Abstract
Introduction
Several scores were introduced to diagnose and to classify osteomyelitis in practice. Mouse models are often used to study the pathophysiology of bone infection and to test therapeutic strategies. Aim of the present study was to design a score to diagnose and quantify implant-associated infection in a murine experimental model.
Materials and methods
Four independent parameters were developed: existence of callus, consolidation of the fracture, structural changes of the medullary cavity and number of bacteria. The score was assessed in a standardized implant-associated mouse model with 35 BALB/c-mice. The left femur was osteotomized, fixed by a titanium locking plate and infection was induced by inoculation of Staphylococcus aureus into the fracture gap. For the sham group, the procedure was performed without inoculation of bacteria. The score was assessed on days 7, 14 and 28. Each item of the score showed lower values for the infection group compared to the controls after 4 weeks.
Results
Regardless of the assessed time point, the overall total score was significantly higher in the control group compared to the infection group (p < 0.0001). Analysis revealed a sensitivity of 0.85, specificity of 1.0, negative predictive value of 0.67 and positive predictive value of 1.0.
Conclusion
The proposed score assessing severity of fracture-related infection in an implant-associated murine model was easy to access, feasible to diagnose and estimate bone healing and infection in a murine bone infection with a high sensitivity. Therefore, this score might be a useful tool to quantify infection-related changes after fracture in further future preclinical studies.
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References
Sabaté BM, O’Mahony L, Zeiter S et al (2017) Influence of fracture stability on Staphylococcus epidermidis and Staphylococcus aureus infection in a murine femoral fracture model. Eur Cell Mater 34:321–340
Metsemakers WJ, Kuehl R, Moriarty TF et al (2018) Infection after fracture fixation: current surgical and microbiological concepts. Injury 49(3):511–522
Willey M, Karam M (2016) Impact of infection on fracture fixation. Orthop Clin 47(2):357–364
Uçkay I, Hoffmeyer P, Lew D, Pittet D (2013) Prevention of surgical site infections in orthopaedic surgery and bone trauma: state-of-the-art update. J Hosp Infect 84(1):5–12
Papakostidis C, Kanakaris NK, Pretel J et al (2011) Prevalence of complications of open tibial shaft fractures stratified as per the Gustilo-Anderson classification. Injury 42(12):1408–1415
Geipel U, Herrmann M (2004) Das infizierte Implantat. Orthopäde 33(12):1411–1428
Schmelz A, Kinzl L, Einsiedel T (2006) Osteitis. Chirurg 77(10):943–962
Walter G, Hoffmann R (2009) Implantat-assoziierte Infektionen in Orthopädie und Unfallchirurgie. Krankenh-Hyg Infekt 31(1):8–14
Seybold D, Schildhauer T (2010) Knocheninfekte. Orthopädie und Unfallchirurgie essentials: Intensivkurs zur Weiterbildung. Georg Thieme-Verlag, Stuttgart, pp 135–142
Birt MC, Anderson DW, Bruce Toby E, Wang J (2017) Osteomyelitis: recent advances in pathophysiology and therapeutic strategies. J Orthop 14(1):45–52
Montanaro L, Speziale P, Campoccia D et al (2011) Scenery of Staphylococcus implant infections in orthopedics. Futur Microbiol 6(11):1329–1349
Cierny GI, Mader JT, Penninck JJ (2003) The classic: a clinical staging system for adult osteomyelitis. Clin Orthop 414:7–24
Schmidt HGK, Tiemann AH, Braunschweig R et al (2011) Zur definition der diagnose osteomyelitis—osteomyelitis-diagnose-score (ODS). Z Für Orthop Unfallchirurgie 149(04):449–460
Metsemakers W, Kortram K, Morgenstern M et al (2018) Definition of infection after fracture fixation: a systematic review of randomized controlled trials to evaluate current practice. Injury 49(3):497–504
Metsemakers W, Morgenstern M, McNally MA et al (2018) Fracture-related infection: a consensus on definition from an international expert group. Injury 49(3):505–510
Morgenstern M, Athanasou NA, Ferguson JY et al (2018) The value of quantitative histology in the diagnosis of fracture-related infection. Bone Jt J 100B(7):966–972
Windolf CD, Meng W, Lögters TT et al (2013) Implant-associated localized osteitis in murine femur fracture by biofilm forming Staphylococcus aureus: a novel experimental model. J Orthop Res 31(12):2013–2020
Windolf CD, Lögters T, Scholz M, et al. (2014) Lysostaphin-coated titan-implants preventing localized osteitis by Staphylococcus aureus in a mouse model. PLoS One 9(12) (cited 9 Aug 2015). http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4275259/
Swiderska Z, Korzynska A, Markiewicz T, et al. (2015) Comparison of the manual, semiautomatic, and automatic selection and leveling of hot spots in whole slide images for Ki-67 quantification in meningiomas. Anal Cell Pathol (cited 1 Oct 2018). https://www.hindawi.com/journals/acp/2015/498746/abs/
Tiemann AH, Braunschweig R, Hofmann GO (2012) Knocheninfektionen. Unfallchirurg 115(6):480–488
Lew DP, Waldvogel FA (2004) Osteomyelitis. The Lancet 364(9431):369–379
Ciampolini J, Harding KG (2000) Pathophysiology of chronic bacterial osteomyelitis. Why do antibiotics fail so often? Postgrad Med J 76(898):479–483
Seok J, Warren HS, Cuenca AG et al (2013) Genomic responses in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci 110(9):3507–3512
Takao K, Miyakawa T (2015) Genomic responses in mouse models greatly mimic human inflammatory diseases. Proc Natl Acad Sci 112(4):1167–1172
Acknowledgements
We thank Prof. Dr. H. E. Gabbert and the Institute for Pathology and Prof. Dr. C. R. MacKenzie and the Institute for Medical Microbiology at the Heinrich-Heine-University for valuable advice. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
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All authors have read and approved the final submitted manuscript. CB: literature search, study design, data collection, data analysis, data interpretation and writing. MH: study design, data collection, data analysis, data interpretation. TL and CDW: study design, data collection, data analysis, data interpretation and critical revision. JW: critical revision.
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Büren, C., Hambüchen, M., Windolf, J. et al. Histological score for degrees of severity in an implant-associated infection model in mice. Arch Orthop Trauma Surg 139, 1235–1244 (2019). https://doi.org/10.1007/s00402-019-03188-6
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DOI: https://doi.org/10.1007/s00402-019-03188-6