Lan Wei,1,* Yali Yu,2,* Shaohua Wang,3 Guixiang Dong,2 Yanli Niu4 

1Zhengzhou Orthopaedic Hospital, Zhengzhou, People’s Republic of China; 2Department of Clinical Laboratory, Zhengzhou Orthopaedic Hospital, Zhengzhou, People’s Republic of China; 3Department of Joint Disease, Zhengzhou Orthopaedic Hospital, Zhengzhou, People’s Republic of China; 4School of Basic Medical Sciences, Henan University, Kaifeng, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yanli Niu, School of Basic Medical Sciences, Henan University, Kaifeng, People’s Republic of China, Email nyl0925@henu.edu.cn

Background: This study evaluated the applicability of histopathology, culture, and Metagenomic next-generation sequencing (mNGS) in diagnosing periprosthetic joint infection (PJI).
Methods: In this prospective trial, 215 consecutive patients with suspected knee PJI were enrolled. Tissue specimens were aseptically collected and processed for histopathological analysis, culture, and mNGS. PJI diagnosis was primarily based on the 2011 MSIS criteria, with reference to the 2018 ICM criteria for improved diagnostic accuracy. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) of each diagnostic method were calculated.
Results: Among 58 patients included in the final analysis, 38 were diagnosed with PJI and 20 without PJI. The mNGS assay demonstrated a sensitivity of 63.2% (95% CI: 53.6– 77.7%), specificity of 80.0% (75.7– 90.1%), PPV of 85.7% (76.4– 95.3%), NPV of 53.3% (44.6– 61.2%), PLR of 1.84 (1.22– 2.77), and NLR of 0.27 (0.10– 0.40). Culture showed higher specificity at 95.0% (84.6– 99.8%) and PPV at 96.5% (88.7– 99.7%), with sensitivity of 68.4% (58.2– 78.9%). Histopathology exhibited 52.6% sensitivity and perfect specificity (100%). The most commonly detected pathogens by both culture and mNGS were Staphylococcus aureus and coagulase-negative Staphylococci, which are frequently implicated in PJI.
Conclusion: mNGS shows promise as a complementary tool for diagnosing PJI, especially in culture-negative or atypical cases. However, it did not outperform conventional methods in accuracy. Its limitations-including a high false-positive rate, interpretive challenges, and lack of susceptibility data-warrant cautious use. Further large-scale studies are needed to define its role in clinical decision-making.

Keywords: periprosthetic joint infection, metagenomic next-generation sequencing, bacterial culture, histopathology, diagnosis