Epidemiology and Antifungal Susceptibility Profile of <i>Aspergillus</i> Species: Comparison between Environmental and Clinical Isolates from Patients with Hematologic Malignancies

Abstract

Global data on the epidemiology and susceptibility of <i>Aspergillus</i> are crucial in the management of invasive aspergillosis. Here, we aimed to determine the characteristics of clinical and environmental <i>Aspergillus</i> isolates, focusing mainly on hematologic malignancy patients. We prospectively collected all consecutive cases and clinical isolates of culture-positive proven/probable invasive aspergillosis patients from January 2016 to April 2018 and sampled the air inside and outside the hospital. Cryptic species-level identification of <i>Aspergillus</i>, antifungal susceptibilities, and <i>cyp51</i> gene sequencing were performed, and clinical data were analyzed. This study was conducted as part of the <u>Ca</u>tholic Hematology Hospital <u>F</u>ungi <u>E</u>pidemiology (CAFÉ) study. A total of 207 proven/probable invasive aspergillosis and 102 clinical and 129 environmental <i>Aspergillus</i> isolates were included in this analysis. The incidence of proven/probable invasive aspergillosis was 1.3 cases/1,000 patient-days during the study period. Cryptic <i>Aspergillus</i> species accounted for 33.8%, with no differences in proportions between the clinical and environmental isolates. Section <i>Nigri</i> presented a high proportion (70.5%) of cryptic species, mainly from <i>A. tubingensis</i> and <i>A. awamori</i>: the former being dominant in environmental samples, and the latter being more common in clinical isolates (<i>P</i> < 0.001). Of 91 <i>A. fumigatus</i> isolates, azole-resistant <i>A. fumigatus</i> was found in 5.3% of all <i>A. fumigatus</i> isolates. Three isolates presented the TR₃₄/L98H mutation of the <i>cyp51A</i> gene. Patients with invasive aspergillosis caused by azole-resistant <i>A. fumigatus</i> showed 100% all-cause mortality at 100 days. This study demonstrates the significant portion of cryptic <i>Aspergillus</i> species and clinical implications of azole resistance and underscores the comparison between clinical and environmental isolates.