A 28-year-old woman from Mumbai, newly diagnosed with HIV (CD4 200 cells/μL, VL 150,000 copies/mL), presents with severe headache, fever, and neck stiffness for 5 days. CSF analysis shows: protein 180 mg/dL, glucose 35 mg/dL (serum glucose 90 mg/dL), cell count 120/μL (80% lymphocytes). India ink stain is positive. What is the most appropriate initial management?

Explanation

## Cryptococcal Meningitis: Diagnosis & Management ### Clinical Diagnosis **Key Point:** India ink–positive CSF in a patient with CD4 < 200 is diagnostic of cryptococcal meningitis (CM). The CSF profile (low glucose, elevated protein, lymphocytic pleocytosis) is classic. ### Why Amphotericin B + Fluconazole? 1. **Induction therapy**: Amphotericin B deoxycholate (0.7–1.0 mg/kg/day IV) is the gold standard induction agent for CM. It achieves high CNS penetration and fungicidal activity. 2. **Combination synergy**: Adding fluconazole (400–800 mg/day) to amphotericin B improves CSF sterilization and reduces mortality compared to monotherapy. 3. **Opening pressure assessment**: Elevated intracranial pressure (ICP) is common in CM and is associated with poor outcomes. Measuring opening pressure guides the need for therapeutic LP or ventriculostomy. 4. **Timing**: Induction therapy should begin immediately upon diagnosis; delays worsen prognosis. ### Treatment Algorithm ```mermaid flowchart TD A[Cryptococcal Meningitis Confirmed]:::outcome --> B[Measure Opening Pressure]:::action B --> C{ICP elevated?}:::decision C -->|Yes| D[Therapeutic LP or ventriculostomy]:::action C -->|No| E[Continue medical management]:::action A --> F[Start Amphotericin B IV]:::action A --> G[Add Fluconazole PO/IV]:::action F --> H[Induction: 2 weeks]:::action H --> I[Consolidation: Fluconazole 400-800 mg/day × 8 weeks]:::action I --> J[Maintenance: Fluconazole 200 mg/day indefinitely until CD4 > 100 × 3 months]:::action ``` ### CSF Profile in CM | Parameter | Finding | Significance | |-----------|---------|---------------| | **India ink stain** | Positive (50–80% sensitivity) | Diagnostic | | **Cryptococcal antigen (CrAg)** | Positive (95–100% sensitivity) | Gold standard; also positive in serum | | **Glucose** | Low (often < 40 mg/dL) | Indicates severe infection | | **Protein** | Elevated (100–500 mg/dL) | Reflects CNS inflammation | | **Cell count** | 20–500/μL, lymphocytic | Mild pleocytosis is typical | **High-Yield:** Serum CrAg is positive in > 95% of patients with CM and should be checked in all CD4 < 100 patients as part of screening. **Clinical Pearl:** Opening pressure > 25 cm H~2~O occurs in 50% of CM cases and is an independent predictor of mortality. Therapeutic LP (removing 20–30 mL CSF to reduce ICP) should be performed if pressure is elevated. **Mnemonic — CM Management: AFIC** — **A**mphotericin B, **F**luconazole, **I**ntracranial pressure assessment, **C**ontinue for 2 weeks induction then 8 weeks consolidation.