Author: "Pathogénie des Staphylocoques – Staphylococcal Pathogenesis" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Pathogénie des Staphylocoques – Staphylococcal Pathogenesis"' showing total 281 results

Start Over Author "Pathogénie des Staphylocoques – Staphylococcal Pathogenesis"

281 results on '"Pathogénie des Staphylocoques – Staphylococcal Pathogenesis"'

101. Changing patterns of human migrations shaped the global population structure of Mycobacterium tuberculosis in France

Author: Ghislaine Blasquez, Charlotte Genestet, Gérard Carret, Catherine Pichat, Isabelle Fredenucci, Florence Ader, Sandrine Boisset, Anne Carricajo, Jean-Pierre Flandrois, Jean-Philippe Rasigade, Thierry Wirth, Maxime Barbier, Gerard Lina, Michèle Pérouse de Montclos, Anne-Sophie Ronnaux-Baron, Philip Supply, Christine Godin-Benhaim, Véronique Jacomo, Oana Dumitrescu, Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Comité Départemental d’Hygiène Sociale - CLAT69 [Lyon), Agence régionale de santé Auvergne Rhône Alpes (ARS), Laboratoire de Bactériologie, CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Unité de contrôle infectieux [CHU Saint Etienne], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Biomnis Laboratory, Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), Département PEGASE [LBBE] (PEGASE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, DNA, Bacterial, Tuberculosis, Human Migration, Population, lcsh:Medicine, Datasets as Topic, Minisatellite Repeats, Article, Mycobacterium tuberculosis, 03 medical and health sciences, Global population, Africa, Northern, medicine, Humans, education, Tuberculosis incidence, lcsh:Science, Retrospective Studies, education.field_of_study, Multidisciplinary, biology, Human migration, business.industry, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Incidence, lcsh:R, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Phylogeography, 030104 developmental biology, Minisatellite, Geography, Cross-Sectional Studies, Haplotypes, Evolutionary biology, lcsh:Q, France, business, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: Mycobacterium tuberculosis (Mtb) exhibits a structured phylogeographic distribution worldwide linked with human migrations. We sought to infer how the interactions between distinct human populations shape the global population structure of Mtb on a regional scale. We applied the recently described timescaled haplotypic density (THD) technique on 638 minisatellite-based Mtb genotypes from French tuberculosis patients. THD with a long-term (200 y) timescale indicated that Mtb population in France had been mostly influenced by interactions with Eastern and Southern Europe and, to a lesser extent, Northern and Middle Africa, consistent with historical migrations favored by geographic proximity or commercial exchanges with former French colonies. Restricting the timescale to 20 y, THD identified a sustained influence of Northern Africa, but not Europe where tuberculosis incidence decreased sharply. Evolving interactions between human populations, thus, measurably influence the local population structure of Mtb. Relevant information on such interactions can be inferred using THD from Mtb genotypes.
Published: 2018
Full Text: View/download PDF

102. Vaccination post-allogeneic hematopoietic stem cell transplantation: what is feasible?

Author: Florence Ader, Florent Valour, Anne Conrad, Vincent Alcazer, Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hématologie clinique, CHU Lyon, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, chronic graft-versus-host disease, medicine.medical_treatment, Immunology, Graft vs Host Disease, chemical and pharmacologic phenomena, Hematopoietic stem cell transplantation, immune response, 03 medical and health sciences, 0302 clinical medicine, Immune system, Drug Discovery, hyposplenism, Humans, Medicine, Immunization Schedule, Pharmacology, Vaccines, business.industry, Vaccination, vaccine-preventable infection, immune reconstitution, Pneumococcus, Hematologic Diseases, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Influenza, 3. Good health, Hematological Diseases, surgical procedures, operative, Curative treatment, Hematologic Neoplasms, 030220 oncology & carcinogenesis, hematopoietic stem cell transplantation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Molecular Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, 030215 immunology
Abstract: International audience; INTRODUCTION: Allogeneic hematopoietic stem cell transplantation (HSCT) is a major curative treatment option for malignant and non-malignant hematological diseases, but is associated with an increased risk for infections, of which some are preventable by vaccination. Vaccination guidelines recommend repeated doses of most inactivated vaccines to achieve long-lasting immune responses. However, the efficacy of immunization is often hampered by graft-versus-host disease or severe opportunistic infections. Areas covered: This review summarizes the vaccine recommendations for adult allogeneic HSCT recipients and discusses the challenges and future directions regarding vaccine immunization in these patients. Expert commentary: Vaccination is a well-tolerated therapeutic intervention to prevent infections after allogeneic HSCT. Allogeneic HSCT recipients could benefit from experience regarding vaccine efficacy capitalized through specific data registries. An individualized immunization approach, modulating inception and intensity of vaccination schedule according to transplant characteristics, transplant-related complications and immune recovery status, might help to improve vaccine efficacy in this specific population. Identification of surrogate markers of the immune status and of vaccine efficacy, beyond antibody testing, as well as development of new vaccines are exciting fields of future research.
Published: 2018
Full Text: View/download PDF

103. Impact of currently marketed tampons and menstrual cups on Staphylococcus aureus growth and TSST-1 production in vitro

Author: Nonfoux, Louis, Chiaruzzi, Myriam, Badiou, Cédric, Baude, Jessica, Tristan, Anne, Thioulouse, Jean, Muller, Daniel, Prigent Combaret, Claire, Lina, Gérard, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Labex Ecofect of the Universite de Lyon within the program Investissements d'Avenir ANR-11-LABX-0048 ANR-11IDEX-0007, FINOVI Foundation, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: menstrual cup, Staphylococcus aureus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, toxic shock syndrome toxin 1, [SDV.IMM]Life Sciences [q-bio]/Immunology, tampon, equipment and supplies, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, biofilm, elastomer, fiber
Abstract: International audience; Fifteen currently marketed intravaginal protection products (11 types of tampon and four menstrual cups) were tested by the modified tampon sac method to determine their effect on Staphylococcus aureus growth and toxic shock toxin 1 (TSST-1) production. Most tampons reduced S. aureus growth and TSST-1 production, with differences based on brand and composition, and S. aureus growth was higher in de-structured than in unaltered tampons. We observed higher S. aureus growth and toxin production in menstrual cups than in tampons, potentially due to the additional air introduced to the bag by cups, with differences based on cup composition and size.Importance Menstrual toxic shock syndrome is a rare but severe disease. It occurs in healthy women vaginally colonized by Staphylococcus aureus producing toxic shock syndrome toxin 1 using intravaginal protection such as tampons or menstrual cups. Intravaginal protection induces TSS production by collecting catamenial products which act as a growth medium for S. aureus Previous studies have evaluated the impact of tampon composition on S. aureus producing toxic shock syndrome toxin 1, but they are not recent and did not include menstrual cups. This study demonstrates that highly reproducible results for S. aureus growth and TSST-1 production can be obtained using a simple protocol that reproduces the physiological conditions of tampon and cup usage as closely as possible, providing recommendations for tampon or cup use to both manufacturers and consumers. Notably, our results do not show that menstrual cups are safer than tampons and suggest that they require similar precautions.
Published: 2018
Full Text: View/download PDF

104. Clonal dissemination of OXA-48-producing Enterobacter cloacae isolates from companion animals in Algeria

Author: Christophe de Champs, Bourouis Asma, Massilia Yousfi, Thomas Guillard, Brazane Mira, Abdelaziz Touati, Anaëlle Muggeo, Lucien Brasme, Ecole Nationale d'Ingénieurs de Gabès (ENIG), Université de Gabès, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA), Laboratoire de Bactériologie–Virologie-Hygiène Hospitalière, Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims), Ecole Nationale d'Ingénieurs de Gabès, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Microbiology (medical), Imipenem, Klebsiella pneumoniae, [SDV]Life Sciences [q-bio], 030106 microbiology, Immunology, Cat Diseases, Microbiology, beta-Lactamases, Birds, 03 medical and health sciences, chemistry.chemical_compound, Dogs, Bacterial Proteins, Enterobacter cloacae, medicine, Immunology and Allergy, Animals, Dog Diseases, Horses, ComputingMilieux_MISCELLANEOUS, biology, Bird Diseases, Enterobacteriaceae Infections, Pets, biology.organism_classification, 3. Good health, RAPD, Anti-Bacterial Agents, chemistry, Ticarcillin, Algeria, Cats, Multilocus sequence typing, Horse Diseases, MacConkey agar, Ertapenem, medicine.drug
Abstract: Objectives The aim of this study was to investigate carbapenemase-producing Enterobacteriaceae (CPE) in companion animals. Methods Between October 2015 and April 2016, 533 rectal swabs were obtained from healthy and diseased pets in different cities in Algeria. Samples were plated on MacConkey agar supplemented with ertapenem (0.5 mg/L). Isolates were identified by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS). Antimicrobial susceptibility testing was performed by the disk diffusion method. Carbapenemase, plasmid-mediated AmpC (pAmpC), extended-spectrum β-lactamase (ESBL) and plasmid-mediated quinolone resistance genes were characterised by PCR. Plasmids were extracted by the Kieser extraction method and were analysed by PCR-based replicon typing (PBRT). The epidemiological relationship between Enterobacter cloacae isolates was determined by random amplified polymorphic DNA (RAPD) analysis and multilocus sequence typing (MLST). Results From 533 rectal swabs, 12 Enterobacteriaceae (2.3%), including 2 Escherichia coli, 2 Klebsiella pneumoniae and 8 E. cloacae, were recovered from selection plates. The 12 strains were resistant to amoxicillin/clavulanic acid, ticarcillin, piperacillin/tazobactam and ertapenem. All isolates were susceptible to aminoglycosides, imipenem and extended-spectrum cephalosporins. PCR and sequencing identified the blaOXA-48 gene in all isolates. qnrB1 was identified in all E. cloacae isolates. Plasmid analysis showed that the blaOXA-48 gene was localised on a 7-kb untypeable plasmid. RAPD analysis demonstrated the presence of the same profile pattern in the eight E. cloacae isolates. MLST analysis showed that the E. cloacae isolates belonged to ST527. Conclusions This study reports for the first time the presence of CPE in horses and pet birds in the world.
Published: 2018
Full Text: View/download PDF

105. Chronic and severe prosthetic joint infection complicated by amyloid A amyloidosis with renal and bladder impairment

Author: Cyril Courtin, Tristan Ferry, Mikhail Dziadzko, Francois Vandenesch, Frederic Laurent, Stanislas GUNST, Florent Valour, Florence ADER, Marc Janier, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Chirurgie Orthopédique [Centre Albert Trillat], Centre Albert Trillat [Hôpital de la Croix-Rousse - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Prosthesis-Related Infections, Images In…, medicine.medical_treatment, 030232 urology & nephrology, Bone Neoplasms, medicine.disease_cause, Prosthesis, Amputation, Surgical, 03 medical and health sciences, 0302 clinical medicine, Medicine, Synovial fluid, Humans, Femur, Medical history, 030212 general & internal medicine, Renal Insufficiency, ComputingMilieux_MISCELLANEOUS, Aged, Hematuria, Serum Amyloid A Protein, business.industry, Amyloidosis, Urinary Bladder Diseases, General Medicine, bone and joint infections, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Surgery, Superinfection, Orthopedic surgery, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Methicillin Resistance, business, Knee Prosthesis, Bandage, orthopaedics
Abstract: A 66-year-old woman presented with renal failure and purulent discharge associated with a chronic prosthetic joint infection (PJI) of the left knee. Her medical history consisted of an untreated chronic hepatitis B and recurrent giant-cell tumour of bone revealed by spontaneous fractures 20 years previously. Multiple tumour resections led to knee prosthesis implantation in 1992 with no tumour relapse thereafter. The patient experienced a methicillin-susceptible Staphylococcus aureus chronic PJI in the following months that required two-stage prosthesis replacement and a prolonged antibiotherapy. A clinical suspicion of superinfection was confirmed in 2002 by a puncture of the synovial fluid that found a methicillin-resistant Staphylococcus epidermidis . The patient declined both surgical and medical treatment and was lost to follow-up. She subsequently presented in 2015 with partial impotence, no flexion of the left knee and multiple fistulae with purulent discharge (figure 1A) that had evolved for years and that had been treated with a self-made bandage. X-ray (figure 1B) and CT scan (figure 1C) found extensive periostea reaction of the femur, bone destruction and prosthesis loosening. Lab results found …
Published: 2018
Full Text: View/download PDF

