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1ïžâ£ AMBITION-cm Trial 2022
- Single dose liposomal AmB 10 mg/kg alternative to 2-week induction
- For HIV-related cryptococcal meningitis in resource-limited settings
- Non-inferior to 7-day AmB + flucytosine in mortality
- WHO 2022+ recommendation
- Reduces drug requirements, hospital stay, cost
- Game-changer for sub-Saharan Africa
2ïžâ£ Sub-Saharan Africa Burden
- 70%+ of global cryptococcal meningitis deaths
- HIV-related primarily
- Limited access to flucytosine + liposomal AmB
- WHO + Gilead access programs improving
- Mortality 30-40% with optimal Tx; up to 60-70% without
3ïžâ£ Cryptococcal Meningitis IRIS
- Paradoxical worsening with HIV + ART
- More common with delayed ART (4-6 wk)
- Headache + meningitis features recurrence
- Repeat LP
- Continue ART + cryptococcal Tx
- Steroid for severe (controversial)
4ïžâ£ Repeat LP â Procedure
- Opening pressure measurement essential
- Drain CSF to reduce ICP (often 20-30 mL)
- Repeat daily or every-other-day
- Continue until pressure normalized
- Lumbar drain or VP shunt for refractory high ICP
- Most institutions: protocol-based LP for high ICP
5ïžâ£ Solid Organ Transplant + Cryptococcal
- Reduced immunosuppression often beneficial
- Treatment same as HIV
- IRIS-like reaction possible with immune restoration
- Variable maintenance duration
6ïžâ£ C. gattii Cerebral Cryptococcomas
- Mass lesions often
- May need neurosurgical intervention
- Surgery + antifungal
- Long-term follow-up
7ïžâ£ Resistance
- Fluconazole resistance reported (especially after exposure)
- Rare in C. neoformans + C. gattii overall
- AmB + flucytosine resistance very rare
- AST in failure cases
8ïžâ£ å¥ä¿ / Taiwan
- éå ± mandatory
- å¥ä¿ AmB + flucytosine + fluconazole + voriconazole
- ID + neurology + neurosurgery consultation
- Sub-tropical Taiwan endemic; sporadic cases including in immunocompetent
9ïžâ£ Future + Vaccines
- Cryptococcal vaccine in research (subunit)
- Newer antifungals
- Encochleated AmB (oral) in development for cryptococcal meningitis (resource-limited)
10. Diagnostic Updates
- Lateral flow immunoassay (LFA) for serum + CSF CrAg â POC
- Rapid + sensitive + cheap
- WHO-prequalified
- Expanding access in resource-limited