Past, present, and emerging antifungals against Fusarium and other rare non-Aspergillus hyalohyphomycetes: a narrative review.

INTRODUCTION: Invasive fungal infections caused by Fusarium and other rare hyalohyphomycetes, such as Scopulariopsis and Paecilomyces species, can lead to devastating localized and disseminated infections in vulnerable patient populations. Currently employed antifungal agents exhibit limited effectiveness for these molds. Over the past few years, the approval of new antifungals and the ongoing development of others in clinical trials offer promising new therapeutic options for treating these infections.

AREAS COVERED: In this review, utilizing PubMed literature review, we delve into selected hyalohyphomycoses and provide an overview of the pharmacokinetics and pharmacodynamics of rezafungin, ibrexafungerp, olorofim, and fosmanogepix. We examine the available in-vitro and in-vivo efficacy data for these antifungals. Rezafungin and ibrexafungerp inhibit different steps in the synthesis of (1,3) β-d-glucan, and rezafungin is a notably long-acting echinocandin; however, both have primarily been studied against candidiasis. Olorofim and fosmanogepix, in contrast, are novel antifungals in development with unique mechanisms of action with activity against hyalohyphomycoses.

EXPERT OPINION: Both rezafungin and ibrexafungerp have limited efficacy and clinical experience in treating mold infections. Fosmanogepix and olorofim hold promise for treating invasive mold infections, including hyalohyphomycoses; however, given in-vitro antifungal susceptibility variability against hyalohyphomycetes, and lack of clinical trial information, future studies are needed.