106. Outpatient parenteral antibiotic therapy: Evaluation of practices and limits of use in rural areas in France

Author: Thomas Perpoint, Christian Chidiac, S. Le Ngoc Tho, Tristan Ferry, Florent Valour, Claire Triffault-Fillit, Florence Ader, L. Adelaide, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, 0301 basic medicine, Health Knowledge, Attitudes, Practice, Parenteral Nutrition, medicine.medical_specialty, Time Factors, Geographic isolation, 030106 microbiology, Milieu rural, Injections, Bon usage, 03 medical and health sciences, 0302 clinical medicine, Ambulatory Care, Humans, Medicine, 030212 general & internal medicine, Rural area, Intensive care medicine, Antibiothérapie parentérale ambulatoire, Antibiotic stewardship, Outpatient parenteral antibiotic therapy, Therapy Evaluation, business.industry, Overwork, Parenteral antibiotic, Bacterial Infections, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Anti-Bacterial Agents, 3. Good health, Catheter, Infectious Diseases, Bacteremia, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Ceftriaxone, [SDV.IMM]Life Sciences [q-bio]/Immunology, Drug Therapy, Combination, Female, France, Rural Health Services, business, medicine.drug
Abstract: International audience; OBJECTIVES: To evaluate outpatient parenteral antibiotic therapy (OPAT) practices in a French rural area. MATERIAL AND METHODS: Descriptive study assessing knowledge, practices, and limitations of OPAT use among hospital practitioners (HP), family physicians (FP), and private nurses (PN). RESULTS: OPAT (mainly ceftriaxone and penicillins) was used by 69.6%, 73.3%, and 97.7% of the 23 HPs, 45 FPs, and 46 PNs mostly for respiratory or urinary tract infections, bacteremia, and/or multidrug-resistant bacterial infections. Overall, 65.2% of HPs and 37.8% of FPs were in contact with an infectious disease specialist. Knowledge of OPAT benefits and risks was lower for FPs than HPs. The main obstacles were the patient's geographic isolation (HPs), the availability of a venous catheter, the lack of training (FPs), and the expected OPAT-associated overwork (PNs). CONCLUSION: OPAT practice is weak in rural areas. Declared obstacles constitute fields of improvement for its essential expansion.; Objectif Évaluer les pratiques d’antibiothérapie parentérale ambulatoire (APA) en milieu rural.Matériel et méthodesÉtude descriptive interrogeant les médecins hospitaliers (MH), libéraux (ML) et infirmiers libéraux (IDE) sur les connaissances, pratiques et freins concernant l’APA.RésultatsL’APA (ceftriaxone et pénicillines majoritairement) était utilisée par 69,6 %, 73,3 % et 97,7 % des 23 MH, 45 ML et 46 IDE pour infections respiratoires ou urinaires, bactériémies et/ou infections à germes multirésistants, en lien avec un médecin référent pour l’antibiothérapie pour 65,2 % des MH et 37,8 % des ML. Les risques/bénéfices de l’APA étaient moins connus des ML que des MH. Les principaux freins étaient l’isolement géographique du patient (MH), l’accessibilité à une voie veineuse/le manque de formation (ML) et la surcharge de travail pressentie (IDE).ConclusionLes freins à l’APA, peu utilisée en milieu rural, dégagent des axes d’amélioration au développement indispensable de cette pratique.
Published: 2018
Full Text: View/download PDF

107. Tigecycline-based prolonged salvage therapy in patients presenting with complex bone and joint infection

Author: Wach, J., Dinh, A., Dutronc, H., Sipahi, O. R., Candevir, A., VALOUR, Florent, Zeller, V., Lustig, S., Laurent, Frédéric, Chidiac, Christian, Ferry, Tristan, group, Lyon BJI, Service de rhumatologie, Hospices Civils de Lyon (HCL)-Affiliation nécessaire..., Service des Maladies Infectieuses et Tropicales [CHU Raymond Poincaré], Hôpital Raymond Poincaré [AP-HP], CHU de Bordeaux Pellegrin [Bordeaux], Ege university, Cukurova University, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Groupe Hospitalier Diaconesses Croix Saint-Simon, Service de Chirurgie Orthopédique [Centre Albert Trillat], Centre Albert Trillat [Hôpital de la Croix-Rousse - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Laboratoire de Bactériologie de l'Hôpital de la Croix-Rousse, Hospices Civils de Lyon (HCL), Çukurova Üniversitesi, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, Turkey, Drug Resistance, Salvage therapy, Minocycline, Tigecycline, Cohort Studies, Drug Resistance, Multiple, Bacterial, 80 and over, Osteitis, Aged, 80 and over, Tigécycline, Bacterial, Infectious, Middle Aged, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, Combination, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Vomiting, [SDV.IMM]Life Sciences [q-bio]/Immunology, Drug Therapy, Combination, Female, France, medicine.symptom, Multiple, medicine.drug, Adult, medicine.medical_specialty, Bone and joint infection, 030106 microbiology, Asymptomatic, Infection ostéoarticulaire, 03 medical and health sciences, Pharmacotherapy, Drug Therapy, Internal medicine, medicine, Humans, Adverse effect, Aged, Retrospective Studies, Salvage Therapy, Arthritis, Infectious, business.industry, Arthritis, Retrospective cohort study, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Discontinuation, Surgery, Pancreatitis, Drug Evaluation, business, Follow-Up Studies
Abstract: WOS: 000428357400008 PubMed ID: 29031650 Objectives. - To assess the clinical experience of tigecycline-based salvage therapy in patients presenting with Bone and Joint Infections (BJI). Patients and methods. - Multicenter retrospective cohort study in France and Turkey (2007-2014). Results. - Thirty-six patients (age 58.2 +/- 17.8 years; 21 men) were included. The most frequently isolated bacteria were Enterobacteriaceae and staphylococci. Tigecycline (50 mg BID, mainly in combination (69.4%), mean duration of 58 days) was indicated for multidrug resistance (90.6%) and/or previous antibiotic intolerance (36.1%), and/or as second- or third-line therapy (69.4%). Six patients (16.7%) experienced early treatment discontinuation for adverse event (4 severe vomiting, 1 pancreatitis, 1 asymptomatic lipase increase). Clinical success was observed in 23 of 30 assessable patients who completed the tigecycline therapy (mean follow-up: 54.1 +/- 57.7 weeks). Conclusion. - Prolonged tigecycline-based therapy could be an alternative in patients presenting with BJI requiring salvage therapy, especially if multidrug-resistant Enterobacteriaceae and/or staphylococci are involved. (C) 2017 Elsevier Masson SAS. All rights reserved.
Published: 2018
Full Text: View/download PDF

108. Correction of Linezolid-Induced Myelotoxicity After Switch to Tedizolid in a Patient Requiring Suppressive Antimicrobial Therapy for Multidrug-Resistant Staphylococcus epidermidis Prosthetic-Joint Infection

Author: Cyril Courtin, Tristan Ferry, Jérôme JOSSE, Yannick HERRY, Mikhail Dziadzko, Frederic Laurent, Stanislas GUNST, Florent Valour, Florence ADER, Camille Kolenda, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre interrégional de référence Rhône-Alpes - Auvergne des infections ostéo-articulaires complexes, Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Blood transfusion, Anemia, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, 030106 microbiology, Hematocrit, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Medicine, 030212 general & internal medicine, medicine.diagnostic_test, business.industry, medicine.disease, 3. Good health, Infectious Diseases, Oncology, chemistry, Concomitant, Anesthesia, Linezolid, Vancomycin, Tedizolid, Daptomycin, business, medicine.drug
Abstract: [PubMed Central:\hrefhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198638PMC6198638] [DOI:\hrefhttps://dx.doi.org/10.1093/ofid/ofy24610.1093/ofid/ofy246] [PubMed:\hrefhttps://www.ncbi.nlm.nih.gov/pubmed/2937035029370350]; International audience; A 71-year-old man (85 kg) has a past history of vitiligo, ischemic myocardiopathy, and bilateral knee arthroplasties. A 1-stage exchange of the right prosthetic-joint infection (PJI) was done in 2016 for a mechanical prosthetic loosening. A massive constrained prosthetic joint was used to compensate for the bone loss (Supplementary Figure S1A). Iterative postoperative dislocations were followed by occurrence of a fistula in January 2017 and prosthetic loosening (Supplementary Figure S1B) without any pain. Because it was impossible to imagine a 2-stage exchange, a debridement and implant retention (DAIR) procedure followed by suppressive antimicrobial therapy was proposed. Daptomycin (700 mg/day) and ceftaroline (1200 mg/day) were prescribed after the surgery. A multidrug-resistant Staphylococcus epidermidis, which is only susceptible to daptomycin, vancomycin, fosfomycin, and linezolid, was found in culture from all operative samples. After 6 weeks of intravenous antimicrobial therapy, 600 mg of linezolid bid was prescribed in August 2017. Concomitant medications were ramipril, bisoprolol, furosemide, and aspirin. Under therapy, the patient experienced a progressive decrease of hemoglobin and hematocrit (without decrease of white blood cells or platelets). Five months after linezolid introduction, the patient developed asthenia related to anemia, with a decrease of hemoglobin to 65 mg/dL, and without leucopenia or thrombocytopenia (Figure 1). The patient did not take any treatment with potential bone marrow toxicity, except linezolid. The patient has no other adverse drug reactions. A blood transfusion (2 bags) was performed, which led to an immediate increase of the hemoglobin level to 84 mg/dL, and linezolid was switched to 200 mg of tedizolid once a day. In May 2018, 9 months after the DAIR surgery and 4 months after the switch, the patient was perfectly fine, walked despite rupture of the right knee extensor apparatus (video S2), without any pain, without any local signs of relapse (Supplementary Figure S1C), without clinical signs of neuropathy, and he experienced a continuous increase of the hemoglobin to 14 mg/dL under tedizolid therapy. No other treatment was changed or introduced.
Published: 2018
Full Text: View/download PDF

109. Innovations for the treatment of a complex bone and joint infection due to XDR Pseudomonas aeruginosa including local application of a selected cocktail of bacteriophages

Author: Thomas Perpoint, Guillaume L'Hostis, Frédéric Laurent, Tristan Ferry, Christian Chidiac, Gilles Leboucher, Joseph Chateau, F. Boucher, Lyon Bone, Jérôme Josse, Cindy Fevre, Charlotte Petitjean, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre interrégional de référence Rhône-Alpes - Auvergne des infections ostéo-articulaires complexes, Service de chirurgie des brûlés, plastique, reconstructrice et esthétique (Hôpital de la Croix Rousse, Hospices civils de Lyon), Pherecydes Pharma, Laboratoire de Bactériologie de l'Hôpital de la Croix-Rousse, Hospices Civils de Lyon (HCL), Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Service Pharmacie, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France, parent, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Microbiology (medical), Male, medicine.medical_specialty, Fatal outcome, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, 030106 microbiology, Drug resistance, medicine.disease_cause, 03 medical and health sciences, Fatal Outcome, Drug Resistance, Multiple, Bacterial, Osteoarthritis, medicine, Combined Modality Therapy, Humans, Pharmacology (medical), Pseudomonas Infections, Phage Therapy, Pharmacology, Debridement, business.industry, Pseudomonas aeruginosa, Small Cell Lung Carcinoma, 3. Good health, Surgery, Anti-Bacterial Agents, 030104 developmental biology, Infectious Diseases, business
Abstract: [DOI:\hrefhttps://dx.doi.org/10.1093/jac/dky26310.1093/jac/dky263] [PubMed:\hrefhttps://www.ncbi.nlm.nih.gov/pubmed/3006000230060002]; International audience
Published: 2018
Full Text: View/download PDF

110. Safety study and therapeutic drug monitoring of the oral tablet formulation of posaconazole in patients with haematological malignancies

