What is the recommended treatment regimen for Tuberculosis (TB) meningitis?

Treatment Regimen for Tuberculosis Meningitis

The recommended treatment regimen for tuberculosis (TB) meningitis consists of rifampicin, isoniazid, pyrazinamide, and a fourth drug (ethambutol or streptomycin) for the initial 2 months, followed by rifampicin and isoniazid for a total treatment duration of 12 months. 1

First-Line Treatment Regimen

The standard treatment approach includes:

• Initial Phase (First 2 Months):

  • Rifampicin: 10-15 mg/kg/day (up to 600 mg daily)
  • Isoniazid: 5 mg/kg/day (up to 300 mg daily) 2
  • Pyrazinamide: Standard weight-based dosing
  • Fourth drug: Either ethambutol or streptomycin

• Continuation Phase (10 Additional Months):

  • Rifampicin and isoniazid for the remaining treatment period

The World Health Organization (WHO) recommends these first-line agents due to their good cerebrospinal fluid (CSF) penetration, particularly isoniazid and pyrazinamide 1.

Fourth Drug Selection

The choice of the fourth drug should be guided by the following considerations:

• Ethambutol: May be used despite poor CSF penetration when meninges are inflamed 1

  • Caution: Regular monitoring of visual acuity and color discrimination is essential
  • Not recommended in young children whose visual acuity cannot be monitored 1, 2

• Streptomycin: Administered at 15 mg/kg/day (maximum 1g/day) parenterally as a single daily dose 1

  • Requires monitoring: Baseline and periodic audiometry and renal function tests
  • Contraindicated in pregnancy and severe renal impairment

• Fluoroquinolones: Levofloxacin or moxifloxacin may be preferred as fourth drugs due to better CSF penetration than ethambutol or streptomycin 1

  • Particularly valuable in areas with high drug resistance

Adjunctive Corticosteroid Therapy

Corticosteroids are strongly recommended for moderate to severe TB meningitis (stages II and III) 1, 3:

• Dexamethasone: 6-12 mg/day initially
• Prednisone: 60-80 mg/day initially
• Taper over 4-8 weeks
• Note: If rifampicin is used, the maintenance dose of corticosteroids should be doubled due to drug interactions 1

Special Considerations

Drug Resistance

• In areas with high drug resistance (>4% isoniazid resistance), ensure at least two active anti-tubercular drugs are included in therapy 1, 3
• For isoniazid-resistant TB: 6 months of rifampicin, ethambutol, pyrazinamide, and levofloxacin 1

Treatment Modifications

• If pyrazinamide cannot be tolerated or is omitted, treatment should be prolonged to 18 months 1
• For pregnant patients, streptomycin should be avoided (risk of congenital deafness), and pyrazinamide is not recommended due to inadequate teratogenicity data 2

CSF Drug Penetration

Understanding CSF penetration is crucial for effective treatment:

• Good penetration: Isoniazid, pyrazinamide, ethionamide
• Moderate penetration: Rifampicin
• Poor penetration: Ethambutol, streptomycin 1

Treatment Monitoring

• Regular clinical assessment for treatment response
• Monitor for adverse effects, particularly:
  • Visual disturbances with ethambutol
  • Ototoxicity and nephrotoxicity with streptomycin
  • Hepatotoxicity with isoniazid, rifampicin, and pyrazinamide

Emerging Evidence

Recent research suggests that intensified regimens with high-dose rifampicin (13 mg/kg intravenously) may improve survival in severe TB meningitis 4. This approach led to three times higher drug concentrations in CSF and was associated with reduced mortality (35% vs 65%) without increased toxicity. While promising, this approach is not yet incorporated into standard guidelines but may represent a future direction for treatment.