A comparative study of the efficacy of standard multidrug-resistant tuberculosis chemotherapy regimen for MDR-TB patients with pyrazinamide resistance or not

doi:10.3969/j.issn.1000-6621.2019.04.015

Abstract

Abstract:

Objective To explore the the short-term and long-term efficacy of standard multidrug-resistant tuberculosis (MDR-TB) chemotherapy regimen including PZA for MDR-TB patients with or without pyrazinamide resistance. Methods A retrospective cohort study was conducted to select 60 MDR-TB patients treated in Guangzhou Chest Hospital from January 1, 2015 to December 31, 2015; sputum culture showed the growth of Mycobacterium tuberculosis using BACTEC MGIT 960, and resistance to Isoniazid, Rifampicin and PZA (Z ^R-MDR group) were found by drug sensitive test. According to the 1∶1 principle, 60 multidrug resistant-tuberculosis patients were selected as control group (Z ^S-MDR group), the age difference was less than 5 years and the concurrent drug sensitivity test showed that they are sensitive to PZA. All patients were treated with chemotherapy regimen with 6Am-Lfx(Mfx)-PZA-Pto-Cs(PAS)/18Lfx(Mfx)-PZA-Pto-Cs(PAS). The sputum negative conversion rate, the absorption rate of lesions, the rate of cavity reduction, the cure rate and failure rate were conducted and analysed statistically. Results At the end of the 2,6,12, and 24 months after undergoing the treatment, sputum negative conversion rates of Z ^S-MDR patients were 70.00% (42/60), 90.00% (54/60), 86.67% (52/60) and 86.67% (52/60), respectively, which were statistically higher than those of Z ^R-MDR group (46.67% (28/60), 66.67% (40/60), 70.00% (42/60) and 70.00% (42/60), respectively; χ ²=6.720, 9.624, 4.910 and 4.910, respectively; and all P<0.05).At the end of the treatment, the absorption rate of lesions (81.67% (49/60) vs. 65.00% (39/60), χ ²=4.264,P=0.019), cure rate (86.67% (52/60) vs. 70.00% (42/60), χ ²=4.910, P=0.016) and failure rate (13.33% (8/60) vs. 30.00% (18/60), χ ²=4.910, P=0.016) in Z ^S-MDR group were statistically different from those in Z ^R-MDR group. However, as to the rate of cavity reduction, there was no statistically significant difference between the two groups (76.92% (40/52)vs. 62.00% (31/50, χ ²=2.681, P=0.098). Conclusion The efficacy of standard MDR-TB chemotherapy regimen in MDR-TB patients with PZA resistance for the whole course, was worse than in MDR-TB patients without PZA. Therefore, MDR-TB patients with PZA resistance were recommended tobe treated with the multi-drug regimen without PZA.

Key words: Tuberculosis, pulmonary, Tuberculosis, multidrug-resistant, Pyrazinamide, Drug therapy, combination, Comparative effectiveness research

Bi-tong WU,Hao-bin KUANG,Zhi-hui LIU,Xing-shan CAI,Hong-juan QIN,Fan-rong MENG,Li-lan WU,Zhao-yuan LIN,De-hu PENG,Shou-yong TAN. A comparative study of the efficacy of standard multidrug-resistant tuberculosis chemotherapy regimen for MDR-TB patients with pyrazinamide resistance or not[J]. Chinese Journal of Antituberculosis, 2019, 41(4): 447-451. doi: 10.3969/j.issn.1000-6621.2019.04.015

Figures/Tables 2

临床特征	Z^R-MDR组(60例)	Z^S-MDR组(60例)	统计检验值	P值
性别			χ²=0.178	0.153
男	44(73.33)	46(76.67)
女	16(26.67)	14(23.33)
年龄(岁, $x ˉ$ ±s)	38.47±12.22	42.40±14.94	t=1.582	0.081
患者类型			χ²=1.429	0.078
初治	15(25.00)	21(40.00)
复治	45(75.00)	39(60.00)
并发症
支气管结核	34(56.67)	28(46.67)	χ²=1.201	0.080
糖尿病	12(20.00)	10(16.67)	χ²=0.223	0.167
影像学检查			χ²=1.600	0.076
病灶范围≤3个肺野	12(20.00)	18(30.00)
病灶范围>3个肺野	48(80.00)	42(70.00)
肺部空洞(例)	50(83.33)	52(86.67)	χ²=0.252	0.172

