Short, Highly Effective, and Inexpensive Standardized Treatment of Multidrug-resistant Tuberculosis
Short, Highly Effective, and Inexpensive Standardized Treatment of Multidrug-resistant Tuberculosis
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DOI：
10.1164/rccm.201001-0077oc
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发表时间：
2010-09-01
影响因子：
24.7
通讯作者：
Rieder, Hans L.
中科院分区：
文献类型：
--
作者：
Van Deun, Armand;Maug, Aung Kya Jai;Rieder, Hans L.
基本原理：根据专家意见，全球耐多药结核病管理指南规定了漫长且通常耐受性较差的治疗方法。目的：这项观察性研究评估了标准化治疗方案对低收入国家中未经二线药物治疗的已证实耐多药结核病患者的有效性。方法：同意的患者被顺序分配到六种标准化治疗方案之一。后续队列采用根据既往队列结果调整的方案进行治疗。这项研究的目的是尽量减少失败和默认，同时减少总治疗时间，而不增加复发frequency.Measurements和主要结果：我们报告的治疗结果与实验室确诊的，多药耐药肺结核患者从1997年5月至2007年12月。最有效的治疗方案需要在整个治疗期间使用加替沙星、氯法齐明、乙胺丁醇和吡嗪酰胺治疗至少9个月，并在至少4个月的强化期补充丙硫异烟胺、卡那霉素和高剂量异烟肼，在206例患者中，无复发治愈率为87.9%（95%置信区间，82.7-91.6）。主要药物不良反应不常见且可管理。与221例患者治疗方案的基础上氧氟沙星和常见的丙硫异烟胺在整个，任何不良后果的风险比为0.39（95%置信区间，0.26-0.59）conclusions：系列方案制定的指导下，整体治疗效果的治疗结果与一线治疗。需要在人类免疫缺陷病毒合并感染水平高的人群和对二线药物初始耐药率较高的人群中进行正式的确证性试验。
Rationale: Based on expert opinion, the global guidelines for management of multidrug-resistant tuberculosis impose lengthy and often poorly tolerated treatments.Objectives: This observational study evaluates the effectiveness of standardized regimens for patients with proven multidrug-resistant tuberculosis previously untreated with second-line drugs in low-income countries.Methods: Consenting patients were sequentially assigned to one of six standardized treatment regimens. Subsequent cohorts were treated with regimens adapted according to results in prior cohorts. The study was designed to minimize failure and default while reducing total treatment duration without increasing relapse frequency.Measurements and Main Results: We report the treatment outcome of all patients with laboratory-confirmed, multidrug-resistant tuberculosis enrolled from May 1997 to December 2007. The most effective treatment regimen required a minimum of 9 months of treatment with gatifloxacin, clofazimine, ethambutol, and pyrazinamide throughout the treatment period supplemented by prothionamide, kanamycin, and high-dose isoniazid during an intensive phase of a minimum of 4 months, giving a relapse-free cure of 87.9% (95% confidence interval, 82.7-91.6) among 206 patients. Major adverse drug reactions were infrequent and manageable. Compared with the 221 patients treated with regimens based on ofloxacin and commonly prothionamide throughout, the hazard ratio of any adverse outcome was 0.39 (95% confidence interval, 0.26-0.59).Conclusions: Serial regimen formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with first-line treatment. Confirmatory formal trials in populations with high levels of human immunodeficiency virus coinfection and in populations with a higher initial prevalence of resistance to second-line drugs are required.