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Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 33 - 33
1 Oct 2022
Ferry T Kolenda C Briot T Craighero F Conrad A Lustig S Bataillers C Laurent F
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Background

Bacteriophages are natural viruses of interest in the field of PJI. A paper previously reported the PhagoDAIR procedure (use of phages during DAIR) in three patients with PJI for whom explantation was not desirable. As the need to isolate the pathogen before surgery to perform phage susceptibility testing is a strong hindrance for the development of this procedure, we developed post-operative phage injections using ultrasound, in patients infected with S. aureus and/or P. aeruginosa who were eligible for the PhagoDAIR procedure, but for whom phages were not available at the time of surgery.

Materials/Methods

We performed a single center, exploratory, prospective cohort study including patients with knee PJI who received phage therapy with ultrasound after performance of a DAIR or a partial prosthesis exchange. All patients had PJI requiring conservative surgery and suppressive antimicrobial therapy (SAT) as salvage procedure. Each case was discussed in multidisciplinary meetings in agreement with French health authority, based on the clinical presentation, and the phage susceptibility testing. The cocktail of highly concentrate active phages (5 mL; about 10e9 PFU/mL) was extemporaneous prepared and administered three times directly into the joint using sonography (1 injection per week during 3 weeks) during the postoperative period, before switching antibiotics to SAT.


Background

Exebacase, an antistaphylococcal lysin in Phase 3 of development as a treatment for S. aureus bacteremia/right-sided endocarditis has demonstrated antibiofilm activity in vitro and has previously been used as salvage therapy in four patients with relapsing multidrug-resistant (MDR) S. epidermidis knee prosthetic joint infection (PJI) using a procedure called LysinDAIR (administration of the lysin during the performance of an arthroscopic DAIR).

Materials/methods

We performed a single center, exploratory, open-label prospective study using the LysinDAIR procedure in patients with chronic (inoculation >3 months prior to treatment) coagulase-negative staphylococci (CNS) PJI of the knee with two different clinical presentations and treatment paradigms. Cohort A: first episode of CNS knee PJI, for whom the LysinDAIR was followed by clindamycin + levofloxacin planned to be prescribed for three months and then stopped; and Cohort B: relapsing episodes of MDR CNS knee PJI for whom the LysinDAIR was followed by primary antimicrobial therapy for three months, followed by suppressive antimicrobial therapy (SAT). Exebacae susceptibility testing was performed before treatment for each patient. In agreement with the French Health authority, exebacase (2 to 3.5 total mg in 30–50 ml (∼0.067 – 0.075 mg/m) was administered directly into the joint during arthroscopy.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 71 - 71
1 Oct 2022
Ferry T Arvieux C Stendel E Nich C Delobel P Zeller V Sotto A Dauchy F RONDE-OUSTAU C Tizon A
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Aim

To describe the management of PJI due to S. aureus in CRIOAcs in 2019 and to particularly focus on the evaluation of the efficacy of DAIR regarding control of infection and risk factors for failure up to 12 months.

Method

Thirteen CRIOAcs were selected to participate to the study. Data concerning the management of all the PJI in the year 2019 were retrospectively collected and registered in eCRFs. Inclusion criteria were: ≥ 18 years old patients with S. aureus ± other bacteria (in per surgical procedure sample); knee or hip PJI and with clinical signs of infection. Patients treated with bacteriophages were excluded. All eligible patients were notified by an information letter. Patients treated by the DAIR procedure were selected, and rate of control of infection (no inflammatory local signs or no new surgical procedure or no S. aureus in case of puncture) was analyzed using Kaplan Meier method and risk factors for failure at 12 months were assessed using Cox regression model.


The Bone & Joint Journal
Vol. 104-B, Issue 1 | Pages 183 - 188
1 Jan 2022
van Sloten M Gómez-Junyent J Ferry T Rossi N Petersdorf S Lange J Corona P Araújo Abreu M Borens O Zlatian O Soundarrajan D Rajasekaran S Wouthuyzen-Bakker M

Aims

The aim of this study was to analyze the prevalence of culture-negative periprosthetic joint infections (PJIs) when adequate methods of culture are used, and to evaluate the outcome in patients who were treated with antibiotics for a culture-negative PJI compared with those in whom antibiotics were withheld.

Methods

A multicentre observational study was undertaken: 1,553 acute and 1,556 chronic PJIs, diagnosed between 2013 and 2018, were retrospectively analyzed. Culture-negative PJIs were diagnosed according to the Muskuloskeletal Infection Society (MSIS), International Consensus Meeting (ICM), and European Bone and Joint Society (EBJIS) definitions. The primary outcome was recurrent infection, and the secondary outcome was removal of the prosthetic components for any indication, both during a follow-up period of two years.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 9 - 9
1 Dec 2021
Ferry T Conrad A Senneville E Roux S Dupieux-Chabert C Dinh A Lustig S Goutelle S Briot T Pham T Valour F
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Aim

Tedizolid is an oxazolidinone antibiotic that: (i) is recommended at the dose of 200 once daily in patients with skin and soft tissue infection; (ii) seems to have a better long-term hematological and neurological safety profile in comparison with linezolid; (iii) remains active on multidrug-resistant (MDR) Gram-positive pathogens. Consequently, it might represent an option as suppressive antimicrobial treatment (SAT) in patients with complex implant-associated bone and joint infection (BJI) due to MDR Gram-positive pathogens.

Method

We performed a cohort study (2017–2020) to evaluate the long-term safety of tedizolid (200mg qd) as SAT in patients with implant-associated BJI. In all cases, the use of tedizolid was validated as the last oral treatment option during multidisciplinar meetings in a reference center for the management of BJI. Serious adverse events, any reason for discontinuation, and standard biological data, were prospectively collected.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 64 - 64
1 Dec 2021
Sloten MV Gómez-Junyent J Ferry T Nicolò R Petersdorf S Lange J Corona P Abreu M Borens O Zlatian OM Soundarrajan D Rajasekaran S Wouthuyzen-Bakker M
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Aim

To analyse the prevalence of culture negative periprosthetic joint infections (PJI) when adequate culture techniques are applied, and to evaluate the outcome of patients who were treated with antibiotics for a culture negative PJI versus those in whom treatment was withheld.

Method

A multicenter observational study in which acute and chronic PJIs diagnosed between 2013 and 2018 were analyzed. Culture negative PJIs were diagnosed according to the MSIS, ICM and EBJIS definitions.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 49 - 49
1 Dec 2021
Trecourt A Brevet M Champagnac A Conrad A Josse J Dupieux-Chabert C Valour F Ferry T
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Aim

The aim of this study was to confirm that Mirra's criterion (≥ 5 Polymorphonuclears (PMNs) per field in 5 high power fields (HPFs)) is not adequate for diagnosis of chronic bone and joint infections (BJIs) due to Cutibacterium acnes (C. acnes). The second objective was to determine if plasma-cell infiltration, that is a classical marker of chronic inflammation, could be useful for the diagnosis of chronic BJIs due to C. acnes.

Methods

We retrospectively selected 25 patients from 2009 to 2013 with chronic BJIs due to C. acnes. In addition of Mirra's criterion, the number of plasma-cells (≥5 plasma-cells/5 HPFs, defined as “CRIOAc Lyon's criterion”) was implemented in the histopathological analysis. Patients were defined as infected, if at least one of the two criteria were present.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 86 - 86
1 Dec 2021
Kolenda C Medina M Legendre T Blazere L Bergot M Arnaud V Souche A Roussel-Gaillard T Martins-Simoes P Tristan A Ferry T Laurent F
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Aim

Bacteriophages, viruses specific of bacteria, are receiving substantial attention as alternative antibacterial agents to treat bacteria frequently multi-resistant to antibiotics and/or able to form biofilms, such as staphylococci. The latter are responsible for very difficult to treat bone and joint infections (BJIs). In this context, our consortium aims to develop a production of therapeutic phages in accordance with the will of ANSM (French National Agency for the Safety of Medicines and Health Products) to encourage the development of a national academic platform for phage therapy. We report the isolation and characterization of new anti-Staphylococcus phages as well as the evaluation of their activity on a collection of clinical strains of S. aureus (SA) and coagulase-negative staphylococci (CNS) in order to assess their therapeutic potential.

Method

Seventeen phages were isolated from wastewater samples. Their identification was obtained by Illumina whole genome sequencing. To evaluate their spectrum of activity, 30 genetically characterized SA strains representative of the main genetic backgrounds as well as 32 strains belonging to 7 CNS species responsible for BJIs were included. The spot test technique, based on the determination of the Efficiency Of Plating ratio, was used (EOP, ratio between the phage titer obtained on a tested strain/titer on a reference strain, close to 1 if high sensitivity to the phage).


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 23 - 23
1 Dec 2021
Kokenda C Legendre T Abad L Graue C Jay C Ferry T Dupieux-Chabert C kensinger B Laurent F
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Aim

Bone and Joint Infections (BJIs) present with non-specific symptoms and can be caused by a wide variety of bacteria and fungi, including many anaerobes and microorganisms that can be challenging to culture or identify by traditional microbiological methods. Clinicians currently rely primarily on culture to identify the pathogen(s) responsible for infection. The BioFire® FilmArray® Bone and Joint Infection (BJI) Panel (BioFire Diagnostics, Salt Lake City, UT) was designed to detect 15 gram-positive (seven anaerobes), 14 gram-negative bacteria (one anaerobe), two yeast, and eight antimicrobial resistance (AMR) genes from synovial fluid specimens in an hour. The objective of this study was to evaluate the performance of an Investigational Use Only (IUO) version of the BioFire BJI Panel (BBJIP) compared to conventional used as reference methods.

Method

In a monocentric study, leftover synovial fluid specimens were collected in a single institution including 4 hospitals and tested using conventional bacterial culture (Standard of Care (SoC)) according to routine procedures following French national recommendations. Specimen has been placed in a refrigerator (4°C) as soon as possible after collection and stored for less than or equal to 7 days before enrollment. Performance of the IUO version of the BBJIP was determined by comparison to SoC for species identification.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 78 - 78
1 Dec 2021
Benech N LEVAST B Gasc C Cecile B Senneville E Lustig S Boutoille D Dauchy F Zeller V Cazanave C Josse J Laurent F Ferry T
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Aim

Bone and joint infections (BJI) need frequently prolonged antibiotic treatment at high dosage for a total of 6 or 12 weeks depending the type of infection. Impact of such prolonged antibiotic exposure on the gut microbiota has never been assessed.

Method

We performed a national multicentric prospective study of patients with BJI to monitor the gut microbiota dynamic all along antimicrobial treatment. Clinical data and stool collection were performed at the baseline visit (B) within 24h before starting antibiotics, at the end of the treatment (EOT) and 2 weeks after antibiotic withdrawal during a follow-up visit (FU). Microbiota composition was determined by shotgun metagenomic sequencing. Biological markers of gut permeability and inflammation were monitored at each time point.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 79 - 79
1 Dec 2021
Souche A Kolenda C Schuch R Ferry T Laurent F Josse J
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Aim

Staphylococcus epidermidis (S. epidermidis) is one of the main pathogens responsible for bone and joint infections especially those involving prosthetic materials (PJI). Although less virulent than S. aureus, S. epidermidis is involved in chronic infections notably due to its ability to form biofilm. Moreover, it is frequently multiresistant to antibiotics. In this context, the development of additional or alternative antibacterial therapies targeting the biofilm is a priority.

Method

The aim of this study was to evaluate in vitro the activity of phage lysin exebacase (CF-301) against biofilms formed by 19 S. epidermidis clinical strains responsible for PJI. We determined the remaining viable bacteria inside the biofilm (counting after serial dilution and plating) and the biomass (bacteria and extracellular matrix, using crystal violet staining) after 24h of exposition to exebacase at different concentrations, alone (0.05; 0.5; 5; 50 and 150 mg/L) or in combination (5, 50 and 150 mg/L) with antibiotics commonly used to treat multi-resistant S. epidermidis PJI (rifampin (1 mg/L), vancomycin (10mg/L) and daptomycin (10mg/L)). In this study, synergy was defined as a significantly higher effect of the association in comparison to the sum of the effect of each molecule.


Bone & Joint Research
Vol. 9, Issue 10 | Pages 635 - 644
1 Oct 2020
Lemaignen A Grammatico-Guillon L Astagneau P Marmor S Ferry T Jolivet-Gougeon A Senneville E Bernard L

Aims

The French registry for complex bone and joint infections (C-BJIs) was created in 2012 in order to facilitate a homogeneous management of patients presented for multidisciplinary advice in referral centres for C-BJI, to monitor their activity and to produce epidemiological data. We aimed here to present the genesis and characteristics of this national registry and provide the analysis of its data quality.