References 13

[1]	包昌琳, 易恒仲, 唐益 , 等. 耐多药肺结核患者化学治疗疗效及其影响因素分析. 中国防痨杂志, 2018,40(5):525-530. doi: 10.3969/j.issn.1000-6621.2018.05.016 URL
[2]	中国防痨协会. 耐药结核病化学治疗指南(2015). 中国防痨杂志, 2015,37(5):421-469. doi: 10.3969/j.issn.1000-6621.2015.05.001 URL
[3]	World Health Organization. Treatment guideline for drug-resistant tuberculosis,2016 update.WHO/HTM/TB/2016.04.Geneva, World Health Organization, 2016.
[4]	Senol G, Coulter C, Weston J , et al. Investigation of pyrazinamide resistance in multidrug-resistant tuberculosis cases in hospital of pulmonary disease. Mikrobiyol Bul(Turkey), 2008,42(4):591-597. doi: 10.1099/mic.0.2008/019562-0 URL pmid: 19149080
[5]	Kim HJ, Kwak HK, Lee J , et al. Patterns of pncA mutations in drug-resistant Mycobacterium tuberculosis isolated from patients in South Korea. Int J Tuberc Lung Dis, 2012,16(1):98-103. doi: 10.5588/ijtld.10.0739 URL pmid: 22236853
[6]	Shenai S, Rodrigues C, Sadani M , et al. Comparison os phenotypic and genotypic methods for pyrazinamide susceptibility testing. Indian J Tuberc, 2009,56(2):82-90. doi: 10.1002/1097-4660(200010)75:10<933::AID-JCTB301>3.3.CO;2-3 URL pmid: 19810590
[7]	饶运帷, 谭耀驹, 谭守勇 , 等. 吡嗪酰胺耐药对初治菌阳肺结核疗效的影响. 实用医学杂志, 2014,30(1):127-129. doi: 10.3969/j.issn.1006-5725.2014.01.043 URL
[8]	黄盛晶, 饶运帷, 谭守勇 . 吡嗪酰胺耐药对初治菌阳肺结核复发的影响. 实用医学杂志, 2016,32(13):2224-2226. doi: 10.3969/j.issn.1006-5725.2016.13.044 URL
[9]	Parsons LM, Somoskovi A, Urbanczik R , et al. Laboratory diagnostic aspects of drug resistant tuberculosis. Front Biosci, 2004,9(10):2086-2105. doi: 10.2741/1290 URL pmid: 15353272
[10]	Whitfield MG, Soeters HM, Warren RM , et al. A global perspective on pyrazinamide resistance:systematic review and meta-analysis(Reviw). PLoS One, 2015,10(7):e0133869. doi: 10.1371/journal.pone.0133869 URL pmid: 4517823
[11]	卢峰岳, 张天宇, 谭耀驹 , 等. 吡嗪酰胺敏感性检测在结核病治疗中的应用. 广东医学, 2015,36(10):1509-1511.
[12]	Falzon D, Jaramillo E, Sehanemann HJ , et al. WHO guideline for the programmatic management of drug-resistant tuberculosis:2011 update. Eur Respir, 2011,38(3):516-528. doi: 10.1183/09031936.00073611 URL
[13]	唐神结, 高文 . 临床结核病学.北京: 人民卫生出版社, 2011: 191-200.

