AbstractIn recent years methicillin-resistant Staphylococcus aureus has posed a challenge in treating skin and soft tissue infections. Finding new antimicrobial agents has therefore become imperative. We evaluated the in vitro antimicrobial activity of a synthetic peptide, P6, against multidrug resistant clinical strains of Staphylococcus aureus isolated from skin and soft tissue infections. The P6 antimicrobial effect was evaluated in vitro by determining MIC/MBC, the ratio of live/dead cells and the effects induced at membrane level. The therapeutic efficiency was determined against human skin cells. P6 inhibited growth for all strains between 8 and 16 mg/L and killed all bacterial strains at 16 mg/L. The therapeutic potential was found to be 30 and 15 in the presence of BSA. We showed that P6 localizes at membrane level, where it acts slowly, by depolarizing it and affecting its integrity. P6 can be considered a good candidate for use as an antimicrobial agent in topical applications.