抗结核新药药效学特点及相互作用研究

doi:10.3969/j.issn.1000-6621.2021.09.018

摘要/Abstract

摘要：

结核病的治疗仍以化疗为主,现有的化疗方案存在疗程长、不良反应多、效果不佳等问题。临床迫切需要开发有效的药物组合方案以提高疗效和缩短疗程。作者对近些年上市和处于研究阶段的抗结核新药药效学特点及相互作用进行简要综述,为抗结核药物的研发及新的药物联合治疗方案提供借鉴。

关键词: 分枝杆菌,结核, 抗结核药, 药物疗法,联合, 综述文献(主题)

Abstract:

Treatment of tuberculosis currently still relies on chemotherapy,however,there are multitude problems in the existing chemotherapy regimens, such as long treatment course, various adverse reactions, and suboptimal outcomes.There is an urgent need to exploit potent drug combinations to improve the treatment efficacy and shorten the course of treatment.Herein, the pharmacodynamic characteristics and interactions of novel anti-tuberculosis drugs launched in recent years,as well as those in the research stage, are briefly reviewed to provide reference for the research and development of anti-tuberculosis drugs and new drug combination regimens.

Key words: Mycobacterium tuberculosis, Auti-tuberculosis drugs, Drug therapy,combination, Review literature as topic

祁雪婷, 陆宇, 陈效友. 抗结核新药药效学特点及相互作用研究[J]. 中国防痨杂志, 2021, 43(9): 965-969. doi: 10.3969/j.issn.1000-6621.2021.09.018

QI Xue-ting, LU Yu, CHEN Xiao-you. Pharmacodynamic characteristics and interaction of new antituberculosis drugs[J]. Chinese Journal of Antituberculosis, 2021, 43(9): 965-969. doi: 10.3969/j.issn.1000-6621.2021.09.018

