Course: Opportunistic Fungi in the Immunocompromised Patient
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Therapeutic Approaches to Fungal Disease
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Azole Antifungal Agents

In recent years, ketoconazole, itraconazole, and fluconazole have become frequent therapeutic alternatives to AmB. These azole compounds inhibit 14-demethylation of lanosterol by binding to fungal cytochrome P450 enzymes. Ergosterol in the cytoplasmic membrane is reduced, leading to inhibition of cell growth. These drugs are considered fungistatic, as opposed to the fungicidal actions of the polyenes, although newer azoles demonstrate in vitro fungicidal activity for Aspergillus spp and other moulds. Their greatest benefit over AmB is their oral formulation and limited toxicity. Fluconazole and itraconazole are better tolerated than ketoconazole. One limitation of this group of antifungal compounds is the frequency of their interactions with coadministered drugs. Decreased absorption is particularly a problem with itraconazole [88], but not with fluconazole. Absorption of itraconazole has been improved with an oral suspension, and the newly available IV formulation. Increasing emergence of fungal organisms resistant to fluconazole, especially the Candida species, is becoming problematic, a turn of events traceable in part to the prophylactic and empiric use of fluconazole and the other azoles.

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Therapeutic Approaches to Fungal
   Amphotericin B
   Lipid Formulations of Amphotericin B
   Azole Antifungal Agents
   New Azoles Undergoing Clinical Trials
   Echinocandin/Pneumocandin Agents

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Course Number: V035B.043001

This CME Expires on July 1, 2003; no tests will be accepted after this date.

This course is accredited by The University of Pittsburgh School of Medicine, Center for Continuing Education

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