Abstract：This study is aimed to analyze the drug-susceptibility of bedaquiline and delamanid in multidrug-resistant Mycobacterium tuberculosis in Chongqing, in order to provide reference for the proper use of bedaquiline and delamanid in clinical treatment. A total of 111 MDR-TB strains isolated from Chongqing Public Health Medical Center during Nov. 2017 to Nov. 2018 were collected. Minimum inhibitory concentrations (MIC) of Bdq and Dlm against these isolates were detected and analyzed. Drug susceptibility test of Bdq for 111 MDR-TB isolates with the MIC50 and MIC90 was 0.016 mg/L and 0.125 mg/L, and drug resistant rate of Bdq was 4.50% (5/111). Drug susceptibility test of Dlm for 109 MDR-TB isolates indicated that the MIC50 and MIC90 was 0.016 mg/L and 0.063 mg/L, and drug resistant rate of Dlm was 4.59% (5/109). There was no significant difference in Bdq and Dlm resistance between MDR-TB and the other groups of different drug resistance. In conclusion, most of the MDR-TB clinical isolates in Chongqing are susceptible to Bdq and Dlm, however, primary resistance has been already existed. Therefore, it is still necessary to pay attention to the drug susceptibility test of new drugs when developing MDR-TB treatment regimens.
罗明, 张汇征, 严晓峰, 曹培明, 廖传玉, 何瑛, 李晓旭, 王静, 李同心, 陈耀凯. 重庆市耐多药结核分枝杆菌对贝达喹啉和德拉马尼的药物敏感性研究[J]. 中国人兽共患病学报, 2020, 36(2): 100-104.
LUO Ming, ZHANG Hui-zheng, YAN Xiao-feng, CAO Pei-ming, LIAO Chuan-yu, HE Ying, LI Xiao-xu, WANG Jing, LI Tong-xin, CHEN Yao-kai. Analysis of drug-susceptibility of bedaquiline and delamanid against multidrug-resistant Mycobacterium tuberculosis in Chongqing. Chinese Journal of Zoonoses, 2020, 36(2): 100-104.
[1] World Health Organization. Global tuberculosis report 2019[M]. Geneva: World Health Organization, 2019. https://www.who.int/tb/publications/global_report/en/ [2] 中华医学会结核病学分会. 抗结核新药贝达喹啉临床应用专家共识 [J]. 中华结核和呼吸杂志, 2018, 6(41): 461-466. DOI: 10.3760/cma.j.issn.1001-0939.2018.06.005 [3] Diacon AH, Pym A, Grobusch M, et al. The diarylquinoline TMC207 for multidrug-resistant tuberculosis [J]. N Engl J Med, 2009, 360(23): 2397-2405. DOI: 10.1056/NEJMoa0808427 [4] Gler MT, Skripconoka V, Sanchez-Garavito E, et al. Delamanid for multidrug-resistant pulmonary tuberculosis [J]. N Engl J Med, 2012, 366(23): 2151-60. DOI: 10.1056/NEJMoa1112433 [5] 中国防痨协会基础专业委员会. 结核病诊断实验室检验规程 [M]. 北京: 中国教育文化出版社, 2006. [6] World Health Organization. Companion handbook to the WHO guidelines for the programmatic management of drug-resistant tuberculosis [M]. Geneva: World Health Organization, 2014. https://www.who.int/tb/publications/pmdt_companionhandbook/en/ [7] Pang Y, Zong Z, Huo F, et al. In vitro drug susceptibility of bedaquiline, delamanid, linezolid, clofazimine, moxifloxacin, and gatifloxacin against extensively drug-resistant tuberculosis in Beijing, China [J]. Antimicrob Agents Chemother, 2017, 61(10): e00900-17. DOI: 10.1128/AAC.00900-17 [8] Testing TECOAS. Breakpoint tables for interpretation of MICs and zone diameters[M]. Version 9.0, 2019. http://www.eucast.org. [9] World