化疗加免疫长疗程方案治疗耐多药结核病的随机对照研究

中国防痨杂志 ›› 2009, Vol. 31 ›› Issue (1): 10-14.

化疗加免疫长疗程方案治疗耐多药结核病的随机对照研究

初乃惠¹；罗永艾²；朱莉贞¹；傅瑜³；叶志忠⁴；肖和平⁵；王巍⁶；苑松林⁷；张侠⁸；卢水华⁹；马丽萍¹；聂玉生¹⁰；陈威¹¹；陈晓红¹²；刘志成¹³；李凫坚¹⁴；王丽花¹⁵；尚好珍¹⁶

1.北京市结核病胸部肿瘤研究所北京 101149； 2.重庆医科大学附属第一医院重庆 400016； 3.北京市结核病胸部肿瘤研究所，中国CDC结核病防治临床中心北京 101149； 4.厦门市第一医院厦门 361002； 5.上海市肺科医院上海 200433； 6.中国人民解放军总医院第二附属医院北京 100091； 7.天津市海河医院天津300222； 8.南京市胸科医院南京 210029； 9.复旦大学公共卫生学院上海 200032； 10.山西省阳泉市第三人民医院阳泉 045000； 11.沈阳市胸科医院沈阳 110044； 12.福建省福州肺科医院福州 350008； 13.武汉结核病院武汉 430083； 14.杭州市红十字会医院杭州 310003； 15.山西省太原市结核病医院太原 030053； 16.新乡医学院一附院新乡 453100

出版日期:2009-01-10 发布日期:2011-11-03
基金资助:
国家“十五”科技攻关资助项目（2001BA705B04）

A controlled clinical study of long course chemotherapy regimens combined with immunopotentiator in the treatment of multi-drug resistant pulmonary tuberculosis

1.Department of Tuberculosis, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149,China

Online:2009-01-10 Published:2011-11-03

摘要/Abstract

摘要： 目的评价化疗加免疫长疗程方案治疗耐多药肺结核的疗效和安全性。方法对203例耐多药肺结核患者，采用1∶1随机、平行对照的方法，分为治疗组和对照组，2组患者除采用对氨基水杨酸异烟肼、利福喷汀、左旋氧氟沙星、丙硫异烟胺（Pt）、克拉霉素和阿米卡星治疗外，治疗组患者加用免疫调节剂母牛分枝杆菌菌苗（M.vaccae,微卡），对照组患者不加用母牛分枝杆菌菌苗，疗程共18个月。结果治疗结束时（18个月）治疗组和对照组痰抗酸菌涂片阴性同时痰结核分枝杆菌培养阴性（涂阴培阴）分别为74.5%（73/98）和72.5%（66/91），（χ²=0.09，P=0.7599）。2组比较差异无统计学意义。X线影像结果表明，2组的病灶显效率分别为72.4%（71/98）和47.3%（43/91），差异有统计学意义（χ²＝12.52，P=0.0004，P>0.05）；有效率分别为90.8%（89/98）和82.4%（75/91），差异无统计学意义（χ²＝2.90，P=0.0886，P>0.05）；空洞闭合率分别为33.3%（27/81）和22.1%（17/77），差异无统计学意义（秩和检验F=1.52，P=0.1294，P>0.05）。免疫学指标CD8阳性原细胞在治疗6个月时治疗组高于对照组，CD3阳性原细胞治疗后与治疗前免疫指标差值在3和9个月差异有统计学意义外，其余CD4, CD4/CD8,NK细胞,IL-2R等免疫学指标在各治疗阶段，治疗组与对照组近似，差异无统计学意义。临床症状咳嗽、咳痰、胸痛，呼吸困难，乏力等症状有改善；治疗组改善程度均大于对照组。结论本研究所设计的方案对耐多药肺结核病均有明确的疗效，具有有效的杀菌、抑菌作用，加用免疫调节剂在促进病灶吸收，症状改善方面有一定的作用。

关键词: 结核, 抗多种药物性/治疗, 结核, 肺/治疗, 分枝杆菌, 牛, 随机对照试验

Abstract: ObjectiveTo evaluate the efficacy and safety of long course chemotherapy regimens combined with immunopotentiator in the treatment of multi-drug resistant pulmonary tuberculosis. MethodsDuring 18 months treatment, 203 patients with multi-drug resistant pulmonary tuberculosis were randomized 1∶1 to a treatment group (rifapentine,pasiniazide,levofloxacin,ethambutol,ethionamide,amikacin, clarithromycin and M. vaccae for 3 months, followed by rifapentine, pasiniazide, levofloxacin, ethambutol, ethionamide, clarithromycin and M. vaccae for 6 months, and rifapentine, pasiniazide, levofloxacin, ethambutol, clarithromycin for 9 months), and a control group (the same chemotherapy regimen alone,without M. vaccae). ResultsAt the end of the treatment, the sputum negative conversion rate (smear negative, culture negative) was 74.5% (73/98) in the treatment group, and was 72.5% (66/91) in the control group.There was no statistically significant difference between groups(χ²＝0.09, P=0.759 9). The marked effective rates of chest X-ray in the treatment group and the control group were 72.4% (71/98) and 47.3% (43/91) with statistically significant difference(χ²＝12.52, P=0.000 4),and the effective rates were 90.8% (89/98) and 82.4% (75/91) without statistically significant difference(χ²＝2.90, P=0.088 6, P>0.05) between two groups. The cavity closure rates were 33.3% (27/81) and 22.1% (17/77) without statistically significant difference(F=1.52，P=0.1294, P>0.05). CD3 count was improved statistically significant difference after 3 months and 6 months treatment in the treatment group, and the difference of CD8 in treatment group was also higher than that of control group after 6 months treatment. CD4, CD8, CD4/CD8, NK, IL-2R were similar in two groups at any stage of treatment without statistically significant difference. The symptom of cough, expectoration, chest pain, hypodynamia were improved in the treatment group better than those in control group. ConclusionsOur study showed regimens combined with immunopotentiator were very effective in bactericidal activity and bacteriostatic activity for the treatment of multi-drug resistant pulmonary tuberculosis. It had also an activity to lesion absorption and the improvement in symptoms.

Key words: tuberculosis，multidrug-resistant/therapy, pulmonary tuberculosis/therapy, Mycobacterium bovis, randomized controlled trial

初乃惠,罗永艾,朱莉贞,傅瑜,叶志忠,肖和平,王巍,苑松林,张侠,卢水华,马丽萍,聂玉生,陈威,陈晓红,刘志成,李凫坚,王丽花,尚好珍. 化疗加免疫长疗程方案治疗耐多药结核病的随机对照研究[J]. 中国防痨杂志, 2009, 31(1): 10-14.

Chu Naihui¹, Luo Yongai, Zhu Lizhen, Fu Yu, Ye Zhizhong, Xiao Heping, Wang Wei, Yuan Songlin, Zhang Xia, Lu Shuihua, Ma Liping, Nie Yusheng, Chen Wei, Chen Xiaohong, Liu Zhicheng, Li Fujian, Wang Lihua,Shang Haozhen.. A controlled clinical study of long course chemotherapy regimens combined with immunopotentiator in the treatment of multi-drug resistant pulmonary tuberculosis[J]. Chinese Journal of Antituberculosis, 2009, 31(1): 10-14.