Analysis of clarithromycin resistance and its influencing factors in 254 patients with drug-resistant tuberculosis

doi:10.3969/j.issn.1000-6621.2020.03.015

Abstract

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

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

Figures/Tables 5

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

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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