In vitro study on the potential fungicidal effects of atorvastatin in combination with some azole drugs against multidrug resistant Candida albicans

This study investigates the potential fungicidal effects of atorvastatin (ATO) combinations with fluconazole (FLU), itraconazole (ITR), ketoconazole (KET) and voriconazole (VOR) against thirty-four multidrug-resistant (MDR)C. albicans using checkerboard and time-kill methods. Results showed that 94.12% of these isolates were MDR to  ≥ two azole drugs, whereas 5.88% of them were susceptible to azole drugs. The tested isolates exhibited high resistance rates to FLU (58.82%), ITR (52.94%), VOR (47.06%) and KET (35.29%), whereas only three representative (8.82%) isolates were resistant to all tested azoles. Remarkably, the i nhibition zones of these isolates were increased at least twofold with the presence of ATO, which interacted in a synergistic (FIC index ≤ 0.5) manner with tested azoles. In silico docking study of ATO and the four azole drugs were performed against the Lanosterol 14-alpha demethylase enzyme ( ERG11) ofC. albicans. Results showed that the mechanism of action of ATO againstC. albicans is similar to that of azole compounds, with a docking score ( −4.901) lower than azole drugs (≥5.0) due to the formation a single H-bond with Asp 225 and a pi–pi interaction with Thr 229. Importantly, ATO combinations with ITR, VOR and KET achieved fungicidal effects (≥ 3 Log10 cfu/ml reduction) against the representative isolates, whereas a fungistatic effect ( ≤ 3 Log10 cfu/ml reduction) was observed with FLU combination. Thus, the combination of ATO ...
Source: World Journal of Microbiology and Biotechnology - Category: Microbiology Source Type: research