Extended Continuous β-Lactam Infusion With Oral Acetaminophen in Childhood Bacterial Meningitis: A Randomized, Double-blind Clinical Trial

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.

Keywords: acetaminophen; bacterial meningitis; children; continuous infusion; paracetamol.