What is the treatment for Tuberculosis (TB) meningitis with hydrocephalus in children?

Treatment of TB Meningitis with Hydrocephalus in Children

Children with TB meningitis and hydrocephalus should receive a minimum 12-month regimen of rifampicin and isoniazid, supplemented by pyrazinamide and a fourth drug (streptomycin or ethambutol) for the initial 2 months, along with adjunctive corticosteroids, while hydrocephalus management may require CSF shunting or medical therapy with acetazolamide and furosemide. 1, 2

Antimicrobial Therapy

Initial Intensive Phase (First 2 Months)

• Rifampicin 10-20 mg/kg/day (maximum 600 mg) 2, 3
• Isoniazid 10-15 mg/kg/day (maximum 300 mg) 1, 3
• Pyrazinamide 15-30 mg/kg/day 1, 3
• Fourth drug - either:
  • Ethambutol 15-25 mg/kg/day (preferred in most guidelines) 1, 2, OR
  • Streptomycin 15 mg/kg/day 1
  • Note: Ethambutol should be used with caution in unconscious patients (stage III disease) as visual acuity cannot be monitored 1

Continuation Phase (10 Additional Months)

• Rifampicin and Isoniazid continued for total duration of 12 months 1, 2, 4
• This extended duration is critical because shorter 6-month regimens used for pulmonary TB are inadequate for meningitis 1

Drug Penetration Considerations

• Isoniazid and pyrazinamide penetrate well into CSF 1, 2
• Rifampicin penetrates less well but remains essential 1, 2
• Streptomycin and ethambutol only achieve adequate CSF concentrations when meninges are inflamed during early treatment 1, 2
• Intrathecal streptomycin is unnecessary 1

Alternative Shorter Regimen (Emerging Evidence)

Recent research suggests a 6-month intensive regimen (6HRZEto) using higher-dose isoniazid and rifampicin with pyrazinamide and ethionamide (instead of ethambutol) may be effective, with treatment success of 94.6% versus 75.4% for the standard 12-month regimen 5. However, this is based on limited studies and the 12-month regimen remains the established standard in most guidelines 1, 2.

Adjunctive Corticosteroid Therapy

Corticosteroids are strongly recommended for all children with TB meningitis, particularly those with moderate to severe disease (stages II and III). 1, 2, 4

Dosing Options

• Dexamethasone 0.4 mg/kg/day (or 6-12 mg/day) for 3 weeks, then gradually tapered over following 3 weeks 2, 4, OR
• Prednisolone 60-80 mg/day initially, tapered over 6-8 weeks 1, 2

Benefits

• Reduces mortality (strong recommendation with moderate certainty of evidence) 1, 4
• Decreases neurological sequelae 2, 4
• Prevents complications including hydrocephalus progression 2

Management of Hydrocephalus

Assessment and Monitoring

• Hydrocephalus is a common complication requiring prompt neurosurgical evaluation 1, 4
• Monitor intracranial pressure (ICP) and ventricular size clinically and with neuroimaging 6
• Repeated lumbar punctures should be considered to monitor CSF changes (cell count, glucose, protein) 1

Treatment Options for Hydrocephalus

CSF Shunting

• Indicated for severe or progressive hydrocephalus not responding to medical management 6
• Ventriculoperitoneal shunting is the definitive surgical intervention 4, 6

Medical Management

• Acetazolamide and furosemide combination is significantly more effective than antituberculous drugs alone in achieving normal ICP 6
• This approach is particularly useful for communicating hydrocephalus 6

Ventricular Drainage with Intrathecal Therapy

• Lateral ventricular drainage with injection of isoniazid (100 mg) and dexamethasone (2 mg) through drainage tube can rapidly decrease ICP 7
• This approach may normalize CSF within 2-4 weeks 7
• Consider in severe cases with brain herniation 7

Supportive Care and Monitoring

Pyridoxine Supplementation

• Recommended for breastfed infants, malnourished children, and HIV-infected children 1, 3
• Prevents peripheral neuropathy from isoniazid 1

Dosing Adjustments

• Dosages should be rounded up to facilitate administration of appropriate syrup volumes or tablet strengths 1, 3
• Recalculate doses with weight gain during prolonged therapy 1, 3

Monitoring Requirements

• Regular clinical assessment for neurological improvement or deterioration 2
• Monitor for hepatotoxicity (rifampicin, isoniazid, pyrazinamide) 2
• Baseline and periodic liver function tests, especially in first 2 months 1
• Visual acuity monitoring if using ethambutol in older children 1
• Audiometry if using aminoglycosides 1

Common Pitfalls to Avoid

Duration of Therapy

• Do not use 6-month regimens for TB meningitis - this is the most critical error, as meningitis requires 12 months minimum 1, 2, 3
• Premature discontinuation leads to higher relapse rates 8

Drug Selection

• Avoid ethambutol as sole fourth drug in unconscious patients where visual monitoring is impossible 1
• Do not use streptomycin in areas with high streptomycin resistance without susceptibility testing 1

Hydrocephalus Management

• Do not delay neurosurgical consultation when hydrocephalus is present 1, 4
• Medical management alone (antituberculous drugs without acetazolamide/furosemide) is often insufficient for hydrocephalus 6

Corticosteroid Use

• Do not omit corticosteroids - they provide mortality benefit with strong evidence 1, 2, 4
• Ensure adequate tapering period (6-8 weeks total) 1, 2

Drug Dosing

• Current standard rifampicin doses may achieve suboptimal CSF concentrations; some experts advocate for higher doses (up to 30 mg/kg orally or 15 mg/kg IV) based on pharmacokinetic modeling 9
• However, standard dosing remains the guideline recommendation pending definitive trial results 1

Prognosis Considerations

• Nearly two-thirds of children with stage II TB meningitis who survive have mild disability 6
• Nearly half of children with stage III disease who survive have severe disability 6
• This emphasizes the critical importance of early diagnosis and treatment initiation 6
• Hydrocephalus management significantly impacts neurological outcomes 6, 7