Published 6/1/2015
Jennie McKee

Expert Explores Advances in Diagnosing PJI

Recent research has focused on synovial biomarkers

Periprosthetic joint infection (PJI) is one of the most dreaded complications of total joint arthroplasty,” noted Javad Parvizi, MD, FRCS. The problem is compounded, he said, because as yet, no single test delivers “a reliable, expeditious, and accurate PJI diagnosis.”

But recent studies on using synovial biomarkers to diagnose PJI have shown encouraging results. Dr. Parvizi explored some of the latest research on synovial biomarkers and PJI diagnosis during the 2015 Knee Society/American Association of Hip and Knee Surgeons Specialty Day, noting that “the future holds promise for orthopaedic surgeons as molecular biology and molecular genetics continue to evolve.”

A difficult diagnosis
According to Dr. Parvizi, the organisms that can infect a prosthetic joint often exist in the form of biofilm.

“Thus,” he said, “they can evade the usual diagnostic methods that rely on isolation of planktonic organisms. In addition, some of the organisms causing PJI are capable of crossing the cellular membrane and taking refuge inside the cytoplasmic space. Hence, their detection becomes extremely difficult using conventional methods for diagnosis of infection, such as taking a culture. Similarly, one cannot look at radiographs and determine whether an infection is present.”

In their efforts to find an optimal strategy for diagnosing PJI, researchers have focused on a wide variety of standard laboratory tests, including the following:

    • erythrocyte sedimentation rate (ESR)

    • serum C-reactive protein (CRP)

    • synovial fluid leukocyte count and leukocyte differential

    • radiologic tests not specifically developed for the diagnosis of PJI

“As a result, the optimal thresholds for these tests and the accuracy of each test for diagnosis of PJI have varied widely, failing to provide a direct, unambiguous method for practicing orthopaedic surgeons to diagnose PJI,” stated Dr. Parvizi. He noted that the Musculoskeletal Infection Society (MSIS) defines PJI as follows in its Proceedings of the International Consensus Meeting (ICM) on Periprosthetic Joint Infection, 2013:

  • two positive periprosthetic cultures with phenotypically identical organisms, or
  • a sinus tract communicating with the joint, or
  • having three of the following minor criteria:
  • elevated serum CRP and ESR counts
  • elevated synovial fluid white blood cell (WBC) count or positive change on leukocyte esterase test strip
  • elevated synovial fluid polymorphonuclear neutrophil (PMN) percentage
  • positive histologic analysis of periprosthetic tissue

A single positive culture
“The criteria introduced by the MSIS was recently endorsed and updated by the International Consensus Meeting on Periprosthetic Joint Infection (ICM) and has also been accepted by the Centers for Disease Control and Prevention (CDC) as the accepted definition of PJI,” said Dr. Parvizi. In addition, the ICM has proposed an algorithmic approach to diagnosing PJI (
Fig. 1) that is mostly based on the Clinical Practice Guidelines issued by the AAOS for diagnosing PJI of the hip and knee.

Synovial fluid biomarkers
In recent years, numerous investigators have evaluated the role of synovial fluid biomarkers that have the potential to enable rapid and accurate diagnosis of PJI.

“The literature has already demonstrated the promising capability of synovial fluid biomarkers to diagnose PJI,” Dr. Parvizi noted. These biomarkers, he explained, include inflammatory proteins such as cytokines, as well as proteins that are known to be intimately involved in the host response to a pathogen, such as antimicrobial peptides.

“Recently,” he continued, “synovial α-defensin (human neutrophil peptide) and synovial CRP have been identified as very accurate diagnostic biomarkers,” he said.

He noted that a study published in 2013 analyzed systemic and intra-articular levels of proinflammatory cytokines and antimicrobial peptides as diagnostic markers for PJI. The prospective, single-center, controlled clinical trial—which involved 20 control patients with aseptic loosening of total hip and knee replacements and 15 consecutive patients with Staphylococcal PJIs—found significantly elevated levels of the antimicrobial peptides HBD-3 and LL-37 in joint aspirates from patients with PJI, compared with patients with aseptic loosening. The authors concluded that the study “showed promising results for the use of antimicrobial peptides and other biomarkers in synovial fluid for the diagnosis of periprosthetic joint infection.” The researchers also found that “analysis of the levels in synovial fluid was more accurate than analysis of serum.”

Dr. Parvizi also referenced his own 2014 study exploring the breadth of organisms that may cause a positive synovial fluid α-defensin test result as it relates to PJI. The study also evaluated the magnitude of the α-defensin result in terms of various pathogen characteristics.

The α-defensin test delivered consistent results, regardless of Gram stain type, organism type, virulence of the organism, or species. They recommended that the α-defensin test should be considered a “standard diagnostic tool” when evaluating PJI and that future research focus on using this test in specific clinical scenarios, such as immediately after surgery in severely immunocompromised patients.

“Based on studies from our institution and others, the specificity and sensitivity of α-defensin for diagnosis of PJI stands at 97 percent and 96 percent, respectively,” said Dr. Parvizi. He concluded by encouraging additional studies, noting that recent and future advances in the diagnosis of PJI “will no doubt serve the profession of orthopaedic surgery—and, more importantly—orthopaedic patients.”

Dr. Parvizi reports potential conflicts of interest. For more information, visit www.aaos.org/disclosure

Jennie McKee is a senior science writer for AAOS Now. She can be reached at mckee@aaos.org

Bottom Line

  • It can be challenging to diagnose PJI, as conventional methods are often not effective and optimal thresholds for tests such as ESR and CRP have varied widely.
  • The MSIS definition of PJI was recently endorsed and updated by the International Consensus Meeting on Periprosthetic Joint Infection and has also been accepted by the CDC. In addition, the AAOS has issued a Clinical Practice Guideline on preventing PJI in total hip and total knee arthroplasty patients.
  • Recent studies on using synovial biomarkers—such as synovial α-defensin and synovial CRP—to diagnose PJI have shown encouraging results.

Additional Information
Proceedings of the International Consensus Meeting on Periprosthetic Joint Infection


  1. Deirmengian C, Kardos K, Kilmartin P, Cameron A, Schiller K, Parvizi J. Combined measurement of synovial fluid α-Defensin and C-reactive protein levels: highly accurate for diagnosing periprosthetic joint infection. J Bone Joint Surg Am. 2014 Sep 3;96(17):1439-45. doi: 10.2106/JBJS.M.01316.
  2. Deirmengian C, Kardos K, Kilmartin P, Cameron A, Schiller K, Booth RE Jr, Parvizi J. The alpha-defensin test for periprosthetic joint infection outperforms the leukocyte esterase test strip. Clin Orthop Relat Res. 2015 Jan;473(1):198-203. doi: 10.1007/s11999-014-3722-7.
  3. Tischler EH, Cavanaugh PK, Parvizi J.Leukocyte esterase strip test: matched for musculoskeletal infection society criteria. J Bone Joint Surg Am. 2014 Nov 19;96(22):1917-20. doi: 10.2106/JBJS.M.01591.