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    Effects of calcineurin inhibitors, cyclosporine A and tacrolimus (FK506), on the activity of antifungal drugs against Candida spp
    (Microbiology Soc, 2021) Kaya, Sümeyye Şen; Kiraz, Nuri; Barış, Ayşe; Turan, Deniz; Öz, Yasemin; Dağ, İlknur; Aygün, Gökhan
    Introduction. The simultaneous use of antifungals with immunosuppressive agents has become a necessity for patients taking immunosuppressive therapy. However, antifungal drugs are problematic because of their limited target. Hypothesis. Scientists have been searching for new antifungals and some compounds with at least additive effects on antifungals. Calcineurin inhibitors used as immunosuppressive agents also attract attention due to their antifungal property. Aim. To evaluate the activity of two calcineurin inhibitors alone and in combination with amphotericin B (AMB), caspofungin (CAS), itraconazole (ITR), voriconazole (VOR) and fluconazole (FLU). Methodology. MICs of AMB, CAS, ITR, VOR, FLU and cyclosporine A (CsA) and tacrolimus (TAC) as calcineurin inhibitors were evaluated by the broth microdilution method against Candida albicans (n=13), C. krusei (n=7) and C. glabrata (n=10). Checkerboard and time-kill methods were performed to investigate the activity of combining calcineurin inhibitors with antifungal drugs. Results. The lowest MIC values were detected with VOR for all Candida isolates tested. Although we did not detect any inhibition for CsA or TAC alone at concentrations tested in this study, the combinations of CAS with CsA showed the highest synergistic activity (36.7%) by the checkerboard method, and CAS with CsA and ITR with TAC combinations exhibited apparent synergistic interaction by the time-kill method. However, the combinations of both CsA and TAC with AMB resulted in antagonistic interactions, especially against C. krusei isolate in time-kill testing. Conclusion. Synergistic interactions in the combinations of TAC or CsA with antifungal drugs, except for AMB. in many concentrations was found to be promising in terms of the treatment of patients with fungal infections.
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    The Investigation of the Susceptibility of Candida Species to Fluconazole, Voriconazole, and Amphotericin B by Disc Diffusion and the Microdilution Method
    (2020) Sav, Hafize; Barış, Ayşe; Turan, Deniz; Özakkaş, Fatma; Altınbaş, Rabiye; Şen, Sümeyye; Kiraz, Nuri
    In this study, we aimed to investigate the antifungal susceptibility profile of Candida isolates obtained in our hospitalwith two methods. A total of 200 Candida isolates were obtained from samples of patients in various departments of our hospital.Identification of each strain was performed using conventional (germ tube formation, microscopic morphology in corn meal-Tween80 agar), and commercial kit API 20C (Biomerieux, France). MIC values of fluconazole (FLU), voriconazole (VORI), andamphotericin B (AMB) were evaluated according to Clinical Laboratory Standards Institute broth microdilution and disk diffusion(DD) method. Totally isolated 200 Candida species were identified as 100 C. albicans, 25 C. glabrata, 7 C. krusei, 43 C.parapsilosis, and 25 C. tropicalis. All isolates were susceptible to VORI. High resistance rate (22,5%) was detected for AMBantifungal by reference microdilution method. Between two methods, the best categorical ratio was calculated as VORI (99%), FLU(84.9%), and AMB (72,5%) respectively. Voriconazole exhibited better activity in vitro than fluconazole, even in isolatesfluconazole resistant and disk diffusion method can be considered as alternative antifungal sensitivity method for VORI.