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Fig. 1 AP (A) and lateral (B) radiographs showing an infected TKA.(Reproduced from Krempec JA, Masonis JL, Fehring TK: Infection in Total Knee Arthroplasty in Glassman AH, Lachiewicz PF, Tanzer M (eds): Orthopaedic Knowledge Update: Hip and Knee Reconstruction 4, Rosemont, Ill., American Academy of Orthopaedic Surgeons, 2011, pp 201–215)

AAOS Now

Published 11/1/2011
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Javad Parvizi, MD, FRCS

A new definition for periprosthetic joint infection

By Javad Parvizi, MD, FRCS

Workgroup proposes a standard definition for universal adoption

Both the orthopaedic community and the surveillance authorities such as the Centers for Disease Control and Prevention (CDC) continue to be frustrated by the lack of a standard definition for periprosthetic joint infection (PJI). Interpretation of available literature is becoming increasingly difficult because centers and investigators use different—and at times conflicting—definitions for PJI.

To address this major issue, the Musculoskeletal Infection Society (MSIS) recently convened a workgroup to evaluate the available literature and propose a standard definition for PJI that can be universally adopted by all. The 21-member workgroup (See “Workgroup Members,” pg. 8) successfully achieved the objectives established by the MSIS. On Aug. 4, 2011, the workgroup voted on the final definition of PJI, which is outlined below. Three members of the CDC were also involved in the process and provided input in the development of the new definition.

The establishment of a standard definition will enable clinicians to be confident in their diagnosis and provide appropriate treatment. Additionally, adoption of this definition for research purposes will support consistency between studies and potentially improve the quality of the published body of evidence.

Defining PJI
Based on the proposed criteria, a definite diagnosis of PJI can be made when the following conditions are met:

  1. A sinus tract communicating with the prosthesis; or
  2. A pathogen is isolated by culture from two separate tissue or fluid samples obtained from the affected prosthetic joint; or
  3. Four of the following six criteria exist:
    1. Elevated serum erythrocyte sedimentation rate (ESR) or serum C-reactive protein (CRP) concentration
    2. Elevated synovial white blood cell (WBC) count
    3. Elevated synovial neutrophil percentage (PMN%)
    4. Presence of purulence in the affected joint
    5. Isolation of a microorganism in one culture of periprosthetic tissue or fluid
    6. Greater than five neutrophils per high-power field in five high-power fields observed from histologic analysis of periprosthetic tissue at 400 times magnification

However, it should be noted that PJI may be present even if fewer than four of these criteria are met.

Considerations
Microbiologic testing
—Tissue for culture must be obtained from representative periprosthetic tissue or fluid. To limit the risk of contamination, each sample should be taken with separate, sterile instruments. The definition of phenotypically identical organisms should be based on phenotypic similarities and in vitro antimicrobial susceptibility testing because confirmation of genetic identity is not routinely performed on clinical isolates.

At least three—and no more than five—periprosthetic specimen culture samples should be taken and incubated in both aerobic and anaerobic environments. Fungal and mycobacterial cultures should not be done routinely, but should be reserved for higher risk scenarios. The time of culture incubation has not yet been standardized.

Isolation of a single low virulent pathogen such as coagulase negative Staphylococcus, Propionibacterium acnes, or Corynebacterium in the absence of other criteria is not believed to represent a definite infection. Isolation of a single virulent organism such as S. aureus may represent a PJI. Furthermore, recent evidence has identified that certain tests, such as Gram stain of periprosthetic tissue or fluid, are not sensitive in diagnosing PJI.

Serum tests—Based on previous publications, an ESR of greater than 30 mm/h and CRP greater than10 mg/L would represent elevated levels. However, it is important to note that there are variations in measuring these markers among laboratories. Furthermore, the level of these serum markers is affected by the age, gender, and medical comorbidities of the patient. It has also been reported that these markers can be elevated for approximately 30 to 60 days in the immediate postoperative period.

