Duration of therapy for 3-phase antifungal therapy for cryptococcosis

The duration of induction therapy for cryptococcosis is typically 2 to 6 weeks, but may vary depending on:

culture conversion
the presence of neurological dysfunction or cerebral cryptococcomas
whether the patient is immunocompromised
the species of Cryptococcus (C. gattii typically requires 4 to 6 weeks and C. neoformans typically requires 2 weeks).

Continue induction therapy until cerebrospinal fluid (CSF) is culture negative, or for the specified durations in Three-phase antifungal therapy for cryptococcosis, whichever is longer. Once induction therapy has been completed, start consolidation therapy.

The total duration of therapy (induction + consolidation + eradication) is typically 12 to 18 months, depending on whether the patient remains immunocompromised, and the presence or resolution of cerebral cryptococcomas – for more information, see Three-phase antifungal therapy for cryptococcosis.

In patients with HIV infection who respond to antiretroviral therapy, continue eradication therapy for at least 1 year, and until CD4 count is more than 100 cells/microlitre for 3 months or longer.

For patients who do not have HIV infection but are persistently immunocompromised (eg transplant recipients), long-term suppression therapy is recommended – seek expert advice.

Table 1. Three-phase antifungal therapy for cryptococcosis
Chang 2023 Chang 2021 Chang 2024
Exclude underlying immunodeficiency before starting treatment for cryptococcosis. See Diagnosing and assessing cryptococcosis for more information.
	Drug regimen	Duration of therapy
Induction therapy	amphotericin B liposomal (adult and child) 3 to 4 mg/kg intravenously, daily PLUS flucytosine (adult and child) 25 mg/kg orally, 6-hourly	Until the cerebrospinal fluid (CSF) is culture negative but for a minimum of: Cryptococcus gattii: 4 weeks Cryptococcus neoformans: 2 weeks
Consolidation therapy	fluconazole 400 to 800 mg (child: 12 mg/kg up to 800 mg) orally, daily [NB1]	8 weeks
Eradication or suppression therapy	fluconazole 200 mg to 400 mg (child: 6 mg/kg up to 400 mg) orally, daily	Immunocompetent: 12 months Immunosuppressed: at least 12 months then as long as the patient remains immunosuppressed
Note: NB1: In adults, higher fluconazole doses may be required for heavier patients (eg BMI 30 kg/m² or more), when the fluconazole minimum inhibitory concentration (MIC) is elevated (eg 8 mg/L) or when induction therapy cannot be completed.