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Published in: Clinical Orthopaedics and Related Research® 8/2010

01-08-2010 | Symposium: Papers Presented at the 2009 Meeting of the Musculoskeletal Infection Society

Synovial Fluid Biomarkers for Periprosthetic Infection

Authors: Carl Deirmengian, MD, Nadim Hallab, PhD, Abdul Tarabishy, MD, Craig Della Valle, MD, Joshua J. Jacobs, Jess Lonner, MD, Robert E. Booth Jr, MD

Published in: Clinical Orthopaedics and Related Research® | Issue 8/2010

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Abstract

Background

We have previously described a unique gene expression signature exhibited by synovial fluid leukocytes in response to bacterial infection, identifying a number of potential biomarkers for infection. However, the diagnostic performance of these potential biomarkers in an immunoassay format is unknown.

Questions/purposes

We therefore evaluated the sensitivity, specificity, and accuracy of several potential synovial fluid biomarkers for infection, and compared them to current standards of testing for periprosthetic infection.

Methods

We prospectively collected synovial fluid from 14 patients classified as having a periprosthetic infection and 37 patients classified as having an aseptic failure. The synovial fluid samples were tested for 23 potential biomarkers for periprosthetic infection. We then determined differences in biomarker levels between infected and aseptic groups, then computed the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for select biomarkers, and finally compared those to current standard tests for infection.

Results

Twelve synovial fluid biomarkers had substantially higher average levels in the synovial fluid of infected versus aseptic patients. Synovial fluid levels of IL-1 were a mean of 258 times higher in patients with a periprosthetic infection compared to patients having revision for aseptic diagnoses. Synovial fluid IL-1 and IL-6 levels correctly classified all patients in this study with a sensitivity, specificity, positive predictive value, negative predictive value and accuracy equal to 1. Several markers tested in this study outperformed the ESR and CRP tests.

Conclusions

Patients with a periprosthetic infection have elevated levels of numerous synovial fluid biomarkers, when compared to patients with aseptic diagnoses. Several of these biomarkers exhibited nearly ideal sensitivity, specificity, and accuracy in this study, suggesting that synovial fluid biomarkers could be a valuable tool for diagnosing periprosthetic infection.

