Heightened efficacy of anidulafungin when used in combination with manogepix or 5-flucytosine against Candida auris in vitro
Heightened efficacy of anidulafungin when used in combination with manogepix or 5-flucytosine against Candida auris in vitro
复制标题
阿尼芬净与 manogepix 或 5-氟胞嘧啶联合使用可提高体外抗念珠菌的功效
DOI：
10.1101/2022.12.16.520848
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
John L
中科院分区：
文献类型：
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作者：
John L
金黄色念珠菌是一种新出现的耐多药真菌病原体，可导致难治性定植和危及生命的侵袭性医院感染。表现出抗真菌耐药性的高比例金黄色葡萄球菌严重限制了治疗选择。联合治疗提供了一种可能的策略，通过这种策略可以增强抗真菌效果，防止出现进一步的耐药性。因此，我们检查了使用已经在临床使用或正在进行临床试验的抗真菌药物的药物组合。通过棋盘试验，我们筛选了5-氟胞嘧啶和manogepix(新型抗真菌药物Fosmanogepix的活性形式)与anidulafungin、两性霉素B或伏立康唑的组合，以对抗来自分支I和III的耐药和敏感的金黄色葡萄球菌。观察到anidulafungin与manogepix或5-flucytosine的组合的分数抑制浓度指数(FICI值)分别为0.28至0.75和0.36至1.02，表明协同作用。利用活细胞微流体辅助的真菌生长成像证实了这些anidulafungin组合的高效性。综上所述，anidulafungin与manogepix或5-flucytosine的组合对耐药和敏感的金黄色葡萄球菌菌株都显示出巨大的潜力。
Candida auris is an emerging, multidrug-resistant fungal pathogen that causes refractory colonization and life-threatening, invasive nosocomial infections. The high proportion of C. auris isolates that display antifungal resistance severely limits treatment options. Combination therapies provide a possible strategy by which to enhance antifungal efficacy and prevent the emergence of further resistance. Therefore, we examined drug combinations using antifungals that are already in clinical use or are undergoing clinical trials. Using checkerboard assays, we screened combinations of 5-flucytosine and manogepix (the active form of the novel antifungal drug fosmanogepix) with anidulafungin, amphotericin B, or voriconazole against drug resistant and susceptible C. auris isolates from clades I and III. Fractional inhibitory concentration indices (FICI values) of 0.28 to 0.75 and 0.36 to 1.02 were observed for combinations of anidulafungin with manogepix or 5-flucytosine, respectively, indicating synergistic activity. The high potency of these anidulafungin combinations was confirmed using live-cell microfluidics-assisted imaging of the fungal growth. In summary, combinations of anidulafungin with manogepix or 5-flucytosine show great potential against both resistant and susceptible C. auris isolates.
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艾沙康唑和棘白菌素对抗耳念珠菌的体外协同相互作用。
DOI：
10.3390/antibiotics10040355
发表时间：
2021-03-28
期刊：
Antibiotics (Basel, Switzerland)
影响因子：
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作者：
Caballero U;Kim S;Eraso E;Quindós G;Vozmediano V;Schmidt S;Jauregizar N
通讯作者：
Jauregizar N
影响因子：
4.9
作者：
Pfaller, Michael A.;Messer, Shawn A.;Castanheira, Mariana
通讯作者：
Castanheira, Mariana
影响因子：
5.2
作者：
Dupont, H.;Massias, L.;Montravers, P.
通讯作者：
Montravers, P.
影响因子：
3.7
作者：
Robbins, Nicole;Wright, Gerard D.;Cowen, Leah E.
通讯作者：
Cowen, Leah E.
影响因子：
16.6
作者：
通讯作者：
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