MICROBIOLOGICAL SCREENING OF IRISH AUTOIMMUNE POLYENDOCRINOPATHY-CANDIDIASIS-ECTODERMAL DYSTROPHY (APECED) PATIENTS REVEALS PERSISTENCE OF CANDIDA ALBICANS STRAINS, GRADUAL REDUCTION IN SUSCEPTIBILITY TO AZOLES AND INCIDENCES OF CLINICAL SIGNS OF ORAL CANDIDIASIS WITHOUT CULTURE EVIDENCE

Abstract

Patients with Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) are prone to chronic mucocutaneous candidiasis, which is often treated with azoles. The purpose of this study was to characterize the oral Candida populations from 16 Irish APECED patients, approximately half the total number identified in Ireland, and to examine the effect of intermittent antifungal therapy on the azole susceptibility patterns of Candida isolates. Patients attended between one and four clinical evaluations over a five-year period, providing oral rinses and/or oral swab samples each time. Candida was recovered from 14/16 patients and Candida albicans was the only Candida species identified. Interestingly, clinical diagnosis of candidiasis did not correlate with microbiological evidence of Candida infection at 7/22 (32%) clinical assessments. Multilocus sequence typing (MLST) analysis of C. albicans isolates recovered from the same patients on separate occasions identified the same sequence type each time. Fluconazole resistance was detected in isolates from one patient, and isolates exhibiting a progressive reduction in itraconazole and/or fluconazole susceptibility were identified in a further 3/16 patients, in each case correlating with upregulation of CDR- and MDR-encoded efflux pumps. Mutations were also identified in the ERG11 and the TAC1 genes of isolates from these four patients, some of which have previously been associated with azole resistance. The study suggests that alternative Candida treatment options, other than azoles such as chlorhexidine, should be considered in APECED patients and that clinical diagnosis of oral candidiasis should be confirmed by culture prior to the commencement of anti-Candida therapy.