# Utilization of cell-free DNA metagenomic analysis for early detection and microbial identification in prosthetic joint infections: a prospective cohort study in Korea

## TL;DR

This study shows that cell-free DNA in joint fluid can help detect prosthetic joint infections and identify bacteria, even after antibiotic use.

## Contribution

The study demonstrates the diagnostic potential of cfDNA metagenomic analysis in PJI, including detection in antibiotic-treated patients.

## Key findings

- cfDNA concentration was significantly higher in PJI patients compared to non-PJI patients.
- cfDNA sequencing detected pathogens in 65% of PJI cases, including those with prior antibiotic use.
- cfDNA results showed substantial agreement with synovial culture results.

## Abstract

Prosthetic joint infection (PJI) is a severe complication of hip or knee arthroplasty, often necessitating invasive intervention and posing a high risk of adverse outcomes. Early diagnosis and tailored antibiotic therapy are critical for the effective management of PJI. This study evaluated the utility of cell-free deoxyribonucleic acid (cfDNA) extracted from synovial fluid to diagnose PJI and identify the causative pathogens.

This prospective, single-center study included a PJI group consisting of patients with confirmed infections based on the European Bone and Joint Infection Society criteria and a non-PJI group comprising patients without suspected PJIs who underwent joint surgery or aspiration. Synovial fluid samples were collected from all patients, and various culture methods, including conventional synovial fluid, sonication, and tissue and blood cultures, were applied along with cfDNA analysis.

A total of 35 patients were included, with 20 diagnosed with PJI and 15 classified as non-PJI. The median cfDNA concentration in synovial fluid was significantly higher in the PJI group (4.560 ng/μl, interquartile range (IQR) [3.320–6.348]) compared with the non-PJI group (0.028 ng/μl, IQR [0.009–0.273]) (p < 0.001). The Youden index identified a cfDNA concentration ≥ 1.59 ng/μl as strong likelihood of PJI. Culture positivity rates in the PJI group were as follows: synovial culture (10/20, 50.0%), sonication culture (8/9, 88.9%), tissue culture (2/8, 25.0%), and blood culture (2/12, 16.7%). The bacterial detection rate of cfDNA was 65.0% (13/20).

cfDNA concentration was significantly higher in the PJI group, with synovial cultures showing substantial agreement. Additionally, cfDNA sequencing detected pathogens in patients who had received prior antibiotic therapy and identified multiple pathogens in polymicrobial infections. These findings highlight cfDNA analysis as a valuable diagnostic tool for PJI, with the potential to enhance current diagnostic approaches.