Methods

A centralized online secured database gathering the electronic case report forms (eCRFs) was filled for every patient presented in multidisciplinary meetings (MM) among the 24 French referral centres. Metrics of this registry were described between 2012 and 2016. Data quality was assessed by comparing essential items from the registry with a controlled dataset extracted from medical charts of a random sample of patients from each centre. Internal completeness and consistency were calculated.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 27 - 27
1 Dec 2019
Triffault-Fillit C Eugenie M Karine C Becker A Evelyne B Michel T Goutelle S Fessy M Dupieux C Laurent F Lustig S Chidiac C Ferry T Valour F
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Aim

The use of piperacillin/tazobactam with vancomycin as empirical antimicrobial therapy (EAT) for prosthetic joint infection (PJI) has been associated with an increased risk of acute kidney injury (AKI), leading to propose cefepim as an alternative since 2017 in our reference center. The present study compared microbiological efficacy and tolerance of these two EAT strategies.

Method

All patients with PJI empirically treated by vancomycin-cefepim (n=90) were prospectively enrolled in an observational study, and compared with vancomycin-piperacillin/tazobactam-treated historical controls (n=117), regarding: i) the proportion efficacious empirical regimen (i.e., at least one of the two molecules active against the identified organism(s) based on in vitro susceptibility testing); and ii) the incidence of empirical therapy-related adverse events (AE), classified according to the Common terminology criteria for AE (CTCAE).


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 26 - 26
1 Dec 2019
Kolenda C Josse J Medina M Fevre C Lustig S Ferry T Laurent F
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Aim

Staphylococcus aureus is the first causative agent of bone and joints infections (BJI). It causes difficult-to-treat infections because of its ability to form biofilms, and to be internalized and persist inside osteoblastic cells. Recently, phage therapy has emerged as a promising therapy to improve the management of chronic BJI. In the present study, we evaluated the efficacy of an assembly of three bacteriophages previously used in a clinical case report (Ferry, 2018) against S. aureus in in vitro models of biofilm and intracellular osteoblast infection.

Methods

Using HG001 S. aureus, the bactericidal activities of the assembly of the three bacteriophages (Pherecydes Pharma) used alone or in association with vancomycin or rifampicin were compared by quantifying the number of viable bacteria in mature biofilms and infected osteoblasts after 24h of exposure.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 4 - 4
1 Dec 2018
Becker A Triffault-Fillit C Forestier E Lesens O Cazorla C Descamps S Chidiac C Lustig S Montbarbon E Batailler C Boyer B Ferry T
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Aim

S. aureus and coagulase-negative staphylococci are the most frequent bacteria responsible for PJI. In patients with acute PJI (i.e. <1 month following the implantation), DAIR with exchange of removal components followed by a combination of antibiotics that includes rifampin (particularly rifampin+fluoroquinolone) are recommended. Unfortunately, some patients could not receive rifampin due to drug-drug interaction or stopped it due to an adverse event. Finally, it was unclear if the dose and the duration of rifampin influenced the prognosis.

Method

We performed a retrospective cohort study in 4 hospitals and included patients with staphylococcal acute post-operative (< 1 month) PJI treated with DAIR in 2011–2016 period. Univariate and multivariate Cox analysis and Kaplan Meier curves were used to determine the risk factors for treatment failure (persistence of clinical signs, new surgery w/o persistence or superinfection, infection-related death).


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 68 - 68
1 Dec 2018
Abad L Diot A Josse J Tasse J Lustig S Ferry T Laurent F Valour F
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Aim

Leading etiology of Bone and Join infections (BJI), Staphylococcus aureus (SA) is responsible for difficult-to-treat infections mainly because of three persistence factors: (i) biofilm formation, (ii) persistence within bone cells and (iii) switch to the small colony variant (SCV) phenotype. The impact of rifampin on these mechanisms gave it a prominent place in orthopedic device-associated BJI. However, resistance emergence, intolerance and drug interactions cause significant concerns. In this context, other rifamycins – namely rifapentine and rifabutin – have poorly been evaluated, particularly toward their ability to eradicate biofilm-embedded and intracellular reservoirs of SA.

