Dexamethasone in Bacterial Meningitis
Direct Recommendation
Administer dexamethasone 10 mg IV every 6 hours for 4 days to all adults with suspected bacterial meningitis in high-income countries, starting 10-20 minutes before or concomitant with the first antibiotic dose. 1
For children, give dexamethasone 0.15 mg/kg IV every 6 hours for 2-4 days, using the same timing relative to antibiotics. 1
Evidence-Based Rationale
Mechanism of Benefit
Dexamethasone attenuates the subarachnoid space inflammatory response that drives morbidity and mortality in bacterial meningitis. 2 It specifically reduces:
- Cerebral edema and increased intracranial pressure 2
- Altered cerebral blood flow and cerebral vasculitis 2
- Neuronal injury mediated by pro-inflammatory cytokines 2
The inflammatory cascade is initiated when bacterial products interact with Toll-like receptors, triggering MyD88-dependent cytokine production and massive neutrophil recruitment that causes collateral brain tissue damage. 3
Adult Patients
Mortality and Morbidity Benefits
The landmark European Dexamethasone Study demonstrated that adjunctive dexamethasone significantly reduces unfavorable outcomes (15% vs 25%, P=0.03) and mortality (7% vs 15%, P=0.04) in adults with bacterial meningitis. 2
For pneumococcal meningitis specifically, the benefits are even more pronounced:
- Unfavorable outcomes: 26% vs 52% (P=0.006) 2
- Mortality: 14% vs 34% (P=0.02) 2
- Independent risk factor analysis confirms absence of dexamethasone therapy predicts death (P=0.05) 4
The greatest benefit occurs in patients with moderate-to-severe disease on the Glasgow Coma Scale. 2
Timing Considerations
If antibiotics have already been started, dexamethasone can still be administered up to 4 hours after the first antibiotic dose. 1 However, optimal benefit requires administration 10-20 minutes before or concomitant with antibiotics. 2, 1
Pediatric Patients
H. influenzae Type B Meningitis
The evidence most strongly supports dexamethasone use in H. influenzae type b meningitis, with confirmed reduction in hearing impairment (OR 0.31; 95% CI 0.14-0.69). 2, 1 The recommended regimen is 0.15 mg/kg every 6 hours for 2-4 days. 2
Pneumococcal Meningitis in Children
For pneumococcal meningitis in children, the evidence is more controversial. 2 Early administration suggests benefit for severe hearing loss (OR 0.09; 95% CI 0.0-0.71). 1 The American Academy of Pediatrics states that adjunctive dexamethasone "may be considered after weighing potential benefits and possible risks," acknowledging that data are insufficient to demonstrate clear benefit. 2
Critical Caveat
Do not administer dexamethasone to infants and children who have already received antimicrobial therapy, as it is unlikely to improve outcomes in this circumstance. 2
Pathogen-Specific Guidance
When to Continue or Discontinue
Streptococcus pneumoniae: Continue dexamethasone for the full 4-day course—this pathogen shows the strongest evidence for benefit. 2, 1
Haemophilus influenzae type b: Continue dexamethasone for the full course, particularly in children where hearing protection is well-established. 2, 1
Neisseria meningitidis: The benefit is less clear due to lower event rates in studies. 1 Some experts recommend discontinuing dexamethasone if this organism is identified, while others advise continuing regardless of causative organism. 1
Other organisms: Discontinue dexamethasone if the causative organism is neither H. influenzae nor S. pneumoniae. 1
Non-bacterial diagnosis: Stop dexamethasone immediately if the patient is discovered not to have bacterial meningitis. 1
Important Caveats and Pitfalls
Antibiotic-Resistant Pneumococci
Dexamethasone significantly decreases vancomycin and ceftriaxone penetration into CSF and delays CSF sterilization. 5 When treating meningitis caused by antibiotic-resistant pneumococci, use combination antibiotic therapy (vancomycin plus third-generation cephalosporin) to mitigate the risk of treatment failure. 2, 5
Geographic Considerations
No beneficial effects have been identified in studies performed in low-income countries. 1 The recommendation for routine use applies specifically to high-income countries. 1
Neonatal Meningitis
Dexamethasone is not currently recommended for neonatal bacterial meningitis. 1
Adverse Events
Dexamethasone does not increase the risk of gastrointestinal bleeding compared to placebo (2 vs 5 patients in the landmark trial). 6 Treatment with dexamethasone reduces both systemic and neurological complications during hospitalization. 4
Conflicting Evidence Acknowledgment
A 2016 meta-analysis of 2,459 patients found that dexamethasone was not associated with significant reduction in mortality (OR 0.91, P=0.14) or severe neurological sequelae (OR 0.84, P=0.42), though it did reduce hearing loss (OR 0.76, P=0.03). 7 However, this meta-analysis is superseded by the more definitive European Dexamethasone Study and current guideline recommendations from the Infectious Diseases Society of America and American Academy of Pediatrics, which prioritize the highest quality single trial over pooled heterogeneous data. 2, 1, 6