Search

Sonia Benammar,1,2 Alix Pantel,3,4 Fabien Aujoulat,5 Messaoud Benmehidi,1,2 René Courcol,6,7 Jean-Philippe Lavigne,3,4 Sara Romano-Bertrand,5,8 Hélène Marchandin3,5 1Department of Microbiology, University Hospital Center Touhami Benflis, Batna, Algeria; 2Department of Medicine, University Batna 2, Batna, Algeria; 3Department of Microbiology, Nîmes University Hospital, Nîmes, France; 4Faculty of Medicine, National Institute of Health and Medical Research, INSERM U1047, University of Montpellier, Nîmes, France; 5HydroSciences Montpellier, CNRS, IRD, University of Montpellier, University Hospital of Montpellier-Nîmes, Montpellier, France; 6Faculty of Medicine, University of Lille, Lille, France; 7Department of Bacteriology, Institute of Microbiology, Lille University Hospital, Lille, France; 8Department of Infection Control, Montpellier University Hospital, Montpellier, France Purpose: Vancomycin-resistant Enterococcus (VRE) faecium (VREfm) are highly resistant bacteria emerging worldwide and rarely studied using molecular tools in Algeria since their first report in 2006. The aim of the study was to investigate healthcare-associated infections (HAIs) involving the first VRE in Batna University Hospital, Algeria, and characterize isolates using molecular tools.Patients and methods: Medical charts were reviewed for patients with VREfm. van genes were detected by multiplex polymerase chain reaction (PCR), and strains were characterized by automated repetitive sequence-based PCR (rep-PCR), multiplex rep-PCR, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST).Results: During a 6-month period, VREfm infections occurred in four patients hospitalized in three wards. The four isolates were E. faecium vanA belonging to the hospital-adapted clonal complex 17. PCR-based methods did not discriminate the isolates but MLST and PFGE delineated a subgroup of three VREfm of identical pulsotype and sequence type (ST) 80 (yet identified for five isolates in the international PubMLST database) while the fourth isolate was of ST789 (not previously identified for a VREfm) and displayed an unrelated pulsotype. The three genotypically related isolates were recovered in patients who underwent surgery in the same department, suggesting an outbreak for which the source and route of transmission remained unidentified.Conclusion: This first molecular epidemiology study of VRE in Algeria was useful in delimiting an outbreak involving three of the four HAI cases and revealed rarely encountered genotypes. Considering the threat and burden of VRE infections worldwide, particularly in the USA, and the late emergence in Algeria, our study supports the urgent need for improved and early adequate infection control measures to avoid VRE spread in North African hospitals. Keywords: outbreak, genotyping, MLST, rep-PCR, PFGE, molecular epidemiology

Objective: To extend our previous work on evaluating the use of oligonucleotide arrays to discriminate colonization from infection owing to Staphylococcus aureus in diabetic foot ulcers (DFUs).Research Design and Methods: Patients admitted to 14 French diabetic foot departments for a DFU were screened for entry into the study. At admission, ulcers were classified based on clinical examination according to the Infectious Diseases Society of America system. Only patients with monomicrobial culture for S. aureus were included. In persons with an uninfected ulcer, a second wound bacterial specimen was obtained 1 month later. Using oligonucleotide arrays, S. aureus resistance and virulence genes were determined, and each isolate was affiliated to a clonal complex (CC).Results: S. aureus was initially isolated from 75 uninfected and 120 infected ulcers; 35 were methicillin resistant. A total of 44 (59%) strains from uninfected DFUs belonged to CC5/CC8 clones vs. 6 (5%) from infected DFUs (P < 0.001). During follow-up, 57 (76%) of uninfected DFUs healed or had a favorable outcome; the strain in 49 (86%) of them belonged to CC5/CC8. Conversely, 18 (24%) had a poor outcome but not a single strain belonged to CC5/CC8 clone. Moreover, lukDE was significantly associated with a favorable outcome of the wound.Conclusions: As suggested by our previous study, the use of DNA arrays appears to be a promising technique that might help distinguishing uninfected from infected wounds, predicting ulcer outcome and then contributing to a more adequate use of antibiotics. [ABSTRACT FROM AUTHOR]

Background: Prosthetic joint infection (PJI) caused by Candida spp is a severe complication of arthroplasty. We investigated the outcomes of Candida PJI., Methods: This was a retrospective observational multinational study including patients diagnosed with Candida-related PJI between 2010 and 2021. Treatment outcome was assessed at 2-year follow-up., Results: A total of 269 patients were analyzed. Median age was 73.0 (interquartile range [IQR], 64.0-79.0) years; 46.5% of patients were male and 10.8% were immunosuppressed. Main infection sites were hip (53.0%) and knee (43.1%), and 33.8% patients had fistulas. Surgical procedures included debridement, antibiotics, and implant retention (DAIR) (35.7%), 1-stage exchange (28.3%), and 2-stage exchange (29.0%). Candida spp identified were Candida albicans (55.8%), Candida parapsilosis (29.4%), Candida glabrata (7.8%), and Candida tropicalis (5.6%). Coinfection with bacteria was found in 51.3% of cases. The primary antifungal agents prescribed were azoles (75.8%) and echinocandins (30.9%), administered for a median of 92.0 (IQR, 54.5-181.3) days. Cure was observed in 156 of 269 (58.0%) cases. Treatment failure was associated with age >70 years (OR, 1.811 [95% confidence interval {CI}: 1.079-3.072]), and the use of DAIR (OR, 1.946 [95% CI: 1.157-3.285]). Candida parapsilosis infection was associated with better outcome (OR, 0.546 [95% CI: .305-.958]). Cure rates were significantly different between DAIR versus 1-stage exchange (46.9% vs 67.1%, P = .008) and DAIR versus 2-stage exchange (46.9% vs 69.2%, P = .003), but there was no difference comparing 1- to 2-stage exchanges (P = .777)., Conclusions: Candida PJI prognosis seems poor, with high rate of failure, which does not appear to be linked to immunosuppression, use of azoles, or treatment duration., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Cefiderocol is a siderophore-conjugated cephalosporin increasingly used in the management of Achromobacter infections. Testing for cefiderocol susceptibility is challenging with distinct recommendations depending on the pathogens., Objectives: We evaluated the performance of commercial tests for testing cefiderocol susceptibility in the Achromobacter genus and reviewed the literature., Methods: Diffusion (disks, MIC gradient test strips [MTS], Liofilchem) and broth microdilution (BMD) methods (ComASP™, Liofilchem; UMIC ® , Bruker) were compared with the BMD reference method according to the EUCAST guidelines on 143 Achromobacter strains from 14 species with MIC 50/90 of ≤ 0.015/0.5 mg/L. A literature search was conducted regardless of method or species., Results: None of the methods tested fulfilled an acceptable essential agreement (EA). MTS displayed the lowest EA (30.8%) after UMIC ® (49%) and ComASP™ (76.9%). All methods achieved an acceptable bias, with MICs either underestimated using MTS (-1.3%) and ComASP™ (-14.2%) or overestimated with UMIC ® (+ 9.1%). Inhibition zone diameters ranged from 6 to 38 mm (IZD 50/90 =33/30 mm). UMIC ® and ComASP™ failed to categorize one or the two cefiderocol-resistant strains of this study as resistant unlike the diffusion-based methods. The literature review highlighted distinct performance of the available methods according to pathogens and testing conditions., Conclusions: The use of MTS is discouraged for Achromobacter spp. Disk diffusion can be used to screen for susceptible strains by setting a threshold diameter of 30 mm. UMIC ® and ComASP™ should not be used as the sole method but have to be systematically associated with disk diffusion to detect the yet rarely described cefiderocol-resistant Achromobacter sp. strains., (© 2024. The Author(s).)

