Antifungal Agents

• Amphotericin B: (Fungizone, Amphotec)

  • Routes of administration:

    • colloidal preparation -- intravenous or intrathecal

  • Pharmacokinetics: amphotericin B

    • very slow catabolism

    • poor penetration into CNS/vitreous humor

    • amphotericin B concentrations in pleural, peritoneal, articular exudates- adequate for many mycoses

• Clinical use: amphotericin B

  • Most effective in treating:

    • histoplasmosis

    • blastomycosis

    • paracoccidioidomycosis

    • candidiasis

    • cryptococcosis

  •  Less responsive:

    • Coccidiodomycosis

    • extraarticular sporotricosis

    • Aspergillosis

    • mucormycosis

  •  Very poor responding:

    • chromoblastomycosis

    • mycetoma

    • pseudallescheriasis

•  Adverse Effects:Amphotericin B (Fungizone, Amphotec)

  •  febrile reactions (many poorly tolerated by patients with compromised cardiopulmonary function) -- recommend test dose

  •  Premedication with aspirin/acetaminophen or addition of hydrocortisone: reduces chills and fever associated with aphotericin B infusion

  •  saline infusion: may reduce azotemia

  •  permanent loss of renal function: dependent on total amphotericin B dose {usually noted in adult patients receiving > 3 grams}

  •  anemia, hypokalemia, renal tubular acidosis, nausea, anorexia, weight loss, phlebitis, hypomagnesemia

  •  intrathecal amphotericin B: considerable toxicity -- used in coccidioidal meningitis and refractory cryptococcal meningitis.

• Special Preparations:amphotericin B:

  • amphotericin B lipid complex (ABLC)--

    • reduced nephrotoxicity

    • comparative efficacy unknown

    • on the basis of uncontrolled clinical trials, ABLC is marketed in the United States for the narrow indication of refractory Aspergillosis (1998)

• Flucytosine: (Ancobon)

  • Clinical Use:Flucytosine

    • cryptococcosis

    • candidiasis

    • chromoblastomycosis

• Mechanism of Action-- flucytosine: converted to 5-fluorouracil (antimetabolite)

  • used as single agent: drug resistance develops rapidly

  • typically combined with amphotericin B

• Pharmacokinetics: flucytosine (Ancobon)

  • well absorbed from the GI tract

  • effective CNS penetration

  • excreted unchanged by the kidney

  • flucytosine blood levels very sensitive to kidney function