What is the most appropriate treatment for a patient with signs and symptoms of meningitis, low cerebrospinal fluid (CSF) glucose, elevated CSF protein, and predominant lymphocytes?

Treatment for Tuberculous Meningitis

The most appropriate treatment is Option A: Intravenous Ceftriaxone and Vancomycin, but this must be immediately followed by anti-tuberculous therapy once bacterial meningitis is excluded, as the CSF findings (low glucose, elevated protein, lymphocytic predominance) are classic for tuberculous meningitis. 1, 2

Immediate Empirical Management

Start Broad-Spectrum Antibiotics First

• Initiate ceftriaxone 2g IV every 12 hours (or 4g daily) plus vancomycin 60 mg/kg/day IV divided every 6 hours within one hour of presentation 3, 4
• This covers bacterial meningitis (pneumococcal, meningococcal) which remains in the differential despite atypical CSF findings 3, 5
• Bacterial meningitis can present with lymphocytic predominance in up to 20% of cases, particularly if partially treated or caused by atypical organisms 3
• Do not delay antibiotics while awaiting further diagnostic confirmation, as mortality increases with treatment delays 1, 3

Add Anti-Tuberculous Therapy Immediately

Given the CSF profile (CSF glucose 5 mmol/L, protein 700 mg/L, lymphocytic predominance), tuberculous meningitis is the most likely diagnosis and anti-tuberculous therapy should be started empirically alongside antibiotics 1, 2, 6

The four-drug regimen should include:

• Isoniazid (INH) 5 mg/kg/day (maximum 300 mg daily) 1
• Rifampin (RIF) 10 mg/kg/day (maximum 600 mg daily) 1
• Pyrazinamide (PZA) 25-30 mg/kg/day 1
• Ethambutol (EMB) 15-20 mg/kg/day 1

Critical Diagnostic Features Supporting TB Meningitis

CSF Analysis Interpretation

• CSF glucose of 5 mmol/L is critically low and characteristic of TB meningitis 2, 7
• The CSF/plasma glucose ratio in TB meningitis is typically <0.5, which is very low compared to viral meningitis where the ratio remains >0.36 2
• CSF protein of 700 mg/L is markedly elevated, typical of TB meningitis where protein is usually >1 g/L 2, 7
• Lymphocytic predominance is the hallmark of TB meningitis, though neutrophils may predominate early in the disease course 2, 7

Why Other Options Are Incorrect

Option B (Methylprednisolone alone) is incorrect because corticosteroids are adjunctive therapy only and must never be given without concurrent anti-tuberculous or antibacterial treatment 1

Option C (Antifungal therapy alone) is incorrect because fungal meningitis typically presents in immunocompromised patients and would not be first-line empirical therapy without additional risk factors 3

Option D (Acyclovir alone) is incorrect because viral meningitis typically presents with normal or only slightly low CSF glucose, and the CSF/plasma glucose ratio remains >0.36, not the critically low ratio seen here 2

Adjunctive Corticosteroid Therapy

Add dexamethasone 0.15 mg/kg IV every 6 hours (or prednisolone equivalent) immediately, either shortly before or simultaneously with the first dose of anti-tuberculous drugs 1

• Corticosteroids provide a mortality benefit in tuberculous meningitis with moderate certainty of evidence 1
• Taper corticosteroids over 6-8 weeks 1
• The greatest benefit is seen in patients with Stage II disease (lethargic presentation) 1

Duration and Monitoring

Treatment Duration

• Continue the four-drug regimen (INH, RIF, PZA, EMB) for 2 months 1, 6
• After 2 months, discontinue PZA and EMB, and continue INH and RIF for an additional 7-10 months (total treatment duration of 9-12 months) 1, 6

Essential Monitoring

• Perform repeated lumbar punctures to monitor CSF cell count, glucose, and protein, especially early in therapy 1
• Send CSF for TB PCR, fungal culture, and viral PCR (HSV, VZV, enterovirus) 3
• Discontinue ceftriaxone and vancomycin after 48-72 hours if bacterial cultures remain negative and clinical response to anti-tuberculous therapy is adequate 3

Critical Pitfalls to Avoid

• Do not dismiss bacterial meningitis based solely on lymphocytic predominance, as this occurs in 20% of bacterial cases 3
• Do not use corticosteroids as monotherapy; they must always be combined with antimicrobial treatment 1
• Do not delay anti-tuberculous therapy while waiting for microbiological confirmation, as treatment delay is strongly associated with death 6
• Do not stop empirical antibiotics prematurely; continue until bacterial meningitis is definitively excluded by negative cultures at 48-72 hours 1, 3