高剂量莫西沙星短程方案对利福平耐药肺结核的疗效及适用性研究

doi:10.19982/j.issn.1000-6621.20220297

摘要/Abstract

摘要：

目的: 分析高剂量莫西沙星短程方案对利福平耐药肺结核(rifampicin-resistant pulmonary tuberculosis,RR-PTB)的疗效和安全性及制约其临床应用的相关因素。方法: 采用回顾性研究方法,收集西安市胸科医院2020年1月至2021年6月收治并获得治疗结局的272例RR-PTB患者作为研究对象,将使用高剂量莫西沙星短程方案治疗的27例患者作为观察组,使用长疗程治疗方案的127例患者作为对照组,比较两组患者治疗结局和不良事件发生率,并分析245例患者未使用短程方案治疗的原因。结果: 观察组治愈15例、治疗完成6例,治疗成功率为77.8%(21/27),与对照组治疗成功率[71.7%(91/127)]的差异无统计学意义(χ²=0.421,P=0.516);观察组不良事件发生率[88.9%(24/27)]和3级及以上不良事件发生率[40.7%(11/27)]均明显高于对照组[分别为50.4%(64/127)和21.3%(27/127)],差异均有统计学意义(χ²=13.473,P<0.001;χ²=4.546,P=0.033)。245例患者未使用高剂量莫西沙星短程方案治疗的前4位原因依次为氟喹诺酮类药物耐药[87例(35.5%)]、因使用二线抗结核药物超过1个月[52例(21.2%)]、合并气管结核[40例(16.3%)]和糖尿病控制不良[20例(8.1%)]。结论: 高剂量莫西沙星短程方案治疗RR-PTB患者具有较高的治疗成功率,但不良事件发生率较高,可适用患者比例低。应关注不良事件并开展基于我国患者实际情况的RR-PTB短程方案研究。

关键词: 结核,肺, 抗多种药物性, 药物疗法, 方案评价, 可行性研究

Abstract:

Objective: To analyze the efficacy and safety of high-dose moxifloxacin short-course regimen in patients with rifampicin-resistant pulmonary tuberculosis (RR-PTB), as well as the factors restricting the clinical application. Methods: A retrospective cohort study was conducted in 272 RR-PTB patients admitted to Xi’an Chest Hospital and had treatment outcome from January 2020 to June 2021. The observation group included 27 patients who was treated with high-dose moxifloxacin short course regimen, while the other 127 patients treated with long course regimen were in the control group. The treatment outcomes and the occurrence of adverse events were compared between the two groups, and the causes 245 patients not using short-course regimen were also analyzed. Results: In the observation group, 15 patients were cured, and 6 patients completed the treatment. There was no significant difference between the treatment success rate in observation group and in control group (77.8% (21/27) vs.71.7% (91/127); χ²=0.421, P=0.516). The occurrence of adverse events in observation group and adverse events at grade 3 or above were significantly higher than those in the control group (88.9% (24/27) vs. 50.4% (64/127), χ²=13.473, P<0.001; and 40.7% (11/27) vs. 21.3% (27/127),χ²=4.546, P=0.033, respectively). The top 4 reasons for 245 patients high-dosenot using high-dose moxifloxacin short-course regimen were fluoroquinolone resistance (n=87, 35.5%), the second-line anti-tuberculosis drugs had been used for more than 1 month (n=52, 21.2%), combined tracheobronchial tuberculosis (n=40, 16.3%), and uncontrolled diabetes (n=20, 8.1%). Conclusion: High-dose moxifloxacin short-course regimens for RR-PTB patients could obtain a high success rate, while the incidence of adverse events was higher and the proportion of eligible patients was lower. We should pay more attention to the adverse events of short-course regimen and applicability studies should be carried out based on the actual conditions of Chinese patients.

