Vancomycin-eluting ultra-high molecular weight polyethylene to treat periprosthetic joint infection

Introduction About 2% of primary total joint replacement arthroplasty (TJA) procedures become infected. Periprosthetic joint infection (PJI) is currently one of the main reasons requiring costly TJA revisions, posing a burden on patients, physicians and insurance companies. 1 Currently used drug-eluting polymers such as bone cements offer limited drug release profiles, sometimes unable to completely clear out bacterial microorganisms within the joint space. For this study we determined the safety and efficacy of an antibiotic-eluting UHMWPE articular surface that delivered local antibiotics at optimal concentrations to treat PJI in a rabbit model. Materials and Methods Skeletally mature adult male New Zealand White rabbits received either two non-antibiotic eluting UHMWPE (CONTROL, n=5) or vancomycin-eluting UHMWPE (TEST, n=5) (3 mm in diameter and 6 mm length) in the patellofemoral groove ( Fig. 1 ). All rabbits received a beaded titanium rod in the tibial canal (4 mm diameter and 12 mm length). Both groups received two doses of 5 × 10 7 cfu of bioluminescent S. aureus (Xen 29, PerkinElmer 119240) in 50 µL 0.9 % saline in the following sites: (1) distal tibial canal prior to insertion of the rod; (2) articular space after closure of the joint capsule ( Fig. 1 ). None of the animals received any intravenous antibiotics for this study. Bioluminescence signal (photons/second) was measured when the rabbits expired, or at the study endpoint (day 21). The metal rods were stained with BacLight ® Bacterial Live-Dead Stain and imaged using two-photon microscopy to detect live bacteria. Hardware, polyethylene implants and joint tissues were sonicated to further quantify live bacteria via plate seeding. Results All control rabbits expired within 7 days ( Fig. 2a). One rabbit in the test group expired at day 7 and another at day 15. All control rabbits had positive bioluminescence (live bacteria), while none of the test rabbits did (Fig 2b). Kidney (creatinine and BUN) and liver functions (ALT and ALP) remained normal for all rabbits. All control rabbits showed positive bacterial culture after sonication, while all test rabbits were negative. Two-photon imaging showed 75±10 % viability for bacteria adhered to the metal rods in the control and no viability in the test group. Discussion This rabbit model showed that vancomycin eluted from UHMWPE is sufficient to eradicate S. aureus in joint space and in between the bone-implant interface of tibial canal. One limitation of this study is the lack of intravenous antibiotic treatment, which is standard clinical practice. In addition, joint infections are often associated with already formed biofilms, which were not tested in this study. However, safety data (normal kidney and liver functions) and complete eradication of S. aureus is an encouraging finding. Conclusion Vancomycin-eluting UHMWPE effectively eliminated bacteria in a rabbit model of acute peri-prosthetic joint infection. This material is promising as a replacement liner to treat joint infections in revision surgery. For any figures or tables, please contact authors directly (see Info & Metrics tab above).