JAC Advance Access published online on August 17, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm299
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Decreased susceptibility of Candida albicans to azole antifungals: a complication of long-term treatment in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patients
1 Department of Microbiology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland 2 Department of Bacteriology, Helsinki University Central Hospital HUSLAB, Helsinki, Finland 3 Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland 4 Department of Mycology, Helsinki University Hospital HUSLAB, Helsinki, Finland 5 Medical Microbiology Division, Department of Pathology, College of Medicine, University of Iowa, Iowa City, IA, USA 6 The Hospital for Children and Adolescents, Helsinki University Central Hospital and University of Helsinki, Finland
Received 29 May 2007; returned 29 June 2007; revised 13 July 2007; accepted 13 July 2007
* Correspondence address. Department of Bacteriology and Immunology, Haartman Institute, PO Box 21 (Haartmaninkatu 3), University of Helsinki, FIN-00014, Helsinki, Finland. Tel: +358-9-19126377; Fax: +358-9-19126382; E-mail: riina.richardson{at}helsinki.fi
Background: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, APS1) is an autosomal recessive disease exceptionally common in Finland. Most patients have chronic oral candidiasis from early childhood and this infection has been shown to be carcinogenic. Hence, patients receive repeated treatment and prophylactic courses of antifungals throughout life. In Finland, 92 patients have been diagnosed with APECED and 66 of them are currently alive. Our aim was to study the effect of long-term azole treatment on the candidal colonization of APECED patients and the influence on antifungal susceptibilities.
Methods: We evaluated the culture reports from 1994 to 2004 of 56 APECED patients followed in Helsinki University Central Hospital. Candida albicans strains of all 11 patients initially reported resistant (n = 27) and 12 patients reported susceptible (n = 16) to fluconazole were re-analysed for their susceptibility to fluconazole. Antifungal usage was analysed up to 30 years back.
Results: A total of 162 fungal cultures had been performed. Of these, 75% had been reported positive for Candida and 63% for C. albicans. Eleven patients (31.4%) had been reported to harbour at least once a C. albicans strain resistant to fluconazole. Re-analysis of the stored C. albicans strains originally reported to be resistant to fluconazole revealed a mean MIC of 19.5 mg/L.
Conclusions: Multiple courses (>6) of fluconazole annually and low dose prophylaxis are major risk factors for persistent colonization with C. albicans with decreased susceptibility in APECED patients.
Key Words: oral candidiasis , C. albicans , APS1 , CMC