Department of Medical Microbiology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Department of Medical Microbiology, Faculty of Medicine, Namık Kemal University, Tekirdag, Turkey.
J Med Microbiol. 2021 Apr;70(4). doi: 10.1099/jmm.0.001354.
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. 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. 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). 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 (=13), (=7) and (=10). Checkerboard and time-kill methods were performed to investigate the activity of combining calcineurin inhibitors with antifungal drugs. The lowest MIC values were detected with VOR for all 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 isolate in time-kill testing. 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.
同时使用抗真菌药物和免疫抑制剂已成为接受免疫抑制治疗的患者的必要措施。然而，抗真菌药物的作用有限，存在一定的局限性。科学家一直在寻找新的抗真菌药物和一些对现有抗真菌药物具有至少相加作用的化合物。作为免疫抑制剂的钙调神经磷酸酶抑制剂由于其抗真菌特性也引起了人们的关注。为了评估两种钙调神经磷酸酶抑制剂单独使用以及与两性霉素 B（AMB）、卡泊芬净（CAS）、伊曲康唑（ITR）、伏立康唑（VOR）和氟康唑（FLU）联合使用的活性，采用肉汤微量稀释法评估 AMB、CAS、ITR、VOR、FLU 和环孢素 A（CsA）和他克莫司（TAC）作为钙调神经磷酸酶抑制剂对 （=13）、（=7）和 （=10）株的 MIC。通过棋盘法和时间杀伤法研究了钙调神经磷酸酶抑制剂与抗真菌药物联合使用的活性。所有测试的分离株对 VOR 的 MIC 值最低。尽管在本研究中测试的浓度下，单独使用 CsA 或 TAC 未检测到任何抑制作用，但 CAS 与 CsA 的组合通过棋盘法显示出最高的协同活性（36.7%），而 CAS 与 CsA 和 ITR 与 TAC 的组合通过时间杀伤法显示出明显的协同相互作用。然而，CsA 和 TAC 与 AMB 的组合导致拮抗相互作用，特别是在时间杀伤试验中对 株。在许多浓度下，TAC 或 CsA 与抗真菌药物联合使用的协同作用，除 AMB 外，在治疗真菌感染患者方面具有很大的应用前景。
