Experimental implant-associated orthopaedic infections

University dissertation from Stockholm : Karolinska Institutet, Center for Surgical Sciences CFSS

Abstract: Although indispensable in today's medicine, orthopaedic implants may also cause adverse reactions. A foreign body increases the local susceptibility to colonisation by microorganisms, and hence the risk of infections. These infections are rare, but many result in prolonged or permanent impairment. In orthopaedic infections staphylococci are the commonest pathogens, but less aggressive anaerobic bacteria are also encountered. The first objective was to develop an animal model for investigating the role of anaerobic bacteria in orthopaedic infections. In rabbits, polyvinyl sponges were placed bilaterally in the proximal tibial metaphyses, and Bacteroides fragilis was injected unilaterally. All animals developed bilateral osteomyelitis, suggesting haematogenous seeding to the control side. Metronidazole treatment was ineffective, despite adequate serum levels, illustrating the difficulties of treating orthopaedic infections, without removal of the implants. To study the importance of implant design and material, rabbits had a plate applied with screws on die tibia. Either standard stainless steel dynamic compression plates (SS-DCP), identically designed titanium plates (Ti-DCP), or titanium PC-FIX plates (Ti-PC-FIX) were used. The local injection of Staphylococcus aureus resulted in similar infection rates in SS-DCP- and Ti-PC-FIX-plated animals. Plated animals had a higher infection rate than shamoperated rabbits did. In contrast, intravenous injection of the S. aureus strain caused a higher infection rate in SS-DCP animals than in Ti-PC-FIX animals, and sham-operated ones. The risk of infection was intermediate with Ti-DCP. Adherence of microorganisms to matrix proteins may be another pathomechanism in infections. In a mouse model, we studied collagen and fibronectin binding of S. aureus in implant-associated osteomyelitis. Bacterial strains, with or without collagen- or fibronectin-binding ability, were injected close to an intramedullary tibial nail. Unlike the collagenbinding ability, fibronectin-binding ability seemed to enhance the microorganisms' capacity to induce an infection. Our studies illustrated some characteristics in experimental models of orthopaedic infections. Implants facilitate the establishment of an infection. Also, the bacterial inoculum size is critical within a narrow dose range, usually around 107-8 colony-forming units, below which no infection occurs and, if exceeded, there is a high risk of a fatal outcome. The clinical presentations of implant-related infections vary, and the understanding of the underlying pathomechanisms is dependent on experimental studies. Further investigations of the importance of different microorganisms in orthopaedic infections, the importance of implant features, and the ecology and interactions at an implant site, are necessary for future progress in treatment of biomaterial-associated infections.

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