含贝达喹啉耐药结核治疗方案对患者心电图QT间期的影响

doi:10.3969/j.issn.1004-583X.2024.07.008

摘要/Abstract

摘要：

目的探索含贝达喹啉耐药结核治疗方案对患者心电图QT间期的影响。方法选取2018年8月-2022年12月在昆明市第三人民医院结核科接受耐药治疗结核病患者204例。治疗方案含贝达喹啉(观察组)84例,其中退出4例、死亡2例,最终78例。治疗方案不含贝达喹啉(对照组)120例,死亡1例、退出4例,最终115例。收集并记录两组治疗不同阶段心电图QT间期和临床资料。结果与基线比较,观察组治疗的第2、4、8、12、16、20、24周心电图QT间期均较高,差异有统计学意义(P<0.05)。观察组治疗第16、20、24周较对照组QT期间长,差异均有统计学意义(P<0.05)。观察组QT间期大于500 ms有15例(19.2%,15/78),其中7例背景方案含氯法齐明和莫西沙星。结论含贝达喹啉的治疗方案会引起患者心电图QT间期的延长,但背景方案含氯法齐明和喹诺酮类更会加重QT间期的延长,因此使用贝达喹啉联合氯法齐明和喹诺酮类时更应加强心电图监测及心脏检查。

关键词: 结核, 抗多种药物性, QT间期延长, 贝达喹啉, 氯法齐明, 喹诺酮

Abstract:

Objective To explore the effect of treatment regimen containing Bedaquiline for drug-resistant tuberculosis on the QT interval of electrocardiogram. Methods A total of 204 patients with drug-resistant tuberculosis admitted in the Department of Tuberculosis, Kunming Third People's Hospital from August 2018 to December 2022 were selected. Eighty-four patients treated with Bedaquiline-containing regimen were included in the observation group. After excluding 4 dropouts and 2 deaths, 78 cases were finally included in the observation group. A total of 120 patients treated with the regimen without Bedaquiline were enrolled in the control group, and finally 115 were eligible (4 dropouts and 1 death).The QT interval and clinical data of two groups at different stages of treatment were compared. Results Compared with the baseline, the QT interval of electrocardiogram in the observation group was significantly higher at the 2 nd, 4 th, 8 th, 12 th, 16 th, 20 th and 24 th weeks of treatment significantly (P<0.05). The QT period of the observation group was significantly longer than that of the control group at the 16 th, 20 th and 24 th week of treatment(P<0.05). In the observation group, there were 15 cases (19.2%, 15/78 ) with QT interval greater than 500 ms, including 7 cases of background regimen containing clofazimine and moxifloxacin. Conclusion Treatment regimen containing Bedaquiline for drug-resistant tuberculosis prolongs QT interval, but the background regimen containing Clofazimine and Quinolones aggravates the prolonged QT interval. Therefore, electrocardiogram monitoring and cardiac examination should be strengthened when using betamethasone in combination with Clofazimine and Quinolones.

Key words: tuberculosis, multidrug-resistant, QT interval prolongation, bedaquiline, clofazimine, quinolone

中图分类号:

万荣, 李光妹, 季永静, 刘蕾, 崔灿灿, 李明武. 含贝达喹啉耐药结核治疗方案对患者心电图QT间期的影响[J]. 临床荟萃, 2024, 39(7): 630-634.

Wan Rong, Li Guangmei, Ji Yongjing, Liu Lei, Cui Cancan, Li Mingwu. Effect of treatment regimen containing Bedaquiline for drug-resistant tuberculosis on the QT interval of electrocardiogram[J]. Clinical Focus, 2024, 39(7): 630-634.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2024.07.008

https://huicui.hebmu.edu.cn/CN/Y2024/V39/I7/630

图/表 3

表1 两组一般情况比较[例(%)]

Tab.1 General information between groups

项目	观察组( $n$ =78)	对照组( $n$ =115)	χ²值	P值
性别[例(%)]
男女	45(57.6) 33(42.4)	64(55.6) 51(44.4)	0.079	0.779
耐药类型[例(%)]
RR-TB	4(5.1)	18(15.7)	5.097	0.024
MDR-TB	34(43.6)	68(59.1)	4.505	0.034
Pre-XDR-TB	29(37.2)	24(20.9)	6.207	0.013
XDR-TB	11(14.1)	5(4.3)	5.817	0.016
治疗史[例(%)]
初治复治	29(37.2) 49(62.8)	41(35.7) 74(64.3)	0.047	0.829
背景方案[例(%)]
左氧氟沙星	2(2.6)	11(9.6)	3.626	0.057
莫西沙星	4(5.1)	15(13.0)	3.281	0.070
氯法齐明	22(28.2)	29(25.2)	0.213	0.644
左氧氟沙星+氯法齐明	19(24.4)	26(22.6)	0.080	0.778
莫西沙星+氯法齐明	15(19.2)	34(29.6)	2.620	0.105
QT间期>500 ms[例(%)]
背景方案为左氧氟沙星	0	0
背景方案为莫西沙星	0	0
背景方案为氯法齐明	4(4/22, 18.2)	1(1/29, 3.4)	3.071	0.080
背景方案为左氧氟沙星+氯法齐明	4(4/19, 21.1)	1(1/26, 3.8)	3.291	0.070
背景方案为莫西沙星+氯法齐明	7(7/15, 46.7)	2(2/34, 5.9)	11.546	0.001

