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
- Preferred regimen: (Amphotericin B deoxycholate 0.7-1.0 mg/kg IV q24h for 2 weeks AND Flucytosine 100 mg/kg/day PO/IV q6h for 2 weeks) THEN Fluconazole 400 mg (6 mg/kg) PO qd for ≥ 8 weeks
- Preferred regimen (renally impaired): (Liposomal AmB 3-4 mg/kg IV q24h AND Flucytosine 100 mg/kg/day PO/IV q6h for 2 weeks) THEN Fluconazole 400 mg (6 mg/kg) PO qd for ≥ 8 weeks
- Preferred regimen (renally impaired): (Amphotericin B lipid complex (ABLC) 5 mg/kg IV q24h AND Flucytosine 100 mg/kg/day PO/IV q6h for 2 weeks) THEN Fluconazole 400 mg (6 mg/kg) PO qd for ≥ 8 weeks
- Alternative regimen (1): Amphotericin B deoxycholate 0.7-1.0 mg/kg IV q24h OR Liposomal AmB 3-4 mg/kg IV q24h OR Amphotericin B lipid complex 5 mg/kg IV q24h for 4-6 weeks
- Alternative regimen (2): (Amphotericin B deoxycholate 0.7 mg/kg IV q24h AND Fluconazole 800 mg PO qd for 2 weeks) THEN Fluconazole 800 mg PO qd for ≥ 8 weeks
- Alternative regimen (3): Fluconazole 800-1200 mg PO qd AND Flucytosine 100 mg/kg/day PO qid for 6 weeks
- Alternative regimen (4): Fluconazole PO 800-2000 mg PO qd for 10-12 weeks
- 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
- 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) OR Liposomal AmB 3-4mg/kg IV qd OR Amphotericin B lipid complex (ABLC) 5mg/kg IV qd) PLUS Flucytosine 100mg/kg/day PO or IV qid for at least 2 weeks followed by fluconazole 400mg (6mg/kg) PO qd for at least 8 weeks
- Note: Consider surgery if lesions are larger than 3cm, accessible lesions with mass effect or lesions that are enlarging and not explained by IRIS
- 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
- Mild-moderate symptoms, without severe immunosupression and absence of diffuse pulmonary infiltrates:
- Preferred regimen: Fluconazole 400 mg PO qd for 6-12 months
- Severe pneumonia, disseminated disease, or CNS infection:
- Preferred regimen: treat like CNS cryptococcosis
- 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
- Mild-moderate symptoms, without severe immunosupression and absence of diffuse pulmonary infiltrates:
- Preferred regimen: Fluconazole 400 mg PO qd for 6-12 months
- Alternative regimen: If fluconazole is unavailable or contraindicated, Itraconazole 200mg PO bid, voriconazole 200 mg PO bid, and posaconazole 400mg PO BID
- If the patient has severe pneumonia, disseminated disease, or CNS infection:
- Preferred regimen: Treat like CNS cryptococcosis for 6-12 months
- 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: treat like CNS infection
- If infection occurs at a single site and no immunosupressive risk factors
- Preferred regimen: Fluconazole 400mg PO qd for 6-12 months
- 1.7. Cryptococcosis in children
- Preferred regimen for induction and consolidation: Amphotericin B deoxycholate 1.0 mg/kg qd IV PLUS Flucytosine 100mg/kg PO or IV qid for 2 weeks followed by fluconazole 10-12mg/kg PO qd for 8 weeks
- Alternative regimen (renally impaired): Change amphotericin B deoxycholate by liposomal AmB 5mg/kg IV qd or amphotericin B lipid complex (ABLC) 5mg/kg IV qd
- Preferred regimen for maintenance: Fluconazole 6mg/kg PO qd. Discontinuation of maintenance therapy is poorly studied and should be individualized
- 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
- Disseminated cryptococcosis or CNS disease:
- Preferred regimen: Treatment is the same as C. neoformans
- 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
- ↑ 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.