Effect of 18 months regimen in the treatment of multidrug-resistant pulmonary tuberculosis

doi:10.3969/j.issn.1000-6621.2019.03.010

Abstract

Abstract:

Objective We observed and analyzed the effect of 18 months regimen containing 6 drugs in the treatment of multidrug-resistant pulmonary tuberculosis (MDR-PTB) with the purpose to provide evidence for shortening the treatment course of MDR-TB.Methods Six hundred and eighty-one confirmed MDR-TB patients were enrolled from 20 TB specialized hospitals in China from July, 2009 to December, 2015 among which 515 were treated with the 18 months regimen containing 6 drugs (observation group) and 166 were treated with 24 months regimen containing 5 drugs (control group). Results of TB bacilli culture, complete blood count, hepatic and renal function, electrocardiograph,etc were collected throughout the treatment. The treatment outcome (success, death, failure and lost to follow-up) and adverse effect were assessed at the end of treatment.Data were analyzed using SPSS 22.0 software. Measurement data were analyzed by t test or z test.Enumeration data were analyzed by Chi-square test.The clinical indicator with significant difference before treatment were further analyzed by logistic regression to identify the risk factors associated with treatment success rate.P<0.05 was considered significant difference statistically.Results The treatment success rate (64.66%, 333/515) in the observation group was higher than that of the control group (54.22%, 90/166) (χ ²=5.818, P=0.002) and the death rate in the observation group (2.33%, 12/515) was lower than that of the control group (5.42%, 9/166) (χ ²=4.015, P=0.045). The rate of failure (17.86% (92/515) vs 23.49% (39/166))(χ ²=2.561, P=0.109) and lost to follow-up ((11.46%, 59/515) vs 11.45% (19/166)(χ ²=0.000, P=0.997)) were similar between the two groups. The total incidence of adverse reactions in the observation group (24.85%, 128/515)was close to that of the control group (25.90%, 43/166)(χ ²=0.095, P=0.757). Analysis using logistic regression showed that ≥50 age (β=0.549,s $\bar{x}$=0.204,Wald χ ²=7.262,P=0.007,OR(95%CI)=1.731(1.161-2.579)) and selection of ethambutol (β=0.485,s$\bar{x}$=0.190,Wald χ ²=6.516,P=0.011,OR(95%CI)=1.625(1.119-2.359)) in the regimen were the risk factors for treatment success. Conclusion The efficacy of the 18 months regimen containing 6 drugs was equivalent to the regimen of standard 24 months regimen and didn’t increase the adverse reaction occurrence. Therefore, it is worth for clinical application.

Key words: Tuberculosis, multidrug-resistant, Drug combined therapy, Regimen evaluation, Efficacy Comparative study

Qi LI,Xiao-ying JIANG,Meng-qiu GAO,Yu-hong LIU,Kun-yun YANG,Xiao-hong KAN,Jian-qin LIANG,Ming TIAN,Jin-cheng LIU,Wen-yu CUI,Wen LIU,De-mei YU,Shou-yong TAN,Shen-jie TANG,Yu-qin LIU,Xuan LIANG,Li-hua QIU,Shi-feng SHAO,Fei GAO,Li JIE,Bao-yun CAI,Jian-ling BU,Li-ping MA,Zhi LIU,Lin XU,Juan DU,Min CAO,Jing-tao GAO,Wei SHU,Liang LI. Effect of 18 months regimen in the treatment of multidrug-resistant pulmonary tuberculosis[J]. Chinese Journal of Antituberculosis, 2019, 41(3): 294-301. doi: 10.3969/j.issn.1000-6621.2019.03.010

Figures/Tables 5

基本资料	对照组(166例)	观察组(515例)	统计检验值	P值
性别[例(构成比,%)]			χ²=0.151	0.697
男	112(67.47)	341(66.21)
女	54(32.53)	174(33.79)
年龄(岁, $x ˉ$ ±s)	41.34±12.69	37.51±12.62	t=3.402	0.001
中位病程[月,M(Q₁,Q₃)]	24.27(12.10,24.92)	24.30(15.17,51.45)	Z=3.148	0.002
耐药种数( $x ˉ$ ±s)	3.63±1.33	3.50±1.39	t=0.923	0.356
复治[例(构成比,%)]	124(74.70)	365(70.87)	χ²=1.107	0.294
治疗次数(次, $x ˉ$ ±s)	1.94±0.85	1.78±0.52	t=1.013	0.312
空洞
例数(率,%)	112(67.47)	379(73.59)	χ²=2.014	0.156
数量(个, $x ˉ$ ±s)	2.15±1.82	2.26±1.93	t=0.565	0.573
病变所占肺野数(个, $x ˉ$ ±s)	3.64±1.79	3.89±1.69	t=1.488	0.137
体质量指数( $x ˉ$ ±s)	20.77±3.46	20.26±2.99	t=1.722	0.086
症状评分(分, $x ˉ$ ±s)	4.80±1.39	4.59±2.88	t=0.712	0.477
并发糖尿病[例(并发率,%)]	5(3.01)	35(6.80)	χ²=3.251	0.071
既往核心药物应用[例(使用率,%)]
Z	144(86.75)	443(86.02)	χ²=0.155	0.194
Am	41(24.70)	106(20.58)	χ²=2.825	0.244
Lfx	51(30.72)	121(23.50)	χ²=3.897	0.143
Mfx	3(1.81)	21(4.08)	χ²=2.207	0.332
Clr	8(4.82)	37(7.18)	χ²=1.104	0.293
方案中使用药物[例(使用率,%)]
E	97(58.43)	360(69.90)	χ²=6.941	0.008
Pto	109(65.66)	342(66.41)	χ²=0.007	0.932
PAS	31(18.67)	205(39.81)	χ²=24.300	0.000

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治疗转归	对照组(166例)	观察组(515例)	χ²值	P值
治疗成功	90(54.22)	333(64.66)	5.818	0.002
失败	39(23.49)	92(17.86)	2.561	0.109
死亡	9(5.42)	12(2.33)	4.015	0.045
丢失	19(11.45)	59(11.46)	0.000	0.997
无法评估	9(5.42)	19(3.69)	0.567	0.452

药物不良反应	对照组(166例)	观察组(515例)	χ²值	P值
药物性肝损伤	17(10.24)	51(9.90)	0.022	0.882
消化道反应	8(4.82)	40(7.77)	1.623	0.203
粒细胞减少	7(4.22)	16(3.11)	0.492	0.483
肾功能减退	6(3.61)	0(0.00)	-	0.000
过敏反应	2(1.20)	12(2.33)	-	0.600
听力减退	3(1.81)	9(1.75)	-	>0.999
合计	43(25.90)	128(24.85)	0.095	0.757

变量赋值
因变量	治疗成功=0;治疗不成功(失败、丢失、死亡、无法评估)=1
协变量
年龄	年龄<50岁=0;年龄≥50岁=1
病程	病程<2年=0;病程≥2年=1
使用E	未使用=0;使用=1
使用PAS	未使用=0;使用=1

指标	β值	$s_{\bar{x}}$值	Wald χ²值	P值	OR值	95%CI值
年龄≥50岁	0.549	0.204	7.262	0.007	1.731	1.161~2.579
病程≥2年	-0.189	0.179	1.117	0.291	0.828	0.583~1.175
方案使用E	0.485	0.190	6.516	0.011	1.625	1.119~2.359
方案使用PAS	0.231	0.187	1.533	0.291	1.260	0.874~1.818