5 versus 10 days of treatment with ceftriaxone for bacterial meningitis in children: a double-blind randomised equivalence study

Summary Background Bacterial meningitis is an important cause of morbidity and mortality in developing countries, but the duration of treatment is not well established. We aimed to compare the efficacy of 5 and 10 days of parenteral ceftriaxone for the treatment of bacterial meningitis in children. Methods We did a multicountry, double-blind, placebo-controlled, randomised equivalence study of 5 versus 10 days of treatment with ceftriaxone in children aged 2 months to 12 years with purulent meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae type B, or Neisseria meningitidis . Our study was done in ten paediatric referral hospitals in Bangladesh, Egypt, Malawi, Pakistan, and Vietnam. We randomly assigned children who were stable after 5 days of treatment, through site-balanced computer-generated allocation lists, to receive a further 5 days of ceftriaxone or placebo. Patients, their guardians, and staff were masked to study-group allocation. Our primary outcomes were bacteriological failure or relapse. Our analysis was per protocol. This study is registered with the International Standard Randomised Controlled Trial Number Register, number ISRCTN38717320. Findings We included 1004 of 1027 children randomly assigned to study groups in our analyses; 496 received treatment with ceftriaxone for 5 days, and 508 for 10 days. In the 5-day treatment group, two children (one infected with HIV) had a relapse; there were no relapses in the 10-day treatment group and there were no bacteriological failures in either study group. Side-effects of antibiotic treatment were minor and similar in both groups. Interpretation In children beyond the neonatal age-group with purulent meningitis caused by S pneumoniae, H influenzae type b, or N meningitidis who are stable by day 5 of ceftriaxone treatment, the antibiotic can be safely discontinued. Funding United States Agency for International Development.