Ignite Creation Date:
2024-05-06 @ 7:35 PM
Last Modification Date:
2024-10-26 @ 3:09 PM
Study NCT ID:
NCT06062251
Status:
RECRUITING
Last Update Posted:
2024-03-22
First Post:
2023-09-25
Brief Title:
Assessing the Performance of Shotgun Metagenomics in the Diagnosis of Complex Prosthetic Joint Infections
Sponsor:
University Hospital Brest
Organization:
University Hospital Brest
Study Overview
Official Title:
Assessing the Performance of Shotgun Metagenomics in the Diagnosis of Complex Prosthetic Joint Infections METAGENOS
Status:
RECRUITING
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
METAGENOS
Brief 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
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
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 andor 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 aerobicanaerobicintracellularmycobacterial 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 andor 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 733 specificity of 955 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 902 and 930 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
Appropriate diagnosis and medical and surgical management of PJI are therefore essential to preserve andor 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 aerobicanaerobicintracellularmycobacterial 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 andor 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 733 specificity of 955 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 902 and 930 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None