Cryptococcosis

l Meningoencephalitis Non-HIV-Infected and Nontransplant Patients Transplant Recipientsk Induction Therapy Induction Therapy AmBd (0.7-0.1 mg/kg per day) plus flucytosine (100 mg/kg per day) Duration: ≥ 4 weekse, f (B-II) Liposomal AmB (3-4 mg/kg per day) plus flucytosine (100 mg/kg per day) Duration: 2 weeks (B-III) OR Alternatives to Induction Therapy Liposomal AmB (6 mg/kg per day) or ABLC (5 mg/kg per day) Duration: 4-6 weeks (B-III) OR AmBd (0.7-1.0 mg/kg per day)g Duration: ≥ 6 weekse, f (B-II) AmBd (0.7 mg/kg per day)l Duration 4-6 weeks (B-III) OR Consolidation Liposomal AmB (3-4 mg/kg per day) or ABLC (5 mg/kg per day) combined with flucytosine, if possibleh Duration: ≥ 4 weekse, f (B-III) Fluconazole (400-800 mg per day) Duration: 8 weeks (B-III) OR AmBd (0.7 mg/kg per day) plus flucytosine (100 mg/kg per day)i Duration: 2 weeks (B-III) Maintenance Fluconazole (200 mg per day) Duration: 6-12 months (B-III) Consolidation a Begin HAART 2-10 weeks after the start of initial antifungal treatment. 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. e Four weeks are reserved for patients with meningitis who have no Maintenance neurological complications, who have no significant underlying diseases or immunosuppression, and for whom the cerebrospinal fluid culture performed at the end of 2 weeks of treatment does not yield viable yeasts. During the second 2 weeks, LFAmB may be substituted for AmBd. f Fluconazole is given at 200 mg per day to prevent relapse after induction Fluconazole f therapy, and consolidation therapy is recommended. (200 mg per day) g For flucytosine-intolerant patients. Duration: 6-12 months (B-III) h For AmBd-intolerant patients. i 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. j 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. k Immunosuppressive management may require sequential or step-wise reductions. l 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. b Fluconazole (400-800 mg per day)j Duration: 8 weeks (B-III) 5

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