Amphotericin B

Background

• Last choice of antifungal due to side effect profile, but effective
• Binds to ergosterol in fungal cell membrane and creates pores that cause leakage of monovalent ions
• Causes renal dysfunction, among other things

Spectrum of Activity

• Very broad antifungal
• However, there is often non-susceptibility with Candida auris, Candida lusitaniae, Sporothrix, Fusarium, Scedosporium, and Aspergillus terreus

Clinical Breakpoints

Species	ECV (μg/mL)	Breakpoints (μg/mL)				Breakpoints (mm)
		S	SDD	I	R	S	SDD	I	R
Candida albicans	2
Candida dubliniensis
Candida glabrata	2
Candida guilliermondii
Candida krusei	2
Candida lusitaniae
Candida parapsilosis	2
Candida tropicalis	2
Cryptococcus neoformans	0.5
Cryptococcus gattii	0.5-1
Aspergillus flavus	4	—			—
Aspergillus fumigatus	1	≤1			>1
Aspergillus nidulans	4	—			—
Aspergillus niger	0.5	≤1			>1
Aspergillus terreus	8	—			—
Aspergillus versicolor	2	—			—

Dosing

Amphotericin B Deoxycholate (Conventional)

• Usual dose: 0.3 to 1.5 mg/kg IV daily
• Disseminated aspergillosis: 0.6 to 0.7 mg/kg IV daily for 3 to 6 months
• Blastomycosis: 0.7 to 1 mg/kg IV daily for 1 to 2 weeks followed by itraconazole
• Candidiasis
  • CNS infection: 0.01 to 0.5 mg/2mL in D5W intraventricularly
  • Endophthalmitis: 5 to 10 mcg/0.1 mL intravitreally
  • Esophageal: 0.3 to 0.7 mg/kg IV daily
  • Invasive: 0.5 to 0.7 mg/kg IV daily; consider higher dosing up to 1 mg/kg for Candida glabrata or Candida krusei
  • Oropharyngeal: 100 mg suspended in 1 mL 4 times daily
  • Urinary tract infection:
    • Cystitis: 0.3 to 0.6 mg/kg IV daily for 1 to 7 days
    • Pyelonephritis: 0.3 to 0.6 mg/kg IV daily for 1 to 7 days, with or without flucytosine

Liposomal Amphotericin B (AmBisome)

• Usual dose: 3 to 6 mg/kg IV daily
• Aspergillosis: 3 to 5 mg/kg IV daily; up to 7.5 mg/kg for CNS infections
• Candidiasis:
  • Candidemia: 3 to 5 mg/kg IV daily
  • CNS: 5 mg/kg IV daily
  • Hepatosplenic: 3 to 5 mg/kg IV daily
  • Invasive: 3 to 5 mg/kg IV daily
  • Endocarditis: 3 to 5 mg/kg IV daily +/- flucytosine
  • Endophthalmitis: 3 to 5 mg/kg IV daily +/- flucytosine
  • Osteomyelitis: 3 to 5 mg/kg IV daily
  • Septic thrombophlebitis: 3 to 5 mg/kg IV daily
• Coccidiomycosis:
  • Disseminated with HIV: 3 to 4 mg/kg IV daily with flucytosine
  • Meningitis with HIV: 3 to 4 mg/kg IV daily with flucytosine
• Fungal sinusitis: 3 to 10 mg/kg IV daily
• Histoplasmosis
  • Acute pulmonary: 3 to 5 mg/kg IV daily for 1 to 2 weeks, followed by itraconazole
  • Disseminated: 3 mg/kg IV daily for 2 weeks, followed by itraconazole
  • Meningitis: 5 mg/kg IV daily for 4 to 6 weeks, followed by itraconazole