Background: Orthopaedic infection is a major medical challenge complicated by a growing frequency of antibiotic resistant microbial strains. There is a need to identify new methods for infection prophylaxis and treatment in the context of bone surgery. The growth of biofilms around orthopaedic implants can complicate treatment, as can the capacity of bacteria to invade the bone compartment and evade the host cellular immune system.
Methods: We have standardized or in the process of developing a number of reproducible models for orthopaedic infection using Staphylococcus aureus. The first is a rat fracture model, where an open osteotomy is inoculated at the time of surgery. The second is a rat joint replacement surgery model featuring a press-fit porous titanium implant at the knee. This can be infected locally or systemically. The third is a murine tibial drill-hole model, which has undergone many rounds of refinement to enable a low-cost yet replicable model of bone infection for drug screening. Interventions including antibiotics and surface coatings have been successfully examined using these models.
Results: The rat fracture model was found to show physiological and radiographic deterioration that was rescuable with local antibiotic therapy with CSA-90, but not with local anabolic bone morphogenetic protein-2. The rat knee implant model also reliably created an infection that was prevented by surface coating with CSA-90. The murine drill-hole model has had iterative improvements in terms of hole diameter, bacterial load, and addition of a metallic surface in the form of an intramedullary pin.
Discussion: There are numerous complexities associated with preclinical infection models that are both technical (in terms of operative reproducibility) and ethical (in terms of animal welfare and minimising harm). Establishment of reliable models will be essential for screening the next generation of antimicrobial therapies to combat ever increasing microbial threats.