Resistance of Candida species to antifungal agents: molecular mechanisms and clinical consequences.
Candida albicans and related species pathogenic for man become resistant to antifungal agents, in particular triazole compounds, by expression of efflux pumps that reduce drug accumulation, alteration of the structure or concentration of antifungal target proteins, and alteration of membrane sterol composition. The clinical consequences of antifungal resistance can be seen in treatment failures in patients and in changes in the prevalences of Candida species causing disease. These effects were seen unequivocally in HIV-infected patients with oropharyngeal candida infections, but their incidence has decreased dramatically with the introduction of highly active antiretroviral therapy. The evidence for similar emergence of antifungal-resistant yeast strains and species in other types of candida infections is confounded by non-standardised susceptibility testing methods and definitions of a resistant fungal isolate. Recent large-scale surveys of yeasts isolated from blood cultures, based on standardised methodology and resistance definitions, do not support the view that antifungal resistance in pathogenic yeasts constitutes a significant or growing therapeutic problem.
Sanglard
Dominique
D
Institute of Microbiology, University Hospital Lausanne, Lausanne, Switzerland.
Odds
Frank C
FC
D000666:Amphotericin B / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology; D002175:Candida / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D025141:Drug Resistance, Fungal / Q000235:genetics*; D005437:Flucytosine / Q000494:pharmacology; D016469:Fungemia / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D010088:Oxidoreductases / Q000235:genetics; D058886:Sterol 14-Demethylase; D014230:Triazoles / Q000494:pharmacology
D000935:Antifungal Agents; D001393:Azoles; C548418:CYP51A1 protein, human; D014230:Triazoles; D000666:Amphotericin B; D003577:Cytochrome P-450 Enzyme System; D005437:Flucytosine; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase