Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis
Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis
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DOI：
10.1056/nejmoa1507062
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发表时间：
2016-01-14
影响因子：
158.5
通讯作者：
Farrar, Jeremy J.
中科院分区：
文献类型：
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作者：
Heemskerk, A. Dorothee;Bang, Nguyen D.;Farrar, Jeremy J.
慢性脑膜炎常常是致命的。早期抗结核治疗和糖皮质激素的连续治疗可提高生存率，但仍有近三分之一的患者死亡。我们假设，强化抗结核治疗将提高杀死脑内结核分枝杆菌的有机体和降低死亡率patients.METHODSWe进行了一项随机，双盲，安慰剂对照试验，涉及人类免疫缺陷病毒（HIV）感染的成年人和HIV未感染的成年人与结核性脑膜炎的临床诊断谁被接纳的两个越南医院之一。我们比较了一个标准的，9个月的抗结核治疗方案（其中包括10毫克利福平每公斤体重每天）与强化方案，包括更高剂量的利福平（15毫克每公斤每天）和左氧氟沙星（20毫克每公斤每天）的前8周的治疗。主要结局是随机分组后9个月内的死亡。共有817例患者（其中349例为HIV感染者）入组，409例随机分配接受标准方案，408例接受强化治疗。在9个月的随访中，强化治疗组有113例患者死亡，标准治疗组有114例患者死亡（风险比，0.94; 95%置信区间，0.73 - 1.22; P=0.66）。在总体人群或任何亚组中，没有证据表明强化治疗的显著差异效应，感染异烟肼耐药M的患者可能除外。结核治疗组之间的次要结局也无显著差异。导致治疗中断的不良事件总数在两个治疗组之间没有显著差异（标准治疗组64起事件，强化治疗组95起事件，P=0.08）。（由Wellcome Trust和Li Ka Shing Foundation资助; Current Controlled Trials编号，ISRCTN 61649292。
BACKGROUNDTuberculous meningitis is often lethal. Early antituberculosis treatment and adjunctive treatment with glucocorticoids improve survival, but nearly one third of patients with the condition still die. We hypothesized that intensified antituberculosis treatment would enhance the killing of intracerebral Mycobacterium tuberculosis organisms and decrease the rate of death among patients.METHODSWe performed a randomized, double-blind, placebo-controlled trial involving human immunodeficiency virus (HIV)-infected adults and HIV-uninfected adults with a clinical diagnosis of tuberculous meningitis who were admitted to one of two Vietnamese hospitals. We compared a standard, 9-month antituberculosis regimen (which included 10 mg of rifampin per kilogram of body weight per day) with an intensified regimen that included higher-dose rifampin (15 mg per kilogram per day) and levofloxacin (20 mg per kilogram per day) for the first 8 weeks of treatment. The primary outcome was death by 9 months after randomization.RESULTSA total of 817 patients (349 of whom were HIV-infected) were enrolled; 409 were randomly assigned to receive the standard regimen, and 408 were assigned to receive intensified treatment. During the 9 months of follow-up, 113 patients in the intensified-treatment group and 114 patients in the standard-treatment group died (hazard ratio, 0.94; 95% confidence interval, 0.73 to 1.22; P=0.66). There was no evidence of a significant differential effect of intensified treatment in the overall population or in any of the subgroups, with the possible exception of patients infected with isoniazid-resistant M. tuberculosis. There were also no significant differences in secondary outcomes between the treatment groups. The overall number of adverse events leading to treatment interruption did not differ significantly between the treatment groups (64 events in the standard-treatment group and 95 events in the intensified-treatment group, P=0.08).CONCLUSIONSIntensified antituberculosis treatment was not associated with a higher rate of survival among patients with tuberculous meningitis than standard treatment. (Funded by the Wellcome Trust and the Li Ka Shing Foundation; Current Controlled Trials number, ISRCTN61649292.)