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

Abstract

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.