The 2018 Definition of Periprosthetic Hip and Knee Infection: An Evidence-Based and Validated Criteria is shown below.
By this set of criteria, the presence of a periprosthetic hip or knee infection may be inferred without actually demonstrating the presence of live bacteria doing harm. The authors point out that the proposed criteria may be inaccurate in patients with adverse local tissue reaction, crystalline deposition arthroplasty, flare of inflammatory arthropathy, and infection with slow growing organisms such as Cutibaterium and coagulase negative Staphylococcus.
In a subsequent publication, An Enhanced Understanding of Culture-Negative Periprosthetic Joint Infection with Next-Generation Sequencing: A Multicenter Study the authors identified 301 joints meeting the International Consensus Meeting (ICM) criteria for periprosthetic infections (PJI) shown above. Of these 85 (28.2%) had negative intraoperative cultures. A number of factors could contribute to the reported discordance between the culture results and the ICM criteria for a PJI:
lack of specificity of the minor ICM criteria,
administration of antibiotics prior to sampling,
the inability of viable bacteria to form colonies on laboratory media,
bacteria concealed in a biofilm on the implants,
an intracellular location of the organisms,
inadequate tissue sampling,
inadequate culture protocols, and
a too-short period of culture observation.
In 56 (65.9%) of the culture-negative patients, bacterial DNA was identified by Next Generation Sequencing (NGS). The DNA of seventeen species was commonly found. NGS revealed polymicrobial DNA in 91.1% of the culture-negative cases that met the ICM criteria, with the commonest species contributing to 82.4% of polymicrobial profiles. Escherichia coli, Cutibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus ranked highest in terms of incidence and study-wide mean relative abundance and were most frequently the dominant organism when occurring in polymicrobial infections.
The authors concluded that in cases meeting the ICM criteria for PJI but without positive tissue cultures, the DNA of multiple organisms was often found in tissue samples.
Comment: In this study, 301 patients met the 2018 International Consensus Meeting (ICM) criteria for PJI. Of these patients, 216 had one or more positive cultures. While not presented in this paper, it would be of great interest to know the NGS data for these patients with obvious PJI to reveal the degree to which NGS findings concurred with the culture findings. This analysis would enable us to assess the effective sensitivity of NGS in detecting PJI. As pointed out in Revision shoulder arthroplasty – what is the role of next-generation sequencing?, NGS may fail to detect the DNA of live bacteria isolated from tissue cultures.
Furthermore, as also discussed in Revision shoulder arthroplasty – what is the role of next-generation sequencing?, NGS often detects DNA of non-pathogenic bacteria and NGS cannot distinguish the DNA from live bacteria from that of dead bacteria.
Our knowledge of the role of NGS in diagnosing PJI would be greatly enhanced by using NGS to seek bacterial DNA from samples from uninfected joints, such as those undergoing primary arthroplasty. This analysis would enable us to assess the effective selectivity of NGS in detecting PJI.
It would also be of interest to know the NGS results of negative control samples, such as a sterile swab or gauze. This is important because some of the DNA recovered by NGS is from common laboratory contaminants.
We need to better understand the implications of NGS for treatment. What antibiotics would be used to treat a joint with NGS finding of DNA for both E. Coli and S. Aureus?
Ultimately we need to know if the use of NGS sampling at revision arthroplasty improves patient outcomes to a degree that offsets the cost.
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