title: 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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  Level II, diagnostic study. See Instructions for Authors for a complete description of levels of evidence.
authors.affiliation: CD Diagnostics Inc, Lankenau Institute for Medical Research, 100 Lancaster Avenue, MOB 456, Wynnewood, PA, 19096, USA, carl.deirmengian@rothmaninstitute.com.
authors.forename: Carl
authors.initials: C
authors.lastname: Deirmengian
authors.forename: Keith
authors.initials: K
authors.lastname: Kardos
authors.forename: Patrick
authors.initials: P
authors.lastname: Kilmartin
authors.forename: Alexander
authors.initials: A
authors.lastname: Cameron
authors.forename: Kevin
authors.initials: K
authors.lastname: Schiller
authors.forename: Javad
authors.initials: J
authors.lastname: Parvizi
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023181:Antimicrobial Cationic Peptides / Q000032:analysis; D001170:Arthritis, Infectious / Q000175:diagnosis* / Q000382:microbiology; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects; D015415:Biomarkers / Q000032:analysis*; D001798:Blood Proteins / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis; D019544:Equipment Failure Analysis; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000032:analysis; D006622:Hip Prosthesis / Q000009:adverse effects*; D006801:Humans; D053582:Interleukin-1alpha / Q000032:analysis; D007593:Joint Instability / Q000209:etiology; D007720:Knee Prosthesis / Q000009:adverse effects*; D007781:Lactoferrin / Q000032:analysis; D019272:Leukocyte Elastase / Q000032:analysis; D000071068:Lipocalin-2; D054834:Lipocalins / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016459:Prosthesis-Related Infections / Q000175:diagnosis* / Q000209:etiology; D011518:Proto-Oncogene Proteins / Q000032:analysis; D012372:ROC Curve; D012680:Sensitivity and Specificity; D013582:Synovial Fluid / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D023084:alpha-Defensins / Q000032:analysis
chemical_list: D000209:Acute-Phase Proteins; D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D001798:Blood Proteins; D053582:Interleukin-1alpha; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D023084:alpha-Defensins; C021623:bactericidal permeability increasing protein; D016179:Granulocyte Colony-Stimulating Factor; D002097:C-Reactive Protein; D007781:Lactoferrin; D019272:Leukocyte Elastase