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

Author:

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

Abstract

AbstractImplant-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.

Funder

National Institute of Arthritis and Musculoskeletal and Skin Diseases

CEC MSCI-ITN

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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