Assessing the Performance of Shotgun Metagenomics in the Diagnosis of Complex Prosthetic Joint Infections (METAGENOS)

Assessing the Performance of Shotgun Metagenomics in the Diagnosis of Complex Prosthetic Joint Infections (METAGENOS)

The objectiveof this of a prospective, multicentre study is to evaluate the performance of shotgun metagenomics in the diagnosis of chronic Prosthetic joint infection (PJI) in comparison with the adapted MSIS diagnostic score..

The main questions it aims to answer are:

• To evaluate the performance of shotgun metagenomics in the diagnosis of chronic PJI in comparison with culture.
• To describe the epidemiology of bacterial species responsible for chronic PJI in Western France and their potential resistance to antibiotics.
• Analyzing the diagnostic performance of shotgun culture and metagenomics as a function of potentially administered antibiotic treatments A total of 143 patients sampled will be included. Six intraoperative samples will be taken for each patient, as part of routine care. In addition to the standard preoperative check-up, an extra volume of blood will be taken for CRP measurement at inclusion.

Study Overview

• Status: Completed
• Conditions: Prosthetic Joint Infection

Detailed Description

Prosthetic joint infection (PJI) is one of the most serious and devastating complications of orthopaedic surgery, leading to a high risk of recurrence and disability, as well as increased mortality and management costs. Despite improvements in antibiotic prophylaxis procedures and surgical asepsis measures, the significant increase in the number of prostheses fitted worldwide has been accompanied by an increase in the number of infections. The infection rate has been estimated at between 1% and 2% after hip and knee arthroplasty.

Appropriate diagnosis and medical and surgical management of PJI are therefore essential to preserve and/or restore adequate motor function, minimise the risk of complications and prevent excessive morbidity. The microbiological diagnosis of PJI must be as early and exhaustive as possible in order to introduce rapid and effective antibiotic therapy and avoid the development of a biofilm (gangue around the material) or chronic infection (quiescent bacteria).

However, the diagnosis of PJI can be difficult to make in certain situations. Learned societies have established a definition of PJI and defined diagnostic scores combining clinical, biological, anatomopathological and cytological criteria. An initial definition was approved in 2011 by the Musculoskeletal Infection Society (MSIS). This definition was modified and subject to an international consensus review in 2013 (MSIS diagnostic score). In 2018, an international consensus meeting reviewed and adapted the MSIS score. This adapted score is more appropriate to current Medical Biology practices and to the non-accessibility of all diagnostic tests in laboratories (leucocyte esterase, alpha-defensin, ...).

In this definition of PJI, the positivity of 2 intra-operative samples to the same bacterial species is considered to be a major criterion. A wide range of bacteria can cause PJI: aerobic/anaerobic/intracellular/mycobacterial; somePJI can be polymicrobial. It is therefore essential to accurately identify these pathogens in order to administer appropriate antibiotic therapy and avoid chronicity of infection. Despite the optimisation of practices, culture of samples is negative in 5 to 30% of cases, despite the presence of diagnostic criteria for PJI. The most common causes are a lack of culture sensitivity, prior antibiotic administration and/or the presence of difficult or slow-growing pathogens. In these cases, intravenous broad-spectrum antibiotic therapy is administered, resulting in additional management costs, the occurrence of adverse treatment effects and the risk of acquiring resistance or intestinal dysbiosis.

In this context, "classic" molecular techniques are routinely used to overcome the limitations of culture for microbiological detection: bacterial-specific (including PCR targeting Staphylococcus aureus) or non-specific (bacterial universal PCR targeting the gene encoding 16S rDNA) (Figure 1). The latter approach was previously evaluated by the CRIOGO group (3Centre de Référence en Infections Ostéo-articulaires du Grand Ouest") with detection performance deemed disappointing in the context of PJI (sensitivity of 73.3%, specificity of 95.5%). Innovative molecular techniques for Next Generation Sequencing (NGS) are being developed, including shotgun metagenomics (sequencing of all the genetic material in a sample). Recent studies have evaluated the sensitivity of shotgun metagenomics in PJI, estimated at between 90.2% and 93.0% compared with bacterial culture and at around 95% compared with the MSIS diagnostic score.

However, these few recent studies evaluating shotgun metagenomics have only been carried out on a single sample per patient, which is insufficient according to the recommendations of the international and national consensuses on the management of PJI. In fact, four or even five intraoperative samples must be taken and analysed in microbiology to make the diagnosis of PJI. This high number of samples improves the sensitivity and completeness of bacterial detection and facilitates the interpretation of positive cultures for potentially contaminating skin bacteria (coagulase-negative Staphylococci, Cutibacterium acnes, etc.). To date, only one study has assessed the performance of shotgun metagenomics applied to several intraoperative samples per patient. Further studies are therefore needed to refine the performance of shotgun metagenomics in the context of PJI and to better assess the contribution of this costly technique, which requires considerable expertise to perform and interpret.

The setting up of a prospective, multicentre study in centres associated with the CRIOGO will make it possible to assess the performance of shotgun metagenomics in the management of chronic PJI. The performance of shotgun metagenomics will be assessed on the basis of four different samples per patient, in six centers specialising in the diagnosis of PJI, which makes the METAGENOS study unique compared with other studies. At the end of the project, the aim is to define the indications for using this innovative technique and to harmonise future regional practices.

• Study Type: Observational
• Enrollment (Actual): 144

Contacts and Locations

Study Locations

• France
  • Angers, France
    • Dr Rachel CHENOUARD
  • Nantes, France
    • Dr Stéphane CORVEC
  • Poitiers, France
    • Dr Chloé PLOUZEAU
  • Rennes, France
    • Dr REISSIER Sophie
  • Tours, France
    • Dr Marie-Frédérique LARTIGUE
  • Brest
    • Brest, Brest, France, 29200
      • Brest University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with suspected chronic prosthetic joint infection

Description

Inclusion Criteria:

• Male or female ≥ 18 years
• Patients being considered for surgery for suspected chronic PJI (time between joint replacement surgery and patient inclusion > 3 months)
• Social security affiliation
• No objection to participating in the study

Exclusion Criteria:

• Suspicion or documentation (positive blood cultures) of acute bacteremia at time of inclusion
• Patients under guardianship or trusteeship
• Pregnant or breastfeeding woman
• Patient deprived of liberty by legal or administrative decision
• Patients in psychiatric care

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PJI diagnosis	PJI diagnosis (positive/negative) obtained by shotgun metagenomics and by the adapted MSIS criteria (gold standard)MSIS diagnostic score (gold standard).	from samples taken during surgery. Shotgun metagenomics will be performed at the end of the inclusion of all patients, i.e. one year after the start of the study

Secondary Outcome Measures

Outcome Measure	Time Frame
PJI diagnosis (positive/negative) obtained by shotgun metagenomics and by culture	from samples taken during surgery. Shotgun metagenomics will be performed at the end of the inclusion of all patients, i.e. one year after the start of the study
Presence/absence of a bacterial species (by culture and/or shotgun metagenomics) in a patient sample considered infected according to the appropriate MSIS score	: from samples taken during surgery. Shotgun metagenomics will be performed at the end of the inclusion of all patients, i.e. one year after the start of the study
Resistance/sensitivity to antibiotics tested	immediate post-operative period (usually within 3-15 days following surgery)
PJI diagnosis (positive/negative) obtained by shotgun metagenomics and by culture in case of presence/absence of antibiotic therapy the month before surgery	from samples taken during surgery. Shotgun metagenomics will be performed at the end of the inclusion of all patients, i.e. one year after the start of the study

Collaborators and Investigators

• Sponsor: University Hospital, Brest
• Investigators: Principal Investigator: Rachel CHENOUARD, Dr, Angers HU; Principal Investigator: Stéphane CORVEC, PhD, Nantes HU; Principal Investigator: Chloé PLOUZEAU, Dr, Poitier HU; Principal Investigator: Sophie REISSIER, Dr, Rennes HU; Principal Investigator: Marie-Frédérique LARTIGUE, Dr, Tours HU

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2024
• Primary Completion (Actual): March 13, 2026
• Study Completion (Actual): March 13, 2026

Study Registration Dates

• First Submitted: September 25, 2023
• First Submitted That Met QC Criteria: September 25, 2023
• First Posted (Actual): October 2, 2023

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 9, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Prosthetic joint infection; shotgun metagenomics; microbiological diagnosis
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Pathologic Processes; Disease Attributes; Arthritis; Joint Diseases; Infections; Communicable Diseases; Arthritis, Infectious
• Other Study ID Numbers: 29BRC22.0208

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected data that underlie results in a publication
• IPD Sharing Time Frame: All collected data that underlie results in a publication
• IPD Sharing Access Criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No