重症肝病合并侵袭性真菌感染诊治专家共识

中国研究型医院学会肝病专业委员会重症肝病学组; 中华医学会肝病学分会重型肝病与人工肝学组

doi:10.3969/j.issn.1001-5256.2022.02.011

重症肝病合并侵袭性真菌感染诊治专家共识

DOI: 10.3969/j.issn.1001-5256.2022.02.011

利益冲突声明：所有作者均声明不存在利益冲突。

胡瑾华，13910020608@163.com；韩涛，hantaomd@126.com

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出版历程
- 收稿日期: 2022-02-14
- 录用日期: 2022-02-16
- 出版日期: 2022-02-20

Consensus on diagnosis and treatment of invasive fungal infection in patients with severe liver disease

摘要

摘要: 重症肝病合并侵袭性真菌感染(IFI)预后差，临床表现常不典型，而抗真菌药物又多在肝脏代谢，毒副作用大，临床诊治困难。中国研究型医院学会肝病专业委员会和中华医学会肝病学分会组织相关专家，根据重症肝病患者的特点，形成专家共识，以供医务人员在制定重症肝病合并IFI诊治决策时参考。
- 肝疾病 /
- 侵袭性真菌感染 /
- 共识
Abstract: The prognosis of severe liver disease combined with invasive fungal infection (IFI) is poor, and the clinical manifestations are often atypical. Moreover, most of the antifungal drugs are metabolized in the liver, with severe toxicities and side effects, making clinical diagnosis and treatment difficult. The Professional Committee for Hepatology, the Chinese Research Hospital Association and the Hepatology Branch of China Medical Association organized relevant experts to formulate an expert consensus based on the characteristics of patients with severe liver disease combined with IFI, in order to provide reference for medical personnel in making decisions on the diagnosis and treatment.
- Liver Diseases /
- Invasive Fungal Infections /
- Consensus

HTML全文

表 1 推荐意见的证据等级和推荐强度

级别	说明
证据等级
高质量(A)	进一步研究也不可能改变该疗效评估结果的可信度
中等质量(B)	进一步研究很可能影响该疗效评估结果的可信度
低质量(C)	进一步研究极有可能影响该疗效评估结果的可信度
推荐等级
强推荐(1)	显示干预措施利大于弊或者弊大于利
弱推荐(2)	显示利弊不确定或无论质量高低的证据均显示利弊相当

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表 2 重症肝病常见侵袭性真菌的分类及特征

类别	菌属	菌种	形态特征	天然耐药抗生素
酵母样菌	念珠菌属	白念珠菌热带念珠菌近平滑念珠菌光滑念珠菌	假菌丝，菌丝成分短而弯曲，可与圆形、椭圆形或伸长的酵母细胞共存
		克柔念珠菌		氟康唑
		季也蒙念珠菌
		葡萄牙念珠菌
	隐球菌属	新型隐球菌	细胞大小不一，常呈球形，出芽常为单个并有压痕，常有明显的荚膜	卡泊芬净、米卡芬净
霉菌	曲霉属	烟曲霉	菌丝有隔，可有分枝
		黄曲霉		氟康唑
		黑曲霉		氟康唑
		土曲霉		氟康唑
	镰刀霉属	茄病镰刀霉尖孢镰刀霉	暗色多形态菌丝，可见串珠状被吞噬的细胞	氟康唑、伊曲康唑、卡泊芬净、米卡芬净
		毛霉属		氟康唑、伊曲康唑、伏立康唑、卡泊芬净、米卡芬净
	组织胞浆菌属	组织胞浆菌		氟康唑、卡泊芬净、米卡芬净

