Diagnosing periprosthetic joint infection: has the era of the biomarker arrived?

Abstract

Background: The diagnosis of periprosthetic joint infection (PJI) remains a serious clinical challenge. There is a pressing need for improved diagnostic testing methods; biomarkers offer one potentially promising approach.

Questions/purposes: We evaluated the diagnostic characteristics of 16 promising synovial fluid biomarkers for the diagnosis of PJI.

Methods: Synovial fluid was collected from 95 patients meeting the inclusion criteria of this prospective diagnostic study. All patients were being evaluated for a revision hip or knee arthroplasty, including patients with systemic inflammatory disease and those already receiving antibiotic treatment. The Musculoskeletal Infection Society (MSIS) definition was used to classify 29 PJIs and 66 aseptic joints. Synovial fluid samples were tested by immunoassay for 16 biomarkers optimized for use in synovial fluid. Sensitivity, specificity, and receiver operating characteristic curve analysis were performed to assess for diagnostic performance.

Results: Five biomarkers, including human α-defensin 1-3, neutrophil elastase 2, bactericidal/permeability-increasing protein, neutrophil gelatinase-associated lipocalin, and lactoferrin, correctly predicted the MSIS classification of all patients in this study, with 100% sensitivity and specificity for the diagnosis of PJI. An additional eight biomarkers demonstrated excellent diagnostic strength, with an area under the curve of greater than 0.9.

Conclusions: Synovial fluid biomarkers exhibit a high accuracy in diagnosing PJI, even when including patients with systemic inflammatory disease and those receiving antibiotic treatment. Considering that these biomarkers match the results of the more complex MSIS definition of PJI, we believe that synovial fluid biomarkers can be a valuable addition to the methods utilized for the diagnosis of infection.

Level of evidence: Level II, diagnostic study. See Instructions for Authors for a complete description of levels of evidence.

Fig. 1A–E

Log-scale dot plots demonstrate the diagnostic separation of study groups achieved by the five biomarkers achieving 100% sensitivity and specificity: (A) α-defensin, (B) ELA-2, (C) BPI, (D) lactoferrin, and (E) NGAL. The lowest reportable value was used for any samples that had a concentration below the limit of detection for each assay. Horizontal line = median; bars = interquartile range.

Fig. 2A–D

Log-scale dot plots demonstrate the diagnostic separation of study groups achieved by traditional tests for PJI: (A) ESR, (B) serum CRP, (C) neutrophil percentage, and (D) synovial fluid WBC count. Horizontal bar = median; error bars = interquartile range.