Abstract

PurposeFracture-related infection (FRI) is a serious complication in orthopedic trauma surgery worldwide. Especially, the distinction of infection from sterile inflammation and the detection of low-grade infection are highly challenging. The objective of the present study was to obtain proof-of-principle for the use of bacteria-targeted fluorescence imaging to detect FRI on extracted osteosynthesis devices as a step-up towards real-time image-guided trauma surgery.MethodsExtracted osteosynthesis devices from 13 patients, who needed revision surgery after fracture treatment, were incubated with a near-infrared fluorescent tracer composed of the antibiotic vancomycin and the fluorophore IRDye800CW (i.e., vanco-800CW). Subsequently, the devices were imaged, and vanco-800CW fluorescence signals were correlated to the results of microbiological culturing and to bacterial growth upon replica plating of the imaged devices on blood agar.ResultsImportantly, compared to culturing, the bacteria-targeted fluorescence imaging of extracted osteosynthesis devices with vanco-800CW allows for a prompt diagnosis of FRI, reducing the time-to-result from days to less than 30 min. Moreover, bacteria-targeted imaging can provide surgeons with real-time visual information on the presence and extent of infection.ConclusionHere, we present the first clinical application of fluorescence imaging for the detection of FRI. We conclude that imaging with vanco-800CW can provide early, accurate, and real-time visual diagnostic information on FRI in the clinical setting, even in the case of low-grade infections.Graphical abstract

Highlights

  • Fracture-related infection (FRI) is a devastating complication after bone fracture treatment, resulting in severe patient morbidity and loss of quality of life

  • The investigated patient cohort consisted of 13 patients who underwent revision surgery in the University Medical Center Groningen (UMCG) between January 2018 and February 2020 to extract osteosynthesis devices after a bone fracture treatment

  • One-half of the plate was used for fluorescence imaging with vanco-800CW, whereas the other half was used for regular diagnostic microbiological culturing (Table S1)

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Summary

Introduction

FRI is a devastating complication after bone fracture treatment, resulting in severe patient morbidity and loss of quality of life. FRIs can be differentiated into (1) acute infections. A major challenge is a distinction between noninfected and infected areas and devices during surgery, especially in the case of low-grade infections. Surgeons rely on tactile and visual information to establish whether and to what extent wound areas are affected by the suspected infection. A definitive preoperative diagnosis of FRI is often not possible in the case of low-grade infections due to the absence of unambiguous clinical symptoms of infection. The results from diagnostic modalities, such as white blood cell scintigraphy, fluorodeoxyglucose positron emission tomography (FDG-PET), or magnetic resonance imaging (MRI), are often inconclusive [3, 5, 6]. A diagnostic imaging tool enabling early, accurate, and realtime visualization of the infecting bacteria themselves, rather than inflammatory responses elicited by the infection, would provide a solution to this clinical problem

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