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氟胞嘧啶与两性霉素B、伏立康唑或米卡芬净的抗真菌联合用药未显示出拮抗作用。

antifungal combination of flucytosine with amphotericin B, voriconazole, or micafungin against shows no antagonism.

作者信息

Bidaud A L, Botterel F, Chowdhary A, Dannaoui E

机构信息

Paris-Descartes University, Faculty of Medicine, APHP, European Georges Pompidou Hospital, Parasitology-Mycology Unit, Microbiology department, Paris, France.

Dynamyc Research Group, Paris Est Créteil University (UPEC, EnvA), France.

出版信息

Antimicrob Agents Chemother. 2019 Sep 9;63(12). doi: 10.1128/AAC.01393-19. Epub 2019 Oct 7.

Abstract

is an emerging, multidrug resistant pathogen, responsible for invasive hospital-acquired infections. Flucytosine is an effective anti- drug, but which cannot be used as a monotherapy because of the risk of development of resistant mutants during treatment. It is therefore noteworthy to test possible combinations with flucytosine that may have a synergistic interaction. In this study, we determined the interaction between flucytosine and amphotericin B, micafungin, or voriconazole. These combinations have been tested against 15 isolates. The MIC range (Gmean) of flucytosine, amphotericin B, micafungin and voriconazole were 0.125 to 1 μg/mL (0.42 μg/ml), 0.25 to 1 μg/ml (0.66 μg/ml), 0.125 to 0.5 μg/ml (0.3 μg/ml) and 0.03 to 4 μg/ml (1.05 μg/ml), respectively. When tested in combination, indifferent interactions were mostly observed with fractional inhibitory concentration index values from 0.5 to 1, 0.31 to 1.01 and 0.5 to 1.06 for the combination of flucytosine with amphotericin B, micafungin and voriconazole, respectively. A synergy was observed for the strain CBS 10913 from Japan. No antagonism was observed for any combination. Combination of flucytosine with amphotericin B or micafungin may be relevant for the treatment of infections.

摘要

是一种新兴的多重耐药病原体,可导致医院获得性侵袭性感染。氟胞嘧啶是一种有效的抗真菌药物,但由于在治疗过程中存在产生耐药突变体的风险,不能作为单一疗法使用。因此,测试与氟胞嘧啶可能具有协同相互作用的可能组合是值得注意的。在本研究中,我们确定了氟胞嘧啶与两性霉素B、米卡芬净或伏立康唑之间的相互作用。这些组合已针对15株分离株进行了测试。氟胞嘧啶、两性霉素B、米卡芬净和伏立康唑的MIC范围(几何平均值)分别为0.125至1μg/mL(0.42μg/ml)、0.25至1μg/ml(0.66μg/ml)、0.125至0.5μg/ml(0.3μg/ml)和0.03至4μg/ml(1.05μg/ml)。当联合测试时,氟胞嘧啶与两性霉素B、米卡芬净和伏立康唑组合的部分抑制浓度指数值大多为0.5至1、0.31至1.01和0.5至1.06,观察到的相互作用为无关相互作用。对来自日本的CBS 10913菌株观察到协同作用。任何组合均未观察到拮抗作用。氟胞嘧啶与两性霉素B或米卡芬净的组合可能与真菌感染的治疗相关。

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