The Alpha Defensin-1 Biomarker Assay can be Used to Evaluate the Potentially Infected Total Joint Arthroplasty

Abstract

Background Diagnosing a periprosthetic joint infection (PJI) requires a complex approach using various laboratory and clinical criteria. A novel approach to diagnosing these infections uses synovial fluid biomarkers. Alpha defensin-1 (AD-1) is one such synovial-fluid biomarker. However little is known about the performance of the AD-1 assay in the diagnosis of PJI. Questions/purposes We sought to (1) determine the sensitivity and specificity of the AD-1 assay in a population of patients being evaluated for PJI, using the Musculoskeletal Infection Society (MSIS) criteria as the reference standard, and (2) compare the AD-1 assay with other currently available clinical tests, specifically cell count, culture, erythrocyte sedimentation rate, and C-reactive protein.Patients and Methods A retrospective review was performed of all patients undergoing workup for a PJI at our institution from January to June 2013. Sixty-one AD-1 assays were done in 57 patients. The group included 51 patients with 55 painful joints and six patients who underwent aspiration before second-stage reimplantation. Patients were considered to have a PJI if they met the MSIS criteria. We calculated the sensitivity and specificity of the AD-1 synovial fluid assay, and compared it with the sensitivity and specificity of the synovial fluid cell count, culture, erythrocyte sedimentation rate, and C-reactive protein. There were 19 diagnosed infections in the 61 aspirations, with 21 positive and 40 negative AD-1 assays. There were two false positive and no false negatives AD-1 assays. Results The sensitivity and specificity for the AD-1 assay were 100% (95% CI, 79%-100%) and 95% (95% CI, 83%-99%), respectively. The sensitivity and specificity of the other tests ranged from 68% to 95% and 66% to 88%, respectively. The AD-1 assay results outperformed the other tests but did not reach statistical significance except for the sensitivity of the erythrocyte sedimentation rate. Conclusion The sensitivity and specificity of the synovial fluid AD-1 assay exceeded the sensitivity and specificity of the other currently available clinical tests evaluated here but did not reach significance. The AD-1 assay offers another test with high sensitivity and specificity for diagnosing a PJI especially in the case where the diagnosis of PJI is uncertain, but larger studies will be needed to determine significance and cost effectiveness. Level of Evidence Level III, diagnostic study. See the Instructions for Authors for a complete description of levels of evidence.

Synovial Cytokines and the MSIS Criteria Are Not Useful for Determining Infection Resolution After Periprosthetic Joint Infection Explantation

“…Techniques to enhance the sensitivity of intraoperative cultures such as sonication cultures of explanted components were not routinely performed in our institution, possibly overestimating culture-negative PJIs. Lastly, recent studies from the last 2 years have shown that both synovial fluid CRP and a-defensin are highly accurate markers of PJI [1,5,6]; however, neither was included in this study. The reason for this was the lack of supportive data for either of those markers at the time this study was conceptualized in 2012.…”

“…The four synovial fluid biomarkers with the highest patient numbers evaluated for this purpose were CRP [5,6,13,15,16,18,20,21], IL-6 [4,6,[9][10][11][12]19], adefensin [1,5,6], and IL-1b [4,6,9,12], respectively. Although a-defensin clearly shows the highest diagnostic accuracy, it has only been evaluated in three studies to the date of our review, two of which emanate from the same group of researchers.…”

The Alpha-Defensin Immunoassay and Leukocyte Esterase Colorimetric Strip Test for the Diagnosis of Periprosthetic Infection

“…MSIS = Musculoskeletal Infection Society, PJI = periprosthetic joint infection, ESR = erythrocyte sedimentation rate, CRP = C-reactive protein, and WBC = white blood cell, and HPF = high-power field. Sensitivity and specificity of alpha-defensin in the diagnosis of PJI, according to Deirmengian et al 17 , Deirmengian et al 27 , Bingham et al 26 , and…”

“…here were 10 articles reporting 11 evaluations 13,14,17,18,[26][27][28][29][30][31] that contributed to our estimates of diagnostic accuracy for both tests. Six studies explored the diagnostic accuracy of alpha-defensin for PJI 13,17,[26][27][28]31 , while the remaining 5 studies explored the diagnostic accuracy of leukocyte esterase for PJI 14,17,18,29,30 .…”

CORR Insights®: The Alpha-defensin Test for Periprosthetic Joint Infection is Not Affected by Prior Antibiotic Administration

“…In 2014, Deirmengian et al [3] published the evolving use of biomarkers for the investigation of patients with potential PJI. Synovial alpha defensin 1 is one such biomarker that shows accurate results, with nearly 100% sensitivity and specificity [1,2,4].…”