i Azole resistance in Aspergillus fumigatus has emerged as a worldwide public health problem. We sought here to demonstrate the occurrence and characteristics of azole resistance in A. fumigatus from different parts of China. A total of 317 clinical and 144 environmental A. fumigatus isolates from 12 provinces were collected and subjected to screening for azole resistance. Antifungal susceptibility, cyp51A gene sequencing, and genotyping were carried out for all suspected azole-resistant isolates and a subset of azole-susceptible isolates. As a result, 8 (2.5%) clinical and 2 (1.4%) environmental A. fumigatus isolates were identified as azole resistant. Five azole-resistant strains exhibit the TR 34 /L98H mutation, whereas four carry the TR 34 /L98H/S297T/F495I mutation in the cyp51A gene. Genetic typing and phylogenetic analysis showed that there was a worldwide clonal expansion of the TR 34 / L98H isolates, while the TR 34 /L98H/S297T/F495I isolates from China harbored a distinct genetic background with resistant isolates from other countries. High polymorphisms existed in the cyp51A gene that produced amino acid changes among azolesusceptible A. fumigatus isolates, with N248K being the most common mutation. These data suggest that the wide distribution of azole-resistant A. fumigatus might be attributed to the environmental resistance mechanisms in China.

The use of azole fungicides in agriculture is believed to be one of the main reasons for the emergence of azole resistance in Though widely used in agriculture, imidazole fungicides have not been linked to resistance in This study showed that elevated MIC values of imidazole drugs were observed against isolates with TR/L98H/S297T/F495I mutation, but not among isolates with TR/L98H mutation. Short-tandem-repeat (STR) typing analysis of 580 isolates from 20 countries suggested that the majority of TR/L98H/S297T/F495I strains from China were genetically different from the predominant major clade comprising most of the azole-resistant strains and the strains with the same mutation from the Netherlands and Denmark. Alignments of sterol 14α-demethylase sequences suggested that F495I in was orthologous to F506I in and F489L in , which have been reported to be associated with imidazole resistance. antifungal susceptibility testing of different recombinants with mutations further confirmed the association of the F495I mutation with imidazole resistance. In conclusion, this study suggested that environmental use of imidazole fungicides might confer selection pressure for the emergence of azole resistance in.

Carriage of qacA/B, although it had a low prevalence, might be the main reason for declining susceptibility to chlorhexidine in MRSA from Chinese patients and is probably associated with spa-t037 and the presence of the mupA gene.