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器官移植受者侵袭性真菌病临床诊疗技术规范(2019版)

中华医学会器官移植学分会

中华医学会器官移植学分会. 器官移植受者侵袭性真菌病临床诊疗技术规范(2019版)[J]. 器官移植, 2019, 10(3): 227-236. doi: 10.3969/j.issn.1674-7445.2019.03.002
引用本文: 中华医学会器官移植学分会. 器官移植受者侵袭性真菌病临床诊疗技术规范(2019版)[J]. 器官移植, 2019, 10(3): 227-236. doi: 10.3969/j.issn.1674-7445.2019.03.002
Branch of Organ Transplantation of Chinese Medical Association. Technical specifcation for clinical diagnosis and treatment for invasive fungal disease in organ transplant recipients (2019 edition)[J]. ORGAN TRANSPLANTATION, 2019, 10(3): 227-236. doi: 10.3969/j.issn.1674-7445.2019.03.002
Citation: Branch of Organ Transplantation of Chinese Medical Association. Technical specifcation for clinical diagnosis and treatment for invasive fungal disease in organ transplant recipients (2019 edition)[J]. ORGAN TRANSPLANTATION, 2019, 10(3): 227-236. doi: 10.3969/j.issn.1674-7445.2019.03.002

器官移植受者侵袭性真菌病临床诊疗技术规范(2019版)

doi: 10.3969/j.issn.1674-7445.2019.03.002
基金项目: 

国家自然科学基金 81570680

国家自然科学基金 81571555

详细信息
    通讯作者:

    石炳毅,Email:shibingyi666@126.com

  • 中图分类号: R617, R519

Technical specifcation for clinical diagnosis and treatment for invasive fungal disease in organ transplant recipients (2019 edition)

  • 摘要: 为了进一步规范实体器官移植(SOT)受者侵袭性真菌病(IFD)的诊断和治疗,中华医学会器官移植学分会结合近期国内外临床证据,从SOT受者IFD的流行病学特点、诊断、预防、治疗等方面,在2017年版《器官移植受者侵袭性真菌病临床诊疗指南》的基础上制定本规范,以期为器官移植和相关学科的同道提供帮助。

     

  • 图  1  SOT受者肺曲霉病及支气管-肺曲霉病高分辨率CT的不同表现

    A图为肺移植术后患者,CT显示片状空腔实变伴有小结节(箭头所示);B图为心脏移植术后患者,支气管-肺曲霉病,轴向CT显示细支气管周围结节(箭头所示),与支气管-肺曲霉病表现一致,通过气管镜诊断为曲霉感染

    Figure  1.  Different manifestations of high-resolution CT in SOT recipients with pulmonary aspergillosis and broncho-pulmonary aspergillosis

    图  2  肾移植受者术后曲霉感染的影像学演变过程

    A图示远端支气管实变和结节;B图示小叶中心结节伴有晕轮;C图示数日至数周的治疗后演变成空腔

    Figure  2.  Imaging evolution of aspergillus infection in recipients after renal transplantation

    图  3  肺假丝酵母菌病的影像学表现

    主要表现为双肺多发结节、斑片状或融合性实变区、磨玻璃样渗出影及光晕征

    Figure  3.  Imaging performance of pulmonary candidiasis

    图  4  肾移植术后播散性隐球菌病的影像学表现

    A图示肺隐球菌病在CT表现为肺部结节影;B图示脑隐球菌病肉芽肿性病变的头颅MRI表现;C图示脑隐球菌病囊肿样改变的头颅MRI表现

    Figure  4.  Imaging findings of disseminated cryptococcosis after renal transplantation

    表  1  常见IFD的病原菌、发生率及患者病死率

    Table  1.   Pathogenic fungus, incidence and fatality rate of patients with common IFD

