What is the role of dexamethasone (corticosteroid) in the treatment of meningitis?

Role of Dexamethasone in Bacterial Meningitis

Dexamethasone should be administered empirically to all adults and children with suspected bacterial meningitis in high-income countries, given before or with the first dose of antibiotics, as it significantly reduces hearing loss, neurological sequelae, and mortality in pneumococcal meningitis. 1, 2

Dosing Recommendations

Adults:

• 10 mg intravenously every 6 hours for 4 days 1, 2

Children:

• 0.15 mg/kg intravenously every 6 hours for 2-4 days 1, 2

Neonates (<1 month):

• Dexamethasone is NOT recommended due to insufficient evidence 1

Timing of Administration

The first dose must be given 10-20 minutes before or at minimum concomitant with the first antibiotic dose to prevent the inflammatory response from bacterial lysis. 1, 2

• If antibiotics have already been started, dexamethasone can still be initiated up to 4 hours after the first antibiotic dose, though earlier is better 1, 2
• Beyond 4 hours, the benefit becomes uncertain and administration is not recommended 1

Evidence for Clinical Outcomes

Mortality reduction:

• Overall mortality is not significantly reduced across all bacterial meningitis 1
• However, in pneumococcal meningitis specifically, mortality drops dramatically from 34% to 14% with dexamethasone (relative risk 0.48) 3, 2
• In adults with pneumococcal meningitis, unfavorable outcomes decrease from 52% to 26% 3, 2

Neurological and audiological sequelae:

• Dexamethasone significantly reduces hearing loss and neurological complications across all bacterial meningitis 1
• For H. influenzae type b meningitis, hearing impairment is reduced (OR 0.31) 2
• For severe hearing loss in pneumococcal meningitis in children, early dexamethasone shows marked benefit (OR 0.09) 2
• Long-term follow-up shows sequelae rates of 14% with dexamethasone versus 38% without treatment (relative risk 3.8 for placebo) 4

Pathogen-Specific Considerations

When to CONTINUE dexamethasone:

• Streptococcus pneumoniae: Strong evidence for benefit; continue full 4-day course 1
• Haemophilus influenzae: Strong evidence for reducing hearing loss; continue full course 1, 2

When to STOP dexamethasone:

• Non-bacterial meningitis (viral, fungal, etc.) confirmed: discontinue immediately 1
• Listeria monocytogenes: Stop dexamethasone, as observational data shows increased mortality (13% treated had higher death rates) 1

Controversial/unclear benefit:

• Neisseria meningitidis: No clear benefit or harm demonstrated; decision can be individualized, though guidelines suggest stopping 1
• Other bacterial pathogens: Consider stopping, though some experts recommend continuing regardless of organism 1

Geographic and Resource Considerations

High-income countries:

• Strong Grade A recommendation for routine use 1, 2
• Benefits clearly demonstrated in settings with high standard of medical care 1

Low-income countries:

• No beneficial effects identified in studies from resource-limited settings 1, 2
• The lack of benefit may relate to delayed presentation, malnutrition, HIV co-infection, or limited supportive care 5

Mechanism of Action

Dexamethasone attenuates the subarachnoid space inflammatory response that drives morbidity and mortality by: 6, 2

• Decreasing cerebral edema and intracranial pressure
• Improving cerebral blood flow and perfusion pressure 4
• Reducing cerebral vasculitis
• Inhibiting pro-inflammatory cytokines (TNF-alpha, IL-1, platelet-activating factor) 4
• Preventing neuronal injury from excessive inflammation 6, 2

Critical Pitfalls to Avoid

Antibiotic penetration concerns:

• Dexamethasone decreases CSF penetration of vancomycin and some cephalosporins 7
• This is particularly concerning with antibiotic-resistant S. pneumoniae 7
• However, clinical trials showing benefit were conducted in the era of resistant pneumococci, and no increased treatment failures were observed 1, 3

Delayed administration:

• The most common error is giving dexamethasone after antibiotics have already been started 1
• Ideally, dexamethasone should be in the same syringe draw or immediate sequence as antibiotics 1, 2

Continuing unnecessarily:

• Do not continue the full 4-day course if Listeria is identified 1
• Reassess daily once pathogen identification occurs 1

Special Populations

HIV-associated tuberculous meningitis:

• Evidence for dexamethasone benefit is limited in HIV-positive patients with TB meningitis 8
• Concerns about immune reconstitution inflammatory syndrome (IRIS) when combined with antiretroviral therapy 8
• ART should be delayed 8 weeks in TB meningitis patients 8

Enteric fever encephalopathy:

• Dexamethasone may have a role similar to bacterial meningitis, using the same dosing regimens 6
• Mechanism involves reducing cerebral edema and inflammatory response 6