结核性脑膜炎治疗中存在的若干问题与看法

doi:10.3969/j.issn.1000-6621.2019.04.002

摘要/Abstract

摘要：

结核性脑膜炎有着较高的死亡率和致残率,是结核病最严重的类型。随着结核病呈现出高耐药率、并发HIV感染等新的流行特点,给结核性脑膜炎的治疗带来了严峻的挑战。要采取综合治疗措施提高结核性脑膜炎的治疗效果,作者就目前关于结核性脑膜炎治疗方面存在的问题,以及综合治疗方法及其合理应用等结合文献和临床经验进行论述。

关键词: 结核, 脑膜, 思考, 评论, 综合疗法

Abstract:

Tuberculous meningitis (TBM) is most serious type of TB with high mortality and disability rate. With the emergence of new epidemic characteristics of tuberculosis, such as high drug resistance rate and concurrent HIV infection, treatment of TBM faces serious challenges, and comprehensive treatment measures should be taken to improve the treatment effect of TBM. The author discussed the existing problems in the treatment of tuberculous meningitis, and the comprehensive treatment methods and their rational application combined with literature and clinical experience.

Key words: Tuberculosis, meningeal, Thinking, Comments, Comprehensive therapy

马艳,高微微. 结核性脑膜炎治疗中存在的若干问题与看法[J]. 中国防痨杂志, 2019, 41(4): 371-376. doi: 10.3969/j.issn.1000-6621.2019.04.002

Yan MA,Wei-wei GAO. Some opinions and problems on the treatment of tuberculous meningitis[J]. Chinese Journal of Antituberculosis, 2019, 41(4): 371-376. doi: 10.3969/j.issn.1000-6621.2019.04.002

