In Vitro Antifungal Activity of Sertraline and Synergistic Effects in Combination with Antifungal Drugs against Planktonic Forms and Biofilms of Clinical Trichosporon asahii Isolates.

In Vitro Antifungal Activity of Sertraline and Synergistic Effects in Combination with Antifungal Drugs against Planktonic Forms and Biofilms of Clinical Trichosporon asahii Isolates.
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舍曲林的体外抗真菌活性以及与抗真菌药物组合对临床毛孢子菌分离株的浮游形式和生物膜的协同作用

DOI:
10.1371/journal.pone.0167903
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Yang R
Yang R
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cong L;Liao Y;Yang S;Yang R

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Asahii(T. Asahii)是侵袭性毛孢子菌病的主要病原体,其主要发生在免疫功能低下的患者中。T. Asahii可能是抗真菌药物耐药性的原因,并导致高死亡率。舍曲林是一种常用的抗抑郁药,已被证明对多种病原真菌,特别是隐球菌属真菌具有体外和体内抗真菌活性。本文研究了舍曲林单独或与氟康唑、伏立康唑、伊曲康唑、卡泊芬净和阿替霉素B联合应用对21株临床分离的结核分枝杆菌的体外抗结核活性。分别用微量肉汤稀释棋盘法和XTT还原法对asahii菌株进行了评价。分数抑制浓度指数(FICI)用于解释药物相互作用。舍曲林单独对两种T. asahii细胞(MIC,4-8 μg/ml)和T. Asahii生物膜(SMIC,16-32 μg/ml)。SRT对T. asahii细胞与阿替霉素B、卡泊芬净或氟康唑(FICI≤0.5)联合应用对T. asahii生物膜与阿氏菌素B组合(FICI≤0.5)。SRT对T表现出大多数无关的相互作用。Asahii生物膜与三种唑的组合。舍曲林-黄曲霉素B组合对两种T. asahii细胞(90.5%)和T. Asahii生物膜(81.0%)。未观察到拮抗相互作用。我们的研究表明舍曲林对侵袭性T。asahii感染,尤其是导管相关T. Asahii感染。需要进一步的体内研究来验证我们的发现。
Trichosporon asahii (T. asahii) is the major pathogen of invasive trichosporonosis which occurred mostly in immunocompromised patients. The biofilms formation ability of T. asahii may account for resistance to antifungal drugs and results a high mortality rate. Sertraline, a commonly prescribed antidepressant, has been demonstrated to show in vitro and in vivo antifungal activities against many kinds of pathogenic fungi, especially Cryptococcus species. In the present study, the in vitro activities of sertraline alone or combined with fluconazole, voriconazole, itraconazole, caspofungin and amphotericin B against planktonic forms and biofilms of 21 clinical T. asahii isolates were evaluated using broth microdilution checkerboard method and XTT reduction assay, respectively. The fractional inhibitory concentration index (FICI) was used to interpret drug interactions. Sertraline alone exhibited antifungal activities against both T. asahii planktonic cells (MICs, 4–8 μg/ml) and T. asahii biofilms (SMICs, 16–32 μg/ml). Furthermore, SRT exhibited synergistic effects against T. asahii planktonic cells in combination with amphotericin B, caspofungin or fluconazole (FICI≤0.5) and exhibited synergistic effects against T. asahii biofilms in combination with amphotericin B (FICI≤0.5). SRT exhibited mostly indifferent interactions against T. asahii biofilms in combination with three azoles in this study. Sertraline-amphotericin B combination showed the highest percentage of synergistic effects against both T. asahii planktonic cells (90.5%) and T. asahii biofilms (81.0%). No antagonistic interaction was observed. Our study suggests the therapeutic potential of sertraline against invasive T. asahii infection, especially catheter-related T. asahii infection. Further in vivo studies are needed to validate our findings.
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