Louise Kruse Jensen1, Janne Koch2, Kirstine Dich-Jorgensen1, Bent Aalbaek1, Andreas Petersen3, Kurt Fuursted3, Thomas Bjarnsholt4,5, Kasper Nørskov Kragh4, Mikkel Tøtterup6,7, Mats Bue6,8, Pelle Hanberg6, Kjeld Søballe6, Peter M H Heegaard9, Henrik Elvang Jensen1. 1. Department of Veterinary Disease Biology, University of Copenhagen, Ridebanevej 3, 1870, Frederiksberg C, Denmark. 2. Department of Experimental Medicine, University of Copenhagen, Blegdamsvej 2, 2200, Copenhagen N, Denmark. 3. Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark. 4. Costerton Biofilm Center, Institute of Immunology and Microbiology, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark. 5. Department of Clinical Microbiology, Copenhagen University Hospital, Juliane Maries Vej 22, 2100, Copenhagen Ø, Denmark. 6. Orthopedic Research Unit, Aarhus University Hospital, Building 1A, Nørrebrogade 44, 8000, Aarhus, Denmark. 7. Department of Orthopedic Surgery, Randers Regional Hospital, Skovlyvej 15, 8930, Randers NØ, Denmark. 8. Department of Orthopedic Surgery, Horsens Regional Hospital, Sundvej 30, 8700, Horsens, Denmark. 9. Innate Immunology Group, National Veterinary Institute, Technical University of Denmark, Bülowsvej 27, 1870, Frederiksberg C, Denmark.
Abstract
Pigs are favorable experimental animals for infectious diseases in humans. However, implant-associated osteomyelitis (IAO) models in pigs have only been evaluated using high-inoculum infection (>108 CFU) models in 1975 and 1993. Therefore, the aim of this paper was to present a new low inoculum porcine model of human IAO based on 42 experimental pigs. The model was created by drilling an implant cavity in the tibial bone followed by insertion of a small steel implant and simultaneous inoculation of Staphylococcus aureus bacteria (n = 32) or saline (n = 10). The infected pigs were either inoculated with 104 CFU (n = 26) or 102 and 103 CFU (n = 6). All animals were euthanized 5 days after insertion of implants. Pigs receiving the high-inoculum infections showed a significantly higher volume of bone lesion, number of neutrophils around the implant, concentrations of acute phase proteins in serum, and enlargement of regional lymph nodes. A positive correlation was present between a high number of surrounding neutrophils and high values of all other parameters. Furthermore, a threshold of 40 neutrophils per 10 high power fields for the histopathological diagnosis of high grade IAO was defined. IN CONCLUSION: This paper describes a novel low-inoculum S. aureus porcine model of IAO which was demonstrated to be reliable, reproducible and discriminative to human IAO, and represents a requested and valuable tool in orthopedic research.
Pigs are favorable experimental animals for infectious diseases in humans. However, implant-associated osteomyelitis (IAO) models in pigs have only been evaluated using high-inoculum infection (>108 CFU) models in 1975 and 1993. Therefore, the aim of this paper was to present a new low inoculum porcine model of human IAO based on 42 experimental pigs. The model was created by drilling an implant cavity in the tibial bone followed by insertion of a small steel implant and simultaneous inoculation of Staphylococcus aureus bacteria (n = 32) or saline (n = 10). The infected pigs were either inoculated with 104 CFU (n = 26) or 102 and 103 CFU (n = 6). All animals were euthanized 5 days after insertion of implants. Pigs receiving the high-inoculum infections showed a significantly higher volume of bone lesion, number of neutrophils around the implant, concentrations of acute phase proteins in serum, and enlargement of regional lymph nodes. A positive correlation was present between a high number of surrounding neutrophils and high values of all other parameters. Furthermore, a threshold of 40 neutrophils per 10 high power fields for the histopathological diagnosis of high grade IAO was defined. IN CONCLUSION: This paper describes a novel low-inoculum S. aureus porcine model of IAO which was demonstrated to be reliable, reproducible and discriminative to human IAO, and represents a requested and valuable tool in orthopedic research.
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