Recent Antifungal Pipeline Developments against Candida auris: A Systematic Review

Area of Science:

• Infectious Diseases
• Mycology
• Pharmacology

Background:

• Multidrug-resistant *Candida auris* poses a significant global health threat.
• Limited effective therapeutic options exacerbate the challenge of treating *C. auris* infections.
• Development of novel antifungal agents is crucial to combat emerging resistant strains.

Purpose of the Study:

• To systematically review and synthesize data on the in vitro activity and in vivo efficacy of investigational antifungals against *Candida auris*.
• To identify promising new agents and assess their potential for treating *C. auris* infections.
• To provide an overview of the current landscape of novel antifungal drug development for *C. auris*.

Main Methods:

• Systematic literature search of MEDLINE, EMBASE, Web of Science, and Scopus up to June 27, 2022.
• Inclusion of studies reporting in vitro activity (MIC values) and in vivo efficacy data for investigational antifungals against *C. auris*.
• Analysis of data from 27 eligible articles out of 592 initially retrieved.

Main Results:

• Manogepix/fosmanogepix exhibited the lowest MIC90 (0.03 mg/L), followed by rezafungin (MIC mode: 0.25 mg/L) and ibrexafungerp (MIC90: 1 mg/L).
• Investigational agents included new additions to existing classes (rezafungin, opelconazole) and first-in-class drugs (ibrexafungerp, manogepix/fosmanogepix, olorofim, tetrazoles, ATI-2307, MGCD290, VL-2397).
• All evaluated compounds demonstrated significant improvements in survival and reduced fungal burden in animal models of *C. auris* candidemia.

Conclusions:

• Several investigational antifungal agents show significant promise in preclinical studies against multidrug-resistant *Candida auris*.
• Manogepix/fosmanogepix, ibrexafungerp, and rezafungin are among the most promising agents currently under development.
• Continued research and development of novel antifungals are essential to address the growing threat of *C. auris* infections.