double-blind, placebo-controlled randomized controlled trial including
598 children 2 months to 13 years old admitted to Queen Elizabeth Central
Hospital, Blantyre, Malawi with bacterial meningitis.1
children (51%) were randomly assigned to dexamethasone and 295 (49%)
were randomly allocated to receive dexamethasone (0.4 mg/kg) or placebo
(water) q12h X 48h. Vials were identical, labeled only with study numbers,
neither the childrens' health care providers nor their parents nor outcomes
assessors knew which arm the child had been assigned to.
criteria: age 2 months to 13 years old and one of: admission LP with
> 100 WBCs, mostly granulocytes, or positive gram stain, or culture
grew bacteria. Initial enrollment was based on clinical story and initial
csf hazy or cloudy.
criteria: If csf later did not meet definition of meningitis as described
above, child was then removed from study. Children also were excluded
if they had received broad-spectrum antibiotics up to 24 hours prior
measures: death, full recovery, hearing loss or reduction, or various
cases of meningitis caused by four types of bacteria: S pneumoniae (238,
40%), H influenzae type b (67, 11%), N meningitidis (67, 11%), Salmonella
species (29, 5%). >1/3 had received antibiotics prior to admission,
mainly cotrimoxazole or penicillin, mostly orally.
analysis was performed according to causative agents.
didn't improve overall mortality (31% in both groups, RR 1.00, p = 0.093),
development of neurologic sequelae (28% in both groups, RR 0.99, p =
0.97) at discharge or on 6 month followup, likelihood of discharge after
full recovery, or the proportion/degree of hearing disorders in children
with bacterial meningitis of all causes.
with steroids were four times more likely than placebo to develop hydrocephalus.
therapy was needed and imaging abnormalities on ultrasound were found
more often in kids with H influenzae and Salmonella meningitis.
Salmonella > S pneumoniae > H influenzae >> N meningitidis.
follow-up, the two groups had similar number of kids with neurological
disorders and hearing loss.
was much lower in patients who had received ceftriaxone v. penicillin/
chloramphenicol alone; in latter group, mortality/morbidity not affected
by steroids, in ceftriaxone group, lower incidence of hearing loss (and
and neurologic sequelae were associated with age (inversely), malnutrition,
low coma score, HIV-1 seropositivity, and by causative organism.
seropositive children were more malnourished, more likely to be left
with neurologic sequelae in cases of S pneumoniae meningitis, more likely
to have recurrent meningitis, and had higher case fatality rates.
reported in other studies, there were no deleterious side effects recorded
related to the dexamethasone.