Amphotericin B: Difference between revisions

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== Background ==
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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
 
*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 ===
== Clinical Breakpoints ==
 
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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]]
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===Clinical Breakpoints===
 
{| class="wikitable"
 
{| class="wikitable"
 
! rowspan="2" |Species
 
! rowspan="2" |Species
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|[[Aspergillus flavus]]
 
|[[Aspergillus flavus]]
 
|4
 
|4
|
+
|
  +
| colspan="2" rowspan="6" |
|
 
|
+
|
  +
| colspan="4" rowspan="6" |
|
 
|
 
|
 
|
 
|
 
 
|-
 
|-
 
|[[Aspergillus fumigatus]]
 
|[[Aspergillus fumigatus]]
|2
+
|1
  +
|≤1
|
 
|
+
|>1
|
 
|
 
|
 
|
 
|
 
|
 
 
|-
 
|-
|[[Aspergillus species]]
+
|[[Aspergillus nidulans]]
|2
 
|
 
|
 
|
 
|
 
|
 
|
 
|
 
|
 
|-
 
|[[Aspergillus species]]
 
 
|4
 
|4
|
+
|
|
+
|
|
+
|-
 
|[[Aspergillus niger]]
|
 
|
+
|0.5
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|≤1
|
 
|
+
|>1
|
+
|-
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|[[Aspergillus terreus]]
 
|8
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|—
  +
|—
 
|-
 
|-
 
|[[Aspergillus versicolor]]
 
|[[Aspergillus versicolor]]
 
|2
 
|2
|
+
|
|
+
|
|
 
|
 
|
 
|
 
|
 
|
 
 
|}
 
|}
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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
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** Esophageal: 0.3 to 0.7 mg/kg IV daily
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** Invasive: 0.5 to 0.7 mg/kg IV daily; consider higher dosing up to 1 mg/kg for [[Candida glabrata]] or [[Candida krusei]]
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** 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
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* Aspergillosis: 3 to 5 mg/kg IV daily; up to 7.5 mg/kg for CNS infections
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* Candidiasis:
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** Candidemia: 3 to 5 mg/kg IV daily
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** CNS: 5 mg/kg IV daily
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** 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]]
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** Endophthalmitis: 3 to 5 mg/kg IV daily +/- [[flucytosine]]
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** Osteomyelitis: 3 to 5 mg/kg IV daily
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** Septic thrombophlebitis: 3 to 5 mg/kg IV daily
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* Coccidiomycosis:
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** Disseminated with HIV: 3 to 4 mg/kg IV daily with [[flucytosine]]
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** Meningitis with HIV: 3 to 4 mg/kg IV daily with [[flucytosine]]
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* Fungal sinusitis: 3 to 10 mg/kg IV daily
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* Histoplasmosis
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** Acute pulmonary: 3 to 5 mg/kg IV daily for 1 to 2 weeks, followed by [[itraconazole]]
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** 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]]
 
[[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