Evidence-based management of Cryptococcal Meningitis according to Uganda Clinical Guidelines 2023

Diagnosis Algorithm

ART naive patient with CD4 <100 or suspected treatment failure: Do serum CRAG test. If positive: evaluate for signs of meningitis. If symptomatic, do Lumbar Puncture (LP) and CSF CRAG test. Treat based on results.

Induction Phase (2 weeks)

Recommended: Amphotericin B liposomal (10mg/kg) + Flucytosine (100mg/kg/day in 4 doses) + Fluconazole 1200mg/day for 14 days. OR Amphotericin B deoxycholate (1mg/kg/day) + Flucytosine (100mg/kg/day) for 1 week, followed by 1 week of Fluconazole (1200 mg/day for adults, 12 mg/kg/day for children). OR Fluconazole (1200 mg/day) + Flucytosine (100 mg/kg/day). OR Amphotericin B deoxycholate (1mg/kg/day) + Fluconazole 1200mg/day.

Preventing Amphotericin Toxicity

Pre-hydration with 1L normal saline. Monitor serum potassium and creatinine. Routine administration of 40 mEq/day potassium chloride (or 600mg tablet twice daily). Magnesium supplementation (Magnesium Chloride 310mg daily or Magnesium trisilicate 250mg).

Consolidation Phase (8 weeks)

Fluconazole 800mg/day (or 6-12mg/kg/day in children and adolescents). Initiate ART 4–6 weeks after starting CM treatment.

Maintenance Phase (18 months)

Fluconazole 200mg/day (or 6 mg/kg/day up to 200mg in children). Criteria to stop: minimum 18 months, VL<1,000 copies/mm3 & CD4 ≥ 200 after 12 and 18 months.

Management of Elevated CSF Pressure

All patients with CSF Pressure >250mm H2O need a therapeutic LP the following day to reduce pressure to <200 mm. Removing 20-30mL of CSF is often adequate. Most patients need 2-3 LPs during induction.

ART Timing with Cryptococcal Meningitis

ART Naive: Wait for 4-6 weeks then start 1st line. ART Experienced (non-adherent >6 mo): Wait 4-6 weeks then restart. ART Experienced (adherent >6 mo): Continue ART at admission. ART Experienced (<6 mo): Stop ART at admission, wait 4-6 weeks to restart.