表1 两组一般情况比较[例(%)]

Tab.1 General information between groups

项目	观察组( $n$ =78)	对照组( $n$ =115)	χ²值	P值
性别[例(%)]
男女	45(57.6) 33(42.4)	64(55.6) 51(44.4)	0.079	0.779
耐药类型[例(%)]
RR-TB	4(5.1)	18(15.7)	5.097	0.024
MDR-TB	34(43.6)	68(59.1)	4.505	0.034
Pre-XDR-TB	29(37.2)	24(20.9)	6.207	0.013
XDR-TB	11(14.1)	5(4.3)	5.817	0.016
治疗史[例(%)]
初治复治	29(37.2) 49(62.8)	41(35.7) 74(64.3)	0.047	0.829
背景方案[例(%)]
左氧氟沙星	2(2.6)	11(9.6)	3.626	0.057
莫西沙星	4(5.1)	15(13.0)	3.281	0.070
氯法齐明	22(28.2)	29(25.2)	0.213	0.644
左氧氟沙星+氯法齐明	19(24.4)	26(22.6)	0.080	0.778
莫西沙星+氯法齐明	15(19.2)	34(29.6)	2.620	0.105
QT间期>500 ms[例(%)]
背景方案为左氧氟沙星	0	0
背景方案为莫西沙星	0	0
背景方案为氯法齐明	4(4/22, 18.2)	1(1/29, 3.4)	3.071	0.080
背景方案为左氧氟沙星+氯法齐明	4(4/19, 21.1)	1(1/26, 3.8)	3.291	0.070
背景方案为莫西沙星+氯法齐明	7(7/15, 46.7)	2(2/34, 5.9)	11.546	0.001

表2 两组QT间期比较( x -±s,ms)

Tab.2 QT intervals between groups( x -±s,ms)

治疗时间 (周)	观察组		对照组		$t$ 值	P值
治疗时间 (周)	例数	QT间期	例数	QT间期	$t$ 值	P值
0	78	424.99±24.35	115	414.15±17.01	2.101	0.182
2	75	440.77±25.99^*	113	443.25±24.45	0.412	0.486
4	75	446.20±30.78^*	112	441.54±29.19	0.508	0.792
8	74	453.81±30.38^*	112	441.47±16.13	1.738	0.115
12	72	452.07±36.44^*	110	435.69±19.55	1.822	0.081
16	69	450.93±30.15^*	110	435.23±16.14	3.737	<0.001
20	65	451.74±28.51^*	110	431.29±27.60	4.783	<0.001
24	68	457.69±26.46^*	110	436.00±24.13	1.939	0.031

表2 两组QT间期比较( x -±s,ms)

Tab.2 QT intervals between groups( x -±s,ms)

治疗时间 (周)	观察组		对照组		$t$ 值	P值
治疗时间 (周)	例数	QT间期	例数	QT间期	$t$ 值	P值
0	78	424.99±24.35	115	414.15±17.01	2.101	0.182
2	75	440.77±25.99^*	113	443.25±24.45	0.412	0.486
4	75	446.20±30.78^*	112	441.54±29.19	0.508	0.792
8	74	453.81±30.38^*	112	441.47±16.13	1.738	0.115
12	72	452.07±36.44^*	110	435.69±19.55	1.822	0.081
16	69	450.93±30.15^*	110	435.23±16.14	3.737	<0.001
20	65	451.74±28.51^*	110	431.29±27.60	4.783	<0.001
24	68	457.69±26.46^*	110	436.00±24.13	1.939	0.031

表3 观察组15例QT间期大于500 ms患者的临床特点

Tab.3 Clinical characteristics of 15 patients with a QT interval more than 500 ms in the observation group