参考文献 46

[1]	Harding E. WHO global progress report on tuberculosis elimination. Lancet Respir Med, 2020, 8(1):19. doi: 10.1016/S2213-2600(19)30418-7. doi: 10.1016/S2213-2600(19)30418-7 URL
[2]	邢丽, 田瑞飞, 慕杨娜. 肺结核治疗药物发展现状及合理应用. 临床合理用药杂志, 2020, 13(30):179-181. doi: 10.15887/j.cnki.13-1389/r.2020.30.077. doi: 10.15887/j.cnki.13-1389/r.2020.30.077
[3]	Caesar LK, Cech NB. Synergy and antagonism in natural product extracts:when 1+1 does not equal 2. Nat Prod Rep, 2019, 36(6):869-888. doi: 10.1039/c9np00011a. doi: 10.1039/c9np00011a URL
[4]	Maltempe FG, Caleffi-Ferracioli KR, do Amaral RCR, et al. Activity of rifampicin and linezolid combination in Mycobacterium tuberculosis. Tuberculosis (Edinb), 2017, 104:24-29. doi: 10.1016/j.tube.2017.02.004. doi: 10.1016/j.tube.2017.02.004 URL
[5]	Foo CS, Lechartier B, Kolly GS, et al. Characterization of DprE1-Mediated Benzothiazinone Resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother, 2016, 60(11):6451-6459. doi: 10.1128/AAC.01523-16. doi: 10.1128/AAC.01523-16 URL
[6]	Zhang G, Sheng L, Hegde P, et al. 8-cyanobenzothiazinone analogs with potent antitubercular activity. Medicinal Chemistry Research, 2021, 30(2):449-458. doi: 10.1007/s00044-020-02676-4. doi: 10.1007/s00044-020-02676-4 URL
[7]	Shi J, Lu J, Wen S, et al. In Vitro Activity of PBTZ169 against Multiple Mycobacterium Species. Antimicrob Agents Chemother, 2018, 62(11):e01314-18. doi: 10.1128/AAC.01314-18. doi: 10.1128/AAC.01314-18
[8]	Lechartier B, Hartkoorn RC, Cole ST. In vitro combination studies of benzothiazinone lead compound BTZ043 against Mycobacterium tuberculosis. Antimicrob Agents Chemother, 2012, 56(11):5790-5793. doi: 10.1128/AAC.01476-12. doi: 10.1128/AAC.01476-12 pmid: 22926573
[9]	Makarov V, Manina G, Mikusova K, et al. Benzothiazinones Kill Mycobacterium tuberculosis by Blocking Arabinan Synthesis. Science, 2009, 324(5928):801-804. doi: 10.1126/science.1171583. doi: 10.1126/science.1171583 pmid: 19299584
[10]	Makarov V, Lechartier B, Zhang M, et al. Towards a new combination therapy for tuberculosis with next generation benzothiazinones. EMBO Mol Med, 2014, 6(3):372-383. doi: 10.1002/emmm.201303575. doi: 10.1002/emmm.201303575 pmid: 24500695
[11]	Lupien A, Vocat A, Foo CS, et al. Optimized Background Regimen for Treatment of Active Tuberculosis with the Next-Generation Benzothiazinone Macozinone (PBTZ169). Antimicrob Agents Chemother, 2018, 62(11):e00840-18. doi: 10.1128/AAC.00840-18. doi: 10.1128/AAC.00840-18
[12]	Lechartier B, Cole ST. Mode of Action of Clofazimine and Combination Therapy with Benzothiazinones against Mycobacterium tuberculosis. Antimicrob Agents Chemother, 2015, 59(8):4457-4463. doi: 10.1128/AAC.00395-15. doi: 10.1128/AAC.00395-15 pmid: 25987624
[13]	Zhang Q, Liu Y, Tang S, et al. Clinical benefit of delamanid (OPC-67683) in the treatment of multidrug-resistant tuberculosis patients in China. Cell Biochem Biophys, 2013, 67(3):957-963. doi: 10.1007/s12013-013-9589-5. doi: 10.1007/s12013-013-9589-5 pmid: 23546935
[14]	Chandramohan Y, Padmanaban V, Bethunaickan R, et al. In vitro interaction profiles of the new antitubercular drugs bedaquiline and delamanid with moxifloxacin against clinical Mycobacterium tuberculosis isolates. J Glob Antimicrob Resist, 2019, 19:348-353. doi: 10.1016/j.jgar.2019.06.013. doi: S2213-7165(19)30157-2 pmid: 31226332
[15]	Matsumoto M, Hashizume H, Tomishige T, et al. OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice. PLoS Med, 2006, 3(11):e466. doi: 10.1371/journal.pmed.0030466. doi: 10.1371/journal.pmed.0030466 URL
[16]	Lee M, Mok J, Kim DK, et al. Delamanid, linezolid, levofloxacin, and pyrazinamide for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (Treatment Shortening of MDR-TB Using Existing and New Drugs, MDR-END): study protocol for a phase II/III, multicenter, randomized, open-label clinical trial. Trials, 2019, 20(1):57. doi: 10.1186/s13063-018-3053-1. doi: 10.1186/s13063-018-3053-1 URL
