体外伊曲康唑、他克莫司、环孢素 A 或西罗莫司与毛霉目真菌的相互作用。
In vitro interactions between isavuconazole and tacrolimus, cyclosporin A or sirolimus against Mucorales.
机构信息
Department of Internal Medicine, Respiratory and Critical Care Medicine, University Hospital Marburg, Marburg, Germany.
Center for Invasive Mycoses and Antifungals, Philipps University Marburg, Marburg, Germany.
出版信息
J Antimicrob Chemother. 2019 Jul 1;74(7):1921-1927. doi: 10.1093/jac/dkz102.
OBJECTIVES
To evaluate the in vitro interactions of isavuconazole with immune suppressors (tacrolimus, cyclosporin A or sirolimus) against 30 Mucorales isolates belonging to the most common species responsible for mucormycosis in humans (Rhizopus arrhizus, Rhizopus delemar, Rhizopus microsporus, Lichtheimia corymbifera, Lichtheimia ramosa, Mucor circinelloides and Rhizomucor pusillus).
METHODS
In vitro interaction was evaluated by a microdilution chequerboard technique.
RESULTS
Combination of isavuconazole with tacrolimus, cyclosporin A or sirolimus, was synergistic for 50%, 46% and 7% of the isolates, respectively. Antagonistic interaction was observed for 4% of the isolates for the combination with cyclosporin A (one R. arrhizus isolate) and for 32% of the isolates for the combination with sirolimus (six R. arrhizus isolates and three R. pusillus isolates).
CONCLUSIONS
These in vitro data show that calcineurin inhibitors are more likely than inhibitors of the mTOR pathway to enhance the activity of isavuconazole against Mucorales. These in vitro results warrant further animal experiments.
目的
评估伊曲康唑与免疫抑制剂（他克莫司、环孢素 A 或西罗莫司）在体外对 30 株蕈菌的相互作用，这些蕈菌属于引起人类毛霉病的最常见物种（根毛霉、德氏根毛霉、微小根毛霉、伞枝犁头霉、光滑犁头霉、卷枝毛霉和少根根毛霉）。
方法
采用微量稀释棋盘法评估体外相互作用。
结果
伊曲康唑与他克莫司、环孢素 A 或西罗莫司联合使用，对 50%、46%和 7%的分离株分别表现为协同作用。与环孢素 A 联合使用时，有 4%的分离株表现为拮抗作用（一株根毛霉分离株），与西罗莫司联合使用时，有 32%的分离株表现为拮抗作用（六株根毛霉分离株和三株少根根毛霉分离株）。
结论
这些体外数据表明，钙调神经磷酸酶抑制剂比 mTOR 通路抑制剂更有可能增强伊曲康唑对毛霉属的活性。这些体外结果值得进一步进行动物实验。
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