The Role of Biomarkers for the Diagnosis of Implant-Related Infections in Orthopaedics and Trauma

Abstract

Diagnosis of implant-related (periprosthetic joint) infections poses a major challenge to infection disease physicians and orthopaedic surgeons. Conventional diagnostic tests continue to suffer from issues of accuracy and feasibility. Biomarkers are used throughout medicine for diagnostic and prognostic purposes, as they are able to objectively determine the presence of a disease or a biological state. There is increasing evidence to support the measurement of specific biomarkers in serum and/or synovial fluid of patients with suspected periprosthetic joint infections. Promising serum biomarkers include interleukin (IL)-4, IL-6, tumour necrosis factor (TNF)-α, procalcitonin, soluble intercellular adhesion molecule 1 (sICAM-1), and D-dimer. In addition to c-reactive protein and leucocyte esterase, promising biomarkers that can be measured in synovial fluid include antimicrobial proteins such as human β-defensin (HBD)-2 and human β-defensin (HBD)-3, and cathelicidin LL-37, as well as several interleukins such as IL-1β, IL-6, IL-8, IL-17, TNF- α, interferon-δ, and vascular endothelial growth factor.

Current Recommendations for the Diagnosis of Acute and Chronic PJI for Hip and Knee—Cell Counts, Alpha-Defensin, Leukocyte Esterase, Next-generation Sequencing

“…It has shown to rise in response to lowvirulence organisms and is unaffected by prior antibiotic administration [17,23,71,73,74]. Unlike LE, alphadefensin is quite expensive with each test costing approximately $760; however, as a diagnostic tool, it has proven to be highly accurate for early detection and diagnosis of PJI [75].…”

Diagnostic accuracy of alpha-defensin in periprosthetic joint infection: a systematic review and meta-analysis

“…Given this issue, the Musculoskeletal Infection Society (MSIS) published a new definition of PJI (Table S1) in 2011, which combined clinical data and laboratory tests and sought to give doctors a rough indication of diagnosis [18]. In addition, some scientists have attempted to use serum and synovial fluid biomarkers to diagnose the joint infection, and the results of many studies have shown that biomarkers in synovial fluid are more reliable than those in serum [21,34,35]. Alpha-defensin from synovial fluid, a synovial biomarker that could be used as a new preoperative and intra-operative tests for diagnosis, has become increasingly reported.…”

Diagnostic Value of Next-Generation Sequencing to Detect Periprosthetic Joint Infection

“…Several biomarkers have been studied in recent years to improve the accuracy of diagnosing PJI, such as C-reactive protein (CRP) [6] , α-defensin [7] , leukocyte esterase [8] , interleukin-6 (IL-6) [9] , vascular endothelial growth factor [10] , and granulocyte colony-stimulating factor [11] , but the overall sensitivity (77-97%) and speci city (86-96%) remain inadequate [12] . PCR was once considered a reliable method for diagnosing PJI [13] .…”