Level of Evidence

Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.
Literature
1.
go back to reference Archibeck MJ, Rosenberg AG, Sheinkop MB, Berger RA, Jacobs JJ. Gout-induced arthropathy after total knee arthroplasty: a report of two cases. Clin Orthop Relat Res. 2001;392:377–382.CrossRefPubMed Archibeck MJ, Rosenberg AG, Sheinkop MB, Berger RA, Jacobs JJ. Gout-induced arthropathy after total knee arthroplasty: a report of two cases. Clin Orthop Relat Res. 2001;392:377–382.CrossRefPubMed
2.
go back to reference Atkins BL, Athanasou N, Deeks JJ, Crook DW, Simpson H, Peto TE, McLardy-Smith P, Berendt AR. Prospective evaluation of criteria for microbiological diagnosis of prosthetic-joint infection at revision arthroplasty. The OSIRIS Collaborative Study Group. J Clin Microbiol. 1998;36:2932–2939.PubMed Atkins BL, Athanasou N, Deeks JJ, Crook DW, Simpson H, Peto TE, McLardy-Smith P, Berendt AR. Prospective evaluation of criteria for microbiological diagnosis of prosthetic-joint infection at revision arthroplasty. The OSIRIS Collaborative Study Group. J Clin Microbiol. 1998;36:2932–2939.PubMed
3.
go back to reference Austin MS, Ghanem E, Joshi A, Lindsay A, Parvizi J. A simple, cost-effective screening protocol to rule out periprosthetic infection. J Arthroplasty. 2008;23:65–68.CrossRefPubMed Austin MS, Ghanem E, Joshi A, Lindsay A, Parvizi J. A simple, cost-effective screening protocol to rule out periprosthetic infection. J Arthroplasty. 2008;23:65–68.CrossRefPubMed
4.
go back to reference Bare J, MacDonald SJ, Bourne RB. Preoperative evaluations in revision total knee arthroplasty. Clin Orthop Relat Res. 2006;446:40–44.CrossRefPubMed Bare J, MacDonald SJ, Bourne RB. Preoperative evaluations in revision total knee arthroplasty. Clin Orthop Relat Res. 2006;446:40–44.CrossRefPubMed
5.
go back to reference Bozic KJ, Kurtz SM, Lau E, Ong K, Chiu V, Vail TP, Rubash HE, Berry DJ. The epidemiology of revision total knee arthroplasty in the United States. Clin Orthop Relat Res. 2010;468:45–51.CrossRefPubMed Bozic KJ, Kurtz SM, Lau E, Ong K, Chiu V, Vail TP, Rubash HE, Berry DJ. The epidemiology of revision total knee arthroplasty in the United States. Clin Orthop Relat Res. 2010;468:45–51.CrossRefPubMed
6.
go back to reference Bozic KJ, Kurtz SM, Lau E, Ong K, Vail TP, Berry DJ. The epidemiology of revision total hip arthroplasty in the United States. J Bone Joint Surg Am. 2009;91:128–133.CrossRefPubMed Bozic KJ, Kurtz SM, Lau E, Ong K, Vail TP, Berry DJ. The epidemiology of revision total hip arthroplasty in the United States. J Bone Joint Surg Am. 2009;91:128–133.CrossRefPubMed
7.
go back to reference Deirmengian C, Lonner JH, Booth RE, Jr. The Mark Coventry Award: white blood cell gene expression: a new approach toward the study and diagnosis of infection. Clin Orthop Relat Res. 2005;440:38–44.CrossRefPubMed Deirmengian C, Lonner JH, Booth RE, Jr. The Mark Coventry Award: white blood cell gene expression: a new approach toward the study and diagnosis of infection. Clin Orthop Relat Res. 2005;440:38–44.CrossRefPubMed
8.
go back to reference Del Pozo JL, Patel R. Clinical practice. Infection associated with prosthetic joints. N Engl J Med. 2009;361:787–794.CrossRefPubMed Del Pozo JL, Patel R. Clinical practice. Infection associated with prosthetic joints. N Engl J Med. 2009;361:787–794.CrossRefPubMed
9.
go back to reference Della Valle CJ, Sporer SM, Jacobs JJ, Berger RA, Rosenberg AG, Paprosky WG. Preoperative testing for sepsis before revision total knee arthroplasty. J Arthroplasty. 2007;22:90–93.CrossRefPubMed Della Valle CJ, Sporer SM, Jacobs JJ, Berger RA, Rosenberg AG, Paprosky WG. Preoperative testing for sepsis before revision total knee arthroplasty. J Arthroplasty. 2007;22:90–93.CrossRefPubMed
10.
go back to reference Di Cesare PE, Chang E, Preston CF, Liu CJ. Serum interleukin-6 as a marker of periprosthetic infection following total hip and knee arthroplasty. J Bone Joint Surg Am. 2005;87:1921–1927.CrossRefPubMed Di Cesare PE, Chang E, Preston CF, Liu CJ. Serum interleukin-6 as a marker of periprosthetic infection following total hip and knee arthroplasty. J Bone Joint Surg Am. 2005;87:1921–1927.CrossRefPubMed
11.
go back to reference Kobayashi N, Inaba Y, Choe H, Iwamoto N, Ishida T, Yukizawa Y, Aoki C, Ike H, Saito T. Rapid and sensitive detection of methicillin-resistant Staphylococcus periprosthetic infections using real-time polymerase chain reaction. Diagn Microbiol Infect Dis. 2009;64:172–176.CrossRefPubMed Kobayashi N, Inaba Y, Choe H, Iwamoto N, Ishida T, Yukizawa Y, Aoki C, Ike H, Saito T. Rapid and sensitive detection of methicillin-resistant Staphylococcus periprosthetic infections using real-time polymerase chain reaction. Diagn Microbiol Infect Dis. 2009;64:172–176.CrossRefPubMed
12.
