Analysis of fluoroquinolones resistance in multidrug-resistant tuberculosis patients in Chongqing from 2020 to 2022

doi:10.19983/j.issn.2096-8493.20230099

Abstract

Abstract:

Objective: To analyze the resistance of multidrug-resistant tuberculosis (MDR-TB) patients to fluoroquinolones (FQs) and its influencing factors in Chongqing. Methods: A simple random sampling method was used in 165 MDR-TB patients from 39 districts (counties) in Chongqing from January 2020 to December 2022 (study subjects), and basic information of the study subjects was collected. All the 165 strains of multidrug-resistant Mycobacterium tuberculosis (MDR-MTB) isolated from the study subjects were confirmed through strain identification and proportional drug sensitivity testing. Using the micro broth dilution method, the drug sensitivities of clinical isolates to ofloxacin (Ofx), levofloxacin (Lfx), and moxifloxacin (Mfx) were tested, and the drug resistance of the strains to FQs and related influencing factors were analyzed. Results: The total resistance rate of 165 MDR-MTB isolates to FQs was 37.6% (62/165), and the resistance rates to Ofx, Lfx, and Mfx were 37.6% (62/165), 37.0% (61/165), and 29.7% (49/165), respectively. Multivariate logistic regression analysis showed that no history of FQs medication was a protective factor for FQs resistance (OR (95%CI)=0.348 (0.169-0.717)). Conclusion: The FQs resistance rate of MDR-TB patients in Chongqing is relatively high, and patients with a history of FQs medication have a higher risk of FQs resistance.

Key words: Mycobacterium tuberculosis, Quinolones, Drug resistance, multiple, Risk factors

CLC Number:

R521
R825.2

You Guoqing, Liu Wenguo, Feng Xin, Yu Min, Shi Lin, Hu Yan. Analysis of fluoroquinolones resistance in multidrug-resistant tuberculosis patients in Chongqing from 2020 to 2022[J]. Journal of Tuberculosis and Lung Disease , 2023, 4(6): 475-479. doi: 10.19983/j.issn.2096-8493.20230099

Figures/Tables 4

因素	β值	s $x ˉ$ 值	Wald χ²值	P值	OR(95%CI)值
无氟喹诺酮类药物用药史	-1.506	0.369	8.201	0.004	0.348(0.169~0.717)
链霉素耐药	0.800	0.398	4.037	0.045	2.226(1.020~4.859)
职业(以“家务及待业组”为参照)
农民	0.095	0.529	0.033	0.857	1.100(0.390~3.105)
民工	2.434	1.217	3.999	0.046	11.408(1.050~123.984)
其他^a	0.612	0.645	0.898	0.343	1.843(0.520~6.532)

References 17

[1]	World Health Organization. Global tuberculosis report 2022. Geneva: World Health Organization, 2022.
[2]	首都医科大学附属北京胸科医院/北京市结核病胸部肿瘤研究所, 中国防痨协会, 《中国防痨杂志》编辑委员会. 耐药肺结核全口服化学治疗方案中国专家共识(2021年版). 中国防痨杂志, 2021, 43(9):859-866. doi:10.3969/j.issn.1000-6621.2021.09.002.
[3]	World Health Organization. Meeting report of the WHO expert consultation on the definition extensively drug-resistant tuberculosis, 27-29 October 2020. Geneva: World Health Organization, 2021.
[4]	Zhang Z, Lu J, Wang Y, et al. Prevalence and molecular chara-cterization of fluoroquinolone-resistant Mycobacterium tuberculosis isolates in China. Antimicrob Agents Chemother, 2014, 58(1):364-369. doi:10.1128/AAC.01228-13.
[5]	Li Y. China’s misuse of antibiotics should be curbed. BMJ, 2014, 348:g1083. doi:10.1136/bmj.g1083.
[6]	Hu Y, Liu J, Shen J, et al. Genotyping and Molecular Chara-cterization of Fluoroquinolone’s Resistance Among Multidrug-Resistant Mycobacterium tuberculosis in Southwest of China. Microb Drug Resist, 2021, 27(7):865-870. doi:10.1089/mdr.2019.0339.
[7]	赵雁林, 陈明亭. 中国结核病防治工作技术指南. 北京: 人民卫生出版社, 2021.
[8]	Clinical and Laboratory Standards Institute. Performance Standards for Susceptibility Testing of Mycobacteria, Nocardia spp., and Other Aerobic Actinomycetes. 2nd ed. Los Angeles: Clinical and Laboratory Standards Institute, 2023.
[9]	World Health Organization. WHO treatment guidelines for multidrug- and rifampicin-resistant tuberculosis, 2018 update. Geneva: World Health Organization, 2018.
[10]	World Health Organization. WHO consolidated guidelines on tuberculosis: module 4: treatment: drug-resistant tuberculosis treatment. Geneva: World Health Organization, 2020.
[11]	马进宝, 任斐, 曾令城, 等. 2015—2019年西安市680例耐多药结核病患者耐药情况分析. 中国防痨杂志, 2020, 42(6):609-613. doi:10.3969/j.issn.1000-6621.2020.06.013.
[12]	季乐财, 张乐平, 吕建文, 等. 全基因组测序预测深圳市耐多药结核分枝杆菌的耐药性分析. 中国防痨杂志, 2021, 43(2):166-170. doi:10.3969/j.issn.1000-6621.2021.02.012.
[13]	石文卉, 初乃惠. 耐药肺结核患者氟喹诺酮类药物耐药情况及影响因素. 中国防痨杂志, 2021, 43(9):905-909. doi:10.3969/j.issn.1000-6621.2021.09.009.
[14]	梁雅雪, 王华. 耐多药肺结核患者氟喹诺酮耐药因素分析. 实用医学杂志, 2022, 38(13):1604-1608. doi:10.3969/j.issn.1006-5725.2022.13.007.
[15]	Pang Y, Zhang Z, Wang Y, et al. Genotyping and Prevalence of Pyrazinamide- and Moxifloxacin-Resistant Tuberculosis in China, 2000 to 2010. Antimicrob Agents Chemother, 2017, 61(2):e02170-16. doi:10.1128/AAC.02170-16.
[16]	Hu Y, Chi Y, Feng X, et al. Comparison of the Diagnostic Performance of MeltPro and Next-Generation Sequencing in Determining Fluoroquinolone Resistance in Multidrug-Resistant Tuberculosis Isolates. J Mol Diagn, 2023, 25(6):342-351. doi:10.1016/j.jmoldx.2023.02.003. pmid: 37208048
[17]	Bernard C, Veziris N, Brossier F, et al. Molecular diagnosis of fluoroquinolone resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother, 2015, 59(3):1519-1524. doi:10.1128/AAC.04058-14.

