First reports of azole-resistant Aspergillus fumigatus isolates carrying TR34/L98H mutation in Taiwan

Chi-Jung Wu, Hsuan-Chen Wang, Ching-Tzu Dai, Pei-Hsin Chou, Yee-Chun Chen


Aspergillus fumigatus was the leading pathogen causing invasive mold diseases in humans. To survey the prevalence of azole resistance, we investigated 27 consecutive clinical A. fumigatus isolates cultivated from 19 patients from two hospitals located in the southern and northern parts of Taiwan, respectively. The strain identification was based on the morphological characteristics and sequence analysis of the internal transcribed spacer region, β-tubulin, and calmodulin genes. The azole minimal inhibitory concentrations were determined according to the guidelines of the CLSI document M38-A2. The results showed that three isolates obtained from the respiratory samples of two patients, one of whom was azole-naive, displayed multi-azole resistance. The per-patient analysis showed a prevalence of azole resistance rate of 10.5%. Sequence analysis of cyp51A indicated the presence of TR34/L98H mutation in isolate A31 (itraconazole-, posaconazole-, and voriconazole-resistant) from southern Taiwan and TR34/L98H, S297T, F495I mutation in isolates a44 and a51 (itraconazole- and posaconazole-resistant) from northern Taiwan. The three TR34/L98H isolates also displayed cross-resistance to azole fungicides, ie. tebuconazole and penconazole which have been authorized for use in Taiwan with widespread application. Phylogenetic analysis using microsatellite genotyping of 9 short tandem repeat loci revealed that A31 clustered with those from the Netherlands and Iran, while a44 and a51 clustered with wild-type strains in Taiwan but not with strains from other countries, suggesting the genetic diversity of TR34/L98H A. fumigatus isolates in Taiwan. The identification of TR34/L98H isolates in the clinical setting raises the concern that these isolates might have already existed in the environment in Taiwan and this report adds to the expanding list of regions where fungicide-driven route of resistance is found. Further systematic and periodic surveillance to determine the prevalence of azole resistance in clinical and environmental A. fumigatus isolates in Taiwan are warranted.


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19th Congress of the International Society for Human and Animal Mycology
    • ISHAM 19th (2015)