Abstract
ABSTRACTProsthetic joint infection (PJI) following total knee arthroplasty (TKA) remains the leading cause for revision surgery, with Staphylococcus aureus the bacterium most frequently responsible. We describe a novel rat model of implant-associated S. aureus infection of the knee using orthopaedic materials relevant to modern TKA. Male Sprague-Dawley rats underwent unilateral knee implant surgery, which involved placement of a cementless, porous titanium implant into the femur, and an ultra-highly cross-linked polyethyelene (UHXLPE) implant into the proximal tibia within a mantle of gentamicin-laden bone cement. S. aureus biofilms were established on the surface of titanium implants prior to implantation into the femur of infected animals, whilst control animals received sterile implants. Compared to controls, the time taken to full weight-bear and recover pre-surgical body weight was greater in the infected group. Neutrophils and C-reactive protein levels were significantly higher in infected compared to control animals at day 5 post surgery, returning to baseline levels for the remainder of the 28-day experimental period. Blood cultures remained negative and additional plasma inflammatory markers were comparable for control and infected animals, consistent with the clinical presentation of delayed-onset PJI. S. aureus was recovered from joint tissue and implants at day 28 post surgery from all animals that received pre-seeded titanium implants, despite the use of antibiotic-laden cement. Persistent localised infection was associated with increased inflammatory responses and radiological changes in peri-implant tissue. The availability of a preclinical model that is reproducible based on the use of current TKA materials and consistent with clinical features of delayed-onset PJI will be valuable for evaluation of innovative therapeutic approaches.
Highlights
More than 4.7 million and 600,000 people in the USA and Australia, respectively, are estimated to be living with a total knee arthroplasty (TKA), with conservative projections estimating a 143% increase in incidence rates of TKA by 2050 (Maradit Kremers et al, 2015; AOANJRR, 2017; Inacio et al, 2017)
Akin to the features of delayed-onset prosthetic joint infection (PJI), we demonstrate the establishment of a persistent infection that is localised to the implanted knee in all animals at 4 weeks after surgery, in the absence of bacteraemia and systemic inflammation
Based on improved clinical scores, pain relief was ceased for all animals by day 5 post surgery with no adverse clinical effects observed through the remainder of the experimental period
Summary
More than 4.7 million and 600,000 people in the USA and Australia, respectively, are estimated to be living with a total knee arthroplasty (TKA), with conservative projections estimating a 143% increase in incidence rates of TKA by 2050 (Maradit Kremers et al, 2015; AOANJRR, 2017; Inacio et al, 2017). Significant advancements to preoperative and surgical protocols and orthopaedic materials have reduced postoperative infection rates to less than 2%, peri-prosthetic joint infection (PJI) remains the leading cause of implant failure following TKA (Springer et al, 2017; Tande and Patel, 2014). Delayed-onset PJIs result from the introduction of less virulent microbes during surgery, and as such tend to become clinically apparent between 3 months to 1 year post surgery. Late-onset PJIs present more than 1 year post surgery and are frequently due to haematogenous seeding of the implanted joint from a distant site of infection. Delayed and lateonset PJIs typically involve implant-associated biofilms (Beam and Osmon, 2018)
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