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.