Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06062251 |
| Other study ID # |
29BRC22.0208 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
February 27, 2024 |
| Est. completion date |
June 2026 |
Study information
| Verified date |
October 2023 |
| Source |
University Hospital, Brest |
| Contact |
claudi LAMOUREUX, Dr |
| Phone |
02.21.74.31.84 |
| Email |
claudie.lamoureux[@]chu-brest.fr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
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.
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.