    病原菌 发病率 常见菌群 起病时间 好发对象 临床表现 病死率
    假丝酵母菌 侵袭性假丝酵母菌病全球发病率2%~4%。除肺移植外,侵袭性假丝酵母菌病占IFD的53%~59% 白假丝酵母菌、光滑假丝酵母菌、近平滑假丝酵母菌、热带假丝酵母菌、克柔假丝酵母菌 好发于移植后1个月内 在腹腔SOT中更常见,而少或罕见于心、肺移植 假丝酵母菌血症 移植后1年内侵袭性假丝酵母菌病总的病死率达34%
    曲霉 侵袭性曲霉病的发病率为0.1%~3.5%。除肺移植外,侵袭性曲霉病占18%~30%(肺移植后感染比例可达44%~63%) 常见烟曲霉感染,其次为黄曲霉、黑曲霉和土曲霉 一般在移植2~3个月后发病,中位发病时间为移植后6个月 最常见于肺移植 临床一般表现为急性侵袭性肺部感染 病死率高达67%~82%
    隐球菌 欧美国家发生侵袭性隐球菌病的比例是0~1.5%。除肺移植外,侵袭性隐球菌病约占8%   典型的晚发型感染,一般起病于移植后16~21个月 肾脏和心脏移植 一半以上受者表现为播散性疾病,累及中枢神经系统,33%会出现真菌血症 病死率为14%~27%
    下载: 导出CSV

    表  2  不同SOT受者人群发生IFD的危险因素

    Table  2.   Risk factors of IFD in different SOT recipients

    移植器官 发生IFD的危险因素
    假丝酵母菌 曲霉 接合菌
    早期 晚期(移植后>4个月)
    移植物功能丧失和血液透析;移植后血液透析;长时间大剂量使用糖皮质激素;巨细胞病毒感染;过度免疫抑制 巨细胞病毒感染;过度免疫抑制
    手术时间延长或重复操作;再次移植;假丝酵母菌定植;胆总管空肠吻合术;术中大量输血 再次移植;肾衰竭(尤其是移植后血液透析);暴发性肝衰竭;手术复杂或再次手术;使用单抗药物 移植后第3个月内泼尼松使用量累计 > 6 g;移植后肾衰竭;移植后血液透析;白细胞减少(< 0.5×109/L);移植物慢性功能丧失 肾衰竭;排斥反应和过度免疫抑制;糖皮质激素;控制不佳的糖尿病;持续中性粒细胞减少;使用铁螯合剂如去铁胺;镰刀菌病;巨噬细胞功能减退
    长时间使用广谱抗生素;中心静脉导管;血液透析 支气管吻合口缺血或支架置换;急性排斥反应;单肺移植;移植前或移植后1年内曲霉定植 移植物慢性功能丧失
    长时间使用广谱抗生素;中心静脉导管;血液透析 呼吸道曲霉定植;再次手术;移植后血液透析;低丙种球蛋白血症(IgG < 4 g/L) 再入重症监护室;肾移植;急性排斥反应 > 2次
    胰腺 空肠内引流;静脉血栓;输血后胰腺炎
    小肠 排斥反应或移植物功能丧失;吻合口破裂;多器官联合移植
    下载: 导出CSV

    表  3  临床诊断IFD的依据

    Table  3.   Clinical diagnosis basis of IFD

    项目 诊断依据
    宿主因素 (1)近期发生中性粒细胞缺乏(中性粒细胞计数<0.5×109/L)并持续10 d以上
    (2)接受异基因造血干细胞移植
    (3)应用糖皮质激素超过3周[0.3 mg/(kg·d)以上,变应性支气管肺曲霉病除外]
    (4)90 d内应用过抗T淋巴细胞制剂(如肿瘤坏死因子-α,多克隆抗淋巴细胞免疫球蛋白、阿仑单抗等)或核苷类似物
    (5)IFD病史
    (6)受者同时患有艾滋病或遗传性免疫缺陷(如慢性肉芽肿或联合免疫缺陷病)
    临床标准 (1)肺真菌病。CT检查至少存在以下三项之一:①致密、边界清楚的病变,伴或不伴晕征;②空气新月征;③空洞
    (2)气道真菌病。支气管镜检发现以下表现:气管和支气管溃疡、结节、伪膜、斑块或结痂
    (3)鼻窦真菌病。至少符合以下一项:①局部出现急性疼痛(包括放射至眼部的疼痛);②鼻部溃疡伴黑痂;③从鼻窦侵蚀骨质,包括扩散至颅内
    (4)中枢神经系统真菌病。至少符合以下一项:①影像学检查提示局灶性病变;②MRI或CT检查提示脑膜强化
    (5)播散性假丝酵母菌病。此前2周内出现假丝酵母菌血症,并伴有以下至少一项:①肝或脾牛眼征;②眼科检查提示进展性视网膜渗出
    微生物标准 (1)直接检查(细胞学、直接镜检或培养):①在痰、支气管肺泡灌洗液、支气管刷取物、窦吸取物中发现至少以下一项提示曲霉感染,即发现真菌成分显示为曲霉或培养提示曲霉;②痰或支气管肺泡灌洗液经培养新型隐球菌阳性或经直接镜检、细胞学检查发现隐球菌
    (2)间接检查(检测抗原或细胞壁成分):①曲霉,血浆、血清、支气管肺泡灌洗液或脑脊液检测半乳甘露聚糖抗原阳性;②侵袭性真菌
    (3)血浆、血清、支气管肺泡灌洗液检测隐球菌荚膜多糖抗原阳性
    下载: 导出CSV

    表  4  SOT受者靶向预防真菌感染用药

    Table  4.   Targeted use of drug to prevent fungal infection in SOT recipients

    移植器官 靶向人群 抗真菌药选择 疗程
    肾脏 不需要
    肝脏 高危人群
    (1)主要因素:①再次行移植手术、暴发性肝衰竭、MELD≥30分;②肾衰竭,需要替代治疗
    (2)次要因素:①MELD 20~30分、劈离式、活体供者、Roux-en-Y胆总管空肠吻合术;②输血过多(血细胞组分制品≥40 U);③肾衰竭,不需要替代治疗(肌酐清除率 < 50 mL/min);④早期再次介入治疗、假丝酵母菌多点定植或感染
    存在1个主要或2个次要因素:
    (1)米卡芬净
    (2)卡泊芬净
    (3)两性霉素B脂质体
    2~4周或至危险因素去除
    胰腺 所有移植受者 氟康唑 1~2周
    小肠 所有移植受者高危因素
    (1)急性排斥反应和初始移植物功能低下
    (2)血液透析
    (3)移植后再行剖腹手术、吻合口异常
    氟康唑存在高危因素者:
    (1)两性霉素B脂质体
    (2)卡泊芬净
    (3)米卡芬净
    3~4周或至吻合口愈合和排斥反应消失存在高危因素者:
    (1)疗程取决于危险因素是否去除
    (2)至吻合口愈合和排斥反应消失
    肺或心肺 推荐所有移植受者预防或指导性预防用药对象:
    (1)使用阿伦单抗或抗胸腺细胞球蛋白
    (2)急性排斥反应
    (3)单肺移植
    (4)曲霉定植(移植前或移植后1年内)
    (5)获得性低丙种球蛋白血症(IgG < 4 g/L)
    预防用药:
    (1)雾化两性霉素B脂质体25 mg至支气管吻合口愈合,每周3次
    (2)2~6个月为每周1次
    (3) > 6个月时每2周1次指导性预防用药:负荷剂量25 mg,每周3次,2周后每周1次
    预防用药:使用雾化两性霉素B脂质体没有限制,或至少用12个月指导性预防用药:用至危险因素去除
    心脏 高危移植受者:
    (1)急性排斥反应血液透析
    (2)移植后再次手术
    (3)气道内曲霉大量定植
    伊曲康唑 至少3个月
    MELD为终末期肝病模型评分
    下载: 导出CSV
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出版历程
  • 收稿日期:  2019-02-15
  • 网络出版日期:  2021-01-19
  • 刊出日期:  2019-05-15

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