Barchiesi F, Di Francesco L F, Compagnucci P, Arzeni D, Giacometti A, Scalise G
Institute of Infectious Diseases & Public Health, University of Ancona, Italy.
J Antimicrob Chemother. 1998 Jan;41(1):59-65. doi: 10.1093/jac/41.1.59.
A chequerboard titration broth microdilution method, performed according to the recommendations of the National Committee for Clinical Laboratory Standards, was applied to study the in-vitro interaction of terbinafine with amphotericin B, fluconazole and itraconazole against 30 strains of Candida albicans isolated from the oral cavities of AIDS patients. MICs were determined spectrophotometrically at 490 nm and read at either 24 h or 48 h. The end-point was defined as the drug concentration resulting in > or = 90% inhibition of growth relative to control growth. Synergy, defined as a fractional inhibitory concentration (FIC) index of < or = 0.50, was observed in 93% (28 of 30) of terbinafine-amphotericin B interactions, in 47% (14 of 30) of terbinafine-fluconazole interactions and in 43% (13 of 30) of terbinafine-itraconazole interactions; antagonism (FIC > 2.0) was not observed. Where synergy was not achieved, there was still a decrease, although not as dramatic, in the MIC of one or both drugs when used in combination. Reading the MICs on day 2 did not significantly affect the mode of interaction of terbinafine-triazoles, while for terbinafine-amphotericin B the proportion of synergic interactions dropped from 93% (28 of 30) to 30% (nine of 30; P = 0.0001). Antagonism was not observed for any drug combination even at 48 h. Minimum fungicidal concentrations (MFCs) of all drugs alone and in combination were determined against five isolates. Neither terbinafine nor the two triazoles showed fungicidal activity when tested alone or in combination. The fungicidal activity of amphotericin B was slightly enhanced when combined with terbinafine, there being a decrease of two-fold dilutions in the amphotericin B MFCs against all five isolates tested. Thus terbinafine enhances the activities of amphotericin B and triazoles against C. albicans in vitro. Clearly, clinical studies are warranted to elucidate further the potential utility of these combination therapies.
按照美国国家临床实验室标准委员会的建议，采用棋盘滴定肉汤微量稀释法，研究特比萘芬与两性霉素B、氟康唑及伊曲康唑对从艾滋病患者口腔分离出的30株白色念珠菌的体外相互作用。通过分光光度法在490nm处测定MIC，并在24小时或48小时读取结果。终点定义为相对于对照生长导致生长抑制≥90%的药物浓度。协同作用定义为分数抑菌浓度（FIC）指数≤0.50，在93%（30例中的28例）的特比萘芬-两性霉素B相互作用、47%（30例中的14例）的特比萘芬-氟康唑相互作用和43%（30例中的13例）的特比萘芬-伊曲康唑相互作用中观察到；未观察到拮抗作用（FIC＞2.0）。在未实现协同作用的情况下，联合使用时一种或两种药物的MIC仍有降低，尽管不显著。在第2天读取MIC对特比萘芬-三唑类药物的相互作用模式没有显著影响，而对于特比萘芬-两性霉素B，协同相互作用的比例从93%（30例中的28例）降至30%（30例中的9例；P = 0.0001）。即使在48小时，也未观察到任何药物组合的拮抗作用。针对5株分离株测定了所有药物单独及联合使用时的最低杀菌浓度（MFC）。单独或联合测试时，特比萘芬和两种三唑类药物均未显示杀菌活性。两性霉素B与特比萘芬联合使用时，其杀菌活性略有增强，针对所有5株测试分离株，两性霉素B的MFC降低了两倍稀释度。因此，特比萘芬在体外增强了两性霉素B和三唑类药物对白色念珠菌的活性。显然，有必要进行临床研究以进一步阐明这些联合治疗的潜在效用。
