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高度耐药肺结核的治疗
Treatment of Highly Drug-Resistant Pulmonary Tuberculosis


Francesca Conradie ... 呼吸系统疾病 • 2020.03.05
相关阅读
• 理解广泛耐药结核的流行病学 • 利福平耐药结核的短疗程方案试验 • 耐药结核病治疗指南

摘要


背景

高度耐药结核病患者的可选治疗方案有限,且历来结局不良。

 

方法

我们在一项开放标签、单组研究(随访工作正在南非的三个研究中心进行)中研究了三种口服药物(贝达喹啉、pretomanid和利奈唑胺),这些药物对结核有杀菌活性,而且之前几乎没有耐药性。在广泛耐药结核病患者以及治疗无效或因副作用而停用二线治疗方案的耐多药结核病患者中,我们评价了将这些药物联合用药26周的安全性和疗效。主要终点是不良结局的发生率,不良结局的定义为治疗失败(细菌学或临床)或随访期间(随访持续至治疗结束后6个月)复发。如果患者的临床疾病消退、培养结果呈阴性并且尚未被归类为有不良结局,则将患者归类为在6个月时有良好结局。我们还评价了其他疗效终点和安全性。

 

结果

共计109例患者被纳入本研究,并被纳入疗效和安全性终点评估。在意向治疗分析中,在治疗结束后6个月时,11例患者(10%)有不良结局,98例患者(90%;95%置信区间,83~95)有良好结局。11例不良结局包括7例死亡(治疗期间的6例死亡和随访期间的1例不明原因死亡),1例在治疗期间撤回知情同意,2例在随访期间复发,以及1例失访。利奈唑胺的预期毒性作用包括周围神经病(81%的患者)和骨髓抑制(48%),这些毒性作用虽然常见,但可以控制,常导致利奈唑胺减量或中断用药。

 

结论

在高度耐药结核病患者中,在治疗结束后6个月时,贝达喹啉、pretomanid和利奈唑胺联合治疗使高比例的患者有良好结局;我们观察到一些相关毒性作用(由结核病联盟[TB Alliance]等资助,在ClinicalTrials.gov注册号为NCT02333799)。





作者信息

Francesca Conradie, M.B., B.Ch., Andreas H. Diacon, M.D., Nosipho Ngubane, M.B., B.Ch., Pauline Howell, M.B., B.Ch., Daniel Everitt, M.D., Angela M. Crook, Ph.D., Carl M. Mendel, M.D., Erica Egizi, M.P.H., Joanna Moreira, B.Sc., Juliano Timm, Ph.D., Timothy D. McHugh, Ph.D., Genevieve H. Wills, M.Sc., Anna Bateson, Ph.D., Robert Hunt, B.Sc., Christo Van Niekerk, M.D., Mengchun Li, M.D., Morounfolu Olugbosi, M.D., and Melvin Spigelman, M.D. for the Nix-TB Trial Team*
From the Clinical HIV Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg (F.C., N.N., P.H.), Sizwe Tropical Disease Hospital, Sandringham (F.C., P.H.), Task Applied Science and Stellenbosch University, Cape Town (A.H.D.), King DiniZulu Hospital Complex, Durban (N.N.), and the TB Alliance, Pretoria (C.V.N., M.O.) — all in South Africa; the TB Alliance, New York (D.E., C.M.M., E.E., J.M., J.T., M.L., M.S.); and the MRC Clinical Trials Unit at UCL (A.M.C., G.H.W.) and the UCL Centre for Clinical Microbiology (T.D.M., A.B., R.H.), University College London, London.Address reprint requests to Dr. Crook at the MRC Clinical Trials Unit at UCL, 90 High Holborn, London, WC1V 6LJ, United Kingdom, or at angela.crook@ucl.ac.uk. *Additional team members are listed in the Supplementary Appendix, available at NEJM.org.

 

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