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隐球菌病实验室诊断与治疗的现状与进展
刘 淇1,2,鲁炳怀1,2
1.中日友好临床医学研究所,北京 100029;2.中日友好医院呼吸与危重症医学科临床微生物与感染实验室,北京 100029
摘要:
[摘要] 隐球菌病是全球重要的真菌感染性疾病之一,主要由新型隐球菌和格特隐球菌引起,尤其在人类免疫缺陷病毒(HIV)感染等免疫缺陷人群中危害显著。多位点序列分型是常用的隐球菌分型方法,新型隐球菌以ST5最为常见。诊断隐球菌病的实验室方法逐渐增多,传统方法如墨汁染色和真菌培养各有优劣势,分子生物学方法为快速诊断提供了新的选择。隐球菌的耐药机制复杂,主要与靶基因(如ERG11FCY2)突变、染色体倍性变化及应激通路激活等有关。在治疗上,两性霉素B联合5-氟胞嘧啶是治疗重症隐球菌病的首选方案,同时耐药性问题也推动了对新靶点(如毒力因子、应激调节蛋白)和药物[如糖基磷脂酰肌醇锚定蛋白壁转移蛋白1(Gwt1)抑制剂APX001、四唑类化合物VT-1598]的探索,免疫疗法和联合用药策略也展现出潜力。该文基于最新的研究进展,综述了隐球菌的分型方法、诊断学进展、常见的耐药机制以及治疗新方法,旨在为隐球菌病的诊断和治疗提供新的借鉴和启示。
关键词:  隐球菌  隐球菌病  耐药机制  诊断
DOI:10.3969/j.issn.1674-3806.2025.07.04
分类号:R 519.4
基金项目:国家科技重大专项课题(编号:2023ZD0506200,2023ZD0506203)
Current status and advances in laboratory diagnosis and treatment of cryptococcosis
LIU Qi1,2, LU Binghuai1,2
1.China-Japan Friendship Institute of Clinical Medicine, Beijing 100029, China; 2.Clinical Microbiology and Infection Laboratory, Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing 100029, China
Abstract:
[Abstract] Cryptococcosis is one of the significant global fungal infectious diseases, primarily caused by Cryptococcus neoformans and Cryptococcus gattii. It is particularly harmful to immunodeficient populations such as those infected with human immunodeficiency virus(HIV). Multilocus sequence typing(MLST) is a widely used method for typing of Cryptococcus, with C. neoformans ST5 being the most prevalent sequence type. Laboratory diagnostic methods for cryptococcosis are gradually increasing. The traditional methods for diagnosing cryptococcosis, such as India ink staining and fungal culture, have their own advantages and disadvantages. Molecular biological methods offer new options for the rapid diagnosis of cryptococcosis. The drug resistance mechanisms of Cryptococcus are complex, primarily involving target gene(such as ERG11 and FCY2) mutations, ploidy variation and activation of stress pathways. In the treatment of cryptococcosis, the combination of amphotericin B and 5-flucytosine is the first-line regimen for severe cases. Meanwhile, the problem of drug resistance has also driven the exploration of new targets(such as virulence factors and stress regulatory proteins) and drugs[such as glycosylphosphatidylinositol(GPI) wall transfer protein 1(Gwt1) inhibitor APX001 and tetrazole compound VT-1598]. Immunotherapy and combination therapy strategies have also shown promising potential. Based on the latest research progress, this paper reviews the typing methods, diagnostic advancements, common drug resistance mechanisms, and new treatment methods of Cryptococcus, aiming to provide new reference and enlightenment for the diagnosis and treatment of cryptococcosis.
Key words:  Cryptococcus  Cryptococcosis  Drug resistance mechanisms  Diagnosis