Adjunctive dexamethasone in bacterial meningitis: a meta-analysis of individual patient data.
BACKGROUND
Dexamethasone improves outcome for some patients with bacterial meningitis, but not others. We aimed to identify which patients are most likely to benefit from dexamethasone treatment.


METHODS
We did a meta-analysis of individual patient data from the randomised, double-blind, placebo-controlled trials of dexamethasone for bacterial meningitis in patients of all ages for which raw data were available. The pre-determined outcome measures were death at the time of first follow-up, death or severe neurological sequelae at 1 month follow-up, death or any neurological sequelae at first follow-up, and death or severe bilateral hearing loss at first follow-up. Combined odds ratios (ORs) and tests for heterogeneity were calculated using conventional Mantel-Haenszel statistics. We also did exploratory analysis of hearing loss among survivors and other exploratory subgroup analyses by use of logistic regression.


RESULTS
Data from 2029 patients from five trials were included in the analysis (833 [41.0%] aged <15 years). HIV infection was confirmed or likely in 580 (28.6%) patients and bacterial meningitis was confirmed in 1639 (80.8%). Dexamethasone was not associated with a significant reduction in death (270 of 1019 [26.5%] on dexamethasone vs 275 of 1010 [27.2%] on placebo; OR 0.97, 95% CI 0.79-1.19), death or severe neurological sequelae or bilateral severe deafness (42.3%vs 44.3%; 0.92, 0.76-1.11), death or any neurological sequelae or any hearing loss (54.2%vs 57.4%; 0.89, 0.74-1.07), or death or severe bilateral hearing loss (36.4%vs 38.9%; 0.89, 0.73-1.69). However, dexamethasone seemed to reduce hearing loss among survivors (24.1%vs 29.5%; 0.77, 0.60-0.99, p=0.04). Dexamethasone had no effect in any of the prespecified subgroups, including specific causative organisms, pre-dexamethasone antibiotic treatment, HIV status, or age. Pooling of the mortality data with those of all other published trials did not significantly change the results.


CONCLUSIONS
Adjunctive dexamethasone in the treatment of acute bacterial meningitis does not seem to significantly reduce death or neurological disability. There were no significant treatment effects in any of the prespecified subgroups. The benefit of adjunctive dexamethasone for all or any subgroup of patients with bacterial meningitis thus remains unproven.


BACKGROUND
Wellcome Trust UK.
van de Beek
Diederik
D
Department of Neurology, Centre of Infection and Immunity Amsterdam, Academic Medical Center, Amsterdam, Netherlands.
Farrar
Jeremy J
JJ
de Gans
Jan
J
Mai
Nguyen Thi Hoang
NT
Molyneux
Elizabeth M
EM
Peltola
Heikki
H
Peto
Tim E
TE
Roine
Irmeli
I
Scarborough
Mathew
M
Schultsz
Constance
C
Thwaites
Guy E
GE
Tuan
Phung Quoc
PQ
Zwinderman
A H
AH
D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000639:trends; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D016920:Meningitis, Bacterial / Q000188:drug therapy* / Q000453:epidemiology; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone