An Enhanced Understanding of Culture-Negative Periprosthetic Joint Infection with Next-Generation Sequencing

Abstract

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.

Hip & Pelvis

“…In this multicentre prospective study from across the USA , the authors enrolled 301 patients who met the criteria for PJI diagnosis, with negative cultures seen in 85 patients (28.2%). 1 The major positive finding of this study is that NGS was able to identify an organism in 56 of the 85 culture-negative patients (65.9%), with the highest yield of positive results being from tissue sampling (46.6%) followed by swabs (34.1%) and synovial fluid (19.3%). The authors were able to identify 176 different organisms in this cohort, with over 90% being considered uncommon or atypical organisms for PJI.…”

Infection of the periprosthetic joint: Current views and forecasts

“…According to certain researchers, negative reimplantation results are linked to positive reimplantation cultures. In contrast, only one of the five reimplantation cases that tested positive for culture in the study failed [36] .…”

“…Over the implant's lifetime, longer prosthesis indwelling duration is linked to a higher overall risk for hematogenous infections. Even persistent illnesses that would have gone unnoticed in the past are now found thanks to the advancement of sophisticated detection techniques for microbial biofilms [2,3] . The management of PJI necessitates sophisticated therapeutic approaches, such as numerous surgical revisions and protracted antimicrobial therapy.…”

Imaging in Hip Arthroplasty Management Part 2: Postoperative Diagnostic Imaging Strategy

“…No test offers great sensibility or specificity for diagnosing PJI. The diagnosis of PJI is based on a combination of clinical findings, laboratory evaluation of blood and synovial fluid, and intraoperative findings [ 97 ]. The gold standard remains articular fluid aspiration and culture.…”

“…A recent study showed that almost 30% of PJI were culture-negative after intra-operative sampling. In those cases, next-generation sequencing showed infection in 66% of the cases, which was polymicrobial in 91% [ 97 ]. Blood tests are often negative and should not be mistaken for aseptic loosening before articular fluid analysis [ 97 ].…”