Purpose: The vaginal microbiota offers valuable insights into women's sexual health and the risk of developing sexually transmitted infections (STIs) and bacterial vaginosis. Despite the public health implications of changes in the vaginal environment, existing data on this topic remain sparse., Methods: Following the PRISMA statement guidelines, we consulted five bibliographic databases, focusing on five main daily habits and behaviors. We included only studies published up to October 2023, investigating the influence of personal hygiene, sexual behaviors, hormonal contraception, smoking, alcohol consumption, and psychosocial stress on the vaginal microbiota using next-generation sequencing., Results: Based on our inclusion criteria, we incorporated 37 studies into this review. Hormonal contraception and personal hygiene were found to promote eubiosis of the vaginal microbiota. In contrast, sexual behaviors, smoking, alcohol consumption, and psychosocial stress were associated with an increased susceptibility to bacterial vaginosis, STIs, and severe pelvic inflammatory diseases due to a modified vaginal microbiota. Black ethnicity emerged as a confounding factor, with this population showing unstable vaginal microbiota. Oral contraception and a stable male sexual partner were found to favor Lactobacillus colonization, acting as a protective factor. Conversely, non-hormonal contraception and unprotected or non-penile/vaginal sexual activity increased the incidence of vaginal inflammation and bacterial vaginosis by disturbing the vaginal microbiota and reducing Lactobacillus abundance., Conclusion: Daily habits and lifestyle can influence the composition of the vaginal microbiota, thereby affecting vaginal health. Disturbances in the vaginal microbiota could be associated factors for STIs and vaginosis. Therefore, prioritizing more appropriate management of the vaginal microbiota is crucial., (© 2024. The Author(s).)

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., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

An emergence of multidrug-resistant (MDR) Staphylococcus haemolyticus has been observed in the neonatal intensive care unit (NICU) of Nîmes University Hospital in southern France. A case-control analysis was conducted on 96 neonates, to identify risk factors associated with S. haemolyticus infection, focusing on clinical outcomes. Forty-eight MDR S. haemolyticus strains, isolated from neonates between October 2019 and July 2022, were investigated using routine in vitro procedures and whole-genome sequencing. Additionally, five S. haemolyticus isolates from adult patients were sequenced to identify clusters circulating within the hospital environment. The incidence of neonatal S. haemolyticus was significantly associated with low birth weight, lower gestational age, and central catheter use ( p  < 0.001). Sepsis was the most frequent clinical manifestation in this series (20/46, 43.5%) and was associated with five deaths. Based on whole-genome analysis, three S. haemolyticus genotypes were predicted: ST1 (6/53, 11%), ST25 (3/53, 5.7%), and ST29 (44/53, 83%), which included the subcluster II-A, predominantly emerging in the neonatal department. All strains were profiled in silico to be resistant to methicillin, erythromycin, aminoglycosides, and fluoroquinolones, consistent with in vitro antibiotic susceptibility tests. Moreover, in silico prediction of biofilm formation and virulence-encoding genes supported the association of ST29 with severe clinical outcomes, while the persistence in the NICU could be explained by the presence of antiseptic and heavy metal resistance-encoding genes. The clonality of S. haemolyticus ST29 subcluster II-A isolates confirms healthcare transmission causing severe infections. Based on these results, reinforced hygiene measures are necessary to eradicate the nosocomial transmission of MDR strains.

Background: Achromobacter spp. are opportunistic pathogens, mostly infecting immunocompromised patients and patients with cystic fibrosis (CF) and considered as difficult-to-treat pathogens due to both intrinsic resistance and the possibility of acquired antimicrobial resistance. Species identification remains challenging leading to imprecise descriptions of resistance in each taxon. Cefiderocol is a broad-spectrum siderophore cephalosporin increasingly used in the management of Achromobacter infections for which susceptibility data remain scarce. We aimed to describe the susceptibility to cefiderocol of a collection of Achromobacter strains encompassing different species and isolation sources from CF or non-CF (NCF) patients., Methods: We studied 230 Achromobacter strains (67 from CF, 163 from NCF patients) identified by nrdA gene-based analysis, with available susceptibility data for piperacillin-tazobactam, meropenem and trimethoprim-sulfamethoxazole. Minimal inhibitory concentrations (MICs) of cefiderocol were determined using the broth microdilution reference method according to EUCAST guidelines., Results: Strains belonged to 15 species. A. xylosoxidans represented the main species (71.3%). MICs ranged from ≤ 0.015 to 16 mg/L with MIC 50/90 of ≤ 0.015/0.5 mg/L overall and 0.125/2 mg/L against 27 (11.7%) meropenem-non-susceptible strains. Cefiderocol MICs were not related to CF/NCF origin or species although A. xylosoxidans MICs were statistically lower than those of other species considered as a whole. Considering the EUCAST non-species related breakpoint (2 mg/L), 228 strains (99.1%) were susceptible to cefiderocol. The two cefiderocol-resistant strains (A. xylosoxidans from CF patients) represented 3.7% of meropenem-non-susceptible strains and 12.5% of MDR strains., Conclusions: Cefiderocol exhibited excellent in vitro activity against a large collection of accurately identified Achromobacter strains, irrespective of species and origin., (© 2024. The Author(s).)

