Comparison of two fluorescent probes in preclinical non-invasive imaging and image-guided debridement surgery of Staphylococcal biofilm implant infections

Howard Y Park,Gideon Blumstein,John Hoang,Francisco Romero Pastrana,Zachary Burke,Marina Sprague,Marleen Van Oosten,Marina López-Álvarez,William Sheppard,Christopher Hamad,Mafalda Bispo,Julie Czupryna,Lloyd S Miller,Ryan Smith,Nicholas M Bernthal,Stephen D Zoller,Kevin P Francis,Jan Maarten Van Dijl,Vishal Hegde

doi:10.1038/s41598-020-78362-7

Abstract

Implant-associated infections are challenging to diagnose and treat. Fluorescent probes have been heralded as a technologic advancement that can improve our ability to non-invasively identify infecting organisms, as well as guide the inexact procedure of surgical debridement. This study’s purpose was to compare two fluorescent probes for their ability to localize Staphylococcus aureus biofilm infections on spinal implants utilizing noninvasive optical imaging, then assessing the broader applicability of the more successful probe in other infection animal models. This was followed by real-time, fluorescence image-guided surgery to facilitate debridement of infected tissue. The two probe candidates, a labelled antibiotic that targets peptidoglycan (Vanco-800CW), and the other, a labelled antibody targeting the immunodominant Staphylococcal antigen A (1D9-680), were injected into mice with spine implant infections. Mice were then imaged noninvasively with near infrared fluorescent imaging at wavelengths corresponding to the two probe candidates. Both probes localized to the infection, with the 1D9-680 probe showing greater fidelity over time. The 1D9-680 probe was then tested in mouse models of shoulder implant and allograft infection, demonstrating its broader applicability. Finally, an image-guided surgery system which superimposes fluorescent signals over analog, real-time, tissue images was employed to facilitate debridement of fluorescent-labelled bacteria.

Highlights

Implant-associated infections are challenging to diagnose and treat
The findings presented in this study address the pressing clinical shortcomings in the diagnosis and treatment of implant infections
Successful biopsy or culture of the bacterial foci are vital to successful treatment, yet current techniques suffer from considerable false-negative and false-positive results, which contribute to treatment failures and patient m orbidity[17,18,25]

Summary

Introduction

Implant-associated infections are challenging to diagnose and treat. Fluorescent probes have been heralded as a technologic advancement that can improve our ability to non-invasively identify infecting organisms, as well as guide the inexact procedure of surgical debridement. This study’s purpose was to compare two fluorescent probes for their ability to localize Staphylococcus aureus biofilm infections on spinal implants utilizing noninvasive optical imaging, assessing the broader applicability of the more successful probe in other infection animal models. This was followed by real-time, fluorescence image-guided surgery to facilitate debridement of infected tissue. Biofilm-associated implant infections across all medical and surgical disciplines often require a combination of debridement surgery of wound beds, explantation of implants, and long-term antibiotic t reatment[5,6,7] Despite these aggressive surgical interventions, treatment failure is common and highly morbid to the p atient[5,6,7]. Image-guided surgical debridement, achieved using a specialized fluorescence camera system in the surgical suite, may improve the accuracy of infection excision, which currently relies solely on the surgeon’s discretion based on imprecise visual inspection of infected tissue

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Conclusion