Image-guided in situ detection of bacterial biofilms in a human prosthetic knee infection model: a feasibility study for

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ORIGINAL ARTICLE

Image-guided in situ detection of bacterial biofilms in a human prosthetic knee infection model: a feasibility study for clinical diagnosis of prosthetic joint infections Jorrit W. A. Schoenmakers 1,2 & Marjolein Heuker 2 & Marina López-Álvarez 2 & Wouter B. Nagengast 3 & Gooitzen M. van Dam 4 & Jan Maarten van Dijl 2 & Paul C. Jutte 1 & Marleen van Oosten 2 Received: 18 April 2020 / Accepted: 28 July 2020 # The Author(s) 2020

Abstract Purpose Due to an increased human life expectancy, the need to replace arthritic or dysfunctional joints by prosthetics is higher than ever before. Prosthetic joints are unfortunately inherently susceptible to bacterial infection accompanied by biofilm formation. Accurate and rapid diagnosis is vital to increase therapeutic success. Yet, established diagnostic modalities cannot directly detect bacterial biofilms on prostheses. Therefore, the present study was aimed at investigating whether arthroscopic optical imaging can accurately detect bacterial biofilms on prosthetic joints. Methods Here, we applied a conjugate of the antibiotic vancomycin and the near-infrared fluorophore IRDye800CW, in short vanco-800CW, in combination with arthroscopic optical imaging to target and visualize biofilms on infected prostheses. Results We show in a human post-mortem prosthetic knee infection model that a staphylococcal biofilm is accurately detected in real time and distinguished from sterile sections in high resolution. In addition, we demonstrate that biofilms associated with the clinically most relevant bacterial species can be detected using vanco-800CW. Conclusion The presented image-guided arthroscopic approach provides direct visual diagnostic information and facilitates immediate appropriate treatment selection. Keywords Infection imaging . Prosthetic joint . Biofilm . Optical tracer . Fluorescence

Marjolein Heuker and Marina López-Álvarez contributed equally to this work. This article is part of the Topical Collection on Infection and inflammation Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00259-020-04982-w) contains supplementary material, which is available to authorized users. * Jan Maarten van Dijl [email protected] 1

Department of Orthopaedics, University of Groningen, University Medical Center Groningen (UMCG), Groningen, The Netherlands

2

Department of Medical Microbiology, University of Groningen, UMCG, Hanzeplein 1, PO Box 30001, 9700 RB Groningen, The Netherlands

3

Department of Gastroenterology and Hepatology, University of Groningen, UMCG, Groningen, The Netherlands

4

Department of Surgery, University of Groningen, UMCG, Groningen, The Netherlands

Introduction Human life expectancy is presently higher than ever before. The need for biomaterials to replace arthritic or dysfunctional body parts by prosthetics has, therefore, never been greater [1]. Total joint replacement with a prosthesis is nowadays the most performed substitute, which usually contributes to an enhanced quality of life. Appro