Routine use of antifungal medications is not recommended for primary prophylaxis of cryptococcal infections in children (BIII).
Combination therapy with amphotericin B deoxycholate (or liposomal amphotericin B) and flucytosine for 2 weeks (induction therapy) followed by fluconazole for a minimum of 8 weeks (consolidation therapy) is recommended for central nervous system disease (AI*). Amphotericin B lipid complex is another alternative to amphotericin B deoxycholate (BII*).
Liposomal amphotericin B is preferred over amphotericin B deoxycholate for patients with or at risk of renal insufficiency (AI*); amphotericin B lipid complex is an alternative (BII*).
In patients who cannot tolerate flucytosine or if flucytosine is unavailable, amphotericin B deoxycholate (or liposomal amphotericin B or amphotericin B lipid complex) with or without high-dose fluconazole can be used for initial therapy (BI*). Fluconazole plus flucytosine is superior to fluconazole alone and an option in patients who cannot tolerate any form of amphotericin (BII*).
Echinocandins are not active against cryptococcal infections and should not be used (AIII).
After a minimum of 2 weeks of induction therapy, if there is clinical improvement and a negative cerebrospinal fluid culture after repeat lumbar puncture, amphotericin B and flucytosine can be discontinued and consolidation therapy with fluconazole administered for a minimum of 8 weeks (AI*); itraconazole is a less preferable alternative to fluconazole (BI*).
Secondary prophylaxis with fluconazole (AI*) or itraconazole (less preferable) (BI*) is recommended for a minimum of 1 year.
Discontinuing secondary prophylaxis (after receiving secondary prophylaxis for ≥ 1 year) can be considered for asymptomatic children aged ≥6 years with CD4 counts ≥100 cells/mm3 and an undetectable viral load on ≥3 months of combination antiretroviral therapy (CIII). Secondary prophylaxis should be reinitiated if the CD4 count decreases to <100 cells/mm3
(AIII). Most experts would not discontinue secondary prophylaxis for patients younger than age 6 years (CIII).
Patients with severe pulmonary disease or disseminated cryptococcosis should be treated with amphotericin B with or without the addition of flucytosine, as for CNS disease (AIII). Those with mild-to-moderate pulmonary illness or other localized disease can be managed with fluconazole monotherapy (AIII).
In antiretroviral-naive patients newly diagnosed with cryptococcal meningitis or disseminated disease, delay in initiation of potent antiretroviral therapy may be prudent until the end of the first 2 weeks of induction therapy (CIII).
