Clinical and Genomic Insights into Antifungal Resistance in Aspergillus Isolates from Thailand.

Aspergillus species are major opportunistic pathogens responsible for invasive aspergillosis, with antifungal resistance posing increasing challenges to their treatment worldwide. We investigated the antifungal susceptibility and genomic features of Aspergillus isolates from sterile clinical specimens collected at a tertiary hospital in Thailand between January and December 2023. In total, 24 isolates were identified via culture and tested for amphotericin B and voriconazole susceptibility using CLSI M38 broth microdilution, and whole-genome sequencing was performed on selected isolates to characterize resistance mechanisms. Aspergillus fumigatus was the most frequent species (54%), followed by A. flavus (29%) and other less common species. Voriconazole exhibited potent activity against most isolates, although two A. fumigatus strains showed elevated MICs (2-4 µg/mL), meeting resistance thresholds. One isolate (CUAFU23) was confirmed to harbor the cyp51A TR34/L98H mutation, marking the first identification of this canonical azole resistance mechanism in a clinical specimen from Thailand and supporting earlier environmental findings of azole-resistant A. fumigatus carrying the same allele. Genomic profiling of CUAFU23 further revealed subtle but distinct shifts in domain composition compared with susceptible strains, suggesting broader adaptive changes. The above findings underscore the emergence of azole-resistant A. fumigatus in Thailand and highlight the importance of ongoing surveillance using combined phenotypic and molecular approaches.