Assessment of selection and resistance risk for demethylation inhibitor fungicides in Aspergillus fumigatus in agriculture and medicine: a critical review.

BACKGROUND: An increasing number of publications have claimed that demethylation inhibitor (DMI) fungicides are confronted with resistance development in the fungus Aspergillus fumigatus and that the origin of resistant isolates may also be outside the medical area. For resistance risk assessment and sourcing the origin of DMI resistance, the primary exposure events ofA. fumigatus with DMI treatments have been analysed case by case, resulting in the pathogen exposure risk (PER).

RESULTS: The calculated maximum exposure concentrations (MEC) are highest during medical treatments (human and veterinary), certain fruit and seed treatments and wood preservation, and are much lower for crop protection applications. Most agricultural DMIs are intrinsically ∼10-100 times less active than medical DMIs for A. fumigatus control and potential resistance selection. However, imazalil is used in agriculture and veterinary medicine (as enilconazole) expressing strong intrinsic activity against A. fumigatus. The majority of mutations in the target gene, cyp51, of DMI-resistant isolates are different in A. fumigatus(e.g. TR34/L98H) in comparison with plant pathogens (e.g. A379G, I381V).

CONCLUSIONS: The assumed selection risk, ASR (MEC × PER) for resistance evolution to DMIs in A. fumigatus is estimated to be highest for human and veterinary applications. However, environmental origin of DMI-resistant spores from certain sites cannot be ruled out.