Background: Pancreatic cancer, predominantly characterized by ductal adenocarcinoma (PDAC) accounts for 90% of cases and is the fourth leading cause of cancer-related deaths globally. Its incidence is notably increasing. This poor prognosis is primarily due to late-stage diagnosis (approximately 70% to 80% of patients are diagnosed at an advanced stage), aggressive tumor biology, and low sensitivity to chemotherapy. Consequently, it is crucial to identify and develop a simple, feasible and reproducible blood-based signature (i.e., combination of biomarkers) for early detection of PDAC., Methods: The PANLIPSY study is a multi-center, non-interventional prospective clinical trial designed to achieve early detection of PDAC with high specificity and sensitivity, using a combinatorial approach in blood samples. These samples are collected from patients with resectable, borderline or locally advanced, and metastatic stage PDAC within the framework of the French Biological and Clinical Database for PDAC cohort (BACAP 2). All partners of the BACAP consortium are eligible to participate. The study will include 215 PDAC patients, plus 25 patients with benign pancreatic conditions from the PAncreatic Disease Cohort of TOuLouse (PACTOL) cohort, and 115 healthy controls, totaling 355 individuals. Circulating biomarkers will be collected in a total volume of 50 mL of blood, divided into one CellSave tube (10 mL), two CELL-FREE DNA BCT® preservative tubes (18 mL), and five EDTA tubes (22 mL in total). Samples preparation will adhere to the guidelines of the European Liquid Biopsy Society (ELBS). A unique feature of the study is the AI-based comparison of these complementary liquid biopsy biomarkers. Main end-points: i) to define a liquid biopsy signature that includes the most relevant circulating biomarkers, ii) to validate the multi-marker panel in an independent cohort of healthy controls and patients, with resectable PDAC, and iii) to establish a unique liquid biopsy biobank for PDAC study., Discussion: The PANLIPSY study is a unique prospective non-interventional clinical trial that brings together liquid biopsy experts. The aim is to develop a biological signature for the early detection of PDAC based on AI-assisted detection of circulating biomarkers in blood samples (CTCs, ctDNA, EVs, circulating immune system, circulating cell-free nucleosomes, proteins, and microbiota)., Trial Registration: ClinicalTrials.gov Identifier: NCT06128343 / NCT05824403. Registration dates: June 8,2023 and April 21, 2023., (© 2024. The Author(s).)

Background: Non-surgical chronic wounds, including diabetes-related foot diseases (DRFD), pressure injuries (PIs) and venous leg ulcers (VLU), are common hard-to-heal wounds. Wound evolution partly depends on microbial colonisation or infection, which is often confused by clinicians, thereby hampering proper management. Current routine microbiology investigation of these wounds is based on in vitro culture, focusing only on a limited panel of the most frequently isolated bacteria, leaving a large part of the wound microbiome undocumented., Methods: A literature search was conducted on original studies published through October 2022 reporting metagenomic next generation sequencing (mNGS) of chronic wound samples. Studies were eligible for inclusion if they applied 16 S rRNA metagenomics or shotgun metagenomics for microbiome analysis or diagnosis. Case reports, prospective, or retrospective studies were included. However, review articles, animal studies, in vitro model optimisation, benchmarking, treatment optimisation studies, and non-clinical studies were excluded. Articles were identified in PubMed, Google Scholar, Web of Science, Microsoft Academic, Crossref and Semantic Scholar databases., Results: Of the 3,202 articles found in the initial search, 2,336 articles were removed after deduplication and 834 articles following title and abstract screening. A further 14 were removed after full text reading, with 18 articles finally included. Data were provided for 3,628 patients, including 1,535 DRFDs, 956 VLUs, and 791 PIs, with 164 microbial genera and 116 species identified using mNGS approaches. A high microbial diversity was observed depending on the geographical location and wound evolution. Clinically infected wounds were the most diverse, possibly due to a widespread colonisation by pathogenic bacteria from body and environmental microbiota. mNGS data identified the presence of virus (EBV) and fungi (Candida and Aspergillus species), as well as Staphylococcus and Pseudomonas bacteriophages., Conclusion: This study highlighted the benefit of mNGS for time-effective pathogen genome detection. Despite the majority of the included studies investigating only 16 S rDNA, ignoring a part of viral, fungal and parasite colonisation, mNGS detected a large number of bacteria through the included studies. Such technology could be implemented in routine microbiology for hard-to-heal wound microbiota investigation and post-treatment wound colonisation surveillance., (© 2024. The Author(s).)

Objectives: Full median sternotomy (FMS) is the common surgical access for patients undergoing replacement of the ascending aorta (AA) with or without aortic valve replacement (AVR). The right anterior mini-thoracotomy (RAMT) approach has been increasingly adopted for AVR. This approach has been shown to decrease blood loss and hospital length of stay (LOS) compared with FMS. The RAMT approach may also be beneficial in selected patients requiring AA procedures with or without AVR. We present our initial clinical experience of patients who have undergone a RAMT for supracommissural replacement of the tubular AA with or without AVR., Methods: This is a single-center retrospective review of 10 patients who underwent an elective RAMT for replacement of the tubular AA with or without AVR between November 2019 and January 2022. Clinical outcomes evaluated include 30-day mortality, intensive care and hospital LOS, time to extubation, operative times, as well as postoperative complications such as stroke and bleeding., Results: Median cross-clamp and cardiopulmonary bypass times were 109 and 148 min, respectively. Median time to extubation was 2.5 h and median intensive care unit and hospital stay were 2 and 10 days, respectively. There were two re-thoracotomies for postoperative bleeding and two cases of sub-xiphoidal pericardial drainage for pericardial effusion. There were no strokes and no in-hospital nor 30-day mortalities., Conclusions: The replacement of the AA with or without concomitant AVR can be performed through a RAMT in carefully selected patients. However, the safety of this approach, as compared to full/partial median sternotomy, remains to be proven.

In forensic sciences, body fluids, or biological traces, are a major source of information, and their identification can play a decisive role in criminal investigations. Currently, the nature of biological fluids is assessed using immunological, physico-chemical, mRNA and epigenetic methods, but these have limits in terms of sensitivity and specificity. The emergence of next-generation sequencing technologies offers new opportunities to identify the nature of body fluids by determining bacterial communities. The aim of this pilot study was to assess whether analysis of the bacterial communities in isolated and mixed biological fluids could reflect the situation observed in real forensics labs. Several samples commonly encountered in forensic sciences were tested from healthy volunteers: saliva, vaginal fluid, blood, semen and skin swabs. These samples were analyzed alone or in combination in a ratio of 1:1. Sequencing was performed on the Ion Gene Studio TM S5 automated sequencer. Fluids tested alone revealed a typical bacterial signature with specific bacterial orders, enabling formal identification of the fluid of interest, despite inter-individual variations. However, in biological fluid mixtures, the predominance of some bacterial microbiomes inhibited interpretation. Oral and vaginal microbiomes were clearly preponderant, and the relative abundance of their bacterial communities and/or the presence of common species between samples made it impossible to detect bacterial orders or genera from other fluids, although they were distinguishable from one another. However, using the beta diversity, salivary fluids were identified and could be distinguished from fluids in combination. While this method of fluid identification is promising, further analyses are required to consolidate the protocol and ensure reliability.

