What is the recommended treatment for Cryptococcal (CCM) Meningitis?

Treatment of Cryptococcal Meningitis

The recommended treatment for cryptococcal meningitis is induction therapy with amphotericin B deoxycholate (0.7-1.0 mg/kg/day) plus flucytosine (100 mg/kg/day) for 2 weeks, followed by fluconazole (400 mg/day) for 8 weeks as consolidation therapy, and then fluconazole (200 mg/day) for maintenance. 1, 2

Treatment Approach Based on Patient Population

HIV-Infected Patients

• Induction Phase (First 2 weeks):

  • First-line: Amphotericin B deoxycholate (0.7-1.0 mg/kg/day IV) plus flucytosine (100 mg/kg/day orally in 4 divided doses) for 2 weeks 1, 2
  • For renal concerns: Liposomal amphotericin B (3-4 mg/kg/day) or ABLC (5 mg/kg/day) plus flucytosine 1
  • For flucytosine-intolerant patients: Amphotericin B alone for 4-6 weeks 1

• Consolidation Phase (Next 8 weeks):

  • Fluconazole 400 mg daily 1, 3

• Maintenance Phase:

  • Fluconazole 200 mg daily for at least 1 year 1, 4
  • Can discontinue maintenance therapy if CD4 count ≥100 cells/μL and undetectable viral load for ≥3 months with minimum of 1 year of antifungal therapy 1

• Antiretroviral Therapy:

  • Initiate 2-10 weeks after starting antifungal treatment to reduce risk of IRIS 1, 2

Non-HIV, Non-Transplant Patients

• Induction Phase:

  • Amphotericin B deoxycholate (0.7-1.0 mg/kg/day) plus flucytosine (100 mg/kg/day) for 2 weeks 1
  • Alternative: Amphotericin B (0.7-1.0 mg/kg/day) for 4-6 weeks if flucytosine is unavailable 1

• Consolidation Phase:

  • Fluconazole 400 mg daily for 8-10 weeks 1

• Maintenance Phase:

  • Optional: Fluconazole 200 mg daily for 6-12 months 1

Transplant Recipients

• Induction Phase:

  • Liposomal amphotericin B (3-4 mg/kg/day) or ABLC (5 mg/kg/day) plus flucytosine (100 mg/kg/day) for 2 weeks 1
  • Alternative: Lipid formulation of amphotericin B alone for 4-6 weeks 1

• Consolidation and Maintenance:

  • Fluconazole 400-800 mg daily for 8 weeks, then 200-400 mg daily for 6-12 months 1
  • Consider immunosuppression reduction 1

Management of Complications

Increased Intracranial Pressure

• Measure opening pressure during initial lumbar puncture 1
• For pressure >200 mm H₂O, perform daily lumbar punctures to reduce pressure 1, 2
• Consider CSF shunting for patients who don't tolerate or respond to repeated lumbar punctures 1

Monitoring Treatment Response

• Perform follow-up lumbar puncture after 2 weeks of treatment to document CSF sterilization 1
• Patients with positive cultures at 2 weeks may require longer induction therapy 1
• Monitor renal function, electrolytes, and complete blood counts regularly during amphotericin B therapy 2, 4

Alternative Regimens

• When amphotericin B cannot be used: Fluconazole (1200 mg daily) plus flucytosine (100 mg/kg/day) 2, 5
• When flucytosine is unavailable: Amphotericin B plus fluconazole (400-800 mg daily) 2
• Recent evidence suggests single high-dose liposomal amphotericin B (10 mg/kg) plus 14 days of flucytosine and fluconazole may be non-inferior to standard therapy with fewer adverse events 6

Common Pitfalls and Caveats

• Failure to test for HIV in patients with cryptococcal meningitis 1, 2
• Inadequate management of increased intracranial pressure, which is associated with high mortality 1, 2
• Premature initiation of antiretroviral therapy in HIV patients (should wait 2-10 weeks) 1, 2
• Failure to monitor for drug toxicities, especially with amphotericin B (renal toxicity) and flucytosine (bone marrow suppression) 2, 4
• Relying solely on cryptococcal antigen titers to guide treatment decisions 2, 4
• Difficulty distinguishing between treatment failure and immune reconstitution inflammatory syndrome (IRIS) if symptoms worsen during or after treatment 1, 2

Dosage Adjustments

• For flucytosine, monitor serum levels (target: 30-80 μg/mL) and adjust dose based on renal function 1
• For fluconazole in renal impairment: If creatinine clearance ≤50 mL/min, reduce dose by 50%; for hemodialysis patients, give 100% of dose after each dialysis 3
• For pediatric patients: Fluconazole 12 mg/kg on first day, then 6 mg/kg daily for cryptococcal meningitis 3