What is the recommended dosage of Amphotericin B (antifungal medication) for treating systemic fungal infections?

Amphotericin B Dosage for Systemic Fungal Infections

For systemic fungal infections, conventional amphotericin B deoxycholate should be dosed at 0.5-0.7 mg/kg/day IV for standard infections and up to 1.0 mg/kg/day for severe or life-threatening infections, while liposomal amphotericin B (the preferred lipid formulation) should be dosed at 3-5 mg/kg/day IV. 1, 2, 3

Conventional Amphotericin B Deoxycholate Dosing

Initial Dosing Strategy

• Start with a test dose of 1 mg in 20 mL of 5% dextrose administered over 20-30 minutes, monitoring vital signs every 30 minutes for 2-4 hours 3
• In patients with good cardio-renal function and well-tolerated test dose, initiate therapy at 0.25 mg/kg/day 3
• For severe and rapidly progressive fungal infections, begin at 0.3 mg/kg/day 3
• In patients with impaired cardio-renal function or severe test dose reaction, start with 5-10 mg daily and gradually increase by 5-10 mg increments 3

Maintenance Dosing

• Standard infections: 0.5-0.7 mg/kg/day IV 1, 2, 3
• Severe or life-threatening infections: 0.7-1.0 mg/kg/day IV 1, 4
• Maximum daily dose: Never exceed 1.5 mg/kg/day, as overdoses can result in potentially fatal cardiac or cardiopulmonary arrest 3
• Infusion duration: Administer over 2-6 hours at a concentration of 0.1 mg/mL (1 mg/10 mL) 3

Nephrotoxicity Prevention

• Administer 1 liter of 0.9% normal saline 30 minutes before infusion in patients who can tolerate fluids 1, 5
• Pre-medicate with acetaminophen or diphenhydramine to reduce infusion-related reactions (fever, chills, nausea) 4, 5

Lipid Formulations of Amphotericin B

Liposomal Amphotericin B (L-AmB) - Preferred Lipid Formulation

• Standard dosing: 3-5 mg/kg/day IV 1, 2
• CNS involvement: 5-10 mg/kg/day IV 5
• This formulation provides the greatest renal protection among all lipid formulations 2
• Significantly less nephrotoxic than conventional amphotericin B with equivalent or superior efficacy 6

Alternative Lipid Formulations

• Amphotericin B lipid complex (ABLC): 5 mg/kg/day IV 1, 2, 5
• Amphotericin B colloidal dispersion (ABCD): 3-6 mg/kg/day IV 2, 5
• Note: ABCD has higher rates of acute infusion reactions compared to liposomal amphotericin B 6

Evidence Supporting Lower Doses

• Low-dose liposomal amphotericin B (1 mg/kg/day) may be equally effective for some indications with comparable clinical improvement and survival rates 7
• However, avoid dosages as low as 1 mg/kg for initial treatment of fulminant fungal infections, as efficacy may be inferior 8

Infection-Specific Dosing

CNS Candidiasis (Meningitis)

• Initial treatment: Liposomal AmB 5 mg/kg/day IV, with or without flucytosine 25 mg/kg four times daily 1
• Continue until all signs, symptoms, CSF abnormalities, and radiological findings resolve 1

Candidal Chorioretinitis

• Fluconazole/voriconazole-resistant isolates: Liposomal AmB 3-5 mg/kg/day IV, with or without flucytosine 1
• With macular involvement or vitritis: Add intravitreal injection of amphotericin B deoxycholate 5-10 μg/0.1 mL sterile water 1, 5
• Duration: At least 4-6 weeks, continuing until lesion resolution on repeated ophthalmological examinations 1

Candiduria Requiring Treatment

• Patients undergoing urologic procedures: Amphotericin B deoxycholate 0.3-0.6 mg/kg/day for several days before and after the procedure 1
• Bladder irrigation (rarely indicated): 50 mg/L sterile water daily for 5 days 5

Neonatal Disseminated Candidiasis

• Amphotericin B deoxycholate 0.5-1 mg/kg/day for a total dose of 10-25 mg/kg 1
• Amphotericin B is well tolerated in neonates 1

Sporotrichosis

• Therapy may range up to 9 months with a total dose up to 2.5 g 3

Aspergillosis

• Treatment may extend up to 11 months with a total dose up to 3.6 g 3

Rhinocerebral Phycomycosis

• Cumulative dose of at least 3 g is recommended, with 3-4 g being a reasonable minimum for deep tissue invasion 3
• This fulminating disease requires aggressive therapy and restoration of diabetic control 3

Special Administration Routes

Intraventricular Administration

• For CNS devices that cannot be removed: Amphotericin B deoxycholate 0.01-0.5 mg in 2 mL of 5% dextrose in water 1, 5

Intravitreal Injection

• Amphotericin B deoxycholate 5-10 μg/0.1 mL sterile water 1, 5

Duration of Therapy

Candidemia

• Continue treatment for 14 days after the last positive blood culture and resolution of signs and symptoms 2, 4

Disseminated Candidiasis

• Treatment may last 3-6 months until resolution or calcification of radiologic lesions 2

Cryptococcal Meningitis

• At least 2 weeks of amphotericin B followed by fluconazole 2, 4

Monitoring Requirements

• Monitor renal function, electrolytes (especially potassium), and liver function tests regularly 2, 4, 5
• Watch for infusion-related reactions: fever, chills, nausea, vomiting, chest pain, dyspnea, hypoxia, severe abdominal/flank/leg pain, flushing, urticaria 5
• If infusion reactions occur, temporarily interrupt infusion and administer IV diphenhydramine 5
• For persistent candidemia despite appropriate therapy, investigate for deep tissue focus of infection 2, 4

Critical Preparation and Administration Warnings

• Never reconstitute with saline solutions—this causes precipitation 3
• Do not use diluents containing bacteriostatic agents (e.g., benzyl alcohol)—this causes precipitation 3
• Strict aseptic technique is mandatory, as no preservative is present 3
• If using an in-line membrane filter, the mean pore diameter must not be less than 1 micron 3
• Do not use if any evidence of precipitation or foreign matter is present 3

Common Pitfalls to Avoid

• Do not exceed 1.5 mg/kg/day of conventional amphotericin B—potentially fatal cardiac arrest can occur 3
• Do not skip pre-hydration with normal saline—this significantly increases nephrotoxicity risk 1, 5
• Do not use conventional amphotericin B when lipid formulations are available for patients with renal impairment 5
• Do not use low doses (1 mg/kg) for initial treatment of fulminant infections—efficacy may be compromised 8