Crossover between the control of fungal pathogens in medicine and the wider environment,and the threat of antifungal resistance

Fungal propagules existing in the natural environment can easily be transmitted to the human body, mostly by inhalation of contaminated air or direct contact onto the skin, nails, and mucosa. Fungal infections in humans are, as compared to viral and bacterial infections, rarely serious (life-threatening) unless the immune system is weakened. Because azole fungicides (demethylation inhibitors, DMIs) are among the most important antifungal compounds used broadly in human and animal medicine as well as in agriculture and material protection, fungal propagules may come into contact with azoles almost everywhere, presenting a potential “crossover-use-pattern” and “cross-contamination-risk” for resistant propagules in all areas. A “hot-spot” in terms of the emergence of azole resistance in a fungal species is defined as a habitat in which the species is actively propagating and exposed to a fungicidally effective azole at available concentrations high enough to select for resistant individuals, potentially multiplying and spreading to other habitats. Intrinsic antifungal resistance may exist in less sensitive or insensitive species independent of previous exposure to antifungal compounds, whereas acquired antifungal resistance can evolve if triggered by the exposure of an originally sensitive species (or population) to agricultural or medical antifungal agents, resulting in the selection of resistant individuals. The origin and risks of these developments in medical settings and the wider environment are elucidated for the most relevant life-threatening fungal human pathogens, including several species of Cryptococcus, Candida, Pneumocystis, Aspergillus, Histoplasma, Coccidioides, Rhizopus, Mucor, Fusarium, and Scedosporium.