Report of Four Azole-Resistant Aspergillus fumigatus Isolates with TR34 or TR46 Mutations in Japan Referred to a Mycosis Reference Center for Examination.

In recent years, increased azole-resistant Aspergillus fumigatus (ARAf) isolation has been reported worldwide, and it poses a major threat. The main cause of resistance originates from mutations in the cyp51A gene, which encodes 14α-demethylase. Among the clinical isolates we received before 2024, a designated point mutation in their Cyp51A protein was the main mechanism of resistance for ARAf. However, from 2024, ARAf with tandem repeats (TRs) of 34 or 46 base-pairs in the promoter region of the cyp51A gene and amino acid substitutions in the coding region (TR-ARAf), which have been widely reported overseas but seldom found in Japan, has become isolated more frequently. Among the 111 A. fumigatus strains referred to our institution in 2024, ten strains were ARAf, of which four were TR-ARAf. Our study indicates that the prevalence of TR-ARAf in Japan is potentially on the rise, possibly posing a serious threat to public health. This trend might have serious implications for the management of aspergillosis in the country in the near future.