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An Enhanced Understanding of Culture-Negative Periprosthetic Joint Infection with Next-Generation Sequencing: A
Karan Goswami1, Samuel Clarkson1, Caleb D Phillips2
1Rothman Institute at Thomas Jefferson, Philadelphia, Pennsylvania.
Background:
The challenges of culture-negative periprosthetic joint infection (PJI) have led to the emergence of molecular methods of pathogen identification, including next-generation sequencing (NGS). While its increased sensitivity compared with traditional culture techniques is well documented, it is not fully known which organisms could be expected to be detected with use of NGS. The aim of this study was to describe the NGS profile of culture-negative PJI.
Methods:
Patients undergoing revision hip or knee arthroplasty from June 2016 to August 2020 at 14 institutions were prospectively recruited. Patients meeting International Consensus Meeting (ICM) criteria for PJI were included in this study. Intraoperative samples were obtained and concurrently sent for both routine culture and NGS. Patients for whom NGS was positive and standard culture was negative were included in our analysis.
Results:
The overall cohort included 301 patients who met the ICM criteria for PJI. Of these patients, 85 (28.2%) were culture-negative. A pathogen could be identified by NGS in 56 (65.9%) of these culture-negative patients. Seventeen species were identified as common based on a study-wide incidence threshold of 5%. NGS revealed a polymicrobial infection in 91.1% of culture-negative PJI cases, with the set of common 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.
Conclusions:
NGS provides a more comprehensive picture of the microbial profile of infection that is often missed by traditional culture. Examining the profile of PJI in a multicenter cohort using NGS, this study demonstrated that approximately two-thirds of culture-negative PJIs had identifiable opportunistically pathogenic organisms, and furthermore, the majority of infections were polymicrobial.
Level Of Evidence:
Diagnostic Level II . See Instructions for Authors for a complete description of levels of evidence.
Insights
Next-generation sequencing (NGS) identifies common pathogens in culture-negative periprosthetic joint infections (PJI), revealing polymicrobial infections are frequent. This molecular method offers a more comprehensive microbial profile than traditional cultures for diagnosing PJI.
Area of Science:
- Microbiology
- Orthopedic Surgery
- Infectious Diseases
- Genomics
Background:
- Culture-negative periprosthetic joint infection (PJI) presents diagnostic challenges.
- Next-generation sequencing (NGS) offers a sensitive molecular alternative to traditional culture methods for pathogen identification.
- The specific microbial profiles detected by NGS in culture-negative PJI remain incompletely understood.
Purpose of the Study:
- To characterize the comprehensive microbial profile of culture-negative periprosthetic joint infections (PJI) using next-generation sequencing (NGS).
- To identify common pathogens and assess the prevalence of polymicrobial infections in culture-negative PJI cases.
Main Methods:
- Prospective recruitment of 301 patients meeting International Consensus Meeting (ICM) criteria for PJI across 14 institutions.
- Intraoperative samples were collected concurrently for both routine culture and NGS analysis.
- Analysis focused on the 85 culture-negative PJI cases where NGS identified pathogens.
Main Results:
- Next-generation sequencing (NGS) successfully identified pathogens in 65.9% (56/85) of culture-negative periprosthetic joint infection (PJI) cases.
- Seventeen species were identified as common, with Escherichia coli, Cutibacterium acnes, Staphylococcus epidermidis, and Staphylococcus aureus being most frequent.
- Polymicrobial infections were prevalent, occurring in 91.1% of culture-negative PJI cases, with common species contributing significantly to these profiles.
Conclusions:
- Next-generation sequencing (NGS) provides a significantly more detailed microbial profile of periprosthetic joint infections (PJI) compared to standard culture methods.
- A substantial proportion (approximately two-thirds) of culture-negative PJIs harbor identifiable opportunistic pathogens via NGS.
- The majority of culture-negative PJIs are polymicrobial, highlighting the complexity of these infections.
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