Employing diclofenac sodium as a novel therapeutic frontier for Staphylococcus epidermidis infections

The spread of biofilm-forming multidrug-resistant pathogenic bacteria is an alarming public health issue requiring significant research. Drug repurposing is a novel approach to combating bacterial infections that is currently being studied. Here, we explored diclofenac sodium's potential antibacterial and antibiofilm action on Staphylococcus epidermidis bacteria. Diclofenac sodium revealed antibacterial action on S. epidermidis isolates with minimum inhibitory concentrations of 500 to 2000 µg/mL. It also exposed antibiofilm action using the crystal violet assay and scanning electron microscope. Using qRT-PCR, diclofenac sodium has downregulated the expression of the biofilm genes (cna, fnbA, and ica) in 20% of the isolates. An animal model revealed the effect of diclofenac sodium on a systemic infection with S. epidermidis in mice. Diclofenac sodium has improved the liver, spleen, and kidney architecture. Molecular docking was used to explore the possible mechanism for the activity of diclofenac sodium against S. epidermidis, which revealed the high affinity of diclofenac sodium toward S. epidermidis protein and TcaR enzymes. Thus, diclofenac sodium could be a clinical solution for disseminating resistance among S. epidermidis and could be investigated for its combination with different antibiotics in future studies.