Gallic acid synergistically enhances the antibacterial activity of azithromycin in MRSA

The rise of antibiotic resistance in existing pathogens has been identified as a major threat to global healthcare in the twenty-first century. This resistance has consequences such as increased cost and prolonged hospital stays, treatment failure, and ultimately increased risk of patient mortality. It is therefore imperative to develop strategies to combat drug resistance. Combined treatment of common antibiotics and natural compounds is one of the most effective methods against resistant bacterial infections. Gallic acid (GA) is a natural secondary metabolite abundantly found in plants and has significant medicinal effects in various aspects of health. In this research, the antibacterial effects of azithromycin (AZM) and GA alone and in combination with each other were investigated on planktonic and biofilm forms of methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa (P. aeruginosa). The results showed that the combination of AZM/GA had an additive effect against MSSA and P. aeruginosa and a synergistic effect against MRSA. In addition, combining these two agents significantly reduced the minimum biofilm inhibitory concentration (MBIC) of AZM and GA in the MRSA strain. Finally, the level of ROS generation in the effect of AZM plus GA was evaluated in the bacteria. Among the studied strains, ROS production was significantly increased in combination treatment compared to AZM alone in MRSA. The results show that the combination of AZM and GA has a significant effect against MRSA and can be considered as an effective treatment option.