What is the treatment for Meningoencephalitis tuberculosa?

Treatment for Tuberculous Meningitis

The standard treatment for tuberculous meningitis consists of a 12-month regimen with isoniazid, rifampin, pyrazinamide, and ethambutol for the initial 2 months, followed by isoniazid and rifampin for 10 months, along with adjunctive corticosteroid therapy using dexamethasone tapered over 6-8 weeks. 1

Initial Treatment Regimen

First-line Medications (Initial Phase - 2 months)

• Isoniazid (INH)
• Rifampin (RIF)
• Pyrazinamide (PZA)
• Ethambutol (EMB)

Continuation Phase (7-10 months)

• Isoniazid (INH)
• Rifampin (RIF)

Drug Administration Considerations

• Parenteral forms of isoniazid, rifampin, and fluoroquinolones are available for patients with altered mental status who cannot take oral medications 2
• CSF penetration varies by medication 1:
  • Good penetration: Isoniazid, Pyrazinamide, Fluoroquinolones
  • Moderate penetration: Rifampin
  • Poor penetration: Ethambutol

Adjunctive Corticosteroid Therapy

Adjunctive corticosteroid therapy is strongly recommended based on evidence showing mortality benefit 2, 1:

• Dexamethasone: 12 mg/day for adults (8 mg/day for children <25 kg)
• Duration: Initial 3 weeks, then tapered gradually over the following 3 weeks
• Alternative: Prednisolone tapered over 6-8 weeks 1

Monitoring and Follow-up

CSF Monitoring

• Repeated lumbar punctures should be performed to monitor changes in:
  • CSF cell count
  • Glucose
  • Protein levels
• Especially important early in the course of therapy 2

Additional Monitoring

• Neurological status assessment
• Liver function tests (weekly for first two weeks, then every two weeks during initial phase) 1
• Visual acuity and color discrimination testing for patients on ethambutol 1

Management of Complications

Neurosurgical Intervention

• Prompt neurosurgical referral for:
  • Hydrocephalus (may require ventriculoperitoneal or ventriculoatrial shunting)
  • Tuberculous cerebral abscess
  • Paraparesis 2, 1

Special Populations

HIV Co-infection

• HIV-infected patients may have higher mortality despite treatment 1
• Once-weekly isoniazid-rifapentine and twice-weekly isoniazid-rifampin/rifabutin regimens are not recommended in patients with CD4+ counts <100/mm³ 1
• Consider therapeutic drug monitoring due to potential drug absorption issues 1

Pregnancy

• Standard treatment can be used, but:
  • Avoid streptomycin (risk of fetal ototoxicity)
  • Routine use of pyrazinamide is not recommended due to inadequate teratogenicity data 1

Renal Failure

• Medications should be administered after dialysis 1

Common Pitfalls and Caveats

1. Delayed diagnosis: TBM is typically a subacute disease with symptoms that may persist for weeks before diagnosis 3. Early recognition and treatment initiation are crucial for improved outcomes.

2. Inadequate CSF sampling: CSF acid-fast smear and culture have relatively low sensitivity, but yield increases with multiple, large volume samples 3.

3. Relying solely on negative PCR: Nucleic acid amplification of CSF by PCR is highly specific but has suboptimal sensitivity, so a negative test does not rule out TBM 3.

4. Inadequate drug penetration: The blood-brain barrier significantly restricts delivery of anti-tuberculous medications to the CNS, potentially leading to subtherapeutic drug levels 4. Isoniazid is the only first-line bactericidal agent that easily crosses the blood-brain barrier 5.

5. Overlooking complications: Complications like hydrocephalus, vasculitis, and tuberculous cerebral abscess require prompt recognition and management 1, 4.

6. Stopping treatment too early: Treatment completion is determined by the number of doses taken, not just duration. The full regimen should be completed within the recommended timeframe 1.