Treatment of vascular graft infections: gentamicin-coated ePTFE grafts reveals strong antibacterial properties in vitro

Dominik Pförringer,Bettina Dietmair,Jochen Schneider,Albert Busch,Igor Lazic,Rüdiger Von Eisenhart-Rothe,Peter Biberthaler,Rainer Burgkart,Jutta Tübel,Andreas Obermeier,Wolfgang E Kempf

doi:10.1007/s10856-022-06650-x

Abstract

Vascular graft infections (VGI) are severe complications in prosthetic vascular surgery with an incidence ranging from 1 to 6%. In these cases, synthetic grafts are commonly used in combination with antimicrobial agents. Expanded polytetrafluoroethylene (ePTFE) is in clinical use as a synthetic graft material and shows promising results by influencing bacterial adhesion. However, the literature on antibiotic-bound ePTFE grafts is scarce. Gentamicin is a frequently used antibiotic for local treatment of surgical site infections, but has not been evaluated as antimicrobial agent on ePTFE grafts. In this study, we examine the antimicrobial efficacy and biocompatibility of novel types of gentamicin-coated ePTFE grafts in vitro. ePTFE grafts coated with gentamicin salt formulations with covalently-bound palmitate were evaluated in two drug concentrations (GP1.75% and GP3.5%). To investigate effects from types of formulations, also suspensions of gentamicin in palmitate as well as polylactide were used at comparable levels (GS + PA and GS + R203). Antibacterial efficacies were estimated by employing a zone of inhibition, growth inhibition and bacterial adhesion assay against Staphylococcus aureus (SA). Cytotoxicity was determined with murine fibroblasts according to the ISO standard 10993-5. Gentamicin-coated ePTFE grafts show low bacterial adherence and strong antibacterial properties in vitro against SA. Bactericidal inhibition lasted until day 11. Highest biocompatibility was achieved using gentamicin palmitate GP1.75% coated ePTFE grafts. ePTFE grafts with gentamicin-coating are effective in vitro against SA growth and adherence. Most promising results regarding antimicrobial properties and biocompatibility were shown with chemically bounded gentamicin palmitate GP1.75% coatings.Graphical abstract

Highlights

Vascular graft infections (VGI) represent severe complications in routinely prosthetic vascular surgery
The bacteria were cultivated in Mueller Hinton II broth (MHB), as well as Mueller Hinton II agar (MHA), both supplied by BD, Germany
We demonstrated an effective inhibition of bacterial growth using gentamicincoated expanded polytetrafluoroethylene (ePTFE) grafts up to 11 days

Summary

Introduction

Vascular graft infections (VGI) represent severe complications in routinely prosthetic vascular surgery. The risk of amputation is estimated to range between 8 and 75% [2]. Treatment implies surgical graft explantation, vascular reconstruction, and antimicrobial agents. For this purpose, autologous or homologous grafts are available for vascular reconstruction, which can be reimplanted anatomically or extra-anatomically. In the case of VGI, anatomical reconstruction is often impractical, so that an autologous or homologous graft must be implanted extra-anatomically. High rates of reinfection have been reported in extra-anatomic procedures. Further complications associated with extra-anatomic procedures include occlusion, extended procedure time and risk of rupture with high rate of amputation. Seeger reported a treatment-related mortality of 19.4% and an amputation rate of 11% [1]. Especially in case of infections, requires synthetic grafts with antimicrobial properties. Rifampicin-impregnated, or silver-coated vascular grafts are commonly used (Table 1)

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