[17]	Stephanie F, Saragih M, Tambunan USF. Recent Progress and Challenges for Drug-Resistant Tuberculosis Treatment. Pharmaceutics, 2021, 13(5):592. doi: 10.3390/pharmaceutics13050592. doi: 10.3390/pharmaceutics13050592 URL
[18]	Wen S, Jing W, Zhang T, et al. Comparison of in vitro activity of the nitroimidazoles delamanid and pretomanid against multidrug-resistant and extensively drug-resistant tuberculosis. Eur J Clin Microbiol Infect Dis, 2019, 38(7):1293-1296. doi: 10.1007/s10096-019-03551-w. doi: 10.1007/s10096-019-03551-w URL
[19]	Tasneen R, Li SY, Peloquin CA, et al. Sterilizing activity of novel TMC207- and PA-824-containing regimens in a murine model of tuberculosis. Antimicrob Agents Chemother, 2011, 55(12):5485-5492. doi: 10.1128/AAC.05293-11. doi: 10.1128/AAC.05293-11 pmid: 21930883
[20]	Xu J, Li SY, Almeida DV, et al. Contribution of Pretomanid to Novel Regimens Containing Bedaquiline with either Linezolid or Moxifloxacin and Pyrazinamide in Murine Models of Tuberculosis. Antimicrob Agents Chemother, 2019, 63(5):e00021-19. doi: 10.1128/AAC.00021-19. doi: 10.1128/AAC.00021-19
[21]	Burki T. BPaL approved for multidrug-resistant tuberculosis. Lancet Infect Dis, 2019, 19(10):1063-1064. doi: 10.1016/S1473-3099(19)30489-X. doi: 10.1016/S1473-3099(19)30489-X URL
[22]	Reddy VM, Dubuisson T, Einck L, et al. SQ109 and PNU-100480 interact to kill Mycobacterium tuberculosis in vitro. J Antimicrob Chemother, 2012, 67(5):1163-1166. doi: 10.1093/jac/dkr589. doi: 10.1093/jac/dkr589 URL
[23]	Chen P, Gearhart J, Protopopova M, et al. Synergistic interactions of SQ109, a new ethylene diamine, with front-line antitubercular drugs in vitro. J Antimicrob Chemother, 2006, 58(2):332-337. doi: 10.1093/jac/dkl227. doi: 10.1093/jac/dkl227 URL
[24]	Lounis N, Vranckx L, Gevers T, et al. In vitro culture conditions affecting minimal inhibitory concentration of bedaquiline against M.tuberculosis. Med Mal Infect, 2016, 46(4):220-225. doi: 10.1016/j.medmal.2016.04.007. doi: 10.1016/j.medmal.2016.04.007 URL
[25]	Wallis RS, Jakubiec W, Mitton-Fry M, et al. Rapid evaluation in whole blood culture of regimens for XDR-TB containing PNU-100480 (sutezolid), TMC207, PA-824, SQ109, and pyrazinamide. PLoS One, 2012, 7(1):e30479. doi: 10.1371/journal.pone.0030479. doi: 10.1371/journal.pone.0030479 URL
[26]	Lounis N, Guillemont J, Veziris N, et al. R207910 (TMC207): un nouvel antibiotique pour le traitement de la tuberculose [R207910 (TMC207): a new antibiotic for the treatment of tuberculosis]. Med Mal Infect, 2010, 40(7):383-390. doi: 10.1016/j.medmal.2009.09.007. doi: 10.1016/j.medmal.2009.09.007 URL
[27]	首都医科大学附属北京胸科医院, 中国防痨协会临床试验专业分会, 中国防痨杂志编辑委员会. 氯法齐明治疗结核病的临床应用指南. 中国防痨杂志, 2020, 42(5):409-417. doi: 10.3969/j.issn.1000-6621.2020.05.001. doi: 10.3969/j.issn.1000-6621.2020.05.001
[28]	Yu W, Chiwala G, Gao Y, et al. TB47 and clofazimine form a highly synergistic sterilizing block in a second-line regimen for tuberculosis in mice. Biomed Pharmacother, 2020, 131:110782. doi: 10.1016/j.biopha.2020.110782. doi: 10.1016/j.biopha.2020.110782 URL
[29]	Lee BY, Clemens DL, Silva A, et al. Ultra-rapid near universal TB drug regimen identified via parabolic response surface platform cures mice of both conventional and high susceptibility. PLoS One, 2018, 13(11):e0207469. doi: 10.1371/journal.pone.0207469. doi: 10.1371/journal.pone.0207469 URL
[30]	Tyagi S, Ammerman NC, Li SY, et al. Clofazimine shortens the duration of the first-line treatment regimen for experimental chemotherapy of tuberculosis. Proc Natl Acad Sci U S A, 2015, 112(3):869-874. doi: 10.1073/pnas.1416951112. doi: 10.1073/pnas.1416951112 URL
[31]	张叶, 陆宇. 亚胺吩嗪类药物抗结核作用研究进展. 中华结核和呼吸杂志, 2019, 42(2):118-121. doi: 10.3760/cma.j.issn.1001-0939.2019.02.008. doi: 10.3760/cma.j.issn.1001-0939.2019.02.008