Synovial tests—Multiple studies have provided thresholds for synovial WBC count and PMN%. Reports of synovial WBC counts in the chronically infected knee arthroplasty have ranged from 1,100 to 4,000 cells/µL, with PMN% ranging from 64 percent to 69 per-cent. In patients with acute infections, the level of synovial WBC count and PMN% are much higher (approximately 20,000 cells/μL and 89 percent, respectively). Acute infections are those that occurred less than 3 months from the index surgery or the onset of symptoms.

The level of synovial WBC count and PMN% in the infected hip arthroplasty is not well delineated. A single study has provided a threshold of 3,000 cells/µL for leukocytes and 80 percent for PMN% for the infected hip arthroplasty.

Patients with underlying inflammatory arthropathies and related diseases, however, have not been included in any studies on infected hip or knee arthroplasties. Current research is proceeding to provide more definitive thresholds for all patients.

Histology—Examination of periprosthetic tissues for evidence of neutrophils has been traditionally conducted by specially trained musculoskeletal pathologists. Consequently, histologic examination may be operator dependent. It is, therefore, incumbent on the surgeon to ensure that the pathologist agrees with the diagnostic criteria for periprosthetic infection.

When examining for the presence of neutrophils, the histopathologist should disregard neutrophils entrapped in superficial fibrin or adherent to endothelium or small veins. Also, caution should be exercised in analyzing this test in patients who might be expected to have elevated neutrophil counts, such as those with recent periprosthetic fractures or inflammatory arthropathy.

Future developments
This proposed definition was based on evidence supporting the role of various diagnostic tests for PJI that are available according to the literature. Numerous other tests—including the measurement of CRP from the synovial fluid, synovial leukocyte esterase, sonication of explanted prosthetics, and molecular techniques such as polymerase chain reaction and other molecular markers such as interleukin-6—are currently under evaluation.

Disclosure information: Dr. Parvizi— Biomet; Covidien; National Institutes of Health (National Institute of Arthritis and Musculoskeletal and Skin Diseases[NIAMS] and National Institute of Child Health and Human Development [NICHD]); Salient Surgical; Smith & Nephew; Stryker; TissueGene; Zimmer; 3M; Musculoskeletal Transplant Foundation; Saunders/Mosby-Elsevier; SLACK Incorporated; Wolters Kluwer Health - Lippincott Williams & Wilkins; CD Diagnostics; SmartTech; United Healthcare

Javad Parvizi, MD, FRCS, served on the workgroup to develop a new definition of periprosthetic joint infection. He is professor of orthopaedic surgery and director of research at Jefferson Medical College in Philadelphia.

Workgroup members

Name

Affiliation

Thomas W. Bauer, MD

Department of Pathology, Cleveland Clinic, Cleveland, Ohio

Elie F. Berbari, MD

Department of Infectious Diseases, Mayo Clinic, Rochester, Minn.

Robert L. Barrack, MD

Department of Orthopaedics, Washington University, St Louis

Keith R. Berend, MD

Joint Implant Surgeons, New Albany, Ohio

Craig J. Della Valle, MD

Rush Presbyterian Hospital, Chicago

John L. Esterhai Jr, MD

Department of Orthopaedics, University of Pennsylvania, Philadelphia

Thomas K. Fehring, MD

OrthoCarolina, Charlotte, N.C.

Kevin L. Garvin, MD

Department of Orthopaedics, University of Nebraska

Terence J. Gioe, MD

Department of Orthopaedics, Minneapolis VAMC, Minneapolis

Steven M. Kurtz, PhD

Exponent, University of Drexel, Philadelphia

Bassam A. Masri, MD

Department of Orthopaedics, University of Vancouver, Vancouver, Canada

Michael A. Mont, MD

Rubin Institute, Baltimore, Md.

Arvind D. Nana, MD

Health Sciences Center, Fort Worth, Texas

Douglas R. Osmon, MD

Department of Infectious Disease, Mayo Clinic, Rochester, Minn.

Javad Parvizi, MD, FRCS

The Rothman Institute at Thomas Jefferson University, Philadelphia

John Segreti, MD

Rush Presbyterian Hospital, Chicago

Mark J. Spangehl, MD

Department of Orthopaedics, Mayo Clinic, Scottsdale, Ariz.

Bryan D. Springer, MD

Ortho Carolina, Charlotte, N.C.

