Invasive Mycoses
Cryptococcosis
Last Updated: August 17, 2016; Last Reviewed: June 14, 2017
Recommendations for Treating Cryptococcosis
Treating Cryptococcal Meningitis
Treatment for cryptococcosis consists of 3 phases: induction, consolidation, and maintenance therapy.
Induction Therapy (For At Least 2 Weeks, Followed by Consolidation Therapy)
Preferred Regimens:
- Liposomal amphotericin B 3–4 mg/kg IV daily plus flucytosine 25 mg/kg PO QID (AI); or
- Amphotericin B deoxycholate 0.7–1.0 mg/kg IV daily plus flucytosine 25 mg/kg PO QID (AI)—if cost is an issue and the risk of renal dysfunction is low
Note: Flucytosine dose should be adjusted in renal impairment (see Table 7).
Alternative Regimens:
- Amphotericin B lipid complex 5 mg/kg IV daily plus flucytosine 25 mg/kg PO QID (BII); or
- Liposomal amphotericin B 3–4 mg/kg IV daily plus fluconazole 800 mg PO or IV daily (BIII); or
- Amphotericin B (deoxycholate 0.7-1.0 mg/kg IV daily) plus fluconazole 800 mg PO or IV daily (BI); or
- Liposomal amphotericin B 3–4 mg/kg IV daily alone (BI); or
- Amphotericin B deoxycholate 0.7–1.0 mg/kg IV daily alone (BI); or
- Fluconazole 400 mg PO or IV daily plus flucytosine 25 mg/kg PO QID (BII); or
- Fluconazole 800 mg PO or IV daily plus flucytosine 25 mg/kg PO QID (BIII); or
- Fluconazole 1200 mg PO or IV daily alone (CI)
Consolidation Therapy (For At Least 8 Weeks, Followed by Maintenance Therapy)
- To begin after at least 2 weeks of successful induction therapy (defined as substantial clinical improvement and a negative CSF culture after repeat LP)
Preferred Regimen:
- Fluconazole 400 mg PO or IV once daily (AI)
Alternative Regimen:
- Itraconazole 200 mg PO BID (CI)
Maintenance Therapy
Preferred Regimen:
- Fluconazole 200 mg PO for at least 1 year (AI)—see below for recommendation of when to stop maintenance therapy
Stopping Maintenance Therapy
If the Following Criteria are Fulfilled (BII):
- Completed initial (induction, consolidation) therapy, and at least 1 year on maintenance therapy, and
- Remains asymptomatic from cryptococcal infection, and
- CD4 count ≥100 cells/µL for ≥3 months and suppressed HIV RNA in response to effective ART
Restarting Maintenance Therapy:
- If CD4 count declines to ≤100 cells/µL (AIII)
Treating Non-CNS, Extrapulmonary Cryptococcosis and Diffuse Pulmonary Disease:
- Same treatment as for CNS disease (BIII)
Treating Non-CNS Cryptocococcosis Focal Pulmonary Disease and Isolated Cryptococcal Antigenemia:
- Fluconazole 400 mg PO daily for 12 months (BIII)
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Other Considerations:
- Addition of flucytosine to amphotericin B has been associated with more rapid sterilization of CSF, decreased risk for subsequent relapse, and improved survival.
- When flucytosine is used, serum levels (if available) should be monitored (2 hours post-dose, after 3–5 doses) and drug concentration should be between 25–100 mg/L).
- Opening pressure should always be measured when a LP is performed. Repeated LPs or CSF shunting are essential to effectively manage symptomatic increased ICP.
- In a randomized, controlled trial, a 6-week course of tapering doses of dexamethasone as adjunctive therapy for cryptococcal meningitis did not improve 10-week survival when compared to placebo, and resulted in a higher rate of adverse events. Corticosteroids should not be routinely used during induction therapy unless it is used for management of IRIS (AI).
- Corticosteroids and mannitol are ineffective in reducing ICP and are NOT recommended (BII).
- Infection due to C. gattii should be treated similarly to C. neoformans (BIII).
- All the triazole antifungals have the potential to interact with certain antiretroviral agents and other anti-infective agents. These interactions are complex and can be bidirectional. Table 5 lists these interactions and recommends dosage adjustments where feasible.
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U.S. Department of Health and Human Services
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