Dexamethasone in

adults with bacterial

meningitis
Group 4 - Toby, Samson, Jimena, Aurora, Jerry
Introduction to the treatment of meningitis
● A randomized, double-blind, multicenter trial was conducted to evaluate the use of
dexamethasone as an adjuvant treatment for adults with acute bacterial meningitis.

● The study concluded that early treatment with dexamethasone improves outcomes
without increasing the risk of gastrointestinal bleeding.

● The trial included patients who were 17 years of age or older, with suspected
meningitis and specific criteria for inclusion, such as cloudy cerebrospinal fluid or
bacteria in cerebrospinal fluid.

● The most commonly prescribed initial antibiotics in the trial were amoxicillin and
penicillin, with high rates of microbiologic coverage.

● Overall, the trial recommended administering dexamethasone as an adjuvant

treatment for adults with acute bacterial meningitis to improve outcomes and reduce
mortality.
 Hypothesis & Clinical rationale:

Early treatment with dexamethasone as an adjuvant therapy for adults with acute bacterial
meningitis would lead to improved outcomes

A animal study has been done that corticosteroids has beneficial effects, like reducing
inflammation in the cerebrospinal fluid.

Many experiment have be done to determine the outcome of acute bacterial meningitis, but
do not point the beneficial result

The high mortality and morbidity rates among adults with acute bacterial meningitis despite
the use of appropriate antimicrobial agents
 Overall outcome
Primary outcome:
Early treatment with dexamethasone improves the outcome in
adults with acute bacterial meningitis

Secondary outcome:
Dexamethasone did not have a beneficial effect on neurologic
sequelae, including hearing loss.

However, they were usually seen in most severely ill patients. Most
of these patients was found to survived to be tested larger in
dexamethasone group compared to placebo group.
Concern 1
Causative agents and Selective Bias

Causative agents:
S. pneumoniae → large number of patients
Seen with beneficial effect

N. meningitis → small number of patients

Were not seen with beneficial effect

Conclusion: dexamethasone recommended for all acute bacterial

meningitis patients.
Concern 1
Causative agents and Selective Bias
Selection Bias:
Control method→ compare baseline characteristics with 634
nationwide cohort patients(adults) with acute bacterial meningitis
who enrolled study with prospective data collected from 1998 to
2002

With respect to score on Glasgow Coma Scale on admission

Result: no significant differences

In addition, mortality among placebo group patients in present

study and the nationwide cohort were similar

Conclusion: selection bias did not confound the results

Concern 1
Causative agents and Selective Bias
Selection Bias:
Control method→ compare baseline characteristics with 634
nationwide cohort patients(adults) with acute bacterial meningitis
who enrolled study with prospective data collected from 1998 to
2002
Concern 2 - delay in starting the antibiotic therapy

● Informed-consent procedures
● Cranial CT has to be performed before lumbar puncture
—> to rule out brain shift, papilledema or hemiparesis
- Inclusion criteria: presence of cerebrospinal fluid
abnormalities
- Dexamethasone was administered before or with the
first dose of antibiotics
Concern 3 - duration & timing of dexamethasone therapy

● A 4-day regimen has been used in most clinical trials in

children with bacterial meningitis
- 2-day or 4-day regimen are shown to be equal effective
- also beneficial in children with pneumococcal meningitis
(only if it is given before or with the first dose of
antibiotics)
● Recommendation: 4-day regimen with dexamethasone
therapy started before or with the first dose of antibiotics
 Concern 4

● Most patient initially received monotherapy with amoxicillin or

penicillin
● As penicillin-resistant pneumococci‘s prevalence has increased,
the vancomycin is frequently used as a combination therapy
● Though dexamethasone is not associated with the adverse
event, it has been concerning about that it may impede the
penetration of vancomycin into the subarachnoid space
● Treatment with dexamethasone
○ In children - no reduction in the vancomycin levels in
cerebrospinal fluid
○ In adults - treatment failures was reported
 Concern 5

● Cognitive impairment occurs in adults survived with bacterial

meningitis
● It’s still unknown whether dexamethasone prevents death but
worsening cerebral cortical functioning
● In this study, it only shows that dexamethasone does not
increase the rate of neurological sequelae
● Overall, the results of this study showed that adjunctive
dexamethasone therapy improves the outcome in adults with
acute bacterial meningitis and this treatment does not
increase the risk of gastrointestinal bleeding