Amphotericin B: Difference between revisions

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== Background ==
* Last choice of antifungal due to side effect profile, but effective
* Causes renal dysfunction, among other things


*Last choice of antifungal due to side effect profile, but effective
[[Category:Antifungals]]
*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===
{| class="wikitable"
! rowspan="2" |Species
! rowspan="2" |ECV (μg/mL)
! colspan="4" |Breakpoints (μg/mL)
! colspan="4" |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
|—
| colspan="2" rowspan="6" |
|—
| colspan="4" rowspan="6" |
|-
|[[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]]

[[Category:Polyenes]]

Latest revision as of 13:01, 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