Montri D. Wongworawat, MD

Department of Orthopaedics, Loma Linda University, Loma Linda, Calif.

Charalampos G. Zalavras, MD

Department of Orthopaedics, University of Southern California, Los Angeles

Benjamin Zmistowski, BS

The Rothman Institute at Thomas Jefferson University, Philadelphia

References:

  1. Bedair H, Ting N, Jacovides C, et al: The Mark Coventry Award: Diagnosis of early postoperative TKA infection using synovial fluid analysis. Clin Orthop Relat Res 2010;469(1):34-40. Available at: http://www.ncbi.nlm.nih.gov.proxy1.lib.tju.edu:2048/pubmed/20585914 [Accessed August 30, 2010].
  2. Berbari E, Mabry T, Tsaras G, et al: Inflammatory blood laboratory levels as markers of prosthetic joint infection: A systematic review and meta-analysis. J Bone Joint Surg Am 2010;92(11):2102-2109.
  3. Bilgen O, Atici T, Durak K, Karaeminoğullari, Bilgen MS: C-reactive protein values and erythrocyte sedimentation rates after total hip and total knee arthroplasty. J. Int Med Res 2001;29(1):7-12.
  4. 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(9):1921-1927.
  5. Deirmengian C, Hallab N, Tarabishy A, et al: Synovial fluid biomarkers for periprosthetic infection. Clin Orthop Relat Res 2010;468(8):2017-2023.
  6. 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(6 Suppl 2):90-93.
  7. Ghanem E, Ketonis C, Restrepo C, Joshi A, Barrack R, Parvizi J: Periprosthetic infection: Where do we stand with regard to Gram stain? Acta Orthop 2009;80(1):37-40.
  8. Ghanem E, Parvizi J, Burnett RS, et al: Cell count and differential of aspirated fluid in the diagnosis of infection at the site of total knee arthroplasty. J Bone Joint Surg Am 2008;90(8):1637-1643.
  9. Larsson S, Thelander U, Friberg S. C-reactive protein (CRP) levels after elective orthopedic surgery. Clin Orthop Relat Res 1992;(275):237-242.
  10. Mariani BD, Martin DS, Levine MJ, Booth RE Jr, Tuan RS: The Coventry Award: Polymerase chain reaction detection of bacterial infection in total knee arthroplasty. Clin Orthop Relat Res 1996;(331):11-22.
  11. 11. Parvizi J, Ghanem E, Menashe S, Barrack RL, Bauer TW: Periprosthetic infection: What are the dianostic challenges? J Bone Joint Surg Am 2006;88 Suppl 4:138-147.
  12. Parvizi J, Jacovides C, Adeli B, Jung KA, Hozack WJ: Mark B. Coventry Award: Synovial C-reactive Protein: A Prospective Evaluation of a Molecular Marker for Periprosthetic Knee Joint Infection. Clin Orthop Relat Res 2011. Available at http://www.ncbi.nlm.nih.gov/pubmed/21786056 [Accessed August 11, 2011].
  13. Parvizi J, Azzam K, Jacovides C, Antoci V, Ghanem E. Diagnosis of Periprosthetic Joint Infection: The Role of a Simple, yet Unrecognized, Enzyme. Academy of Orthopaedic Surgeons AAOS, New Orleans, LA, March 10-13, 2010.
  14. Parvizi J, Jacovides C, Zmistowski B, Jung KA: Definition of periprosthetic joint infection: Is there a consensus? Clin Orthop Relat Res 2011;469(11):3022-3030. Available at http://www.ncbi.nlm.nih.gov/pubmed/21751038 [Accessed July 14, 2011].
  15. 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(9):1869-1875.
  16. Trampuz A, Hanssen AD, Osmon DR, Mandrekar J, Steckelberg JM, Patel R: Synovial fluid leukocyte count and differential for the diagnosis of prosthetic knee infection. Am J Med 2004;117(8):556-562.
  17. Trampuz A, Piper KE, Jacobson MJ, et al:. Sonication of removed hip and knee prostheses for diagnosis of infection. N Engl J Med 2007;357(7):654-663.