Current microbiome investigations of patients with pressure ulcers (PU) are mainly based on wound swabs and/or biopsy sequencing, leaving the colonization scenario unclear. Urinary microbiota has been never studied. As a part of the prospective ESCAFLOR study, we studied urinary microbiota of spinal cord injury (SCI) patients with PU without any urinary tract infection at the inclusion, collected at two times (at admission [D0] and after 28 days [D28]) during the patient's care, investigated by 16S rDNA metagenomics next generation sequencing. Subgroup analyses were carried out between patients with wounds showing improved evolution versus stagnated/worsened wounds at D28. Analysis was done using EPISEQ® 16S and R software. Among the 12 studied patients, the urinary microbiota of patients with improved wound evolution at D28 (n = 6) presented a significant decrease of microbial diversity. This modification was associated with the presence of Proteobacteria phylum and an increase of Escherichia-Shigella (p = 0.005), as well as the presence of probiotic anaerobic bacteria Lactobacillus and Bifidobacterium. In contrast, Proteus abundance was significantly increased in urine of patients with stagnated/worsened wound evolution (n = 6) (p = 0.003). This study proposes urinary microbiota as a complementary factor indirectly associated with the wound evolution and patient cure. It opens new perspectives for further investigations based on multiple body microbiome comparison to describe the complete scenario of the transmission dynamics of wound-colonizing microorganisms., (© 2024 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: The transition from colonization to invasion is critical in diabetic foot ulcer (DFU). Staphylococcus aureus can colonize DFU, or invade the underlying tissues, causing serious infections. The ROSA-like prophage has previously been implicated in strain colonization characteristics of S aureus isolates in uninfected ulcers., Methods: In this study, we investigated this prophage in the S aureus-colonizing strain using an in vitro chronic wound medium mimicking the chronic wound environment., Results: Chronic wound medium reduced bacterial growth and increased biofilm formation and virulence in a zebrafish model., Conclusions: The ROSA-like prophage promoted intracellular survival of S aureus-colonizing strain in macrophages, keratinocytes, and osteoblasts., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Sepsis is a life-threatening organ dysfunction with high mortality rate. The gut origin hypothesis of multiple organ dysfunction syndrome relates to loss of gut barrier function and the ensuing bacterial translocation. The aim of this study was to describe the evolution of gut microbiota in a cohort of septic shock patients over seven days and the potential link between gut microbiota and bacterial translocation., Methods: Sixty consecutive adult patients hospitalized for septic shock in intensive care units (ICU) were prospectively enrolled. Non-inclusion criteria included patients with recent or scheduled digestive surgery, having taken laxatives, pre- or probiotic in the previous seven days, a progressive digestive neoplasia, digestive lymphoma, chronic inflammatory bowel disease, moribund patient, and pregnant and lactating patients. The primary objective was to evaluate the evolution of bacterial diversity and richness of gut microbiota during seven days in septic shock. Epidemiological, clinical and biological data were gathered over seven days. Gut microbiota was analyzed through a metagenomic approach. 100 healthy controls were selected among healthy blood donors for reference basal 16S rDNA values., Results: Significantly lower bacterial diversity and richness was observed in gut microbiota of patients at Day 7 compared with Day 0 (p<0.01). SOFA score at Day 0, Acute Gastrointestinal Injury (AGI) local grade, septic shock origin and bacterial translocation had an impact on alpha diversity. A large increase in Enterococcus genus was observed at Day 7 with a decrease in Enterobacterales, Clostridiales, Bifidobacterium and other butyrate-producing bacteria., Discussion: This study shows the importance of bacterial translocation during AGI in septic shock patients. This bacterial translocation decreases during hospitalization in ICUs in parallel to the decrease of microbiota diversity. This work highlights the role of gut microbiota and bacterial translocation during septic shock., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Magnan, Lancry, Salipante, Trusson, Dunyach-Remy, Roger, Lefrant, Massanet and Lavigne.)

Daptomycin (DAP) represents an interesting alternative to treat methicillin-resistant Staphylococcus aureus (MRSA) infections. Different mechanisms of DAP resistance have been described; however, in vivo-acquired resistance is uncharacterized. This study described the phenotypic and genotypic evolution of MRSA strains that became resistant to DAP in two unrelated patients with bacteremia under DAP treatment, in two hospitals in the South of France. DAP MICs were determined using broth microdilution method on the pairs of isogenic (DAP-S/DAP-R) S. aureus isolated from bloodstream cultures. Whole genome sequencing was carried out using Illumina MiSeq Sequencing system. The two cases revealed DAP-R acquisition by MRSA strains within three weeks in patients treated by DAP. The isolates belonged to the widespread ST5 (patient A) and ST8 (patient B) lineages and were of spa -type t777 and t622, respectively. SNP analysis comparing each DAP-S/DAP-R pair confirmed that the isolates were isogenic. The causative mutations were identified in MprF (Multiple peptide resistance Factor) protein: L826F (Patient A) and S295L (Patient B), and in Cls protein: R228H (Patient B). These proteins encoded both proteins of the lipid biosynthetic enzymes. The resistance to DAP is particularly poorly described whereas DAP is highly prescribed to treat MRSA. Our study highlights the non-systematic cross-resistance between DAP and glycopeptides and the importance of monitoring DAP MIC in persistent MRSA bacteremia.

Staphylococcus sp. is the most common bacterial genus in infections related to diabetic foot ulcers (DFUs). The emergence of multidrug-resistant bacteria places a serious burden on public health systems. Phage therapy is an alternative treatment to antibiotics, overcoming the issue of antibiotic resistance. In this study, six phages (SAVM01 to SAVM06) were isolated from effluents and were used against a panel of staphylococcal clinical samples isolated from DFUs. A genomic analysis revealed that the phages belonged to the Herelleviridae family, with sequences similar to those of the Kayvirus genus. No lysogeny-associated genes, known virulence or drug resistance genes were identified in the phage genomes. The phages displayed a strong lytic and antibiofilm activity against DFU clinical isolates, as well as against opportunistic pathogenic coagulase-negative staphylococci. The results presented here suggest that these phages could be effective biocontrol agents against staphylococcal clinical isolates from DFUs.

