Harman S, Ashbee H R, Evans E G V
Mycology Reference Centre, Division of Microbiology, University of Leeds and General Infirmary, Leeds, UK.
J Dermatolog Treat. 2004 Apr;15(2):104-7. doi: 10.1080/09546630410025988.
Fungal infections of the nail are a common and chronic problem. The main pathogens responsible for onychomycosis are dermatophytes, yeasts and moulds. Despite significant improvements, approximately 20% of patients with onychomycosis still fail on antifungal therapy. The successful exploitation of drug synergy may provide a useful approach to improve cure rates.
The minimum inhibitory concentrations (MIC(80)) were recorded for pathogens that are most frequently responsible for onychomycosis against combinations of several antifungal agents, namely, fluconazole, itraconazole, terbinafine and amorolfine. Fractional inhibitory concentrations (FICs) were then calculated from the MIC(80) results and the FIC values for each drug in the combinations added to determine the degree of synergy. A combined value of <1 was taken to suggest synergy; a value of 1-2 indicated an additive effect or indifference; and a combined FIC value of >2 was taken to suggest antagonism.
Overall, 46% of amorolfine combinations showed results suggestive of synergy, with the most synergistic results seen against dermatophytes (54%) and moulds (52%).
Some combinations of drugs may have synergistic activity in vitro; however, the importance of this in a clinical setting is yet to be established, and more studies are justified.
甲真菌病是一种常见的慢性疾病。引起甲癣的主要病原体是皮肤癣菌、酵母菌和霉菌。尽管取得了显著进展,但仍有大约20%的甲癣患者抗真菌治疗失败。成功利用药物协同作用可能为提高治愈率提供一种有用的方法。
记录了几种抗真菌药物(即氟康唑、伊曲康唑、特比萘芬和阿莫罗芬)联合使用时,对最常引起甲癣的病原体的最低抑菌浓度(MIC(80))。然后根据MIC(80)结果计算分数抑菌浓度(FIC),并将每种药物在联合用药中的FIC值相加,以确定协同程度。联合值<1表示协同作用;值为1-2表示相加作用或无差异;联合FIC值>2表示拮抗作用。
总体而言,46%的阿莫罗芬联合用药显示出协同作用的结果,其中对皮肤癣菌(54%)和霉菌(52%)的协同作用最为明显。
某些药物组合在体外可能具有协同活性;然而,其在临床环境中的重要性尚未确定,需要更多的研究。