Antifungal Resistance and the Role of New Therapeutic Agents

Advances in health care over time have led to an evolution in the epidemiology of invasive fungal infections. There is an increasing concern for antifungal resistance and emergence of less common fungal species for which optimal therapies are not well defined. The purpose of this review is to describe mechanisms of antifungal resistance and to evaluate the modern role of new and investigational antifungals.

Isavuconazole and ibrexafungerp represent the two newest antifungal agents. Evidence from in vivo and in vitro studies has been published recently to help define their place in therapy and potential roles in treating resistant fungi. Isavuconazole is a broad-spectrum triazole antifungal with evidence to support its use in invasive aspergillosis and mucormycosis. Its utility in treating voriconazole-resistant Candida should be confirmed with susceptibility testing if available. Ibrexafungerp is an oral glucan synthase inhibitor with little cross-resistance among currently available antifungals, including echinocandins. It is a promising new agent for invasive candidiasis, including azole-resistant Candida species, and in combination therapy with voriconazole for aspergillosis. Multiple antifungals, some with novel mechanisms, are in development, including rezafungin, oteseconazole, olorofim, fosmanogepix, and opelconazole.

Both isavuconazole and ibrexafungerp are welcome additions to the arsenal of antifungals, and the prospect of more antifungal options in the future is encouraging. Such an array of antifungals will be important as antifungal resistance continues to expand alongside evolving medical practices. However, managing resistant fungal infections will grow in complexity as the unique role of each new agent is defined.