In Vitro Interactions of Echinocandins with Triazoles Against Multidrug-Resistant Candida auris
Hamid Badalii
Abstract
Hamid Badalii
Abstract
Abstract Background Blood stream infections due to Candida auris are related to a high mortality rate and treatment failure attributed to resistance to fluconazole, voriconazole, amphotericin B, and caspofungin. Thus, the precise identification of agents and in vitro antifungal susceptibility testing is highly recommended. Novel therapeutic strategies, such as combination therapy, are essential for increasing the efficacy and reducing the toxicity of antifungal agents. Therefore, we investigated the in vitro combination of micafungin plus voriconazole against multidrug-resistant C. auris isolated from cases of candidemia. Methods The in vitro interactions between echinocandins and azoles were determined against ten multidrug-resistant Candida auris strains by using a microdilution checkerboard technique. Results Results revealed that MICs range for voriconazole and micafungin were 0.5–8 and 0.25–8 mg/l, respectively. The checkerboard analysis revealed that the combination of micafungin with voriconazole exhibited synergistic activity against all 10 multidrug-resistant C. auris isolates (FICI range: 0.15–0.5). Overall, no antagonistic effects were observed in this experiments. Conclusion In vitro studies have previously suggested that among azoles isavuconazole and posaconazole are more active drugs against C. auris. In addition, the majority of isolates reported are resistant to fluconazole. Remarkably, unsuccessful treatment of C. auris infections with fluconazole, voriconazole, amphotericin B, caspofungin, and anidulafungin has been already on record. Here in we demonstrates that interaction between micafungin with voriconazole exhibited synergistic activity against multidrug-resistant C. auris isolates. It seems that lower concentrations of drugs cause fewer side-effects and improve the treatment outcomes. However, in vivo studies with suitable animal models of C. auris infection is highly recommended. Disclosures All authors: No reported disclosures.
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Abstract Background Blood stream infections due to Candida auris are related to a high mortality rate and treatment failure attributed to resistance to fluconazole, voriconazole, amphotericin B, and caspofungin. Thus, the precise identification of agents and in vitro antifungal susceptibility testing is highly recommended. Novel therapeutic strategies, such as combination therapy, are essential for increasing the efficacy and reducing the toxicity of antifungal agents. Therefore, we investigated the in vitro combination of micafungin plus voriconazole against multidrug-resistant C. auris isolated from cases of candidemia. Methods The in vitro interactions between echinocandins and azoles were determined against ten multidrug-resistant Candida auris strains by using a microdilution checkerboard technique. Results Results revealed that MICs range for voriconazole and micafungin were 0.5–8 and 0.25–8 mg/l, respectively. The checkerboard analysis revealed that the combination of micafungin with voriconazole exhibited synergistic activity against all 10 multidrug-resistant C. auris isolates (FICI range: 0.15–0.5). Overall, no antagonistic effects were observed in this experiments. Conclusion In vitro studies have previously suggested that among azoles isavuconazole and posaconazole are more active drugs against C. auris. In addition, the majority of isolates reported are resistant to fluconazole. Remarkably, unsuccessful treatment of C. auris infections with fluconazole, voriconazole, amphotericin B, caspofungin, and anidulafungin has been already on record. Here in we demonstrates that interaction between micafungin with voriconazole exhibited synergistic activity against multidrug-resistant C. auris isolates. It seems that lower concentrations of drugs cause fewer side-effects and improve the treatment outcomes. However, in vivo studies with suitable animal models of C. auris infection is highly recommended. Disclosures All authors: No reported disclosures.
Key concepts: Candida auris, Caspofungin, Voriconazole, Micafungin, Anidulafungin, Fluconazole, Posaconazole, Echinocandins