Antibiotic-coated ePTFE decreases graft colonization and neointimal hyperplasia.

BACKGROUND: Synthetic vascular conduits used in traumatic or infected fields have a high failure rate leading to catastrophic consequences including amputation and death. Although efforts to coat vascular grafts with antibiotics have had varying results, we developed a novel coating technique for expanded-polytetrafluoroethylene (ePTFE), which has proven to be effective in vitro. Thus, we hypothesized that the coated grafts would resist infection and have decreased neointimal hyperplasia when used in vivo in a large animal model. METHODS: Minocycline and rifampin suspended in a mixture of methacrylates were coated onto a 3cm segment of 6mm ePTFE (Bard, Tempe, AZ). An antibiotic-coated (ABX), adhesive-coated (AC), or control (C) ePTFE graft was then placed as an end-to-side graft into the left iliac artery of a male mongrel pig. Sterile saline or innoculum containing 3x10(8)Staphylococcus aureus (SA) or Staphylococcus epidermidis (SE) was then placed directly on the graft and the reflected peritoneum re-approximated to confine the bacteria. After 6 wk, the graft was harvested, cultured, and morphometric analyses of neointimal hyperplasia were performed. RESULTS: Twenty-seven pigs had grafts placed (9 ABX, 9 AC, 9 C) and harvested. Of the nine grafts exposed to SA, the uncoated and adhesive-coated grafts averaged greater than 50,000 colonies of SA while the antibiotic-coated grafts averaged less than 50 colonies. Although not statistically significant, neointimal hyperplasia was decreased by 15% to 20% when using an ABX graft in an infected field. CONCLUSIONS: The coated grafts appeared to decrease NIH formation although not significantly in this small pilot study. The methacrylate antibiotic-coated ePTFE graft did provide resistance to infection when used in infected fields.

Prosthetic vascular conduit in contaminated fields: a new technology to decrease ePTFE infections.

Vascular reconstruction using prosthetic materials in contaminated fields can lead to infection, graft loss, and subsequent amputation. We hypothesized that minocycline and rifampin bound to an ePTFE graft using a unique methacrylate technology would provide for resistance from infection and controlled antibiotic elution. Kirby Bauer susceptibility testing was performed on plates overlaid with Staph aureus (SA) and Staph epidermidis (SE) using 6 mm diameter discs of uncoated graft or antibiotic coated graft (ABX). Zones of inhibition (ZIH) were determined after 24 hours. ABX grafts were then placed in a continuous water bath and a recirculating, pulsatile flow device. Susceptibility testing and high performance liquid chromatography with mass spectroscopy was performed to determine graft performance and antibiotic elution rate. ABX grafts had an average ZIH of 35 mm for SA and 44 mm for SE (each P < 0.0001). After the 1 week water bath, the ZIH of the ABX grafts was 23 mm on both the SA and SE plates. The high performance liquid chromatography with mass spectroscopy revealed that after 24 hours, 50 per cent of the antibiotics remained on the graft, and there was a sustained elution for 7 days. Minocycline and rifampin can be bound to ePTFE vascular grafts using a unique methacrylate method. In vitro, the grafts provide a slow elution of antibiotics that provide resistance from infection by SA and SE for up to 2 weeks after graft insertion.

The effect of bacterial contamination on neointimal hyperplasia in vascular grafts.

Neointimal hyperplasia (NH) is the most significant contributing factor to long-term vascular graft failure. Inflammation is known to be important in its development; however, the role of bacterial infection is unclear. We examined the effect of contamination with common organisms on the development of NH in expanded polytetrafluoroethylene grafts. Thirty adult pigs were randomized into one of four groups: no infection, contamination with Staphylococcus aureus, mucin-producing Staphylococcus epidermidis, or Pseudomonas aeruginosa. An expanded polytetrafluoroethylene graft (6 mm x 3 cm) was placed as a common iliac artery interposition graft and was inoculated with 1-2 x 10(8) of the selected organism before closure. Grafts were explanted 6 weeks postoperatively. Microbiologic, histological, and morphometric evaluations were performed. All grafts were patent at the time of euthanasia. The mean areas of NH were 5.45 mm(2) in sterile grafts, 8.36 mm(2) in S. aureus, 7.63 mm(2) in S. epidermidis, and 11.52 mm(2) in P. aeruginosa grafts. Comparison of means via analysis of variance showed that P. aeruginosa grafts had significantly higher formation of NH than sterile grafts (P = 0.025). NH production in infected grafts appears to be organism specific and is significantly higher with P. aeruginosa than common Gram-positive organisms. Increased NH from subclinical infection may be a significant factor contributing to late graft failures.