Abstract
Aim
Implant-associated infection remains one of the biggest challenges facing orthopaedics and there is an urgent clinical need to develop new prophylactic strategies. We have previously shown that CSA-90, a broad-spectrum antimicrobial, prevented infection in an infected open fracture model. In this study we developed a novel model of implant-associated infection, in which to further test the potential of CSA-90 as a prophylactic agent.
Method
All studies were approved by the local animal ethics committee. 3D-printed porous titanium implants were implanted into the distal femora of 18 week-old male Wistar rats under general anaesthesia. The treatment groups' (n=10) implants were pre-coated with 500μg CSA-90 in saline. Staphylococcus aureus* was inoculated either directly around the implant (1×104 CFU) or injected intravenously immediately post-operatively (1×105 CFU). No systemic antibiotic prophylaxis was used. The study ran for six weeks and animals were reviewed daily for signs of infection. An independent, blinded veterinarian reviewed twice-weekly radiographs, and rats demonstrating osteolysis and/or declining overall health were culled early at their instruction. The primary outcome was implant infection, incorporating survival, microbiological, radiological, and histological measures.
Results
All untreated animals inoculated with S. aureus developed clinical and radiographic evidence of implant infection and were culled within 14 days of surgery (Figure 1A). CSA-90 treatment significantly increased median survival in groups inoculated with S. aureus (p<0.001). Swab culture demonstrated that CSA-90 treated implants had a significantly reduced rate of infection compared to untreated implants in both the local (p< 0.01) and systemic (p<0.001) groups (Figure 1B).
Conclusions
This study demonstrates clinical potential for CSA-90 as a novel prophylactic antimicrobial for orthopaedics. Further in vivo evaluation is required in conjunction with existing systemic antibiotic prophylaxis.
Acknowledgements
This work was funded by NHMRC grant 1106982. Implants and CSA-90 were donated in kind support from Stryker and N8 Medical respectively.
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