编号	性别	年龄	影响QT间期延长药物	电解质钾水平(mmol/L)	是否合并心脏病患	基线QT 间期	QTC 峰值	QT间期峰值时间点	治疗过程
1	女	32	氯法齐明	4.62	否	437	505	4周	腰椎结核,脓液MDR-TB药,后未超500 ms,完成贝达喹啉24周
2	男	44	氯法齐明	3.94	否	427	565	8周	肺结核,Pre-XDR-TB,经停药,也有超500 ms,间断服药完成贝达喹啉24周
3	女	48	氯法齐明	3.97	否	425	505	8周	肺结核,Pre-XDR-TB,经停药,后未超500 ms,完成贝达喹啉24周
4	男	59	氯法齐明	4.11	否	441	517	8周	肺结核,Pre-XDR-TB,经停药,后未超500 ms,完成贝达喹啉24周
5	男	57	氯法齐明+左氧氟沙星	4.17	否	435	519	8周	肺结核,MDR-TB,经停药,后未超500 ms,完成贝达喹啉24周
6	男	52	氯法齐明+左氧氟沙星	3.87	否	430	557	12周	肺结核,MDR-TB,经停药,后未超500 ms,完成贝达喹啉24周
7	女	29	氯法齐明+左氧氟沙星	3.35	有先心病	417	505	12周	肺结核,MDR-TB,有先心病病史血钾偏低,经停药,后反复试药无法继续贝达喹啉,未完成贝达喹啉24周,更改方案
8	男	43	氯法齐明+左氧氟沙星	4.66	否	450	512	12周	肺结核,MDR-TB,经停药,后未超500 ms,完成贝达喹啉24周
9	女	24	氯法齐明+莫西沙星	3.83	否	438	505	20周	肺结核,MDR-TB,经停药,后通过换掉氯法齐明,未超500 ms,完成贝达喹啉24周
10	男	27	氯法齐明+莫西沙星	3.65	否	423	518	4周	肺结核,颈淋巴结结核,培养示Pre-XDR-TB,经停药,后未超500 ms,完成贝达喹啉24周
11	女	46	氯法齐明+莫西沙星	3.83	否	440	597	12周	肺结核,MDR-TB,经停药,后反复试药无法继续贝达喹啉,未完成贝达喹啉24周,更改方案
12	女	33	氯法齐明+莫西沙星	4.04	否	445	507	2周	肺结核,MDR-TB,经停药,后未超500 ms,完成贝达喹啉24周
13	男	44	氯法齐明+莫西沙星	4.04	否	431	508	16周	肺结核,MDR-TB,经停药,后反复试药无法继续贝达喹啉,未完成贝达喹啉24周,更改方案
14	女	35	氯法齐明+莫西沙星	3.32	否	437	518	20周	肺结核,结核性脑炎,MDR-TB,经停药,后未超500 ms,完成贝达喹啉24周
15	男	56	氯法齐明+莫西沙星	3.44	否	433	527	12周	肺结核,胸椎结核,MDR-TB,经停药,后未超500 ms,完成贝达喹啉24周

表3 观察组15例QT间期大于500 ms患者的临床特点

Tab.3 Clinical characteristics of 15 patients with a QT interval more than 500 ms in the observation group

编号	性别	年龄	影响QT间期延长药物	电解质钾水平(mmol/L)	是否合并心脏病患	基线QT 间期	QTC 峰值	QT间期峰值时间点	治疗过程
1	女	32	氯法齐明	4.62	否	437	505	4周	腰椎结核,脓液MDR-TB药,后未超500 ms,完成贝达喹啉24周
2	男	44	氯法齐明	3.94	否	427	565	8周	肺结核,Pre-XDR-TB,经停药,也有超500 ms,间断服药完成贝达喹啉24周
3	女	48	氯法齐明	3.97	否	425	505	8周	肺结核,Pre-XDR-TB,经停药,后未超500 ms,完成贝达喹啉24周
4	男	59	氯法齐明	4.11	否	441	517	8周	肺结核,Pre-XDR-TB,经停药,后未超500 ms,完成贝达喹啉24周
5	男	57	氯法齐明+左氧氟沙星	4.17	否	435	519	8周	肺结核,MDR-TB,经停药,后未超500 ms,完成贝达喹啉24周
6	男	52	氯法齐明+左氧氟沙星	3.87	否	430	557	12周	肺结核,MDR-TB,经停药,后未超500 ms,完成贝达喹啉24周
7	女	29	氯法齐明+左氧氟沙星	3.35	有先心病	417	505	12周	肺结核,MDR-TB,有先心病病史血钾偏低,经停药,后反复试药无法继续贝达喹啉,未完成贝达喹啉24周,更改方案
8	男	43	氯法齐明+左氧氟沙星	4.66	否	450	512	12周	肺结核,MDR-TB,经停药,后未超500 ms,完成贝达喹啉24周
9	女	24	氯法齐明+莫西沙星	3.83	否	438	505	20周	肺结核,MDR-TB,经停药,后通过换掉氯法齐明,未超500 ms,完成贝达喹啉24周
10	男	27	氯法齐明+莫西沙星	3.65	否	423	518	4周	肺结核,颈淋巴结结核,培养示Pre-XDR-TB,经停药,后未超500 ms,完成贝达喹啉24周
11	女	46	氯法齐明+莫西沙星	3.83	否	440	597	12周	肺结核,MDR-TB,经停药,后反复试药无法继续贝达喹啉,未完成贝达喹啉24周,更改方案
12	女	33	氯法齐明+莫西沙星	4.04	否	445	507	2周	肺结核,MDR-TB,经停药,后未超500 ms,完成贝达喹啉24周
13	男	44	氯法齐明+莫西沙星	4.04	否	431	508	16周	肺结核,MDR-TB,经停药,后反复试药无法继续贝达喹啉,未完成贝达喹啉24周,更改方案
14	女	35	氯法齐明+莫西沙星	3.32	否	437	518	20周	肺结核,结核性脑炎,MDR-TB,经停药,后未超500 ms,完成贝达喹啉24周
15	男	56	氯法齐明+莫西沙星	3.44	否	433	527	12周	肺结核,胸椎结核,MDR-TB,经停药,后未超500 ms,完成贝达喹啉24周

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