Decreased susceptibility of Candida albicans to azole antifungals: a complication of long-term treatment in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patients.
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.
Rautemaa
Riina
R
Department of Microbiology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland. riina.richardson@helsinki.fi
Richardson
Malcolm
M
Pfaller
Michael
M
Koukila-Kähkölä
Pirkko
P
Perheentupa
Jaakko
J
Saxén
Harri
H
D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001393:Azoles / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000302:isolation & purification; D002648:Child; D025141:Drug Resistance, Fungal; D005387:Finland; D006801:Humans; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000150:complications* / Q000382:microbiology
D000935:Antifungal Agents; D001393:Azoles