What is the best course of treatment for a patient with meningitis, characterized by hypoglycorrhachia (low glucose level in cerebrospinal fluid), lymphocytic pleocytosis (elevated lymphocyte count in cerebrospinal fluid), and no response to antibiotics and acyclovir (antiviral medication)?

Tuberculous Meningitis: Initiate Anti-TB Therapy Immediately

This CSF profile—glucose 8 mg/dL (0.44 mmol/L), lymphocytic pleocytosis with only 5 cells, and failure to respond to antibiotics and acyclovir—is most consistent with tuberculous (TB) meningitis, and you should start empiric four-drug anti-tuberculous therapy immediately without waiting for microbiological confirmation. 1

Why This is TB Meningitis

CSF Glucose is Critically Low

• Your patient's CSF glucose of 8 mg/dL (0.44 mmol/L) is far below the threshold of 2.2 mmol/L (40 mg/dL) that characterizes TB meningitis with 68% sensitivity and 96% specificity 1
• This profound hypoglycorrhachia essentially rules out viral meningitis, where CSF glucose remains normal or only slightly low with CSF/plasma glucose ratio >0.36 2, 3, 4
• Bacterial meningitis would typically show neutrophil predominance (80-95%), not lymphocytic predominance, making this diagnosis unlikely 1

Lymphocytic Pleocytosis Fits TB Pattern

• TB meningitis characteristically shows lymphocytic predominance, though the total cell count can be surprisingly low (5-500 cells/μL range) 2, 1
• Your patient's 5 lymphocytes is at the lower end but still compatible with TB meningitis, particularly in early disease or immunocompromised states 2, 5
• Neutrophils may predominate only early in TB meningitis course, but would shift to lymphocytes over time 1, 5

Failure to Respond to Standard Therapy is Key

• The lack of response to antibiotics rules out typical bacterial meningitis 2
• The lack of response to acyclovir makes HSV/VZV meningitis extremely unlikely 2, 6
• TB meningitis has a subacute to chronic course and would not respond to these agents 1, 5

Critical Diagnostic Pitfall You Must Address

Calculate the CSF/plasma glucose ratio immediately 1, 4. The absolute CSF glucose can be misleading if the patient has abnormal serum glucose:

• If CSF/plasma glucose ratio is <0.5, TB meningitis is highly likely 1
• If ratio is <0.36, bacterial meningitis becomes more likely (though lymphocytic predominance argues against this) 4
• Normal ratio is >0.66 4

Immediate Management Algorithm

Step 1: Start Anti-TB Therapy Now

Begin four-drug regimen immediately based on clinical suspicion—do not wait for microbiological confirmation 1:

• Isoniazid
• Rifampin
• Pyrazinamide
• Ethambutol (or streptomycin)

Continue for 2 months, then two-drug continuation for 10 months (total 12 months) 1

Step 2: Additional Diagnostic Workup

While starting treatment, obtain:

• CSF protein level: TB meningitis typically shows markedly elevated protein (>1 g/L), which would further support diagnosis 1, 4
• CSF opening pressure: Should be raised in TB meningitis 2, 1
• HIV testing: Critical because HIV-positive patients have higher incidence and mortality from TB meningitis 1
• CSF PCR for TB and acid-fast bacilli staining/culture (though these may take weeks and should not delay treatment) 2
• Chest imaging: Look for pulmonary TB 5

Step 3: Look for Supporting Clinical Features

• Duration of symptoms >5 days is independently predictive of TB meningitis with 93% sensitivity 1
• Subacute course >3 weeks strongly favors TB meningitis 1
• Headache is a key diagnostic criterion 1
• Check for IV drug use or other HIV risk factors 1

Alternative Diagnoses to Consider (But Less Likely)

Fungal Meningitis (Histoplasmosis, Cryptococcus)

• Would also show lymphocytic pleocytosis, low glucose, and raised protein 2
• Histoplasma meningitis presents with similar CSF findings: lymphocytic pleocytosis, protein elevation, and hypoglycorrhachia 2
• If TB treatment fails or patient is immunocompromised, consider fungal causes and obtain:
  • Cryptococcal antigen testing
  • Fungal cultures
  • Histoplasma antigen in urine/blood (if endemic area)
• Treatment for Histoplasma meningitis: Amphotericin B 0.7-1 mg/kg/day for 3-4 months, followed by fluconazole 800 mg daily for 9-12 months 2

Partially Treated Bacterial Meningitis

• Prior antibiotics can shift bacterial meningitis from neutrophilic to lymphocytic predominance 2
• However, CSF glucose this low with only 5 cells makes this unlikely 2
• CSF cultures may be negative within 2-4 hours of antibiotic administration 2

Common Pitfalls to Avoid

1. Do not wait for positive cultures: TB meningitis has poor culture yield and takes weeks; empiric treatment based on clinical suspicion is standard of care 1, 5

2. Do not be falsely reassured by low cell count: TB meningitis can present with surprisingly low CSF WBC counts, especially in immunocompromised patients 2, 1, 5

3. Do not dismiss TB because of atypical presentation: TB meningitis can have normal protein, normal glucose, or neutrophil predominance in atypical cases 5

4. Do not delay treatment for "more testing": Mortality is 20-40% even with treatment, and incorrect or inadequate therapy has disastrous outcomes 2, 5