[32]	Zhang D, Liu Y, Zhang C, et al. Synthesis and biological evaluation of novel 2-methoxypyridylamino-substituted riminophenazine derivatives as antituberculosis agents. Molecules, 2014, 19(4):4380-4394. doi: 10.3390/molecules19044380. doi: 10.3390/molecules19044380 URL
[33]	Zhang Y, Zhu H, Fu L, et al. Identifying Regimens Containing TBI-166, a New Drug Candidate against Mycobacterium tuberculosis In Vitro and In Vivo. Antimicrob Agents Chemother, 2019, 63(7):e02496-18. doi: 10.1128/AAC.02496-18. doi: 10.1128/AAC.02496-18
[34]	Wang A, Wang H, Geng Y, et al. Design, synthesis and antimycobacterial activity of less lipophilic Q203 derivatives containing alkaline fused ring moieties. Bioorg Med Chem, 2019, 27(5):813-821. doi: 10.1016/j.bmc.2019.01.022. doi: 10.1016/j.bmc.2019.01.022 URL
[35]	Pethe K, Bifani P, Jang J, et al. Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis. Nat Med, 2013, 19(9):1157-1160. doi: 10.1038/nm.3262. doi: 10.1038/nm.3262 URL
[36]	Lee BS, Hards K, Engelhart CA, et al. Dual inhibition of the terminal oxidases eradicates antibiotic-tolerant Mycobacterium tuberculosis. EMBO Mol Med, 2021, 13(1):e13207. doi: 10.15252/emmm.202013207. doi: 10.15252/emmm.202013207
[37]	Yang C, Lei H, Wang D, et al. In vitro activity of linezolid against clinical isolates of Mycobacterium tuberculosis, including multidrug-resistant and extensively drug-resistant strains from Beijing, China. Jpn J Infect Dis, 2012, 65(3):240-242. doi: 10.7883/yoken.65.240. doi: 10.7883/yoken.65.240 URL
[38]	Zhao W, Zheng M, Wang B, et al. Interactions of linezolid and second-line anti-tuberculosis agents against multidrug-resistant Mycobacterium tuberculosis in vitro and in vivo. Int J Infect Dis, 2016, 52:23-28. doi: 10.1016/j.ijid.2016.08.027. doi: 10.1016/j.ijid.2016.08.027 URL
[39]	Pieterman ED, Keutzer L, van der Meijden A, et al. Superior efficacy of a bedaquiline, delamanid and linezolid combination regimen in a mouse-TB model. J Infect Dis, 2021: jiab043. doi: 10.1093/infdis/jiab043. doi: 10.1093/infdis/jiab043
[40]	Yip PC, Kam KM, Lam ET, et al. In vitro activities of PNU-100480 and linezolid against drug-susceptible and drug-resistant Mycobacterium tuberculosis isolates. Int J Antimicrob Agents, 2013, 42(1):96-97. doi: 10.1016/j.ijantimicag.2013.03.002. doi: 10.1016/j.ijantimicag.2013.03.002 URL
[41]	Williams KN, Brickner SJ, Stover CK, et al. Addition of PNU-100480 to first-line drugs shortens the time needed to cure murine tuberculosis. Am J Respir Crit Care Med, 2009, 180(4):371-376. doi: 10.1164/rccm.200904-0611OC. doi: 10.1164/rccm.200904-0611OC URL
[42]	Butler MS, Paterson DL. Antibiotics in the clinical pipeline in October 2019. J Antibiot (Tokyo), 2020, 73(6):329-364. doi: 10.1038/s41429-020-0291-8. doi: 10.1038/s41429-020-0291-8 URL
[43]	Tiberi S, du Plessis N, Walzl G, et al. Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies. Lancet Infect Dis, 2018, 18(7):e183-e198. doi: 10.1016/S1473-3099(18)30110-5. doi: 10.1016/S1473-3099(18)30110-5
[44]	Jahan S, Davis H, Ashcraft DS, et al. Evaluation of the in vitro interaction of fosfomycin and meropenem against metallo-β-lactamase-producing Pseudomonas aeruginosa using Etest and time-kill assay. J Investig Med, 2021, 69(2):371-376. doi: 10.1136/jim-2020-001573. doi: 10.1136/jim-2020-001573 URL
[45]	Dooley KE, Phillips PP, Nahid P, et al. Challenges in the clinical assessment of novel tuberculosis drugs. Adv Drug Deliv Rev, 2016, 102:116-122. doi: 10.1016/j.addr.2016.01.014. doi: 10.1016/j.addr.2016.01.014 URL
[46]	Wallis RS, Ginindza S, Beattie T, et al. Adjunctive host-directed therapies for pulmonary tuberculosis: a prospective, open-label, phase 2, randomised controlled trial. Lancet Respir Med,2021,S2213-2600(20)30448-3. doi: 10.1016/S2213-2600(20)30448-3. doi: 10.1016/S2213-2600(20)30448-3