Cryptococcosis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Serge Korjian M.D.; Yazan Daaboul, M.D.

Overview

The standard regimen of treatment in non-AIDS patients is intravenous amphotericin B combined with oral flucytosine. AIDS patients often have a reduced response to amphotericin B and flucytosine, therefore after initial treatment as above, oral fluconazole can be used.

Medical Therapy

The standard regimen of treatment in non-AIDS patients is intravenous amphotericin B combined with oral flucytosine. AIDS patients often have a reduced response to amphotericin B and flucytosine, therefore after initial treatment as above, oral fluconazole can be used.

Antimicrobial Regimens

  • 1. Cryptococcus neoformans
  • 1.1 Meningoencephalitis in HIV infected patients[1]
  • 1.1.1 Induction and consolidation
  • 1.1.2 Maintenance and prophylactic therapy
  • Preferred regimen: Fluconazole 200 mg PO qd AND HAART 2-10 weeks after initiation of antifungal therapy
  • Alternative regimen (1): Itraconazole 200 mg PO bid
  • Alternative regimen (2): Amphotericin B deoxycholate 1 mg/kg IV qw
  • Note (1): Consider discontinuing therapy if CD4 count is higher than 100 cells/uL AND undetectable OR very low HIV RNA level for > 3 months
  • Note (2): Consider reinstitution of maintenance therapy if CD4 count <100 cells/uL
  • 1.2. Cerebral cryptococcomas
  • 1.3. Cryptococcus neoformans meningitis in HIV negative patients
  • Preferred regimen: Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd PLUS Flucytosine 100mg/kg/day PO or IV qid for at least 4 weeks (which may be extended to 6 weeks if there is any neurological complication) followed by fluconazole 400mg PO qd for 8 weeks. If there's toxicity to amphotericin B deoxycholate, consider changing to liposomal AmB in the second 2 weeks
  • Note (1): After induction and consolidation therapy, start fluconazole 200mg (3mg/kg) PO qd for 6-12 months
  • Note (2): If flucytosine is not given, consider lengthening the induction therapy for at least 2 weeks
  • 1.4. Cryptococcus neoformans pulmonary disease - immunosupressed
  • Preferred regimen: Fluconazole 400 mg PO qd for 6-12 months
  • Note (1): In HIV-infected patients, treatment should be stopped after 1 year if CD4 count is > 100 and a cryptococcal antigen titer is < 1:512 and not increasing.
  • Note (2): Consider corticosteroid if ARDS is present in a context which it might be attributed to IRIS
  • 1.5 Cryptococcus neoformans pulmonary disease - non-immunosupressed
  • 1.6 Cryptococcus neoformans non-lung, non-CNS infection
  • Cryptococcemia or disseminated cryptococcic disease (involvement of at least 2 noncontiguous sites or cryptococcal antigen titer > 1:512):
  • Preferred regimen: Fluconazole 400mg PO qd for 6-12 months
  • 1.7. Cryptococcosis in children
  • Preferred regimen: Fluconazole 6-12mg/kg PO qd for 6-12 months
  • 1.8. Cryptococcosis in pregnant women
  • Preferred regimen for induction and consolidation: Amphotericin B deoxycholate 0.7-1.0 mg/kg IV qd (consider using lipid formulations for patients with renal dysfunction - liposomal AmB 3-4mg/kg IV qd OR amphotericin B lipid complex (ABLC) 5mg/kg IV qd). Consider using flucytosine in relationship to benefit risk basis, since it is a category C drug for pregnancy
  • Start fluconazole after delivery
  • Avoid use during first trimester and consider use in the last 2 trimesters with the need for continuous antifungal therapy during pregnancy
  • Note: If pulmonary cryptococcosis, perform close follow-up and administer fluconazole after delivery.
  • 2. Cryptococcus gatti
  • Pulmonary disease: Single and small cryptococcoma
  • Preferred regimen: Fluconazole 400mg per day PO for 6-18 months
  • Pulmonary disease: Very large or multiple cryptococcomas
  • Preferred regimen: Administer flucytosine AND Amphotericin B deocycholate for 4-6 weeks, followed by fluconazole for 6-18 months
  • Note: Surgery should be considered if there is compression of vital structures OR failure to reduce the size of the cryptococcoma after 4 weeks of therapy

References

  1. Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ; et al. (2010). "Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america". Clin Infect Dis. 50 (3): 291–322. doi:10.1086/649858. PMID 20047480.

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