August 25, 2025
2 min read
Key takeaways:
- Aspergillus fumigatus has become increasingly resistant to azoles over the last 30 years.
- Experts recommend combination therapy for respiratory disease ICU patients who are infected with the fungus.
Clinical management of aspergillosis has become more challenging as Aspergillus fumigatus develops increasing resistance to azoles, the antifungals primarily used to treat the infection, according to a review.
Researchers studied clinical A. fumigatus isolates collected from hospitals in the Netherlands from 1994 through 2022.
Most A. fumigatus resistance to triazole therapy does not occur in patients, but rather in agriculture, including in flower production. Image: Adobe Stock
“We now have collected about 2,000 resistant fungal strains, 17% of which show variations in resistance mutations,” Paul E. Verweij, MD, chair of clinical mycology and professor of medical science at Radboud University in the Netherlands, said in a press release.
According to experts, triazole-resistant A. fumigatus has become an increasing concern over the last decade, with other studies reporting levels of resistant isolates similar to those reported by Verweij and colleagues in their new study, which was published in The Lancet Microbe.
Verweij said the fungus has not developed resistance among humans, but rather in agriculture, where azoles used in food production and in cultivating flowers “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 out for a while,” he said.
Some experts, including Verweij, have in recent years recommended that clinicians move away from azole monotherapy when resistance is detected, in places where environmental resistance has been detected or when resistance rates exceed 10%.
In the new study, Verweij and colleagues analyzed all A. fumigatus isolates collected at hospitals in the Netherlands between Jan. 6, 1994, and Dec. 31, 2022, for triazole resistance. They further performed whole-genome sequencing on isolates that had specific genomic variants and mutations, as well as wild-type strains. Additionally, the researchers collected clinical information, including age, underlying disease, diagnosis, therapy and outcome, for patients whose isolates were cultured at the Radboud University Medical Center between Jan. 1, 2017, and Dec. 31, 2022.
According to the study, of the 12,679 isolates that the researchers analyzed, 1,979 15.6% harbored resistant mutations. Two resistant mutations were dominant among these — TR34/Leu98His sensu stricto in 1,338 (67.6%) of the isolates and TR46/Tyr121Phe/Thr289Ala sensu stricto in 332 (16.8%) of the isolates — and further phenotype and genotype variations were seen in 17.2% of the resistant isolates.
Among infections, the researchers also reported that among 13 patients with triazole-resistant infections, 11 were infected with mixed genotypes and were more likely to have a higher number of treatment changes than those with triazole-susceptible infections.
Mixed infections are likely the next major challenge in managing triazole resistance, the researchers wrote, making it important for clinicians to more accurately predict the triazole phenotype of an infection and to reconsider standard monotherapy among infected patients.
“We see [these] fungal infections, for example, in people who are in the ICU with severe influenza or COVID-19,” Verweij said, adding that people with conditions such as COPD, leukemia or who had an organ transplant are also at risk for A. fumigatus infection.
“Their risk of death doubles when they contract an infection,” he said, and as a result of rising azole resistance, “if we now culture A. fumigatus in a patient in the ICU with influenza or COVID-19, we immediately start combination therapy.”
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Sources/Disclosures
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Disclosures:
Verweij reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