氟喹诺酮类药物	最低抑菌浓度(株)											临界浓度 (μg/ml)	耐药 [株(耐药率,%)]
氟喹诺酮类药物	≤0.03 μg/ml	0.06 μg/ml	0.125 μg/ml	0.25 μg/ml	0.5 μg/ml	1 μg/ml	2 μg/ml	4 μg/ml	8 μg/ml	16 μg/ml	≥32 μg/ml	临界浓度 (μg/ml)	耐药 [株(耐药率,%)]
氧氟沙星	0	0	2	11	64	21	5	31	17	11	3	2	62(37.6)
左氧氟沙星	0	2	5	60	30	7	19	25	14	3	0	1	61(37.0)
莫西沙星	1	6	37	48	12	12	27	16	5	1	0	1	49(29.7)

因素	合计 (165例)	FQs^a耐药 (62例)	FQs敏感 (103例)	OR (95%CI)值	P值
性别[例(构成比,%)]
女性	34(20.6)	11(17.7)	23(22.3)	1.000
男性	131(79.4)	51(82.3)	80(77.7)	1.333(0.599~2.966)	0.480
年龄组[例(构成比,%)]
≤40岁	37(22.4)	17(27.4)	20(19.4)	1.000
41~59岁	68(41.2)	23(37.1)	45(43.7)	0.601(0.265~1.364)	0.222
≥60岁	60(36.4)	22(35.5)	38(36.9)	0.681(0.296~1.567)	0.365
治疗分类[例(构成比,%)]
初治	97(58.8)	34(54.8)	63(61.2)	1.000
复治	68(41.2)	28(45.2)	40(38.8)	1.297(0.685~2.455)	0.424
行政区划[例(构成比,%)]
主城区	76(46.1)	25(40.3)	51(49.6)	1.000
渝东北	42(25.4)	16(25.8)	26(25.2)	1.255(0.572~2.753)	0.570
渝东南	47(28.5)	21(33.9)	26(25.2)	1.648(0.780~3.482)	0.189
职业[例(构成比,%)]
农民	110(66.7)	39(62.9)	71(68.9)	1.491(0.576~3.857)	0.408
家务及待业	26(15.8)	7(11.3)	19(18.4)	1.000
民工	6(3.6)	5(8.1)	1(1.0)	13.571(1.340~137.454)	0.035
其他^b	23(13.9)	11(17.7)	12(11.7)	2.488(0.756~8.193)	0.130
糖尿病[例(构成比,%)]
无	132(80.0)	53(85.5)	79(76.7)	1.000
有	33(20.0)	9(14.5)	24(23.3)	0.559(0.241~1.297)	0.172
尘肺[例(构成比,%)]
无	157(95.1)	59(95.2)	98(95.1)	1.000
有	8(4.9)	3(4.8)	5(4.9)	0.997(0.230~4.323)	1.000
FQs用药史[例(构成比,%)]
否	119(72.1)	37(59.7)	82(79.6)	1.000
是	46(27.9)	25(40.3)	21(20.4)	2.638(1.313~5.303)	0.006
耐药情况[例(耐药率,%)]
链霉素	110(66.7)	49(79.0)	61(59.2)	2.595(1.255~5.368)	0.009
乙胺丁醇	19(11.5)	11(17.7)	8(7.8)	2.561(0.969~6.771)	0.052
对氨基水杨酸	43(26.1)	16(25.8)	27(26.2)	0.979(0.477~2.009)	0.954
阿米卡星	18(10.9)	9(14.5)	9(8.7)	1.774(0.663~4.742)	0.249

变量	赋值
氟喹诺酮类药物耐药情况	0=敏感;1=耐药
氟喹诺酮类药物用药史	0=无;1=有
链霉素耐药情况	0=敏感;1=耐药
职业	0=家务及待业;1=农民;2=民工;3=其他^a