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表 3 用于确诊重症肝病合并IFI的真菌微生物学证据

真菌	显微镜检	培养	抗原检测
霉菌	正常无菌部位通过无菌技术针吸或活检样本的组织病理学、细胞病理学或直接显微镜检查发现菌丝或黑色酵母样形态，并伴有组织损伤证据	从正常无菌但临床或放射影像提示感染的部位(不包括肺泡灌洗液、鼻窦或乳突窦腔标本和尿液)通过无菌技术获得标本进行培养发现透明或有色霉菌；血培养霉菌阳性(不包括曲霉和除马尔尼菲青霉的其他青霉菌)，且临床符合致病菌感染的症状和体征	不适用
酵母样菌	从正常无菌部位(黏膜除外)针吸或活检样本的组织病理学、细胞病理学或直接显微镜检查发现酵母菌(隐球菌属可见芽生酵母，念珠菌属可见假菌丝或真菌丝)	从正常无菌但临床或放射影像提示感染的部位(包括24 h内放置的尿管)通过无菌技术获得的标本中培养出酵母菌；血培养发现酵母菌或酵母样真菌，且临床符合致病菌感染的症状和体征	脑脊液或血液中隐球菌荚膜多糖抗原检测阳性
肺孢子菌	组织、肺泡灌洗液、痰液涂片经六胺银或免疫荧光染色显微镜下检测到肺孢子菌	不适用	不适用
其他侵袭性真菌	从感染部位获得的样本经病理或直接显微镜检查检出特征性真菌	血流等感染部位的标本培养真菌阳性	不适用

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表 4 用于临床诊断重症肝病合并IFI的真菌微生物学证据

霉菌

任何从痰、支气管肺泡灌洗液、支气管刷取物或吸出标本、鼻窦吸取物涂片发现真菌成分或培养提示霉菌
曲霉菌
(1)血浆、血清、支气管肺泡灌洗液或脑脊液GM试验阳性；
(2)曲霉PCR检测阳性：①血浆、血清或全血连续2次以上PCR阳性；②支气管肺泡灌洗液2次以上重复PCR阳性；③血清、血浆或全血至少1次，且支气管肺泡灌洗液也存在至少1次曲霉PCR阳性
念珠菌
(1)血清G试验连续2次阳性且排除其他原因；
(2)对于非无菌标本，同一部位多次培养阳性或多个部位同时分离出同一种念珠菌
隐球菌
任何非无菌部位所获标本培养出隐球菌或经直接镜检/细胞学检查发现隐球菌
肺孢子菌
血清G试验连续2次阳性且排除其他原因；呼吸道标本实时荧光定量PCR检测出耶氏肺孢子菌DNA

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表 5 常见重症肝病合并IFI的治疗药物选择

真菌感染性疾病	一线治疗	挽救治疗	疗程	说明
侵袭性念珠菌病	卡泊芬净，Child-Pugh A级：负荷剂量70 mg/d×1 d，维持剂量50 mg/d；Child-Pugh B级：负荷剂量同上，维持剂量35 mg/d；Child-Pugh C级：参考B级患者米卡芬净，100~150 mg/d氟康唑，负荷剂量800 mg(12 mg/kg)/d×1 d，维持剂量400 mg(6 mg/kg)/d	L-AmB，3~5 mg·kg ^-1·d ^-1	首次血培养阴性后14 d	氟康唑可作为敏感菌株的序贯或降阶梯治疗
侵袭性曲霉病	伏立康唑，Child-Pugh A级或B级：负荷剂量6 mg/kg，1次/12 h×1 d，维持剂量2 mg/kg，1次/12 h。重症肝病患者建议行血药浓度监测调整剂量，维持血药谷浓度1~5 μg/mL。无条件者可采用负荷剂量200 mg，1次/12 h×1 d，维持剂量100 mg，1次/dL-AmB，用法同侵袭性念珠菌病艾沙康唑，第1、2天负荷剂量200 mg，1次/8 h，维持剂量100 mg，1次/d(可根据血药浓度监测结果调整剂量)	棘白菌素(如卡泊芬净、米卡芬净)，使用方法同侵袭性念珠菌病泊沙康唑，首次200 mg，1次/6 h；病情稳定后400 mg，口服，1次/12 h	通常治疗疗程12周，至少应用至临床和影像学改变恢复正常，曲霉相关微生物学检查阴性	对于单药治疗失败的危重患者，可采用联合用药方案
其他
肺孢子菌肺炎	SMZco：SMZ 18.75~25 mg/kg及TMP 3.75~5 mg/kg，1次/6 h	卡泊芬净，用法同侵袭性念珠菌病	3周
侵袭性毛霉菌病、组织胞浆菌病以及球孢子菌病	L-AmB，用法同侵袭性念珠菌病	泊沙康唑、艾沙康唑		球孢子菌病维持治疗可改用氟康唑

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