Drug Resistance in Candida krusei: A Literature Review on Mechanisms and Pathways

Abstract

Candida krusei has been identified as a potential multi-drug resistant (MDR) pathogen. In vitro antifungal tests have shown a significant decrease in the susceptibility of C. krusei to fluconazole. Candida krusei commonly causes systemic infections. Effective systemic antifungal agents for invasive candidiasis are divided into 4 groups: the first group, Polyenes, includes amphotericin B (AmB) deoxycholate, liposomal AmB, AmB lipid complex (ABLC), and AmB colloidal dispersion (ABCD). The second group, Triazoles, includes fluconazole, itraconazole, voriconazole, and posaconazol. This group is the most commonly used for the treatment of candidiasis worldwide. Due to its widespread use, it has led to antifungal resistance, especially in certain types of Candida, such as C. krusei. The third group, Echinocandins, includes caspofungin, anidulafungin, and micafungin. Currently, this classification of antifungals is widely used for the treatment of Candida and is effective for certain types of Candida. The fourth group used is Flucytosine.1 Polyenes and azoles (imidazoles and triazoles) are the most commonly used antifungal agents. Fluconazole, one of the most widely used triazoles for antifungals, is a low molecular weight triazole that is highly active against several pathogens that cause systemic mycosis. Fluconazole has unique pharmacokinetics, high water solubility, weak protein binding, high cerebrospinal fluid penetration, and is well absorbed after oral administration. Fluconazole belongs to the azole drug class, where its target is the cytochrome P450-dependent lanosterol 14α demethylase Erg11p enzyme, which is encoded by the ERG11 gene. This enzyme catalyzes the sterol 14α demethylase reaction in ergosterol biosynthesis. ...