Ceftriaxone as effective as long-acting chloramphenicol in short-course treatment of meningococcal meningitis

308 www.thelancet.com Vol 366 July 23, 2005 Introduction Epidemics of meningitis due to Neisseria meningitidis serogroup A are reported almost every year from subSaharan African countries, representing more than 600 000 affected individuals in the 1990s alone. The case fatality ratio (CFR) is estimated to be 10%, with a further 10–20% of patients developing neurological sequelae. During these epidemics with high numbers of people with meningitis, over-worked health staff often need effective, cheap, and easy-to-use antibiotics to handle the large influx of patients. Long-acting chloramphenicol (oily suspension) was first proven effective against epidemic meningococcal meningitis in the mid-1970s, and has been recommended by WHO as a regimen of one or two intramuscular injections since 1995· Even though oily chloramphenicol remains active against N meningitidis serogroup A and is critical for the management of meningitis epidemics, continuation of the production of the drug is uncertain, mainly because of the absence of financial market perspectives for this product. Alternative antimicrobial drugs with proven efficacy against N meningitidis include intravenous benzylpenicillin, ampicillin, and intravenous or intramuscular chloramphenicol or ceftriaxone. However, protocols using multiple injections every day are impractical to use in epidemics and only drugs with simple treatment schedules provide an alternative to oily chloramphenicol. Several studies have shown the efficacy of a daily dose of ceftriaxone for 4 days in the treatment of bacterial meningitis. Short-course protocols could also be effective because of the pharmacological properties of ceftriaxone that include a long half-life in blood (8 h) and in cerebrospinal fluid (CSF; 14 h), as well as residual amounts in CSF above the minimal inhibitory concentration of most of the organisms 24–48 h after injection. Short-course protocols have been tested in two randomised trials. In a study undertaken by Epicentre in 1995, 47 children aged 2–35 months with meningococcal meningitis did not show any substantial difference in clinical failure rates among those receiving a two-injection regimen of ceftriaxone (9%) or oily chloramphenicol (8%). The second small trial compared 2 days of ceftriaxone with 6 days of benzylpenicillin in 36 adults with bacterial meningitis. Recovery rates were 81% and 95%, respectively, with no significant difference shown. We undertook a multicentre, randomised, open-label, non-inferiority trial comparing the efficacy of shortcourse treatment of ceftriaxone with that of oily chloramphenicol in individuals with meningitis recruited during an epidemic in Niger in 2003. Lancet 2005; 366: 308–313