What is the role of steroids, specifically dexamethasone, in the management of bacterial meningitis in adults and pediatric patients?

Steroids in Bacterial Meningitis

Primary Recommendation

Start dexamethasone 10 mg IV every 6 hours for adults (or 0.15 mg/kg IV every 6 hours for children) immediately with or 10-20 minutes before the first antibiotic dose in all patients with suspected bacterial meningitis in high-income countries, then discontinue if the pathogen is identified as something other than S. pneumoniae or H. influenzae type b. 1, 2

Dosing and Administration Algorithm

Adults

• Dexamethasone 10 mg IV every 6 hours for 4 days 1, 2
• The first dose must be given 10-20 minutes before or at minimum concomitant with the first antimicrobial dose 1, 2
• Timing is absolutely critical—the benefit is maximized only when given before or with antibiotics, as it prevents the inflammatory response from antibiotic-induced bacterial lysis 2

Pediatric Patients

• Dexamethasone 0.15 mg/kg IV every 6 hours for 2-4 days 1, 2
• Same timing requirement: administer 10-20 minutes before or with the first antibiotic dose 1
• The 1991 landmark pediatric trial demonstrated that early dexamethasone reduced neurologic or audiologic sequelae from 38% to 14% (relative risk 3.8 for placebo vs dexamethasone) 3

Pathogen-Specific Tailoring

Continue Dexamethasone For:

• Streptococcus pneumoniae: Strong evidence for mortality reduction (from 34% to 14%) and decreased neurological sequelae (unfavorable outcomes reduced from 52% to 26%) 1, 2
• Haemophilus influenzae type b: Confirmed benefit for reducing hearing impairment (OR 0.31; 95% CI 0.14-0.69) 1, 2

Discontinue Dexamethasone For:

• Listeria monocytogenes: May increase mortality—stop immediately 2
• Staphylococcus aureus (including MRSA): No evidence of benefit; discontinue once identified 1
• Any organism other than S. pneumoniae or H. influenzae: The European Society of Clinical Microbiology and Infectious Diseases provides Grade B recommendation to stop dexamethasone 1

Mechanism of Benefit

Dexamethasone works by attenuating the subarachnoid space inflammatory response through multiple pathways 1:

• Decreases cerebral edema and intracranial pressure 1
• Reduces altered cerebral blood flow and cerebral vasculitis 1
• Prevents neuronal injury mediated by pro-inflammatory cytokines 1
• The 1991 pediatric study demonstrated that by 12 hours, dexamethasone-treated children had improved cerebrospinal pressure, decreased meningeal inflammation, and reduced CSF concentrations of tumor necrosis factor alpha and platelet-activating factor 3

Special Populations

Tuberculous Meningitis

• Use dexamethasone 0.4 mg/kg/day (maximum 12 mg/day) IV for 3 weeks, then taper over the following 3 weeks 1, 4
• For adults and children ≥25 kg: 12 mg/day initially; for children <25 kg: 8 mg/day initially 4
• Start concurrently with antituberculous therapy 1, 4
• The American Thoracic Society strongly recommends this, as it reduces mortality and neurological sequelae, particularly in Stage II disease (lethargic patients) where mortality decreased from 40% to 15% 4

Cryptococcal Meningitis

• Dexamethasone is NOT recommended—it may worsen outcomes 2

Low-Income Countries

• Benefits of dexamethasone are only demonstrated in high-income countries with high standards of medical care 1, 2
• No beneficial effects were identified in low-income country studies 1

Critical Pitfalls to Avoid

Timing Errors

• Never delay dexamethasone administration—benefit is lost if not given before or with antibiotics 1
• The inflammatory cascade begins immediately with antibiotic-induced bacterial lysis; dexamethasone must be present to prevent this 2

Antibiotic Penetration Concerns

• Do not withhold dexamethasone due to concerns about decreased CSF antibiotic concentrations 1
• While dexamethasone may theoretically decrease CSF antibiotic levels, the overall clinical benefit outweighs this concern when appropriate antibiotics are used 1

Pathogen-Specific Continuation

• Do not continue dexamethasone for all pathogens—actively discontinue for Listeria and other non-pneumococcal/non-H. influenzae organisms 1, 2

Evidence Quality Considerations

The evidence base shows some divergence. A 2016 meta-analysis of 2,459 patients found that dexamethasone was not associated with significant reduction in mortality (OR 0.91,95% CI 0.80-1.03) or severe neurological sequelae (OR 0.84,95% CI 0.54-1.29), but did reduce hearing loss among survivors (OR 0.76,95% CI 0.59-0.98) 5. Similarly, a 2010 individual patient data meta-analysis of 2,029 patients found no significant reduction in death or severe neurological sequelae overall, but suggested benefit for hearing loss prevention 6.

However, current guideline consensus from the Infectious Diseases Society of America, American Academy of Pediatrics, and European Society of Clinical Microbiology and Infectious Diseases all recommend empiric dexamethasone use based on pathogen-specific benefits, particularly for pneumococcal and H. influenzae meningitis 1, 2. The 1993 Swiss study showed a trend toward reduced sequelae (16% vs 5%, p=0.066) with relative risk of 3.27 7, and the 2006 European Dexamethasone Study demonstrated reduction in unfavorable outcomes from 25% to 15% in adults 8.