254例耐药肺结核患者克拉霉素耐药情况及影响因素分析

doi:10.3969/j.issn.1000-6621.2020.03.015

摘要/Abstract

摘要：

目的分析耐药肺结核患者克拉霉素耐药情况及相关危险因素,为其临床应用提供依据。方法收集2017年1月至2018年1月在首都医科大学附属北京胸科医院确诊为耐药肺结核的254例患者的临床资料和药物敏感性试验(简称“药敏试验”)结果进行回顾性分析。采用比例法对克拉霉素等16种抗结核药物进行药敏试验检测。采用logistic回归法分析克拉霉素耐药的临床相关危险因素。结果 (1)254例耐药肺结核患者中,17例耐多药/广泛耐药患者对克拉霉素耐药,耐药率为6.69%(17/254),低于其余15种抗结核药物[12.60%(32/254)~95.67%(243/254)]。(2)对克拉霉素耐药的耐多药/广泛耐药患者,对莫西沙星(47.06%,8/17)、氯法齐明(70.59%,12/17)、乙胺丁醇(82.35%,14/17)、阿米卡星(52.94%,9/17)、对氨基水杨酸(76.47%,13/17)、对氨基水杨酸异烟肼(88.24%,15/17)、卷曲霉素(76.47%,13/17)的耐药率均高于对克拉霉素敏感的患者[莫西沙星(11.32%,24/212)、氯法齐明(9.91%,21/212)、乙胺丁醇(41.51%,88/212)、阿米卡星(21.70%,46/212)、对氨基水杨酸(35.85%,76/212)、对氨基水杨酸异烟肼(52.83%,112/212)、卷曲霉素(28.77%,61/212)],差异均有统计学意义(χ ²值分别为16.721、46.987、10.628、6.793、10.930、7.986、16.370,P值均<0.05)。(3)logistic回归分析显示耐药的药品数目>7个[OR(95%CI)=9.328(2.058~42.290)]是克拉霉素耐药的危险因素。结论耐药肺结核患者克拉霉素的耐药率低于其他常用抗结核药物,多发生在耐多药/广泛耐药患者,耐药的药品数目>7个是患者对克拉霉素产生耐药的主要危险因素。

关键词: 结核, 肺, 克拉霉素, 抗结核药, 抗药性, 因素分析, 统计学

Abstract:

Objective To analyze the clarithromycin resistance and related risk factors in drug-resistant tuberculosis patients, and provide reference for the clinical application of clarithromycin. Methods The clinical data and drug sensitivity test results (referred to as “drug sensitivity tests”) of 254 patients diagnosed with drug-resistant tuberculosis in Beijing Chest Hospital affiliated to Capital Medical University from January 2017 to January 2018 were collected for retrospective analysis. Among them, the sensitivity of 16 kinds of antituberculosis drugs including clarithromycin was tested using the proportional method. Logistic regression was used to analyze clinical relevant influencing factors for clarithromycin resistance. Results (1) Among 254 patients with drug-resistant tuberculosis, 17 multi-drug resistant/extensive drug-resistant patients were resistant to clarithromycin, and the drug resistance rate was 6.69% (17/254), which was lower than the remaining 15 anti-tuberculosis drugs (12.60% (32/254) to 95.67% (243/254)). (2) The drug resistance rates of moxifloxacin (47.06%, 8/17), clofazimine (70.59%, 12/17), ethambutol (82.35%, 14/17), amikacin (52.94%,9/17), p-aminosalicylic acid (76.47%,13/17), para-aminosalicylic acid isoniazid (88.24%,15/17), and capreomycin (76.47%,13/17) of MDR/XDR-TB patients were higher in the clarithromycin-resistant group than that in the sensitive group (moxifloxacin (11.32%, 24/212), clofazimine (9.91%, 21/212), ethambutol (41.51%, 88/212), amikacin (21.70%, 46/212), P-aminosalicylic acid (35.85%, 76/212), para-aminosalicylic acid isoniazid (52.83%, 112/212), capreomycin (28.77%, 61/212), the differences were statistically significant (χ ² values were separately 16.721,46.987,10.628,6.793,10.930,7.986,16.370,P values were all <0.05). (3) Logistic regression results showed that the number of resistant drugs exceeding seven (OR(95%CI)=9.328 (2.058-42.290) was the risk factor for clarithromycin resistance. Conclusion The drug resistance rate of clarithromycin in drug-resistant tuberculosis patients is lower than that of other commonly used anti-tuberculosis drugs. It occurs more common in multidrug-resistant/extensive multidrug-resistant patients. The number of resistant drugs exceeding 7 is the main risk factor for patients resistant to clarithromycin.