Backgroung: Antimicrobial resistance (AMR) is on the rise worldwide. Tools such as dynamic regression (DR) models can correlate antimicrobial consumption (AMC) with AMR and predict future trends to help implement antimicrobial stewardship programs (ASPs)., Main Body: We carried out a systematic review of the literature up to 2023/05/31, searching in PubMed, ScienceDirect and Web of Science. We screened 641 articles and finally included 28 studies using a DR model to study the correlation between AMC and AMR at a hospital scale, published in English or French. Country, bacterial species, type of sampling, antimicrobials, study duration and correlations between AMC and AMR were collected. The use of β-lactams was correlated with cephalosporin resistance, especially in Pseudomonas aeruginosa and Enterobacterales. Carbapenem consumption was correlated with carbapenem resistance, particularly in Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Fluoroquinolone use was correlated with fluoroquinolone resistance in Gram-negative bacilli and methicillin resistance in Staphylococcus aureus. Multivariate DR models highlited that AMC explained from 19 to 96% of AMR variation, with a lag time between AMC and AMR variation of 2 to 4 months. Few studies have investigated the predictive capacity of DR models, which appear to be limited., Conclusion: Despite their statistical robustness, DR models are not widely used. They confirmed the important role of fluoroquinolones, cephalosporins and carbapenems in the emergence of AMR. However, further studies are needed to assess their predictive capacity and usefulness for ASPs., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Manual closure of the bronchial stump can be challenging during minimally invasive thoracic surgery. An automated fastener has been used for more than a decade in minimally invasive heart valve surgery to eliminate the need for manual knot tying during the suturing of prosthetic valves. Herein, we describe the use of the COR-KNOT automated fastener (LSI SOLUTIONS ® , Victor, NY, USA) in a case of video-assisted left upper lobectomy with open section of the bronchus and manual closure with interrupted resorbable sutures for a malignant bronchial tumor located on the proximal part of the left upper lobe bronchus. This case represents, to our knowledge, the first case using the COR-KNOT device for minimally invasive pulmonary surgery.

Purpose: Helcococcus kunzii is a skin commensal, Gram-positive bacterium, mostly isolated from infected chronic wounds. This opportunistic pathogen is usually co-isolated with Staphylococcus aureus. The present dataset explores the production and secretion of H. kunzii bacterial virulence interacting proteins in a growth medium mimicking chronic wounds in exponential and stationary growth phases., Experimental Design: The H. kunzii cellular proteome and exoproteome were assessed by analyzing three biological replicates per condition tested. Samples were analyzed using a Q-Exactive HF mass spectrometer. Comparative and functional analyses were performed to profile the identified protein set., Results: The H. kunzii's cellular proteome encompassed 969 proteins, among which 64 and 53 were specifically identified in the exponential and stationary phase of growth, respectively. Its exoproteome comprised 58 proteins, among which 16 and 14 were characteristic of each growth stage. Metabolic differences between the two phases of growth are discussed. Besides, the production of previously shortlisted and novel putative H. kunzii targets involved in modulating the virulence of S. aureus is investigated., Conclusion and Clinical Relevance: This work, pioneering the study of H. kunzii physiology in a chronic wound-like environment, should assist future research on this opportunistic pathogen and the search for innovative approaches for wound management., (© 2023 The Authors. Proteomics - Clinical Applications published by Wiley-VCH GmbH.)

The use of peripherally inserted central catheters (PICCs) has increased in cancer patients. This study aimed to compare the incidence of PICC-related bloodstream infections (PICCR-BSIs) in cancer patients treated with chemotherapy and in noncancer patients. We performed a secondary analysis from a retrospective, single-center, observational cohort. The PICCR-BSI incidence rates in cancer and noncancer patients were compared after 1:1 propensity-score matching. Then, the factors associated with PICCR-BSI were assessed in a Cox model. Among the 721 PICCs (627 patients) included in the analysis, 240 were placed in cancer patients for chemotherapy and 481 in noncancer patients. After propensity-score matching, the PICCR-BSI incidence rate was 2.6 per 1000 catheter days in cancer patients and 1.0 per 1000 catheter days in noncancer patients ( p < 0.05). However, after adjusting for variables resulting in an imbalance between groups after propensity-score matching, only the number of PICC lumens was independently associated with PICCR-BSI (adjusted hazard ratio 1.81, 95% confidence interval: 1.01-3.22; p = 0.04). In conclusion, the incidence rate of PICCR-BSI is higher in cancer patients treated with chemotherapy than in noncancer patients, but our results also highlight the importance of limiting the number of PICC lumens in such patients.

A 43-year-old woman presented with right-sided chest discomfort associated with dyspnea. The symptoms were related to the menstrual cycle and the patient has already presented several similar episodes. The Chest computed tomography (chest-CT) showed a partial right pneumothorax. A thoracoscopy was performed and demonstrated some diaphragmatic fenestrations. The diagnosis of a catamenial pneumothorax was established. The catamenial pneumothorax is a rare condition affecting the women in the reproductive period and is located most of the time in the right-side. The treatment is mainly surgical with the realization of a thoracoscopy. However, a medical treatment may be sometimes necessary.

Enterococcal bone and joint infections (BJIs) are reported to have poor outcomes, but there are conflicting results. This study aimed to describe the clinical characteristics and outcomes of patients with enterococcal BJI and to assess the factors associated with treatment failure. We conducted a retrospective cohort study at Nimes University Hospital from January 2007 to December 2020. The factors associated with treatment failure were assessed using a Cox model. We included 90 consecutive adult patients, 11 with native BJIs, 40 with prosthetic joint infections and 39 with orthopedic implant-associated infections. Two-thirds of patients had local signs of infection, but few (9%) had fever. Most BJIs were caused by Enterococcus faecalis ( n = 82, 91%) and were polymicrobial ( n = 75, 83%). The treatment failure rate was 39%, and treatment failure was associated with coinfection with Staphylococcus epidermidis (adjusted hazard ratio = 3.04, confidence interval at 95% [1.31-7.07], p = 0.01) and with the presence of local signs of inflammation at the time of diagnosis (aHR = 2.39, CI 95% [1.22-4.69], p = 0.01). Our results confirm the poor prognosis of enterococcal BJIs, prompting clinicians to carefully monitor for local signs of infection and to optimize the medical-surgical management in case of coinfections, especially with S. epidermidis .

