EPIDEMIOLOGY OF ORAL CANDIDIASIS IN HIV-INFECTED PATIENTS - COLONIZATION, INFECTION, TREATMENT, AND EMERGENCE OF FLUCONAZOLE RESISTANCE

PURPOSE: To study the epidemiology of oral candidiasis and the effect of treatment of thrush in human immunodeficiency virus (HIV)-infected patients. PATIENTS AND METHODS: We conducted a prospective observation al study of 92 patients over 1 year, including a nonblinded, randomize d treatment trial of thrush with clotrimazole troches or oral fluconaz ole. Oral sites were cultured monthly and when thrush occurred. Candid a albicans strains were typed by contour-clamped homogeneous electric field (CHEF) electrophoresis. Changes in strains were evaluated over t ime and in regard to their associations with particular sites, episode s of thrush, relapse after treatment, and colonization of sexual partn ers. Susceptibility to fluconazole was tested and CHEF analysis was do ne on these strains to determine the epidemiology of fluconazole resis tance. RESULTS: Yeasts colonized 84% of patients. C albicans accounted for 81% of all isolates and was separated into 34 distinct strains. M ost patients had persistent carriage of 1 or 2 dominant strains of C a lbicans. Three couples shared strains. Nineteen different C albicans s trains caused 82 episodes of thrush in 45 patients. CD4 <200/mu L was associated with development of thrush. Clinical cure rates were simila r with fluconazole (96%) and clotrimazole (91%), but mycologic cure wa s better with fluconazole (49%) than clotrimazole (27%). Following myc ologic cure, colonization recurred with the same strain 74% of the tim e. Colonization with Torulopsis glabrata and Saccharomyces cerevisiae increased after treatment with either drug, but these organisms were n ever a sole cause of thrush. In a subset of 35 patients followed for o ver 3 months in whom fluconazole susceptibilities were performed, mini mum inhibitory concentrations (MICs) to fluconazole increased only in those on fluconazole prophylaxis. Clinical failure of fluconazole was associated with an MIC greater than or equal to 64 mu g/mL in 3 patien ts, and with an MIC of 8 mu g/mL in 1 patient. In 2 of these 4 patient s, the prior colonizing strain developed fluconazole resistance. In th e other 2, new resistant strains were acquired. CONCLUSIONS: Many diff erent strains of C albicans colonize and cause thrush in patients infe cted with HIV. Patients are usually persistently colonized with a sing le strain, and recurrences following treatment are usually due to the same strain. Transmission of strains may occur between couples. Flucon azole and clotrimazole are equally effective in treating thrush, but m ycologic cure occurs more often with fluconazole. Fluconazole resistan ce in C albicans occurs most often in patients who have low CD4 counts and are taking fluconazole prophylactically for recurrent thrush. Flu conazole resistance may occur through acquisition of a new resistant s train or by development of resistance in a previously susceptible stra in.