%0 Journal Article %T Unveiling the synergistic potency of chlorhexidine and azithromycin in combined action. %A Samgane G %A Karaçam S %A Tunçer Çağlayan S %J Naunyn Schmiedebergs Arch Pharmacol %V 0 %N 0 %D 2024 Feb 20 %M 38376540 %F 3.195 %R 10.1007/s00210-024-03010-0 %X The growing challenge of antibiotic resistance necessitates novel approaches for combating bacterial infections. This study explores the distinctive synergy between chlorhexidine, an antiseptic and disinfectant agent, and azithromycin, a macrolide antibiotic, in their impact on bacterial growth and virulence factors using Escherichia coli strain Crooks (ATCC 8739) as a model. Our findings reveal that the chlorhexidine and azithromycin combination demonstrates enhanced anti-bacterial effects compared to individual treatments. Intriguingly, the combination induced oxidative stress, decreased flagellin expression, impaired bacterial motility, and enhanced bacterial autoaggregation. Notably, the combined treatment also demonstrated a substantial reduction in bacterial adherence to colon epithelial cells and downregulated NF-κB in the epithelial cells. In conclusion, these results shed light on the potential of the chlorhexidine and azithromycin synergy as a compelling strategy to address the rising challenge of antibiotic resistance and may pave the way for innovative therapeutic interventions in tackling bacterial infections.