图/表 1

参考文献 32

[1]	He Y, Han C, Chang KF , et al. Total delay in treatment among tuberculous meningitis patients in China: a retrospective cohort study. BMC Infect Dis, 2017,17(1):341. doi: 10.1186/s12879-017-2447-0 URL pmid: 28499348
[2]	雷春侠, 胡绢利, 高婷 , 等. 超声评估与引导外周置入中心静脉导管治疗结核性脑膜炎患者的体会. 中国防痨杂志, 2018,40(11):1237-1239.
[3]	陈宇, 樊丽超, 陈禹 , 等. 持续腰大池引流术在结核性脑膜炎治疗中的应用. 结核病与肺部健康杂志, 2018,7(3):221-224. doi: 10.3969/j.issn.2095-3755.2018.03.016 URL
[4]	康万里, 唐神结 . 成人结核性脑膜炎患者的强化抗结核治疗(文献速递). 结核病与肺部健康杂志, 2016,5(2):134-134.
[5]	马艳, 高微微, 周林 . 结核性脑膜炎防治现状与展望. 中国防痨杂志, 2019,41(1):5-8.
[6]	Thwaites GE, van Toorn R, Schoeman J . Tuberculous meningitis: more questions, still too few answers. Lancet Neurol, 2013,12(10):999-1010. doi: 10.1016/S1474-4422(13)70168-6 URL pmid: 23972913
[7]	Heemskerk AD, Nguyen MTH, Dang HTM , et al. Clinical outcomes of patients with drug-resistant tuberculous meningitis treated with an intensified antituberculosis regimen. Clin Infect Dis, 2017,65(1):20-28. doi: 10.1093/cid/cix230 URL pmid: 28472255
[8]	Dian S, Yunivita V, Ganiem AR , et al. Double-blind, randomized, placebo-controlled phase Ⅱ dose-finding study to evaluate high-dose rifampin for tuberculous meningitis. Antimicrob Agents Chemother, 2018, 62(12). pii:e01014-18.
[9]	中华医学会. 临床诊疗指南:结核病分册. 北京:人民卫生出版社, 2005: 6.
[10]	严碧涯, 端木宏谨 . 结核病学. 北京北京出版社, 2003.
[11]	Davis A, Meintjes G, Wilkinson RJ . Treatment of tuberculous meningitis and its complications in adults. Curr Treat Options Neurol, 2018,20(3):5. doi: 10.1007/s11940-018-0490-9 URL pmid: 29492737
[12]	陈广田 . 大剂量异烟肼配合其他抗结核药物治疗成人结核性脑膜炎(初步报告). 中华结核病科杂志, 1956,4(1):20-24.
[13]	李洪智, 张翰明, 马亚秋 . 地塞米松冲击治疗结核性脑膜炎疗效观察. 中国实用神经疾病杂志, 2016,19(21):26-27. doi: 10.3969/j.issn.1673-5110.2016.21.013 URL
[14]	张文宏 . 复杂性布氏菌病临床诊治亟待重视. 中华内科杂志, 2017,56(10):721-722.
[15]	Kalita J, Misra UK, Prasad S , et al. Safety and efficacy of levofloxacin versus rifampicin in tuberculous meningitis: an open-label randomized controlled trial. J Antimicrob Chemother, 2014,69(8):2246-2251. doi: 10.1093/jac/dku103 URL pmid: 24752957
[16]	Thwaites GE . Advances in the diagnosis and treatment of tuberculous meningitis. Curr Opin Neurol, 2013,26(3):295-300. doi: 10.1097/WCO.0b013e3283602814 URL pmid: 23493162
[17]	Ruslami R, Ganiem AR, Dian S , et al. Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial. Lancet Infect Dis, 2013,13(1):27-35. doi: 10.1016/S1473-3099(12)70264-5 URL pmid: 23103177
[18]	周晛, 孙峰, 张文宏 . 结核性脑膜炎治疗新策略的研究进展. 中华临床感染病杂志, 2016,9(5):477-480. doi: 10.3760/cma.j.issn.1674-2397.2016.05.023 URL
[19]	Rizvi I, Malhotra HS, Garg RK , et al. Fluoroquinolones in the management of tuberculous meningitis: Systematic review and meta-analysis. J Infect, 2018,77(4):261-275. doi: 10.1016/j.jinf.2018.06.009 URL
[20]	李秀杰 . 莫西沙星辅助治疗难治性结核性脑膜炎的疗效及安全性观察. 中国民康医学, 2018,30(15):14-16.
[21]	陈宇 . 莫西沙星与抗结核药物联用治疗难治性结核性脑膜炎的疗效观察. 中国现代医生, 2018,56(3):74-76,79.
[22]	World Health Organization . Guidelines for treatment of drug-susceptible tuberculosis and patient care (2017 update). Geneva: World Health Organization, 2017.
[23]	Blumberg HM, Burman WJ, Chaisson RE , et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med, 2003,167(4):603-662. doi: 10.1164/rccm.167.4.603 URL pmid: 12588714
[24]	Thwaites G, Fisher M, Hemingway C , et al. British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children. J Infect, 2009,59(3):167-187. doi: 10.1016/j.jinf.2009.06.011 URL pmid: 19643501
[25]	Jullien S, Ryan H, Modi M , et al. Six months therapy for tuberculous meningitis. Cochrane Database Syst Rev, 2016, 9:CD012091. doi: 10.1002/14651858.CD012091.pub2 URL
[26]	孔文琴, 马淑萍, 张培元 , 等. 鞘内注入丁胺卡那霉素脑脊液浓度动态观察. 中国防痨杂志, 1998,20(3):121-122.
[27]	闫世明, 于关成, 王莉 , 等. 放脑脊液治疗结核性脑膜炎并高颅压的临床探讨. 中华结核和呼吸杂志, 1999,22(11):687. doi: 10.3760/j:issn:1001-0939.1999.11.027 URL
[28]	陈永芳, 任鹏飞, 陈裕 . 脑脊液置换联合鞘内注药治疗结核性脑膜炎临床分析. 中国实用神经疾病杂志, 2018,21(8):861-863. doi: 10.12083/SYSJ.2018.08.216 URL
[29]	闫红梅, 兰小艳, 顾燕梅 , 等. 鞘内注射联合脑脊液置换治疗结核性脑膜炎的效果观察. 宁夏医学杂志, 2018,40(6):528-530.
[30]	李倩, 张建树, 孟艺哲 . 地塞米松联合异烟肼鞘内注射治疗结核性脑膜炎效果观察. 解放军医药杂志, 2017,29(11):80-83. doi: 10.3969/j.issn.2095-140X.2017.11.021 URL
[31]	林文, 张月辉, 詹成 . 结核性脑膜炎68例临床分析. 华西医学, 2009,24(3):727-728.
[32]	郭义平 . 儿童结核性脑膜炎治疗中类赫氏反应的观察. 临床肺科杂志, 2012,17(10):1915-1916. doi: 10.3969/j.issn.1009-6663.2012.10.095 URL

抗结核药物	标准剂量	CSF/血浆药物浓度比值(%)	评价(药物透过血脑屏障能力)
INH	0.3g	80~90	良好
RFP	0.45(体质量<50g)或0.6g(体质量≥5kg)	10~20	较差
EMB	0.015g/kg	20~30	较差
PZA	1.5g(体质量<50kg)或2.0g(体质量≥50kg)	90~100	良好
Sm	0.015g/kg(最大剂量1g)	10~20	较差
Lfx	1g	70~80	较好
Mfx	0.4g	70~80	较好
Am	(0.015~0.02)g/kg	10~20	较差
Km	0.015g/kg	10~20	较差
Cm	(0.015~0.02)g/kg	-
PAS	10~12g	-	较差
Pto	(0.015~0.02)g/kg(最大剂量1g)	80~90	良好
Cs	(0.01~0.015)g/kg	80~90	良好
Lzd	1.2g	40~70	差异较大