Health Organization. Technical report on critical concentrations for TB drug susceptibility testing of medicines used in the treatment of drug-resistant TB [M]. Geneva: World Health Organization, 2018. https://www.who.int/tb/publications/2018/WHO_technical_report_concentrations_TB_drug_susceptibility/en/ [10] Lakshmanan M, Xavier AS. Bedaquiline- The first ATP synthase inhibitor against multi drug resistant tuberculosis [J]. J Young Pharm, 2013, 5(4): 112-115. DOI: 10.1016/j.jyp.2013.12.002 [11] GOEL D. Bedaquiline: A novel drug to combat multiple drug-resistant tuberculosis [J]. J Pharmacol Pharmacother, 2014, 5(1): 76-78. DOI: 10.4103/0976-500X.124435 [12] Field SK, Fisher D, Jarand JM, et al. New treatment options for multidrug-resistant tuberculosis [J]. Ther Adv Respir Dis, 2012, 6(5): 255-68. DOI: 10.1177/1753465812452193 [13] Esposito S, Bianchini S, Blasi F. Bedaquiline and delamanid in tuberculosis [J]. Expert Opin Pharmacother, 2015, 16(15): 2319-30. DOI: 10.1517/14656566.2015.1080240 [14] World Health Organization. WHO consolidated guidelines on drug-resistant tuberculosis treatment [M]. Geneva:World Health Organization,2019. https://www.who.int/tb/publications/2019/consolidated-guidelines-drug-resistant-TB-treatment/en/ [15] Li Y, Sun F, Zhang W. Bedaquiline and delamanid in the treatment of multidrug-resistant tuberculosis: Promising but challenging [J]. Drug Dev Res, 2019, 80(1): 98-105. DOI: 10.1002/ddr.21498 [16] Ismail NA, Omar SV, Joseph L, et al. Defining bedaquiline susceptibility, resistance, cross-resistance and associated genetic determinants: a retrospective cohort study [J]. E Bio Medicine, 2018, 28: 136-42. DOI: 10.1016/j.ebiom.2018.01.005 [17] 胡彦, 郑惠文, 赵雁林, 等. 耐多药结核分枝杆菌对贝达喹啉的耐药性及其与基因型关系分析[J]. 中华微生物学和免疫学杂志, 2016, 36(12):906-911. DOI: 10.3760/cma.j.issn.0254-5101.2016.12.005 [18] Yang JS, Kim KJ, Choi H, et al. Delamanid, bedaquiline, and linezolid minimum inhibitory concentration distributions and resistance-related gene mutations in multidrug-resistant and extensively drug-resistant tuberculosis in Korea [J]. Ann Lab Med, 2018, 38(6): 563-68. DOI: 10.3343/alm.2018.38.6.563 [19] Hoffmann H, Kohl TA, Hofmann-Thiel S, et al. Delamanid and bedaquiline resistance in Mycobacterium tuberculosis ancestral Beijing genotype causing extensively drug-resistant tuberculosis in a Tibetan Refugee [J]. Am J Respir Crit Care Med, 2016, 193(3): 337-40. DOI: 10.1164/rccm.201502-0372LE [20] Andries K, Villellas C, Coeck N, et al. Acquired resistance of Mycobacterium tuberculosis to bedaquiline [J]. PLoS One, 2014, 9(7): e102135-e. DOI: 10.1371/journal.pone.0102135 [21] Hartkoorn RC, Uplekar S, Cole ST. Cross-resistance between clofazimine and bedaquiline through upregulation of MmpL5 in Mycobacterium tuberculosis [J]. Antimicrob Agents Chemother, 2014, 58(5): 2979-81. DOI: 10.1128/AAC.00037-14 [22] Zumla A, Nahid P, Cole ST. Advances in the development of new tuberculosis drugs and treatment regimens [J]. Nat Rev Drug Discov, 2013, 12(5): 388-404. DOI: 10.1038/nrd4001
2020, Vol. 36 
