CNS Tuberculosis Drug Regimen
For CNS tuberculosis (including tuberculous meningitis), use a 12-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (or alternative fourth drug) for 2 months, followed by rifampin and isoniazid for 10 additional months, with adjunctive corticosteroids for severe disease. 1
Initial Intensive Phase (2 Months)
Four-drug therapy is mandatory:
- Rifampin 10 mg/kg daily (maximum 600 mg) 2
- Isoniazid 5 mg/kg daily (maximum 300 mg) 2, 3
- Pyrazinamide 35 mg/kg daily for patients <50 kg or 2.0 g daily for patients ≥50 kg 2
- Fourth drug: Ethambutol 15 mg/kg daily is standard 2, BUT use streptomycin or ethionamide instead in unconscious patients since visual monitoring for ethambutol optic neuritis is impossible 1
Drug selection rationale: Isoniazid, pyrazinamide, and ethionamide penetrate well into cerebrospinal fluid, while rifampin penetrates less effectively 1. Streptomycin and ethambutol only achieve adequate CSF concentrations when meninges are inflamed during early treatment 1.
Continuation Phase (10 Months)
Two-drug therapy:
The 10-month continuation phase (total 12 months treatment) is essential to prevent relapse in CNS disease 4, 1. This differs critically from the 4-month continuation phase used for pulmonary TB 4.
Adjunctive Corticosteroid Therapy
Corticosteroids are strongly recommended for stages II and III CNS tuberculosis:
- Prednisolone 60 mg daily initially, tapering over several weeks 1
- Alternatively, dexamethasone may be used 2
- Duration: First 6-8 weeks of treatment 2
- Benefits: Decreases neurologic sequelae, improves outcomes, and reduces mortality when administered early 1
Essential Supportive Care
Pyridoxine (vitamin B6) supplementation is mandatory:
- Dose: 25-50 mg daily 2, 1
- Purpose: Prevents peripheral and central nervous system side effects from isoniazid 1
Administration Schedule
Daily dosing is mandatory for CNS tuberculosis 1. Never use intermittent (twice or thrice weekly) dosing for CNS disease, even though it may be acceptable for pulmonary TB 1.
Directly Observed Therapy (DOT) should be implemented to ensure adherence 2, 3.
Monitoring
Baseline hepatic function tests (AST/ALT and bilirubin) are essential, especially in:
- HIV-infected patients 2
- Pregnant women 2
- Patients with history of chronic liver disease 2
- Regular alcohol users 2
Monitor serum transaminases twice weekly during the first 2 weeks, then every 2 weeks during the first 2 months, then monthly 5. If AST/ALT rises to >5 times normal or bilirubin rises, stop rifampin, isoniazid, and pyrazinamide 4.
Special Populations
HIV co-infection:
- Use the same 12-month regimen 1
- Be aware of significant drug interactions between rifampin and protease inhibitors/NNRTIs 1
- Screen antimycobacterial drug levels in advanced HIV disease to prevent malabsorption and emergence of resistance 4
Pediatric patients:
- Minimum 12 months of therapy 1, 6
- Adjust dosing by weight: isoniazid 10-15 mg/kg daily (max 300 mg), rifampin 10-15 mg/kg daily, pyrazinamide 35 mg/kg daily 3
Pregnant women:
- Avoid streptomycin (causes congenital deafness) 3, 6
- Pyrazinamide use is controversial but increasingly accepted 6
Critical Pitfalls to Avoid
Never use a 6-month regimen for CNS tuberculosis - this is the single most dangerous error, as CNS disease requires 12 months minimum to prevent relapse 4, 1.
Never use intermittent dosing (twice or thrice weekly) for CNS TB - daily administration is mandatory 1.
Never omit the fourth drug in the initial phase, even in low-resistance settings, as CNS disease severity demands optimal treatment 1.
Never use ethambutol as the fourth drug in unconscious patients without considering alternatives (streptomycin or ethionamide), since visual monitoring is impossible 1.
Never forget corticosteroids in stages II and III disease - they significantly reduce mortality and neurologic sequelae 1.
Never add a single drug to a failing regimen - this leads to further drug resistance 4, 7.
Drug-Resistant CNS Tuberculosis
For multidrug-resistant (MDR) CNS TB, consultation with a TB specialist is mandatory 4, 6. Construct individualized regimens using: