A prospective multicentre evaluation of BioFire® Joint Infection Panel for the rapid microbiological documentation of acute arthritis.

OBJECTIVES: To assess the performance of the rapid syndromic BioFire® Joint Infection Panel (BF-JIP) to detect bacterial and fungal pathogens, as well as antibiotic resistance genes, directly in synovial fluid specimens collected from patients with acute arthritis. METHODS: The study was conducted in six French bacteriological laboratories. To assess the performances of BF-JIP, results were compared with those of synovial fluid 14-day culture and, in case of discrepancy, with those of complementary molecular methods and intraoperative samples. A total of 308 synovial fluid specimens were tested after collection from 308 adults and children presenting with clinical and biological suspicion of acute arthritis; patients presenting with acute periprosthetic joint infection were included according to the European Bone and Joint Infection Society 2021 criteria. RESULTS: Only one specimen failed (no result). On the basis of the consolidated data, the BF-JIP was concordant with the 14-day culture in 280 (91.2%) of the 307 specimens finally included in the study. The positive percentage agreement was 84.9% (95% CI, 78.8-89.8%) and the negative percentage agreement was 100% (95% CI, 97.2-100%). The positive predictive value was extremely high (100%; 95% CI, 97.6-100%), whereas the negative predictive value was lower (82.6%; 95% CI, 75.7-88.2%), partially explained by the missing target species in the panel. DISCUSSION: The BF-JIP showed high performances to detect pathogens involved in acute arthritis.

Comparative effectiveness of empirical antibiotic treatments in methicillin-susceptible Staphylococcus aureus infective endocarditis: A post hoc analysis of a prospective French cohort study.

OBJECTIVES: The empirical treatment of infective endocarditis is still debated. The aim of this study was to compare the impact of empirical treatment with antistaphylococcal penicillin (ASP) or cefazolin vs. other treatments in methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis. METHODS: A post hoc analysis of a prospective cohort study of patients hospitalized in a French reference centre with MSSA endocarditis was conducted between 2013 and 2022. The primary outcome was the duration of bacteraemia under treatment. RESULTS: Of the 208 patients included, 101 patients (48.6%) were classified in the reference group (ASP or cefazolin) and 107 (52.4%) in the non-reference group. Empirical treatment with ASP/cefazolin was associated with a shorter duration of bacteraemia compared to other treatments (3.6 d vs. 4.6 d, P = 0.01). This difference was not corrected by the addition of an aminoglycoside (3.6 d vs. 4.7 d, P < 0.01). In multivariate analysis, empirical treatment with ASP/cefazolin was associated with a duration of bacteraemia ≤72 h (P = 0.02), whereas endocarditis on native valves (P = 0.01), and intracardiac abscess were associated with longer duration of bacteraemia (P = 0.01). CONCLUSIONS: Empirical treatment of endocarditis with ASP or Cefazolin is more effective than other treatments in MSSA endocarditis, even when the other treatments are combined with aminoglycosides.

Staphylococcus succinus Infective Endocarditis, France.

Infective endocarditis is a rare condition in humans and is associated with high illness and death rates. We describe a case of infective endocarditis caused by Staphylococcus succinus bacteria in France. We used several techniques for susceptibility testing for this case to determine the oxacillin profile.

Clinical, Bacteriological, and Genetic Characterization of Bone and Joint Infections Involving Linezolid-Resistant Staphylococcus epidermidis: a Retrospective Multicenter Study in French Reference Centers.

The choice of the best probabilistic postoperative antibiotics in bone and joint infections (BJIs) is still challenging. Since the implementation of protocolized postoperative linezolid in six French referral centers, linezolid-resistant multidrug-resistant Staphylococcus epidermidis (LR-MDRSE) strains were isolated in patients with BJI. We aimed here to describe clinical, microbiological, and molecular patterns associated with these strains. All patients with at least one intraoperative specimen positive for LR-MDRSE between 2015 and 2020 were included in this retrospective multicenter study. Clinical presentation, management, and outcome were described. LR-MDRSE strains were investigated by MIC determination for linezolid and other anti-MRSA antibiotics, characterization of genetic determinants of resistance, and phylogenetic analysis. Forty-six patients (colonization n = 10, infection n = 36) were included in five centers, 45 had prior exposure to linezolid, 33 had foreign devices. Clinical success was achieved for 26/36 patients. Incidence of LR-MDRSE increased over the study period. One hundred percent of the strains were resistant to oxazolidinones, gentamicin, clindamycin, ofloxacin, rifampicin, ceftaroline, and ceftobiprole, and susceptible to cyclins, daptomycin, and dalbavancin. Susceptibility to delafloxacin was bimodal. Molecular analysis was performed for 44 strains, and the main mutation conferring linezolid resistance was the 23S rRNA G2576T mutation. All strains belonged to the sequence type ST2 or its clonal complex, and phylogenetic analysis showed emergence of five populations corresponding geographically to the centers. We showed the emergence of new clonal populations of highly linezolid-resistant S. epidermidis in BJIs. Identifying patients at risk for LR-MDRSE acquisition and proposing alternatives to systematic postoperative linezolid use are essential. IMPORTANCE The manuscript describes the emergence of clonal linezolid-resistant strains of Staphylococcus epidermidis (LR-MDRSE) isolated from patients presenting with bone and joint infections. Incidence of LR-MDRSE increased over the study period. All strains were highly resistant to oxazolidinones, gentamicin, clindamycin, ofloxacin, rifampicin, ceftaroline, and ceftobiprole, but were susceptible to cyclins, daptomycin, and dalbavancin. Susceptibility to delafloxacin was bimodal. The main mutation conferring linezolid resistance was the 23S rRNA G2576T mutation. All strains belonged to the sequence type ST2 or its clonal complex, and phylogenetic analysis showed emergence of five populations corresponding geographically to the centers. LR-MDRSE bone and joint infections seem to be accompanied by an overall poor prognosis related to comorbidities and therapeutic issues. Identifying patients at risk for LR-MDRSE acquisition and proposing alternatives to systematic postoperative linezolid use become essential, with a preference for parenteral drugs such as lipopeptids or lipoglycopeptids.

Xpert MTB/RIF Ultra Trace Results: Decision Support for the Treatment of Extrapulmonary Tuberculosis in Low TB Burden Countries.

OBJECTIVES: Extrapulmonary tuberculosis (EPTB) can be difficult to diagnose, especially in severe forms. The Xpert MTB/RIF Ultra test introduced an additional category called trace to reference very small amounts of Mycobacterium tuberculosis complex (MTBC) DNA. The objective of our multicenter study was to evaluate whether the trace result on an extrapulmonary (EP) sample is a sufficient argument to consider diagnosing tuberculosis and starting treatment, even in severe cases. METHODS: A retrospective, multicenter cohort study was conducted from 2018 to 2022. Patients strongly suspected of EPTB with a trace result on an EP specimen were included. Hospital records were reviewed for clinical, treatment, and paraclinical data. RESULTS: A total of 52 patients were included, with a severe form in 22/52 (42.3%) cases. Culture was positive for MTBC in 33/46 (71.7%) cases. Histological analysis showed granulomas in 36/45 (80.0%) cases. An Ultra trace result with a presumptive diagnosis of TB led to the decision to treat 41/52 (78.8%) patients. All patients were started on first-line anti-TB therapy (median duration of 6.1 months), with a favorable outcome in 31/35 (88.6%) patients. The presence of a small amount of MTBC genome in EPTB is a sufficient argument to treat patients across a large region of France.

Genetic Diversity and Population Structure of Mycobacterium bovis at the Human-Animal-Ecosystem Interface in France: "A One Health Approach".

Mycobacterium bovis infects cattle and wildlife, and also causes a small proportion of tuberculosis cases in humans. In most European countries, M. bovis infections in cattle have been drastically reduced, but not eradicated. Here, to determine the M. bovis circulation within and between the human, cattle, and wildlife compartments, we characterized by spoligotyping and mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing the genetic diversity of M. bovis isolates collected from humans, cattle, and wildlife in France from 2000 to 2010. We also assessed their genetic structure within and among the different host groups, and across time and space. The M. bovis genetic structure and its spatiotemporal variations showed different dynamics in the human and animal compartments. Most genotypes detected in human isolates were absent in cattle and wildlife isolates, possibly because in patients, M. bovis infection was contracted abroad or was the reactivation of an old lesion. Therefore, they did not match the genetic pool present in France during the study period. However, some human-cattle exchanges occurred because some genotypes were common to both compartments. This study provides new elements for understanding M. bovis epidemiology in France, and calls for increased efforts to control this pathogen worldwide.

Synovial calprotectin: A potentially useful biomarker for the diagnosis of Kingella kingae native arthritis.

Kingella kingae is a bacteria involved in developing arthritis in children. Its diagnosis remains difficult. We report a case for which a new biomarker, calprotectin measured in the synovial fluid, was strongly positive and a specific molecular test was the only way to diagnose it specifically.

A fatal case associated with Catabacter hongkongensis bacteremia in lung cancer patient: A case report.

Catabacter hongkongensis is a bacterium first isolated in 2007 and has since been detected in the blood of about fifteen patients with disease such as gastrointestinal malignancy, intestinal obstruction, or acute intestinal infection. We describe herein the case of a patient newly diagnosed with metastatic lung cancer, who died from a fatal infection possibly related to Catabacter hongkongensis bacteremia. By reviewing all cases reported in the literature, our case report supports that this infection is associated with a very high mortality in cancer patients.

Clinical Features and Outcome of Multidrug-Resistant Osteoarticular Tuberculosis: A 12-Year Case Series from France.

The optimal treatment for osteoarticular infection due to multidrug-resistant tuberculosis strains (MDR-OATB) remains unclear. This study aims to evaluate the diagnosis, management and outcome of MDR-OATB in France. We present a case series of MDR-OATB patients reviewed at the French National Reference Center for Mycobacteria between 2007 and 2018. Medical history and clinical, microbiological, treatment and outcome data were collected. Twenty-three MDR-OATB cases were reported, representing 3% of all concurrent MDR-TB cases in France. Overall, 17 were male, and the median age was 32 years. Six patients were previously treated for TB, including four with first-line drugs. The most frequently affected site was the spine (n = 16). Bone and joint surgery were required in 12 patients. Twenty-one patients (91%) successfully completed the treatment with a regimen containing a mean of four drugs (range, 2-6) for a mean duration of 20 months (range, 13-27). Overall, high rates of treatment success were achieved following WHO MDR-TB treatment guidelines and individualized patient management recommendations by the French National TB Consilium. However, the optimal combination of drugs, duration of treatment and role of surgery in the management of MDR-OATB remains to be determined.

Genotypic Characterization and Biofilm Production of Group B Streptococcus Strains Isolated from Bone and Joint Infections.

Bone and joint infections (BJI) represent the second cause of invasive Group B Streptococcus (GBS) infections. Biofilm formation plays a major role in BJI. This study's aim was to analyze the genetic features and biofilm production of GBS strains. In six French laboratories, 77 GBS strains isolated from BJI and 57 strains from vaginal human colonization (Hcol) were characterized and compared by Multi-Locus Sequence Typing (MLST). PCR was used to search for the adhesins (bsaB, lmb, scpB, fbsA, fbsB, hvgA, bibA, bca, srr-1, and srr-2) and Pilus Islands (PI) related genes (PI-1, PI-2a, PI-2b). Biofilm production was studied by crystal violet assay. Strains were categorized into three groups, based on Specific Biofilm Formation (SBF) values defined as: weak, moderate, or strong producers. Molecular study revealed three major clonal complexes (CC) in BJI strains: CC1 (42%), CC23 (22%) and CC10 (14%). Several associations between CC and adhesin/pili were identified: CC1 with srr2, PI-1 + 2a; CC10 with srr-1, bca, PI-1 + 2a; CC17 with fbsB, hvgA, srr-2, PI-1+PI-2b; CC19 with bibA, srr-1, PI-1 + 2a; CC23 with fbsB, bibA, srr-1, PI-2a. The biofilm production was significantly different according to CC, adhesins and pili gene detection. CC10, CC23 and strains harboring fbsB produce more biofilm than CC1, PI-1 + 2a (independently). Finally, SBF values were significantly stronger for Hcol strains rather than for BJI strains (76% versus 40%). This study revealed that Hcol strains appeared to produce stronger biofilm than BJI strains, though they belonged to similar CCs and had the same adhesin and pili content. IMPORTANCE Bone and joint infections (BJI) are pathologies that can be life-threatening and result in compromised functional prognosis for patients. Relapses are common and often related to biofilm formation. Group B streptococci (GBS) BJI increased since the last decade. However, few data are available on this subject in the literature. Our study aims to highlight genotype and biofilm production of GBS isolates from BJI. Seventy-seven GBS strains isolated from BJI and 57 from asymptomatic human vaginal colonization were characterized by multilocus sequence typing (MLST), adhesins content, nature of the pili and the ability to form biofilm. Our results revealed that vaginal human colonization strains produced stronger biofilm than BJI strains, despite belonging to the same phylogenetic lineage and having the same adhesin and pili content.

In vitro and in vivo activity of new strains of Bacillus subtilis against ESBL-producing Escherichia coli: an experimental study.

AIMS: The gastro-intestinal tract is a major reservoir of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli. Bacillus spores may be used as probiotics to decrease digestive colonization by ESBL-E. coli. Our aim was to assess the in vitro and in vivo activity of new Bacillus strains against ESBL-E. coli. METHODS AND RESULTS: We screened the in vitro activity of 50 Bacillus strains against clinical isolates of ESBL-E. coli and selected B. subtilis strains CH311 and S3B. Both strains decreased ESBL-E. coli titers by 4 log10 CFU L-1 in an in vitro model of gut content, whereas the B. subtilis CU1 strain did not. In a murine model of intestinal colonization by ESBL-E. coli, CH311 and S3B did not decrease fecal titers of ESBL-E. coli. Ten sequences of putative antimicrobial peptides were identified in the genomes of CH311 and S3B, but not in CU1. CONCLUSIONS: Two new B. subtilis strains showed strong in vitro activity against ESBL-E. coli. SIGNIFICANCE AND IMPACT OF STUDY: Despite strong in vitro activities of new B. subtilis strains against ESBL-E. coli, intestinal colonisation was not altered by curative Bacillus treatment even if their spores proved to germinate in the gut. Thus, this work underlines the importance of in vivo experiments to identify efficient probiotics. The use of potential antimicrobial compounds identified by genome sequencing remains an attractive alternative to explore.

Evaluation of the Use of Antibiofilmogram Technology in the Clinical Evolution of Foot Ulcers Infected by Staphylococcus aureus in Persons Living with Diabetes: A Pilot Study.

Infected diabetic foot ulcers (DFUs) represent a serious threat to public health because of their frequency and the severity of their consequences. DFUs are frequently infected by bacteria in biofilms, obstructing antibiotic action. Antibiofilmogram was developed to assess the impact of antibiotics to inhibit biofilm formation. This pilot study aimed to determine the benefits of this technology in predicting antibiotic activity on the outcome of 28 patients with Grade 2 DFUs that were infected by a monomicrobial Staphylococcus aureus. Patients with diabetes were followed during the antibiotic treatment (day 14) and the follow-up period of the study (day 45). The contribution of Antibiofilmogram was compared between patients with non-concordant results (n = 13) between antibiogram and Antibiofilmogram versus concordant results (n = 15). The clinical improvement of wounds (80.0% vs. 38.5%, p = 0.0245) and the absence of exudates (0% vs. 33.3%, p = 0.0282) were observed in concordant vs. discordant groups. This pilot study provides promising results for the interest of Antibiofilmogram in the prescription of antibiotics to prevent biofilm formation in infected DFUs.

Impact of Phage Therapy on Multidrug-Resistant Escherichia coli Intestinal Carriage in a Murine Model.

INTRODUCTION: The growing resistance of bacteria to antibiotics is a major global public health concern. An important reservoir of this resistance is the gut microbiota. However, limited data are available on the ability of phage therapy to reduce the digestive carriage of multidrug-resistant bacteria. MATERIALS AND METHODS: Four novel lytic phages were isolated in vitro for efficacy against an extended-spectrum beta-lactamase-producing (ESBL) Escherichia coli strain also resistant to carbapenems through a carbapenemase OXA-48. The first step was to develop models of ESBL E. coli digestive carriage in mice. The second step was to test the efficacy of an oral and rectal phage therapy (a cocktail of four phages or microencapsulated phage) to reduce this carriage. RESULTS: The two most intense models of digestive carriage were obtained by administering amoxicillin (0.5 g·L-1) continuously in the drinking water (Model 1) or pantoprazole (0.1 g·L-1) continuously in the drinking water, combined with amoxicillin (0.5 g·L-1), for the first 8 days (Model 2). Oral administration of the phage cocktail to Model 1 resulted in a transient reduction in the concentration of ESBL E. coli in the faeces 9 days after the bacterial challenge (median = 5.33 × 108 versus 2.76 × 109 CFU·g-1, p = 0.02). In contrast, in Model 2, oral or oral + rectal administration of this cocktail did not alter the bacterial titre compared to the control (area under the curve, AUC, 3.49 × 109; 3.41 × 109 and 3.82 × 109 for the control, oral and oral + rectal groups, respectively; p-value > 0.8 for each two-by-two group comparison), as well as the administration of an oral microencapsulated phage in Model 1 (AUC = 8.93 × 109 versus 9.04 × 109, p = 0.81). CONCLUSIONS: Oral treatment with amoxicillin promoted digestive carriage in mice, which was also the case for the addition of pantoprazole. However, our study confirms the difficulty of achieving efficacy with phage therapy to reduce multidrug-resistant bacterial digestive carriage in vivo.

Management of patients with pulmonary mycobacteriosis in France: a multicenter retrospective cohort study.

BACKGROUND: Recent studies report very low adherence of practitioners to ATS/IDSA recommendations for the treatment of nontuberculous mycobacteria pulmonary disease (NTM-PD), as well as a great variability of practices. Type of management could impact prognosis. METHODS: To evaluate management and prognosis of patients with NTM-PD cases with respect to ATS recommendations, we conducted a multicenter retrospective cohort study (18 sentinel sites distributed throughout France), over a period of six years. We collected clinical, radiological, microbiological characteristics, management and outcome of the patients (especially death or not). RESULTS: 477 patients with NTM-PD were included. Respiratory comorbidities were found in 68% of cases, tuberculosis sequelae in 31.4% of patients, and immunosuppression in 16.8% of cases. The three most common NTM species were Mycobacterium avium complex (60%), M. xenopi (20%) and M. kansasii (5.7%). Smear-positive was found in one third of NTM-PD. Nodulobronchiectatic forms were observed in 54.3% of cases, and cavitary forms in 19.1% of patients. Sixty-three percent of patients were treated, 72.4% of patients with smear-positive samples, and 57.5% of patients with smear-negative samples. Treatment was in adequacy with ATS guidelines in 73.5%. The 2-year mortality was 14.4%. In the Cox regression, treatment (HR = 0.51), age (HR = 1.02), and M. abscessus (3.19) appeared as the 3 significant independent prognostic factors. CONCLUSION: These findings highlight the adequacy between French practices and the ATS/IDSA guidelines. Treatment was associated with a better survival.

Assessment of a Multiplex LAMP Assay (Eazyplex® CSF Direct M) for Rapid Molecular Diagnosis of Bacterial Meningitis: Accuracy and Pitfalls.

