Systemic candidiasis - Emerging treatments

Rezafungin

Rezafungin is a newer echinocandin antifungal that is structurally similar to anidulafungin. It is approved in the US and Europe for the treatment of candidaemia and invasive candidiasis in adults with no alternative treatment. Rezafungin has an extended half-life allowing for once-weekly dosing. However, it is not yet routinely prescribed. In one phase 3 clinical trial, rezafungin was shown to be non-inferior to caspofungin for the primary endpoints of day-14 global cure and 30-day all-cause mortality for adult patients with candidaemia or invasive candidiasis.[81] Pooled data from the phase 2 STRIVE and phase 3 ReSTORE trials indicated that rezafungin has potential early treatment benefits, such as higher rates of mycological eradication at day 5 and faster time to negative blood cultures.[82]

Ibrexafungerp

Ibrexafungerp is a triterpenoid antifungal that inhibits glucan synthase and has broad activity against most pathogenic Candida species. One phase 2 trial comparing ibrexafungerp with standard of care demonstrated comparable efficacy and safety for treatment of invasive candidiasis.[44][83]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: Candidiasis (Mucocutaneous). 2024 [internet publication]. Ibrexafungerp is approved in the US for vulvovaginal candidiasis but not systemic candidiasis. It is not approved in Europe for either indication as yet.

Combination antifungal therapy

Using 2 antifungal agents from 2 drug classes with different mechanisms of action has not been shown to offer any advantage and should not be considered for most cases with systemic candidiasis. Rare exceptions include patients with mixed Candida species infection or Candida endocarditis.

Fosmanogepix

Fosmanogepix is an investigational, first-in-class guanosine monophosphate inhibitor with broad activity against all pathogenic Candida species with the exception of Candida krusei. Excellent tolerance and efficacy was demonstrated in one phase 2 trial of fosmanogepix for invasive candidiasis primarily caused by fluconazole-resistant organisms.[44]

Candida vaccine

In mouse candidiasis studies, active immunisation seemed to protect infected animals. A number of potential fungal vaccine candidates have reached early human clinical trials.[84]