A nearly three-decade study has revealed a significant rise in triazole-resistant Aspergillus fumigatus, a fungus responsible for invasive aspergillosis, in clinical isolates across Dutch hospitals. The findings, published after an extensive genomic and phenotypic investigation spanning 1994 to 2022, highlight the growing threat resistance poses to frontline antifungal therapies.
Researchers screened 12,679 clinical isolates, identifying triazole resistance mutations in 1,979 samples (15.6%). The majority carried well-established resistance mechanisms linked to mutations in the cyp51A gene: TR34/Leu98His (67.6% of resistant isolates) and TR46/Tyr121Phe/Thr289Ala (16.8%). Notably, 325 isolates demonstrated variations in resistance profiles, including 12 previously uncharacterised cyp51A genotype variants.
Whole-genome sequencing revealed that TR34- and TR46-related variants largely arose from distinct fungal populations, though overlap was observed. In a clinical subset from Radboud University Medical Centre, 59 cases of proven or probable invasive aspergillosis were identified between 2017 and 2022. Thirteen involved triazole-resistant infections, often linked to mixed-genotype strains. Patients with resistant infections required significantly more treatment changes compared with those infected by susceptible strains.
The study underscores the urgent need for improved diagnostic methods and surveillance, as antifungal resistance continues to erode treatment reliability, with potentially serious consequences for immunocompromised patients.
Helena Bradbury, EMJ
Reference
Song Y et al. Triazole-resistant Aspergillus fumigatus in the Netherlands between 1994 and 2022: a genomic and phenotypic study. The Lancet Microbe. 2025;6(8):101114.
