Prosthetic graft infection with methicillin-resistant Staphylococcus aureus (MRSA) is one of the most serious complications of cardiovascular surgery. Seeking to prevent graft infection, we evaluated the efficacy of a new biodegradable hydrogel glue (new-glue) composed of aldehyded dextran and epsilon-poly(L-lysine) which acts as a local sustained-release carrier of vancomycin. Rats (n=40) were implanted with 1-cm(2) Dacron grafts in the subcutaneous pockets. Groups (n=10 each) were as follows: no treatment (group A), topical vancomycin solution (group B), new-glue without vancomycin (group C) or new-glue containing 1 mg of vancomycin (group D). Twenty-four h after the implantation, 2.0x10(7) colony-forming units of MRSA was inoculated onto the graft surface. Seven days thereafter, the graft was sampled and cultured. The quantity of MRSA was significantly lower in group D than in the other groups (P<0.0001). About 95% of the total vancomycin was released from the new-glue over the 72 h experimental period, and the tissue concentration of vancomycin remained above the minimum inhibitory concentration for the MRSA strain throughout the experiment. This new vancomycin-containing glue effectively prevented prosthetic graft infection and thus may be a promising biodegradable drug vehicle.