AUTHOR=Yang Xinyu , Chen Wei , Liang Tianyu , Tan JingWen , Liu Weixia , Sun Yi , Wang Qian , Xu Hui , Li Lijuan , Zhou Yabin , Wang Qiqi , Wan Zhe , Song Yinggai , Li Ruoyu , Liu Wei 

TITLE=A 20-Year Antifungal Susceptibility Surveillance (From 1999 to 2019) for Aspergillus spp. and Proposed Epidemiological Cutoff Values for Aspergillus fumigatus and Aspergillus flavus: A Study in a Tertiary Hospital in China

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.680884

DOI=10.3389/fmicb.2021.680884

ISSN=1664-302X

ABSTRACT=<p>The emergence of resistant <italic>Aspergillus</italic> spp. is increasing worldwide. Long-term susceptibility surveillance for clinically isolated <italic>Aspergillus</italic> spp. strains is warranted for understanding the dynamic change in susceptibility and monitoring the emergence of resistance. Additionally, neither clinical breakpoints (CBPs) nor epidemiological cutoff values (ECVs) for <italic>Aspergillus</italic> spp. in China have been established. In this study, we performed a 20-year antifungal susceptibility surveillance for 706 isolates of <italic>Aspergillus</italic> spp. in a clinical laboratory at Peking University First Hospital from 1999 to 2019; and <italic>in vitro</italic> antifungal susceptibility to triazoles, caspofungin, and amphotericin B was determined by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. It was observed that <italic>Aspergillus fumigatus</italic> was the most common species, followed by <italic>Aspergillus flavus</italic> and <italic>Aspergillus terreus</italic>. Forty isolates (5.7%), including <italic>A. fumigatus</italic>, <italic>A. flavus</italic>, <italic>A. terreus</italic>, <italic>Aspergillus niger</italic>, and <italic>Aspergillus nidulans</italic>, were classified as non-wild type (non-WT). Importantly, multidrug resistance was observed among <italic>A. flavus</italic>, <italic>A. terreus</italic>, and <italic>A. niger</italic> isolates. <italic>Cyp51A</italic> mutations were characterized for 19 non-WT <italic>A. fumigatus</italic> isolates, and TR<sub>34</sub>/L98H/S297T/F495I was the most prevalent mutation during the 20-year surveillance period. The overall resistance trend of <italic>A. fumigatus</italic> increased over 20 years in China. Furthermore, based on ECV establishment principles, proposed ECVs for <italic>A. fumigatus</italic> and <italic>A. flavus</italic> were established using gathered minimum inhibitory concentration (MIC)/minimum effective concentration (MEC) data. Consequently, all the proposed ECVs were identical to the CLSI ECVs, with the exception of itraconazole against <italic>A. flavus</italic>, resulting in a decrease in the non-WT rate from 6.0 to 0.6%.</p>