Learning to control antifungal drug resistance from the environment
By GAtherton

Spores of fungi including Aspergillus fumigatus, the main species that causes aspergillosis, have been found to propagate the growth of strains of fungi that are already resistant to those antifungal medications most commonly used in medical clinics to treat aspergillosis. This can render the most common treatments for aspergillosis useless, which is a concern for doctors.

Where do these strains come from? Most experts suggest that the use of commercial fungicides by farmers exposes the fungus to pesticides that closely resemble the antifungal drugs used by doctors. This exposure is likely to enrich the numbers of resistant spores found in the environment ie in compost, soil, and of course in/on the plant material produced by the farmers e.g. food crops, and flowering plants.

Can we stop using these antifungal chemicals as pesticides? A multi-disciplinary meeting designed to bring together experts from all sides of the debate took place in London on 13th July and those representing the growers outlined how important it is that farmers use these fungicides to prevent crop damage and to produce enough food to feed us all! Completely stopping their use on crops does not seem to be an option.

Given that it seems that there will be antifungal-resistant spores in the environment we live in for the foreseeable future we need to:

  • know where they are
  • know how to avoid inhaling them

Where might patients come into contact with most antifungal-resistant spores?

Farmers use antifungal pesticides on many crops including:

  • Fruits: Apples, grapes, peaches, strawberries, and tomatoes
  • Vegetables: Potatoes, onions, corn, and soybeans
  • Grains: Wheat, corn, and rice.
  • Nursery crops:  Roses, trees, and shrubs

Researchers have found antifungal-resistant Aspergillus fumigatus spores on many of these crops or the soil around them, at low levels (0 – 10% of samples).

Is this level of antifungal-resistant spores increasing?

When scientists looked at spore numbers they found that the number of resistant spores increased during the growing season as antifungal pesticides were applied to the crops, but this resistance did not survive the winter (1) and levels were back down to where they were the previous year.

It is apparent that handling crops, or the soil around them is a potential way to come into contact with some spores that are resistant to antifungal medications given in the clinic.

What is the likelihood of these spores causing an antifungal-resistant infection?

Researchers (1) have looked at how resistant the resistant spores are to the level of antifungal medication they will be exposed to in a patient and found that the proportion of the isolates that were resistant to the levels of antifungal medication used in patients was 1-4% – so very low.

Which crops are worst affected?

The most common material found to contain antifungal-resistant material was plant material waste originating from cut flowers and flowering bulbs and other types of waste produced in the industry in The Netherlands (2), so it is clear that composting can promote the growth of resistant spores. Ways to prevent this from happening are under development.

Other materials tested were household waste, wheat grain, poultry manure, cattle manure, horse manure, maize silage & fruit waste and of those antifungal-resistant spores were found only in fresh household waste.

Other researchers across the world (3) have detected antifungal-resistant spores in a range of crops and soils. Highest numbers of resistant spores (or perhaps in places where most research has been done) tend to be in India (rice), China (maize, some house plants, potato), USA (wheat, roses, apples), The Netherlands (orchids), Spain (onions, strawberries), Colombia (carrots) & Italy (grapes).

These were not exhaustive studies and we know that Aspergillus fumigatus (i.e. not antifungal-resistant) itself is found on far more plants/fruits/vegetables, so it stands to reason that if they are treated with antifungal pesticides then it may be possible to isolate resistant spores from them. It is clear that although there is a risk of inhaling antifungal-resistant spores from this plant material, the risk to the domestic consumer is low. Nonetheless, out of an abundance of caution, it might be best to take a few precautions:

a. Avoid handling cut flowers and flowering bulbs from The Netherlands

b. After purchase wash fruit and vegetables prior to storage in the home

c. Dispose of household waste in a timely manner

Action is being proposed and taken nationally and internationally to reduce the risk to aspergillosis patients in particular of inhaling antifungal-resistant spores of A. fumigatus and other fungi (4). Research is ongoing to learn more about what are the causal factors responsible for the increase in resistant spores, which are the main risks to human health and what we can do about it.

In time we should be able to prevent the growth of resistant isolates, ensuring that we have useful antifungal medication for years to come.

1. Effects of Agricultural Fungicide Use on Aspergillus fumigatus Abundance, Antifungal Susceptibility, and Population Structure

Authors: Amelia E. Barber https://orcid.org/0000-0002-3399-1037Jennifer RiedelTongta Sae-OngKang KangWerner BrabetzGianni PanagiotouHolger B. DeisingOliver Kurzai https://orcid.org/0000-0002-7277-2646AUTHORS INFO & AFFILIATIONS

DOI: https://doi.org/10.1128/mbio.02213-20

2. Emerg Infect Dis. 2019 Jul; 25(7): 1347–1353. doi: 10.3201/eid2507.181625

Environmental Hotspots for Azole Resistance Selection of Aspergillus fumigatus, the Netherlands

Sijmen E. Schoustra, Alfons J.M. DebetsAntonius J.M.M. Rijs, 1 Jianhua ZhangEveline SneldersPeter C. LeendertseWillem J.G. MelchersAnton G. RietveldBas J. Zwaan, and Paul E. Verweij

3. Azole-resistant Aspergillus fumigatus in the environment by cburks817 · MapHub

4. Nat Rev Microbiol. 2022; 20(9): 557–571.

Published online 2022 Mar 29. doi: 10.1038/s41579-022-00720-1

Tackling the emerging threat of antifungal resistance to human health

Matthew C. Fisher,1 Ana Alastruey-Izquierdo,2 Judith Berman,3 Tihana Bicanic,4 Elaine M. Bignell,5 Paul Bowyer,6 Michael Bromley,6 Roger Brüggemann,7 Gary Garber,8 Oliver A. Cornely,9 Sarah. J. Gurr,10 Thomas S. Harrison,4,5 Ed Kuijper,11 Johanna Rhodes,1 Donald C. Sheppard,12 Adilia Warris,5 P. Lewis White,13 Jianping Xu,14 Bas Zwaan,15 and Paul E. Verweij11,16

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