英国伦敦大学学院Angela M. Crook团队取得一项新突破。他们研究出高耐药肺结核的治疗方案。该研究于2020年3月5日发表于国际一流学术期刊《新英格兰医学杂志》上。

具有高度耐药性的结核病患者的治疗选择有限，并且历来结局较差。

研究组在南非的三个地点进行了一项开放标签、单组研究，调查了三种口服药物（贝达喹啉，Pretomanid和利奈唑胺）的治疗效果，这些药物对结核病具有杀菌活性，而且几乎没有耐药性。

研究组招募了109名广泛耐药结核病患者和对治疗无反应或因副作用而终止二线治疗的多药耐药结核病患者，采用该药物组合治疗26周。

治疗结束后6个月，有11例患者（10％）预后不良，而98例患者（90％）预后良好。11例不良预后中有7例死亡，治疗期间1例撤回同意书，随访期间2例复发，以及1例失访。预期的利奈唑胺毒性作用很常见，其中周围神经病发生率为81%，骨髓抑制发生率为48％，但仍可控制，通常会导致剂量降低或利奈唑胺治疗中断。

总之，苯达喹啉+pretomanid+利奈唑胺的组合治疗高耐药性结核病患者6个月后预后良好，但需注意药物的毒副作用。

附：英文原文

Title: Treatment of Highly Drug-Resistant Pulmonary Tuberculosis

Author: 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.

Issue&Volume: 2020-03-04

Abstract: BACKGROUNDPatients with highly drug-resistant forms of tuberculosis have limited treatment options and historically have had poor outcomes.METHODSIn an open-label, single-group study in which follow-up is ongoing at three South African sites, we investigated treatment with three oral drugs — bedaquiline, pretomanid, and linezolid — that have bactericidal activity against tuberculosis and to which there is little preexisting resistance. We evaluated the safety and efficacy of the drug combination for 26 weeks in patients with extensively drug-resistant tuberculosis and patients with multidrug-resistant tuberculosis that was not responsive to treatment or for which a second-line regimen had been discontinued because of side effects. The primary end point was the incidence of an unfavorable outcome, defined as treatment failure (bacteriologic or clinical) or relapse during follow-up, which continued until 6 months after the end of treatment. Patients were classified as having a favorable outcome at 6 months if they had resolution of clinical disease, a negative culture status, and had not already been classified as having had an unfavorable outcome. Other efficacy end points and safety were also evaluated.RESULTSA total of 109 patients were enrolled in the study and were included in the evaluation of efficacy and safety end points. At 6 months after the end of treatment in the intention-to-treat analysis, 11 patients (10%) had an unfavorable outcome and 98 patients (90%; 95% confidence interval, 83 to 95) had a favorable outcome. The 11 unfavorable outcomes were 7 deaths (6 during treatment and 1 from an unknown cause during follow-up), 1 withdrawal of consent during treatment, 2 relapses during follow-up, and 1 loss to follow-up. The expected linezolid toxic effects of peripheral neuropathy (occurring in 81% of patients) and myelosuppression (48%), although common, were manageable, often leading to dose reductions or interruptions in treatment with linezolid.CONCLUSIONSThe combination of bedaquiline, pretomanid, and linezolid led to a favorable outcome at 6 months after the end of therapy in a high percentage of patients with highly drug-resistant forms of tuberculosis; some associated toxic effects were observed.

DOI: NJ202003053821005

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1901814