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