In this study, silver/copper (Ag/Cu)-coated catheters were investigated for their efficacy in preventing methicillin-resistant Staphylococcus aureus (MRSA) infection in vitro and in vivoAg and Cu were sputtered (67/33% atomic ratio) on polyurethane catheters by Direct Current Magnetron Sputtering. In vitro, Ag/Cu-coated and uncoated catheters were immersed in PBS or rat plasma and exposed to 10(4)-10(8) CFU/ml of MRSA ATCC 43300. In vivo, Ag/Cu-coated and uncoated catheters were placed in the jugular vein of rats. Close by, MRSA (10(7) CFU/ml) was inoculated in the tail vein. Catheters were removed 48 h later and cultured.In vitro, Ag/Cu-coated catheters pre-incubated in PBS and exposed to 10(4)-10(7) CFU/ml, prevented the adherence of MRSA (0-12% colonization) compared to uncoated catheters (50-100% colonization; P< 0.005), Ag/Cu-coated catheters retained their activity (0-20% colonization) when pre-incubated in rat plasma while colonization of uncoated catheters increased (83-100%; P< 0.005). Ag/Cu-coating protection diminished with 10(8) CFU/ml in both PBS and plasma (50-100% colonization). In vivo, Ag/Cu-coated catheters reduced the incidence of catheter infection compared to uncoated catheters (57% vs 79%, respectively; P= 0.16) and bacteremia (31% vs 68%, respectively; P< 0.05). Scanning electron microscopy of explanted catheters suggests that the suboptimal activity of Ag/Cu catheters in vivo was due to the formation of a dense fibrin sheath over their surface.Ag/Cu-coated catheters have a potential for preventing MRSA infections. Their activity might be improved by limiting plasma protein adsorption on their surface.