What is the treatment for tuberculosis meningitis?

Treatment of Tuberculosis Meningitis

Tuberculosis meningitis should be treated for a minimum of 12 months with rifampicin and isoniazid, supplemented by pyrazinamide and a fourth drug (either streptomycin or ethambutol) for at least the first two months, along with corticosteroids for moderate to severe disease. 1

Standard Treatment Regimen

Initial Phase (First 2 Months)

• Isoniazid (penetrates well into CSF)
• Rifampicin (penetrates less well into CSF)
• Pyrazinamide (penetrates well into CSF)
• Fourth drug: either streptomycin or ethambutol 1
  • Note: Ethambutol should be used with caution in unconscious patients (stage III) as visual acuity cannot be tested

Continuation Phase (10 Months)

• Isoniazid and rifampicin for remaining 10 months 1

Disease Staging and Adjunctive Therapy

Disease Staging

• Stage I: Fully conscious, rational, no neurologic signs
• Stage II: Confused or has neurologic signs (cranial nerve palsy, hemiparesis)
• Stage III: Comatose or stuporous with severe neurologic signs 2

Corticosteroid Therapy

• Strongly recommended for more severe disease (stages II and III) 1
• Corticosteroids have been shown to improve mortality in TB meningitis 1, 3
• Dosing: Dexamethasone 6-12 mg/day or prednisone 60-80 mg/day initially, tapered over 4-8 weeks 2
• Caution: Symptoms of CNS inflammation may recur if corticosteroid taper is implemented too soon or too fast 2

Special Considerations

Drug Penetration into CSF

• Isoniazid, pyrazinamide, and prothionamide/ethionamide penetrate well into CSF
• Rifampicin penetrates less well
• Streptomycin and ethambutol only penetrate in adequate concentrations when meninges are inflamed in early treatment stage 1, 4

Treatment Duration Modifications

• If pyrazinamide is omitted or cannot be tolerated, treatment should be prolonged to 18 months 1
• For cerebral tuberculoma(s) without meningitis, the 12-month regimen is still recommended 1

Treatment in Children

• Same regimen as adults: rifampicin and isoniazid for 12 months, with pyrazinamide and a fourth drug (streptomycin or ethambutol) for the first two months 1

Management of Complications

• Hydrocephalus may require ventriculoperitoneal or ventriculoatrial shunting 2
• Lumbar puncture should be performed in cases of miliary TB to rule out meningeal involvement 1

Common Pitfalls and Caveats

1. Delayed Diagnosis: TBM is typically a subacute disease with symptoms that may persist for weeks before diagnosis. Early treatment is critical for improved outcomes 5

2. Inadequate CSF Sampling: CSF acid-fast smear and culture have relatively low sensitivity but yield increases with multiple, large volume samples 5

3. Drug Resistance: If local incidence of drug resistance is greater than 4% or unknown, a fourth drug should be added to the initial regimen 2

4. Monitoring Treatment Response: If cultures remain positive for extended periods or symptoms respond slowly, therapy should be extended to 18 months 2

5. Corticosteroid Tapering: Too rapid tapering of corticosteroids may lead to recurrence of CNS inflammation 2

6. Drug Interactions: Rifampicin reduces the efficacy of oral contraceptives and corticosteroids (maintenance dose of corticosteroids should be doubled if rifampicin is used) 1

The treatment of tuberculosis meningitis requires prompt initiation of appropriate anti-tuberculous therapy and careful management of complications to improve survival and reduce neurological sequelae.