activity against Candida spp. In a murine invasive candidiasis model with WT and echinocandin-resistant (ER) C. glabrata, ibrexafungerp significantly reduced kidney fungal burden in both groups as compared to placebo.
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