Assessing the potential risk of human pathogen resistance to medical antifungal treatments arising from agricultural use of fungicides with the same mode of action

Abstract A mechanistic basis is described for assessment of resistance risk to medical antifungal treatments from agricultural use of fungicides of the same mode of action. The following need to occur in landscape environments for a risk to be posed by dual use: (i) emergence, whereby a resistant strain emerges by mutation and invasion; (ii) selection, whereby a mutation conferring a fitness advantage is selected for in the presence of fungicide; and (iii) exposure of humans to resistant strains from the landscape, potentially resulting in invasive fungal infection. We identify 20 human pathogens for which there is evidence that all three processes above could, in principle, occur. A model is derived to explore what determines resistance emergence and selection in human pathogens in landscape environments. Knowledge gaps are identified in key parameters. The analysis suggests that emergence and selection were particularly affected by fitness cost associated with the resistance mutation(s) and fungicide concentration. Emergence was also determined by the amount of pathogen reproduction (related to pathogen population size). If fungicide resistance is associated with even a small fitness cost, then environments with low fungicide concentrations, such as field soils, may not be conducive to resistance emergence or selection. These general findings were related to a specific case of observational data from the Netherlands for Aspergillus fumigatus . The analysis supports previous work that compost is towards the high‐risk end of the spectrum for this species. Agricultural soils, nonagricultural land and grassland were lower risk.