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

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.

Bacteria-targeted fluorescence imaging of extracted osteosynthesis devices for rapid visualization of fracture-related infections

“…3. The latter observation is consistent with our previous observations that there is no fluorescence signal of bacterial biofilms, human tissues, or osteosynthesis materials detectable in the near-infrared range prior to vanco-800CW administration [9,10,12], and this conclusion is fully supported by the absent or marginal fluorescence signals as observed for extracted culture-negative osteosynthesis devices shown in Fig. 4.…”

Antibiotic-chemoattractants enhance neutrophil clearance of Staphylococcus aureus

“…Using super-resolution confocal microscopy, binding of the labelled antibiotic-fPep conjugate was observed to have a similar binding distribution as the labelled vancomycin alone to MSSA and MRSA strains. This correlates with the findings of previous studies investigating labelled glycopeptide antibiotic (GPA) binding [24][25][26] , with binding to the septum in S. aureus also similar for vancomycin and the conjugate (Supplementary Fig. 1).…”

Radiological and Imaging Evidence in the Diagnosis and Management of Microbial Infections: An Update

“…Bacterial probes, including Vanco-800CW and labeled antibodies targeting the immunodominant Staphylococcal antigen A (1D9-680), were positively applied to efficiently debride the infected tissue in animal models. These experiments re-emphasize the role of imaging in the surgical debridement of infected tissues [ 28 ].…”