What is the treatment for tubercular meningitis?

Treatment of Tubercular Meningitis

Treat tubercular meningitis with rifampicin and isoniazid for 12 months, supplemented by pyrazinamide and a fourth drug (ethambutol or streptomycin) for the first 2 months, plus adjunctive corticosteroids for moderate to severe disease (stages II and III). 1, 2

Standard Treatment Regimen

Intensive Phase (First 2 Months)

• Rifampicin 10 mg/kg daily (maximum 600 mg) 1, 2
• Isoniazid 5 mg/kg daily (maximum 300 mg) 1, 3
• Pyrazinamide 35 mg/kg daily (maximum 2 g) 1, 4
• Fourth drug - either ethambutol 15 mg/kg daily OR streptomycin 15 mg/kg daily 5, 1, 2

Continuation Phase (Months 3-12)

• Rifampicin and isoniazid continued for the remaining 10 months 5, 1, 2
• Total treatment duration: 12 months minimum 5, 1, 6

Adjunctive Corticosteroid Therapy

Corticosteroids are essential for stages II and III disease and should be started immediately. 1, 2, 7

• Dexamethasone 6-12 mg/day OR prednisolone/prednisone 60-80 mg/day 1, 6
• Taper gradually over 6-8 weeks 1, 2
• Benefits include reduced mortality, decreased neurological sequelae, and prevention of complications 2, 6
• Stage II patients (confused or with focal neurologic signs) and Stage III patients (comatose/stuporous) should receive corticosteroids 5, 6

Drug Selection Rationale

CSF Penetration Considerations

• Good penetration: Isoniazid, pyrazinamide, ethionamide 5, 1, 4
• Moderate penetration: Rifampicin (still essential despite lower penetration) 5, 4
• Poor penetration: Streptomycin and ethambutol (adequate only when meninges inflamed early in treatment) 5, 1, 4
• Intrathecal streptomycin is unnecessary and not recommended 5, 4

Fourth Drug Selection

• Use ethambutol 15 mg/kg daily as first choice for the fourth drug 5, 1
• Caution: Avoid ethambutol in unconscious patients (stage III) since visual acuity cannot be monitored 5
• Alternative: Streptomycin 15 mg/kg daily if ethambutol contraindicated 5, 2
• Add a fourth drug if local isoniazid resistance exceeds 4% or is unknown 3, 6

Pediatric Considerations

• Same 12-month duration with rifampicin and isoniazid 5, 2, 4
• Initial 2 months include pyrazinamide plus either streptomycin or ethambutol 5, 4
• Weight-based dosing: Isoniazid 10-15 mg/kg (max 300 mg), rifampicin adjusted per weight 5
• Recalculate doses as child gains weight 5, 4
• Pyridoxine supplementation only for breast-fed infants and malnourished children 5, 4

Emerging Pediatric Evidence

• A 6-month intensive regimen (6HRZEto) using higher-dose isoniazid/rifampicin with ethionamide instead of ethambutol showed 94.6% treatment success versus 75.4% with the standard 12-month regimen in a 2022 meta-analysis 8
• However, this shorter regimen is not yet widely adopted in major guidelines and requires further validation 8

Critical Pitfalls to Avoid

• Inadequate treatment duration: TB meningitis requires 12 months, NOT the 6 months used for pulmonary TB - this is the most dangerous error 1, 2
• Omitting corticosteroids in moderate to severe disease (stages II-III) increases mortality and neurological sequelae 1, 2
• Using ethambutol in unconscious patients without ability to monitor visual acuity 5
• Premature corticosteroid taper: CNS inflammation may recur if steroids tapered too quickly 6
• Failing to extend treatment to 18 months if pyrazinamide is omitted or not tolerated 5

Monitoring Requirements

• Regular neurological assessment for improvement or deterioration 2, 6
• Hepatotoxicity monitoring essential given hepatotoxic potential of isoniazid, rifampicin, and pyrazinamide 1, 2
• Repeated lumbar punctures to monitor CSF parameters (cell count, glucose, protein) especially early in therapy 1
• Monitor for hydrocephalus requiring ventriculoperitoneal shunting 6, 9

Special Circumstances

If Pyrazinamide Cannot Be Used

• Extend total treatment duration to 18 months 5

Drug-Resistant TB Meningitis

• Isoniazid mono-resistance: Rifampicin, pyrazinamide, ethambutol, and fluoroquinolone for 12-15 months 1
• Rifampicin mono-resistance: Isoniazid, pyrazinamide, ethambutol, fluoroquinolone, and injectable agent for 18 months 1
• MDR-TB: Injectable drug for 4-6 months with total duration 18-24 months 1
• Consult TB expert for all drug-resistant cases 3, 6