In vitro Synergistic Interactions of Phytochemicals and Their Synthetic Analogs with Tetracycline Against Diarrhoeal Causing Bacteria

The prevalence of infectious diarrhoea is increasing, posing serious threat to both human and animal lives, as well as causing large cost to society worldwide. Additionally, treatment of pathogens causing diarrhoea has become complicated due to alarming increase in bacterial antimicrobial resistance [1]. Combination of standard antibiotics with phytochemicals and their synthetic analogs seems to be promising direction for development of new preparations with synergistic growth-inhibitory activity against diarrheagenic bacteria. For example, sanguinarine, a benzylisoquinoline alkaloid isolated from Sanguinaria canadensis has been reported to show in vitro synergistic effect in combination with streptomycin against clinical isolates of E. coli [2]. In this study, we determined in vitro synergistic effect of phytochemicals (sanguinarine and tannic acid) and their synthetic analogs (nitroxoline and zinc pyrithione) with tetracycline against standard diarrhoeal causing pathogens (Enterococcus faecalis, Listeria monocytogenes, Shigella flexneri and Yersinia enterocolitica). Minimum inhibitory concentrations of each agent and antibiotics were determined by the broth microdilution method according to Clinical and Laboratory Standards Institute [3] guidelines, whereas the synergistic activity was evaluated according to the sum of fractional inhibitory concentration (ΣFIC) indices obtained by chequerboard method [4]. Several synergistic effects were observed against most of the bacteria tested in this study with ΣFICI ranging from 0.156 to 0.500, whereas the significant ΣFICI (0.156) was shown on combination of tetracycline with zinc pyrithione against S. flexneri. These results can be used for development of new antidiarrhoeal preparations for humans and animals.