- Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality.
- Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies.
- If the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.
Selecting a Treatment Regimen
Stength and Recommendation and Evidence Quality
|Good evidence for or against a recommendation|
|Moderate evidence for or against a recommendation|
|Poor evidence to support a recommendation|
|Evidence from ≥ 1 randomized, controlled trial|
|Evidence from ≥ 1 clinical trial, without randomization, from cohort or case-controlled analytic studies (preferably from > 1 center), from multiple time-series, or dramatic results from uncontrolled experiments|
|Opinions of respected authorities, based on experience, descriptive studies, or reports of expert committees|
Table 1. Antifungal Treatment Recommendations for Nonmeningeal Cryptococcosis
|Patient Group||Initial Antifungal Regimen||Duration||Evidence|
|Immunosuppressed patients and immunocompetent patients with mild-to-moderate cryptococcosis||Fluconazole|
(400 mg per day)
|Immunosuppressed patients a and immunocompetent patients with severe pulmonary cryptococcosis||Same as central nervous system (CNS) disease||12 months||B-III|
|Patients with Nonmeningeal, Nonpulmonary Cryptococcosis|
|Patients with cryptococcemia||Same as CNS disease||12 months||B-III|
|Patients for whom CNS disease has been ruled out with no fungemia, with a single site of infection, and with no immunosuppressive risk factors||Fluconazole|
(400 mg per day)
Table 2. Antifungal Treatment Recommendations for Cryptococcal Meningoencephalitis in Transplant Recipients
|Alternatives for Induction Therapyb|
AmBd (0.7 mg/kg per day)b
|Consolidation therapy: Fluconazole (400-800 mg per day)||8 weeks|
|Maintenance therapy: Fluconazole (200-400 mg per day)||6-12 mos|
b Many transplant recipients have been successfully treated with AmBd. However, issues of renal dysfunction with calcineurin inhibitors are important, and the effective dose is imprecise.
Table 3. Antifungal Treatment Recommendations for Cryptococcal Meningoencephalitis in Non-HIV-Infected and Nontransplant Patients
|≥ 4 weeks a,b|
AmBd (0.7-1.0 mg/kg per day) c
|≥ 6 weeks a,b|
|≥ 4 weeks a,b|
|Consolidation therapy: Fluconazole (400-800 mg per day) f||8 weeks|
|Maintenance therapy: Fluconazole (200 mg per day) b||6-12 mos|
a Four weeks are reserved for patients with meningitis who have no neurological complications, who have no significant underlying diseases or immunosuppression, and for whom the cerebrospinal fluid (CSF) culture performed at the end of 2 weeks of treatment does not yield viable yeasts. During the second 2 weeks, lipid formulations of AmB (LFAmB) may be substituted for AmBd .
b Fluconazole is given at 200 mg per day to prevent relapse after induction therapy, and consolidation therapy is recommended.
c For flucytosine -intolerant patients.
d For AmBd -intolerant patients.
e For patients who have a low risk of therapeutic failure. Low risk is defined as an early diagnosis by history, no uncontrolled underlying condition or severe immunocompromised state, and an excellent clinical response to initial 2-week antifungal combination course.
f A higher dosage of fluconazole (800 mg per day) is recommended if the 2-week induction regimen was used and if there is normal renal function.
Table 4. Antifungal Treatment Recommendations for Cryptococcal Meningoencephalitis in HIV-Infected Individuals
|Alternatives for Induction Therapy b|
|Consolidation therapy: Fluconazole (400 mg per day)||8 weeks|
|Maintenance therapy: Fluconazole (200 mg per day) a||≥1 year c|
|Alternatives for Maintenance Therapy c|
|Itraconazole (400 mg per day) d||≥1 year c|
AmBd (1 mg/kg per week) d
|≥1 year c|
a Begin highly active antiretroviral therapy (HAART) 2-10 weeks after the start of initial antifungal treatment.
b In unique clinical situations in which primary recommendations are not available, consideration of alternative regimens may be made—but not encouraged—as substitutes.
See full guidelines for dosages.
c With successful introduction of HAART, a CD4 cell count ≥100 cells/mL, and low or nondetectable viral load for ≥ 3 months with minimum of 1 year of antifungal therapy.
d Inferior to the primary recommendation.