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The Effectiveness of Metagenomic Next-Generation Sequencing in the Diagnosis of Prosthetic Joint Infection: A Systematic Review and Meta-Analysis

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Abstract
Background: A prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasties with poor prognosis. Identifying an accurate and prompt diagnostic method is particularly important for PJI. Recently, the diagnostic value of metagenomic next-generation sequencing (mNGS) in detecting PJI has attracted much attention, while the evidence of its accuracy is quite limited. Thus, this study aimed to evaluate the accuracy of mNGS for the diagnosis of PJI. Methods: We summarized published studies to identify the potential diagnostic value of mNGS for PJI patients by searching online databases using keywords such as “prosthetic joint infection”, “PJI”, and “metagenomic sequencing”. Ten of 380 studies with 955 patients in total were included. The included studies provided sufficient data for the completion of 2-by-2 tables. We calculated the sensitivity, specificity, and area under the SROC curve (AUC) to evaluate mNGS for PJI diagnosis. Results: We found that the pooled diagnostic sensitivity and specificity of mNGS for PJI were 0.93 (95% CI, 0.83 to 0.97) and 0.95 (95% CI, 0.92 to 0.97), respectively. Positive and negative likelihood ratios were 18.3 (95% CI, 10.9 to 30.6) and 0.07 (95% CI, 0.03 to 0.18), respectively. The area under the curve was 0.96 (95% CI, 0.93 to 0.97). Conclusion: Metagenomic next-generation sequencing displays high accuracy in the diagnosis of PJI, especially for culture-negative cases.
Publication
Frontiers in Cellular and Infection Microbiology
Date
2022-6-10
DOI
10.3389/fcimb.2022.875822
URL
https://www.frontiersin.org/articles/10.3389/fcimb.2022.875822/full
Notes

Summary:

Prosthetic joint infection (PJI) is a significant complication of joint implantation, leading to high costs and a negative impact on quality of life. The current diagnostic methods for PJI, such as blood tests and microbial culture, have limitations in accuracy and reliability. Metagenomic next-generation sequencing (mNGS) has emerged as a promising technology for pathogen detection. However, its diagnostic value for PJI is still uncertain, necessitating further research.

Materials and Methods: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic literature search was conducted to identify studies reporting on the use of mNGS for PJI diagnosis. The selected studies were assessed for quality using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool.

Results: The search process identified 380 articles, of which 10 studies met the inclusion criteria and were included in the meta-analysis. These studies involved a total of 955 patients and were published between 2018 and 2021. The pooled sensitivity and specificity of mNGS for PJI diagnosis were 0.93 and 0.95, respectively, with an AUC of 0.96. Subgroup analysis showed variations in sensitivity and specificity based on ethnicity and sample type.

Discussion: The findings indicate that mNGS has a high diagnostic accuracy for PJI, outperforming other sequencing assays and showing potential for culture-negative cases. The comparison with previous studies and subgroup analysis suggests the superiority of mNGS in PJI diagnosis. The main pathogens identified by mNGS were consistent with known causes of PJI, and the technology detected pathogens that were missed by culture. Likelihood ratios and post-test probabilities support the clinical applicability of mNGS in PJI diagnosis.

Conclusion: The results demonstrate that mNGS has a superior diagnostic accuracy, particularly for culture-negative cases. The findings provide valuable support for the diagnostic performance of mNGS and offer recommendations for clinicians in accurately diagnosing PJI and guiding treatment decisions. However, further large-scale studies are needed to validate these findings and confirm the clinical value of mNGS in PJI patients.

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Citation
1.
Tan J, Liu Y, Ehnert S, et al. The Effectiveness of Metagenomic Next-Generation Sequencing in the Diagnosis of Prosthetic Joint Infection: A Systematic Review and Meta-Analysis. Front Cell Infect Microbiol. 2022;12:875822.
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