Synergistic interaction of terbinafine with triazoles or amphotericin B against Aspergillus species

Synergistic interaction of terbinafine with triazoles or amphotericin B against Aspergillus species
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DOI:
10.1080/mmy.39.1.91.95
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发表时间:
2001-02-01
期刊:
影响因子:
2.9
通讯作者:
Leitner, I
Leitner, I
中科院分区:
医学3区
文献类型:
--
作者:
Ryder, NS;Leitner, I

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以烟曲霉、黄曲霉和黑曲霉为研究对象,测定了特比奈芬单独及与其他抗真菌药物联合应用的体外抗真菌活性。试验在改良的国家临床实验室标准委员会(NCCLS)肉汤分析中进行,交互作用采用棋盘设计进行检验。特比奈芬对曲霉菌的最低抑菌浓度(MIC)为0.01~2mugml(-1),具有基本杀菌作用(最低抑菌浓度[MIC]为0.02~4mug m(-1))。两性霉素B也如预期的那样具有高度的活性和杀伤力(MIC为1杯毫升(-1),MFC为1至4杯毫升(-1))。三氮唑类化合物伊曲康唑和伏立康唑活性较高,但对不同菌株表现出不同程度的杀灭活性,伏立康唑的杀灭活性更强。氟康唑没有明显的抑菌活性(MIC>128mug ml(-1))。药物组合在烟曲霉和黑曲霉菌株中进行了测试。特比奈芬和两性霉素在不同菌株之间表现出协同作用的相加作用。特比奈芬与伊曲康唑或伏立康唑联合使用对所有菌株均显示出较强的协同作用和杀菌活性。令人惊讶的是,尽管特比奈芬本身缺乏活性,但氟康唑也以一种协同的方式增强了特比奈芬的活性。结果提示特比奈芬单独或与两性霉素或三氮唑联合应用于曲霉菌病具有潜在的临床应用价值。
The in vitro activity of terbinafine alone and in combination with other antifungal agents was tested against isolates of Aspergillus fumigatus, A. flavus and A. niger. Testing was performed in a modified National Committee for Clinical Laboratory Standards (NCCLS) macrodilution broth assay, and interactions were examined using a checkerboard design. Terbinafine was highly active against Aspergillus isolates (minimum inhibitory concentration [MIC] 0.01 to 2 mug ml(-1)) with a primary fungicidal action (minimum fungicidal concentration [MIC] 0.02 to 4 mug m(-1)). Amphotericin B was also highly active and cidal as expected (MIC 1 mug ml(-1), MFC 1 to 4 mug ml(-1)). The triazoles itraconazole and voriconazole were highly active but showed a variable degree of cidal activity against the different strains, voriconazole having the more potent cidal activity. Fluconazole had no significant activity (MIC > 128 mug ml(-1)). Drug combinations were tested in the A. fumigatus and A. niger strains. Terbinafine and amphotericin showed an additive to synergistic interaction depending on the isolate. Combinations of terbinafine with itraconazole or voriconazole displayed a potent synergistic interaction and fungicidal activity against all isolates. Surprisingly, fluconazole also potentiated the activity of terbinafine in an additive to synergistic fashion, despite its lack of activity alone. The results suggest potential clinical application of terbinafine in aspergillosis, either alone or in combination with anmphotericin or triazoles.