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A radio- and fluorescently labelled tracer for imaging and quantification of bacterial infection on orthopaedic prostheses: a proof of principle study

AIMS: Arthroplasty surgery of the knee and hip is performed in two to three million patients annually. Periprosthetic joint infections occur in 4% of these patients. Debridement, antibiotics, and implant retention (DAIR) surgery aimed at cleaning the infected prosthesis often fails, subsequently req...

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Autores principales: Welling, Mick M., Warbroek, Kim, Khurshid, Chrow, van Oosterom, Matthias N., Rietbergen, Daphne D. D., de Boer, Mark G. J., Nelissen, Rob G. H. H., van Leeuwen, Fijs W. B., Pijls, Bart G., Buckle, Tessa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The British Editorial Society of Bone & Joint Surgery 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9872039/
https://www.ncbi.nlm.nih.gov/pubmed/36649933
http://dx.doi.org/10.1302/2046-3758.121.BJR-2022-0216.R1
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author Welling, Mick M.
Warbroek, Kim
Khurshid, Chrow
van Oosterom, Matthias N.
Rietbergen, Daphne D. D.
de Boer, Mark G. J.
Nelissen, Rob G. H. H.
van Leeuwen, Fijs W. B.
Pijls, Bart G.
Buckle, Tessa
author_facet Welling, Mick M.
Warbroek, Kim
Khurshid, Chrow
van Oosterom, Matthias N.
Rietbergen, Daphne D. D.
de Boer, Mark G. J.
Nelissen, Rob G. H. H.
van Leeuwen, Fijs W. B.
Pijls, Bart G.
Buckle, Tessa
author_sort Welling, Mick M.
collection PubMed
description AIMS: Arthroplasty surgery of the knee and hip is performed in two to three million patients annually. Periprosthetic joint infections occur in 4% of these patients. Debridement, antibiotics, and implant retention (DAIR) surgery aimed at cleaning the infected prosthesis often fails, subsequently requiring invasive revision of the complete prosthetic reconstruction. Infection-specific imaging may help to guide DAIR. In this study, we evaluated a bacteria-specific hybrid tracer ((99m)Tc-UBI(29-41)-Cy5) and its ability to visualize the bacterial load on femoral implants using clinical-grade image guidance methods. METHODS: (99m)Tc-UBI(29-41)-Cy5 specificity for Stapylococcus aureus was assessed in vitro using fluorescence confocal imaging. Topical administration was used to highlight the location of S. aureus cultured on femoral prostheses using fluorescence imaging and freehand single photon emission CT (fhSPECT) scans. Gamma counting and fhSPECT were used to quantify the bacterial load and monitor cleaning with chlorhexidine. Microbiological culturing helped to relate the imaging findings with the number of (remaining) bacteria. RESULTS: Bacteria could be effectively stained in vitro and on prostheses, irrespective of the presence of biofilm. Infected prostheses revealed bacterial presence on the transition zone between the head and neck, and in the screw hole. Qualitative 2D fluorescence images could be complemented with quantitative 3D fhSPECT scans. Despite thorough chlorhexidine treatments, 28% to 44% of the signal remained present in the locations of the infection that were identified using imaging, which included 500 to 2,000 viable bacteria. CONCLUSION: The hybrid tracer (99m)Tc-UBI(29-41)-Cy5 allowed effective bacterial staining. Qualitative real-time fluorescence guidance could be effectively combined with nuclear imaging that enables quantitative monitoring of the effectiveness of cleaning strategies. Cite this article: Bone Joint Res 2023;12(1):72–79.
