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Treatment of invasive fungal infections (IFI) remains challenging, because of the limitations of the current antifungal agents (i.e. mode of administration, toxicity, drug-drug interactions), and the emergence of resistant fungal pathogens. Therefore, there is an urgent need to expand our antifungal armamentarium. Several compounds are reaching the stage of phase II or III clinical assessment. These include new drugs within the existing antifungal classes or displaying similar mechanism of activity with improved pharmacologic properties (rezafungin, ibrexafungerp) or first-in-class drugs with novel mechanisms of action (olorofim, fosmanogepix). Although critical information regarding the performance of these agents in heavily immunosuppressed patients is pending, they may provide useful additions to current therapies in some clinical scenarios, including IFI caused by azole-resistant Aspergillus or multi-resistant fungal pathogens (e.g. Candida auris, Lomentospora prolificans). However, their limited activity against Mucorales and some other opportunistic molds (e.g. some Fusarium spp.) persists as a major unmet need.

PMID: 34986246