Analysis of drug resistance to bedaquiline, delamanid and linezolid in patients with pulmonary tuberculosis

doi:10.19982/j.issn.1000-6621.20260349

Abstract

Abstract:

Objective: To investigate the characteristics of drug resistance to bedaquiline (Bdq), delamanid (Dlm) and linezolid (Lzd) in patients with pulmonary tuberculosis, and to provide evidence for clinicians to develop individualized treatment regimens for drug-resistant pulmonary tuberculosis cases. Methods: A retrospective study was conducted. Clinical data of 445 outpatient and inpatient pulmonary tuberculosis patients admitted to Beijing Chest Hospital, Capital Medical University from March to December 2025 were collected, including gender, age, occupation, residential area, medical history, treatment regimens and drug susceptibility testing (DST) results. DST was performed with the mycobacterial microplate drug susceptibility testing technique to determine the susceptibility of clinically isolated Mycobacterium tuberculosis strains to 16 anti-tuberculosis agents: isoniazid, rifampicin, ethambutol, Dlm, Bdq, rifabutin, levofloxacin, moxifloxacin, kanamycin, amikacin, cycloserine, protionamide, para-aminosalicylic acid, Lzd, pyrazinamide and clofazimine. We analyzed the baseline characteristics, initial/retreatment status and overall drug resistance profile of the enrolled patients, as well as the resistance rates to Bdq, Dlm and Lzd among patients with prior exposure to these drugs. Results: Among the 445 patients, the overall drug resistance rate to the 16 anti-tuberculosis drugs was 47.9% (213/445), with a rifampicin-resistant tuberculosis rate of 30.1% (134/445),a multidrug-resistant tuberculosis rate of 23.4% (104/445) and an extensively drug-resistant tuberculosis rate of 3.8% (17/445). The resistance rates to Bdq, Dlm and Lzd were 2.7% (12/445), 4.0% (18/445) and 3.8% (17/445), respectively. Retreated patients had significantly higher resistance rates to all three drugs than treatment-naive patients (Bdq: 6.4% (11/171) vs. 0.4% (1/274); Dlm: 7.0% (12/171) vs. 2.2% (6/274); Lzd: 8.8% (15/171) vs. 0.7% (2/274)), with statistically significant differences (χ²=12.552, 6.323 and 16.409, respectively; all P<0.05). The resistance rates to Bdq, Dlm and Lzd in MDR/RR-TB patients were significantly higher than those in non-rifampicin-resistant patients (Bdq: 6.7% (9/134) vs. 1.0% (3/311); Dlm: 7.5% (10/134) vs. 2.6% (8/311); Lzd: 11.9% (16/134) vs. 0.3% (1/311)), with statistically significant differences (χ²=9.717, 5.770 and 31.318, respectively; all P<0.05). Among MDR/RR-TB patients, the co-resistance rates of Bdq+Dlm, Bdq+Lzd, Dlm+Lzd and Bdq+Dlm+Lzd were 4.5% (6/134), 3.7% (5/134), 5.2% (7/134) and 3.0% (4/134), respectively. The Bdq resistance rate in patients with prior Bdq exposure was 8.4% (8/95), significantly higher than that in Bdq-naive patients (1.1% (4/350)). The Dlm resistance rate in patients with prior Dlm exposure reached 9.1% (7/77), significantly higher than that in Dlm-naive patients (3.0% (11/368)). The Lzd resistance rate in patients with prior Lzd exposure was 13.8% (11/80), significantly higher than that in Lzd-naive patients (1.6% (6/365)). All above differences were statistically significant (χ²=12.438, 6.108 and 26.174, respectively; all P<0.05). Conclusion: The overall resistance rates to Bdq, Dlm and Lzd remain relatively low in pulmonary tuberculosis patients. However, higher resistance rates are observed in retreated patients, MDR/RR-TB patients and patients with prior exposure to these new agents. The resistance rate in drug-exposed patients is significantly higher than that in drug-naive patients, indicating that drug resistance monitoring should be intensified during the clinical application of new anti-tuberculosis drugs.

Key words: Tuberculosis, pulmonary, Microbial sensitivity tests, Drug resistance, bacterial, Antitubercular agents

CLC Number:

R521

Su Dahong, Li Xiaoli, Yang Bin, Shi Yiheng, Lin Weibing, Miao Tiantian, Zhao Jinfeng, Ma Shang, Huo Fengmin, Wang Guirong. Analysis of drug resistance to bedaquiline, delamanid and linezolid in patients with pulmonary tuberculosis[J]. Chinese Journal of Antituberculosis, 2026, 48(10): 1523-1530. doi: 10.19982/j.issn.1000-6621.20260349

Figures/Tables 7

References 29

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药品	敏感	中介	耐药	药品	敏感	中介	耐药
利福平	≤0.5	-	≥1	卡那霉素	-	-	≥4
异烟肼	-	-	≥0.2	阿米卡星	-	-	≥1
乙胺丁醇	≤2	4	≥8	环丝氨酸	-	-	≥16
德拉马尼	-	-	≥0.06	丙硫异烟胺	-	-	≥10
贝达喹啉	-	-	≥0.25	对氨基水杨酸	-	-	≥2
利福布汀	-	-	≥0.5	利奈唑胺	-	-	≥1
左氧氟沙星	-	-	≥1	吡嗪酰胺	≤50	-	≥100
莫西沙星	-	-	≥0.5	氯法齐明	-	-	≥0.25

