Abstract

Background

In our previous study in Luanda, Angola, initial continuous β-lactam infusion for 24 hours combined with oral acetaminophen for 48 hours showed promising results as a new treatment for childhood bacterial meningitis. We investigated whether extending this treatment regimen to 4 days would improve the outcomes further.

Methods

We conducted a randomized, double-blind, parallel-group study at the same hospital in Luanda. Children aged 2 months to 15 years presenting to hospital with symptoms and signs of bacterial meningitis were randomized to receive, for the first 4 days, a continuous infusion of cefotaxime (250 mg/kg/day) with simultaneous oral acetaminophen (first dose 30 mg/kg, then 20 mg/kg every 6 hours), or cefotaxime conventionally as boluses (62.5 mg/kg, 4 times per day) with placebo orally. All children received also glycerol orally. The primary outcome was mortality by day 7.

Results

In all, 375 patients were included in the study between 22 January 2012 and 21 January 2017. As 2 children succumbed before treatment initiation, 187 vs 186 participants remained in the intervention and control groups, respectively. On day 7, 61 of 187 (32.6%) children in the intervention group vs 64 of 186 (34.4%) in the control group had died (risk ratio, 0.95 [95% confidence interval {CI}, .71–1.26]; absolute risk difference, 1.8% [95% CI, −7.8 to 11.4]). At discharge from hospital, the corresponding numbers were 71 of 187 (38.0%) and 75 of 186 (40.3%), respectively.

Conclusions

Prolonged continuous β-lactam infusion combined with oral acetaminophen did not improve the gloomy outcomes of childhood bacterial meningitis in Angola.

Clinical Trials Registration

NCT01540838.

中文翻译：

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儿童细菌性脑膜炎连续口服β-内酰胺延长口服对乙酰氨基酚输注：一项随机，双盲临床试验

摘要

背景

在我们先前在安哥拉罗安达进行的研究中，最初的连续β-内酰胺连续24小时输注与口服对乙酰氨基酚持续48小时相结合，显示出作为儿童细菌性脑膜炎的一种新疗法的前景可观。我们调查了将该治疗方案延长至4天是否会进一步改善治疗效果。

方法

我们在罗安达同一家医院进行了一项随机，双盲，平行研究。2个月至15岁到医院就诊并出现细菌性脑膜炎症状和体征的儿童在开始的第4天随机接受头孢噻肟（250 mg / kg /天）的连续输注，同时口服对乙酰氨基酚（第1剂30 mg） / kg，然后每6小时服用20 mg / kg），或常规口服头孢噻肟（62.5 mg / kg，每天4次）口服安慰剂。所有儿童也口服甘油。主要结局是第7天的死亡率。

结果

在2012年1月22日至2017年1月21日期间，总共纳入375名患者。由于有2名儿童在治疗开始前就屈服了，干预组和对照组分别有187和186名参与者。在第7天，干预组187名儿童中有61名（32.6％）死亡，而对照组的186名儿童中有64名（34.4％）死亡（风险比为0.95 [95％置信区间{CI} ，. 71–1.26]；绝对风险差异为1.8％[95％CI，-7.8至11.4]）。出院时，相应的数字分别是187人中的71人（占38.0％）和186人中的75人（占40.3％）。

结论

长时间连续β-内酰胺输注结合口服对乙酰氨基酚不能改善安哥拉儿童细菌性脑膜炎的悲观结局。

临床试验注册

NCT01540838。