Epidemiology and Azole Resistance of Clinical Isolates of Aspergillus fumigatus from a Large Tertiary Hospital in Ningxia, China

Abstract

Yuting Kang,1,* Qiujie Li,2,* Yao Yao,3 Chao Xu,2 Zhuoran Qiu,2 Wei Jia,1,3 Gang Li,1,3 Pengtao Wang1 1Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 3Center of Medical Laboratory, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gang Li; Pengtao Wang, General Hospital of Ningxia Medical University, Technology Building 601, 804 Shengli Road, Yinchuan, People’s Republic of China, Tel [phone], Email [email protected]; [email protected]: The objective of this study was to determine the clinical distribution, in vitro antifungal susceptibility and underlying resistance mechanisms of Aspergillus fumigatus (A. fumigatus) isolates from the General Hospital of Ningxia Medical University between November 2021 and May 2023.Methods: Antifungal susceptibility testing was performed using the Sensititre YeastOne YO10, and isolates with high minimal inhibitory concentrations (MICs) were further confirmed using the standard broth microdilution assays established by the Clinical and Laboratory Standards Institute (CLSI) M38-third edition. Whole-Genome Resequencing and RT-qPCR in azole-resistant A. fumigatus strains were performed to investigate the underlying resistance mechanisms.Results: Overall, a total of 276 A. fumigatus isolates were identified from various clinical departments, showing an increasing trend in the number of isolates over the past 3 years. Two azole-resistant A. fumigatus strains (0.72%) were observed, one of which showed overexpression of cyp51A, cyp51B, cdr1B, MDR1/2, artR, srbA, erg24A, and erg4B, but no cyp51A mutation. However, the other strain harbored two alterations in the cyp51A sequences (L98H/S297T). Therefore, we first described two azole-resistant clinical A. fumigatus strains in Ningxia, China, and reported one azole-resistant strain that has the L98H/S297T mutations in the cyp51A gene without any tandem repeat (TR) sequences in the promoter region.Conclusions: This study emphasizes the importance of enhancing attention and surveillance of azole-resistant A. fumigatus, particularly those with non-TR point mutations of cyp51A or non-cyp51A mutations, in order to gain a better understanding of their prevalence and spread in the region.Keywords: Aspergillus fumigatus, azole resistance, cyp51A mutation, tandem repeat sequences

Keywords

• aspergillus fumigatus
• azole resistance
• cyp51a mutation
• tandem repeat sequences