A 28-year-old man with HIV (CD4 32 cells/μL, not on ART) develops fever, severe headache, and meningismus. CSF: opening pressure 320 mmH2O, WBC 8 cells/μL (lymphocytes), glucose 32 mg/dL, protein 95 mg/dL, India ink positive, CSF cryptococcal antigen titre 1:512. The most critical initial management step based on recent AMBITION clinical trial data is:
- A Start ART immediately alongside antifungals
- B Liposomal amphotericin B 3 mg/kg/day for 14 days plus flucytosine
- C Fluconazole 800 mg/day monotherapy for 6 weeks
- D A single high-dose liposomal amphotericin B 10 mg/kg PLUS flucytosine x 14 days (AMBITION regimen) ✓
Explanation
The AMBITION-cm trial (2022, NEJM) demonstrated that a single high-dose liposomal amphotericin B (10 mg/kg) on day 1 plus 14 days of flucytosine and fluconazole (AMBITION regimen) was non-inferior to 7 days of conventional amphotericin B deoxycholate + flucytosine for HIV-associated cryptococcal meningitis, with significantly less nephrotoxicity. WHO 2022 guidelines now include this as a recommended option, particularly advantageous in resource-limited settings where daily amphotericin B administration is challenging. ART should be deferred 4–6 weeks post-antifungal induction to avoid immune reconstitution inflammatory syndrome (IRIS). Fluconazole monotherapy has inferior fungicidal activity.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.