Author: Lemaitre, Florian, Le Guillou, Adrien, Pugliese, Pascal, Raffi, François, Cuzin, Lise, Katlama, Christine, Allavena, Clotilde, Dramé, Moustapha, Cotte, Laurent, Bani-Sadr, Firouzé, Orticoni, M, Soavi, M, Luquet- Besson, I, Ressiot, E, Carta- Padovani, M, Ducassou, M, Bertone, H, Galie, S, Galinier, A., Monclar, M, Ritleng, A, Ivanova, A., Blanco-Betancourt, C, Lions, C., Poizot-Martin, I., Dhiver, C, Saadia Mokhtari, M, Menard, A., Tissot Dupont, H, Toméi, C, Meddeb, L., Belkhir, A., Ravaux, I., Alvarez, M., Biezunski, N, Debard, A., Delpierre, C, Lansalot, P, Lelievre, L., Martin-Blondel, G., Piffaut, M, Porte, L., Saune, K, Delobel, P., Breaud, S., Ceppi, C, Chirio, D, Cua, E, Dellamonica, P., Demonchy, E, De Monte, A, Durant, J., Etienne, C, Ferrando, S, Garraffo, R, Michelangeli, C, Mondain, V., Bernaud, C, Billaud, E., Biron, C, Bonnet, B, Bouchez, S, Boutoille, D., Brunet-Cartier, C, Deschanvres, C, Gaborit, B., Hall, N, Le Turnier, P., Morineau, P, Reliquet, V., Sécher, S, Cavellec, M, Soria, A., Ferre, V., André-Garnier, E., Rodallec, A., Lefebvre, M, Grossi, O, Aubry, O., Amazzough, K., Benabdelmoumen, G, Bossi, P, Cessot, G, Charlier, C., Consigny, P, Danion, F., Dureault, A, Duvivier, C., Goesch, J, Guery, R., Henry, B., Jidar, K, Lanternier, F., Loubet, P., Lortholary, O., Louisin, C, Lourenco, J, Parize, P., Pilmis, B., Touam, F, Valantin, M, Tubiana, R., Agher, R, Seang, S, Schneider, L, PaLich, R, Blanc, C, Cabié, André, Abel, S., Pierre-François, S, Pasquier, J., Guitteaud, K, Turmel, J, Illiaquer, M, Fischer, P., Partisani, M., Cheneau, C., Priester, M, Batard, M, Bernard-Henry, C, de Mautort, E, Fafi-Kremer, S., Rey, D., Chirouze, C., Gardiennet, Q, Berger, J, N’Guyen, Y, Lambert, D., Hentzien, M., Lebrun, D., Brunet, A, Kmiec, I, Brodard, V, Chidiac, C., Ferry, T., Ader, F., Biron, F., Boibieux, A., Miailhes, P., Perpoint, T., Schlienger, I, Lippmann, J, Braun, E, Koffi, J, Longuet, C., Guéripel, V, Augustin-Normand, C, Brochier, C, Degroodt, S, Atoui, N, Le Moing, V., Makinson, A., Meftah, N., de Boever, C Merle, Montes, B, Montoya Ferrer, A, Reynes, J., Andre, M., Boyer, L, Bouillon, M, Delestan, M, May, T, Hocqueloux, L, Prazuck, T., Gubavu, C, Sève, A, Maka, A, Boulard, C., Thomas, G, Cheret, A, Goujard, C, Quertainmont, Y, Teicher, E., Lerolle, N., Deradji, O, Barrail-Tran, A, Landman, R, Joly, V, Rioux, C., Lariven, S, gervais, a, Lescure, F., Matheron, S., Louni, F, Godard, C, Julia, Z, Chansombat, M, Rahli, D, Mackoumbou-Nkouka, C, Charpentier, c, Descamps, D., Peytavin, G., Yazdanpanah, Y., Tattevin, P., Revest, M., Souala, F., Baldeyrou, M., Patrat-Delon, S, Chapplain, J, Bénézit, F., Dupont, M., Poinot, M., MAILLARD, A, Pronier, C., Guennoun, C, Poisson-Vanier, M, Jovelin, T., Sinteff, J, Arvieux, C, Botelho-Nevers, E., Gagneux-Brunon, A., Frésard, A., Lucht, F., Ajana, F, Aïssi, E, Alcaraz, I, Baclet, V, Bocket, L, Boucher, A, Choisy, P, Huleux, T., Lafon-Desmurs, B., Meybeck, A, Pradier, M, Robineau, O, Viget, N, Valette, M., Hoen, B., Lamaury, I, Fabre, I, Curlier, E, Ouissa, R, Schepers, K, Herrmann-Storck, C, Dournon, N, Merrien, D, Perré, P., Guimard, T, Bollangier, O, Leautez, S, Morrier, M, Boglione-Kerrien, C., Picard, S., Tron, C., Nimubona, S., Gangneux, J.-P., Lalanne, S., Lemaître, F., Bellissant, E., Verdier, M.-C., Petitcollin, A., Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Nice (CHU Nice), Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de maladies infectieuses et tropicales [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), DDSIS 76, Institut national de recherche et de sécurité (Vandoeuvre lès Nancy) (INRS ( Vandoeuvre lès Nancy)), Service des Maladies Infectieuses et Tropicales [Hôpital de la Conception] (SMIT), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Laboratoire de Physique et Chimie Quantique, Université Mouloud Mamerri, Pôle des Maladies Infectieuses et Tropicales Clinique et Biologique, Fédération de Bactériologie-Hygiène-Virologie, Assistance Publique - Hôpitaux de Marseille (APHM), Département de Physique Nucléaire (ex SPhN) (DPHN), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut des Matériaux, de Microélectronique et des Nanosciences de Provence (IM2NP), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Département Etude des Réacteurs (DER), CEA-Direction de l'Energie Nucléaire (CEA-DEN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hopital l'Archet, Centre d'Information et de Soins de I'Immunodéficience Humaine (CISIH). Hôpital l'Archet 1, Hôpital l'Archet, CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôtel-Dieu de Nantes, Service de virologie [CHU Nantes], Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Science et Technologie du Lait et de l'Oeuf (STLO), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Université Paris Descartes - Paris 5 (UPD5), Institut de Physique du Globe de Paris (IPGP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses [CHU Pitié-Salêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Système membranaires, photobiologie, stress et détoxication (SMPSD), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Weill Cornell Medicine [Qatar], Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de Virologie [Strasbourg], GEOMA, Université de Vigo, Universidate de Vigo, Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Laboratoire d'aérologie (LA), Centre National de la Recherche Scientifique (CNRS)-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service des Maladies Infectieuses, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France, parent, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hosp Civils Lyon, Serv Malad Infect, Lyon, France, Equipe 15, Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Recherches Translationnelles sur le VIH et les maladies infectieuses (TransVIHMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Universtié Yaoundé 1 [Cameroun]-Université de Montpellier (UM), Faculté des Mathématiques et des Sciences de la Matière, Université Kasdi Merbah Ouargla, Laboratoire de Géochimie Isotopique Environnementale (GIS) / Université de Nîmes (GIS), Université de Nîmes (UNIMES)-Centre National de la Recherche Scientifique (CNRS), CHU UCL Namur, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des maladies infectieuses et tropicales, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Pharmacie de l'Hôpital Bichat, UMR CNRS 8179, Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et réanimation médicale, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Les Hôpitaux Universitaires de Strasbourg (HUS), Service de pneumologie, Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Unité des Rickettsies et pathogènes émergents (URPE), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Etienne, University Hospital and University Jean Monnet, Centre Hospitalier Tourcoing, CHU de Fort de France, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques, Laboratoire de Génie des Procédés et Matériaux - EA 4038 (LGPM), CentraleSupélec, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: 0301 basic medicine, Male, Cancer Research, Posaconazole, Antifungal Agents, [SDV]Life Sciences [q-bio], Administration, Oral, Dat’AIDS cohort, Pharmacology, 030226 pharmacology & pharmacy, Gastroenterology, 0302 clinical medicine, MESH: Drug Monitoring, Medicine, Prospective Studies, Haematological malignancies, media_common, MESH: Aged, Hematology, MESH: Middle Aged, medicine.diagnostic_test, General Medicine, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 90-90-90 target, 3. Good health, Posaconazole oral tablet, Oncology, Quartile, MESH: Young Adult, Hematologic Neoplasms, MESH: Administration, Oral, Female, Drug Monitoring, Antifungal prophylaxis, Safety, medicine.drug, Tablets, Drug, Adult, medicine.medical_specialty, media_common.quotation_subject, 030106 microbiology, Therapeutic drug monitoring, 03 medical and health sciences, Young Adult, Pharmacokinetics, Invasive fungal infections, Internal medicine, Pharmacovigilance, primary HIV infection, cascade of care, Humans, Aged, MESH: Humans, business.industry, MESH: Adult, TasP, Triazoles, MESH: Antifungal Agents, MESH: Prospective Studies, MESH: Male, MESH: Triazoles, MESH: Tablets, business, Liver function tests, MESH: Female, MESH: Hematologic Neoplasms
Abstract: International audience; PurposePosaconazole is a triazole antifungal widely used for prophylaxis of invasive fungal disease (IFI). Posaconazole tablets allow reaching higher plasma levels than the oral suspension, but safety data with this formulation in real life are scarce. This study aimed at evaluating the safety profile, the pharmacokinetic variability, and the concentration–toxicity relationship of posaconazole tablets in patients with haematological malignancies.MethodsSixty neutropenic patients treated with posaconazole tablets for prophylaxis of IFI were prospectively included in the study. Adverse drug reactions (ADR) were recorded and analyzed by the Regional Pharmacovigilance Centre to assess posaconazole implication. Blood samples were drawn once a week and plasma trough concentrations (C min) were assayed by LC–MS/MS. The rates of ADR by quartile of C min were compared.ResultsEighteen patients (30%) experienced at least one ADR attributed to posaconazole. Liver function test (LFT) abnormalities were encountered in 20% of patients and resulted in four (6.7%) treatment discontinuations. Posaconazole median (range) C min was 1.36 (< 0.1–3.44) µg/mL (inter-patient CV = 43.9%). During follow-up, 28.6% of patients had at least one concentration < 0.7 µg/mL, and 35.7% had at least one concentration > 2 µg/mL. Rates of ADR by quartile of C min were not different.ConclusionsPosaconazole was well tolerated; however, LFT abnormalities were frequent. ADR occurrence was not linked to posaconazole exposure. Because posaconazole concentrations were highly variable, TDM can be helpful to avoid underexposure to the drug and increase its efficacy in preventing IFI. Conversely, a large proportion of patients was overexposed and might have benefited of a dose reduction.
Published: 2018
Full Text: View/download PDF

111. Pott's disease associated with large and multiple abscesses in a 30-year-old migrant from Chad

Author: Conrad, Anne, Ferry, Tristan, Ader, Florence, VALOUR, Florent, group., Lyon BJI Study, Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Tuberculosis, Chad, Images In…, Antitubercular Agents, Physical examination, Disease, Thoracic Vertebrae, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Spinal cord compression, medicine, Vertebral osteomyelitis, Humans, Abscess, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Transients and Migrants, 0303 health sciences, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, General Medicine, Mycobacterium tuberculosis, bone and joint infections, medicine.disease, Magnetic Resonance Imaging, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Surgery, medicine.anatomical_structure, Thoracic vertebrae, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, tb and other respiratory infections, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tuberculosis, Spinal, business, 030217 neurology & neurosurgery
Abstract: After a 1-year history of increasing mechanical back pain, a 30-year-old Chadian man with no medical record progressively developed a voluminous paravertebral mass (figure 1A). He described night sweats without fever for several months associated with a 20 kg weight loss (admission weight at 68 kg). Physical examination revealed no neurological defect. Laboratory tests showed a biological inflammatory syndrome with C reactive protein (CRP) plasmatic level at 80 mg/L and fibrinogen at 5.1 g/L. A vertebral MRI showed a T11–T12 vertebral osteomyelitis with a discal and corporeal abscess surrounded by important adjacent bone oedema, epiduritis causing mild spinal cord compression, as well as voluminous, prevertebral (12×8×5 cm), left psoas (9×8×8 cm) and retrovertebral (16×5×4 cm) liquid collections with peripheral contrast enhancement, suggestive of abscesses (figure 1B–D). Culture of the punctured collection of the retrovertebral abscess yielded multisusceptible Mycobacterium tuberculosis . Body scan revealed no other disease localisation. HIV serological test was negative and CD4 +T cell count (609/mm …
Published: 2018
Full Text: View/download PDF

112. Association between biofilm formation phenotype and clonal lineage in Staphylococcus aureus strains from bone and joint infections

Author: Jason Tasse, Sophie Trouillet-Assant, Jérôme Josse, Patricia Martins-Simões, Florent Valour, Carole Langlois-Jacques, Stéphanie Badel-Berchoux, Christian Provot, Thierry Bernardi, Tristan Ferry, Frédéric Laurent, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), BioFilm Control, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département de Microbiologie Clinique [HCL Groupement Hospitalier Nord, Lyon], Hospices Civils de Lyon (HCL)-HCL Groupement Hospitalier Nord [Lyon], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Arthritis, Infectious, Staphylococcus aureus, Virulence Factors, lcsh:R, lcsh:Medicine, Middle Aged, Staphylococcal Infections, biochemical phenomena, metabolism, and nutrition, Bone Diseases, Infectious, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Phenotype, Bacterial Proteins, Species Specificity, Biofilms, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, Surgical Wound Infection, [SDV.IMM]Life Sciences [q-bio]/Immunology, lcsh:Q, Female, Treatment Failure, lcsh:Science
Abstract: International audience; Biofilm formation is a critical virulence factor responsible for treatment failure and chronicity in orthopaedic device-related infections (ODIs) caused by Staphylococcus aureus. Clonal lineages differ in terms of their biofilm forming capacities. The aim of this study was to investigate the correlation between the clonal complex (CC) affiliation and biofilm phenotype of 30 clinical S. aureus isolates responsible of ODI based on i) early biofilm formation using BioFilm Ring Test\textregistered and mature biofilm formation using crystal violet assays, ii) biofilm composition using DNase and proteinase K activity, and iii) prevention of biofilm formation by cloxacillin, teicoplanin and vancomycin using Antibiofilmogram\textregistered (biofilm minimal inhibitory concentration-bMIC). In terms of early biofilm formation, the CC30 strains were significantly slower than the CC5, CC15 and CC45 strains. CC45 strains produced significantly more mature biofilm than other group of strains did. The formation of biofilms was highly dependent on the presence of extracellular DNA in the CC5, CC15 and CC30 strains whereas it was mostly dependent on the presence of proteins in CC45. Finally, the CC30 group highlighted higher proportion of susceptible (bMIC \textless breakpoints of EUCAST guidelines) for cloxacillin, teicoplanin and vancomycin compared to the other CCs. These results demonstrate that the biofilm phenotype of clinical S. aureus isolates from ODIs is strongly related to their respective CC affiliation.
Published: 2018
Full Text: View/download PDF

113. Human Genetic Susceptibility to Native Valve Staphylococcus aureus Endocarditis in Patients With S. aureus Bacteremia: Genome-Wide Association Study

Author: Moreau, Karen, Clemenceau, Alisson, Le Moing, Vincent, Messika-Zeitoun, David, Andersen, Paal S., Bruun, Niels E., Skov, Robert L., Couzon, Florence, Bouchiat, Coralie, Erpelding, Marie L., van Belkum, Alex, Bossé, Yohan, Duval, Xavier, Vandenesch, François, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Université Laval [Québec] (ULaval), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Statens Serum Institut [Copenhagen], Aalborg University [Denmark] (AAU), Centre National de Reference des Staphylocoques, Université de Lyon, Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), BioMérieux SA [La Balme Les Grottes], Faculté de médecine de l'Université Laval [Québec] (ULaval), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), and Medical Microbiology & Infectious Diseases
Subjects: Microbiology (medical), Staphylococcus aureus, infectious endocarditis, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, GWAS, bacteremia, Microbiology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, SLC7A14
Abstract: International audience; Staphylococcus aureus infective endocarditis (SaIE) is a severe complication of S. aureus bacteremia (SAB) occurring in up to 22% of patients. Bacterial genetic factors and host conditions for SaIE have been intensely studied before; however, to date no study has focused on predisposing host genetic factors to SaIE. The present study aimed to identify genetic polymorphisms associated with SaIE by a Genome-Wide Association Study (GWAS) of 67 patients with definite native valve SaIE (cases) and 72 matched native valve patients with SAB but without IE (controls). All patients were enrolled in the VIRSTA cohort (Le Moing et al., 2015) study. Four single nucleotide polymorphisms (SNPs) located on chromosome 3 were associated with SaIE (P \textless 1 \texttimes 10-5) without reaching conventional genome-wide significance. For all, the frequency of the minor allele was lower in cases than in controls, suggesting a protective effect of the minor allele against SaIE. The same association was observed using an independent Danish verification cohort of SAB with (n = 57) and without (n = 123) IE. Ex vivo analysis of aortic valve tissues revealed that SaIE associated SNPs mentioned above were associated with significantly higher mRNA expression levels of SLC7A14, a predicted cationic amino acid transporter protein. Taken together, our results suggest an IE-protective effect of SNPs on chromosome 3 during the course of SAB. The effects of protective minor alleles may be mediated by increasing expression levels of SLC7A14 in valve tissues. We conclude that occurrence of SaIE may be the combination of a well-adapted bacterial genotype to a susceptible host.
Published: 2018
Full Text: View/download PDF

114. Staphylococcal virulence factors : interaction with human mast cells and modulation of their expression by antibiotics

