Alarming Growth in Antifungal Resistance Tracked Over 30 Years in Dutch Study

A comprehensive study published in The Lancet Microbe reveals a worrying rise in fungal resistance to antifungal medications, particularly in the common fungus Aspergillus fumigatus. The study analyzed more than 12,000 lung samples collected from Dutch hospitals over 30 years.

Since 1994, microbiologist Paul Verweij and his team have been collecting A. fumigatus isolates from patients’ lungs. In the early years, no resistance to antifungal drugs was detected. However, by 2000, a significant DNA mutation was identified that led to resistance. Another key mutation followed in 2009. Over time, numerous smaller genetic changes have also emerged, often appearing in combination, contributing to increasingly diverse and drug-resistant fungal strains.

‘We now have collected about two thousand resistant fungal strains, 17% of which show variations in resistance mutations’, says Verweij. Importantly, these resistant strains nearly always appear as mixtures in patient infections, making treatment more complex.

The primary class of drugs used to treat A. fumigatus infections are azoles. However, resistance to azoles is not primarily caused by their use in medical treatment but by widespread application in agriculture. ‘Azoles are also used in food production and flower cultivation, and are aimed at fungi that make plants sick, such as Fusarium’, explains Verweij. ‘These azoles end up in waste heaps from certain production lines, where A. fumigatus thrives. There, the fungus becomes resistant to azoles, especially when these waste heaps are left for a while.’

While healthy individuals can clear inhaled fungal spores naturally, people with weakened immune systems such as those with COPD, leukemia, or recovering from organ transplants are at high risk. Fungal infections are also common in ICU patients with severe flu or COVID-19, doubling their risk of death.

The growing complexity of fungal resistance has already led to changes in clinical guidelines. Since 2017, ICU patients with suspected A. fumigatus infections are treated immediately with combination antifungal therapy.

As fungal resistance continues to rise, researchers emphasize the urgent need for better monitoring and new treatment strategies.

Reference: Song, Y., Buil, J., Zoll, J., Tehupeiory-Kooreman, M., Zhang, J., Li, R., ... & Verweij, P. E. Characteristics and Dynamics of Triazole-Resistant Aspergillus Fumigatus Variants Emerging Over a 28-Year Period in the Netherlands. Aspergillus Fumigatus