Introduction: The aim of this study was to determine the correlation between antimicrobial consumption (AMC) and antimicrobial resistance (AMR) in Escherichia coli at a hospital level, and assess the capacity of dynamic regression (DR) models to predict AMR for their use in deployment of antimicrobial stewardship programs (ASPs)., Methods: A retrospective epidemiological study was conducted in a French tertiary hospital between 2014 and 2019. DR models were used to assess the correlation between AMC and AMR from 2014 to 2018. The predictive abilities of the models were estimated by comparing the predicted data with those observed in 2019., Results: Rates of fluoroquinolone and cephalosporin resistance decreased. AMC increased overall but decreased for fluoroquinolone. DR models highlighted that the decrease in use of fluoroquinolone and the increase in use of anti-pseudomonal activity penicillin with beta-lactamase inhibitor (AAPBI) explained 54% of the decrease in fluoroquinolone resistance and 15% of the decrease in cephalosporin resistance. In addition, penicillin/beta-lactamase inhibitor (PBI) consumption explained 53% of PBI resistance, and beta-lactam use explained 36% of penicillin resistance, with both remaining stable over time. DR models had predictive capabilities with margins of error from 8% to 34%., Conclusion: Over a six-year period in a French tertiary hospital, decreasing rates of resistance to fluoroquinolones and cephalosporins were correlated with decreasing use of fluoroquinolone and increasing use of AAPBI, whereas rates of resistance to penicillin remained high and stable. The results indicate that DR models should be used with caution for AMR forecasting and ASP implementation., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Heart transplantation (HTx) in adults with congenital heart disease (ACHD) remains challenging because of structural anomalies and often previous procedure. The aim of this retrospective study was to describe the outcomes of heart transplantation (HTx) in a cohort of ACHD patients at our tertiary centre., Patients and Methods: Between January 1993 and December 2010, 223 consecutive adult patients (age > 18 years) underwent HTx at our institution. Fifteen (6.7%) were ACHD patients. Outcomes were reviewed using our institution's HTx database. We looked at 30-day, 1, 5 and 10-years survival, as well as post-transplantation complications., Results: The mean age at HTx of the groups of ACHD was 42 ± 14.4 years, vs 54.2 ± 9.8 years for the non-CHD patients. Prior to transplant, thirteen of the fifteen ACHD had undergone one or more surgical procedures including palliative or corrective open-heart procedures in 66.6% of them. Seven of the fifteen ACHD (47%) required additional surgical procedures at transplantation. The mean follow-up was 95,44 ± 84.3 months. There was no significant difference in survival (ACHD vs non-CHD) at 30 days (87% vs. 90%), 1 year (73% vs. 74.5%) or 5 years (53% vs. 55%). Survival at 10 years was respectively 53% and 41% for ACHD patients and non-CHD patients., Conclusion: Despite the surgical challenge, HTx in ACHD has a good long-term result. However, the small sample size of our cohort limits any definitive conclusions.

In the past 20 years, there has been a real development of aortic valve repair techniques with an increasing number of publications describing the long-term benefits of aortic valve repair in terms of survival, freedom from major adverse valve related-events and reoperations. Aortic valve repair can now be considered as a valuable alternative to prosthetic valve replacement in patients with dystrophic ascending aorta pathology associated or not to aortic insufficiency with pliable leaflets. In this paper, the authors describe the state of the art of aortic valve repair and present their clinical experience with aortic valve repair surgery in the university hospital center of Liege from April 2021 to September 2022.

Background: Diabetic foot infections (DFIs) represent a public health problem because of their frequency and the severity of their consequences, i.e. amputation and mortality. Polymicrobial biofilms on the skin surface of these ulcers complicate wound healing. Few in vitro models exist to study the antibiotics activity in this context., Objectives: This study evaluated the in vitro activity of antibiotics against the two main bacteria isolated in DFI, Staphylococcus aureus and Pseudomonas aeruginosa, using a dynamic system (BioFlux™ 200) and a chronic wound-like medium (CWM) that mimic the foot ulcer environment., Methods: Reference strains and two pairs of clinical S. aureus and P. aeruginosa isolated together from a DFI were cultivated in brain heart infusion and CWM media during 72 h at 37°C, alone and combined in the BioFlux™ 200 system. Antibiotic activity was evaluated after a mechanical debridement. The activities were measured by the reduction of biofilm percentage of bacteria in the microfluidic system using microscopy., Results: Daptomycin for S. aureus and ceftazidime for P. aeruginosa showed excellent activity to reduce biofilm biomass, whereas linezolid action was more mitigated and dalbavancin was ineffective. Ceftazidime + daptomycin presented the most potent in vitro activity on a mixed biofilm., Conclusions: The combination of CWM and the BioFlux™ microfluidic system represents a valuable tool to screen the potential antimicrobial activity of antibiotics under conditions mimicking those encountered in DFI. It could help clinicians in their management of chronic wounds., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Human brucellosis is a zoonoses caused by bacteria of the genus Brucella. Infection results in subacute or chronic debilitating disease with nonspecific clinical manifestations and is often associated with consuming unpasteurized dairy products. We report 2 cases of brucellosis in male patients who were hospitalized in distinct towns of French Guiana, an overseas territory of France located on the northeastern shore of South America. Both men were citizens of Brazil working as clandestine goldminers in the deep Amazonian rainforest. Characterization of the 2 bacterial isolates revealed that they represent a potential new species of Brucella. Medical practitioners working in contact with wildlife in this region of the world should be aware of the existence of these pathogens and the potential for human infection.

Background: Despite their spread in daily practice, few data is available on clinical factors associated with peripherally inserted central catheter (PICC)-related bloodstream infections (PR-BSI). We aimed to assess the PR-BSI incidence, microbiology, and factors associated with PR-BSI with a focus on clinical symptoms., Methods: We conducted a retrospective cohort study in a French university hospital. We screened all PICC insertions performed from April 1st, 2018, to April 1st, 2019, and included PICC insertions in adult patients. We assessed the PR-BSI incidence, the factors associated with PR-BSI using a Cox model, and negative and positive predictive values (NPVs and PPVs) of each clinical sign for PR-BSI., Results: Of the 901 PICCs inserted in 783 patients (38,320 catheters days), 214 PICCs (24%) presented with a complication. The most prevalent complication was PR-BSI (1.9 per 1000 catheter days; 8.1% of inserted PICCs ). Enterobacterales (N = 27, 37%) and coagulase negative Staphylococci (N = 24, 33%), were the main microorganisms responsible for PR-BSI. Factors independently associated with occurrence of PR-BSI were fever (hazard ratio 13.21, 95% confidence interval 6.00-29.11, p < 0.001) and chills (HR 3.66, 95%CI 1.92-6.99, p < 0.001). All clinical signs and a duration of PICC maintenance ≥ 28 days, had a low PPVs (≤ 67.1%) but high NPVs (≥ 92.5%) for PR-BSI., Conclusions: Monitoring of clinical signs, especially fever and chills, with caution and limitation of device maintenance duration, could improve PICC management., (© 2023. The Author(s).)

