How to Use These Notes for 25-Mark Answers

1. Definition (2 marks)
2. Etiology/Classification (3-4 marks)
3. Pathophysiology (3-4 marks)
4. Clinical Features (5-6 marks - use tables and mnemonics)
5. Investigations (3-4 marks - especially CSF table for meningitis)
6. Management (5-6 marks)
7. Prognosis/Complications (1-2 marks)

Topic-Specific Exam Tips

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What's inside the document

• Key numbers and doses to memorise
• One-liner causative organism table
• X-ray signs comparison
• "Must-know treatment" summary for each topic

ATT (Anti-Tuberculous Therapy) for Tuberculous Meningitis (TBM)

Why TBM is Treated Differently from Pulmonary TB

Standard Drug-Susceptible TBM Regimen

Intensive Phase — First 2 Months (8 Weeks)

Note on Rifampicin dose: Standard pulmonary TB uses 10 mg/kg. For TBM, 20–30 mg/kg/day is recommended to ensure adequate CSF concentrations (Red Book 2021; Murray & Nadel). This is a high-yield exam distinction.

Children (AAP recommendation): Initial 4-drug regimen of INH + RIF + PZA + Ethionamide (preferred 4th drug). If ethionamide not available, an aminoglycoside (streptomycin, amikacin) may be substituted. Many experts also add a fluoroquinolone (levofloxacin) for 5-drug coverage in severe cases.

Continuation Phase — Next 7–10 Months

• Can be given daily or 3 times per week (after first 2 months if child has responded well)
• Ethambutol/ethionamide/aminoglycoside stopped once drug susceptibility confirmed or after intensive phase
• Pyrazinamide given for total of 2 months only, then stopped

Total Treatment Duration

Why longer than pulmonary TB? Poor CNS penetration of drugs means sterilisation is slower. Current US guidelines: 2-month intensive phase + 7–10 month continuation phase = 9–12 months total (Murray & Nadel; Harrison's 22e).

Adjunctive Corticosteroids — MANDATORY in TBM

Why Corticosteroids?

Regimen

Important caveat (Harrison's 22e / 2026 Lancet Guideline): The benefit of steroids may be genetically influenced. Patients homozygous for the anti-inflammatory allele (LTA4H) were negatively affected by steroid treatment. This pharmacogenomic consideration is emerging but not yet routine practice.

Corticosteroids are recommended for HIV-negative patients. Use with caution in HIV-positive patients (risk of Kaposi's sarcoma and other OI flares), though most guidelines still recommend them.

Pyridoxine (Vitamin B6) — Always Add

• Pyridoxine 50 mg/day (adults) or 1–2 mg/kg/day (children)
• Prevents isoniazid-induced peripheral neuropathy (isoniazid depletes pyridoxine)
• Especially important in malnourished patients, pregnant women, and children

Summary Treatment Card

TBM — Drug-Susceptible

INTENSIVE PHASE (2 months)
Adults:   H (300 mg) + R (20–30 mg/kg) + Z (30 mg/kg) + E (15–25 mg/kg)  Daily
Children: H (10–15 mg/kg) + R (20–30 mg/kg) + Z (30–40 mg/kg) + Ethionamide (15–20 mg/kg) Daily
         [+ Fluoroquinolone in severe/resistant cases]

CONTINUATION PHASE (7–10 months)
          H + R   Daily (or 3×/week if clinically well)

TOTAL DURATION:  9–12 months
STEROIDS:        Dexamethasone 0.4 mg/kg/day (children) / 8–12 mg/day (adults) × 4 weeks then taper
PYRIDOXINE:      50 mg/day (adults) / 1–2 mg/kg/day (children)

Drug-Resistant TBM

MDR-TBM (Resistant to H + R)

• Use fluoroquinolone (Levofloxacin or Moxifloxacin) as backbone - excellent CNS penetration
• Add: Cycloserine (good CNS penetration) + Pyrazinamide + Ethionamide/Prothionamide
• Bedaquiline: emerging role in MDR-TB including CNS disease
• Avoid aminoglycosides (poor CNS penetration when meninges less inflamed)
• Duration: 18–24 months minimum
• Consult infectious disease specialist

INH-resistant TBM

• Replace INH with a fluoroquinolone
• Continue R + Z + E + Fluoroquinolone

Complications Requiring Additional Management

Monitoring During Treatment

• Monthly clinical assessment (motor function, cognition, cranial nerves)
• Serial CSF analysis (consider repeated LPs until culture-negative)
• Liver function tests: Monthly (isoniazid + rifampicin + pyrazinamide all hepatotoxic)
• Visual acuity + colour vision monthly (if using ethambutol — optic neuritis)
• Hearing (if using aminoglycosides)
• Blood glucose (isoniazid can cause hypoglycaemia)
• Renal function
• Neuroimaging: MRI brain at baseline and after 2 months to assess response

Key Exam Points

1. Total duration 9–12 months (not 6 months like pulmonary TB)
2. Rifampicin dose is higher in TBM: 20–30 mg/kg (not 10 mg/kg) for better CNS penetration
3. Pyrazinamide is the best CNS-penetrating drug (100% CSF levels) - critical in intensive phase
4. Ethambutol has poor/variable CNS penetration - ethionamide or aminoglycoside preferred as 4th drug in children (AAP)
5. Dexamethasone is mandatory adjunctive therapy in HIV-negative TBM
6. Pyridoxine always added to prevent INH neuropathy
7. Hydrocephalus occurs in ~25% and may need VP shunt
8. ATT should be started empirically when there is high clinical suspicion, even before culture results
9. Fluoroquinolones (levofloxacin) have excellent CNS penetration and are increasingly added in severe cases or as 4th/5th drug

Sources: Red Book 2021 (AAP), Harrison's Principles of Internal Medicine 22e (2025), Murray & Nadel's Textbook of Respiratory Medicine, Rosen's Emergency Medicine, Tintinalli's Emergency Medicine; Donovan J et al., "A clinical practice guideline for tuberculous meningitis," Lancet Infect Dis, Feb 2026 [PMID: 40840485] - most recent international guideline from the Tuberculous Meningitis International Research Consortium.