Method

This study aimed at comparing the intracellular activities of and SCV induction by rifampin, rifabutin and rifapentine in an in vitro model of osteoblast infection. Four concentrations were tested (0.1xMIC, MIC, 10xMIC, 100xMIC) against three SA strains (6850 and two clinical isolates involved in recurrent BJI)


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 37 - 37
1 Dec 2018
Dupieux C Verhoeven P Descours G Grattard F Benito Y Vandenesch F Cazorla C Ferry T Lustig S Boyer B Boisset S Laurent F Carricajo A
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Aims

Microbiological diagnosis of bone and joint infections (BJIs) is pivotal. However, no consensus exists about the best choice for techniques to be used and the best indications for molecular methods. Our objectives were: (i) to compare the performance of various microbiological diagnostic methods (cultural and molecular) on synovial fluid specimens and (ii) to select an algorithm for optimizing the diagnosis of BJIs in adults.

Methods

This prospective multicentric study (in Lyon and Saint-Etienne, France) included 423 joint fluid samples, collected from 333 adult patients (median age 69 years) suspected for BJI on the basis of medical history and clinical symptoms. For each inclusion, joint fluid and blood culture were collected concomitantly. The synovial fluid was also inoculated into blood culture bottles. Cytology, culture (using 5 solid media and an enrichment broth, incubated for 15 days), universal 16S rRNA PCR and PCR targeting Staphylococcus spp, S.aureus, Streptococcus spp, S.pneumoniae, Kingella kingae, Borrelia burgdorferi and Propionibacterium acnes were systematically performed on synovial fluid.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 83 - 83
1 Dec 2018
Lemaignen A Astagneau P Marmor S Ferry T Seng P Mainard D Jenny J Laurent F Grare M Jolivet-Gougeon A Senneville E Bernard L
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Aim

Bone and joint infections (BJI) are associated with a heavy morbidity and high health costs. Comorbidities, device associated infections and complicated journeys are associated with increased mortality, treatment failures and costs. For this reason, 24 referral centers (RC) have been created in 2009 in order to advise about management of “complex” BJI in weekly multidisciplinary meetings (MM). Since end of 2012, data from these meetings are gathered in a national database. We aimed to describe the data from this French registry of BJI and determine factors associated with the definition of “complex” BJI.

Method

Demographic, clinical, microbiologic and therapeutic characteristics of patients are systematically recorded in the database. Data from the first presentation in RC for each adult patients are presented. Complexity of BJI is recorded after each meeting according to 4 criteria (first failure, complex antibiotic therapy, precarious underlying conditions or complex surgical procedure). Part of unavailable data have been completed by pattern extraction from text-encoded commentaries. Factors associated with complexity were determined by multivariate logistic regression.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 49 - 49
1 Dec 2017
Becker A Valour F Perpoint T Boussel L Ruffion A Laurent F Senneville E Chidiac C Ferry T
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Aim

Pubic osteomyelitis (PO) is one of less frequent Bone and Joint Infections forms (BJI). Its management is still poorly codified as far as nosological framework is still unclear in medical literature. We aim to describe PO epidemiology and to look for factors associated with management failure.

Method

We performed a retrospective cohort study, carried out in two Reference Centres, including patients with PO in 2010–2016. Treatment failure was defined by: (i) persistence of clinical signs despite treatment; (ii) clinical relapse with same microorganisms; (iii) infection recurrence with one or more different microorganism(s);

(iv) new signs of infection (abscess, sinus tract) in same area, without recourse to get microbiological documentation. Factors associated with management failure were determined by univariate Cox analysis (hazard ratio [HR] and 95% confidence interval calculation). Kaplan-Meier curve were compared between groups by log-rank test.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 75 - 75
1 Dec 2017
Chauvelot P Ferry T Triffault-Fillit C Braun E Perpoint T Laurent F Michel-Henry F Lustig S Chidiac C Valour F
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Aim

Corynebacterium is a rare etiologic agent of BJI. We aimed to describe this rare clinical condition and to assess treatment failure determinants.

Method

All adult patients with proven Corynebacterium BJI (i.e. consistent clinical/radiological signs, AND ≥2 reliable positive bacteriological samples, AND treated as such) were included in a retrospective cohort study. After cohort description, determinants of treatment failure (i.e, infection persistence, relapse, requirement of additional surgical procedure, and BJI-related death) were determined using stepwise logistic regression and Kaplan Meier curve analysis.