In southern France, cases of community-acquired meningitis syndrome (CAM) are typically clustered as outbreaks with determinants which remain unknown. This 61-month retrospective investigation in Nîmes and Marseille university hospital laboratories, yielded 2,209/20,779 (10.63%) documented CAM cases caused by 62 different micro-organisms, represented by seasonal viral etiologies (78.8%), including Enterovirus, Herpes Simplex Virus (HSV), and Varicella-Zoster Virus (VZV; 1,620/2,209 = 73.4%). Multi correspondence analysis revealed an association of infection with age and sex, with the risk of infection being relatively higher in young men, as confirmed by Fisher's exact test ( p < 10 -3 ). Bacterial meningitis accounted for 20% of cases, mostly caused by Streptococcus pneumoniae (27.4% of cases), Neisseria meningitidis (12.5%), and Haemophilus influenzae (9.5%) with bacteria/virus coinfection (0.9%), and only six cases of documented fungal meningitis. In total, 62.6% of cases, of which 88.7% were undocumented, arose from 10 outbreaks. 33.2% of undocumented cases were aged >60 years compared to 19.2% of documented cases ( p  < 0.001), and viral infection was more common in the summer (87.5%) compared to other seasons (72.3%; p  < 0.001). Outbreaks most often started in Nîmes and moved eastward toward Marseille at a speed of ~9 km/day, and these dynamics significantly correlated with atmospheric temperature, especially during summer outbreaks. In particular, the incidence of Enterovirus-driven outbreaks correlated with temperature, revealing correlation coefficients of 0.64 in Nîmes and 0.72 in Marseille, and its occurrence in Marseille lagged that in Nîmes by 1-2 weeks. Tracing the dynamics of CAM outbreak during this retrospective investigation in southern France yielded a speed of displacement that correlated with the variation in temperature between both cities, and these results provide clues for the next occurrence of undocumented outbreaks., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Morsli, Salipante, Kerharo, Boudet, Stephan, Dunyach-Remy, Zandotti, Lavigne and Drancourt.)

Coagulase-negative staphylococci (CoNS) and especially Staphylococcus epidermidis are responsible for health care infections, notably in the presence of foreign material (e.g., venous or central-line catheters). Catheter-related bacteremia (CRB) increases health care costs and mortality. The aim of our study was to evaluate the impact of 15 days of antibiotic exposure (ceftobiprole, daptomycin, linezolid and vancomycin) at sub-inhibitory concentration on the resistance, fitness and genome evolution of 36 clinical strains of S. epidermidis responsible for CRB. Resistance was evaluated by antibiogram, the ability to adapt metabolism by the Biofilm Ring test ® and the in vivo nematode virulence model. The impact of antibiotic exposure was determined by whole-genome sequencing (WGS) and biofilm formation experiments. We observed that S. epidermidis strains presented a wide variety of virulence potential and biofilm formation. After antibiotic exposure, S. epidermidis strains adapted their fitness with an increase in biofilm formation. Antibiotic exposure also affected genes involved in resistance and was responsible for cross-resistance between vancomycin, daptomycin and ceftobiprole. Our data confirmed that antibiotic exposure modified bacterial pathogenicity and the emergence of resistant bacteria.

We aimed to assess the factors associated with mortality in patients treated with tocilizumab for a SARS-CoV-2 pneumonia due to the delta or omicron variants of concern (VOC) and detect an effect of tocilizumab on mortality. We conducted a prospective cohort study in a tertiary hospital from 1 August 2021 to 31 March 2022 including patients with severe COVID-19, treated with tocilizumab. Factors associated with mortality were assessed in a Cox model; then, the 60-day mortality rates of COVID-19 patients treated with standard of care (SoC) +/- tocilizumab were compared after 1:1 propensity score matching. The mortality rate was 22% (N = 26/118) and was similar between delta and omicron cases ( p = 0.6). The factors independently associated with mortality were age (HR 1.06; 95% CI (1.02-1.11), p = 0.002), Charlson index (HR 1.33; 95% CI (1.11-1.6), p = 0.002), WHO-CPS (HR 2.56; 95% CI (1.07-6.22) p = 0.03), and tocilizumab infusion within the first 48 h following hospital admission (HR 0.37, 95% CI (0.14-0.97), p = 0.04). No significant differences in mortality between the tocilizumab plus SoC and SoC alone groups ( p = 0.5) were highlighted. However, the patients treated with tocilizumab within the 48 h following hospital admission had better survival ( p = 0.04). In conclusion, our results suggested a protective effect on mortality of the early administration of tocilizumab in patients with severe COVID-19 regardless of the VOC involved.

Staphylococcus aureus is a major human pathogen whose characteristics support its success in various clinical settings including Cystic Fibrosis (CF). In CF, S. aureus is indeed the most commonly identified opportunistic pathogen in children and the overall population. S. aureus colonization/infection, either by methicillin-susceptible or methicillin-resistant strains, will become chronic in about one third of CF patients. The persistence of S. aureus in CF patients' lungs, despite various eradication strategies, is favored by several traits in both host and pathogen. Among the latter, living in biofilm is a highly protective way to survive despite deleterious environmental conditions, and is a common characteristic shared by the main pathogens identified in CF. This is why CF has earned the status of a biofilm-associated disease for several years now. Biofilm formation by S. aureus , and the molecular mechanisms governing and regulating it, have been extensively studied but have received less attention in the specific context of CF lungs. Here, we review the current knowledge on S. aureus biofilm in this very context, i.e., the importance, study methods, molecular data published on mono- and multi-species biofilm and anti-biofilm strategies. This focus on studies including clinical isolates from CF patients shows that they are still under-represented in the literature compared with studies based on reference strains, and underlines the need for such studies. Indeed, CF clinical strains display specific characteristics that may not be extrapolated from results obtained on laboratory strains.

Few point prevalence surveys (PPS) have been conducted in Vietnam on Surgical Site Infections (SSI) or antimicrobial use in surgery. The objective of this study was to evaluate the PPSs of SSI before and after implementation of antibiotic stewardship programs (ASP) and infection control (IC) in a Vietnamese tertiary care hospital. ASP and IC practices were implemented in operating rooms and the orthopedic department, including antibiotic training, skin preparation, hand hygiene, gloves and sterile instruments, and SSIs risk factors. A PPS of SSIs and antimicrobial use was performed in January 2016 according to methods from the Centers for Disease Control and Prevention, before ASP and IC, and in December 2019. Information recorded included surgical data, antibiotic prophylaxis, microorganisms, and SSI risk factors. Skin preparation compliance assessed preoperative washing and antisepsis. SSI prevalence was 7.8% in 2016 versus 5.4% in 2019 ( p = 0.7). The use of prophylactic antibiotics decreased from 2016 to 2019. A third-generation cephalosporin was prescribed more than 48 h after surgery for most patients. Skin preparation compliance increased from 54.4% to 70.5% between assessments. The decreased SSI, although non-statistically significant, warrants continuing this program. Vietnamese hospitals must provide comprehensive IC education to healthcare workers to address the prevention of SSI and establish IC policies.

