What is the recommended treatment regimen for tuberculous meningitis, including drug selection, dosing, adjunctive corticosteroid therapy, and treatment duration?

TB Meningitis Treatment

For tuberculous meningitis, initiate immediate treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampicin for 7-10 additional months (total 9-12 months), plus adjunctive dexamethasone 12 mg/day IV (or prednisolone 60 mg/day) tapered over 6-8 weeks starting immediately with or before anti-TB drugs. 1, 2, 3

Initial Intensive Phase (First 2 Months)

Drug Selection:

• Isoniazid + Rifampicin + Pyrazinamide + Ethambutol is the standard four-drug regimen 1, 3
• Ethambutol is preferred over streptomycin as the fourth drug in adults based on expert opinion, though both are acceptable 1, 3
• For children, use isoniazid, rifampicin, pyrazinamide, and ethionamide or an aminoglycoside (instead of ethambutol due to difficulty monitoring visual acuity in young children) 1, 3
• Daily dosing is strongly preferred over intermittent regimens 1, 2

Continuation Phase (7-10 Additional Months)

• After 2 months of four-drug therapy, continue isoniazid + rifampicin only for 7-10 additional months 1, 3
• Total treatment duration must be 9-12 months, with 12 months being the preferred duration 2, 3, 4, 5
• This is NOT the 6-month regimen used for pulmonary TB—inadequate treatment duration is the most common critical error 3

Adjunctive Corticosteroid Therapy

This is a strong recommendation with moderate certainty evidence showing approximately 25% mortality reduction. 1, 2, 6

Adult Dosing:

• Dexamethasone 12 mg/day IV (or 0.4 mg/kg/day, maximum 12 mg) for the first 3 weeks, then gradually taper over the subsequent 3 weeks (total 6 weeks) 2, 6
• Alternative: Prednisolone 60 mg/day tapered over 6-8 weeks 1, 2
• Specific tapering schedule for prednisolone: 60 mg/day for 4 weeks, then 30 mg/day for 4 weeks, 15 mg/day for 2 weeks, and 5 mg/day for the final week 2

Pediatric Dosing:

• Children ≥25 kg: Dexamethasone 12 mg/day (same as adults) 2, 6
• Children <25 kg: Dexamethasone 8 mg/day 2, 6
• Same tapering schedule as adults (3 weeks full dose, then 3 weeks taper) 2

Critical Implementation Details:

• Start corticosteroids immediately before or concurrently with the first dose of anti-TB medication—do not delay 2, 6
• Dexamethasone should be given intravenously for the first 3 weeks 2
• Oral prednisolone is acceptable when IV access is problematic 2
• The mortality benefit is most pronounced in Stage II disease (lethargic presentation) 2, 6

Critical Pitfalls and How to Avoid Them

Never Stop Steroids Abruptly:

• Complete the full 6-8 week tapered course regardless of clinical improvement 2, 6
• Abrupt discontinuation causes life-threatening adrenal crisis from HPA axis suppression after prolonged high-dose therapy 2, 6
• Even if the patient appears clinically improved or develops paradoxical tuberculomas during therapy, continue the full taper 2

Treatment Duration Error:

• TB meningitis requires 9-12 months, not 6 months—this is the single most common error 3
• Do not discontinue therapy early even if CSF normalizes 3

Do Not Wait for Microbiological Confirmation:

• TB meningitis is a medical emergency—start empiric treatment immediately when clinical suspicion is supported by initial CSF findings 5
• Treatment delay is strongly associated with death 5

Monitoring Requirements

• Repeated lumbar punctures to monitor CSF cell count, glucose, and protein, especially early in therapy 1, 3, 6
• Regular neurological assessment for improvement or deterioration 3
• Monitor for hepatotoxicity given the hepatotoxic potential of isoniazid, rifampicin, and pyrazinamide 3
• Monitor for steroid complications: hyperglycemia, gastrointestinal bleeding, invasive bacterial infections 6

Neurosurgical Referral Indications

Immediate neurosurgical consultation is warranted for: 1, 3

• Hydrocephalus with symptoms of raised intracranial pressure
• Tuberculous cerebral abscess
• Paraparesis or spinal cord compression

Special Populations

HIV-Positive Patients:

• Delay ART initiation for 8 weeks after starting anti-TB therapy, even with CD4 <50 cells/μL, due to increased risk of severe or fatal neurological complications from IRIS 6
• For moderate to severe paradoxical TB-IRIS, prednisone 1.25 mg/kg/day significantly reduces need for hospitalization 6
• The principles of diagnosis and treatment are the same, but drug interactions and IRIS complicate management 5
• Manage in specialist units with expertise in both HIV and tuberculosis 5

Drug-Resistant TB:

• If drug resistance is suspected or confirmed, refer to centers with experience for close monitoring and regimen adaptation 1
• Initial drug resistance is strongly associated with increased mortality 7