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This study explored the synergistic antibacterial activity of baicalin (traditional Chinese medicine extract) and the narrow\u2010spectrum beta\u2010lactam antibiotic oxacillin sodium, both of which are poorly active against MRSA <jats:italic>in vitro<\/jats:italic>. The combination of baicalin and oxacillin sodium showed a synergistic effect with a fractional inhibitory concentration index of 0.5. Mechanistically, the supplementation of baicalin increased the permeability of bacterial cell walls and cell membranes, enhancing oxacillin sodium entry and bactericidal action. The combination of baicalin and oxacillin sodium also significantly inhibited MRSA USA300 biofilm formation by further reducing polysaccharide intercellular adhesion production. Therefore, the combination of baicalin and oxacillin sodium offers a new therapeutic option for addressing clinical MRSA resistance. 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