Author: Hodille, Elisabeth, STAR, ABES, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Gérard Lina, and Oana Dumitrescu
Subjects: Staphylococcus aureus, Virulence factors, Hémolysine alpha (Hla), Leucocidines de Panton-Valentine (PVL), Hémolysine delta (Hld), Mastocytes, Phénol-solubles modulines (PSM), [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Facteurs de virulence, Panton-Valentine leucocidines (PVL), Mast cells, Phenol-soluble modulins (PSM), Transmission, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Alpha hemolysin (Hla), Delta hemolysin (Hld)
Abstract: S. aureus is a major human pathogen able to produce several virulence factors such as phenol-solublemodulins alpha (PSMalpha) and delta hemolysin (Hld). S. aureus is essentially spread through hand butthe elements promoting its spreading stay unsolved. Mast cells release several soluble mediatorstriggering itching behavior. We suspect the mast cell involvement in spreading of S. aureus strains andin physiopathology of staphylococcal skin infections. Upon human mast cell line, we showed thatPSMalpha1 and Hld induced the release of mediators triggering itching behavior. Moreover, these toxinswere produced in vivo during staphylococcal skin infections. Expression of staphylococcal virulencefactors is regulated by global regulatory system Agr. Interestingly, we observed that S. aureus strainsbelonging in Agr1 produced higher quantity of PSMalpha and Hld than those belonging to Agr2 and Agr3,and were more frequently responsible to skin infections during the last year. This observation supportsour hypothesis whereby a strain producing toxins able to trigger mast cell mediator inducingscratching behavior, spreads electively in the community. Thereafter, we studied modulation of PSMalphaand Hld expression by sub-inhibitory concentration of antibiotics. We reported that oxacillin inducedan inhibitory effect on PSMalpha and Hld expression, while clindamycin resulted in more frequently aninducer effect. These results are discordant with these observed with Panton-Valentine leucocidin andalpha hemolysin and interrogate on clindamycin use for its anti-toxin activity and on benefic ordeleterious effect of oxacillin inhibitory effect, S. aureus est un pathogène majeur de l’Homme capable de produire une grande variété de facteurs de virulence tels que les phénol-solubles modulines alpha (PSM) et l’hémolysine delta (Hld). La transmission de S. aureus est essentiellement manu-portée mais les éléments favorisant sa dissémination dans la population restent inconnus. Les mastocytes étant connus pour libérer des médiateurs pruritogènes, nous avons suspecté leur implication dans la physiopathologie et la transmission des infections cutanées staphylococciques. Sur une lignée de mastocytes humains, l’Hld et les PSM1, montrés pour être produits in vivo, déclenchaient la libération de tels médiateurs. Chez S. aureus, la production des toxines est sous la dépendance du système de régulation globale Agr. Les souches de S. aureus appartenant au type Agr1, produisant significativement plus d’Hld et de PSM que les autres souches, ont été les plus fréquemment retrouvées au cours de l’année 2017 dans les infections cutanées staphylococciques. Ceci corrobore l’hypothèse selon laquelle une souche de S. aureus produisant des toxines capables d’interagir avec les mastocytes et induisant un prurit, diffuse plus facilement dans la population. Nous avons ensuite étudié la modulation de l’expression des PSM et d’Hld par des concentrations sub-inhibitrices d’antibiotiques. L’oxacilline induisait une inhibition de l’expression des PSM et d’Hld alors que la clindamycine entraînait plus fréquemment une induction de leur expression. Ces observations nous ont interrogé sur l’utilisation de la clindamycine considérée habituellement comme anti-toxinique et sur l’effet bénéfique ou délétère de l’effet inhibiteur de l’oxacilline
Published: 2018

115. Oral ofloxacin and clindamycin as an alternative to the classic rifampicin-clindamycin in hidradenitis suppurativa: retrospective analysis of 65 patients

Author: Axel-Patrice Villani, Anne Tristan, A. Boibieux, Denis Jullien, Philippe Guillem, J. Delaunay, Service de dermatologie, consultation d'allergologie, Hôpital Edouard-Herriot, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Clinique du Val d'Ouest, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Microbiologie Clinique [HCL Groupement Hospitalier Nord, Lyon], Hospices Civils de Lyon (HCL)-HCL Groupement Hospitalier Nord [Lyon], Centre National de Reference des Staphylocoques, Université de Lyon, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Centre interrégional de référence Rhône-Alpes - Auvergne des infections ostéo-articulaires complexes, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Ofloxacin, Adolescent, Administration, Oral, Dermatology, medicine.disease_cause, Drug Administration Schedule, Microbiology, 030207 dermatology & venereal diseases, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Pharmacotherapy, medicine, Humans, Hidradenitis suppurativa, 030212 general & internal medicine, Child, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Dose-Response Relationship, Drug, business.industry, Drug Substitution, Clindamycin, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Anti-Bacterial Agents, Hidradenitis Suppurativa, Treatment Outcome, Staphylococcus aureus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Drug Therapy, Combination, Female, Anaerobic bacteria, Coagulase, Rifampin, business, Rifampicin, medicine.drug
Abstract: Rifampicin/Clindamycin (RC) combination is recommended as first line therapy in moderate to severe Hidradenitis Suppurativa (HS) by European S1 guidelines (1–3), notably because a large variety of microorganisms have been isolated from HS lesions: most represented bacteria appear to be Staphylococcus aureus, Coagulase negative staphylococci (CoNS) and anaerobic bacteria from normal skin flora. It has been hypothesized that these bacteria could play a central role in the initiation and maybe in the maintenance of HS lesions, possibly by being a source of antigens in a dysregulated immune response. This article is protected by copyright. All rights reserved.
Published: 2018
Full Text: View/download PDF

116. Bone Environment Influences Irreversible Adhesion of a Methicillin-Susceptible Staphylococcus aureus Strain

Author: Reffuveille, Fany, Josse, Jérôme, Velard, Frederic, Lamret, Fabien, Varin-Simon, Jennifer, Dubus, Marie, Haney, Evan, Hancock, Robert, Mongaret, Céline, Gangloff, Sophie, Biomatériaux et inflammation en site osseux - EA 4691 (BIOS), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Université de Reims Champagne-Ardenne (URCA), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), University of British Columbia (UBC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), DUBUS, MARIE, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Interfaces biomatériaux/tissus hôtes, Université de Reims Champagne-Ardenne (URCA)-IFR53-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Microbiologie de l’Environnement (LME), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Southeastern Louisiana University, Southeastern Lousiana University, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: bone environment, bacterial starvation, bone and joint infections, Microbiology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, biofilm, [SDV.IB.BIO] Life Sciences [q-bio]/Bioengineering/Biomaterials, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, antibiofilm peptides, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, ComputingMilieux_MISCELLANEOUS, Original Research
Abstract: International audience; Prosthesis and joint infections are an important threat in public health, especially due to the development of bacterial biofilms and their high resistance to antimicrobials. Biofilm-associated infections increase mortality and morbidity rates as well as hospitalization costs. Prevention is the best strategy for this serious issue, so there is an urgent need to understand the signals that could induce irreversible bacterial adhesion on a prosthesis. In this context, we investigated the influence of the bone environment on surface adhesion by a methicillin-susceptible Staphylococcus aureus strain. Using static and dynamic biofilm models, we tested various bone environment factors and showed that the presence of Mg2+, lack of oxygen, and starvation each increased bacterial adhesion. It was observed that human osteoblast-like cell culture supernatants, which contain secreted components that would be found in the bone environment, increased bacterial adhesion capacity by 2-fold (p = 0.015) compared to the medium control. Moreover, supernatants from osteoblast-like cells stimulated with TNF-α to mimic inflammatory conditions increased bacterial adhesion by almost 5-fold (p = 0.003) without impacting on the overall biomass. Interestingly, the effect of osteoblast-like cell supernatants on bacterial adhesion could be counteracted by the activity of synthetic antibiofilm peptides. Overall, the results of this study demonstrate that factors within the bone environment and products of osteoblast-like cells directly influence S. aureus adhesion and could contribute to biofilm initiation on bone and/or prosthetics implants.
Published: 2018
Full Text: View/download PDF

117. Understanding the Virulence of Staphylococcus pseudintermedius: A Major Role of Pore-Forming Toxins

Author: Maali, Yousef, Badiou, Cédric, Martins-Simões, Patricia, Hodille, Elisabeth, Bes, Michèle, Vandenesch, François, Lina, Gérard, Diot, Alan, Laurent, Frederic, TROUILLET-ASSANT, Sophie, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Centre National de Reference des Staphylocoques, Université de Lyon, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: pore-forming toxins, phenol-soluble modulins, leukotoxin Luk-I, non-professional phagocytic cells, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, polymorphonuclear neutrophils, cytotoxicity, [SDV.IMM]Life Sciences [q-bio]/Immunology, CXCR2 receptor, Staphylococcus pseudintermedius, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience; Staphylococcus pseudintermedius is responsible for severe and necrotizing infections in humans and dogs. Contrary to S. aureus, the pathophysiological mechanisms involved in this virulence are incompletely understood. We previously showed the intracellular cytotoxicity induced after internalization of S. pseudintermedius. Herein, we aimed to identify the virulence factors responsible for this cytotoxic activity. After addition of filtered S. pseudintermedius supernatants in culture cell media, MG63 cells, used as representative of non-professional phagocytic cells (NPPc), released a high level of LDH, indicating that the cytotoxicity was mainly mediated by secreted factors. Accordingly, we focused our attention on S. pseudintermedius toxins. In silico analysis found the presence of two PSMs (δ-toxin and PSM\varepsilon) as well as Luk-I leukotoxin, the presence of which was confirmed by PCR in all clinical strains tested (n = 17). Recombinant Luk-I leukotoxin had no cytotoxic activity on NPPc but the ectopic expression of the CXCR2 receptor in U937 cells conferred cytotoxity to Luk-I. This is in agreement with the lack of Luk-I effect on NPPc and the previous report of Luk-I cytoxic activity on immune cells. Contrary to Luk-I, synthetic δ-toxin and PSM\varepsilon had a strong cytotoxic activity on NPPc. The secretion of δ-toxin and PSM\varepsilon at cytotoxic concentrations by S. pseudintermedius in culture supernatant was confirmed by HPLC-MS. In addition, the supplementation of such supernatants with human serum, known to inhibit PSM, induced a complete abolition of cytotoxicity which indicates that PSMs are the key players in the cytotoxic phenotype of NPPc. The results suggest that the severity of S. pseudintermedius infections is, at least in part, explained by a combined action of Luk-I that specifically targets immune cells expressing the CXCR2 receptor, and PSMs that disrupt cell membranes whatever the cell types. The present study strengthens the key role of PSMs in virulence of the different species belonging to Staphylococcus genus.
Published: 2018
Full Text: View/download PDF

118. Prospective Cohort Study of the Tolerability of Prosthetic Joint Infection Empirical Antimicrobial Therapy

Author: Triffault-Fillit, Claire, Valour, Florent, Guillo, Ronan, Tod, Michel, Goutelle, Sylvain, Lustig, Sébastien, Fessy, Michel-Henry, Chidiac, Christian, Ferry, Tristan, Group., Lyon Bji Study, Centre de référence des infections ostéo-articulaires complexes Rhône Alpes Auvergne, Hospices Civils de Lyon (HCL), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), service pharmaceutique, Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Service de Chirurgie Orthopédique [Centre Albert Trillat], Centre Albert Trillat [Hôpital de la Croix-Rousse - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Centre Hospitalier Lyon-Sud - Chirurgie orthopédique et Traumatologie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, 030106 microbiology, Penicillanic Acid, Kaplan-Meier Estimate, Clinical Therapeutics, 03 medical and health sciences, Anti-Infective Agents, Interquartile range, Vancomycin, Internal medicine, medicine, Humans, Pharmacology (medical), Prospective Studies, Prospective cohort study, Adverse effect, Cefepime, Aged, Pharmacology, business.industry, Odds ratio, Acute Kidney Injury, Middle Aged, Confidence interval, 3. Good health, Infectious Diseases, Piperacillin, Tazobactam Drug Combination, Tolerability, Piperacillin/tazobactam, Female, Hip Prosthesis, business, medicine.drug
Abstract: [PubMed Central:\hrefhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6153819PMC6153819] [DOI:\hrefhttps://dx.doi.org/10.1128/AAC.00163-1810.1128/AAC.00163-18] [PubMed:\hrefhttps://www.ncbi.nlm.nih.gov/pubmed/2640532326405323]; International audience; The empirical use of vancomycin in combination with a broad-spectrum beta-lactam is currently recommended after the initial surgery of prosthetic joint infection (PJI). However, the tolerability of such high-dose intravenous regimens is poorly known. Adult patients receiving an empirical antimicrobial therapy (EAT) for a PJI were enrolled in a prospective cohort study (2011 to 2016). EAT-related adverse events (AE) were described according to the common terminology criteria for AE (CTCAE), and their determinants were assessed by logistic regression and Kaplan-Meier curve analysis. The EAT of the 333 included patients (median age, 69.8 years; interquartile range [IQR], 59.3 to 79.1 years) mostly relies on vancomycin (n = 229, 68.8%), piperacillin-tazobactam (n = 131, 39.3%), and/or third-generation cephalosporins (n = 50, 15%). Forty-two patients (12.6%) experienced an EAT-related AE. Ten (20.4%) AE were severe (CTCAE grade â‰¥ 3). The use of vancomycin (odds ratio [OR], 6.9; 95% confidence interval [95%CI], 2.1 to 22.9), piperacillin-tazobactam (OR, 3.7; 95%CI, 1.8 to 7.2), or the combination of both (OR, 4.1; 95%CI, 2.1 to 8.2) were the only AE predictors. Acute kidney injury (AKI) was the most common AE (n = 25; 51.0% of AE) and was also associated with the use of the vancomycin and piperacillin-tazobactam combination (OR, 6.7; 95%CI, 2.6 to 17.3). A vancomycin plasma overexposure was noted in nine (37.5%) of the vancomycin-related AKIs only. Other vancomycin-based therapies were significantly less at risk for AE and AKI. The EAT of PJI is associated with an important rate of AE, linked with the use of the vancomycin and the piperacillin-tazobactam combination. These results corroborate recent findings suggesting a synergic toxicity of these drugs in comparison to vancomycin-cefepime, which remains to be evaluated in PJI. (This study has been registered at ClinicalTrials.gov under identifier NCT03010293.).
Published: 2018
Full Text: View/download PDF

