Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis during epidemics: a randomised non-inferiority study.
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.
                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.
                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.
                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.
We found no reliable evidence to support or refute the use of pre-admission antibiotics for suspected cases of non-severe meningococcal disease. Evidence of moderate quality from one RCT indicated that single intramuscular injections of ceftriaxone and long-acting chloramphenicol were equally effective, safe and economical in reducing serious outcomes. The choice between these antibiotics would be based on affordability, availability and patterns of antibiotic resistance.
Further RCTs comparing different pre-admission antibiotics, accompanied by intensive supportive measures, are ethically justifiable in participants with severe illness, and are needed to provide reliable evidence in different clinical settings.