Oropharyngeal yeast flora and fluconazole resistance in HIV-infected patients receiving long-term continuous versus intermittent fluconazole therapy

Objective: To examine the impact of continuous versus intermittent fluconazole therapy on fungal colonization and fluconazole resistance in the oropharynx of HIV-infected patients. Design: Case-control study. Setting: Duke University Adult Infectious Diseases Clinic, a tertiary referral center in North Carolina which provides care for 700 HIV-infected persons. Patients: Nineteen HIV-infected patients on daily continuous fluconazole for a minimum of 6 months and eleven HIV-infected patients on intermittent fluconazole for a minimum of 6 months were matched by sex and CD4 cell count to HIV-infected patients who had not received fluconazole in the preceding 6 months. Main outcome measures: Fungal isolation and fluconazole susceptibility testing were performed on oral saline rinses from each patient. Results: The patients taking continuous fluconazole were more likely than matched controls to have had sterile mouth rinses (14 out of 19 versus five out of 19; P < 0.001), and the yeasts that were isolated were more likely than matched controls to be non-Candida albicans species and to have minimum inhibitory concentrations (MIC) to fluconazole greater than or equal to 16 mu g/ml. None of these isolates were associated with symptoms. In contrast, none of the patients in the intermittent fluconazole group had sterile cultures. When this group was compared to controls, they were more likely to have had non-C. albicans species, and the C. albicans isolates obtained had higher MIC to fluconazole. Conclusions: Long-term continuous therapy with fluconazole may prevent the appearance of Candida in the oral cavity. This finding may reduce recurrence rates and might favorably impact on the clinical appearance of mucosal candidiasis with resistant C. albicans.