Department of Medicine, College of Medicine, Chichiri, Blantyre, Malawi.
Lancet Infect Dis. 2011 Apr;11(4):293-300. doi: 10.1016/S1473-3099(10)70317-0. Epub 2011 Feb 18.
Southern Africa has a high incidence of bacterial meningitis in adults, often associated with HIV co-infection. Mortality exceeds 50%, even with appropriate antibiotic therapy, and is not improved with corticosteroids. Glycerol adjuvant therapy reduces long-term morbidity in bacterial meningitis in children, and its use is being promoted. We aimed to assess the effectiveness of glycerol as an adjuvant therapy for adults with bacterial meningitis in Africa.
The study was done in two phases. First, in an open-label dose-finding study, 45 adult patients with symptoms, signs, and cerebrospinal fluid findings consistent with bacterial meningitis received either 50 mL, 75 mL, or 100 mL of glycerol four times a day for 4 days. We then did a randomised, double-blind, placebo-controlled trial of oral glycerol in adults with bacterial meningitis. Patients with clinical and cerebrospinal fluid findings suggestive of bacterial meningitis were randomly assigned in blocks of 12 by use of a random number list produced by an independent statistician to receive either glycerol or an equivalent volume of sugar solution. Glycerol and placebo were indistinguishable by colour or taste. The primary outcome was mortality at 40 days, with secondary outcomes including disability and mortality restricted to pneumococcal disease. All patients were analysed for the primary outcome excluding those who were lost to follow-up. This trial is registered at controlled-trials.com, number ISRCTN70121840.
75 mL glycerol four times a day was the highest tolerated dose, and was used for the main study. 265 patients were assigned treatment: 137 glycerol and 128 placebo. The trial was stopped early on the advice of the data and safety monitoring board after a planned interim analysis. By day 40, 61 (49%) of 125 patients in the placebo group and 86 (63%) of 136 in the glycerol group had died (adjusted odds ratio 2.4, 95% CI 1.3-4.2, p=0.003). There was no benefit from glycerol for death and disability by day 40, and glycerol did not improve death and disability by day 40 or death at day 40 in patients with proven bacterial disease or pneumococcal disease. Two serious adverse events occurred that were possibly due to the study drug.
Oral glycerol therapy cannot be recommended as an adjuvant therapy in adults with bacterial meningitis in resource-poor settings with a high HIV prevalence.
Meningitis Research Foundation.
南部非洲成人细菌性脑膜炎发病率很高，常伴有 HIV 合并感染。即使给予适当的抗生素治疗，死亡率仍超过 50%，且皮质类固醇治疗并不能改善预后。甘油辅助治疗可降低儿童细菌性脑膜炎的长期发病率，目前正在推广使用。本研究旨在评估甘油作为非洲成人细菌性脑膜炎辅助治疗的有效性。
该研究分两个阶段进行。首先，在一项开放标签剂量探索性研究中，45 例出现症状、体征和符合细菌性脑膜炎的脑脊液表现的成年患者每天接受 50 mL、75 mL 或 100 mL 甘油，每日 4 次，连续 4 天。然后，我们对成人细菌性脑膜炎患者进行了口服甘油的随机、双盲、安慰剂对照试验。采用独立统计学家生成的随机数列表，将具有临床和脑脊液检查提示细菌性脑膜炎表现的患者按 12 例一组进行随机分组，分别接受甘油或等量糖水治疗。甘油和安慰剂在颜色和味道上无法区分。主要结局为 40 天时的死亡率，次要结局包括残疾和仅限于肺炎球菌疾病的死亡率。所有患者均接受了主要结局分析，不包括失访患者。本试验在 controlled-trials.com 注册，编号为 ISRCTN70121840。
每天 4 次给予 75 mL 甘油是最高耐受剂量，因此用于主要研究。共纳入 265 例患者：137 例接受甘油治疗，128 例接受安慰剂治疗。在计划的中期分析后，根据数据和安全监测委员会的建议，提前终止了试验。第 40 天，安慰剂组 125 例患者中有 61 例（49%），甘油组 136 例患者中有 86 例（63%）死亡（校正比值比 2.4，95%CI 1.3-4.2，p=0.003）。第 40 天，甘油治疗对死亡率和残疾率无获益，且不能改善第 40 天细菌性疾病或肺炎球菌疾病患者的死亡率和残疾率。有 2 例严重不良事件可能与研究药物有关。
在资源匮乏、HIV 流行率高的地区，不能推荐口服甘油治疗作为细菌性脑膜炎成人患者的辅助治疗方法。
脑膜炎研究基金会。
