Discussion
PJIs, PJI, infections
INFECTIONS, COMPLICATION
PJI is a catastrophic complication following knee or hip arthroplasty, and microbial culture is considered the gold standard for pathogen identification and diagnosis. However, due to preoperative antimicrobial therapy, the presence of biofilms and fastidious bacteria, the positivity rate has been low (A total of 131 PJIs were included in this study. There were 115 patients with positive mNGS results and 91 patients with positive cultures. The positivity rate of mNGS in synovial fluid (87.8%) is significantly higher than in synovial fluid (50.4%) or deep tissue (61.8%) or the combination of two sources (69.5%). Compared with all cultures from all sources (synovial fluid and deep tissue), synovial fluid mNGS identified identical pathogens in 90.1% (82/91) of culture-positive PJIs, with additional potential pathogens detected in 15.4% (14/91). Meanwhile, new potential pathogens were detected in 70.0% (28/40) of culture-negative PJIs, demonstrating its usefulness in difficult-to-diagnose infections. In our institution, antibiotics were not commonly used in patients with suspected PJI prior to aetiological testing, and vancomycin was used empirically only when PJI was confirmed and the pathogen was unclear. However, 9/26 potential pathogens detected by mNGS in the 40 culture-negative PJIs were not covered by vancomycin. This may be one of the main reasons for the failure of anti-infective therapy. mNGS may have the potential to be a new powerful tool for the diagnosis of PJI. Thoendel et al. used metagenomic shotgun sequencing to detect a wide range of PJI pathogens from 408 cerebrospinal fluid samples and suggested that this method has the potential to improve or change the identification of many difficult-to-detect pathogens (It is well known that the detection of pathogens by culture may be impaired in PJIs previously treated with antibiotics (In this study, no significant differences were found in the positivity rates of deep tissue culture and synovial fluid mNGS between cases with and without prior antimicrobial therapy. However, the positivity rate of synovial fluid culture was higher in cases with previous antimicrobial therapy than in cases without antibiotics (57.9% vs 40.0%, p=0.043). It appears that the administration of antimicrobial therapy had no effect on the diagnostic microbial yield. These findings contrasted with those of previous studies confirming the influence of prior antimicrobial therapy on the detection rate (In this study, the average number of days required for culture was 5.1 days and 1.2 days for mNGS. Although the cost of mNGS was higher than that of culture, considering the higher positivity rate and earlier resolution capability, mNGS was more beneficial for early targeted antibiotic therapy for PJI. According to a study by Another interesting finding in this study was that the trends in culture and mNGS positivity rates with different antimicrobial-free intervals. The positivity rates of deep tissue culture and synovial fluid culture all decreased with shortening of the antimicrobial-free interval (>14 days, 4 to 14 days, 0 to 3 days) in patients receiving antimicrobial therapy prior to sampling. For synovial fluid mNGS, although the positivity rate did not show a consistent downward trend, it did decrease as the antimicrobial-free interval increased from 4 to 14 days to 0 to 3 days. This may mean that antimicrobials should be discontinued more than 3 days before sampling to further increase the positivity rate of mNGS for PJI.There are several limitations to the present study, including the fact that no gold standard has yet been established for the diagnosis of pathogens in PJI. Contaminants would then be a potential interference for mNGS and culture, which could influence the analysis. The low incidence of PJI limited the sample size, which may reduce the accuracy of some statistical results in this study. The high cost of mNGS limited the use of mNGS in deep tissue samples to fully evaluate the influence of prior antimicrobial therapy on the detection rate. The type and duration of previous antimicrobials were not further analysed. In addition, this was a single-centre study, which may be subject to some bias. A multicentre study with a larger sample size should be carried out next.