Treatment Regimen for Tubercular Cerebrospinal Fluid (CSF)
For patients with tubercular cerebrospinal fluid (CSF) findings, a 12-month regimen of rifampicin and isoniazid, supplemented by pyrazinamide and a fourth drug for at least the first two months is strongly recommended. 1
Initial Phase (First 2 Months)
The initial intensive phase should include four drugs 1, 2:
- Rifampicin (10 mg/kg, up to 600 mg daily)
- Isoniazid (5 mg/kg, up to 300 mg daily)
- Pyrazinamide (35 mg/kg, up to 2 g daily)
- Ethambutol (15 mg/kg daily) OR streptomycin
Drug selection considerations for CNS tuberculosis 1, 3:
- Isoniazid and pyrazinamide penetrate well into the cerebrospinal fluid
- Rifampicin penetrates less well but remains a critical component
- Ethambutol and streptomycin only penetrate adequately when meninges are inflamed in early treatment
Continuation Phase (Months 3-12)
- After the initial 2-month phase, continue with 4, 1:
- Rifampicin (10 mg/kg, up to 600 mg daily)
- Isoniazid (5 mg/kg, up to 300 mg daily)
- Total treatment duration should be 12 months for tuberculous meningitis or cerebral tuberculoma
Adjunctive Corticosteroid Therapy
- Corticosteroids are recommended for more severe disease (stages II and III) 1
- High-dose corticosteroid treatment (prednisolone 60 mg/day initially, tapered over several weeks) has shown clear benefit in reducing neurological sequelae 1
- Corticosteroids have been shown to decrease neurologic complications when administered early in the disease course 1
Special Considerations
- If pyrazinamide is omitted or cannot be tolerated, treatment should be prolonged to 18 months 1
- Ethambutol should be used with caution in unconscious patients as visual acuity cannot be tested 1
- Drug susceptibility testing should be performed whenever possible to guide therapy 4
- Consultation with a TB expert is recommended for complex cases, especially when drug resistance is suspected 4
Monitoring
- Response to therapy should be monitored clinically and with neuroimaging 1
- Regular assessment of liver function is important due to potential hepatotoxicity of isoniazid, rifampicin, and pyrazinamide 5, 6
Drug-Resistant Considerations
- If drug resistance is suspected or confirmed, treatment must be individualized based on susceptibility studies 4, 7
- For isoniazid-resistant TB, a regimen containing a fluoroquinolone, rifampicin, ethambutol, and pyrazinamide for 6 months is suggested 4
- For MDR-TB involving the CNS, a combination of levofloxacin, an injectable agent (if susceptible), ethionamide, linezolid, and pyrazinamide would be appropriate due to excellent CSF penetration 7
Important Caveats
- Delayed diagnosis and treatment of tuberculous meningitis significantly increases mortality and morbidity 8
- Treatment should be initiated as soon as clinical suspicion is supported by initial CSF studies, even before confirmation 8
- Never add a single effective drug to a failing regimen as this may lead to development of additional resistance 4
- Intrathecal administration of streptomycin is unnecessary and not recommended 1
The recommended 12-month regimen for tubercular CSF is longer than the standard 6-month regimen for pulmonary TB due to the serious nature of CNS involvement and the need to ensure complete eradication of the infection to prevent neurological sequelae 4, 2.