Investigation of prosthetic vascular graft infections in an ovine model

This thesis examines the in-vitro and in-vz’vo effect of rifampicin (a known antistaphylococcal agent) following prosthetic graft impregnation, to prevent and treat Staphylococcus epidermidis (MRSE) and Staphylococcus aureus (MRSA) prosthetic vascular graft infections. In addition the effects of rifampicin on intirnal hyperplasia were analysed. Using a disc difiusion technique, one square centimetre segments of Gelsofi, Gore-Tex, Fluoropassiv or Thoratec were impregnated with rifampicin at concentrations of 1.2mg/ml, 10 mg/ml or 30 mg/ml and placed on a bacterial lawn of MRSA or MRSE. With increasing rifampicin concentration, all grafis displayed increased initial zones of inhibition and length of time of antibacterial activity. Fluoropassiv and Gelsofi were the superior grafts at all studied rifampicin concentrations. Using an established ovine model in which grafis were interposed in the carotid artery of sheep, it was shown that all grafts studied in-vitro were easily infected with an overwhelming dose of MRSA or MRSE, and once infected would harbour the infective micro—organism. From our preliminary in-vitro and in-vivo results Gelsoft was chosen as the graft of choice for the subsequent in-vivo (ovine model) experimentation. Interposition Gelsofi grafts at concentrations of 1.2mg/ml or 10 mg/ml rifampicin was inoculated with 108 colony forming units (CFU) of MRSE or MRSA and compared to infected non-impregnated Gelsoft grafts. Grafis were harvested at three weeks. Our findings showed that rifampicin at both 1.2 mg/ml and 10 mg/ml reduced the incidence of abscess formation, anastomotic disruption and grafi thrombosis for both MRSE and MRSA. In addition overall positive cultures were significantly reduced with increasing rifampicin concentration for MRSE and MRSA infected grafts. MRSE or MRSA infected Gelsofi grafts were replaced at three weeks with 1.2 mg/ml or 10 mg/ml rifampicin impregnated Gelsofi grafts. The replacement grafts were subsequently removed following a further three weeks. No significant improvements were noted for the recorded macroscopic or bacteriological parameters with increasing rifampicin concentration with the MRSA infected grafts. However, with regards to S. epidermidis, a concentration of 10 mg/ml effectively reduced the total number of infected grafts compared to both the control group and the 1.2 mg/ml rifampicin group. Varying the concentration of rifampicin between nil, 1.2mg/ml and 10 mg/ml had no significant impact on the formation of intimal hyperplasia or platelet aggregation. These results demonstrated that 10 mg/ml rifampicin impregnation of Gelsofi grafts is an effective means of preventing MRSA and MRSE prosthetic graft infection and treating established MRSE graft infection without contributing to intimal hyperplasia