Abstract
PURPOSE: Discrepancies in next-generation sequencing (NGS) results across synovial fluid, periprosthetic tissues and implant sonicate fluid pose a significant clinical challenge in diagnosing periprosthetic joint infection (PJI). We conducted a systematic review and meta-analysis to compare the diagnostic accuracy of these NGS sample types for PJI. METHODS: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive literature search was conducted in PubMed, EMBASE and the Cochrane Library databases from inception to 1 June 2025. Two independent reviewers performed data extraction and assessed study quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. For each specimen type, we estimated the pooled sensitivity and specificity, summary receiver operating characteristic (SROC) curve and the area under the SROC curve (AUC). RESULTS: Following screening, 18 studies were included. Pooled sensitivities of NGS for PJI diagnosis were as follows: synovial fluid 0.86 (95% confidence interval [CI]: 0.79-0.91), periprosthetic tissue 0.86 (95% CI: 0.69-0.95) and sonicate fluid 0.89 (95% CI: 0.77-0.95). Corresponding specificities were 0.94 (95% CI: 0.91-0.96), 0.98 (95% CI: 0.85-1.00) and 0.96 (95% CI: 0.91-0.98). AUCs were 0.93 (0.89-0.95), 0.96 (0.88-0.97) and 0.96 (0.88-0.97), respectively. Pairwise comparisons of AUCs showed no statistically significant differences (p > 0.05). CONCLUSIONS: This meta-analysis suggests that NGS of sonicate fluid demonstrates higher sensitivity compared to NGS of synovial fluid or periprosthetic tissue, while maintaining strong specificity, making it valuable for detecting infection. Periprosthetic tissue NGS demonstrated exceptional specificity and acceptable sensitivity, making it valuable for confirming infection. All specimens show clinically useful AUC values. Sonicate fluid shows promise, but specimen selection warrants careful consideration of the sensitivity-specificity trade-off in clinical practice and requires validation of clinical utility due to the absence of a perfect PJI diagnostic gold standard and the risk of false positives. LEVEL OF EVIDENCE: Level II.