Scarborough Matthew, Gordon Stephen B, Whitty Christopher J M, French Neil, Njalale Yasin, Chitani Alex, Peto Timothy E A, Lalloo David G, Zijlstra Eduard E
College of Medicine, Blantyre, Malawi.
N Engl J Med. 2007 Dec 13;357(24):2441-50. doi: 10.1056/NEJMoa065711.
In sub-Saharan Africa, bacterial meningitis is common and is associated with a high mortality. Adjuvant therapy with corticosteroids reduces mortality among adults in the developed world, but it has not been adequately tested in developing countries or in the context of advanced human immunodeficiency virus (HIV) infection.
We conducted a randomized, double-blind, placebo-controlled trial of dexamethasone (16 mg twice daily for 4 days) and an open-label trial of intramuscular versus intravenous ceftriaxone (2 g twice daily for 10 days) in adults with an admission diagnosis of bacterial meningitis in Blantyre, Malawi. The primary outcome was death at 40 days after randomization.
A total of 465 patients, 90% of whom were HIV-positive, were randomly assigned to receive dexamethasone (233 patients) or placebo (232 patients) plus intramuscular ceftriaxone (230 patients) or intravenous ceftriaxone (235 patients). There was no significant difference in mortality at 40 days in the corticosteroid group (129 of 231 patients) as compared with the placebo group (120 of 228 patients) by intention-to-treat analysis (odds ratio, 1.14; 95% confidence interval [CI], 0.79 to 1.64) or when the analysis was restricted to patients with proven pneumococcal meningitis (68 of 129 patients receiving corticosteroids vs. 72 of 143 patients receiving placebo) (odds ratio, 1.10; 95% CI, 0.68 to 1.77). There were no significant differences between groups in the outcomes of disability and death combined, hearing impairment, and adverse events. There was no difference in mortality with intravenous ceftriaxone (121 of 230 patients) as compared with intramuscular ceftriaxone (128 of 229 patients) (odds ratio, 0.88; 95% CI, 0.61 to 1.27).
Adjuvant therapy with dexamethasone for bacterial meningitis in adults from an area with a high prevalence of HIV did not reduce mortality or morbidity. In this setting, intramuscular administration was not inferior to intravenous administration of ceftriaxone for bacterial meningitis. (Current Controlled Trials number, ISRCTN31371499 [controlled-trials.com].).
在撒哈拉以南非洲地区，细菌性脑膜炎很常见，且死亡率很高。在发达国家，皮质类固醇辅助治疗可降低成人死亡率，但在发展中国家或人类免疫缺陷病毒（HIV）感染晚期的情况下，尚未得到充分验证。
我们在马拉维布兰太尔对入院诊断为细菌性脑膜炎的成人进行了一项地塞米松随机、双盲、安慰剂对照试验（每日两次，每次16mg，共4天）以及一项头孢曲松肌肉注射与静脉注射的开放标签试验（每日两次，每次2g，共10天）。主要结局是随机分组后40天的死亡情况。
共有465例患者，其中90%为HIV阳性，被随机分配接受地塞米松（233例患者）或安慰剂（232例患者）加头孢曲松肌肉注射（230例患者）或静脉注射（235例患者）。在意向性分析中，皮质类固醇组（231例患者中的129例）与安慰剂组（228例患者中的120例）40天时的死亡率无显著差异（比值比，1.14；95%置信区间[CI]，0.79至1.64），当分析仅限于确诊为肺炎球菌脑膜炎的患者时（接受皮质类固醇治疗的129例患者中的68例与接受安慰剂治疗的143例患者中的72例）（比值比，1.10；95%CI，0.68至1.77）。在残疾和死亡合并结局、听力损害及不良事件方面，两组间无显著差异。头孢曲松静脉注射组（230例患者中的121例）与肌肉注射组（229例患者中的
