Treatment of Tuberculosis Meningitis
Tuberculosis meningitis should be treated with rifampicin and isoniazid for 12 months, supplemented by pyrazinamide and a fourth drug (streptomycin or ethambutol) for at least the first two months, along with adjunctive corticosteroids for moderate to severe disease. 1
Standard Treatment Regimen
Initial Phase (First 2 Months)
Continuation Phase (Remaining 10 Months)
- Isoniazid
- Rifampicin 1
Medication Considerations
Drug Penetration into CSF
- Isoniazid, pyrazinamide, and prothionamide/ethionamide penetrate well into the cerebrospinal fluid
- Rifampicin penetrates less well
- Streptomycin and ethambutol only penetrate in adequate concentrations when the meninges are inflamed in the early stage of treatment 2, 1
Special Situations
- If pyrazinamide is omitted or cannot be tolerated, treatment should be prolonged to 18 months 2, 1
- For cerebral tuberculoma(s) without meningitis, the 12-month regimen is still recommended 2
- In areas with high drug resistance (>4%), ensure at least two active anti-tubercular drugs are included in therapy 3
Adjunctive Corticosteroid Therapy
Corticosteroids are strongly recommended for TB meningitis, particularly for moderate to severe disease (stages II and III) 2, 1, 4:
- Stage I: Fully conscious, rational, no neurologic signs
- Stage II: Confused or with neurologic signs (cranial nerve palsy, hemiparesis)
- Stage III: Comatose or stuporous with severe neurologic signs
Corticosteroid Regimen
- Dexamethasone 6-12 mg/day or prednisone 60-80 mg/day initially
- Taper over 4-8 weeks 3
- Note: Rifampicin reduces the efficacy of corticosteroids, so maintenance doses may need to be doubled 1
Monitoring and Complications
Hydrocephalus Management
- May require ventriculoperitoneal or ventriculoatrial shunting if severe 3
- Steroids and diuretics (furosemide, acetazolamide) are sometimes used to treat hydrocephalus 3
Treatment Response
- If cultures remain positive for extended periods or symptoms respond slowly, therapy should be extended to 18 months 3
- Symptoms of CNS inflammation may recur if corticosteroid taper is implemented too soon or too rapidly 3
Special Populations
HIV Co-infection
- May require longer courses of therapy 3
- Important considerations include drug interactions and higher rates of drug-resistant TB 5
Children
- Same regimen as adults: rifampicin and isoniazid for 12 months, with pyrazinamide and a fourth drug for the first two months 1
Emerging Research
Recent research has focused on optimizing treatment regimens:
- Higher doses of rifampicin may improve outcomes due to better CNS penetration 6
- Extended use of pyrazinamide throughout treatment (beyond initial phase) is being investigated 7
Early treatment initiation is crucial for improving outcomes, as mortality remains high despite appropriate therapy, with most deaths occurring within the first month of treatment 6.