Beyond Conventional Antifungals: Combating Resistance Through Novel Therapeutic Pathways
Helal F. Hetta, Tameem Melhem, Hashim M. Aljohani, Ayman Salama, Rehab Ahmed, Hassabelrasoul Elfadil, Fawaz E. Alanazi, Yasmin N. Ramadan, Basem Battah, Michelangelo Rottura, Matthew Gavino Donadu
Abstract
The rising burden of fungal infections presents a significant challenge to global healthcare, particularly with increasing antifungal resistance limiting treatment efficacy. Early detection and timely intervention remain critical, yet fungal pathogens employ diverse mechanisms to evade host immunity and develop resistance, undermining existing therapeutic options. Limited antifungal options and rising resistance necessitate novel treatment strategies. This review provides a comprehensive overview of conventional antifungal agents, their mechanisms of action, and emerging resistance pathways. Furthermore, it highlights recently approved and investigational antifungal compounds while evaluating innovative approaches such as nanotechnology, drug repurposing, and immunotherapy. Addressing antifungal resistance requires a multifaceted strategy that integrates novel therapeutics, enhanced diagnostic tools, and future research efforts to develop sustainable and effective treatment solutions.