Amphotericin B: Difference between revisions

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== Background ==
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= Amphotericin B =
  
   
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* Last choice of antifungal due to side effect profile, but effective
 +
*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
  
  +
*Causes renal dysfunction, among other things
  +
  +
=== Spectrum of Activity ===
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  +
* Very broad antifungal
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* However, there is often non-susceptibility with [[Candida auris]], [[Candida lusitaniae]], [[Sporothrix]], [[Fusarium]], [[Scedosporium]], and [[Aspergillus terreus]]
  +
  +
===Clinical Breakpoints===
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{| class="wikitable"
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! rowspan="2" |Species
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! rowspan="2" |ECV (μg/mL)
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! colspan="4" |Breakpoints (μg/mL)
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! colspan="4" |Breakpoints (mm)
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|-
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!S
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!SDD
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!I
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!R
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!S
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!SDD
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!I
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!R
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|-
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|[[Candida albicans]]
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|2
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|
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|
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|
  +
|
  +
|
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|
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|
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|
  +
|-
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|[[Candida dubliniensis]]
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|-
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|[[Candida glabrata]]
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|2
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|
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|
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|
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|
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|
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|
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|
  +
|
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|-
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|[[Candida guilliermondii]]
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|
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|
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|
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|
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|
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|
  +
|
  +
|
  +
|
  +
|-
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|[[Candida krusei]]
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|2
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|
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|
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|
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|
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|
  +
|
  +
|
  +
|
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|-
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|[[Candida lusitaniae]]
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|
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|
  +
|
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|
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|
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|
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|
  +
|
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|
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|-
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|[[Candida parapsilosis]]
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|2
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|
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|
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|
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|
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|
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|
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|
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|
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|-
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|[[Candida tropicalis]]
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|2
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|
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|
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|
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|
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|
  +
|
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|
  +
|
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|-
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|[[Cryptococcus neoformans]]
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|0.5
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|
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|
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|
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|
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|
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|
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|
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|
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|-
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|[[Cryptococcus gattii]]
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|0.5-1
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|
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|
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|
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|
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|
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|
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|
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|
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|-
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|[[Aspergillus flavus]]
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|4
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|—
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| colspan="2" rowspan="6" |
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|—
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| colspan="4" rowspan="6" |
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|-
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|[[Aspergillus fumigatus]]
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|1
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|≤1
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|>1
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|-
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|[[Aspergillus nidulans]]
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|4
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|—
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|—
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|-
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|[[Aspergillus niger]]
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|0.5
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|≤1
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|>1
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|-
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|[[Aspergillus terreus]]
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|8
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|—
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|—
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|-
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|[[Aspergillus versicolor]]
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|2
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|—
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|—
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|}
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  +
== Dosing ==
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  +
=== Amphotericin B Deoxycholate (Conventional) ===
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  +
* Usual dose: 0.3 to 1.5 mg/kg IV daily
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* 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]]
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* Candidiasis
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** CNS infection: 0.01 to 0.5 mg/2mL in D5W intraventricularly
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** 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
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** Urinary tract infection:
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*** Cystitis: 0.3 to 0.6 mg/kg IV daily for 1 to 7 days
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*** Pyelonephritis: 0.3 to 0.6 mg/kg IV daily for 1 to 7 days, with or without [[flucytosine]]
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  +
=== Liposomal Amphotericin B (AmBisome) ===
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* 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:
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** 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
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** 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]]
  +
  +
[[Category:Polyenes]]

Latest revision as of 09:01, 22 October 2024

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

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
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