New Southern African Clinicians Society Cryptococcal Treatment Guidelines (2012)

CrAg Screening Algorithm

Cryptococcal meningitis or cryptococcemia

PRIMARY

Ampho B 0.7 mg/kg IV q 24 + flucytosine 25 mg/kg po q8 x 2 weeks then

Fluconazole 400 mg po q 24 to complete 10 week course then

Fluconazole 200 mg po q 24 suppressive therapy.

When CD4 > 100 with effective antiretroviral therapy for at least 6 months, fluconazole may be discontinued

SECONDARY

Fluconazole 400 or 800 mg po q 24 (or plus flucytosine 25 mg/kg po q8 x 4-6 weeks then

Fluconazole 400 mg po q 24 to complete 10 week course then

Fluconazole 200 mg po q 24 suppressive therapy.

When CD4 > 100 with effective antiretroviral therapy for at least 6 months, fluconazole may be discontinued.

World Health Organization’s recommended induction, consolidation and maintenance phase treatment and dosage for HIV adults, adolescents and children (2011)

Induction Phase Treatment

For the induction phase of treatment in HIV-infected adults, adolescents and children with cryptococcal disease (meningeal and disseminated non-meningeal), the following two-week anti-fungal regimens are recommended in order of preference.

• Amphotericin B + Flucytosine
• Amphotericin B + Fluconazole
• Amphotericin B short course (5-7 days) + high-dose fluconazole (to complete two weeks of induction) when a minimum package of pre-emptive hydration and electrolyte replacement and toxicity monitoring and management cannot be provided for the full two week induction period.
• Fluconazole high dose + Flucytosine, when amphotericin B is not available
• Fluconazole high dose alone, when Amphotericin  B is not available

Consolidation phase treatment

For the consolidation phase treatment of HIV-infected adults, adolescents and children with cryptococcal    meningitis or disseminated non-meningeal disease, the following eight-week anti-fungal regimen is recommended:

• Fluconazole 400-800 mg/day after a two-week induction with amphotericin B regimen (6-12 mg/kg/day up to 400-800 mg/day if below 19 years).
• Fluconazole800mg/dayafterinductiontreatmentwithshortcourseamphotericin B or a fluconazole based induction regimen (fluconazole 12 mg/kg/day up to 800 mg/day if below 19 years).

Maintenance treatment (or secondary prophylaxis)
For maintenance treatment of cryptococcal disease in HIV-infected adults, adolescents and children, oral fluconazole 200 mg daily (6 mg/kg/day up to 200 mg/day if below 19 years) is recommended.

Localized non-meningeal disease

For localized non-meningeal disease, or in patients with isolated serum CrAg positivity (where active cryptococcal meningitis has been excluded), fluconazole 800 mg/day (or 12 mg/kg/day up to 800 mg/day if below 19 years) for two weeks, then 400 mg/day (or 6 mg/kg/day up to 400-800 mg/day if below 19 years) for eight weeks, and continued maintenance with fluconazole 200 mg/day is recommended. The optimal antifungal regimen in this population remains to be determined.

Infectious Diseases Society of America (2010)
Antifungal Treatment Recommendations for Cryptococcal Meningoencephalitis in Human Immunodeficiency Virus–Infected Individuals

Antifungal Treatment Recommendations for Non-Meningeal Cryptococcal Disease in Human Immunodeficiency Virus–Infected Individuals