Antifungal resistance, combinations and pipeline: oh my!

Area of Science:

• Infectious Diseases
• Pharmacology
• Mycology

Background:

• Invasive fungal infections (IFIs) significantly increase healthcare costs, morbidity, and mortality, particularly in hospitalized patients.
• Historically, *Candida* species accounted for ~15% of nosocomial bloodstream infections, but epidemiology has shifted with increasing prevalence of resistant strains.
• Rising antifungal resistance necessitates the development of novel therapeutic agents.

Purpose of the Study:

• To review the evolving epidemiology of invasive fungal infections, focusing on the increasing prevalence of antifungal resistance.
• To discuss the limitations of current antifungal therapies, including side effects and the emergence of multidrug-resistant pathogens.
• To highlight newer antifungal agents that may address unmet needs in managing IFIs.

Main Methods:

• Literature review of recent studies on invasive fungal infections and antifungal resistance.
• Analysis of the current landscape of antifungal drug development.
• Discussion of emerging antifungal agents and their potential clinical applications.

Main Results:

• The prevalence of resistant *Candida* species has increased, driving demand for new antifungal treatments.
• Existing antifungal therapies can have dose-limiting side effects, and multidrug-resistant pathogens remain a clinical challenge.
• Newer agents such as fosmanogepix, ibrexafungerp, olorofim, and rezafungin offer potential improvements in spectrum of activity and safety profiles.

Conclusions:

• Novel antifungal agents are crucial to combat the growing threat of invasive fungal infections and antifungal resistance.
• Fosmanogepix, ibrexafungerp, olorofim, and rezafungin represent promising additions to the antifungal armamentarium.
• Continued research and development are needed to address complex fungal infections and resistance patterns.