Which Combination is the Best? A Comparison of the Predictive Potential of Serum Biomarker Combinations to Diagnose Periprosthetic Joint Infection

Background: Without a gold-standard test, recent periprosthetic joint infections (PJI) literature has explored the utility of combining serological results, with promising findings. However, previous studies evaluated fewer than 200 patients and often studied only 1 to 2 test combinations. The purpose of this study was to accumulate a large single-institution cohort of revision total joint arthroplasty (rTJA) patients to determine the diagnostic utility of combination serum biomarkers to identify PJI. Methods: A single institution longitudinal database was assessed to identify all patients who underwent rTJA from 2017 to 2020. There were 1,363 rTJA patients (715 rTKA patients and 648 rTHA patients) including 273 PJI cases (20%) analyzed. The PJI was diagnosed post-rTJA utilizing 2011 Musculoskeletal Infection Society (MSIS) criteria. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-dimer, and interleukin 6 (IL-6) were systematically collected for all patients. Results: The rTKA combination markers of CRP thorn ESR (sensitivity: 78.3%, specificity: 88.8%, positive predictive value (PPV): 70.0%, negative predictive value (NPV): 92.5%), CRP thorn D-dimer (sensitivity: 60.5%, specificity: 92.6%, PPV: 63.4%, NPV: 91.7%), and CRP thorn IL-6 (sensitivity: 38.5%, specificity: 100.0%, PPV: 100.0%, NPV: 92.9%) all yielded higher specificity than CRP alone (sensitivity: 94.4%, specificity: 75.0%, PPV: 55.5%, NPV: 97.6%). Similarly, the rTHA combination markers of CRP thorn ESR (sensitivity: 70.1%, specificity: 88.8%, PPV: 58.1%, NPV: 93.1%), CRP thorn D-dimer (sensitivity: 57.1%, specificity: 90.1%, PPV: 43.2%, NPV: 94.1%), and CRP thorn IL-6 (sensitivity: 21.4%, specificity: 98.4%, PPV: 60.0%, NPV: 91.7%) all yielded higher specificity than CRP alone (sensitivity: 84.7%, specificity: 77.5%, PPV: 45.4%, NPV: 95.8%). Conclusion: Overall, in diagnosing PJI for both rTKA and rTHA, 2-marker combinations yielded higher specificity, while 3-marker combinations yielded higher sensitivity compared to CRP alone. However, compared to all 2-marker and 3-marker combinations, CRP demonstrated superior overall diagnostic utility. These findings suggest that routine combination testing of markers for PJI diagnosis may be excessive and an unnecessary use of resources, especially in resource-limited situations. (c) 2023 Elsevier Inc. All rights reserved.

Automated summary

By studying a large cohort of patients who underwent joint replacement surgery, it was found that combination testing of serum biomarkers can improve the specificity and sensitivity of infection diagnosis. However, compared to single markers, C-reactive protein (CRP) demonstrated superior diagnostic utility.