What is the recommended treatment for Cryptococcus meningitis?

Treatment of Cryptococcal Meningitis

The recommended first-line treatment for cryptococcal meningitis is amphotericin B deoxycholate (0.7-1.0 mg/kg/day) plus flucytosine (100 mg/kg/day in 4 divided doses) for 2 weeks as induction therapy, followed by fluconazole for consolidation and maintenance therapy. 1

Treatment Regimens Based on Patient Population

HIV-Infected Patients

• Induction therapy (2 weeks): Amphotericin B deoxycholate (0.7-1.0 mg/kg/day) plus flucytosine (100 mg/kg/day) - strongest evidence (A-I) 1
• For patients with renal concerns: Liposomal amphotericin B (3-4 mg/kg/day) or ABLC (5 mg/kg/day) plus flucytosine (100 mg/kg/day) 1
• For flucytosine-intolerant patients: Amphotericin B alone for 4-6 weeks 1
• Consolidation therapy (8 weeks): Fluconazole 400 mg daily 1, 2
• Maintenance therapy: Fluconazole 200 mg daily for at least 1 year 1, 2
• Initiate antiretroviral therapy 2-10 weeks after starting antifungal treatment 1

Transplant Recipients

• Induction therapy (2 weeks): Liposomal amphotericin B (3-4 mg/kg/day) or ABLC (5 mg/kg/day) plus flucytosine (100 mg/kg/day) 1
• Consolidation therapy: Fluconazole 400-800 mg daily for 6 months to 1 year 1
• Maintenance therapy: Fluconazole 200-400 mg daily 1
• Consider sequential reduction of immunosuppressive medications 1

Non-HIV, Non-Transplant Patients

• Induction therapy: Amphotericin B (0.7-1.0 mg/kg/day) plus flucytosine (100 mg/kg/day) for ≥4 weeks 1
• Consolidation therapy: Fluconazole 400-800 mg daily for 8 weeks 1
• Maintenance therapy: Fluconazole 200 mg daily for 6-12 months 1

Evidence for Combination Therapy

• Amphotericin B plus flucytosine has demonstrated superior fungicidal activity compared to amphotericin B alone or amphotericin B plus fluconazole 3, 4
• The combination of amphotericin B plus flucytosine is associated with:
  • Faster clearance of Cryptococcus from CSF 3, 4
  • 44% reduction in mortality at 2 weeks compared to other regimens 5
  • Improved survival at 70 days compared to amphotericin B alone 4

Alternative Regimens

• When amphotericin B cannot be used: Fluconazole (1200 mg daily) plus flucytosine (100 mg/kg/day) for 2 weeks 6
• When flucytosine is unavailable: Amphotericin B plus fluconazole (400-800 mg daily) 1
• For children: Amphotericin B plus flucytosine for induction, followed by fluconazole (12 mg/kg on first day, then 6 mg/kg daily) 1, 2

Monitoring and Management of Complications

• Monitor for increased intracranial pressure and manage aggressively 1
• For flucytosine therapy: Monitor serum levels (target: 30-80 μg/mL) and adjust dose based on renal function 1, 7
• Monitor complete blood counts regularly due to bone marrow suppression risk with flucytosine 1
• Perform serial lumbar punctures to document CSF sterilization 7
• Distinguish between treatment failure and immune reconstitution inflammatory syndrome (IRIS) if symptoms worsen during or after treatment 1

Common Pitfalls and Caveats

• Failure to test for HIV in patients with cryptococcal meningitis 1
• Inadequate management of increased intracranial pressure 1
• Premature initiation of antiretroviral therapy in HIV patients (should wait 2-10 weeks) 1
• Inappropriate dose adjustments for renal impairment 2
• Failure to monitor for drug toxicities, especially with amphotericin B and flucytosine 1
• Relying solely on cryptococcal antigen titers to guide treatment decisions 7