Development and validation of a preclinical canine model for early onset fracture-related infections.

Fracture-related infections (FRIs) are a challenging complication in orthopaedics. Standard of care management for FRIs typically involves prolonged antibiotic therapies, irrigation and debridement (I&D) of the fracture site, and retention of fracture-fixation implants with or without exchange. Unfortunately, this treatment regimen is associated with treatment failure rates of up to 38 %, such that improved preventive and therapeutic interventions are needed. To test and develop these interventions, clinically relevant preclinical animal models are required. The purpose of this study was to develop and validate a canine model for early onset (<2 weeks) FRI that replicates its clinical, radiographic, bacteriologic, and histologic features. In this model, bilateral proximal fibular 1-cm ostectomies were created to mimic an open fracture, which was then stabilized using a plate and screws pre-incubated in methicillin-resistant Staphylococcus aureus (MRSA). After 7 days, I&D was performed and twice-daily systemic antibiotics were administered until the 17-day endpoint. This model consistently resulted in clinical signs of local infection, compromised wound healing, radiographic evidence for delayed bone healing and implant loosening, and implant-associated biofilm formation. Importantly, MRSA was isolated from deep tissue cultures in all dogs, and histological assessments detected bacteria and bacterial biofilms associated with all fracture-fixation implants at the study endpoint. These clinical, radiographic, bacteriologic, and histologic outcomes in conjunction with the capabilities for standard of care interventions, such as antibiotic treatment and I&D, verify that this preclinical canine model for early onset FRI effectively replicated the pathology associated with this commonly encountered complication of orthopaedic trauma.
Competing Interests: Declaration of competing interest • Aaron M. Stoker receives IP royalties from Musculoskeletal Transplant Foundation. • Cristi R. Cook receives IP royalties, is a paid consultant, paid presenter or speaker, and receives research support from Arthrex, Inc; receives IP royalties, is a paid consultant, paid presenter or speaker, and receives research support from Collagen Matrix Inc; receives IP royalties, is a paid consultant, paid presenter or speaker, and receives research support from Musculoskeletal Transplant Foundation. • James P Stannard is a paid consultant and receives research support from Arthrex, Inc; is a paid consultant for DePuy, A Johnson & Johnson Company; is on the editorial or governing board for the Journal of Knee Surgery; receives research support from National Institutes of Health (NIAMS & NICHD); is a paid consultant for Orthopedic Designs North America; is a paid consultant for Smith & Nephew; receives publishing royalties, financial or material support from Thieme; and receives research support from the U.S. Department of Defense. • James L. Cook receives research support from AANA; receives research support from AO Trauma; receives IP royalties, is a paid consultant and receives research support from Arthrex, Inc; is a paid consultant for Bioventus; is a paid consultant for Boehringer Ingelheim; is a paid consultant and receives research support from Collagen Matrix Inc; receives research support from GE Healthcare; is on the editorial or governing board for the Journal of Knee Surgery; is a board or committee member for Midwest Transplant Network; is a board or committee member, receives IP royalties and research support from Musculoskeletal Transplant Foundation; receives research support from the National Institutes of Health (NIAMS & NICHD); receives research support from OREF; receives research support from Orthopaedic Trauma Association; receives research support from PCORI; receives research support from Regenosine; receives research support from SITES Medical; receives publishing royalties, financial or material support from Thieme; is a paid consultant for Trupanion; and receives research support from U.S. Department of Defense. • Bryce W. Rigden, Chantelle C. Bozynski, Keiichi Kuroki, Tamara Gull have no conflicts of interest to disclose.
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