Preferred regimens | Alternative regimens¶ | Comments | |
Regimens for induction therapyΔ | When resources allow: Liposomal amphotericin B (3 to 4 mg/kg IV once daily) plus flucytosine (100 mg/kg per day orally in 4 divided doses) for a minimum of 2 weeks or Amphotericin B lipid complex (5 mg/kg IV once daily) plus flucytosine (100 mg/kg per day orally in 4 divided doses) for a minimum of 2 weeks If resources are limited: Liposomal amphotericin B (10 mg/kg IV single dose) plus the combination of flucytosine (100 mg/kg/day orally in 4 divided doses) and fluconazole (1200 mg orally once daily) for a minimum of 2 weeks If resources are limited and liposomal amphotericin B is not available: Amphotericin B deoxycholate (1 mg/kg IV once daily) plus flucytosine (100 mg/kg per day orally in 4 divided doses) for 7 days, followed by fluconazole monotherapy (1200 mg orally once daily) for a minimum of 7 days | Amphotericin B deoxycholate (0.7 to 1 mg/kg IV once daily)§ plus flucytosine (100 mg/kg per day orally in 4 divided doses) for a minimum of 2 weeks or Fluconazole (1200 mg orally once daily) plus flucytosine (100 mg/kg orally in 4 divided doses) for a minimum of 2 weeks or Amphotericin B§ plus fluconazole (800 to 1200 mg orally once daily) for a minimum of 2 weeks¥ |
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Consolidation therapy | Fluconazole (400 to 800 mg orally or IV once daily) for a minimum of 8 weeks | Itraconazole (200 mg orally twice daily) for a minimum of 8 weeks† |
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Maintenance therapy | Fluconazole (200 mg orally once daily) for a minimum of 1 year | Itraconazole (200 mg orally once daily) for a minimum of 1 year† |
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ART: antiretroviral therapy; CSF: cerebrospinal fluid; IV: intravenous; LP: lumbar puncture.
* In addition to antifungal therapy, patients who are not receiving ART should initiate treatment for HIV. However, initiation of ART should be delayed several weeks after induction therapy has been started to minimize the risk of developing an immune reconstitution inflammatory syndrome (IRIS). Refer to the UpToDate topic on treatment of patients with cryptococcal meningitis for a detailed discussion of when to initiate HIV therapy.
¶ Selection among alternative regimens depends on why a preferred regimen cannot be used. Refer to the UpToDate topic on treatment of patients with cryptococcal meningitis for a detailed discussion.
Δ The duration should be extended if clinical improvement is not observed and/or if CSF sterilization has not yet been achieved.
§ Lipid formulations of amphotericin B are favored to minimize the risk of toxicity and reduce treatment interruptions. However, amphotericin B deoxycholate remains an effective regimen if lipid formations are not available. When amphotericin B deoxycholate is used, the dose is 0.7 to 1 mg/kg IV once daily. In resource-limited settings, we use the 1 mg/kg/dose, as it has been best studied. However, in resource-available countries, we favor the 0.7 mg/kg dose to reduce the risk of nephrotoxicity.
¥ If it is not feasible to administer amphotericin B for 2 weeks, amphotericin B can be given for 1 week with fluconazole (1200 mg orally once daily), followed by 1 week of fluconazole (1200 mg orally once daily) alone.
‡ The World Health Organization states that in low- and middle-income countries, a routine LP is not indicated after 2 weeks of induction therapy to confirm CSF sterilization if the patient has had a clear clinical response to treatment.
† Levels should be monitored during the course of therapy. Refer to the UpToDate topic on pharmacology of azoles.Do you want to add Medilib to your home screen?