Synergistic Effect of Essential Oils and Antifungal Agents in Fighting Resistant Clinical Isolates of Candida auris

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Recently, a large number of nosocomial infections have been caused by an emerging pathogen that is rising as a worldwide issue in human health: Candida auris. This yeast is considered resistant to antifungals of the first-line therapies, and consequently it is related to morbidity and mortality. Therefore, the aim of this research was to determine the in vitro anti-C. auris activity against twenty-three resistant clinical strains of different essential oils (EOs), pure or in combination with traditional antifungal agents, mainly caspofungin, fluconazole, micafungin and 5-flucytosine. Broth dilution assay was performed to evaluate the fungistatic and fungicidal effectiveness of fifteen EOs towards all the C. auris isolates. The data demonstrated that EOs were able to prevent C. auris growth, with MIC values ranging from 0.03 to 1% for the efficacious EOs (thyme, cinnamon, geranium, clove bud, lemongrass and mentha of Pancalieri), whereas the MICs were >1% for the ineffective ones. Thereafter, the six most effective EOs were used to perform the checkerboard experiments by assaying simultaneously the activity of EOs and traditional antifungals towards two selected strains. The most promising synergic combinations towards C. auris, depending on the isolate, were those with micafungin and geranium, thyme, cinnamon, lemongrass or clove bud EOs, with fluconazole and mentha of Pancalieri EO, and with 5-flucytosine and mentha of Pancalieri EO. These EOs and their combinations with antifungal drugs may provide a useful therapeutic alternative that could reduce the dose of the individual components, limiting the overall side effects. These associations might be a prospective option for the future treatment of infections, thus helping to overcome the challenging issue of resistance in C. auris.

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