中国多中心侵袭性感染毛孢子菌的抗真菌药物敏感性  

Multicenter study of antifungal susceptibility of Trichosporon species causing invasive infection in China

作　　者：于淑颖 张丽 徐英春 郭莉娜 YU Shuying;ZHANG Li;XU Yingchun;GUO Lina(Department,State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medical College Hospital,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100730,China;Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases,Beijing 100730,China)

机构地区：[1]中国医学科学院北京协和医院检验科,疑难重症及罕见病国家重点实验室,北京100730 [2]侵袭性真菌病机制研究与精准诊断北京市重点实验室,北京100730

出　　处：《中国真菌学杂志》2024年第3期250-256,共7页Chinese Journal of Mycology

基　　金：北京市自然科学基金青年项目(7244381);国家重点研发计划“基于组学数据的重要病原微生物耐药监控和预警平台建设”(2021YFC2302005)。

摘　　要：目的本研究旨在调查中国多中心侵袭性感染毛孢子菌的抗真菌药物敏感性分布特征。方法选取2009年8月—2016年7月CHIF-NET监测网43个监测中心收集的133株侵袭性感染毛孢子菌。利用基因测序分析实现菌种的准确鉴定和基因分型,按照美国临床和实验室标准协会(CLSI)推荐的微量肉汤稀释法检测菌株的体外抗真菌药物敏感性。结果中国多中心侵袭性毛孢子菌感染中,共分离到10个菌种,阿萨希毛孢子菌是主要的致病菌(108/133株),血液是最常见的标本类型(36.8%)。利用IGS1序列,将108株阿萨希毛孢子菌分为5个型别,基因型1型(41.7%)、4型(31.5%)和3型(23.1%)是我国主要的基因型。体外药物敏感性结果显示,阿萨希毛孢子菌对两性霉素B的MIC值的总体分布高于非阿萨希毛孢子菌,GM值分别是1.36μg/mL和0.7μg/mL。47.2%的阿萨希毛孢子菌(51/108株)对两性霉素B的MIC值≥2μg/mL,而全部非阿萨希毛孢子菌(25株)对两性霉素B的MIC值小于1μg/mL。25%的阿萨希毛孢子菌(27/108株)、2株T.dohaense、1株星形毛孢子菌、1株黏质毛孢子菌和1株T.faecale对氟康唑呈现较高的MIC值(≥8μg/mL)。伏立康唑对毛孢子菌呈现出最有效的体外抗真菌活性,GM值为0.09μg/mL。我国阿萨希毛孢子菌对氟康唑、伏立康唑、伊曲康唑和泊沙康唑的ECV值分别采用16μg/mL、0.25μg/mL、1μg/mL和1μg/mL,而对两性霉素B和5-氟胞嘧啶的ECV值均采用4μg/mL。结论本研究系统调查了抗真菌药物敏感性分布情况,并试验性建立了我国阿萨希毛孢子菌的流行病学折点。Objective We aimed to investigate the antifungal susceptibility distribution of invasive Trichosporon infections in China.Methods A total of 133 non-duplicated Trichosporon isolates were collected from 43 medical centers which participate the CHIF-NET program during 7-year period,from August,2009 to July,2016.In vitro antifungal susceptibilities were performed using the Clinical and Laboratory Standards Institute(CLSI)broth microdilution method.Results A total of 10 species were identified in the multicenter invasive Trichosporon infections in China.T.asahii remains the leading pathogen(108/133 isolates),and blood is the most common type of specimen(36.8%).By IGS sequencing,five kinds of genotype were identified in T.asahii.Genotype 1(41.7%),genotype 4(31.5%)and genotype 3(23.1%)are the main genotypes in China.The overall distribution of MIC values of T.asahii to amphotericin B was higher than that of non-asahii Trichosporon isolates,with GM values of 1.36μg/mL and 0.7μg/mL,respectively.47.2%of T.asahii(51/108 isolates)have MIC values≥2μg/mL against amphotericin B,while non-asahii Trichosporon isolates(25 isolates)have MIC values<1μg/mL.High fluconazole MICs(≥8μg/mL)were observed for 25%of T.asahii(27/108 isolates),2 isolates of T.dohaense and each one isolate of T.asteroides,T.mucoides and T.faecale.Voriconazole was the most potent antifungal agent in vitro,with a GM of 0.09μg/mL.The tentative ECV values for fluconazole,voriconazole,itraconazole and posaconazole were 16μg/mL,0.25μg/mL,1μg/mL and 1μg/mL,respectively.While the ECV values for amphotericin B and 5-flucytosine were 4μg/mL.Conclusions The antifungal susceptibility distribution of invasive Trichosporon infections were investigated in China.Then we established the tentative ECV values for T.asahii accordingly.

关 键 词：毛孢子菌 药物敏感性 分子分型 流行病学折点 

分 类 号：R519.9[医药卫生—内科学]