Novel Therapeutic Approaches to Invasive Candidiasis: Considerations for the Clinician

Abstract

Invasive candidiasis (IC), due to the yeast pathogen Candida , is still a major cause of in-hospital morbidity and mortality. The limited number of antifungal drug classes and the emergence of multi-resistant Candida species, such as Candida auris and some Candida glabrata isolates, is concerning. However, recent advances in antifungal drug development provide promising perspectives for the therapeutic approach of IC. Notably, three novel antifungal agents, currently in Phase II/III clinical trials, are expected to have an important place for the treatment of IC in the future. Rezafungin is a novel echinocandin with prolonged half-life. Ibrexafungerp and fosmanogepix are two first-in-class antifungal drugs with broad spectrum activity against Candida spp., including C. auris and echinocandin-resistant species. These novel antifungal agents also represent interesting alternative options because of their acceptable oral bioavailability (ibrexafungerp and fosmanogepix) or their large interdose interval (once weekly intravenous administration for rezafungin) for prolonged and/or outpatient treatment of complicated IC. This review discusses the potential place of these novel antifungal drugs for the treatment of IC considering their pharmacologic properties and their preclinical and clinical data.

Antifungal Drug Resistance: An Emergent Health Threat

“…In addition, a new viable strategy is passive immunization with monoclonal antibodies, so as to strengthen the host antifungal immune response [ 41 , 42 ], particularly in immunocompromised patients who are more prone to systemic fungal infections. Finally, three novel antifungal agents, currently in phase II/III clinical trials, might have an important role for the treatment of invasive candidiasis: phase III results showed the efficacy and safety of rezafungin [ 43 ], a novel echinocandin with extended half-life (once-weekly intravenous administration), enhanced tissue penetration/residence time, and limited drug–drug interaction potential; ibrexafungerp (phase III clinical trials) and fosmanogepix are two first-in-class antifungal drugs with acceptable oral bioavailability and broad-spectrum activity against Candida spp., including C. auris and echinocandin-resistant species ( Table 2 ) [ 43 , 44 ]. These three compounds, together with other new products, i.e., VT-1598 and ATI-2307, were found to be effective against candidemia due to C. auris [ 38 ].…”

Clinical Distribution and Drug Susceptibility Characterization of Invasive Candida Isolates in a Tertiary Hospital of Xinjiang Province

“…The incidence of invasive fungal infections is increasing, attributed to the wide usage of glucocorticoids, broad-spectrum antibiotics, immunosuppressants, as well as advances in invasive manipulation techniques and novel therapeutic approaches. 1 , 2 Among these infections, invasive candidiasis is the most common, with Candida albicans being the predominant causative agent; however, due to the widespread use of antifungal medications, there is an epidemiological shift in the prevalence of strains from Candida albicans to non- Candida albicans Candida species (NCAC). 3 The epidemiology and drug sensitivity of invasive Candida strains vary based on different regions, patients, and doctors’ medication practices.Understanding the local distribution of strains and their drug susceptibility brings numerous advantages in terms of prompt detection and therapy, thereby improving the cure rate and reducing drug resistance and adverse reactions caused by long-term empiric and preventive use of antifungal drugs.…”

Brilacidin, a host defense peptide mimetic, potentiates ibrexafungerp antifungal activity against the human pathogenic fungusAspergillus fumigatus

“…IBX binds to the 1,3-β-D-glucan synthase, the same target of echinocandins, but in contrast to this class of compounds, it has oral bioavailability 3,4 . Currently, IBX is approved as an oral drug for the treatment of vulvovaginal candidiasis, and it is in the process of approval against invasive candidiasis and aspergillosis [3][4][5] . Here, we describe brilacidin (BRI), a host defense peptide mimetic, as a potentiating agent of IBX against A. fumigatus.…”