Yet the emerging problem of AMR is shared across the domains of life and many parallels exist between drug-resistant microorganisms (Table 1). Biological differences between fungal (eukaryotic) and bacterial (prokaryotic) pathogens also complicate the integration of fungi into existing AMR programmes. Traditionally, AMR programmes excluded antifungals because fungi have been widely neglected as a threat to public health 8, 9. The increasing public health burden is now officially recognized with the listing of both of these pathogens on the urgent antimicrobial resistance (AMR) threat list published by the US CDC in 2019 (ref. Resistance to antifungal drugs is an emerging concern worldwide in both space and time 4, including novel resistant variants of previously susceptible pathogens (for example, the ubiquitous mould Aspergillus fumigatus 5) as well as entirely new emerging species that are resistant to multiple antifungal drugs (for example, the yeast Candida auris 6). This failure is attributable to an interplay between underlying host immune defects, antifungal drug properties (pharmacokinetics, pharmacodynamics and drug–drug interactions) and fungal characteristics including diverse cell morphologies, antifungal tolerance and antifungal resistance. However, fungi respond nimbly to chemical attack 4 and treatment failure is a common outcome. Historically, treatment has relied heavily on just four classes of systemically acting antifungal drugs: the polyenes, azoles, echinocandins and the pyrimidine analogue 5-flucytosine 3. Similar content being viewed by othersįungi cause diverse diseases in humans, ranging from allergic syndromes to superficial, disfiguring and life-threatening invasive fungal diseases (IFDs), which together affect more than a billion people worldwide 1, 2. We emphasize the global efforts required to steward our existing antifungal armamentarium, and to direct the research and development of future therapies and interventions. These topics include links between the environment and One Health, surveillance, diagnostics, routes of transmission, novel therapeutics and methods to mitigate hotspots for fungal adaptation. We discuss the research and innovation topics that are needed for risk reduction strategies aimed at minimizing the emergence of resistance in pathogenic fungi. In this Review, we highlight the main mechanisms of antifungal resistance and explore the similarities and differences between bacterial and fungal resistance to antimicrobial control. Across a period of profound global environmental change and expanding at-risk populations, human-infecting pathogenic fungi are evolving resistance to all licensed systemic antifungal drugs.

Invasive fungal infections pose an important threat to public health and are an under-recognized component of antimicrobial resistance, an emerging crisis worldwide.

Nature Reviews Microbiology volume 20, pages 557–571 ( 2022) Cite this article Tackling the emerging threat of antifungal resistance to human health

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