Aims

Current treatments of prosthetic joint infection (PJI) are minimally effective against Staphylococcus aureus biofilm. A murine PJI model of debridement, antibiotics, and implant retention (DAIR) was used to test the hypothesis that PlySs2, a bacteriophage-derived lysin, can target S. aureus biofilm and address the unique challenges presented in this periprosthetic environment.

Introduction

PJI is a devastating complication following total joint arthroplasty. In this study, we explore the efficacy of a bacteriophage-derived lysin, PlySs2, against in-vitro biofilm on titanium implant surfaces and in an acute in-vivo murine debridement antibiotic implant retention (DAIR) model of PJI.

The gold standard for PJI treatment comprises the use of antibiotic-loaded bone cement spacers, which are limited in their load bearing capacity[1]. Thus, developing an antibiotic-eluting UHMWPE bearing surface can improve the mechanical properties of spacers and improve the quality of life of PJI patients. In this study, we incorporated vancomycin into UHMWPE to investigate its elution characteristics, mechanical properties and its efficacy against an acute PJI in an animal model.

Vancomycin hydrochloride was incorporated into UHMWPE (2 to 14%) by blending and consolidation. We studied drug elution with blocks in PBS and UV-Vis spectroscopy at 280 nm. We determined the tensile mechanical properties and impact strength [3]. We implanted osteochondral plugs in rabbits using either control UHMWPE, bone cement (40g) containing vancomycin (1g) and tobramycin (3.6g) or vancomycin-eluting UHMWPE (n=5) plugs in the patellofemoral groove of rabbits. All rabbits received a beaded titanium rod in the tibial canal. All groups received two doses of 5×10⁷ cfu of bioluminescent S. aureus in the distal tibial canal prior to insertion of the rod and the articular space after closure of the joint capsule. No intravenous antibiotics were used. Bioluminescence signal was measured when the rabbits expired, or at 21-day post-op. Hardware, polyethylene implants, and joint tissues were sonicated to further quantify live bacteria via plate seeding.

Vancomycin elution increased with increasing drug loading. Vancomycin elution above MIC for 3 weeks and optimized mechanical properties were obtained at 6–7 wt% vancomycin loading in UHMWPE. In our lapine acute infection model using bioluminescent S. aureus, knees treated with UHMWPE without antibiotics and bone cement containing vancomycin and tobramycin had significantly higher bioluminescence compared to those treated with vancomycin-eluting UHMWPE.

These results suggest that an antibiotic-eluting UHMWPE spacer with acceptable properties as a bearing surface could be used to treat periprosthetic joint infection in lieu of bone cement spacers and this could allow safer load bearing and a higher quality of life for the patients during treatment. In addition, this presents a safer alternative in cases where the second stage surgery for the implantation of new components is hindered.