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 |
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− | * Causes renal dysfunction, among other things |
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+ | *Last choice of antifungal due to side effect profile, but effective |
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− | [[Category:Antifungals]] |
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+ | *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 |
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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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+ | |- |
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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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+ | | |
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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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+ | |- |
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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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+ | | |
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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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+ | | |
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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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+ | | |
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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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+ | | |
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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) === |
||
+ | |||
+ | * 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 |
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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 |
||
+ | ** 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 |
||
+ | * 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]] |
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
- 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