[1]	LIU Xiao-li, LEI Li-mei, GUO Zhou-li, HUANG Yin, XU Jing, ZHAO Xia, WANG Yan, FU Li. Study on the relationship of stigma and social support of tuberculosis patients [J]. Chinese Journal of Antituberculosis, 2020, 42(9): 1002-1008.
[2]	Academic Working Committee of Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis . Expert consensus of clinical application of fixed-dose combination formulations [J]. Chinese Journal of Antituberculosis, 2020, 42(9): 885-893.
[3]	JIN Hong-jian. The construction of tuberculosis prevention and control service system at county level in China needs to be strengthened urgently —— Comments and suggestions of an old tuberculosis control and prevention worker [J]. Chinese Journal of Antituberculosis, 2020, 42(9): 896-902.
[4]	ZHANG Can-you, XIA Hui, CHENG Jun. Testing and reporting requirements for Class Ⅱ biosafety cabinet in tuberculosis laboratory [J]. Chinese Journal of Antituberculosis, 2020, 42(9): 903-909.
[5]	ZHOU Lin, LIU Er-yong, MENG Qing-lin, CHEN Ming-ting, ZHOU Xin-hua, GAO Wei-wei, LIN Ming-gui, XIE Ru-ming. Evaluation of the quality of pulmonary tuberculosis diagnosis after the implementation of the newly revised WS 288-2017 Diagnosis for pulmonary tuberculosis standards [J]. Chinese Journal of Antituberculosis, 2020, 42(9): 910-915.
[6]	LIU Er-yong, WANG Qian, ZHOU Lin, ZHANG Guo-qin, ZHANG Xiu-lei, MA Yong-cheng, YANG Shu-min, WANG Cui, MENG Qing-lin, CHEN Ming-ting, LIN Ming-gui, TU De-hua.. Analysis of diagnostic quality of pulmonary tuberculosis with negative etiology in some areas of China [J]. Chinese Journal of Antituberculosis, 2020, 42(9): 916-920.
[7]	MENG Qing-lin, LI Jin-lan, LIN Ding-wen, MA Yong-cheng, HOU Shuang-yi, LIU Nian-qiang, ZHOU Lin. Analysis of the awareness about knowledge on the updated TB diagnosis standard among the practitioners in TB control institutions [J]. Chinese Journal of Antituberculosis, 2020, 42(9): 921-925.
[8]	WANG Qian, ZHOU Lin, LIU Er-yong, ZHAO Yan-lin, LI Tao, CHEN Ming-ting, YANG Li-jia, WANG Jia.. A survey on the diagnostic ability of tuberculosis in the county-level medical institutions in China [J]. Chinese Journal of Antituberculosis, 2020, 42(9): 926-930.
[9]	LI Ting, HE Jin-ge, SU Qian, LI Jing, LI Yun-kui, GAO Wen-feng, GAO Yuan, YANG Wen. Value of tuberculin test in screening tuberculosis infection in HIV infected/AIDS patients in Butuo County, Sichuan Province [J]. Chinese Journal of Antituberculosis, 2020, 42(9): 931-936.
[10]	LI Yun-kui, HE Jin-ge, SU Qian, LI Ting, LI Jing, GAO Wen-feng, YANG Wen, MAO Guang-yu. Value of tuberculin test in screening tuberculosis infection in HIV infected/AIDS patients in Butuo County, Sichuan Province [J]. Chinese Journal of Antituberculosis, 2020, 42(9): 937-941.
[11]	SU Qian, XIA Yong, LU Jia, WANG Dan-xia, HE Jin-ge. Analysis on the epidemiological characteristics of pulmonary tuberculosis among children aged 0-14 in Sichuan Province from 2009 to 2018 [J]. Chinese Journal of Antituberculosis, 2020, 42(9): 942-947.
[12]	DENG Ya-li, ZHANG Tian-hua, LIU Wei-ping, ZHANG Hong-wei, MA Yu, LI Peng.. Temporal and spatial clustering analysis of pulmonary tuberculosis incidence in Shaanxi Province from 2014 to 2018 [J]. Chinese Journal of Antituberculosis, 2020, 42(9): 948-955.
[13]	DONG Xiao, ZHAO Zhen, LIU Nian-qiang, WANG Sen-lu, CUI Yan. Analysis of the finding characteristics of pulmonary tuberculosis in the elderly population in Xinjiang Uygur Autonomous Region during 2009—2017 [J]. Chinese Journal of Antituberculosis, 2020, 42(9): 956-961.
[14]	MA Ting-long, HAN Yi, CHENG Xu, LIU Zhi-dong. Clinical observation on treatment effectiveness of transdermal ultrasound-mediated drug delivery combined with oral anti-tuberculosis drug in patients with chest wall tuberculosis [J]. Chinese Journal of Antituberculosis, 2020, 42(9): 968-972.
[15]	NAN Hai, ZHANG Yun, YANG Xin-ting, DUAN Hong-fei. Meta-analysis on the diagnostic value of GeneXpert MTB/RIF for bone and joint tuberculosis [J]. Chinese Journal of Antituberculosis, 2020, 42(9): 973-980.