Diagnosing periprosthetic joint infection (PJI) in the hip or knee can be challenging, as there is no definitive test to prove its presence or absence. Failure to diagnose PJI can result in delayed complications and increased patient morbidity. Identifying PJI frequently requires a range of diagnostic methods. This article discusses newer techniques available to diagnose this challenging problem.

The Musculoskeletal Infection Society developed diagnostic criteria in 2018 to address this conundrum of accurately detecting PJI. The diagnostic system has 97.7 percent sensitivity and 99.5 percent specificity.

Clinical evaluation of PJI starts with a history and physical. Wound drainage, erythema and swelling, and systemic symptoms such as fever and malaise may make the diagnosis straightforward. A high index of suspicion is critical. Imaging studies can be useful in detecting loosening or migration of components.

Lab tests, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), should be used in cases with increasing pain or concern of infection. If those are elevated, aspiration may be considered as a next step. Surgeons must be aware that CRP and ESR are not valuable in the initial postoperative period, as they peak early in the postoperative period and may not return to normal before 3 weeks. Also, some bacteria, including Cutibacterium acnes and coagulase-negative staphylococci, may not cause elevations in CRP. Other serum markers for infection, including D-dimer, interleukin-6, and procalcitonin, are available but have not gained wide acceptance.

Alpha-defensin appears to be the most promising synovial fluid marker for diagnosing PJI. Alpha-defensin is an antimicrobial peptide that is produced by neutrophils when in the presence of pathogens. It is produced by polymorphonuclear cells in the presence of infectious organisms but not in inflammatory diseases or crystalline arthropathy. It can be identified with an enzyme-linked immunosorbent assay (ELISA ) or with a lateral flow cassette. Lateral flow tests can reveal results within 10 minutes—quicker than ELISA, which can take 24 hours. The alpha-defensin test has sensitivities higher than 95 percent. The lateral flow test has lower specificity than ELISA. Alpha-defensin testing has several unique advantages. It appears to maintain its accuracy even after administration of antibiotics and can maintain accuracy with blood contamination. It is sensitive across a wide range of pathogens, including coagulase-negative staphylococci.

Synovasure^® is a commercially available battery of tests produced by Zimmer Biomet. The panel includes synovial fluid white blood cell count with differential; ELISA alpha-defensin; fluid culture; Synovasure microbial identification; and lactate, neutrophil elastase, and crystal analysis. As Carl Deirmengian, MD, the developer of the alpha-defensin test, has noted, this panel has “democratized” the diagnostic process so that orthopaedic surgeons have access to the full range of diagnostic tests available to identify PJI. He believes that the addition of artificial intelligence will further improve diagnostic accuracy.

Next-generation sequencing (NGS) is a new microbial diagnostic test that detects a range of nucleic acids in synovial fluid. The diagnostic sensitivity of NGS can exceed 90 percent, much higher than that of bacterial culture and other commonly used serologic markers. It may be useful in detecting mycoplasma and C. acnes and low-virulence staphylococcus and streptococcus organisms. It is not meant to be used as a standalone test.

Recently, a French company, BioMerieux, has developed the BioFire system and a joint infection panel that uses polymerase chain reaction testing of synovial fluid to detect common joint pathogens. The BioFire syndromic system isolates, amplifies, and detects microorganism DNA that causes symptoms. Using 0.2 ml synovial fluid, the system tests for 39 common joint pathogens, including methicillin-resistant Staphylococcus aureus and yeast. The results can be prepared in approximately 1 hour after testing of the sample. If the results are positive for one of the organisms in the panel, it may make it unnecessary to use broad-spectrum antibiotics while waiting 48 to 72 hours for cultures to grow. It is 92 percent sensitive and 98 percent specific, and its high negative predictive value can facilitate earlier discontinuation of unneeded antibiotic treatment. One limitation is that this panel does not include testing for coagulase-negative staphylococci or C. acnes. This technique is available in more than 2,200 labs in the United States and in most reference labs. It is important to specify on the lab request to use the BioFire PJI panel.

Intraoperative tissue and fluid cultures continue to have the highest sensitivity. Three to five samples should be submitted and held for as long as 14 days. Specific testing parameters should be requested for optimal culture of facultative anaerobes such as C. acnes. Although there is no one test other than a positive culture that is specific for infection, combining the panel with the clinical presentation of the patient has significantly increased the capability of clinicians to diagnose PJI.

Early diagnosis of PJI after total joint replacement maximizes the opportunity for successful treatment. A comprehensive approach can include clinical assessment, serologic testing, synovial fluid evaluation, radiologic evaluation, and microbiologic evaluation. There is no one gold standard for diagnosing PJI, but the introduction of faster, more reliable, and less invasive tests continues to improve orthopaedic surgeons’ ability to tackle PJI.

Thomas Fleeter, MD, MBA, FAAOS, is in private practice in Reston, Virginia, with Town Center Orthopaedics. He is a member of the AAOS Now Editorial Board and chair of the AAOS Committee on Professionalism.

 References

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3. Huang Z, Li W, Lee GC, et al: Metagenomic next-generation sequencing of synovial fluid demonstrates high accuracy in prosthetic joint infection diagnostics: mNGS for diagnosing PJI. Bone Joint Res 2020;9(7):440-9.
4. Schoenmakers JWA, de Boer R, Gard L, et al: First evaluation of a commercial multiplex PCR panel for rapid detection of pathogens associated with acute joint infections. J Bone Jt Infect 2023;8(1):45-50.
5. Esteban J, Salar-Vidal L, Schmitt BH, et al: Multicenter evaluation of the BioFire joint infection panel for the detection of bacteria, yeast, and AMR genes in synovial fluid samples. J Clin Microbiol 2023;61(11):e0035723.