Journal Article

Adjuvant Glycerol and/or Dexamethasone to Improve the Outcomes of Childhood Bacterial Meningitis: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial

Fernández, Josefina, López, Eduardo, Goyo, José, Bologna, Rosa, Sarna, Seppo, Zavala, Inés, de Andrade, Solange Dourado, Arbo, Antonio, Roine, Irmeli, Mata, Antonio González, Miño, Greta, Peltola, Heikki, Ayala, Silvia González

2007

Overview

Background. Despite favorable meta-analyses, no study involving third-generation cephalosporins for the treatment of childhood bacterial meningitis has documented a benefit of adjuvant dexamethasone therapy if the outcomes are examined individually. Methods. We conducted a prospective, randomized, double-blind trial comparing adjuvant dexamethasone or glycerol with placebo in children aged from 2 months through 16 years in Latin America. Ceftriaxone was administered to all children; children were randomized to also receive dexamethasone intravenously, glycerol orally, both agents, or neither agent. Primary end points were death, severe neurological sequelae, or deafness, with the first 2 end points forming a composite end point. A subgroup analysis for Haemophilus influenzae type b meningitis was undertaken. Intention-to-treat analysis was performed using binary logistic regression models. Results. H. influenzae type b, pneumococci, and meningococci were the main agents found among 654 patients; dexamethasone was given to 166, dexamethasone and glycerol were given to 159, glycerol was given to 166, and placebo was given to 163. No adjuvant therapy significantly affected death or deafness. In contrast, glycerol and dexamethasone plus glycerol reduced severe neurological sequelae, compared with placebo; the odds ratios were 0.31 (95% confidence interval [95% CI], 0.13–0.76; P = .010) and 0.39 (95% CI, 0.17–0.93; P = .033), respectively. For neurological sequelae and death, the odds ratios were 0.44 (95% CI, 0.25–0.76; P = .003) and 0.55 (95% CI, 0.32–0.93; P = .027), respectively. Dexamethasone therapy prevented deafness in patients with H. influenzae type b meningitis only if patients were divided grossly into dexamethasone recipients and nonrecipients and if timing between dexamethasone and ceftriaxone administration was not taken into account (odds ratio, 0.27; 95% CI, 0.09–0.77; P = .014). Conclusion. Oral glycerol therapy prevents severe neurological sequelae in patients with childhood meningitis. Safety, availability, low cost, and oral administration also add to its usefulness, especially in resource-limited settings.

• Publisher: The University of Chicago Press,University of Chicago Press,Oxford University Press
• Subject: Adolescent / Anti-Bacterial Agents - therapeutic use / Anti-Inflammatory Agents - adverse effects / Anti-Inflammatory Agents - therapeutic use / Antimicrobials / Articles and Commentaries / Bacteria / Bacterial diseases / Bacterial diseases of the nervous system. Bacterial myositis / Bacterial meningitis / Biological and medical sciences / Bones, joints and connective tissue. Antiinflammatory agents / Ceftriaxone - therapeutic use / Chemotherapy, Adjuvant - methods / Child / Child, Preschool / Childhood / Children / Children & youth / Clinical trials / Deafness - prevention & control / Death / Dexamethasone - adverse effects / Dexamethasone - therapeutic use / Dosage / Double-Blind Method / Drug therapy / Drug Therapy, Combination / Female / Glycerol - adverse effects / Glycerol - therapeutic use / Haemophilus influenzae / Haemophilus meningitis / Health outcomes / Hearing loss / Human bacterial diseases / Humans / Infectious diseases / Latin America / Male / Medical sciences / Meningitis / Meningitis, Bacterial - complications / Meningitis, Bacterial - drug therapy / Meningitis, Bacterial - microbiology / Meningitis, Haemophilus - complications / Meningitis, Haemophilus - drug therapy / Meningitis, Haemophilus - microbiology / Meningitis, Meningococcal - complications / Meningitis, Meningococcal - drug therapy / Meningitis, Meningococcal - microbiology / Mortality / Nervous System Diseases - prevention & control / Neurological disorders / Operating rooms / Pharmacology. Drug treatments / Placebos / Placebos - administration & dosage / Prospective Studies / Treatment Outcome