Molecular identification, antifungal susceptibility, and resistance mechanisms of pathogenic yeasts from the China antifungal resistance surveillance trial (CARST-fungi) study

Qiqi Wang; Xuan Cai; Yun Li; Jianhong Zhao; Zhiyong Liu; Yan Jiang; Ling Meng; Yanming Li; Shiyang Pan; Xiaoman Ai; Fang Zhang; Ruoyu Li; Bo Zheng; Zhe Wan; Wei Liu

doi:10.3389/fmicb.2022.1006375

Molecular identification, antifungal susceptibility, and resistance mechanisms of pathogenic yeasts from the China antifungal resistance surveillance trial (CARST-fungi) study

Front Microbiol. 2022 Oct 6:13:1006375. doi: 10.3389/fmicb.2022.1006375. eCollection 2022.

Authors

Qiqi Wang¹, Xuan Cai², Yun Li³, Jianhong Zhao⁴, Zhiyong Liu⁵, Yan Jiang⁶, Ling Meng⁷, Yanming Li⁸, Shiyang Pan⁹, Xiaoman Ai¹⁰, Fang Zhang¹¹, Ruoyu Li¹, Bo Zheng³, Zhe Wan¹, Wei Liu¹

Affiliations

¹ Department of Dermatology and Venereology, Peking University First Hospital, National Clinical Research Center for Skin and Immune Diseases, Research Center for Medical Mycology, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Peking University, Beijing, China.
² Department of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.
³ Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, China.
⁴ Department of Clinical Laboratory Medicine, Second Hospital of Hebei Medical University, Shijiazhuang, China.
⁵ Department of Laboratory Medicine, Southwest Hospital, Army Medical University, Chongqing, China.
⁶ Center for Clinical Laboratories, Affiliated Hospital of Guizhou Medical University, Guiyang, China.
⁷ Lanzhou University Second Hospital, Lanzhou, China.
⁸ Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, China.
⁹ First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
¹⁰ Department of Medical Laboratory, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
¹¹ Medical Research and Laboratory Diagnostic Center, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.

Abstract

To have a comprehensive understanding of epidemiology and antifungal susceptibilities in pathogenic yeasts, the China Antifungal Resistance Surveillance Trial (CARST-fungi) study was conducted. All yeast isolates were identified by ribosomal DNA sequencing. Antifungal susceptibilities were performed using CLSI M27-A4 broth microdilution method. Sequence and expression level of resistant-related genes in resistant/non-wide-type (NWT) Candida isolates were analyzed. Totally 269 nonduplicate yeast isolates from 261 patients were collected. About half of the yeast isolates (127, 47.2%) were recovered from blood, followed by ascetic fluid (46, 17.1%). C. albicans remained the most prevalent (120, 44.6%), followed by C. parapsilosis complex (50, 18.6%), C. tropicalis (40, 14.9%), and C. glabrata (36, 13.4%). Fourteen (11.7%) C. albicans isolates and 1 (2.0%) C. parapsilosis isolate were resistant/NWT to triazoles. Only 42.5% (17/40) C. tropicalis were susceptible/WT to all the triazoles, with 19 (47.5%) isolates NWT to posaconazole and 8 (20%) cross-resistant to triazoles. Among C. glabrata, 20 (55.6%) and 8 (22.2%) isolates were resistant/NWT to voriconazole and posaconazole, respectively, and 4 (10.3%) isolates were cross-resistant to triazoles. Isavuconazole was the most active triazole against common Candida isolates. Except for 2 isolates of C. glabrata cross-resistant to echinocandins which were also NWT to POS and defined as multidrug-resistant, echinocandins exhibit good activity against common Candida species. All isolates were WT to AMB. For less common species, Rhodotorula mucilaginosa exhibited high MICs to echinocandins and FLC, and 1 isolate of Trichosporon asahii showed high MICs to all the antifungals except AMB. Among triazole-resistant Candida isolates, ERG11 mutations were detected in 10/14 C. albicans and 6/23 C. tropicalis, while 21/23 C. tropicalis showed MDR1 overexpression. Overexpression of CDR1, CDR2, and SNQ2 exhibited in 14, 13, and 8 of 25 triazole-resistant C. glabrata isolates, with 5 isolates harboring PDR1 mutations and 2 echinocandins-resistant isolates harboring S663P mutation in FKS2. Overall, the CARST-fungi study demonstrated that although C. albicans remain the most predominant species, non-C. albicans species accounted for a high proportion. Triazole-resistance is notable among C. tropicalis and C. glabrata. Multidrug-resistant isolates of C. glabrata and less common yeast have been emerging.

Keywords: Candida spp.; antifungal susceptibility; echinocandins; invasive fungal diseases; multidrug resistance; pathogenic yeasts; triazoles.