Skip to main content
Top
Published in: Archives of Orthopaedic and Trauma Surgery 9/2019

01-09-2019 | Bone Infection | Trauma Surgery

Histological score for degrees of severity in an implant-associated infection model in mice

Authors: Carina Büren, Michael Hambüchen, Joachim Windolf, Tim Lögters, Ceylan Daniela Windolf

Published in: Archives of Orthopaedic and Trauma Surgery | Issue 9/2019

Login to get access

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.
Literature
1.
go back to reference 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 34:321–340CrossRef 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 34:321–340CrossRef
2.
go back to reference Metsemakers WJ, Kuehl R, Moriarty TF et al (2018) Infection after fracture fixation: current surgical and microbiological concepts. Injury 49(3):511–522CrossRef Metsemakers WJ, Kuehl R, Moriarty TF et al (2018) Infection after fracture fixation: current surgical and microbiological concepts. Injury 49(3):511–522CrossRef
3.
go back to reference Willey M, Karam M (2016) Impact of infection on fracture fixation. Orthop Clin 47(2):357–364CrossRef Willey M, Karam M (2016) Impact of infection on fracture fixation. Orthop Clin 47(2):357–364CrossRef
4.
go back to reference 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):5–12CrossRefPubMed 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):5–12CrossRefPubMed
5.
go back to reference 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):1408–1415CrossRef 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):1408–1415CrossRef
6.
go back to reference Geipel U, Herrmann M (2004) Das infizierte Implantat. Orthopäde 33(12):1411–1428CrossRef Geipel U, Herrmann M (2004) Das infizierte Implantat. Orthopäde 33(12):1411–1428CrossRef
8.
go back to reference Walter G, Hoffmann R (2009) Implantat-assoziierte Infektionen in Orthopädie und Unfallchirurgie. Krankenh-Hyg Infekt 31(1):8–14CrossRef Walter G, Hoffmann R (2009) Implantat-assoziierte Infektionen in Orthopädie und Unfallchirurgie. Krankenh-Hyg Infekt 31(1):8–14CrossRef
9.
go back to reference Seybold D, Schildhauer T (2010) Knocheninfekte. Orthopädie und Unfallchirurgie essentials: Intensivkurs zur Weiterbildung. Georg Thieme-Verlag, Stuttgart, pp 135–142 Seybold D, Schildhauer T (2010) Knocheninfekte. Orthopädie und Unfallchirurgie essentials: Intensivkurs zur Weiterbildung. Georg Thieme-Verlag, Stuttgart, pp 135–142
10.
go back to reference Birt MC, Anderson DW, Bruce Toby E, Wang J (2017) Osteomyelitis: recent advances in pathophysiology and therapeutic strategies. J Orthop 14(1):45–52CrossRefPubMed Birt MC, Anderson DW, Bruce Toby E, Wang J (2017) Osteomyelitis: recent advances in pathophysiology and therapeutic strategies. J Orthop 14(1):45–52CrossRefPubMed
11.
go back to reference Montanaro L, Speziale P, Campoccia D et al (2011) Scenery of Staphylococcus implant infections in orthopedics. Futur Microbiol 6(11):1329–1349CrossRef Montanaro L, Speziale P, Campoccia D et al (2011) Scenery of Staphylococcus implant infections in orthopedics. Futur Microbiol 6(11):1329–1349CrossRef
12.
go back to reference Cierny GI, Mader JT, Penninck JJ (2003) The classic: a clinical staging system for adult osteomyelitis. Clin Orthop 414:7–24CrossRef Cierny GI, Mader JT, Penninck JJ (2003) The classic: a clinical staging system for adult osteomyelitis. Clin Orthop 414:7–24CrossRef
13.
go back to reference Schmidt HGK, Tiemann AH, Braunschweig R et al (2011) Zur definition der diagnose osteomyelitis—osteomyelitis-diagnose-score (ODS). Z Für Orthop Unfallchirurgie 149(04):449–460CrossRef Schmidt HGK, Tiemann AH, Braunschweig R et al (2011) Zur definition der diagnose osteomyelitis—osteomyelitis-diagnose-score (ODS). Z Für Orthop Unfallchirurgie 149(04):449–460CrossRef
14.
go back to reference 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):497–504CrossRef 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):497–504CrossRef
15.
go back to reference Metsemakers W, Morgenstern M, McNally MA et al (2018) Fracture-related infection: a consensus on definition from an international expert group. Injury 49(3):505–510CrossRef Metsemakers W, Morgenstern M, McNally MA et al (2018) Fracture-related infection: a consensus on definition from an international expert group. Injury 49(3):505–510CrossRef
16.
go back to reference 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):966–972CrossRef 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):966–972CrossRef
17.
go back to reference 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):2013–2020CrossRefPubMed 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):2013–2020CrossRefPubMed
20.
21.
22.
23.
go back to reference 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):3507–3512CrossRefPubMed 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):3507–3512CrossRefPubMed
24.
go back to reference Takao K, Miyakawa T (2015) Genomic responses in mouse models greatly mimic human inflammatory diseases. Proc Natl Acad Sci 112(4):1167–1172CrossRefPubMed Takao K, Miyakawa T (2015) Genomic responses in mouse models greatly mimic human inflammatory diseases. Proc Natl Acad Sci 112(4):1167–1172CrossRefPubMed
Metadata
Title
Histological score for degrees of severity in an implant-associated infection model in mice
Authors
Carina Büren
Michael Hambüchen
Joachim Windolf
Tim Lögters
Ceylan Daniela Windolf
Publication date
01-09-2019
Publisher
Springer Berlin Heidelberg
Published in
Archives of Orthopaedic and Trauma Surgery / Issue 9/2019
Print ISSN: 0936-8051
Electronic ISSN: 1434-3916
DOI
https://doi.org/10.1007/s00402-019-03188-6

Other articles of this Issue 9/2019

Archives of Orthopaedic and Trauma Surgery 9/2019 Go to the issue