Widespread Use of Azole Fungicides May Increase Resistance Risks of Aspergillus Fungi, Warns EFSA

The widespread use of azole fungicides, particularly in certain agricultural and horticultural practices, could increase the risk of Aspergillus fungi developing resistance to essential antifungal treatments, reports the European Food Safety Authority (EFSA).

This significant finding is highlighted in a report from five EU health and environmental agencies, supported by the European Commission’s Joint Research Centre (JRC). The agencies have collaborated under the One Health approach to address this growing threat.

For the first time, the five EU agencies for health and the environment (EFSA, ECDC, ECHA, EEA, and EMA), supported by the JRC, have analyzed how the use of azole substances outside of human medicine impacts public health.

Azole drugs are crucial for treating aspergillosis, a serious infection caused by Aspergillus fungi. However, these fungi are becoming increasingly resistant to azole therapies, making treatment less effective.

Azole substances are widely used in plant protection products ("pesticides") for controlling fungal diseases in agriculture and horticulture, as veterinary medicines for treating fungal infections in animals, as biocides in wood preservatives, as industrial chemicals (e.g., intermediates and dyes), and in cosmetics (e.g., as anti-dandruff agents).

The joint report emphasizes that their extensive use outside human medicine, particularly in agriculture, contributes to the risk of Aspergillus developing resistance to azoles. Exposure to environments where azole fungicides are used, such as agricultural sites and woodworking operations, can increase the risk of infection with azole-resistant Aspergillus spp.

Data collected from EU/EEA countries (2010–2021) and included in the report details the use of azole fungicides in Europe. Plant protection products account for the majority of reported sales across all sectors.

One Health: Key Recommendations

Addressing azole resistance in Aspergillus requires cross-sector collaboration. The One Health approach brought together EU experts from human and veterinary medicine, agriculture, and environmental sciences to analyze existing evidence, identify factors promoting azole resistance, and propose measures to prevent and control it.

Recognizing the interconnected nature of this challenge, the agency experts recommended the following actions:

• Adding new specific requirements for the approval and authorization processes for azole fungicides.
• Supporting the research and development of new fungicides with innovative mechanisms of action that do not lead to resistance to antifungal drugs used in human treatments.
• Following good agricultural and horticultural practices, proper storage of organic waste, effective waste management, and the responsible use and disposal of products treated with azoles.
• Implementing effective waste management for wood treated with azole-based biocides.
• Collecting more data on the uses of azole-based fungicides and azole-based antifungals.
• Further developing specific technical guidelines and risk assessment methodologies to support regulatory decisions regarding the approval of azole substances and to mitigate the risk of azole resistance in Aspergillus.
• Conducting additional research to address existing uncertainties.

The report reinforces the value of the One Health approach in addressing complex health threats, such as antifungal resistance.