Key words: Tuberculosis, pulmonary, Multi-drug resistance, Drug therapy, Regimens evaluation, Feasibility studies

中图分类号:

任斐, 马进宝, 李荣, 杨翰, 杨虹, 武延琴, 杨新军, 党丽云. 高剂量莫西沙星短程方案对利福平耐药肺结核的疗效及适用性研究[J]. 中国防痨杂志, 2023, 45(1): 52-59. doi: 10.19982/j.issn.1000-6621.20220297

Ren Fei, Ma Jinbao, Li Rong, Yang Han, Yang Hong, Wu Yanqin, Yang Xinjun, Dang Liyun. Efficacy and eligibility of high-dose moxifloxacin short-course regimen for rifampicin-resistant pulmonary tuberculosis[J]. Chinese Journal of Antituberculosis, 2023, 45(1): 52-59. doi: 10.19982/j.issn.1000-6621.20220297

图/表 2

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参考文献 26

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类别	观察组(27例)	对照组(127例)	统计检验值	P值
年龄	33.0(29.0,37.0)	34.0(27.0,53.0)	Z=-0.815	0.415
体质量指数	19.6(18.4,21.4)	20.1(18.1,22.5)	Z=-0.415	0.818
性别			χ²=0.056	0.813
男性	17(63.0)	83(65.4)
女性	10(37.0)	44(34.6)
痰抗酸杆菌镜检			χ²=0.011	0.914
阴性	12(44.4)	55(43.3)
阳性	15(55.6)	72(56.7)
类别	观察组(27例)	对照组(127例)	统计检验值	P值
病灶侵犯肺野数			χ²=0.359	0.549
单肺	17(63.0)	72(56.7)
双肺	10(37.0)	55(43.3)
空洞			χ²=0.102	0.750
有	11(40.7)	56(44.1)
无	16(59.3)	71(55.9)
气管结核			χ²=2.994	0.084
有	11(40.7)	31(24.4)
无	16(59.3)	96(75.6)
淋巴结结核			χ²=0.041	0.839
有	6(22.2)	26(20.5)
无	21(77.8)	101(79.5)
糖尿病			χ²=0.187	0.665
有	2(7.4)	16(12.6)
无	25(92.6)	111(87.4)
疾病类型			χ²=17.180	<0.001
初治	27(100.0)	74(58.3)
复治	0(0.0)	53(41.7)
氟喹诺酮类			χ²=9.989	0.002
耐药	0(0.0)	36(28.3)
敏感	27(100.0)	91(71.7)
阿米卡星			χ²=0.547	0.459
耐药	0(0.0)	7(5.5)
敏感	27(100.0)	120(94.5)
乙胺丁醇			χ²=0.005	0.945
耐药	6(22.2)	29(22.8)
敏感	21(77.8)	98(77.2)
异烟肼			χ²=2.769	0.096
耐药	19(70.4)	109(85.8)
敏感	8(29.6)	18(14.2)
丙硫异烟胺			χ²=0.365	0.546
耐药	0(0.0)	6(4.7)
敏感	27(100.0)	121(95.3)
氯法齐明			-	1.000^a
耐药	0(0.0)	1(0.8)
敏感	27(100.0)	126(99.2)

不良事件类型	观察组(27例)	对照组(127例)	χ²值	P值
QT间期延长	14(51.9)	8(6.3)	34.104	<0.001
胃肠道不良反应	14(51.9)	13(10.2)	23.870	<0.001
肝功能损伤	10(37.0)	22(17.3)	5.257	0.022
痛风/关节疼痛	2(7.4)	10(7.9)	0.098	0.754
神经系统损伤	1(3.7)	28(22.0)	4.902	0.027
血液系统损伤	1(3.7)	3(2.4)	-	0.541^a
血糖异常	1(3.7)	0(0.0)	-	0.175^a
甲状腺功能紊乱	0(0.0)	5(3.9)	-	0.587^a
肾功能损伤	0(0.0)	4(3.1)	-	1.000^a
精神异常	0(0.0)	3(2.4)	-	1.000^a
过敏反应	0(0.0)	2(1.6)	-	1.000^a
合计	24(88.9)	64(50.4)	13.473	<0.001