Background: In the case of intra-abdominal infections (IAI) in beta-lactam (BL) allergic patients, empiric antimicrobial therapy without BL is recommended; however, data regarding the outcome with alternative regimens are scarce. This study aimed to compare the outcomes of BL allergic (BLA) patients with IAI to those who were non-BLA (NBLA). Method: We conducted a case−control study in a French teaching hospital, between 1 January 2016 and 31 August 2021. BLA patients with IAI treated with fluoroquinolone or aztreonam and metronidazole were matched with controls treated with BL, on age, sex, disease severity, IAI localization, and healthcare-associated infection (HAI) status. We compared rates of therapeutic failures, adverse events, and HAI, and then assessed factors associated with therapeutic failure using a logistic regression model. Results: The therapeutic failure rate was 14% (p > 0.99) in both groups of 43 patients, and there was no significant difference in the adverse events rate (p > 0.99) and HAI rate (p = 0.154). Factors independently associated with therapeutic failure were higher BMI (OR 1.16; 95%CI [1.00−1.36]; p = 0.041), longer hospital length of stay (OR 1,20; 95%CI [1.08−1.41]; p = 0.006), and inadequate empiric antimicrobial therapy (OR 11.71; 95%CI [1.43−132.46]; p = 0.025). Conclusion: The outcomes of BLA patients with IAI treated without BL were the same as those for NBLA patients treated with BL.

Staphylococcus pettenkoferi is a recently described coagulase-negative Staphylococcus identified in human diseases, especially in infections of foot ulcers in patients living with diabetes mellitus. To date, its pathogenicity remains underexplored. In this study, whole-genome analysis was performed on a collection of 29 S. pettenkoferi clinical strains isolated from bloodstream and diabetic foot infections with regard to their phylogenetic relationships and comprehensive analysis of their resistome and virulome. Their virulence was explored by their ability to form biofilm, their growth kinetics and in an in vivo zebrafish embryo infection model. Our results identified two distinct clades (I and II) and two subclades (I-a and I-b) with notable genomic differences. All strains had a slow bacterial growth. Three profiles of biofilm formation were noted, with 89.7% of isolates able to produce biofilm and harbouring a high content of biofilm-encoding genes. Two virulence profiles were also observed in the zebrafish model irrespective of the strains' origin or biofilm profile. Therefore, this study brings new insights in S. pettenkoferi pathogenicity.

Introduction: Novel last resort beta-lactam antibiotics are now available for management of infections due to New-Delhi Metallo-Beta-Lactamase (NDM) producing Enterobacterales and non-fermenters with Difficult-to-Treat Resistance. However, data regarding the use of imipenem-cilastatin-relebactam (IMI-REL), cefiderocol (CFD) and ceftazidime-avibactam plus aztreonam (CAZ-AVI-ATM) are scarce in real-life settings. This study aimed to describe the use of last resort beta-lactam antibiotics, the microbiology and the outcome, in patients hospitalized in a tertiary hospital., Methods: We conducted a monocentric observational cohort study from 2020/01/01, to 2022/08/31. We screened all patients admitted to Nimes University Hospital who have received ≥ 1 dose of last resort beta-lactam antibiotics during the study period, using the Pharmacy database. We included patients treated with IMI-REL, CFD and CAZ-AVI-ATM. The primary endpoint was the infection-free survival rate. We also calculated rates of microbiological and clinical cure, recurrent infection, death and adverse events., Results: Twenty-seven patients were included in the study and 30 treatment courses were analyzed: CFD (N=24; 80%), CAZ-AVI-ATM (N=3; 10%) and IMI-REL (N=3; 10%). Antibiotics were used in 21 males (70%) and 9 females (30%) with a median age at 65-year-old [50-73.5] and a median Charlson index at 1 [0-2]. Almost all the patients had ≥ 1 risk factor for carbapenem resistant bacteria, a half of them was hospitalized for severe COVID-19, and most of antibiotic courses (N=26; 87%) were associated with ICU admission. In the study population, the probability of infection-free survival at day-90 after last resort beta-lactam therapy initiation was 48.4% CI95% [33.2-70.5]. Clinical failure rate was at 30%, microbiological failure rate at 33% and mortality rate at 23%. Adverse events were documented in 5 antibiotic courses (17%). In details, P. aeruginosa were mainly treated with CFD and IMI-REL, S. maltophilia with CFD and CAZ-AVI-ATM, A. baumannii with CFD, and NDM producing- K. pneumoniae with CAZ-AVI-ATM and CFD. After a treatment course with CFD, CAZ-AVI-ATM and IMI-REL, the probability of infection-free survival was 48% CI95% [10.4-73.5], 33.3% CI95% [6.7-100], 66.7% CI95% [30-100], respectively., Discussion/conclusion: Use of last resort beta-lactam antimicrobials in real-life settings was a safe and efficient therapeutic option for severe infections related to Gram-negative bacteria with Difficult-to-Treat Resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Larcher, Laffont-Lozes, Roger, Doncesco, Groul-Viaud, Martin, Loubet, Lavigne, Pantel and Sotto.)

Staphylococcus aureus possesses a large arsenal of immune-modulating factors, enabling it to bypass the immune system's response. Here, we demonstrate that the acid phosphatase SapS is secreted during macrophage infection and promotes its intracellular survival in this type of immune cell. In animal models, the SA564 sapS mutant demonstrated a significantly lower bacterial burden in liver and renal tissues of mice at four days post infection in comparison to the wild type, along with lower pathogenicity in a zebrafish infection model. The SA564 sapS mutant elicits a lower inflammatory response in mice than the wild-type strain, while S. aureus cells harbouring a functional sapS induce a chemokine response that favours the recruitment of neutrophils to the infection site. Our in vitro and quantitative transcript analysis show that SapS has an effect on S. aureus capacity to adapt to oxidative stress during growth. SapS is also involved in S. aureus biofilm formation. Thus, this study shows for the first time that SapS plays a significant role during infection, most likely through inhibiting a variety of the host's defence mechanisms.