Antimicrobial and antibiofilm activity of antidepressants Against Staphylococcus aureus

Antimicrobial resistance represents a major health challenge, particularly due to the ability of Staphylococcus aureus to form biofilms and persist under antimicrobial pressure. In this context, drug repurposing has emerged as a promising strategy to identify alternative therapeutic options from approved drugs. This study aimed to evaluate the antimicrobial, antibiofilm, and cytotoxic activities of the antidepressants fluoxetine, paroxetine, and duloxetine against planktonic and biofilm-forming Staphylococcus aureus strains. Antibacterial activity was determined by broth microdilution assays to establish the minimum inhibitory concentration and minimum bactericidal concentration against Staphylococcus aureus ATCC 33591 and ATCC 29213. Antibiofilm activity was assessed in mature biofilms using cell viability assays and biomass quantification. Cytotoxicity was evaluated in RAW 264.7 macrophages using a cell viability assay, with calculation of mean effective concentration values. Fluoxetine and duloxetine exhibited lower inhibitory and bactericidal concentrations compared to paroxetine. In biofilm assays, fluoxetine and duloxetine significantly reduced biofilm cell viability and biomass, whereas paroxetine showed a less consistent effect. Cytotoxicity analysis revealed similar EC₅₀ values among the evaluated drugs, and the concentrations associated with relevant antibacterial and antibiofilm effects were approximately 20-fold higher than the EC₅₀ values determined in macrophages, indicating that, in this in vitro model, antimicrobial and antibiofilm activity occur in a concentration range accompanied by measurable cytotoxicity. Overall, the results indicate that antidepressants, particularly fluoxetine and duloxetine, exhibit in vitro antimicrobial and antibiofilm activity against Staphylococcus aureus, reinforcing the potential of these compounds for future drug repurposing studies.