Table 2.

Current and future antifungal treatment of CAPA, CAM and CAC

Invasive fungal disease/antifungal therapy	First line	Second line	Future treatment first line	Future treatment 1 advantages/disadvantages	Future treatment second line	Future treatment 2 advantages/disadvantages
CAPA	Voriconazole or isavuconazole25	Liposomal amphotericin B25 or posaconazole25	Opelconazole158	Inhaled antifungal, limited systemic toxicity or drug–drug interactions, used for early treatment or prophylaxis	Fosmanogepix158 or olorofim158	New mechanism of action, fewer drug–drug interactions, activity against azole-resistant CAPA, oral formulation only for olorofim
CAM	Liposomal amphotericin B48	Isavuconazole48 or posaconazole48	Fosmanogepix158	New mechanism of action, oral and intravenous formulation, variable activity against Mucorales, potential use in combination with liposomal amphotericin B (synergism in animal model)	Ibrexafungerp158	New mechanism of action, oral formulation, variable activity against Mucorales, potential use in combination with liposomal amphotericin B (synergism in animal model)
CAC	Caspofungin or anidulafungin or micafungin	Fluconazole or liposomal amphotericin B or voriconazole	Ibrexafungerp158 or rezafungin158	Oral formulation (ibrexafungerp), echinocandin with very long half-life allowing for once weekly intravenous therapy (rezafungin), activity against resistant Candida spp.	Fosmanogepix158	Good activity against resistant species, no activity against Candida krusei