Epidemiology of Triazole Resistant Aspergillus fumigatus in Asia: A Systematic Review and Meta-Analysis.

Abstract

Background: Triazoles are the cornerstone of therapy for various forms of aspergillosis. However, the emergence of triazole-resistant Aspergillus fumigatus (TRAF) isolates poses a growing global threat. Although Asia harbours the largest at-risk population, the burden of azole resistance in this region has yet to be systematically evaluated. This study aimed to systematically review available data on TRAF to estimate the overall burden of azole resistance.

Methods: We systematically searched four databases-PubMed, Web of Science, Embase, and Scopus-from inception to May 2025 using appropriate search strings. We included studies from Asia that reported data on azole-resistant Aspergillus isolates obtained from both environmental and clinical samples. The objective was to report the pooled proportion (frequency) of azole-resistant Aspergillus isolates from all studies reported from countries in Asia.

Finding: A total of 1284 studies were identified, of which 498 were screened for eligibility after removing duplicates. Following title and full-text screening, 401 studies were excluded. Ultimately, 97 unique studies were included, providing resistance data on 8,049 clinical and 6,949 environmental isolates of Aspergillus fumigatus. The pooled proportion of triazole-resistant A. fumigatus (TRAF) in clinical isolates (predominantly respiratory > ear > other sources) was 4% (95% CI: 3%-6%); whereas in environmental isolates, it was 14% (95% CI: 9%-20%). The proportion of TRAF varied by country of origin. Among clinical isolates, higher rates were observed in Türkiye (96/1273; 7.5%), India (59/979; 6.0%), Iran (39/522; 7.5%), and Japan (69/958; 7.2%). For environmental isolates, a higher proportion was reported in Iran (203/847; 24.0%), Thailand (27/161; 16.8%), and China (472/3671; 12.8%). Among all TRAF isolates, resistance to itraconazole was most common (86.3%), followed by posaconazole (66.5%) and voriconazole (65.4%). Notably, 53.5% of TRAF isolates were pan-triazole resistant. Mutation analysis for triazole resistance was performed in 408 clinical and 871 environmental isolates. The TR34/L98H mutation was the most frequently reported, detected in 34.5% of clinical and 38.6% of environmental isolates.

Interpretation: This study is the first to systematically review available data on azole resistance in Aspergillus fumigatus isolates obtained from environmental and clinical samples in Asia. The findings reveal a significant burden of azole-resistant isolates in clinical and environmental samples, underscoring their impact on disease management and treatment outcomes. Among the Asian population, triazole-resistant Aspergillus fumigatus (TRAF) can be seen in a small but significant proportion of patients with aspergillosis, most of which have been reported in pulmonary aspergillosis. This is likely linked to the significant burden in environmental isolates, as seen in these studies. In many such cases, multiple triazole drugs may be therapeutically ineffective, highlighting the need for a high degree of suspicion of TRAF in clinical practice. Future research should focus on investigating the underlying causes of resistance and developing potential interventions to address this pressing issue, which poses a serious threat to this vital class of antifungal agents.