Impact of Antibiotic Exposure Duration on Pathogen Detection in Periprosthetic Joint Infection

Objective: Antibiotic exposure affects pathogen detection in periprosthetic joint infection (PJI). This study evaluated the impact of antibiotic duration before sampling on the diagnostic performance of microbiological cultures and metagenomic next-generation sequencing (mNGS). Methods: We conducted a retrospective analysis of 153 patients with PJI treated at our center between January 2013 and March 2024. Patients who had discontinued antibiotics for at least 7 days before sampling and those with no history of antibiotic use were classified into the antibiotic-withdrawal group (AWD group). Based on the duration of antibiotic exposure, those who received antibiotics for ≤ 7 days before sampling was assigned to the short-term antibiotic group (STA group), while those with > 7 days of continuous antibiotic use were included in the long-term antibiotic group (LTA group). By comparing microbiological culture and mNGS results across these groups, we analyzed how antibiotic duration before sampling affects etiological diagnosis in PJI patients. Results: In the AWD group, microbial culture positivity (86.3%, 44/51) was comparable to mNGS (92.2%, 47/51; P=0.338 ). However, mNGS demonstrated superior positivity rates in both the STA (86.7% vs 70.0%, P=0.027) and LTA groups (76.2% vs 54.8%, P=0.039). Prolonged antibiotic use (> 7 days) markedly reduced culture positivity (86.3% to 54.8%, P=0.001 ), whereas the decline in mNGS sensitivity was smaller (92.2% to 76.2%, P=0.032 ), indicating its greater resistance to antibiotic effects. Among culture-negative PJI cases, mNGS maintained robust diagnostic performance across all groups (CN-AWD: 57.1%; CN-STA: 66.7%; CN-LTA: 57.9%), with no significant differences observed. Conclusion: Antibiotic use before sampling significantly impacts PJI pathogen detection. We recommend either: (1) sampling after ≥ 7 days without antibiotics, or (2) for patients on prolonged antibiotics (> 7 days), combining microbial culture with routine mNGS to improve diagnostic accuracy. Keywords: periprosthetic joint infection, microbiological cultures, metagenomic next-generation sequencing, prior use of antibiotics, pathogen diagnosis