AUTHOR=Wang Yuerong , Zhang Luwen , Zhou Longrong , Zhang Min , Xu Yuanhong 

TITLE=Epidemiology, Drug Susceptibility, and Clinical Risk Factors in Patients With Invasive Aspergillosis

JOURNAL=Frontiers in Public Health

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2022.835092

DOI=10.3389/fpubh.2022.835092

ISSN=2296-2565

ABSTRACT=<sec><title>Background</title><p>This study aimed to investigate the <italic>Aspergillus</italic> species distribution, antifungal sensitivities, clinical characteristics, and risk factors of patients with invasive aspergillosis (IA) in a tertiary teaching hospital in Anhui Province.</p></sec><sec><title>Methods</title><p>In the present study, 156 <italic>Aspergillus</italic> isolates were collected from patients admitted to a 2,800-bed comprehensive hospital between January 2019 and April 2021. The epidemiology of <italic>Aspergillus</italic> species was well-examined, and its antifungal susceptibility was specifically measured by the microbroth dilution method. The risk factors of patients with IA were documented and analyzed intensively. In addition, gene sequencing was employed to determine gene mutations of cytochrome P450 14-α sterol demethylase<italic>-Aspergillus</italic> (<italic>cyp51A</italic>) associated with azole resistance among <italic>Aspergillus fumigatus</italic>.</p></sec><sec><title>Results</title><p>The <italic>Aspergillus</italic> species distribution was dominated by <italic>A. fumigatus</italic> (56.41%), <italic>Aspergillus flavus</italic> (20.51%), and <italic>Aspergillus niger</italic> (15.38%) locally. In particular, all <italic>Aspergillus</italic> species showed very low minimum inhibitory concentrations (MICs, ≤ 0.5 μg/ml) for azoles and echinocandins, slightly high MICs (1.66–2.91 μg/ml) for amphotericin B, and exceptionally high MICs (&gt;64 μg/ml) for flucytosine. Azole-resistant rate of <italic>Aspergillus</italic> species in this local region reached up to 5.79%. Correlation analyses of multiple antifungals indicate a significant MIC relevance between isavuconazole and voriconazole (Pearson correlation coefficient was 0.81, <italic>P</italic> &lt; 0.0001). The clinical risk factors for patients with IA were found primarily to be pulmonary diseases (<italic>P</italic> = 0.007) and patients' age (<italic>P</italic> &lt; 0.001). Notably, three mutant loci (TR46/Y121F/T289A) of the <italic>cyp51A</italic> gene were identified in azole-resistant <italic>A. fumigatus</italic>.</p></sec><sec><title>Conclusions</title><p>The <italic>Aspergillus</italic> species emerged increasingly, of which <italic>A. fumigatus</italic> and <italic>A. flavus</italic> remained the main pathogens for invasive <italic>Aspergillus</italic> infections in the local region. The vast majority of <italic>Aspergillus</italic> species exhibited good susceptibility to all the antifungals, except flucytosine. The local occurrence of azole-resistant <italic>Aspergillus</italic> species grew gradually and needed monitoring in time. Pulmonary diseases and age were likely considered as highly associated risk factors for IA. To our knowledge, the clinically isolated azole-resistant <italic>A. fumigatus</italic> with TR46/Y121F/T289A mutations identified here were rarely reported in the area of China.</p></sec>