What is the recommended treatment and dosing regimen for severe fungal infections using liposomal (Liposomal Amphotericin B) amphotericin B?

Liposomal Amphotericin B Treatment for Severe Fungal Infections

For severe fungal infections, liposomal amphotericin B is recommended at a dose of 5 mg/kg/day for patients without CNS involvement and 10 mg/kg/day for those with CNS involvement, administered intravenously for 4-6 weeks during induction and consolidation phases. 1

Dosing Recommendations by Infection Type

Invasive Candidiasis/Candidemia

• Liposomal amphotericin B (3-5 mg/kg/day IV) should be considered if there is persistent candidemia or clinical unresponsiveness to echinocandins without evidence of resistance to amphotericin B 1
• Treatment should continue for 14 days after the last positive blood culture and resolution of signs and symptoms 2
• For neonates with disseminated candidiasis, conventional amphotericin B at 1 mg/kg/day is recommended 1

Mucormycosis

• Primary therapy: Liposomal amphotericin B 5 mg/kg/day IV (without CNS involvement) or 10 mg/kg/day IV (with CNS involvement) 1
• Duration: 4-6 weeks for induction and consolidation treatment 1
• Both antifungal therapy and immediate surgical debridement are recommended for COVID-19 associated mucormycosis 1
• Maintenance therapy should continue for 3-6 months until resolution of clinical signs and symptoms 1

Central Nervous System Fungal Infections

• For CNS fungal infections, liposomal amphotericin B at 5-10 mg/kg/day is recommended 1
• For cryptococcal meningitis, at least 2 weeks of amphotericin B therapy followed by fluconazole is recommended 2

Administration Guidelines

• Administer by slow intravenous infusion over 2-6 hours (depending on dose) 3
• The recommended concentration for IV infusion is 0.1 mg/mL 3
• Pre-medication with diphenhydramine or acetaminophen prior to infusion is recommended to avoid infusion-related reactions 1, 2
• To avoid nephrotoxicity, 1 L of normal saline can be given before and after infusion in patients who can tolerate fluids 1, 2

Monitoring and Adverse Effects

• Monitor renal function, electrolytes, and liver function tests regularly 2, 4
• Nephrotoxicity is the primary concern but occurs less frequently with liposomal formulation compared to conventional amphotericin B 5, 6
• Infusion-related reactions (fever, chills, nausea, vomiting) can occur but are less common with liposomal formulation compared to conventional amphotericin B 5, 6
• Most nephrotoxicity, if it occurs, develops within the first 9 days of treatment 4

Alternative Formulations and Therapies

• If liposomal amphotericin B is unavailable, alternatives include:
  • Amphotericin B deoxycholate (1-1.5 mg/kg/day) administered in 5% dextrose with slow infusion over 6-8 hours 1
  • For maintenance therapy after initial response: posaconazole or isavuconazole 1

Special Considerations

• For lung transplant patients, nebulized liposomal amphotericin B (25 mg) or amphotericin B lipid complex (50 mg) may be used for prophylaxis 1
• For patients with endophthalmitis, intravitreal liposomal amphotericin B injection may be considered in addition to systemic therapy 1
• In patients with renal impairment, liposomal amphotericin B is safer than conventional amphotericin B 4, 6

Clinical Efficacy

• Liposomal amphotericin B has shown efficacy rates of approximately 50% in empirical therapy for febrile neutropenia 5, 6
• For confirmed invasive fungal infections, response rates vary: 66% in aspergillosis and 81% in candidiasis 7
• In a clinical cohort trial, 51.5% of patients showed complete response and 25.9% showed partial response to liposomal amphotericin B treatment 8

Remember that early initiation of appropriate antifungal therapy is crucial for improving outcomes in severe fungal infections, and dosing should be adjusted based on clinical response and tolerability.