Biomarkers for Infection Perform Poorly to Diagnose Residual Infection between First and Second Stage Revision Arthroplasty

Background: Two stage exchange arthroplasty remains the preferred treatment method for the majority of periprosthetic joint infections. This study aims to examine the diagnostic value of bio-markers for residual infection between stage 1 and 2 revisions.

Methods: A retrospective study examining common infection biomarkers to determine their prognostic utility associated with treatment failure. These included: C-Reactive protein (CRP), the synovial fluid white blood cells (WBC) count and Neutrophils percent (Neut%), and the intraoperative histologic synovial WBC count per high power field (HPF). Residual infection was defined as either positive cultures (more than one) at second stage, draining sinus requiring further surgery or any further surgery (amputation, arthrodesis or another two second stage revision). Area under the curves (AUC) and optimal cut-off values were calculated. Sensitivity, specificity, positive and negative predictive values and likelihood ratios were calculated accordingly.

Result: 184 two-stage exchange operations that included 110 (59.8%) prosthetic hips and 74 (40.2%) prosthetic knees met the inclusion criterion. Residual infection was present in 38 (20.7%) of the procedures. The AUC values were 0.677 for CRP (p-value=0.002), 0.506 for aspiration WBC (p-value=0.944), 0.632 for aspiration NEUT % (p-value=0.2) and 0.525 for WBC per HPF (p-value=0.453). Positive and negative predictive values ranged between 26%-57% and 78%-85%, respectively. CRP values at 1,2,3 and 4 months after first stage were also compared and AUC of ROC were 0.581, 0.647, 0.591 and 0.603, respectively. Analyses utilizing specific combinations of biomarkers did not significantly improve predictive values.

Discussion: Biomarkers for infection include CRP, synovial white cell count, synovial neutrophil percent and the number of WBC per HPF in the synovial tissue on microscopy. Our study demonstrates that these biomarkers perform poorly to identify residual infection before second stage revision. Further research is necessary to evaluate diagnosis of the eradication or persistence of infection in staged surgical procedures.