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

Drug Treatment for TB Meningitis

The recommended drug treatment for TB meningitis consists of rifampicin and isoniazid for 12 months, supplemented by pyrazinamide and a fourth drug (ethambutol or streptomycin) for at least the first two months, along with adjunctive corticosteroid therapy. 1, 2

Initial Treatment Regimen

• Initial intensive phase (first 2 months) should include:

  • Isoniazid (INH)
  • Rifampicin (RIF)
  • Pyrazinamide (PZA)
  • Fourth drug: Ethambutol (EMB) or streptomycin 1

• Continuation phase (additional 7-10 months):

  • Isoniazid and rifampicin for a total treatment duration of 9-12 months 1
  • Most guidelines recommend a full 12-month course for TB meningitis 2, 3

Drug Penetration Considerations

• Isoniazid, pyrazinamide, and ethionamide/prothionamide penetrate well into the cerebrospinal fluid 1, 2
• Rifampicin penetrates less well but remains essential for treatment 1, 2
• Streptomycin and ethambutol only penetrate adequately when meninges are inflamed in early treatment stages 1, 2

Adjunctive Corticosteroid Therapy

• Adjunctive corticosteroid therapy with dexamethasone or prednisolone tapered over 6-8 weeks is strongly recommended 1
• Dexamethasone (6-12 mg/day) or prednisolone (60-80 mg/day) for 6-8 weeks with gradual tapering is recommended 2, 3
• Corticosteroids have been shown to reduce mortality in TB meningitis 1

Special Populations

Children

• For children with TB meningitis, treatment should include:
  • Initial 4-drug regimen of INH, RIF, PZA, and ethionamide or an aminoglycoside (instead of EMB) for 2 months 1
  • Followed by 7-10 months of INH and RIF 1
  • Dosing should be weight-based and may need recalculation with weight gain 1, 2

HIV Co-infection

• Similar drug regimen is recommended for HIV-infected patients with TB meningitis 1
• Higher short-term morbidity and mortality is reported regardless of HIV serostatus 1

Monitoring and Follow-up

• Regular clinical assessment for neurological improvement or deterioration 2
• Repeated lumbar punctures should be considered to monitor changes in cerebrospinal fluid cell count, glucose, and protein, especially early in the course of therapy 1
• Monitor for drug-related adverse effects, particularly hepatotoxicity with isoniazid, rifampicin, and pyrazinamide 2, 4

Complications and Management

• Selected complications of tuberculous meningitis warranting neurosurgical referral include:
  • Hydrocephalus
  • Tuberculous cerebral abscess
  • Clinical situations with paraparesis 1
• Ventriculoperitoneal or ventriculoatrial shunting may be required to relieve signs and symptoms of hydrocephalus 3

Common Pitfalls to Avoid

• Inadequate treatment duration - TB meningitis requires longer treatment than pulmonary TB 2
• Insufficient drug penetration into CSF - ensure appropriate drug selection 1, 2
• Delayed initiation of corticosteroids - should be started promptly with antituberculous therapy 1, 3
• Premature discontinuation of corticosteroids - symptoms of CNS inflammation may recur if tapered too soon or too fast 3

Emerging Research

• Higher doses of intravenous rifampicin and fluoroquinolones are being evaluated in adults with tuberculous meningitis 1
• A 6-month intensive regimen with higher doses of isoniazid and rifampicin, pyrazinamide, and ethionamide instead of ethambutol has shown promising results in children 5
• The SURE trial is currently evaluating a 24-week intensified regimen (high-dose isoniazid, rifampicin, pyrazinamide, and levofloxacin) compared to standard 48-week therapy 6