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spelling pubmed-98720392023-02-03 A radio- and fluorescently labelled tracer for imaging and quantification of bacterial infection on orthopaedic prostheses: a proof of principle study Welling, Mick M. Warbroek, Kim Khurshid, Chrow van Oosterom, Matthias N. Rietbergen, Daphne D. D. de Boer, Mark G. J. Nelissen, Rob G. H. H. van Leeuwen, Fijs W. B. Pijls, Bart G. Buckle, Tessa Bone Joint Res Infection AIMS: Arthroplasty surgery of the knee and hip is performed in two to three million patients annually. Periprosthetic joint infections occur in 4% of these patients. Debridement, antibiotics, and implant retention (DAIR) surgery aimed at cleaning the infected prosthesis often fails, subsequently requiring invasive revision of the complete prosthetic reconstruction. Infection-specific imaging may help to guide DAIR. In this study, we evaluated a bacteria-specific hybrid tracer ((99m)Tc-UBI(29-41)-Cy5) and its ability to visualize the bacterial load on femoral implants using clinical-grade image guidance methods. METHODS: (99m)Tc-UBI(29-41)-Cy5 specificity for Stapylococcus aureus was assessed in vitro using fluorescence confocal imaging. Topical administration was used to highlight the location of S. aureus cultured on femoral prostheses using fluorescence imaging and freehand single photon emission CT (fhSPECT) scans. Gamma counting and fhSPECT were used to quantify the bacterial load and monitor cleaning with chlorhexidine. Microbiological culturing helped to relate the imaging findings with the number of (remaining) bacteria. RESULTS: Bacteria could be effectively stained in vitro and on prostheses, irrespective of the presence of biofilm. Infected prostheses revealed bacterial presence on the transition zone between the head and neck, and in the screw hole. Qualitative 2D fluorescence images could be complemented with quantitative 3D fhSPECT scans. Despite thorough chlorhexidine treatments, 28% to 44% of the signal remained present in the locations of the infection that were identified using imaging, which included 500 to 2,000 viable bacteria. CONCLUSION: The hybrid tracer (99m)Tc-UBI(29-41)-Cy5 allowed effective bacterial staining. Qualitative real-time fluorescence guidance could be effectively combined with nuclear imaging that enables quantitative monitoring of the effectiveness of cleaning strategies. Cite this article: Bone Joint Res 2023;12(1):72–79. The British Editorial Society of Bone & Joint Surgery 2023-01-10 /pmc/articles/PMC9872039/ /pubmed/36649933 http://dx.doi.org/10.1302/2046-3758.121.BJR-2022-0216.R1 Text en © 2023 Author(s) et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND 4.0) licence, which permits the copying and redistribution of the work only, and provided the original author and source are credited. See https://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Infection
Welling, Mick M.
Warbroek, Kim
Khurshid, Chrow
van Oosterom, Matthias N.
Rietbergen, Daphne D. D.
de Boer, Mark G. J.
Nelissen, Rob G. H. H.
van Leeuwen, Fijs W. B.
Pijls, Bart G.
Buckle, Tessa
A radio- and fluorescently labelled tracer for imaging and quantification of bacterial infection on orthopaedic prostheses: a proof of principle study
title A radio- and fluorescently labelled tracer for imaging and quantification of bacterial infection on orthopaedic prostheses: a proof of principle study
title_full A radio- and fluorescently labelled tracer for imaging and quantification of bacterial infection on orthopaedic prostheses: a proof of principle study
title_fullStr A radio- and fluorescently labelled tracer for imaging and quantification of bacterial infection on orthopaedic prostheses: a proof of principle study
title_full_unstemmed A radio- and fluorescently labelled tracer for imaging and quantification of bacterial infection on orthopaedic prostheses: a proof of principle study
title_short A radio- and fluorescently labelled tracer for imaging and quantification of bacterial infection on orthopaedic prostheses: a proof of principle study
title_sort radio- and fluorescently labelled tracer for imaging and quantification of bacterial infection on orthopaedic prostheses: a proof of principle study
topic Infection
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9872039/
https://www.ncbi.nlm.nih.gov/pubmed/36649933
http://dx.doi.org/10.1302/2046-3758.121.BJR-2022-0216.R1
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