Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis during epidemics: a randomised non-inferiority study

Lancet. 2005 Jul;366(9482):308-13. doi: 10.1016/S0140-6736(05)66792-X.

Abstract

Background: In sub-Saharan Africa in the 1990s, more than 600,000 people had epidemic meningococcal meningitis, of whom 10% died. The current recommended treatment by WHO is short-course long-acting oily chloramphenicol. Continuation of the production of this drug is uncertain, so simple alternatives need to be found. We assessed whether the efficacy of single-dose treatment of ceftriaxone was non-inferior to that of oily chloramphenicol for epidemic meningococcal meningitis.

Methods: In 2003, we undertook a randomised, open-label, non-inferiority trial in nine health-care facilities in Niger. Participants with suspected disease who were older than 2 months were randomly assigned to receive either chloramphenicol or ceftriaxone. Primary outcome was treatment failure (defined as death or clinical failure) at 72 h, measured with intention-to-treat and per-protocol analyses.

Findings: Of 510 individuals with suspected disease, 247 received ceftriaxone, 256 received chloramphenicol, and seven were lost to follow-up. The treatment failure rate at 72 h for the intention-to-treat analysis was 9% (22 patients) for both drug groups (risk difference 0.3%, 90% CI -3.8 to 4.5). Case fatality rates and clinical failure rates were equivalent in both treatment groups (14 [6%] ceftriaxone vs 12 [5%] chloramphenicol). Results were also similar for both treatment groups in individuals with confirmed meningitis caused by Neisseria meningitidis. No adverse side-effects were reported.

Interpretation: Single-dose ceftriaxone provides an alternative treatment for epidemic meningococcal meningitis--its efficacy, ease of use, and low cost favour its use. National and international health partners should consider ceftriaxone as an alternative first-line treatment to chloramphenicol for epidemic meningococcal meningitis.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / administration & dosage*
  • Ceftriaxone / administration & dosage*
  • Child
  • Child, Preschool
  • Chloramphenicol / administration & dosage*
  • Disease Outbreaks*
  • Female
  • Humans
  • Injections, Intramuscular
  • Male
  • Meningitis, Meningococcal / drug therapy*
  • Meningitis, Meningococcal / epidemiology
  • Meningitis, Meningococcal / mortality
  • Niger / epidemiology
  • Survival Rate
  • Treatment Failure

Substances

  • Anti-Bacterial Agents
  • Chloramphenicol
  • Ceftriaxone