Synergistic Effects of Ketamine and Azole Derivatives on<i>Candida</i>Spp. Resistance to Fluconazole

Abstract

The emergence of <i>Candida</i> spp. with resistance to antifungal molecules, mainly the azole class, is an increasing complication in hospitals around the globe. <b>Aim:</b> In the present research, we evaluated the synergistic effects of ketamine with two azole derivatives, itraconazole and fluconazole, on strains of <i>Candida</i> spp. to fluconazole. <b>Materials & methods:</b> The drug synergy was evaluated by quantifying the fractional inhibitory concentration index and by fluorescence microscopy and flow cytometry techniques. <b>Results:</b> Our achievements showed a synergistic effect between ketamine in addition to the two antifungal agents (fluconazole and itraconazole) against planktonic cells and biofilms of <i>Candida</i> spp. <b>Conclusion:</b> This combination promoted alteration of membrane integrity, generation of reactive oxygen species, damage to and DNA and externalization of phosphatidylserine.