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 |
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*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 |
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*Causes renal dysfunction, among other things |
*Causes renal dysfunction, among other things |
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=== 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]] |
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===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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|[[Candida albicans]] |
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|2 |
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|[[Candida dubliniensis]] |
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|[[Candida glabrata]] |
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|2 |
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|[[Candida guilliermondii]] |
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|[[Candida krusei]] |
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|2 |
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|[[Candida lusitaniae]] |
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|[[Candida parapsilosis]] |
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|2 |
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|[[Candida tropicalis]] |
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|2 |
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|[[Cryptococcus neoformans]] |
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|0.5 |
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|[[Cryptococcus gattii]] |
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|0.5-1 |
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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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|[[Aspergillus fumigatus]] |
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|1 |
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|≤1 |
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|>1 |
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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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|[[Aspergillus terreus]] |
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|8 |
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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 |
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* 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 |
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** Invasive: 3 to 5 mg/kg IV daily |
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** 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]] |
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** Meningitis: 5 mg/kg IV daily for 4 to 6 weeks, followed by [[itraconazole]] |
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[[Category:Polyenes]] |
[[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
- 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