Antifungal treatment guidelines
| Drug | Amphotericin B | Flucytosine | Fluconazole | |
| Mechanism | Fungicidal polyene that creates pores in fungal cell membranes | Fungistatic RNA analogue that disrupts yeast replication | Fungistatic azole that inhibits fungal cell wall synthesis | |
| Phase | Induction | Consolidation and maintenance | ||
| Cryptococcal antigenaemia | Generally omit | Generally omit | 6–12 months of oral fluconazole monotherapy. Pregnancy—seek expert advice | |
| Dose and duration | HIV | Low-income setting—single-dose intravenous liposomal amphotericin B (10 mg/kg)* High-income setting—2 weeks liposomal amphotericin B (3–4 mg/kg/day) | 100 mg/kg/day for 14 days split into four divided doses. | Low-income setting, induction phase 1200 mg once daily for 1 week Consolidation therapy—all settings 400–800 mg once daily for 8 weeks Maintenance therapy—all settings 200mg once daily until viral suppression achieved and CD4 >200 cells/mm3) |
| SOT | 2 weeks low-dose intravenous liposomal amphotericin B (3–4 mg/kg/day) | Consolidation therapy—all settings 400–800 mg once daily for 8 weeks Maintenance therapy—all settings 200 mg once daily for 6–12 months | ||
| NHNT | ||||
| Pregnancy | Intravenous liposomal amphotericin B (1 mg/kg/day) for the first 2 weeks; then seek expert advice | Consider on case-by-case basis but generally omit | Relatively contraindicated. Safe in breastfeeding | |
| Adverse effects | Infusion reaction—chills and rigors (common) Nephrotoxicity and hypokalaemia (common) Hepatotoxicity (common) | Neutropenia (4%) and myelosuppression | Dry skin, alopecia, diarrhoea Transient liver function test (ALT) derangement) | |
| How to detect and mitigate adverse effects | Use liposomal formulation Slow infusion rate (3–6 hours) Prehydration with intravenous fluids. Baseline U&E, repeated twice weekly | Baseline full blood count and urea and electrolytes, then twice weekly Reduce dose in renal impairment Check flucytosine levels weekly | Reduce dose if adverse effects (particularly in women) If intolerant, can switch to itraconazole | |
*This is a recent change in the medical management of cryptococcal meningitis recommended by WHO and a global consensus guideline, based on the AMBITION-cm trial. Please refer to online supplemental material 1 for a detailed discussion.
ALT, alanine transaminase; NHNT, non-HIV, non-transplant; SOT, solid organ transplant; U&E, urea and electrolytes.