go back to reference Kobayashi N, Procop GW, Krebs V, Kobayashi H, Bauer TW. Molecular identification of bacteria from aseptically loose implants. Clin Orthop Relat Res. 2008;466:1716–1725.CrossRefPubMed Kobayashi N, Procop GW, Krebs V, Kobayashi H, Bauer TW. Molecular identification of bacteria from aseptically loose implants. Clin Orthop Relat Res. 2008;466:1716–1725.CrossRefPubMed
13.
go back to reference Muller M, Morawietz L, Hasart O, Strube P, Perka C, Tohtz S. Diagnosis of periprosthetic infection following total hip arthroplasty—evaluation of the diagnostic values of pre- and intraoperative parameters and the associated strategy to preoperatively select patients with a high probability of joint infection. J Orthop Surg. 2008;3:31.CrossRef Muller M, Morawietz L, Hasart O, Strube P, Perka C, Tohtz S. Diagnosis of periprosthetic infection following total hip arthroplasty—evaluation of the diagnostic values of pre- and intraoperative parameters and the associated strategy to preoperatively select patients with a high probability of joint infection. J Orthop Surg. 2008;3:31.CrossRef
14.
go back to reference Parvizi J, Ghanem E, Sharkey P, Aggarwal A, Burnett RS, Barrack RL. Diagnosis of infected total knee: findings of a multicenter database. Clin Orthop Relat Res. 2008;466:2628–2633.CrossRefPubMed Parvizi J, Ghanem E, Sharkey P, Aggarwal A, Burnett RS, Barrack RL. Diagnosis of infected total knee: findings of a multicenter database. Clin Orthop Relat Res. 2008;466:2628–2633.CrossRefPubMed
15.
go back to reference Savarino L, Tigani D, Baldini N, Bochicchio V, Giunti A. Pre-operative diagnosis of infection in total knee arthroplasty: an algorithm. Knee Surg Sports Traumatol Arthrosc. 2009;17:667–675.CrossRefPubMed Savarino L, Tigani D, Baldini N, Bochicchio V, Giunti A. Pre-operative diagnosis of infection in total knee arthroplasty: an algorithm. Knee Surg Sports Traumatol Arthrosc. 2009;17:667–675.CrossRefPubMed
16.
go back to reference Schinsky MF, Della Valle CJ, Sporer SM, Paprosky WG. Perioperative testing for joint infection in patients undergoing revision total hip arthroplasty. J Bone Joint Surg Am. 2008;90:1869–1875.CrossRefPubMed Schinsky MF, Della Valle CJ, Sporer SM, Paprosky WG. Perioperative testing for joint infection in patients undergoing revision total hip arthroplasty. J Bone Joint Surg Am. 2008;90:1869–1875.CrossRefPubMed
17.
go back to reference Stoodley P, Kathju S, Hu FZ, Erdos G, Levenson JE, Mehta N, Dice B, Johnson S, Hall-Stoodley L, Nistico L, Sotereanos N, Sewecke J, Post JC, Ehrlich GD. Molecular and imaging techniques for bacterial biofilms in joint arthroplasty infections. Clin Orthop Relat Res. 2005;437:31–40.CrossRefPubMed Stoodley P, Kathju S, Hu FZ, Erdos G, Levenson JE, Mehta N, Dice B, Johnson S, Hall-Stoodley L, Nistico L, Sotereanos N, Sewecke J, Post JC, Ehrlich GD. Molecular and imaging techniques for bacterial biofilms in joint arthroplasty infections. Clin Orthop Relat Res. 2005;437:31–40.CrossRefPubMed
18.
go back to reference Tarkin IS, Henry TJ, Fey PI, Iwen PC, Hinrichs SH, Garvin KL. PCR rapidly detects methicillin-resistant staphylococci periprosthetic infection. Clin Orthop Relat Res. 2003;414:89–94.CrossRefPubMed Tarkin IS, Henry TJ, Fey PI, Iwen PC, Hinrichs SH, Garvin KL. PCR rapidly detects methicillin-resistant staphylococci periprosthetic infection. Clin Orthop Relat Res. 2003;414:89–94.CrossRefPubMed
19.
go back to reference Trampuz A, Piper KE, Jacobson MJ, Hanssen AD, Unni KK, Osmon DR, Mandrekar JN, Cockerill FR, Steckelberg JM, Greenleaf JF, Patel R. Sonication of removed hip and knee prostheses for diagnosis of infection. N Engl J Med. 2007;357:654–663.CrossRefPubMed Trampuz A, Piper KE, Jacobson MJ, Hanssen AD, Unni KK, Osmon DR, Mandrekar JN, Cockerill FR, Steckelberg JM, Greenleaf JF, Patel R. Sonication of removed hip and knee prostheses for diagnosis of infection. N Engl J Med. 2007;357:654–663.CrossRefPubMed
20.
go back to reference Tunney MM, Patrick S, Curran MD, Ramage G, Hanna D, Nixon JR, Gorman SP, Davis RI, Anderson N. Detection of prosthetic hip infection at revision arthroplasty by immunofluorescence microscopy and PCR amplification of the bacterial 16S rRNA gene. J Clin Microbiol. 1999;37:3281–3290.PubMed Tunney MM, Patrick S, Curran MD, Ramage G, Hanna D, Nixon JR, Gorman SP, Davis RI, Anderson N. Detection of prosthetic hip infection at revision arthroplasty by immunofluorescence microscopy and PCR amplification of the bacterial 16S rRNA gene. J Clin Microbiol. 1999;37:3281–3290.PubMed
Metadata
Title
Synovial Fluid Biomarkers for Periprosthetic Infection
Authors
Carl Deirmengian, MD
Nadim Hallab, PhD
Abdul Tarabishy, MD
Craig Della Valle, MD
Joshua J. Jacobs
Jess Lonner, MD
Robert E. Booth Jr, MD
Publication date
01-08-2010
Publisher
Springer-Verlag
Published in
Clinical Orthopaedics and Related Research® / Issue 8/2010
Print ISSN: 0009-921X
Electronic ISSN: 1528-1132
DOI
https://doi.org/10.1007/s11999-010-1298-4

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