Emergence of azole drug resistance in Candida species from HIV-infected patients receivingprolonged fluconazole therapy for oral candidosis

We examined the effect of different fluconazole treatment regimens on the emergence of azole drug resistance among Candida species recovered from the mouths of 54 HIV-infected individuals. Patients were assigned to one of three treatment groups depending on their history of oral candidosis and fluconazole use. Mouthwashes obtained at regular intervals were cultured and isolates identified using standard methods. Antifungal broth micro-dilution tests were performed to determine IC30s of fluconazole and ketoconazole. Sixty-four Candida albicans isolates from 20 patients with no evidence of oral candidosis who had not received fluconazole all had IC30s of or = 64 mg/L. In contrast, 26 (40%) of 65 C. albicans isolates from 15 patients given long-term fluconazole (50-200 mg/day or 150 mg/week) were classified as resistant having IC30s of fluconazole of > or = 64 mg/L. Ten of these 26 fluconazole-resistant isolates were susceptible to ketoconazole with IC30s of or = 64 mg/L. Our experience with C. albicans in patients with HIV infection, suggests that the long-term azole drug use may be an important factor in the development of fluconazole resistance as such resistance was rare and transient in patients on intermittent short-term treatment.