Key words: Tuberculosis, pulmonary, Clarithromycin, Antitubercular agents, Drug resistance, Factor analysis, statistical

高天慧,舒薇,高静韬,陆宇,李琦. 254例耐药肺结核患者克拉霉素耐药情况及影响因素分析[J]. 中国防痨杂志, 2020, 42(3): 259-265. doi: 10.3969/j.issn.1000-6621.2020.03.015

GAO Tian-hui,SHU Wei,GAO Jing-tao,LU Yu,LI Qi. Analysis of clarithromycin resistance and its influencing factors in 254 patients with drug-resistant tuberculosis[J]. Chinese Journal of Antituberculosis, 2020, 42(3): 259-265. doi: 10.3969/j.issn.1000-6621.2020.03.015

图/表 5

表1

表2

表3

表4

表5

MDR/XDR-TB患者Clr耐药影响因素的logistic回归分析

自变量	β值	$s x ˉ$ 值	Wald χ²值	P值	OR值	95%CI值
耐药数目>7个	2.233	0.771	8.384	0.004	9.328	2.058~42.290
常量	-4.142	0.716	33.466	<0.001	0.016

表5

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药品	耐药肺结核患者(254例)		MDR/XDR-TB组(229例)		MR-TB组(25例)
药品	例数	耐药率(%)	例数	耐药率(%)	例数	耐药率(%)
Clr	17	6.69	17	7.42	0	0.00
Lfx	94	37.01	94	41.05	0	0.00
Mfx	32	12.60	32	13.97	0	0.00
Cfz	33	12.99	33	14.41	0	0.00
EMB	104	40.94	102	44.54	2	8.00
Am	55	21.65	55	24.02	0	0.00
Sm	198	77.95	198	86.46	0	0.00
Pto	50	19.69	50	21.83	0	0.00
PAS	89	35.04	89	38.86	0	0.00
Pa	127	50.00	127	55.46	0	0.00
Km	59	23.23	59	25.76	0	0.00
Cm	74	29.13	74	32.31	0	0.00
RFP	218	85.83	211	92.14	7	28.00
Rpt	226	88.98	217	94.76	9	36.00
Rfb	197	77.56	190	82.97	7	28.00
INH	243	95.67	229	100.00	14	56.00

药品	Clr敏感组(212例)	Clr耐药组(17例)	χ²值	P值
Lfx	84(39.62)	10(58.82)	2.398	0.122
Mfx	24(11.32)	8(47.06)	16.721	<0.01
Cfz	21(9.91)	12(70.59)	46.987	<0.01
EMB	88(41.51)	14(82.35)	10.628	0.001
Pto	47(22.17)	3(17.65)	0.017	0.897
Am	46(21.70)	9(52.94)	6.793	0.009
Sm	183(86.32)	15(88.24)	0.000	1.000
PAS	76(35.85)	13(76.47)	10.930	0.001
Pa	112(52.83)	15(88.24)	7.986	0.005
Km	50(23.58)	8(47.06)	3.428	0.072
Cm	61(28.77)	13(76.47)	16.370	<0.01

临床因素	Clr敏感组(212例)		Clr耐药组(17例)		χ²值		P值
性别					1.168		0.377
男	162(76.42)		11(64.71)
女	50(23.58)		6(35.29)
年龄组(岁)					-0.932		0.351
16~	40(18.88)		6(35.30)
26~	49(23.11)		2(11.76)
36~	25(11.79)		3(17.65)
46~	49(23.11)		2(11.76)
≥56	49(23.11)		4(23.53)
病程(月)					0.136		0.712
≤36	122(57.55)		9(52.94)
>36	90(42.45)		8(47.06)
耐药数目(个)					12.711		<0.001
≤7	120(56.60)		2(11.76)
>7	92(43.40)		15(88.24)
BMI					-1.048		0.295
无数据	15(7.07)		1(5.88)
<18.50	57(26.89)		7(41.18)
18.50~	115(54.25)		8(47.06)
≥25.00	25(11.79)		1(5.88)
临床因素		Clr敏感组(212例)		Clr耐药组(17例)		χ²值		P值
吸烟史						0.124		0.801
无		128(60.38)		11(64.71)
有		84(39.62)		6(35.29)
并发病毒性肝炎		13(6.13)		4(23.53)		6.931		0.027
患者类型						0.293		0.769
初治		50(23.58)		5(29.41)
复治		162(76.42)		12(70.59)
既往Clr治疗史						0.138		0.756
有		32(15.09)		2(11.76)
无		180(84.91)		15(88.24)
痰GeneXpert-rpoB突变结果						2.515		0.133
有		188(88.68)		14(82.35)
无		24(11.32)		3(17.65)
CT扫描显示是否有空洞						1.798		0.180
有		114(53.77)		12(70.59)
无		98(46.23)		5(29.41)

变量	赋值
因变量
Clr耐药与否	Clr敏感=1;Clr耐药=2
自变量
耐药数目	≤7个=1;>7个=2
并发病毒性肝炎	无=1;有=2