Department of Orthopaedic Surgery, David Geffen School of Medicine at University of California Los Angeles, 1250 16th Street, Suite 2100, Santa Monica, CA, 90404, USA.
Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, 9700 RB, The Netherlands.
Sci Rep. 2021 Jan 15;11(1):1622. doi: 10.1038/s41598-020-78362-7.
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.
植入物相关感染的诊断和治疗具有挑战性。荧光探针被认为是一种技术进步,可以提高我们非侵入性识别感染病原体的能力,并指导外科清创术这一不精确的过程。本研究的目的是比较两种荧光探针在利用非侵入性光学成像定位脊柱植入物金黄色葡萄球菌生物膜感染方面的能力,然后评估更成功的探针在其他感染动物模型中的更广泛适用性。随后进行实时荧光图像引导手术,以促进感染组织的清创。两种探针候选物,一种是针对肽聚糖的标记抗生素(Vanco-800CW),另一种是针对免疫显性葡萄球菌抗原 A(1D9-680)的标记抗体,被注射到脊柱植入物感染的小鼠体内。然后,用近红外荧光成像在与两种探针候选物相对应的波长下对小鼠进行非侵入性成像。两种探针都能定位到感染部位,1D9-680 探针随着时间的推移显示出更高的准确性。然后,在肩植入物和同种异体移植物感染的小鼠模型中测试了 1D9-680 探针,证明了其更广泛的适用性。最后,采用一种将荧光信号叠加在模拟、实时组织图像上的图像引导手术系统,以促进荧光标记细菌的清创。