What is the most likely diagnosis for a drug user presenting with a 3-week history of fever and headache, worsening over the past 3 days, and cerebrospinal fluid (CSF) analysis showing hypoglycorrhachia (low glucose), elevated protein, and lymphocytic predominance?

Tuberculous Meningitis

The most likely diagnosis is B. Tuberculous meningitis. The combination of a 3-week subacute presentation, CSF showing lymphocytic predominance, markedly low CSF glucose (<0.4 mmol/L), and elevated protein (3 g/L) in a drug user is pathognomonic for tuberculous meningitis 1, 2.

Key Diagnostic Features Supporting TB Meningitis

The subacute course over 3 weeks is the critical distinguishing feature. TB meningitis characteristically presents with symptoms persisting for weeks before diagnosis, unlike bacterial meningitis which evolves over hours to days 3, 4. A clinical history exceeding 5 days has 93% sensitivity for TB meningitis 1.

The CSF profile is classic for TB meningitis:

• Lymphocytic predominance is characteristic, though neutrophils may predominate very early in the disease course 1, 3
• Markedly elevated protein (3 g/L) is typical of TB meningitis, far exceeding the 100-200 mg/dL commonly seen 1, 2
• Profoundly low CSF glucose (<0.4 mmol/L or <2.2 mmol/L) has 68% sensitivity and 96% specificity for TB meningitis 1
• **The CSF/plasma glucose ratio <0.5** is highly suggestive of TB meningitis, distinguishing it from viral causes where the ratio remains >0.36 1, 2

The drug user status increases TB risk due to higher rates of HIV infection and immunocompromise, which substantially elevate TB meningitis incidence 1.

Why Other Diagnoses Are Excluded

Viral meningitis (Option A) is ruled out because it typically presents with normal or only slightly low CSF glucose, and the CSF/plasma glucose ratio remains normal (>0.36-0.66) 1, 5. The 3-week duration and profoundly low glucose are incompatible with viral etiology 6.

Acute bacterial meningitis (Option C) is excluded by the subacute 3-week timeline and lymphocytic predominance. Bacterial meningitis shows neutrophil predominance (80-95%), evolves over hours to days, and would have caused death or recovery within this timeframe without treatment 6, 1, 5. While partially treated bacterial meningitis can show lymphocytic predominance, the 3-week untreated course makes this implausible 6, 7.

Aseptic meningitis (Option D) is too vague and doesn't account for the specific constellation of findings. This term typically refers to viral causes, which are excluded by the CSF glucose findings 6.

Critical Management Considerations

Start empiric anti-tuberculous therapy immediately without waiting for microbiological confirmation, as delays worsen outcomes significantly 1, 2, 3. The American Thoracic Society recommends a four-drug regimen (isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin) for 2 months, followed by two-drug continuation for 10 months (total 12 months) 1, 3, 4.

However, add empiric broad-spectrum antibiotics (ceftriaxone + vancomycin + ampicillin) until bacterial meningitis is definitively excluded 2, 5. Listeria monocytogenes can present identically with lymphocytic pleocytosis and low glucose, particularly in immunocompromised patients, and accounts for 20-40% of bacterial meningitis in this population 5. Ampicillin is critical because Listeria is resistant to cephalosporins 2, 5.

Essential Diagnostic Workup

Obtain the following immediately:

• CSF AFB smear and culture (though sensitivity is only 10-20%) 2, 3
• CSF PCR for M. tuberculosis (higher sensitivity than culture but still suboptimal) 2, 4
• Brain MRI with contrast to identify basilar meningeal enhancement characteristic of TB meningitis 2, 3
• HIV testing, as HIV dramatically increases TB meningitis risk 1, 2
• Multiple large-volume CSF samples increase diagnostic yield 3, 4

Common Pitfalls to Avoid

Do not wait for microbiological confirmation to start treatment. CSF culture sensitivity is only 10-20%, and PCR has suboptimal sensitivity, so negative tests cannot rule out TB meningitis 2, 3, 4. Treatment must begin based on clinical suspicion supported by CSF findings 1, 3.

Do not rely on absolute CSF glucose values alone. The CSF/plasma glucose ratio is more diagnostically useful than absolute values, particularly when serum glucose is abnormal 1. A ratio <0.5 strongly suggests TB meningitis 1, 2.

Do not assume lymphocytic predominance rules out bacterial causes. Listeria and partially treated bacterial meningitis can show lymphocytic predominance, necessitating empiric antibacterial coverage until excluded 6, 5, 7.