119. Novel enterobacter lineage as leading cause of nosocomial outbreak involving carbapenemase-producing strains

Author: Beyrouthy, Racha, Marion, Marion, Marion, Elodie, Dananché, Cédric, Dauwalder, Olivier, Robin, Frédéric, Gauthier, Lauraine, Jousset, Agnès, Dortet, Laurent, Guérin, François, Bénet, Thomas, Cassier, Pierre, Vanhems, Philippe, Bonnet, Richard, Barets, Marion, Centre National de Référence de la Résistance aux Antibiotiques (CNR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Associé de la Résistance aux Antibiotiques, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), Centre Léon Bérard [Lyon], INSERM, INRA, Universite Clermont Auvergne, Centre Hospitalier Universitaire de Clermont-Ferrand, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Associé de la Résistance aux Antibiotiques [Hôpital Bicêtre AP-HP] (CNRARA/Service de Microbiologie), OUERTANI, jeannette, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Epidemiology, lcsh:Medicine, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Disease Outbreaks, Plasmid, Drug Resistance, Multiple, Bacterial, Immunologie, bacteria, Aged, 80 and over, Cross Infection, biology, Phylogenetic tree, Emerging diseases, Enterobacteriaceae Infections, Enterobacter cloacae complex, Enterobacter, Middle Aged, b-lactamase, Enterobacteriaceae, infection nosocomiale, Anti-Bacterial Agents, 3. Good health, séquence du génome, Infectious Diseases, enterobacter, Female, beta-lactamase, Novel Enterobacter Lineage as Leading Cause of Nosocomial Outbreak Involving Carbapenemase-Producing Strains, Microbiology (medical), Lineage (genetic), 030106 microbiology, Immunology, Maladies émergentes, Gene Expression Regulation, Enzymologic, beta-Lactamases, Microbiology, lcsh:Infectious and parasitic diseases, Carbapenemase, 03 medical and health sciences, Antibiotic resistance, Enterobacter cloacae, Humans, lcsh:RC109-216, Typing, antimicrobial resistance, Aged, Research, lcsh:R, carbapenemase-producing Enterobacteriaceae, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Gene Expression Regulation, Bacterial, CPE, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, nosocomial outbreak, 030104 developmental biology, VIM-4, next-generation sequencing, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract: International audience; We investigated unusual carbapenemase-producing Enterobacter cloacae complex isolates (n = 8) in the novel sequence type (ST) 873, which caused nosocomial infections in 2 hospitals in France. Whole-genome sequence typing showed the 1-year persistence of the epidemic strain, which harbored a blaVIM-4 ST1-IncHI2 plasmid, in 1 health institution and 2 closely related strains harboring blaCTX-M-15 in the other. These isolates formed a new subgroup in the E. hormaechei metacluster, according to their hsp60 sequences and phylogenomic analysis. The average nucleotide identities, specific biochemical properties, and pangenomic and functional investigations of isolates suggested isolates of a novel species that had acquired genes associated with adhesion and mobility. The emergence of this novel Enterobacter phylogenetic lineage within hospitals should be closely monitored because of its ability to persist and spread.
Published: 2018
Full Text: View/download PDF

120. Staphylococcus aureus CC30 Lineage and Absence of sed,j,r-Harboring Plasmid Predict Embolism in Infective Endocarditis

Author: Jean-Philippe Rasigade, Amélie Leclère, François Alla, Adrien Tessier, Michèle Bes, Catherine Lechiche, Véronique Vernet-Garnier, Cédric Laouénan, François Vandenesch, Catherine Leport, The AEPEI Study Group, B. Hoen, X. Duval, F. Alla, A. Bouvet, S. Briancxon, E. Cambau, M. Celard, C. Chirouze, N. Danchin, T. Doco-Lecompte, F. Delahaye, J. Etienne, B. Iung, V. Le Moing, J. F. Obadia, C. Leport, C. Poyart, M. Revest, C. Selton-Suty, C. Strady, P. Tattevin, F. Vandenesch, Y. Bernard, S. Chocron, P. Plesiat, I. Abouliatim, C. De Place, P. Y. Donnio, J. P. Carteaux, C. Lion, N. Aissa, B. Baehrel, R. Jaussaud, P. Nazeyrollas, V. Vernet, P. Nataf, C. Chidiac, H. Aumaître, J. M. Frappier, E. Oziol, A. Sotto, C. Sportouch, M. Bes, P. Abassade, E. Abrial, C. Acar, J. F. Alexandra, N. Amireche, D. Amrein, P. Andre, M. Appriou, M. A. Arnould, P. Assayag, A. Atoui, F. Aziza, N. Baille, N. Bajolle, P. Battistella, S. Baumard, A. Ben Ali, J. Bertrand, S. Bialek, M. Bois Grosse, M. Boixados, F. Borlot, A. Bouchachi, O. Bouche, S. Bouchemal, J. L. Bourdon, L. Brasme, F. Bricaire, E. Brochet, F. J. Bruntz, A. Cady, J. Cailhol, M. P. Caplan, B. Carette, O. Cartry, C. Cazorla, H. Chamagne, H. Champagne, G. Chanques, J. Chastre, B. Chevalier, F. Chometon, C. Christophe, A. Cohen, N. Colin de Verdiere, V. Daneluzzi, L. David, P. De Lentdecker, V. Delcey, P. Deleuze, E. Donal, B. Deroure, V. Descotes-Genon, K. Didier Petit, A. Dinh, V. Doat, F. Duchene, F. Duhoux, M. Dupont, S. Ederhy, O. Epaulard, M. Evest, J. F. Faucher, B. Fantin, E. Fauveau, T. Ferry, M. Fillod, T. Floch, T. Fraisse, J. M. Frapier, L. Freysz, B. Fumery, B. Gachot, S. Gallien, I. Gandjbach, P. Garcon, A. Gaubert, J. L. Genoud, S. Ghiglione, C. Godreuil, A. Grentzinger, L. Groben, D. Gherissi, P. Gue'ret, A. Hagege, N. Hammoudi, F. Heliot, P. Henry, S. Herson, P. Houriez, L. Hustache-Mathieu, O. Huttin, S. Imbert, S. Jaureguiberry, M. Kaaki, A. Konate, J. M. Kuhn, S. Kural Menasche, A. Lafitte, B. Lafon, F. Lanternier, V. Le Chenault, C. Lechiche, S. Lefèvre-Thibaut, A. Lefort, A. Leguerrier, J. Lemoine, L. Lepage, C. Lepouse', J. Leroy, P. Lesprit, L. Letranchant, D. Loisance, G. Loncar, C. Lorentz, P. Mabo, I. Magnin-Poull, T. May, A. Makinson, H. Man, M. Mansouri, O. Marcxon, J. P. Maroni, V. Masse, F. Maurier, M. C. Meyohas, P. L. Michel, C. Michelet, F. Mechaï, O. Merceron, D. Messika-Zeitoun, Z. Metref, V. Meyssonnier, C. Mezher, S. Micheli, M. Monsigny, S. Mouly, B. Mourvillier, O. Nallet, V. Noel, T. Papo, B. Payet, A. Pelletier, P. Perez, J. S. Petit, F. Philippart, E. Piet, C. Plainvert, B. Popovic, J. M. Porte, P. Pradier, R. Ramadan, J. Richemond, M. Rodermann, M. Roncato, I. Roigt, O. Ruyer, M. Saada, J. Schwartz, M. Simon, B. Simorre, S. Skalli, F. Spatz, J. Sudrial, L. Tartiere, A. Terrier De La Chaise, M. C. Thiercelin, D. Thomas, M. Thomas, L. Toko, F. Tournoux, A. Tristan, J. L. Trouillet, L. Tual, A. Vahanian, F. Verdier, V. Vernet Garnier, V. Vidal, P. Weyne, M. Wolff, A. Wynckel, N. Zannad, P. Y. Zinzius, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Reference des Staphylocoques, Université de Lyon, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Service des maladies infectieuses et tropicales, Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Entérobactéries Résistance Acquise - EA 4687 (ERA), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)
Subjects: 0301 basic medicine, Microbiology (medical), Immunology, lcsh:QR1-502, MRSA, medicine.disease_cause, Staphylococcal infections, Microbiology, lcsh:Microbiology, superantigen, 03 medical and health sciences, plasmid, medicine, Endocarditis, business.industry, infective endocarditis, SCCmec, Odds ratio, medicine.disease, S. aureus, Methicillin-resistant Staphylococcus aureus, stroke, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, 030104 developmental biology, Infectious Diseases, Embolism, Staphylococcus aureus, Infective endocarditis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, CC30, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, enterotoxin
Abstract: International audience; Staphylococcus aureus induces severe infective endocarditis (IE) where embolic complications are a major cause of death. Risk factors for embolism have been reported such as a younger age or larger IE vegetations, while methicillin resistance conferred by the mecA gene appeared as a protective factor. It is unclear, however, whether embolism is influenced by other S. aureus characteristics such as clonal complex (CC) or virulence pattern. We examined clinical and microbiological predictors of embolism in a prospective multicentric cohort of 98 French patients with monomicrobial S. aureus IE. The genomic contents of causative isolates were characterized using DNA array. To preserve statistical power, genotypic predictors were restricted to CC, secreted virulence factors and virulence regulators. Multivariate regularized logistic regression identified three independent predictors of embolism. Patients at higher risk were younger than the cohort median age of 62.5 y (adjusted odds ratio [OR] 0.14; 95% confidence interval [CI] 0.05-0.36). S. aureus characteristics predicting embolism were a CC30 genetic background (adjusted OR 9.734; 95% CI 1.53-192.8) and the absence of pIB485-like plasmid-borne enterotoxin-encoding genes sed, sej, and ser (sedjr; adjusted OR 0.07; 95% CI 0.004-0.457). CC30 S. aureus has been repeatedly reported to exhibit enhanced fitness in bloodstream infections, which might impact its ability to cause embolism. sedjr-encoded enterotoxins, whose superantigenic activity is unlikely to protect against embolism, possibly acted as a proxy to others genes of the pIB485-like plasmid found in genetically unrelated isolates from mostly embolism-free patients. mecA did not independently predict embolism but was strongly associated with sedjr. This mecA-sedjr association might have driven previous reports of a negative association of mecA and embolism. Collectively, our results suggest that the influence of S. aureus genotypic features on the risk of embolism may be stronger than previously suspected and independent of clinical risk factors.
Published: 2018
Full Text: View/download PDF

121. Clinical impact of vancomycin heteroresistance in staphylococcal strains involved in neonatal sepsis: Discussion of a case report

Author: Frédéric Laurent, Olivier Claris, Marine Butin, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Parcours santé systémique (P2S), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Population, Bacteremia, Sepsis, Staphylococcus capitis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, 030225 pediatrics, Internal medicine, medicine, Humans, Clinical significance, education, education.field_of_study, Neonatal sepsis, biology, business.industry, Infant, Newborn, Linezolid, Vancomycin Resistance, Staphylococcal Infections, biochemical phenomena, metabolism, and nutrition, medicine.disease, biology.organism_classification, Anti-Bacterial Agents, 3. Good health, chemistry, Pediatrics, Perinatology and Child Health, Vancomycin, business, Infant, Premature, medicine.drug
Abstract: Heteroresistance to vancomycin (HRV) represents a decreased susceptibility to vancomycin and is frequently observed in multidrug-resistant coagulase-negative staphylococci. The clinical significance of such heteroresistance is controversial, but several failures of vancomycin therapy have been related to HRV, especially in the neonatal population. Here we report the case of a preterm neonate, born at 26 weeks of gestation, who developed sepsis due to a multidrug-resistant HRV Staphylococcus capitis isolate. Bacteremia persisted despite adequate vancomycin serum concentration and catheter removal. The patient finally recovered after replacing vancomycin by linezolid. Through this case report, we would like to alert clinicians of the potential clinical impact of HRV and to discuss the lack of therapeutic alternatives in neonates.
Published: 2019
Full Text: View/download PDF

122. Metallosis-associated prosthetic joint infection

Author: T, Barba, J, Wach, S, Lustig, F, Laurent, M, Devouassoux-Shisheboran, F, Valour, C, Chidiac, T, Ferry, Eugénie, Mabrut, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Chirurgie Orthopédique [Centre Albert Trillat], Centre Albert Trillat [Hôpital de la Croix-Rousse - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Centre interrégional de référence Rhône-Alpes - Auvergne des infections ostéo-articulaires complexes, Laboratoire de Bactériologie de l'Hôpital de la Croix-Rousse, Hospices Civils de Lyon (HCL), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomo-Pathologie [Hôpital de la Croix-Rousse - HCL], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, Prosthesis-Related Infections, ARTICULATION HUMAINE, medicine.medical_treatment, Prosthesis, METALLOSE, INFECTION DE PROTHESE ARTICULAIRE, BIOMECANIQUE, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Metallosis, Total joint replacement, 030212 general & internal medicine, Prosthesis-Related Infection, Aged, 80 and over, PROTHESE, 030222 orthopedics, PROSTHETIC JOINT INFECTION, business.industry, Standard treatment, ALVAL, Prosthetic joint infection, Metal debris, Middle Aged, medicine.disease, Hip resurfacing, 3. Good health, Surgery, Infectious Diseases, VARIANTS MICROCOLONIES, Metal-on-Metal Joint Prostheses, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Female, Hip Prosthesis, METALLOSIS, Knee Prosthesis, business, SMALL COLONY VARIANTS
Abstract: Total joint replacement is the standard treatment of advancedosteoarthritis. Metal-on-Metal (MoM) hip resurfacing and hiparthroplasty are associated with long durability and low rates ofdislocations and used to be the standard surgical treatments.Complications due to MoM prostheses have however beenwidely reported. Adverse reactions to metal debris (ARMD)such as metallosis result from the progressive degradation of themetal surface and from metal ions deposition in the surroundingtissues. The formation of 'pseudotumors' leading to prosthe-sis malfunction has been reported after MoM resurfacing. Totalarthroplasty can also lead to the infection of the prosthesis asa consequence of contamination during surgery or bacteremicinfection not related to the prosthesis. Infections remain quitecommon (1-3% of surgical procedures) but reports of associ-ated ARMD are limited. We report the case of three patientspresenting with metallosis-associated infection on joint pros-thesis.
Published: 2015
Full Text: View/download PDF