Background: Automated molecular panels are attractive tools for improving early meningitis diagnosis. This study assessed the Eazyplex® CSF direct M panel (EP), a multiplex real-time Loop-Mediated Isothermal Amplification assay. Methods: From December 2016 to December 2019, cerebrospinal fluid (CSF) samples were routinely tested with the EP V1.0. CSF parameters and microbiological and clinical data were retrospectively collected. Results: Out of 230 CSF samples, the EP yielded positive, negative, and invalid results for 32 (13.9%) (16 N. meningitidis, nine S. pneumoniae, two S. agalactiae, two E. coli, two H. influenzae, one L. monocytogenes), 182 (79.1%), and 16 (7%) samples, respectively. Among the positive samples, 14 (44%) remained negative in culture (antibiotic therapy before lumbar puncture (n = 11), meningococcal meningitis (n = 3)). High CSF protein concentrations and cellularity were associated with LAMP inhibition, counteracted by centrifugation. The automated software yielded 13 false positive and five false negative results. Amplification curve analysis was necessary and enabled the attainment of positive (PPA) and negative percentage agreement and positive and negative predictive values of 91.4%, 100%, 100%, and 98.3%. Three false negative results remained (two E. coli and one N. meningitidis). E. coli presented the poorest PPA (50%). Conclusion: This work confirms the strong performance of the EP, of particular interest in cases of antibiotic therapy before lumbar puncture.

A Short-Course Antibiotic Prophylaxis Is Associated with Limited Antibiotic Resistance Emergence in Post-Operative Infection of Pelvic Primary Bone Tumor Resection.

Resections of primary pelvic bone tumors are frequently complicated by surgical site infections (SSIs), thereby impairing the functional prognosis of patients, especially in case of implant removal. Although prophylactic antibiotics play an essential role in preventing SSIs, there are presently no recommendations that support their appropriate use. This study aimed to assess the impact of a 24 h prophylactic protocol on the bacterial ecology, the resistance pattern, and the SSI healing rate. We hypothesized that this protocol not only limits the emergence of resistance but also results in a good cure rate with implant retention in case of SSI. A retrospective study was performed that included all patients with an SSI following a pelvic bone tumoral resection between 2005 and 2017 who received a 24 h antibiotic prophylaxis protocol. Twenty-nine patients with an SSI were included. We observed a 75.9% rate of polymicrobial infection, with a high prevalence of digestive flora microorganisms and a majority of wild-type phenotypes. We confirmed that there was no significant emergence of resistant flora. After first-line debridement, antibiotics (DA) if any implant was used, or debridement, antibiotics, and implant retention (DAIR) whenever possible, we obtained a 79.3% cure rate, with implant removal in 20% of cases. The absence of an implant was significantly associated with SSI healing. Early infection management and low resistance profiles may also have a positive effect, but this needs to be confirmed in a larger cohort. In light of this, the use of a 24 h prophylactic protocol in primary pelvic bone tumor resections is associated with a favorable infection cure rate and implant retention in case of SSI, and minimal selection of resistant microorganisms.

A prospective, observational study of fidaxomicin use for Clostridioides difficile infection in France.

OBJECTIVE: To describe the characteristics, management and outcomes of hospitalised patients with Clostridioides difficile infection (CDI) treated with and without fidaxomicin. METHODS: This prospective, multicentre, observational study (DAFNE) enrolled hospitalised patients with CDI, including 294 patients treated with fidaxomicin (outcomes recorded over a 3-month period) and 150 patients treated with other CDI therapies during three 1-month periods. The primary endpoint was baseline and CDI characteristics of fidaxomicin-treated patients. RESULTS: At baseline, the fidaxomicin-treated population included immunocompromised patients (39.1%) and patients with severe (59.2%) and recurrent (36.4%) CDI. Fidaxomicin was associated with a high rate of clinical cure (92.2%) and low CDI recurrence (16.3% within 3 months). Clinical cure rates were ≥90% in patients aged ≥65 years, those receiving concomitant antibiotics and those with prior or severe CDI. There were 121/296 (40.9%) patients with adverse events (AEs), 5.4% with fidaxomicin-related AEs and 1.0% with serious fidaxomicin-related AEs. No fidaxomicin-related deaths were reported. CONCLUSIONS: Fidaxomicin is an effective and well-tolerated CDI treatment in a real-world setting in France, which included patients at high risk of adverse outcomes.Trial registration: Description of the use of fidaxomicin in hospitalised patients with documented Clostridium difficile infection and the management of these patients (DAFNE), NCT02214771, www.ClinicalTrials.gov.