全面了解致病性酵母的流行病学和抗真菌敏感性,进行了中国抗真菌药物耐药性监测试验(CARST-真菌)研究。通过核糖体DNA测序鉴定所有酵母分离物。使用CLSIM27-A4肉汤微量稀释法进行抗真菌敏感性。分析了抗性/非广型(NWT)念珠菌分离株中抗性相关基因的序列和表达水平。共收集了261例患者的269种非复制酵母分离株。大约一半的酵母分离株(127,47.2%)从血液中回收,其次是腹水(46,17.1%)。白色念珠菌仍然是最普遍的(120,44.6%),其次是近平滑梭菌复合体(50,18.6%),C.热带(40,14.9%),和C.glabrata(36,13.4%)。14种(11.7%)白色念珠菌分离株和1种(2.0%)近扁平念珠菌分离株对三唑具有抗性/NWT。只有42.5%(17/40)的热带念珠菌对所有三唑类敏感。其中19例(47.5%)NWT对泊沙康唑和8例(20%)对三唑具有交叉抗性。在C.glabrata中,20(55.6%)和8(22.2%)株对伏立康唑和泊沙康唑耐药/NWT,分别,4株(10.3%)对三唑具有交叉抗性。伊沙武康唑是对常见念珠菌分离株活性最高的三唑。除了2株对棘白菌素具有交叉抗性的光滑梭菌分离株对POS也是NWT,并定义为多药耐药外,棘白菌类对常见念珠菌具有良好的活性。所有分离株均为WT至AMB。对于不太常见的物种,黏胶红酵母对棘白菌素和FLC表现出较高的MIC,和1个分离的阿沙希毛孢菌对除AMB以外的所有抗真菌药物均显示出较高的MIC。在对三唑耐药的念珠菌分离株中,在10/14白色念珠菌和6/23热带念珠菌中检测到ERG11突变,而热带21/23C.显示MDR1过表达。CDR1、CDR2和SNQ2的过表达在14、13和8的25种耐三唑的光滑梭菌分离株中,在FKS2中,有5株具有PDR1突变的分离株和2株具有棘白菌素抗性的分离株具有S663P突变。总的来说,CARST-真菌研究表明,尽管白色念珠菌仍然是最主要的物种,非C.白色念珠菌种类所占比例较高。热带梭菌和光滑梭菌对三唑的抗性显著。已经出现了光滑梭菌和不太常见的酵母的多药抗性分离株。
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.