123. EDIN-B Promotes the Translocation of Staphylococcus aureus to the Bloodstream in the Course of Pneumonia

Author: Hubert Lepidi, Coralie Bouchiat, Jean-Philippe Lavigne, Johan Courjon, Eric Ghigo, Patrick Munro, Anne Doye, Laurent Boyer, Orane Visvikis, Emmanuel Lemichez, François Vandenesch, Y. Benito, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Staphylococcus aureus, Health, Toxicology and Mutagenesis, Virulence, lcsh:Medicine, Bacteremia, Biology, methicillin-resistant Staphylococcus aureus, Toxicology, medicine.disease_cause, Staphylococcal infections, virulence factor, Virulence factor, Article, Microbiology, 03 medical and health sciences, Mice, Bacterial Proteins, medicine, Human Umbilical Vein Endothelial Cells, Pneumonia, Bacterial, Animals, Humans, 030304 developmental biology, 0303 health sciences, Mice, Inbred BALB C, Lung, 030306 microbiology, lcsh:R, toxins, Staphylococcal Infections, medicine.disease, bacterial infections and mycoses, Methicillin-resistant Staphylococcus aureus, Virology, 3. Good health, Pneumonia, Disease Models, Animal, medicine.anatomical_structure, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Bacterial Translocation, Female, Gene Deletion
Abstract: International audience; It is crucial to define risk factors that contribute to host invasion by Staphylococcus aureus. Here, we demonstrate that the chromosomally encoded EDIN-B isoform from S. aureus contributes to the onset of bacteremia during the course of pneumonia. Deletion of edinB in a European lineage community-acquired methicillin resistant S. aureus (CA-MRSA) strain (ST80-MRSA-IV) dramatically decreased the frequency and magnitude of bacteremia in mice suffering from pneumonia. This deletion had no effect on the bacterial burden in both blood circulation and lung tissues. Re-expression of wild-type EDIN-B, unlike the catalytically inactive mutant EDIN-R185E, restored the invasive characteristics of ST80-MRSA-IV.
Published: 2015
Full Text: View/download PDF

124. In Vivo Effect of Flucloxacillin in Experimental Endocarditis Caused by mecC -positive Staphylococcus aureus Showing Temperature-Dependent Susceptibility In Vitro

Author: Frédéric Laurent, François Vandenesch, Jacques Vouillamoz, Stefano Mancini, Marlyse Giddey, Philippe Moreillon, José M. Entenza, Tiago Rafael Veloso, Department of Fundamental Microbiology [Lausanne], Université de Lausanne (UNIL), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Methicillin-Resistant Staphylococcus aureus, Microbial Sensitivity Tests, Staphylococcal infections, medicine.disease_cause, Floxacillin, Microbiology, Cefoxitin, 03 medical and health sciences, In vivo, polycyclic compounds, Animals, Medicine, Endocarditis, Experimental Therapeutics, Pharmacology (medical), Aorta, Infusion Pumps, Chromatography, Micellar Electrokinetic Capillary, Oxacillin, 030304 developmental biology, Pharmacology, Chromatography, 0303 health sciences, 030306 microbiology, business.industry, Bacterial, Temperature, Endocarditis, Bacterial, Staphylococcal Infections, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Methicillin-resistant Staphylococcus aureus, In vitro, Anti-Bacterial Agents, Rats, 3. Good health, Infectious Diseases, Staphylococcus aureus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Micellar Electrokinetic Capillary, Flucloxacillin, business, medicine.drug
Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) carrying the mecC gene ( mecC -MRSA) exhibited at 37°C MICs of oxacillin close to those of methicillin-susceptible S. aureus (MSSA). We investigated whether at this temperature, mecC -MRSA strains respond to flucloxacillin treatment like MSSA strains, using a rat model of endocarditis. Flucloxacillin (human-like kinetics of 2 g intravenously every 6 h) cured 80 to 100% of aortic vegetations infected with five different mecC -MRSA strains. These results suggest that mecC -MRSA infections may successfully respond to treatment with β-lactams.
Published: 2015
Full Text: View/download PDF

125. The levels of antibodies to Panton–Valentine leukocidin (PVL) vary with PVL prevalence along a north-to-south gradient

Author: F. Vandenesch, Frédéric Laurent, Cheikh Fall, K. Antri, Gerard Lina, M. Bernelin, J. Etienne, Michèle Bes, Cédric Badiou, Nadjia Ramdani-Bouguessa, Anne Tristan, Sébastien Breurec, Jean-Philippe Rasigade, Sophie Trouillet-Assant, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Reference des Staphylocoques, Université de Lyon, Bactériologie médicale et Environnementale, Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Le centre hospitalier universitaire (CHU) Mustapha Pacha [Alger], Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Leukocidin, Active immunization, medicine.disease_cause, Hemolysin Proteins, Medical microbiology, Leukocidins, Seroepidemiologic Studies, Medicine, skin and connective tissue diseases, education.field_of_study, Geography, biology, Bacterial, General Medicine, Middle Aged, Staphylococcal Infections, respiratory system, Antibodies, Bacterial, Senegal, 3. Good health, Infectious Diseases, Staphylococcus aureus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, Antibody, Adult, Microbiology (medical), medicine.medical_specialty, Bacterial Toxins, Population, Exotoxins, Enzyme-Linked Immunosorbent Assay, Antibodies, Immunity, Humans, education, Aged, Retrospective Studies, business.industry, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Virology, Cross-Sectional Studies, Algeria, Immunology, biology.protein, bacteria, Panton–Valentine leukocidin, business
Abstract: International audience; Recent research on Staphylococcus aureus vaccine development has focused on active immunization against Panton-Valentine leukocidin (PVL), a potent leukotoxin associated with both superficial and severe deep-seated infections. PVL prevalence is highly variable worldwide, but it is unknown to what extent immunity to PVL varies between patients from geographic areas with different PVL-positive S. aureus prevalences. We conducted a retrospective multicentric study of anti-PVL and anti-alpha-toxin (Hla) antibody levels in uninfected adult patients from France (low PVL prevalence; n = 200), Algeria (moderate prevalence; n = 143), and Senegal (high prevalence; n = 228). The antibody levels were quantified by an enzyme-linked immunosorbent assay (ELISA) procedure. Because Hla is present in virtually all S. aureus strains, its corresponding antibody levels were considered to reflect population exposure to S. aureus. Compared with French participants, the average anti-PVL antibody levels were 2.5-fold and 8.2-fold higher in Algerian and Senegalese participants, respectively (p \textless 0.001). Conversely, anti-Hla antibody levels did not differ between participants from the three countries, suggesting that the observed differences in anti-PVL antibody levels were not biased by variations in population exposure to S. aureus. Hence, anti-PVL antibody levels in the general populations of France, Algeria, and Senegal vary widely and match variations in PVL-positive S. aureus strain prevalence, with an increasing north-to-south gradient. To conclude, immunity to PVL in a given population correlates with local PVL prevalence. This finding can help to inform PVL vaccine strategies.
Published: 2015
Full Text: View/download PDF

126. Staphylococcus aureus Targets the Duffy Antigen Receptor for Chemokines (DARC) to Lyse Erythrocytes

Author: Cédric Badiou, Kristina M. Boguslawski, Victor J. Torres, Thomas Henry, Jos A. G. van Strijp, Yves Colin, Michael P. Jennings, Tamara Reyes-Robles, Caroline Le Van Kim, Christopher J. Day, Carla J C Gosselaar-de Haas, Sylvie Cochet, András N. Spaan, François Vandenesch, Kok P. M. van Kessel, Pauline Yoong, Inflammasome, Infections bactériennes et autoinflammation, Inflammasome, Bacterial Infections and Autoinflammation (I2BA), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Medical Center [Utrecht], New York University School of Medicine, NYU System (NYU), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Biologie Intégrée du Globule Rouge (BIGR (UMR_S_1134 / U1134)), Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Université des Antilles (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Glycomics, Griffith University [Brisbane], Inflammasome, Bacterial Infections and Autoinflammation, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Université de La Réunion (UR)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Transfusion Sanguine [Paris] (INTS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Transfusion Sanguine [Paris] (INTS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)
Subjects: Chemokine, Cancer Research, Lysis, Erythrocytes, Receptor expression, Plasma protein binding, medicine.disease_cause, Biochemistry, 0302 clinical medicine, Leukocidins, Receptors, Non-U.S. Gov't, Receptor, 0303 health sciences, Research Support, Non-U.S. Gov't, Hematology, Hemolysis, 3. Good health, medicine.anatomical_structure, Staphylococcus aureus, Cell Surface, Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Protein Binding, Immunology, Virulence, Receptors, Cell Surface, Biology, Staphylococcal infections, Research Support, Microbiology, N.I.H, 03 medical and health sciences, Research Support, N.I.H., Extramural, Virology, Antigen receptor, Immunology and Microbiology(all), medicine, Journal Article, Humans, Molecular Biology, 030304 developmental biology, Innate immune system, Extramural, Cell Biology, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, In vitro, Red blood cell, biology.protein, Parasitology, Duffy Blood-Group System, Bacteria, 030215 immunology
Abstract: Introduction: Staphylococcus aureus is a major human pathogen. Infections by this bacterium range from minor skin and soft tissue infections, to more invasive and life threating infections like sepsis, osteomyelitis, and pneumonia. In order to successfully infect the mammalian host, S. aureus has to overcome iron scarcity within the host. As such, S. aureus is thought to produce toxins that lyse erythrocytes, releasing hemoglobin, a critical iron source for S. aureus in mammals. The bi-component β-barrel pore-forming leukocidins kill human neutrophils and were mostly considered as virulence factors fighting the host innate immune system. We show here thatHlgAB and LukED are two potent hemolytic leukocidins against human erythrocytes. Furthermore, we describe the identification of the Duffy antigen receptor for chemokines (DARC) as the red blood cell receptor for both LukED and HlgAB leukocidins. Results: We took advantage of erythrocyte samples from different Duffy (Fy) genotyped individuals from the French National Blood Transfusion Institute. We evaluated the receptor expression on the surface of erythrocytes (Figure 1). DARC-negative erythrocytes (phenotype Fya-/b-) were fully resistant to HlgAB and LukED. Compared to individuals expressing normal levels of DARC (phenotypes Fya+/b+, Fya+/b+weak, Fya+/a+, and Fyb+/b+), individuals expressing intermediate (phenotype Fyb+weak/b+weak) or very low levels of DARC (phenotype Fyb-/b+weak) showed intermediate susceptibility to both HlgAB and LukED (Figure 1). These data demonstrate that the hemolytic activity of HlgAB and LukED is dependent on the expression of DARC at the red blood cell surface. To better understand the interaction of HlgAB and LukED with DARC, we screened HEK293T cells transfected with plasmids encoding DARC mutants (Tournamille et al, 2003). We demonstrate that while both HlgAB and LukED bind to DARC with nanomolar affinities, they do so by recognizing different domains of the receptor. To directly evaluate whether LukED and HlgAB can promote bacterial replication as a result of erythrocyte lysis, S. aureus was grown in iron-starved medium supplemented with cell-free extracts of erythrocytes treated with LukED or HlgAB. We observed that HlgAB and LukED were each capable of promoting S. aureus growth in a DARC and hemoglobin scavenging system (IsdBH)-dependent manner. These in vitro studies were supported by a murine bacteremia model. Discussion: By combining human studies of DARC polymorphisms with gain and loss of function experiments and biochemical analyses, we demonstrate that DARC is necessary and sufficient to render host cells susceptible to LukED and HlgAB. By targeting DARC, HlgAB and LukED support S. aureus growth in a hemoglobin-acquisition dependent-manner. Thus, these findings provide the missing link of how S. aureus targets and lyses erythrocytes to release one of the scarcest nutrient within the mammalian host. Human epidemiological studies comparing the severity of S. aureus infection in patients with DARC positive or DARC negative erythrocytes are now required to evaluate the contribution of DARC-mediated hemolysis in human staphylococcal diseases. Given the resistance of DARC negative erythrocytes to the parasites Plasmodium vivax and P. knowlesi, and now to the hemolytic activity of the bacterium S. aureus, our findings suggest the possibility of a positive selection event in response to these important human pathogens. (A) Susceptibility of human erythrocytes to S. aureus β-barrel pore forming toxins. The dashed line indicates 50% hemolysis. n = 6. (B) Levels of DARC and CD55 on erythrocytes of donors with different Fy phenotypes. The dashed line indicates the detection threshold. n = 2-7 ± SEM. (C,E) Susceptibility of human erythrocytes with different Fy phenotypes to HlgAB (C) and LukED (E). The dashed line indicates 50% hemolysis. n = 2-7 ± SEM. (D, F) Correlation of half-maximal effective concentrations (EC50) of HlgAB (D) and LukED (F) with the total number of receptors expressed on the erythrocyte surface. For Fyb+weak/Fyb- donors, LukED EC50 could not be calculated. n = 2-7 ± SEM. Figure 1. Hemolytic activity of HlgAB and LukED depends on DARC. Figure 1. Hemolytic activity of HlgAB and LukED depends on DARC. Disclosures No relevant conflicts of interest to declare.
Full Text: View/download PDF

127. Microbiologic epidemiology depending on time to occurrence of prosthetic joint infection: a prospective cohort study

