The yeast Candida albicans occurs in most healthy people as a harmless colonizer in the digestive tract. However, it can also cause life-threatening infections, especially in immunocompromised patients. These infections are usually treated with the drug fluconazole, which inhibits the synthesis of ergosterol in Candida. Ergosterol fulfils similar important functions in fungi as cholesterol in humans. Candida albicans can, however, become resistant to this drug. Scientists have uncovered the main mechanisms of fluconazole resistance in recent years. The group of Professor Joachim Morschhäuser from the Institute for Molecular Infection Biology at Julius-Maximilians-Universität Würzburg (JMU) in Bavaria, Germany, has contributed important findings. Fluconazole is a first-generation triazole antifungal medication. It differs from earlier azole antifungals (such as ketoconazole) in that its structure contains a triazole ring instead of an imidazole ring. While the imidazole antifungals are mainly used topically, fluconazole and certain other triazole antifungals are preferred when systemic treatment is required because of their improved safety and predictable absorption when administered orally. Fluconazole's spectrum of activity includes most Candida species (but not Candida krusei or Candida glabrata), Cryptococcus neoformans, some dimorphic fungi, and dermatophytes, among others. Common uses include: Fungal resistance to drugs in the azole class tends to occur gradually over the course of prolonged drug therapy, resulting in clinical failure in immunocompromised patients (e.g., patients with advanced HIV receiving treatment for thrush or esophageal Candida infection). albicans, resistance occurs by way of mutations in the ERG11 gene, which codes for 14α-demethylase. These mutations prevent the azole drug from binding, while still allowing binding of the enzyme's natural substrate, lanosterol. glabrata is increasing the rate of efflux of the azole drug from the cell, by both ATP-binding cassette and major facilitator superfamily transporters. Development of resistance to one azole in this way will confer resistance to all drugs in the class. Other gene mutations are also known to contribute to development of resistance.
Sixty-five patients with Candida albicans fungaemia, admitted to intensive care units, were treated intravenously with fluconazole. All patients had at least one. Abstract. Candida albicans is responsible for most fungal infections in humans. Fluconazole is well established as a first-line management option for the treatment and prophylaxis of localized and systemic C. albicans infections.