潜伏性结核分枝杆菌感染的预防性治疗

doi:10.3877/cma.j.issn.1674-1358.2016.02.001

潜伏性结核分枝杆菌感染（LTBI）是结核分枝杆菌（Mtb）在体内的稽留状态，其诊断依据为结核纯蛋白衍化物（PPD）皮肤试验或干扰素释放试验（IGRA）阳性，且无临床症状或影像学证据。预防潜伏性结核感染发展为活动性结核病对于控制结核病疫情至关重要，国际上的预防性治疗方案主要有6～9个月单药异烟肼（INH）、3～4个月单药利福平（RIF）、3～4个月异烟肼联合利福平或利福喷丁（RPT）治疗。我国潜伏性结核感染预防性治疗研究数据有限，因此，加强医务工作者对LTBI高危人群的了解，尤其是各种预防性治疗方案在不同高危人群中应用的认识，对医务工作者选择有效的预防性治疗方案有着积极意义。

关键词: 潜伏性结核感染, 预防性治疗方案

Latent Mycobacterium tuberculosis infection is pragmatically defined as infection with M. tuberculosis, as evidenced by a positive tuberculin skin test reaction and (or) a positive interferon-γ release assay (IGRA) result without clinical manifestations of active tuberculosis. Preventive treatment for latent tuberculosis infection (LTBI) plays an important role in tuberculosis (TB) control in public and private health. Internationally, isoniazid therapy for 6-9 months, rifampicin monotherapy for 3-4 months and isoniazid plus rifampicin or rifapentine for 3-4 months have proved to be efficient. However, data about preventive treatment of LTBI in China is limited. It is of great importance for medical workers to cognize the advantages and drawbacks of different regimens in high-risk populations, and to choose efficient preventive therapy in clinical practice.

Key words: Latent tuberculosis infection, Preventive treatment

表1 2015年WHO LTBI管理指南中关于LTBI的检查和治疗在世界不同区域人群中应用

结核发病率< 100/10万	中高收入国家	资源缺乏和中低收入国家
需要进行系统性检查和治疗	接触过肺结核患者的成人或儿童；	HIV（+）患者；
	接受TNF-α治疗的患者；	家中有肺结核患者或接触过肺结核患者的5岁以下儿童
	进行透析后经临床评估的LTBI患者；
	准备接受器官或血液移植的患者；
	矽肺患者
考虑进行系统性检查和治疗	服刑罪犯；健康工人；结核高负担国家移民；流浪者和吸毒者
无需进行系统性检查和治疗	糖尿病患者；酒精滥用者；
无需进行系统性检查和治疗	吸烟者；低体重者

表1 2015年WHO LTBI管理指南中关于LTBI的检查和治疗在世界不同区域人群中应用

结核发病率< 100/10万	中高收入国家	资源缺乏和中低收入国家
需要进行系统性检查和治疗	接触过肺结核患者的成人或儿童；	HIV（+）患者；
	接受TNF-α治疗的患者；	家中有肺结核患者或接触过肺结核患者的5岁以下儿童
	进行透析后经临床评估的LTBI患者；
	准备接受器官或血液移植的患者；
	矽肺患者
考虑进行系统性检查和治疗	服刑罪犯；健康工人；结核高负担国家移民；流浪者和吸毒者
无需进行系统性检查和治疗	糖尿病患者；酒精滥用者；
无需进行系统性检查和治疗	吸烟者；低体重者

表2 HIV阴性LTBI成人患者的预防性治疗方案

治疗方案	单药INH	单药RIF	RIF/PZA	INH/RIF	INH/RPT
用法	（1）15 mg/kg，最大剂量为300 mg/d，1次/d；	10 mg·kg^-1·d^-1，最大剂量为600 mg、2次/周	RIF 10 mg·kg^-1·d^-1，最大剂量为600 mg、2次/周；PZA 20 mg·kg^-1·d^-1；	INH 15 mg/kg，最大剂量为300 mg/d，1次/d；RIF 10 mg·kg^-1·d^-1，最大剂量为600 mg、2次/周	INH 15 mg/kg，最大剂量为300 mg/d，1次/d；RPT 10 mg/kg
用法	（2）15 mg/kg，最大剂量为300 mg/d，2次/周	10 mg·kg^-1·d^-1，最大剂量为600 mg、2次/周	RIF 10 mg·kg^-1·d^-1，最大剂量为600 mg、2次/周；PZA 20 mg·kg^-1·d^-1；		最大剂量为900 mg/d，1次/周
疗程	6～9个月	4个月	2个月	3～4个月	3个月
疗效	90%	与6个月INH差异无统计学意义	IV阴性无随机对照，HIV阳性中等效	至少与6个月INH等效	至少与6个月INH等效
不良反应	无症状的肝酶升高；	肝毒性；	肝毒性普遍而严重	RIF与INH联合更易发生肝毒性；
	药物性肝炎；	皮肤过敏；		胃肠道反应；
	周围神经病变	高敏反应；		皮肤过敏；
		胃肠道反应		高敏反应
美国CDC（2013）	此方案疗程至少6个月，9个月疗效优于6个月，但6个月依从性更好	此方案适用不能够耐受INH或INH耐药	2003年ATS/CDC不推荐	与9个月INH等效
WHO（2015）	9个月和6个月INH可视为等效	是否等效有争议		是否等效有争议	4个月联合与9个月INH等效

表2 HIV阴性LTBI成人患者的预防性治疗方案

治疗方案	单药INH	单药RIF	RIF/PZA	INH/RIF	INH/RPT
用法	（1）15 mg/kg，最大剂量为300 mg/d，1次/d；	10 mg·kg^-1·d^-1，最大剂量为600 mg、2次/周	RIF 10 mg·kg^-1·d^-1，最大剂量为600 mg、2次/周；PZA 20 mg·kg^-1·d^-1；	INH 15 mg/kg，最大剂量为300 mg/d，1次/d；RIF 10 mg·kg^-1·d^-1，最大剂量为600 mg、2次/周	INH 15 mg/kg，最大剂量为300 mg/d，1次/d；RPT 10 mg/kg
用法	（2）15 mg/kg，最大剂量为300 mg/d，2次/周	10 mg·kg^-1·d^-1，最大剂量为600 mg、2次/周	RIF 10 mg·kg^-1·d^-1，最大剂量为600 mg、2次/周；PZA 20 mg·kg^-1·d^-1；		最大剂量为900 mg/d，1次/周
疗程	6～9个月	4个月	2个月	3～4个月	3个月
疗效	90%	与6个月INH差异无统计学意义	IV阴性无随机对照，HIV阳性中等效	至少与6个月INH等效	至少与6个月INH等效
不良反应	无症状的肝酶升高；	肝毒性；	肝毒性普遍而严重	RIF与INH联合更易发生肝毒性；
	药物性肝炎；	皮肤过敏；		胃肠道反应；
	周围神经病变	高敏反应；		皮肤过敏；
		胃肠道反应		高敏反应
美国CDC（2013）	此方案疗程至少6个月，9个月疗效优于6个月，但6个月依从性更好	此方案适用不能够耐受INH或INH耐药	2003年ATS/CDC不推荐	与9个月INH等效
WHO（2015）	9个月和6个月INH可视为等效	是否等效有争议		是否等效有争议	4个月联合与9个月INH等效

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Treatment of latent Mycobacterium tuberculosis infection

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