Course: Opportunistic Fungi in the Immunocompromised Patient
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Therapeutic Approaches to Fungal Disease
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Echinocandin/Pneumocandin Agents

An important new class of antifungal agents called echinocandins is on the horizon [90]. These drugs have been described mechanistically as the "penicillins" of antifungal therapycell- wall synthesis inhibitors. Echinocandins act by inhibiting glucan synthesis via inhibition of 1,3-beta-D-glucan synthase. This interferes with the synthesis of chitin, an important cell-wall component, and results in fungal cell lysis. These drugs have fungicidal activity against Candida species, including fluconazole-resistant C albicans and pathogenic nonalbicans yeasts. In addition, in vitro and in vivo activity against Aspergillus species have been shown [91]. A notable limitation is the lack of activity against C neoformans and Zygomycetes as well as other pathogenic moulds. However, the unique mechanism of action will offer the potential use of the echinocandins in combination with other antifungal regimens.

Of these agents, caspofungin received FDA approval in early 2001 and clinical trials of anidulafungin (previously known as VER 002 or LY 303366), and micafungin (FK 463) are in progress. All these agents require parenteral administration and are minimally cleared by the kidney. They have demonstrated excellent safety profiles in phase I and II clinical trials reported to date.

Preliminary results of phase II trials comparing caspofungin 50 or 70 mg/d IV for 2 weeks (n = 74) with amphotericin B 0.5 mg/kg/d IV for the same period (n = 54) in patients with candidal esophagitis have shown promise for this group of compounds. Efficacy was equivalent in the echinocandin group, and adverse effects, including renal dysfunction, were uncommon in patients receiving caspofungin [92]. Recent studies have also demonstrated the utility of caspofungin in a salvage study of invasive aspergillosis in which response rates of 41% were demonstrated in 54 patients who were intolerant of or were failing standard antifungal regimens [93].

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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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