Why are corticosteroids, such as dexamethasone, given for Tuberculous (TB) meningitis, an infectious disease?

Why Corticosteroids Are Given for TB Meningitis

Corticosteroids, specifically dexamethasone or prednisolone, are strongly recommended for all patients with tuberculous meningitis because they reduce mortality by approximately 25%, despite TB being an infectious disease. 1

The Rationale: Inflammation, Not Infection, Drives Mortality

The key to understanding this paradox is recognizing that death and disability in TB meningitis result primarily from the host's inflammatory response rather than direct bacterial damage. 2 The inflammatory cascade in the subarachnoid space—characterized by leukocytosis (predominantly CD3+CD4+ T lymphocytes), elevated cytokines and chemokines, and blood-brain barrier dysfunction—causes the devastating neurological complications. 3

Evidence for Mortality Benefit

• A systematic review of nine randomized controlled trials (1,337 participants) demonstrated that corticosteroids reduce death by 25% (RR 0.75,95% CI 0.65-0.87) at follow-up from 3-18 months. 4

• The American Thoracic Society/CDC/IDSA guidelines (2016) provide a strong recommendation with moderate certainty in evidence for adjunctive corticosteroid therapy. 1

• Six of eight controlled trials showed benefit in terms of survival, frequency of sequelae, or both. 1, 2

Disease Stage Matters

The greatest mortality benefit occurs in patients with Stage II disease (lethargic/decreased level of consciousness): 1, 2

• Mortality with dexamethasone: 15% (4/27 patients)
• Mortality without dexamethasone: 40% (14/35 patients)
• p = 0.02

For Stage III disease (coma), the benefit was less pronounced but sample sizes were too small to definitively determine effect. 1

Recommended Corticosteroid Regimen

Dexamethasone or prednisolone should be tapered over 6-8 weeks: 1

Dosing

• Adults and children ≥25 kg: 12 mg/day initially 1, 2
• Children <25 kg: 8 mg/day initially 1, 2

Duration

• Initial full dose for 3 weeks 1, 2
• Gradual taper over the following 3-5 weeks 1, 2
• Total duration: 6-8 weeks 1

Timing

Dexamethasone should be started concurrently with antituberculous therapy (isoniazid, rifampin, pyrazinamide, and ethambutol). 2

Important Clinical Nuances

Effect on Disability

Corticosteroids may have little or no effect on disabling neurological deficit in survivors (RR 0.92,95% CI 0.71-1.20), though this outcome is less common than death. 4 The confidence interval includes possible harm, but any potential harm is quantitatively small compared to the mortality reduction. 4

Long-Term Follow-Up

One trial with 5-year follow-up showed the mortality benefit was no longer apparent at this extended time-point (RR 0.93,95% CI 0.78-1.12). 4 This suggests corticosteroids primarily prevent early deaths from severe inflammation rather than altering the long-term disease course.

HIV-Positive Patients

The evidence for HIV-positive patients is limited, with only 98 HIV-positive participants included across trials. 4 In this subgroup, the point estimates for death (RR 0.90,95% CI 0.67-1.20) and disability were similar to HIV-negative participants, but the small sample size means we cannot be certain the mortality benefit is preserved. 4

Mechanism of Action

Interestingly, dexamethasone does not appear to work by significantly attenuating immunological mediators of inflammation in cerebrospinal fluid or suppressing peripheral T cell responses to mycobacterial antigens. 3 The exact mechanism remains unclear, challenging previous theories of corticosteroid action in this disease. 3

Common Pitfalls to Avoid

Do not withhold corticosteroids based on concerns about "feeding the infection"—the evidence clearly shows mortality benefit outweighs theoretical risks. 1

Do not confuse TB meningitis with other forms of meningitis: 5

• Corticosteroids should be suspended if Listeria monocytogenes is identified (associated with increased mortality) 5
• Corticosteroids are not recommended as standard therapy for cryptococcal meningitis 5

Monitor for adverse events including gastrointestinal bleeding, invasive bacterial infections, hyperglycemia, and liver dysfunction, though these occur at similar rates as in controls. 4

Consider repeated lumbar punctures to monitor CSF cell count, glucose, and protein, especially early in therapy. 1