Detection and Significance of Antifungal Resistance in Oropharyngeal Candidiasis

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Antifungal resistance remains an important clinical problem in the management of HIV-infected patients with recurrent oropharyngeal candidiasis. Candida albicans is the most frequent pathogen associated with symptomatic disease but other Candida species, such as C. glabrata, also cause infection. These yeasts are important because they frequently exhibit antifungal resistance. Antifungal resistance has been particularly noted in HIV-infected patients who receive frequent courses or prolonged therapy. Molecular mechanisms of azole resistance include alterations in the target enzyme and increased expression of multidrug efflux pumps. Rapid detection of resistant yeasts could allow prompt initiation of effective therapy. In addition, because colonization with resistant yeasts is an important risk factor in developing systemic infection in susceptible hosts, a rapid test for resistant organisms could impact empirical antifungal therapy in those patients. Thus, the objectives of this proposal are to develop novel diagnostic platforms to rapidly detect resistant yeasts in vivo and to correlate that detection with symptomatic infection and recurrence of oropharyngeal candidiasis. These objectives will be achieved through prospectively evaluating HIV- infected patients presenting with oropharyngeal infection including patients with antifungal resistance. The specific aims of this proposal are: i) to serially evaluate a cohort of HIV-infected patients in order to determine the epidemiology and significance of real-time molecular detection of resistant oral yeasts; ii) to develop molecular diagnostic methods to identify species of yeasts other than Candida albicans, including C. glabrata and to correlate that detection with chromogenic culture techniques; and iii) to develop molecular assays for detecting in vivo molecular mechanisms of resistance including expression of drug efflux pumps. These studies will increase understanding of the epidemiology of resistance mechanisms, determine the impact of in vivo detection of resistant yeasts on recurrence, and ultimately improve management of patients with oropharyngeal candidiasis as well as those at risk for invasive candidiasis. Relevance to public health: Oral yeast infection (thrush) is an important complication in patients with HIV/AIDS. This research is aimed at developing rapid molecular tests to detect yeasts which are resistant to antifungal agents in order to allow early use of more effective therapy.