Method

Sixty-two clinical samples from patients with BJI were sequenced on MinION* using the in-house partial amplification of the 16S rRNA gene. BJI were defined based on the ICM Philly 2018 and EBJIS 2021 criteria. Among the 62 samples, 16 (26%) were culture-positive, including 6 polymicrobial infections, and 46 (74%) were culture-negative from mono- and polymicrobial infections based on Sanger-sequencing. Contamination, background noise definition, bacterial identification, and time-effectiveness issues were addressed.

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 10^e9 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.

Method

BF-JI was performed on synovial fluid from patients with clinical suspicion of acute JI, either septic arthritis or periprosthetic JI, in 6 French centers. The results of BF-JI were compared with the results of culture of synovial fluid and other concomitantly collected osteoarticular samples obtained in routine testing in the clinical microbiology laboratory.

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.

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).

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.

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.

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.

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).

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.

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)

Method

Effect of SA infection (8325–4/FnBP+; DU5883/FnBP-) on the viability, differentiation and mineralization of an OB cell line was measured in vitro by MTT and Phosphatase Alcaline (PAL) activity assays and quantification of calcium deposits using Alizarin red, respectively. A gentamicin protection assay (GPA) confirmed that the effects observed are due solely to the internalized SA. In vivo, X-ray microtomography (μCT) and 3D reconstruction was used to evaluate the impact of SA infection on bone formation and bone resorption in a mouse model of femur infection.

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.

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.

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.

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.

Methods

Using an ex vivo model of intracellular infection of human osteoblast-like cells (MG-63), two strains of S. aureus HG003 wild type and its isogenic mutant HG003 ΔmazEF were compared in terms of : i) internalization and intracellular survival by lysostaphin protective assay and ii) cytotoxicity by quantifying LDH in the culture supernatant, 24h and 48h after infection.

Method

All patients managed in a reference center in France between 2011 and 2016 receiving an empirical antimicrobial therapy for PJI were included in a prospective cohort study. Antimicrobial-related AE upcoming during the empirical treatment phase were describe according to the Common Terminology Criteria for Adverse Events (CTCEA), and severe ones (grade ≥ 3) were reported to pharmacovigilance. AE determinants were assessed using univariate logistic regression.

Method

Adult patients with pressure ulcer-related pelvic osteomyelitis treated by a two-stage surgical strategy were included in a retrospective cohort study. Determinants of superinfection (i.e., additional microbiological findings at reconstruction) and treatment failure were assessed using binary logistic regression and Kaplan-Meier curve analysis.

Method

Methods: Three pairs of VSSA/VISA clinical isolates have been isolated from persistent bloodstream infections during prolonged antibiotic therapy. Clinical pairs were compared for different features: i) biofilm formation ability using the crystal violet staining method (mature biofilm) and the Biofilm test based on measurement of superparamagnetic microbeads mobility trapped by biofilm (early biofilm), ii) cytotoxicity and immune response by quantifying lactate dehydrogenase (LDH) and Interleukin(IL)-6 release and iii) intracellular bacterial persistence using in vitro “lysostaphin protection” infection model of human osteoblasts.