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Activity of posaconazole against clinical isolates of Candida albicans with decreased sensitivity to fluconazole from autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy patients

Abstract number: 1733_770

Rautemaa-Richardson R., Richardson M., Pfaller M., Koukila-Kähkölä P., Perheentupa J., Saxen H.

Objectives: Most patients with APECED (autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy) suffer from chronic oral candidosis from early childhood. Thus most patients receive repeated treatment and maintenance courses of azole antifungals, principally ketoconazole and fluconazole, throughout their lives. This has resulted in both mycological and clinical resistance. Our aim was to determine the susceptibility of patient isolates from Finnish patients with APECED to the new triazole antifungal posaconazole, recently approved for the treatment of oropharyngeal candidosis, including infections refractory to fluconazole. In previous studies posaconazole has been shown to be active against most fluconazole-resistant C. albicans isolates.

Methods: The antifungal susceptibility profiles and antifungal usage of all 56 APECED patients followed in our centre were reviewed for the period 1994–2004. C. albicans isolates of 11 patients reported to have decreased fluconazole sensitivity (n = 27, MIC range: 8–32 mg/L) were tested for their sensitivity to posaconazole using a broth dilution technique as detailed in the CLSI document M23-A2. C. albicans strains of 11 patients APECED patients reported to be sensitive to azoles (n = 16, MIC range: 0.12–2 mg/L) were tested in a similar manner.

Results:C. albicans isolates previously shown to be of decreased susceptibility to fluconazole were uniformly sensitive to posaconazole (MIC range: 0.03–1 mg/L). Isolates previously scored as fluconazole sensitive were equally sensitive to posaconazole (MIC range: 0.12–1 mg/L). The upper limit of posaconazole sensitivity has been tentatively been set at ≤1 mg/L.

Conclusions: Decrease in the susceptibility of the colonising C. albicans strains to antifungals was noted in the mid-1990s. Currently, symptomatic patients are prescribed topical polyenes. In some patients eradication treatment of the fluconazole resistant strains with iv caspofungin or liposomal amphotericin B has been successful in combination with topical polyenes and professional oral hygiene procedures. The present data, which highlights the fungistatic and fungicidal activity of posaconazole against strains with decreased fluconazole sensitivity, suggests that oral posaconazole would be effective for treatment of candidosis caused by strains of C. albicans with decreased sensitivity to fluconazole in APECED patients. Furthermore, posaconazole could be used as a first-line drug for eradication treatment.

Session Details

Date: 31/03/2007
Time: 00:00-00:00
Session name: European Society of Clinical Microbiology and Infectious Diseases
Subject:
Location: ICC, Munich, Germany
Presentation type:
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