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.

Gene polymorphisms of TLR10: effects on bacterial meningitis outcomes in Angolan children

“…The studies were approved by Luanda Children’s Hospital ethics committee. BM patients were included in the study after their guardian(s) granted their informed consent [13, 14].…”

Prevalence and significance of anaemia in childhood bacterial meningitis: a secondary analysis of prospectively collected data from clinical trials in Finland, Latin America and Angola

“…Our study analyses data collected during five prospective, randomised treatment trials of BM on three continents: Europe, Latin America and Africa. [13][14][15][16][17] All the studies were overseen by the same person (HP). The two trials in 12 hospitals in Finland recruited patients from 1984 to 1990.…”

“…16 17 The details of the studies and the approval of the studies have been published previously. [13][14][15][16][17] The studies were performed following the principles of the Declaration of Helsinki. The children were enrolled after their guardian's informed consent was obtained.…”

Gene Polymorphisms of TLR4 and TLR9 and Haemophilus influenzae Meningitis in Angolan Children

“…The exclusion criteria included previous neurological abnormalities or hearing impairment, immunosuppression except for HIV infection, active tuberculosis, known hepatic disease, or pre-treatment with more than one dose of parenteral antibiotic. The patients were included in the study after informed consent was provided by their guardians [36,37]. Oral informed consent was also obtained from the guardians of the controls.…”

“…When available, a latex agglutination test (Pastorex Meningitis, Bio-Rad Laboratories Inc., Marne-La-Coquette, France) was conducted if >100 leukocytes/mm 3 were present and bacterial culture was negative. Whenever possible, the remaining CSF sample was stored at -80 • C and shipped for PCR identification to the National Institute of Health, Lisbon, Portugal, or later to the Centre for Respiratory Diseases and Meningitis (CRDM), National Institute for Communicable Diseases (NICD), Johannesburg, South Africa [37]. Concentrations of MMP-8 were determined with a time-resolved immunofluorometric assay (Medix Biochemica, Espoo, Finland).…”