Fungal Antimicrobial Resistance: Mechanisms, Drivers, and Global Clinical Burden

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Abstract
Fungal antimicrobial resistance (AMR) is a growing concern for world health caused by an increase in multidrug‐resistant infections, an increase in environmental reservoirs, and the ineffectiveness of current antifungal treatments. Fungal infections continue to be largely excluded from AMR initiatives while causing over 1.6 million deaths annually, exceeding malaria and competing with tuberculosis (TB), due to diagnostic blind spots, inadequate monitoring, a limited antifungal arsenal, and long‐standing bacterial‐centric preconceptions. Several mutations, efflux pump upregulation, biofilm‐associated tolerance, aneuploidy, and stress‐induced adaptations are just a few of the mechanisms through which resistance develops. Moreover, agricultural triazoles are also responsible for the widespread azole‐resistant Aspergillus fumigatus . Clinically, treatment failure and significant mortality are increasingly caused by multidrug‐resistant Candidozyma auris , Nakaseomyces glabrata , fluconazole‐resistant Cryptococcus neoformans , and terbinafine‐resistant dermatophytes. Resistant fungi continue to develop mostly unchecked due to a lack of funding, misconceptions regarding fungal infection, and low epidemic visibility. To match global action with the actual burden of fungal resistance, I have summarized the molecular, ecological, clinical, and policy drivers of fungal AMR in this review. I have also identified key priorities, such as increased surveillance, expanded diagnostics, agricultural fungicide regulation, and accelerated antifungal innovation.

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