Asok Kumar Kuppusamy, Mazumdar Kaushiki, Dutta Noton Kumar, Karak Prithviraj, Dastidar Sujata Ghosh, Ray Raja
Division of Microbiology, Department of Pharmaceutical Technology, Jadavpur University, Calcutta, India.
Biol Pharm Bull. 2004 Jul;27(7):1116-20. doi: 10.1248/bpb.27.1116.
Amlodipine, a cardiovascular drug, exhibited remarkable antibacterial action in vitro against 504 bacterial strains belonging to both Gram positive and Gram negative genera, as well as in vivo against a mouse-virulent bacterium. Based on such findings, the present study was undertaken to determine whether the efficacy of this non-antibiotic drug could be enhanced in the presence of any antibiotic. Twelve bacterial strains, sensitive to amlodipine as well as to 6 antibiotics, viz., benzyl penicillin, streptomycin, chloramphenicol, tetracycline, erythromycin and ciprofloxacin were chosen. Disc diffusion test with amlodipine and streptomycin revealed marked synergism between the combination, compared with their individual effects. The synergism was found to be statistically significant (p<0.01). To assess the degree of synergy, the checkerboard analysis was performed. The fractional inhibitory concentration (FIC) index of this combination turned out to be 0.24, which confirmed synergism. This antibiotic-non-antibiotic pair was then administered to mice, challenged with S. typhimurium to determine whether this was effective in vivo. Statistical analysis of the mouse protection tests suggested that the combination was highly synergistic (p<0.001), according to Student's t-test. This synergistic drug combination may help us in enhancing the scope of prolonged antibiotic therapy in various types of infections, and might open a new therapeutic approach to combat drug resistance in bacterial diseases.
氨氯地平是一种心血管药物,在体外对504株革兰氏阳性和革兰氏阴性菌均表现出显著的抗菌作用,在体内对一种小鼠强毒力细菌也有抗菌作用。基于这些发现,本研究旨在确定在存在任何抗生素的情况下,这种非抗生素药物的疗效是否可以增强。选择了12株对氨氯地平和6种抗生素敏感的细菌菌株,这6种抗生素分别是苄青霉素、链霉素、氯霉素、四环素、红霉素和环丙沙星。氨氯地平和链霉素的纸片扩散试验显示,与它们各自的作用相比,二者联合使用时有显著的协同作用。发现这种协同作用具有统计学意义(p<0.01)。为了评估协同程度,进行了棋盘分析。该联合用药的分数抑菌浓度(FIC)指数为0.24,证实了协同作用。然后将这种抗生素-非抗生素组合给予感染鼠伤寒沙门氏菌的小鼠,以确定其在体内是否有效。根据学生t检验,小鼠保护试验的统计分析表明,该组合具有高度协同作用(p<0.001)。这种协同药物组合可能有助于我们扩大长期抗生素治疗在各种感染中的应用范围,并可能为对抗细菌性疾病中的耐药性开辟一种新的治疗方法。