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Case 4: Fluconazole-Resistant Oropharyngeal Candidiasis

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B Fluconazole exerts its effect by inhibiting fungal cell wall synthesis. Fluconazole resistance in Candida species occurs primarily through an increase production in cell wall precursors.

This answer is incorrect. The mechanism of action of fluconazole involves decreasing the synthesis of ergosterol, the key component of the fungal cell membrane. Specifically, fluconazole blocks a step in the conversion of squalene to ergosterol by inhibiting the fungal cytochrome P-450 enzyme 14 alpha-demethylase. Fluconazole does not have activity on fungal cell wall synthesis. Fluconazole resistance results from an alteration in the target enzyme 14 alpha-demethylase (change in binding site or over expression of the enzyme) or enhanced drug efflux caused by plasma membrane transporters. Many strains have developed multiple resistance mechanisms.

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A The most important risk factor identified for the development of fluconazole-resistant oropharyngeal candidiasis is the use of trimethoprim-sulfamethoxazole for longer than 60 days.
C More than 95% of Candida albicans isolates from patients with fluconazole-refractory oropharyngeal candidiasis show resistance to itraconazole (Sporanox). Fewer than 5% of patients with fluconazole-refractory oropharyngeal candidiasis will respond to itraconazole solution at a dose of 200 mg per day.
D Major identified risk factors for the development of fluconazole-resistant candidiasis include low CD4 cell count and cumulative fluconazole use.

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