What is the most appropriate intravenous treatment for a patient presenting with fever, headache, confusion, and a positive Kernig's sign, with cerebrospinal fluid (CSF) analysis showing a predominance of lymphocytes?

Immediate Treatment Recommendation

Acyclovir (D) is the most appropriate intravenous treatment for this patient presenting with lymphocytic meningitis, fever, headache, confusion, and positive Kernig's sign. 1

Clinical Reasoning and Diagnostic Interpretation

CSF Analysis Strongly Indicates Viral Meningitis

• The lymphocytic predominance (90% lymphocytes, 5% neutrophils) with normal protein (0.8 g/L) and normal glucose (3.7 mmol/L) is pathognomonic for viral meningitis, not bacterial meningitis. 1

• Bacterial meningitis characteristically shows neutrophil predominance (80-95%), markedly elevated protein (typically >1 g/L), and CSF/plasma glucose ratio <0.36, none of which are present in this case. 2

• While bacterial meningitis can occasionally present with lymphocytic predominance when the CSF white cell count is <1,000/mm³, this typically occurs in partially treated cases or with specific organisms like Listeria. 2, 3

Why Antibiotics Are Not Indicated

• The normal CSF protein (0.8 g/L, reference range 0.22-0.33 g/L represents only mild elevation) and normal glucose essentially exclude bacterial meningitis. 2

• CSF protein <0.6 g/L makes bacterial meningitis highly unlikely (this patient has 0.8 g/L, which is only mildly elevated). 2

• The CSF glucose of 3.7 mmol/L (reference range 2.50-3.89 mmol/L) is normal, and bacterial meningitis typically shows CSF/plasma glucose ratio <0.36. 2

Acyclovir as First-Line Empiric Therapy

• The Infectious Diseases Society of America recommends initiating IV acyclovir immediately as empiric antiviral therapy until viral PCR results confirm the diagnosis, particularly for HSV-2 meningitis which commonly presents with this clinical picture. 2, 1

• HSV-2 meningitis characteristically presents with fever, headache, photophobia, meningismus, and CSF lymphocytic pleocytosis with mildly elevated protein and normal glucose—exactly matching this patient's presentation. 2

• The recommended dose is acyclovir 10 mg/kg IV every 8 hours until resolution of fever and headache, followed by oral valacyclovir 1 g three times daily to complete a 14-day course. 2, 4

Why Other Options Are Incorrect

Option A (Ceftriaxone + Vancomycin + Steroid) - Incorrect

• Corticosteroids are not indicated as first-line therapy in this presentation, as they are reserved for confirmed bacterial meningitis after infectious causes are appropriately treated. 1

• The lymphocytic predominance with normal protein and glucose excludes bacterial meningitis, making empiric antibiotics unnecessary. 1

Option B (Ceftriaxone + Vancomycin) - Incorrect

• Antibiotics should not be the primary therapy given the lymphocytic predominance and normal protein, which essentially exclude bacterial meningitis. 1

• The CSF profile does not support bacterial etiology requiring broad-spectrum antibiotics. 2

Option C (Ceftriaxone alone) - Incorrect

• Monotherapy with ceftriaxone would be inadequate even if bacterial meningitis were suspected, as empiric coverage typically requires ceftriaxone plus vancomycin for pneumococcal coverage. 2

• More importantly, the CSF findings do not support bacterial meningitis. 1

Critical Diagnostic Considerations

Ruling Out Alternative Diagnoses

• Tuberculous meningitis would typically show CSF/plasma glucose ratio <0.5, markedly elevated protein (>1 g/L), and a subacute course >5 days, which are not present here. 5

• Fungal meningitis presents similarly to TB meningitis with very low glucose and markedly elevated protein, typically in immunocompromised patients. 6

• Partially treated bacterial meningitis can show lymphocytic predominance, but the normal glucose and only mildly elevated protein argue strongly against this. 2, 3

Common Clinical Pitfalls to Avoid

• Early viral meningitis can show neutrophil predominance, but the total CSF white cell count rarely exceeds 2,000 cells/μL, unlike bacterial meningitis. 1

• Approximately 5-10% of adults with HSV encephalitis may have initially normal CSF, requiring repeat lumbar puncture after 24-48 hours if clinical suspicion remains high. 6

• The absolute CSF glucose value can be misleading when serum glucose is abnormal; always calculate the CSF/plasma glucose ratio for accurate interpretation. 5

Confirmatory Testing and Monitoring

• CSF PCR for HSV-1, HSV-2, VZV, and enteroviruses should be sent immediately on the initial CSF sample, as this identifies approximately 90% of viral causes and guides definitive management. 1, 6

• If diagnosis remains uncertain despite negative initial PCR, repeat lumbar puncture in 12-24 hours can demonstrate evolution of CSF findings and confirm viral etiology. 1

• Blood cultures and CSF bacterial culture should still be obtained, but treatment should focus on acyclovir given the overwhelming evidence for viral meningitis. 2, 1