Comparative diagnostic accuracy of next-generation sequencing in different specimen types for periprosthetic joint

Lina Wang1, Shangxiang Feng2, Zhongyuan Zhao2

  • 1Department of Infectious Diseases, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

Abstract

Insights

Next-generation sequencing (NGS) of implant sonicate fluid shows high sensitivity for diagnosing periprosthetic joint infection (PJI), while periprosthetic tissue NGS offers excellent specificity. Both methods are valuable for PJI diagnosis, with careful consideration of trade-offs.

Area of Science:

  • Orthopedic Surgery
  • Infectious Diseases
  • Molecular Diagnostics

Background:

  • Diagnosing periprosthetic joint infection (PJI) is challenging due to inconsistent results from next-generation sequencing (NGS) across different sample types.
  • Synovial fluid, periprosthetic tissues, and implant sonicate fluid are commonly used for NGS-based PJI detection, but their comparative accuracy is not well-established.

Purpose of the Study:

  • To systematically review and meta-analyze the diagnostic accuracy of NGS for periprosthetic joint infection (PJI) using synovial fluid, periprosthetic tissues, and implant sonicate fluid.
  • To compare the sensitivity, specificity, and overall diagnostic performance of these different sample types for PJI.

Main Methods:

  • Adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
  • Comprehensive literature search of PubMed, EMBASE, and Cochrane Library databases up to June 1, 2025.
  • Data extraction and quality assessment using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool; estimation of pooled sensitivity, specificity, and area under the summary receiver operating characteristic curve (AUC) for each specimen type.

Main Results:

  • Eighteen studies were included in the meta-analysis.
  • Pooled sensitivities for NGS were: sonicate fluid (0.89), synovial fluid (0.86), and periprosthetic tissue (0.86).
  • Pooled specificities were: periprosthetic tissue (0.98), sonicate fluid (0.96), and synovial fluid (0.94). Areas under the SROC curves (AUCs) were comparable across all specimen types (0.93-0.96), with no statistically significant differences.

Conclusions:

  • Next-generation sequencing (NGS) of implant sonicate fluid offers the highest sensitivity for periprosthetic joint infection (PJI) diagnosis, while periprosthetic tissue NGS provides exceptional specificity.
  • All tested specimen types (synovial fluid, periprosthetic tissue, sonicate fluid) demonstrate clinically useful diagnostic accuracy (AUC values).
  • Specimen selection for NGS in PJI diagnosis requires careful consideration of the sensitivity-specificity trade-off and validation of clinical utility, given the lack of a perfect gold standard and potential for false positives.