What is the recommended treatment regimen (induction, consolidation, maintenance) and intracranial pressure management for cryptococcal meningitis in immunocompromised patients?

Treatment of Cryptococcal Meningitis in Immunocompromised Patients

For immunocompromised patients with cryptococcal meningitis, initiate induction therapy with amphotericin B deoxycholate (0.7–1.0 mg/kg/day) plus flucytosine (100 mg/kg/day) for at least 2 weeks, followed by fluconazole consolidation (400 mg/day for 8 weeks) and maintenance therapy (200 mg/day for ≥1 year), while aggressively managing intracranial pressure through serial lumbar punctures. 1

Induction Therapy (First 2 Weeks Minimum)

Primary regimen:

• Amphotericin B deoxycholate 0.7–1.0 mg/kg/day IV PLUS flucytosine 100 mg/kg/day orally for 2 weeks 1
• This combination is superior to amphotericin B monotherapy for yeast clearance and survival 1

For patients with renal dysfunction or transplant recipients:

• Liposomal amphotericin B (3–4 mg/kg/day) OR amphotericin B lipid complex (5 mg/kg/day) PLUS flucytosine (100 mg/kg/day) for 2 weeks 1, 2
• Lipid formulations minimize nephrotoxicity, which is critical in transplant recipients already on nephrotoxic immunosuppressants 1, 2

Extend induction to 4–6 weeks if:

• CSF cultures remain positive at 2 weeks 2
• Neurological complications are present 2
• Patient cannot tolerate flucytosine (use amphotericin B monotherapy for longer duration) 1

Critical point: All patients should receive a polyene (amphotericin B formulation) during induction when available—this is a performance measure 1

Consolidation Therapy (8 Weeks)

• Fluconazole 400 mg/day orally for 8 weeks after completing induction 1
• Some sources suggest 400–800 mg/day range 2
• Begin consolidation only after successful completion of induction therapy 1

Maintenance Therapy (≥1 Year)

• Fluconazole 200 mg/day orally for at least 1 year 1
• In HIV patients: Continue until CD4 count ≥100 cells/μL for ≥3 months with undetectable viral load on HAART, with minimum 1 year total antifungal therapy 1
• Dose adjustment required if creatinine clearance <50 mL/min: reduce maintenance dose by 50% after loading dose 2

For HIV patients specifically:

• Initiate HAART 2–10 weeks after starting antifungal treatment to reduce IRIS risk 1

Intracranial Pressure Management

This is one of the most critical determinants of outcome and must be addressed aggressively. 1

Baseline assessment:

• Measure opening pressure at initial lumbar puncture 1
• Determine if ICP >25 cm H₂O 1

If opening pressure >25 cm H₂O with symptoms of elevated ICP:

• Perform therapeutic lumbar puncture to reduce opening pressure by 50% OR to ≤20 cm H₂O 1, 3
• Repeat daily lumbar punctures until ICP and symptoms stabilized for 1–2 days 1
• For persistent elevation despite daily LPs, consider temporary percutaneous lumbar drain or ventriculostomy 1

What NOT to use for ICP management:

• Avoid corticosteroids for controlling elevated intracranial pressure in cryptococcal meningitis 3
• Mannitol has no proven benefit 3
• Acetazolamide should be avoided 3

Special Considerations for Corticosteroid Use

Corticosteroids are generally contraindicated in cryptococcosis except for three specific indications: 3

1. Severe IRIS with CNS inflammation: Prednisone 0.5–1.0 mg/kg/day for 2–6 weeks with gradual taper 3
2. Cryptococcomas with mass effect and surrounding edema 1, 3
3. ARDS in the context of IRIS 1, 3

Critical pitfall: Corticosteroid use is itself a risk factor for developing cryptococcosis, and must never be used as monotherapy or before establishing adequate antifungal coverage 3

Alternative Regimens (When Primary Options Unavailable)

If flucytosine is unavailable or not tolerated:

• Amphotericin B deoxycholate (0.7–1.0 mg/kg/day) OR liposomal amphotericin B (3–4 mg/kg/day) for 4–6 weeks 1
• Amphotericin B plus fluconazole (less effective than amphotericin B plus flucytosine) 1

Monitoring and Performance Measures

Essential monitoring during treatment:

• Patients with symptomatic increased intracranial pressure must be aggressively identified, treated, and monitored 1
• Test all patients with disseminated cryptococcosis or meningoencephalitis for HIV infection 1
• Distinguish treatment failure (drug resistance, compliance issues) from IRIS if symptoms relapse during or after treatment 1

Common pitfall: In immunosuppressed patients with pulmonary cryptococcosis, always rule out meningitis by lumbar puncture, as CNS involvement alters dose and duration of therapy 1