Semis R, Nahmias M, Lev S, Frenkel M, Segal E
Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel; City of Hope, Beckman Research Institute, Department of Immunology, Duarte, California, USA.
Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel.
J Mycol Med. 2015 Mar;25(1):63-70. doi: 10.1016/j.mycmed.2014.12.002. Epub 2015 Jan 29.
The objective of this study was to evaluate the efficacy of combinations of nystatin-intralipid, found previously to be more active than nystatin, with antifungals of different mode of activity, against Aspergillus terreus.
Antifungal activity of combinations of nystatin-intralipid with voriconazole, caspofungin, terbinafine or 5-fluorocytosine were evaluated by the checkerboard and disk diffusion methods. The results were compared to those obtained with nystatin.
The combination of nystatin-intralipid with caspofungin exhibited better antifungal activity than each drug alone and resulted in a synergistic interaction in three out of six tested strains of A. terreus. No such effect was obtained with Nystatin and caspofungin. Nystatin-intralipid or nystatin with voriconazole yielded indifferent interactions. When nystatin-intralipid was combined with terbinafine, a strong antagonism was produced in all six A. terreus strains. This effect was observed both by checkerboard and disk diffusion methods. In contrast no interaction or only slight antagonism was observed in the combination of nystatin with terbinafine. Disk diffusion method revealed similar inhibition zones when disks impregnated with 5-fluorocytosine were placed on plain, nystatin-intralipid or nystatin containing agar plates.
Among four tested combinations, only combination of nytatin-intralipid with caspofungin, a representative of the echinocandin class of antifungals, resulted in synergistic interaction. Antagonism obtained by combining nystatin-intralipid with terbinafine can be explained by existence of hydrophobic interaction between these two compounds interfering with their antifungal action. The fact that nystatin-intralipid and nystatin interact differently with other antifungals, may indicate differences in their mechanisms of activity.
本研究的目的是评估制霉菌素-脂质乳剂（先前发现其活性比制霉菌素更强）与不同作用方式的抗真菌药物联合使用对土曲霉的疗效。
通过棋盘法和纸片扩散法评估制霉菌素-脂质乳剂与伏立康唑、卡泊芬净、特比萘芬或5-氟胞嘧啶联合使用的抗真菌活性。将结果与制霉菌素单独使用时获得的结果进行比较。
制霉菌素-脂质乳剂与卡泊芬净联合使用表现出比单独使用每种药物更好的抗真菌活性，并且在6株受试土曲霉中有3株产生了协同相互作用。制霉菌素和卡泊芬净联合使用未获得这种效果。制霉菌素-脂质乳剂或制霉菌素与伏立康唑联合产生无关相互作用。当制霉菌素-脂质乳剂与特比萘芬联合使用时，在所有6株土曲霉中均产生强烈拮抗作用。通过棋盘法和纸片扩散法均观察到这种效果。相比之下，制霉菌素与特比萘芬联合使用时未观察到相互作用或仅观察到轻微拮抗作用。当将浸有5-氟胞嘧啶的纸片放置在普通、含制霉菌素-脂质乳剂或含制霉菌素的琼脂平板上时，纸片扩散法显示出相似的抑菌圈。
在四种受试联合用药中，只有制霉菌素-脂质乳剂与卡泊芬净（一种棘白菌素类抗真菌药物的代表）联合使用产生了协同相互作用。制霉菌素-脂质乳剂与特比萘芬联合使用产生的拮抗作用可通过这两种化合物之间存在干扰其抗真菌作用的疏水相互作用来解释。制霉菌素-脂质乳剂和制霉菌素与其他抗真菌药物的相互作用不同这一事实，可能表明它们的活性机制存在差异。