项目	合计 (445例)	初治患者 (274例)	复治患者 (171例)
性别[例(构成比,%)]
男性	281(63.1)	165(60.2)	116(67.8)
女性	164(36.9)	109(39.8)	55(32.2)
年龄组[例(构成比,%)]
10~19岁	19(4.3)	13(4.7)	6(3.5)
20~29岁	40(9.0)	25(9.1)	15(8.8)
30~39岁	69(15.5)	44(16.1)	25(14.6)
40~49岁	48(10.8)	34(12.4)	14(8.2)
50~59岁	70(15.7)	37(13.5)	33(19.3)
60~69岁	95(21.4)	57(20.8)	38(22.2)
70~79岁	57(12.8)	32(11.7)	25(14.6)
80~89岁	41(9.2)	29(10.6)	12(7.0)
≥90岁	6(1.3)	3(1.1)	3(1.8)
居住地[例(构成比,%)]
东部	262(58.9)	183(66.8)	79(46.2)
中部	153(34.4)	73(26.6)	80(46.8)
西部	30(6.7)	18(6.6)	12(7.0)
基础疾病[例(患病率,%)]
低蛋白血症	86(19.3)	52(19.0)	34(19.9)
贫血	93(20.9)	52(19.0)	41(24.0)
高尿酸血症	99(22.2)	71(25.9)	28(16.4)
高血压	63(14.2)	40(14.6)	23(13.5)
糖尿病	115(25.8)	67(24.5)	48(28.1)
营养不良	37(8.3)	20(7.3)	17(9.9)
职业[例(构成比,%)]
农民	44(9.9)	22(8.0)	22(12.9)
退(离)休人员	30(6.7)	15(5.5)	15(8.8)
干部职员	4(0.9)	2(0.7)	2(1.2)
工人	7(1.6)	3(1.1)	4(2.3)
学生	15(3.4)	9(3.3)	6(3.5)
其他^a	345(77.5)	223(81.4)	122(71.3)

肺外结核	合计 (445例)	初治患者 (274例)	复治患者 (171例)
疾病种类[例(患病率,%)]
结核性脑膜脑炎	5(1.1)	2(0.7)	3(1.8)
脊椎结核	3(0.7)	1(0.4)	2(1.2)
淋巴结结核	3(0.7)	2(0.7)	1(0.6)
肾结核	1(0.2)	0(0.0)	1(0.6)
肠结核	2(0.4)	2(0.7)	0(0.0)
泌尿系结核	2(0.4)	2(0.7)	0(0.0)
结核性脊髓脊膜炎	1(0.2)	1(0.4)	0(0.0)
胸壁结核	1(0.2)	1(0.4)	0(0.0)
喉结核	3(0.7)	1(0.4)	2(1.2)
结核性腹膜炎	1(0.2)	1(0.4)	0(0.0)
皮肤结核	1(0.2)	1(0.4)	0(0.0)
涉及部位[例(比例,%)]
≥2个	106(23.8)	74(27.0)	32(18.7)
≥3个	10(2.2)	6(2.2)	4(2.3)

耐药类型	合计(445例)	初治患者(274例)	复治患者(171例)	χ²值	P值
总耐药	213(47.9)	109(39.8)	104(60.8)	18.674	<0.001
单耐药	42(9.4)	26(9.5)	16(9.4)	0.002	0.963
利福平耐药	134(30.1)	53(19.3)	81(47.4)	39.296	<0.001
耐多药	104(23.4)	40(14.6)	64(37.4)	30.639	<0.001
多耐药	40(9.0)	20(7.3)	20(11.7)	2.488	0.115
广泛耐药	17(3.8)	2(0.7)	15(8.8)	16.409	<0.001^a

药品	合计(445例)	初治患者(274例)	复治患者(171例)	χ²值	P值
异烟肼	141(31.7)	62(22.6)	79(46.2)	27.025	<0.001
利福平	134(30.1)	53(19.3)	81(47.4)	39.296	<0.001
莫西沙星	105(23.6)	44(16.1)	61(35.7)	22.469	<0.001
利福布汀	99(22.2)	40(14.6)	59(34.5)	24.115	<0.001
左氧氟沙星	98(22.0)	39(14.2)	59(34.5)	25.190	<0.001
吡嗪酰胺	81(18.1)	38(13.9)	43(25.1)	8.994	0.003
卡那霉素	32(7.2)	12(4.4)	20(11.7)	8.445	0.004
对氨基水杨酸	31(7.0)	13(4.7)	18(10.5)	5.431	0.020
氯法齐明	26(5.7)	12(4.4)	14(8.2)	3.109	0.078
阿米卡星	24(5.4)	9(3.3)	15(8.8)	6.213	0.013
德拉马尼	18(4.0)	6(2.2)	12(7.0)	6.323	0.012
利奈唑胺	17(3.8)	2(0.7)	15(8.8)	16.409	<0.001^a
乙胺丁醇	15(3.4)	7(2.6)	8(4.7)	1.458	0.227
贝达喹啉	12(2.7)	1(0.4)	11(6.4)	12.552	<0.001^a
丙硫异烟胺	9(2.0)	3(1.1)	6(3.4)	1.998	0.158^a
环丝氨酸	3(0.7)	1(0.4)	2(1.2)	0.171	0.679^a
任一耐药	213(47.9)	109(39.8)	104(60.8)	18.674	<0.001