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


RESULTS
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.


CONCLUSIONS
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.
Nathan
N
N
Epicentre, Paris, France.
Borel
T
T
Djibo
A
A
Evans
D
D
Djibo
S
S
Corty
J F
JF
Guillerm
M
M
Alberti
K P
KP
Pinoges
L
L
Guerin
P J
PJ
Legros
D
D
D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D002443:Ceftriaxone / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D002701:Chloramphenicol / Q000008:administration & dosage*; D004196:Disease Outbreaks; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008585:Meningitis, Meningococcal / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D009548:Niger / Q000453:epidemiology; D015996:Survival Rate; D017211:Treatment Failure
D000900:Anti-Bacterial Agents; D002701:Chloramphenicol; D002443:Ceftriaxone