肺隐球菌病临床诊疗进展

doi:10.19982/j.issn.1000-6621.20240150

摘要/Abstract

摘要：

肺隐球菌病是呼吸道吸入隐球菌引发的侵袭性真菌病,既可见于免疫功能低下者,也可见于免疫功能正常人群。隐球菌病最初影响患者肺部,可出现全身播散,如脑、血液等播散。其中,隐球菌脑膜炎是导致患者死亡的主要并发症。近年来,肺隐球菌病的发病率呈增长趋势,而其临床表现缺乏特异性,易出现误诊和漏诊。笔者对肺隐球菌病的诊疗进展进行综述,旨在加强临床医生对该疾病的认识及重视程度,以提高该疾病的早诊早治率,改善患者预后。

关键词: 隐球菌病, 肺疾病, 诊断, 治疗学

Abstract:

Pulmonary cryptococcosis is an invasive fungal disease caused by respiratory inhalation of cryptococci, which can happen in both immunocompromised and immunocompetent people. Cryptococcosis initially affects the patient’s lungs and can spread throughout the body, such as in the brain and blood. Among them, cryptococcal meningitis is a major complication leading to patient death. In recent years, the incidence of pulmonary cryptococcosis has shown an increasing trend, while its clinical manifestations are lack of specificity and are prone to misdiagnosis and underdiagnosis. The author reviews the progress of diagnosis and treatment of pulmonary cryptococcosis, aiming to improve clinicians’ awareness and attention towards this disease, so as to increase the rate of early diagnosis and treatment of this disease and improve the prognosis of patients.

Key words: Cryptococcosis, Lung diseases, Diagnosis, Therapeutics

中图分类号:

R563

韩文雅, 周阳煜, 王梅芳, 薛新颖. 肺隐球菌病临床诊疗进展[J]. 中国防痨杂志, 2024, 46(7): 830-838. doi: 10.19982/j.issn.1000-6621.20240150

Han Wenya, Zhou Yangyu, Wang Meifang, Xue Xinying. Progress in clinical diagnosis and treatment of pulmonary cryptococcosis[J]. Chinese Journal of Antituberculosis, 2024, 46(7): 830-838. doi: 10.19982/j.issn.1000-6621.20240150

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类型	既往变种名称	血清型	基因型	新命名
C.neoformans	C.neoformans var.grubii	A	VNⅠ、VNBⅠ、VNⅡ、VNBⅡ、VNⅢ	C.neoformans
	C.neneoformans	D	VNⅣ	C.deneoformans
	C.neoformans hybrid	AD	VNⅢ	C.neoformans×C. deneoformans hybrid
C.gattii	/	B或C	VGⅠ	C.gattii
			VGⅡ	C.deuterogattii
			VGⅢ	C.bacillisporus
			VGⅣ	C.tetragattii
			VGⅤ	未知
			VGⅥ	C.decagattii

患者类型	既往推荐方案	目前指南推荐方案^[43]
无免疫抑制的肺隐球菌病患者
无症状	密切观察或氟康唑200~400mg/d,6个月	氟康唑400mg/d,6~12个月
轻中度症状	氟康唑400mg/d,6~12个月	氟康唑400mg/d,6~12个月
重度症状	诱导治疗:两性霉素B 0.5~0.7mg·kg^-1·d^-1,联合5-氟胞嘧啶100mg·kg^-1·d^-1,疗程≥4周;巩固治疗:氟康唑400mg/d,疗程8周;维持治疗:氟康唑200mg/d,6~12个月	诱导治疗:两性霉素B脂质体3~4mg·kg^-1·d^-1,联合5-氟胞嘧啶100mg·kg^-1·d^-1,疗程≥2周;巩固治疗:氟康唑400~800mg/d,疗程8周;维持治疗:氟康唑200mg/d,12个月
免疫抑制的肺隐球菌病患者
无症状、轻中度症状	氟康唑400mg/d,6~12个月	氟康唑400mg/d,6~12个月
重度症状
HIV感染者	诱导治疗:两性霉素B 0.5~0.7mg·kg^-1·d^-1,联合5-氟胞嘧啶100mg·kg^-1·d^-1,疗程≥2周;巩固治疗:氟康唑400mg/d,≥8周;维持治疗:氟康唑200mg/d,疗程≥1年或直至患者免疫功能恢复	诱导治疗:两性霉素B脂质体3~4mg·kg^-1·d^-1,联合5-氟胞嘧啶100mg·kg^-1·d^-1,疗程≥2周;巩固治疗:氟康唑400~800mg/d,疗程8周;维持治疗:氟康唑200mg/d,疗程≥12个月或直至患者免疫功能恢复
器官移植患者	诱导治疗:两性霉素B脂质体3~4mg·kg^-1·d^-1,联合5-氟胞嘧啶100mg·kg^-1·d^-1,疗程≥2周;巩固治疗:氟康唑400mg/d,≥8周;维持治疗:氟康唑200~400mg/d,疗程6~12个月	同HIV感染者治疗方案
其他患者^a	诱导治疗:两性霉素B 0.5~1.0mg·kg^-1·d^-1,联合5-氟胞嘧啶100mg·kg^-1·d^-1,疗程≥4周;巩固治疗:氟康唑400mg/d,8周;维持治疗:氟康唑200mg/d,6~12个月	同器官移植患者治疗方案

化合物	作用机制	应用阶段
唑类(如氟康唑)	抑制麦角甾醇生物合成酶Erg11,破坏细胞膜完整性	临床应用
嘧啶类似物(如氟胞嘧啶)	导致RNA错误编码和抑制DNA合成的抗代谢物	临床应用
多烯类(如两性霉素B)	与麦角甾醇结合,破坏细胞膜完整性	临床应用
舍曲林	血清素再摄取抑制剂	临床试验阶段
他莫昔芬	选择性雌激素受体调节剂	临床试验阶段
VT-1598	抑制麦角甾醇生物合成酶Erg11,破坏细胞膜完整性	临床试验阶段
APX001	抑制糖磷脂酰肌醇(GPI)锚定生物合成酶Gwt1	临床试验阶段
APX879	真菌选择性钙调磷酸酶抑制剂	基础研究
苯硫脲	抑制晚期高尔基分泌途径,阻碍细胞壁完整性	基础研究
氯法齐明	靶向真菌膜	基础研究
伊博霉素	靶向真菌膜和多泡体(MVB)功能	基础研究
单克隆抗体18B7	与荚膜成分葡萄糖醛酸甘露聚糖结合	基础研究
间苯二甲酸氨基吡唑	真菌选择性热休克蛋白(HSP)90抑制剂	基础研究
肼[如N'-(3-溴-4-羟基苄基)-2-甲基苯并肼,即BHBM]	抑制鞘脂葡萄糖神经酰胺的合成	基础研究