Author: C. Triffault-Fillit, T. Ferry, F. Laurent, P. Pradat, C. Dupieux, A. Conrad, A. Becker, S. Lustig, M.H. Fessy, C. Chidiac, F. Valour, T. Perpoint, A. Boibieux, F. Biron, P. Miailhes, F. Ader, S. Roux, F. Daoud, J. Lippman, E. Braun, Y. Gillet, L. Hees, E. Servien, Y. Herry, R. Gaillard, A. Schneider, M.-H. Fessy, A. Viste, P. Chaudier, R. Desmarchelier, T. Mouton, C. Courtin, L. Louboutin, S. Martres, F. Trouillet, C. Barrey, F. Signorelli, E. Jouanneau, T. Jacquesson, A. Mojallal, F. Boucher, H. Shipkov, J. Château, F. Aubrun, I. Bobineau, C. Macabéo, F. Vandenesch, J.-P. Rasigade, F. Craighero, L. Boussel, J.-B. Pialat, I. Morelec, M. Janier, F. Giammarile, M. Tod, M.-C. Gagnieu, S. Goutelle, S. Gerbier-Colomban, T. Benet, E. Mabrut, Centre interrégional de référence Rhône-Alpes - Auvergne des infections ostéo-articulaires complexes, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Microbiologie Clinique [HCL Groupement Hospitalier Nord, Lyon], Hospices Civils de Lyon (HCL)-HCL Groupement Hospitalier Nord [Lyon], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Service de Chirurgie Orthopédique [Centre Albert Trillat], Centre Albert Trillat [Hôpital de la Croix-Rousse - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Centre Hospitalier Lyon-Sud - Chirurgie orthopédique et Traumatologie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Microbiology (medical), Male, Prosthetic joint infection, medicine.medical_specialty, Prosthesis-Related Infections, Time Factors, Epidemiology, medicine.medical_treatment, Joint Prosthesis, 030106 microbiology, Context (language use), medicine.disease_cause, Bacterial Physiological Phenomena, Microbiology, Prosthesis, Antimicrobial therapy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Aged, Arthritis, Infectious, Bacteria, business.industry, General Medicine, Middle Aged, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, Staphylococcus aureus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Etiology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Vancomycin, Female, business, Empiric, medicine.drug
Abstract: International audience; OBJECTIVES: The high microbiologic diversity encountered in prosthetic joint infection (PJI) makes the choice of empirical antimicrobial therapies challenging, especially in cases of implant retention or one-stage exchange. Despite the risk of dysbiosis and toxicity, the combination of vancomycin with a broad-spectrum β-lactam is currently recommended in all cases, even if Gram-negative bacilli (GNB) might be less represented in late PJI. In this context, this study aimed to describe the microbiologic epidemiology of PJI according to the chronology of infection. METHODS: This prospective cohort study (2011-2016) evaluated the microbiologic aetiology of 567 PJI according to time of occurrence from prosthesis implantation-early (\textless3~months), delayed (3-12~months) and late (\textgreater12~months)-as well as mechanism of acquisition. RESULTS: Initial microbiologic documentation (n~=~511; 90.1%) disclosed 164 (28.9%) Staphylococcus aureus (including 26 (16.1%) methicillin-resistant S.~aureus), 162 (28.6%) coagulase-negative staphylococci (including 81 (59.1%) methicillin-resistant coagulase-negative staphylococci), 80 (14.1%) Enterobacteriaceae, 74 (13.1%) streptococci and 60 (10.6%) Cutibacterium acnes. Considering nonhaematogenous late PJI (n~=~182), Enterobacteriaceae (n~=~7; 3.8%) were less represented than in the first year after implantation (n~=~56; 17.2%; p \textless0.001), without difference regarding nonfermenting GNB (4.6% and 2.7%, respectively). The prevalence of anaerobes (n~=~40; 21.9%; including 32 (80.0%) C.~acnes) was higher in late PJI (p \textless0.001). Consequently, a broad-spectrum β-lactam might be useful in 12 patients (6.6%) with late PJI only compared to 66 patients (20.3%) with early/delayed PJI (p \textless0.001). CONCLUSIONS: Considering the minority amount of GNB in late postoperative PJI, the empirical use of a broad-spectrum β-lactam should be reconsidered, especially when a two-stage exchange is planned.
Published: 2017
Full Text: View/download PDF

128. Assessing the Combined Antibacterial Effect of Isoniazid and Rifampin on Four Mycobacterium tuberculosis Strains Using In Vitro Experiments and Response-Surface Modeling

Author: Sylvain Goutelle, Gerard Lina, Charlotte Genestet, Oana Dumitrescu, Catherine Pichat, Florence Ader, Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Laboratoire de Bactériologie de l'Hôpital de la Croix-Rousse, Hospices Civils de Lyon (HCL), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Drug, Tuberculosis, media_common.quotation_subject, 030106 microbiology, Antitubercular Agents, Antibacterial effect, Microbial Sensitivity Tests, Response surface modeling, Pharmacology, Mycobacterium tuberculosis, 03 medical and health sciences, pharmacodynamics, medicine, Isoniazid, Pharmacology (medical), media_common, biology, mathematical modeling, Drug Synergism, Models, Theoretical, biology.organism_classification, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, In vitro, 3. Good health, 030104 developmental biology, Infectious Diseases, Pharmacodynamics, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Drug Therapy, Combination, Rifampin, medicine.drug
Abstract: While isoniazid and rifampin have been the cornerstone of tuberculosis therapy caused by drug-susceptible Mycobacterium tuberculosis for more than 40 years, their combined action has never been thoroughly assessed by modern quantitative pharmacology approaches. The aims of this work were to perform in vitro experiments and mathematical modeling of the antibacterial effect of isoniazid and rifampin alone and in combination against various strains of Mycobacterium tuberculosis . After MIC determination of H37Rv and three strains belonging to the Beijing, Euro-American, and Indo-Oceanic lineages, the antibacterial effects of isoniazid and rifampin alone and in combination were studied in static time-kill experiments. A sigmoidal maximum effect model (Hill equation) and a response-surface model were used to describe the effect of the drugs alone and in combination, respectively. The killing effect of isoniazid and rifampin alone were well described by the Hill equation. Rifampin displayed a more concentration-dependent effect than isoniazid around the MIC. The pharmacodynamics parameters of each drug (maximal effect, median effect concentration, and coefficient of sigmoidicity) were quite similar between the four strains. The response-surface model from Minto et al. fit data of combined effect very well with low bias and imprecision (C. F. Minto, T. W. Schnider, T. G. Short, K. M. Gregg, A. Gentilini, Anesthesiology 92: 1603–1616, 2000, https://doi.org/10.1097/00000542-200006000-00017 ). Response-surface modeling showed that the combined action of isoniazid and rifampin was synergistic for the H37Rv, Beijing, and Euro-American strains but only additive for the Indo-Oceanic strain. This study can serve as a motivating example for preclinical evaluation of combined action of antituberculous drugs.
Published: 2017
Full Text: View/download PDF

129. Intraosteoblastic activity of daptomycin in combination with oxacillin and ceftaroline against MSSA and MRSA

Author: Christian Chidiac, Michèle Bes, Caroline Camus, Frédéric Laurent, Céline Dupieux, Tristan Ferry, Sophie Trouillet-Assant, Yvonne Benito, Lélia Abad, Florent Valour, Sébastien Lustig, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre interrégional de référence Rhône-Alpes - Auvergne des infections ostéo-articulaires complexes, Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre National de Reference des Staphylocoques, Université de Lyon, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Service de Chirurgie Orthopédique [Centre Albert Trillat], Centre Albert Trillat [Hôpital de la Croix-Rousse - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Microbiology (medical), Staphylococcus aureus, medicine.drug_class, 030106 microbiology, Cephalosporin, Colony Count, Colony Count, Microbial, medicine.disease_cause, Microbiology, Cell Line, 03 medical and health sciences, Microbial, Daptomycin, medicine, polycyclic compounds, Humans, Pharmacology (medical), Oxacillin, Pharmacology, Microbial Viability, Osteoblasts, Chemistry, Intracellular parasite, Drug Synergism, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, Methicillin-resistant Staphylococcus aureus, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, In vitro, 3. Good health, Anti-Bacterial Agents, Cephalosporins, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Methicillin Resistance, Intracellular, Ex vivo, medicine.drug
Abstract: International audience; Background: The Staphylococcus aureus intracellular reservoir is associated with bone and joint infection (BJI) chronicity. As daptomycin is increasingly prescribed in BJI, strategies for improving its reduced intracellular activity should be promoted. Objectives: Based on the known in vitro synergy of daptomycin with β-lactams, the aim of the present study was to evaluate the intracellular activity of these combinations in an ex vivo osteoblast infection model. Methods: Osteoblastic cells infected with an MRSA strain or its isogenic MSSA counterpart were incubated for 24 h with daptomycin, oxacillin or ceftaroline alone or in combination using usual intraosseous therapeutic concentrations. Intracellular bacteria were quantified by plating cell lysates. MICs for MSSA and MRSA were determined using the chequerboard method at pH 5 to mimic conditions expected within lysosomes, the foremost S. aureus intracellular location. Results: Daptomycin failed to reduce the intracellular MSSA inoculum, and was weakly active against MRSA compared with untreated cells (-27.6%; P \textless 10-3). Oxacillin and ceftaroline revealed significant intracellular activity, including oxacillin against MRSA-infected cells (-43.2%; P \textless 10-3). The daptomycin/oxacillin combination was significantly more active against intracellular MSSA and MRSA compared with daptomycin and oxacillin alone (-44.4% and -57.2%, respectively; P \textless 0.05). In contrast, daptomycin/ceftaroline was not more efficient than ceftaroline alone. Interestingly, oxacillin MICs for MRSA decreased in vitro from \textgreater256 to 0.023 mg/L when the pH decreased from 7 to 5, and chequerboards showed an additive effect of the daptomycin/oxacillin combination against MRSA at pH 5. Conclusions: In acidic intracellular conditions, oxacillin enhances daptomycin activity against the intraosteoblastic reservoir of S. aureus, including MRSA.
Published: 2017
Full Text: View/download PDF

130. Staphylococcal Adhesion and Host Cell Invasion: Fibronectin-Binding and Other Mechanisms

Author: Josse, Jérôme, Laurent, Frédéric, Diot, Alan, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre National de Reference des Staphylocoques, Université de Lyon, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: adhesion, Mini Review, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, non-professional phagocytic cell, fibronectin-binding protein, cell invasion, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Microbiology, staphylococci
Abstract: International audience; Opportunistic bacteria from the genus Staphylococcus can cause life-threatening infections such as pneumonia, endocarditis, bone and joint infections, and sepsis. This pathogenicity is closely related to their capacity to bind directly to the extracellular matrix or to host cells. Adhesion is indeed the first step in the formation of biofilm or the invasion of host cells, which protect the bacteria from the host immune system and facilitate chronic infection. Adhesion relies on the expression of a repertoire of surface proteins called adhesins, notably microbial surface components recognizing adhesive matrix molecules. In this short review, we discuss the main pathway (FnBP-Fn-α5β1 integrin), as well as alternatives, through which Staphylococcus aureus adheres to and then invades non-professional phagocytic cells. We then examine the corresponding mechanisms for coagulase negative staphylococci. There is currently a little understanding of the molecular mechanisms that lead to internalization. Filling this gap in the literature would therefore be an important step toward limiting the duration of staphylococci infections in clinical practice.
Published: 2017
Full Text: View/download PDF

131. Minimum inhibitory concentration (MIC) distribution among wild-type strains of Legionella pneumophila identifies a subpopulation with reduced susceptibility to macrolides owing to efflux pump genes

Author: Max Maurin, Marine Vandewalle-Capo, Pierre Alain Billy, Christophe Gilbert, Clémence Massip, Christophe Ginevra, Gerard Lina, S. Jarraud, Joelle Chastang, Joséphine Charavit, Sandrine Boisset, Ghislaine Descours, Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Légionelles (CNR), Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Microbiology (medical), medicine.drug_class, 030106 microbiology, Antibiotics, Drug Resistance, Microbial Sensitivity Tests, Azithromycin, Legionella pneumophila, Microbiology, Macrolide Antibiotics, 03 medical and health sciences, Minimum inhibitory concentration, Drug Resistance, Bacterial, medicine, Humans, Pharmacology (medical), Antiinfective agent, biology, Efflux pump, Broth microdilution, Bacterial, LpeAB, General Medicine, biology.organism_classification, medicine.disease, bacterial infections and mycoses, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, Genes, Genes, Bacterial, Susceptibility, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Legionnaires' disease, Efflux, Macrolides, Legionnaires' Disease, Rifampin, Fluoroquinolones
Abstract: International audience; Legionnaires' disease is a severe pneumonia mainly caused by Legionella pneumophila that is treated by antibiotics. The purpose of this study was to describe the susceptibility of clinical strains of L. pneumophila to eight antibiotics used for treatment of legionellosis. The minimum inhibitory concentrations (MICs) of 109 well-characterised clinical strains of L. pneumophila serogroup 1 were determined by the broth microdilution method without charcoal and were compared with antibiotic-resistant strains selected in vitro. All strains were inhibited by low concentrations of fluoroquinolones, macrolides and rifampicin. The epidemiological cut-off values (ECOFFs) were 0.064 mg/L for ciprofloxacin, 0.064 mg/L for moxifloxacin, 0.032 mg/L for levofloxacin, 1 mg/L for erythromycin, 2 mg/L for azithromycin, 0.064 mg/L for clarithromycin, 2 mg/L for doxycycline and 0.001 mg/L for rifampicin. However, MIC distributions revealed a subpopulation of strains displaying reduced susceptibility to some macrolides (especially azithromycin), which correlated with the presence of the lpeAB genes encoding a macrolide efflux pump found specifically in sequence type (ST) ST1, ST701 and closely related STs. Thus, all isolates could be considered susceptible to the tested antibiotics, although macrolides were less active against some strains harbouring a specific efflux system.
Published: 2017
Full Text: View/download PDF

132. Spread of Klebsiella pneumoniae ST395 non-susceptible to carbapenems and resistant to fluoroquinolones in North-Eastern France

