Multi-Sample Practice For Better Application Choice Of Untargeted Metagenomic Sequencing In Diagnosis Of Periprosthetic Joint Infections

Background:As a proven and comprehensive molecular technique,metagenomic next-generation sequencing(m NGS)has shown its bright prospect in periprosthetic joint infection(PJI)pathogen diagnosis through single specimen type.However,the optimal application approach of m NGS in PJIs has not been explored.This study aims to fully evaluate the diagnostic value of m NGS through multi-sample practice,and further seek for its better detection choice in PJIs.Method: In this prospective study,177 specimens were collected from 59 revision arthroplasties,which included periprosthetic tissues,synovial fluid and prosthetic sonicate fluid,for each case.Each specimen was reasonably divided into two copies:one for culture,and the other for m NGS.The diagnostic criteria of the Musculoskeletal Infection Society(MSIS)was adopted to define PJI(40 cases)and aseptic failure(19cases).Result:Overall,the sensitivity and specificity of m NGS in the PJI diagnosis was95%(95% confidence interval [CI],88% to 100%,85% of culture)and 94.7%(95%CI,84% to 100%,94.7% of culture)for all specimen types,respectively,65%(95%CI,50% to 80%,47.5% of culture)and 100%(100% of culture)for periprosthetic tissues,respectively,87.5%(95%CI,77% to 98%,65% of culture)and 94.7%(95%CI,84% to100%,100% of culture)for synovial fluid,respectively,and 92.5%(95%CI,84% to100%,85% of culture)and 94.7%(95%CI,84% to 100%,94.7% of culture)for prosthetic sonicate fluid.The diagnostic performance of m NGS was better in the PJIs with prior antibiotic and in the detection of difficult-to-detect pathogen.In the aspects of diagnostic sensitivity,pathogen detection rates(84.6%,95%CI,74% to 95%),sequencing reads(>10 folds)and genome coverage rate(>5 folds),m NGS of prosthetic sonicate fluid outperformed that of the other two specimen types.Conclusion:m NGS could serve as an accurate diagnostic tool in PJI pathogen detection for three distinct specimen types.Due to its superior detection performance,m NGS of prosthetic sonicate fluid provides the most value and may partly replace traditional tests in PJIs.