Antimicrobial synergistic effects of dietary flavonoids rutin and quercetin in combination with antibiotics gentamicin and ceftriaxone against E. coli (MDR) and P. mirabilis (XDR) strains isolated from human infections: Implications for food-medicine interactions

Antimicrobial resistance has emerged as a major global concern for public health in the last two decades, which tends to compromise the existing drug regimens in treating common or severe infections. According to WHO, three million laboratory-confirmed bacterial infections have been reported from 70 countries in 2019, caused by pathogens of concern. The drug-resistant bacterial strains are characterized as multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan drug-resistant (PDR) based on the different patterns of resistance. It is believed that novel strategies are essentially required to counter and eliminate drug resistance in a cost-effective manner to benefit the world population. Natural compounds and certain dietary agents show potential antimicrobial properties and these have been used since ancient times to treat human infections. In this study, we have investigated the synergistic effects of dietary flavonoids rutin and quercetin with antibiotics gentami-cin (an aminoglycoside) and ceftriaxone (a third-generation cephalosporin) against the drug-resistant superbugs; clinical isolates including Escherichia coli (MDR), Proteus mirabilis (XDR), and Klebsiella pneumoniae (PDR). Conventional MIC assay and checkerboard test were used as standard protocols. Our results show that rutin and quercetin restore the antimicrobial activity of the antibiotics against MDR and XDR strains, while no such effect was observed in the case of the PDR strain. Quercetin, which is a aglycone of flavonoid rutin, demonstrates higher synergistic effects with ceftriaxone compared to rutin. Since rutin and quercetin are essentially present in human diets as constituents of fruits and vegetables, their use as nutraceuticals in adjuvant therapies in combination with antibiotics against drug resistance is a promising therapeutic strategy against superbug infections.