2017—2021年中国华东地区临床分离侵袭性感染热带念珠菌耐药状况分析

Antifungal susceptibility of clinically isolated invasive Candida tropicalis in East China from 2017 to 2021

目的探讨我国华东地区2017—2021年临床分离侵袭性感染热带念珠菌的标本来源分布及耐药特征。方法采用回顾性分析。华东地区侵袭性真菌感染协作组(East China Invasive Fungal Infection Group,ECIFIG)收集2017年1月至2021年12月间我国华东地区32家医院临床分离的热带念珠菌,由上海市东方医院南院检验科真菌实验室作为中心实验室,以质谱法复核菌株鉴定结果,采用ThermoFisher CMC1JHY比色微量稀释法检测菌株对氟康唑、伏立康唑、伊曲康唑、泊沙康唑、艾沙康唑、阿尼芬净、卡泊芬净、米卡芬净和5-氟胞嘧啶的最低抑菌浓度(minimum inhibitory concentrations,MIC),微量肉汤稀释法检测菌株对两性霉素B的MIC,按美国临床和实验室标准协会(Clinical and Laboratory Standards Institute,CLSI)M27M44s-Ed3和M57s-Ed4判定结果。采用Kruskal-Wallis 检验法和配对t检验进行数据分析。结果共收集到热带念珠菌305株,主要标本来源为血38.0%(116/305)、腹水11.5%(35/305)、导管8.9%(27/305)和引流液8.9%(27/305)。其对氟康唑耐药率为32.5%,对伏立康唑耐药率为28.5%,对氟康唑和伏立康唑交叉耐药率为28.5%;伊曲康唑和泊沙康唑野生型占比分别为79.3%和29.2%。氟康唑与伏立康唑耐药率、MIC50、MIC90、伊曲康唑和泊沙康唑野生型占比等五年间无显著变化。95.0%以上菌株对棘白菌素类药物敏感,但发现1株棘白菌素耐药的多重耐药热带念珠菌。唑类药物中,伏立康唑、伊曲康唑、泊沙康唑和艾沙康唑GM MIC相似,氟康唑GM MIC显著高于伊曲康唑(t=9.95,P<0.05)、泊沙康唑(t=9.99,P<0.05)和伏立康唑(t=10.01,P<0.05),而棘白菌素类药物中,阿尼芬净的GM MIC与卡泊芬净相当(t=1.17,P>0.05),均显著高于米卡芬净(t=11.56,P<0.05,t=4.15,P<0.05)。结论 2017—2021年华东地区临床分离热带念珠菌对棘白菌素类药物较为敏感,对氟康唑和伏立康唑持续呈高耐药水平,应加强对热带念珠菌的耐药性监测。

Objective To explore the epidemiological characteristics of sample distribution and antifungal susceptibilities of clinically invasive C.tropicalis isolates from 2017 to 2021 in East China.Methods Using a retrospective analysis,the East China Invasive Fungal Infection Group(ECIFIG)collected C.tropicalis clinically isolated from 32 hospitals in East China between January 2017 and December 2021.The identification results of the strains were reviewed using mass spectrometry by the central laboratory of the Shanghai East Hospital.The minimum inhibitory concentrations(MICs)of the strains against fluconazole(FLU),voriconazole(VOR),itraconazole(ITR),Posaconazole(POS),isavuconazole(ISA),anidulafungin(ANI),caspofungin(CAS),micafungin(MICA)and 5-fluorocytosine(FCT)were tested by the ThermoFisher CMC1JHY colorimetric microdilution method.The MIC of amphotericin B(AMB)was tested by the broth microdilution method.The MIC results were analyzed based on the clinical breakpoints and epidemiological cutoff values(ECV)published by the Clinical and Laboratory Standards Institute(CLSI)M27 Ed3 and M57 Ed4 documents.Data analysis was conducted using the Kruskal-Wallis test and paired t-test.Results In total,305 C.tropicalis isolates were collected.There were 38.0%(116/305)strains isolated from blood,11.5%(35/305)ascites,8.9%(27/305)catheter and 8.9%(27/305)drainage fluid.The resistance rate of C.tropicalis to FLU was 32.5%,to VOR was 28.5%,and the cross-resistance rate to FLU and VOR was 28.5%.The wild-type proportions for ITR and POS were 79.3%and 29.2%respectively.There was no significant difference in resistance rates,MIC50,and MIC90 of FLU and VOR,or in the wild-type rates of ITR and POS over five years.More than 95.0%of the isolates were susceptible to echinocandins.However,one strain was identified as being multi-drug resistant.In azole antifungals,voriconazole,itraconazole,posaconazole,and isavuconazole have similar GM MIC values.The GM MIC of fluconazole is significantly higher than that of itraconazole(t=9.95,P<0.05),posaconazole(t=9.99,P<0.05),and voriconazole(t=10.01,P<0.05),Meanwhile,among echinocandins,the GM MIC of ANI was comparable to that of CAS(t=1.17,P>0.05),both of which were significantly higher than MICA(t=11.56,P<0.05;t=4.15,P<0.05).Conclusion The clinical isolates of C.tropicalis in East China from 2017 to 2021 were relatively susceptible to echinocandins.However,there was consistently high resistance to fluconazole and voriconazole.More intensive efforts should be made on the monitoring of drug resistance in C.tropicalis.