Author: Fany Reffuveille, Christophe de Champs, Frédéric Klein, Xavier Bertrand, Odile Bajolet, Anamaria Babosan, Thomas Guillard, C. François, Anaëlle Muggeo, Laboratoire de Bactériologie–Virologie-Hygiène Hospitalière, Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire Départemental de l'Orne, Laboratoire de Microbiologie de l’Environnement (LME), Institut National de la Recherche Agronomique (INRA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Université de Reims Champagne-Ardenne (URCA), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Laboratoire de Virologie Médicale et Moléculaire - EA 4684 (CardioVir), Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Université de Reims Champagne-Ardenne ( URCA ) -Centre Hospitalier Universitaire de Reims ( CHU Reims ), Laboratoire de Microbiologie de l’Environnement ( LME ), Institut National de la Recherche Agronomique ( INRA ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Université de Reims Champagne-Ardenne ( URCA ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Laboratoire de Virologie Médicale et Moléculaire ( CardioVir ), Université de Reims Champagne-Ardenne ( URCA ) -Centre Hospitalier Universitaire de Reims ( CHU Reims ) -SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Biomatériaux et inflammation en site osseux - EA 4691 (BIOS), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Institut de Génétique, Environnement et Protection des Plantes (IGEPP), AGROCAMPUS OUEST-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Recherche Agronomique (INRA), Centre Hospitalier Universitaire de Reims (CHU Reims), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre Hospitalier Universitaire de Reims (CHU Reims), University of British Columbia (UBC), and Karlsruhe Institute of Technology (KIT)
Subjects: 0301 basic medicine, Microbiology (medical), QRDR, Carbapenem, ST395, Klebsiella pneumoniae, R Factors, 030106 microbiology, Immunology, Microbial Sensitivity Tests, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Microbiology, beta-Lactamases, PMQR, 03 medical and health sciences, chemistry.chemical_compound, Plasmid, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Drug Resistance, Multiple, Bacterial, medicine, Pulsed-field gel electrophoresis, Humans, Immunology and Allergy, ComputingMilieux_MISCELLANEOUS, biology, chlorhexidine, biology.organism_classification, medicine.disease, Enterobacteriaceae, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Anti-Bacterial Agents, Klebsiella Infections, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Carbapenems, chemistry, Multilocus sequence typing, France, Klebsiella pneumonia, Ertapenem, Fluoroquinolones, Multilocus Sequence Typing, Plasmids, medicine.drug, MLST
Abstract: Objectives Fluoroquinolones (FQs) are a potential treatment for infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae that are susceptible to these agents. Methods Owing to increasing non-susceptibility to carbapenems among Enterobacteriaceae, in this study FQ resistance mechanisms were characterised in 36 ertapenem-non-susceptible Klebsiella pneumoniae isolated from North-Eastern France in 2012. The population structure was described by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Results Among the 36 isolates, 13 (36%) carried a carbapenemase encoding-gene. Decreased expression of the OmpK35-encoding gene might be considered a major resistance determinant that could explain the non-susceptibility to carbapenems. The carbapenemase-producing isolates carried the well-known IncL pOXA-48a plasmid. All 36 K. pneumoniae isolates also harboured a FQ resistance determinant. The aac(6′)-Ib-cr gene was the major plasmid-mediated quinolone resistance (PMQR) determinant found in K. pneumoniae (89%; 32/36). MLST identified five sequence types (STs), with the most common being ST395 (69%; 25/36), followed by ST147 (17%; 6/36). ST395 strains showed ertapenem minimum inhibitory concentrations (MICs) ranging from 0.75–32 μg/mL. Klebsiella pneumoniae ST395 isolates did not show enhanced biofilm formation or environmental survival but showed higher chlorhexidine MICs compared with ST147 isolates. Conclusions These findings showed that (i) K. pneumoniae ST395 carrying pOXA-48a has spread in North-Eastern France, (ii) aac(6′)-Ib-cr is predominant in carbapenem-non-susceptible K. pneumoniae, (iii) K. pneumoniae ST395 is resistant to chlorhexidine and (iv) FQs as an alternative to β-lactams to treat ertapenem-non-susceptible K. pneumoniae are compromised.
Published: 2017
Full Text: View/download PDF

133. Head and neck squamous cell carcinoma in people living with HIV in France

Author: Lionel Piroth, Laurence Arowas, Tristan Ferry, A Picard, Isabelle Heard, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence pour les Papillomavirus Humains - Génétique, Papillomavirus et Cancer Humain (CNR-HPV), Institut Pasteur [Paris], Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut Pasteur [Paris] (IP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Larynx, Oncology, Male, medicine.medical_specialty, Population, Human immunodeficiency virus (HIV), HIV Infections, Disease, medicine.disease_cause, Causes of cancer, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, otorhinolaryngologic diseases, Carcinoma, medicine, Humans, 030212 general & internal medicine, education, Laryngeal Neoplasms, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, education.field_of_study, Hypopharyngeal Neoplasms, business.industry, Squamous Cell Carcinoma of Head and Neck, virus diseases, Cancer, Middle Aged, medicine.disease, Head and neck squamous-cell carcinoma, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, stomatognathic diseases, Infectious Diseases, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Mouth Neoplasms, France, business
Abstract: Objectives Head and neck squamous cell carcinoma (HNSCC), mainly due to smoking, is one of the leading causes of cancer deaths. However, an increasing number of tumors – especially oropharyngeal cancer – are reported in non-smokers in association with the human papillomavirus (HPV). As HIV-infected individuals are particularly at risk of HPV-related disease, we aimed to describe the burden of HNSCC in this population. Methods Retrospective chart review of patients from HIV clinics diagnosed with HNSCC between 2004 and 2014. Case patients were defined using the International Classification of Disease for Oncology (3rd edition). Age at HIV diagnosis and time from HIV diagnosis to HNSCC diagnosis were collected. Oropharyngeal cancers were considered as potentially HPV-related cancers, and their prevalence was compared with other HNSCCs over time. Results The 286 patients enrolled in the study had a median age at HNSCC diagnosis of 52 years; 84% were males and 68% had a history of smoking. The oropharynx was the most frequent site (41%), followed by cancer of the oral cavity (31%), larynx (22%), and hypopharynx (7%). The prevalence (and proportion) of potentially HPV-related cancers increased significantly over time with a mean of 0.78 additional case patient per year. Conclusion The prevalence of HNSCC is modest compared with other cancers in HIV-infected individuals. The prevalence of oropharynx carcinoma, a potentially HPV-related carcinoma, seems to increase over time. Even if tobacco may be an important contributor, the role of HPV in HIV-infected individuals presenting with HNSCC should be investigated.
Published: 2017
Full Text: View/download PDF

134. Legionella pneumophila LPS to evaluate urinary antigen tests

Author: Margot Carpentier, Anne-Gaëlle Ranc, Gerard Lina, Elodie Maisonneuve, Ghislaine Descours, Laetitia Beraud, Jean-Marc Berjeaud, Sophie Jarraud, Julien Verdon, Christophe Ginevra, Centre National de Référence des Légionelles (CNR), Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Microbiologie de l'Eau (MDE), Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: Lipopolysaccharides, 0301 basic medicine, Microbiology (medical), congenital, hereditary, and neonatal diseases and abnormalities, LPS, Urinary system, [SDV]Life Sciences [q-bio], 030106 microbiology, Fluorescent Antibody Technique, Sensitivity and Specificity, Legionella pneumophila, Microbiology, Immunoenzyme Techniques, 03 medical and health sciences, Antigen, Limit of Detection, Humans, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, Antigens, Bacterial, biology, mAb3/1, General Medicine, Urinary antigen, biology.organism_classification, bacterial infections and mycoses, Virology, eye diseases, Pontiac, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Reagent Kits, Diagnostic, Legionnaires' Disease
Abstract: International audience; Three urinary antigen tests were compared using purified Legionella pneumophila (Lp) LPS. For Lp serogroup1, Sofia®FIA and Binax®EIA limits of detection (LOD) were similar; that of BinaxNOW® lower. For all tests the LOD was higher with LPS from non-Pontiac compared to Pontiac-strains. The LOD was variable for other Lp serogroups.
Published: 2017
Full Text: View/download PDF

135. Chromogenic detection procedure for the multidrug-resistant, neonatal sepsis-associated clone Staphylococcus capitis NRCS-A

Author: Marine Butin, Jean-Charles Picaud, Yann Dumont, Patricia Martins Simoes, Louise Hoden, Frédéric Laurent, Jean-Philippe Rasigade, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Réanimation Néonatale, Groupement Hospitalier Est, Hospices Civils de Lyon, Hospices Civils de Lyon (HCL)-Groupement Hospitalier Est, Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Service de Néonatalogie [Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut des Sciences Pharmaceutiques et Biologiques de Lyon - Département de Pharmacie Clinique, de Pharmacocinétique et d'Evaluation du Médicament, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Microbiology (medical), food.ingredient, 030106 microbiology, Clone (cell biology), MRSA, 030501 epidemiology, Microbiology, Sepsis, 03 medical and health sciences, Feces, Staphylococcus capitis, food, Pregnancy, Neonatal, medicine, Agar, Humans, Pathogen, Skin, Bacteriological Techniques, Neonatal sepsis, biology, Chromogenic, Intensive Care, Neonatal ICUs, Infant, Newborn, Chromogenic medium, Infant, General Medicine, Staphylococcal Infections, medicine.disease, biology.organism_classification, Newborn, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Multiple drug resistance, Infectious Diseases, Chromogenic Compounds, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Vagina, Intensive Care, Neonatal, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Neonatal Sepsis, 0305 other medical science
Abstract: International audience; The multiresistant Staphylococcus capitis clone NRCS-A is a major pathogen in neonates worldwide. We show that NRCS-A grows as mauve colonies with a cream-color halo after a 5-day incubation on MRSA Brilliance 2 agar (Oxoid\textregistered). This innovative protocol will ease the screening of clinical and environmental niches of this clone.
Published: 2017
Full Text: View/download PDF

136. Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin

Author: Thomas Henry, Jos A. G. van Strijp, Pauline Abrial, Robert Jan Lebbink, Emilie Bourdonnay, Bart W. Bardoel, Gerard Lina, Kok P. M. van Kessel, François Vandenesch, Michael T. McManus, Angelino T. Tromp, Michiel van Gent, Elisabeth Kruse, Carla J. C. de Haas, Joris P Jansen, András N Spaan, Amandine Martin, Christopher J. Day, Michael P. Jennings, Michael Boettcher, Pieter-Jan A. Haas, University Medical Center [Utrecht], University of Chicago, Inflammasome, Infections bactériennes et autoinflammation, Inflammasome, Bacterial Infections and Autoinflammation (I2BA), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UCSF), University of California, Griffith University [Brisbane], Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Rockefeller University [New York], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of California [San Francisco] (UC San Francisco), University of California (UC), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Microbiology (medical), Staphylococcus aureus, Neutrophils, 030106 microbiology, Immunology, Bacterial Toxins, Leukocidin, Exotoxins, Complement C5a, Biology, medicine.disease_cause, Applied Microbiology and Biotechnology, Microbiology, Cell Line, 03 medical and health sciences, Hemolysin Proteins, Mice, Bacterial Proteins, Leukocidins, Genetics, medicine, Animals, Humans, Receptor, skin and connective tissue diseases, Receptor, Anaphylatoxin C5a, Mice, Knockout, Toxin, Cell Biology, respiratory system, biochemical phenomena, metabolism, and nutrition, Staphylococcal Infections, bacterial infections and mycoses, Phenotype, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bacterial Load, Disease Models, Animal, Cell culture, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, bacteria, [SDV.IMM]Life Sciences [q-bio]/Immunology, Leukocyte Common Antigens, Panton–Valentine leukocidin, CRISPR-Cas Systems, Cellular Tropism
Abstract: International audience; The staphylococcal bi-component leukocidins Panton-Valentine leukocidin (PVL) and γ-haemolysin CB (HlgCB) target human phagocytes. Binding of the toxins' S-components to human complement C5a receptor 1 (C5aR1) contributes to cellular tropism and human specificity of PVL and HlgCB. To investigate the role of both leukocidins during infection, we developed a human C5aR1 knock-in (hC5aR1KI) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1KI mice. Compared to humans, murine hC5aR1KI neutrophils showed a reduced sensitivity to PVL, which was mediated by the toxin's F-component LukF-PV. By performing a genome-wide CRISPR-Cas9 screen, we identified CD45 as a receptor for LukF-PV. The human-specific interaction between LukF-PV and CD45 provides a molecular explanation for resistance of hC5aR1KI mouse neutrophils to PVL and probably contributes to the lack of a PVL-mediated phenotype during infection in these mice. This study demonstrates an unsuspected role of the F-component in driving the sensitivity of human phagocytes to PVL.
Published: 2017
Full Text: View/download PDF

137. Clinical metagenomics of bone and joint infections: a proof of concept study OPEN

Author: William Mouton, Jacques Schrenzel, Vladimir Lazarevic, Frédéric Laurent, Myriam Girard, Tristan Ferry, Etienne Ruppé, Genomic Research Laboratory [Geneva, Switzerland], Geneva University Hospital (HUG), Département de Microbiologie Clinique [HCL Groupement Hospitalier Nord, Lyon], Hospices Civils de Lyon (HCL)-HCL Groupement Hospitalier Nord [Lyon], Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département des Maladies Infectieuses [HCL Groupement Hospitalier Nord, Lyon], Département de Génétique et de Médecine de Laboratoire [Geneva, Switzerland], Laboratoire de Bactériologie [Geneva, Switzerland], Geneva University Hospital (HUG)-Geneva University Hospital (HUG), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), HCL Groupement Hospitalier Nord [Lyon]-Hospices Civils de Lyon (HCL), Dupuis, Christine, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: DNA, Bacterial, Male, Fastidious organism, 0301 basic medicine, medicine.drug_class, Science, Treatment outcome, Antibiotics, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, Joint infections, Proof of Concept Study, Article, Microbiology, 03 medical and health sciences, Antibiotic resistance, Species level, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Resistance, Bacterial, medicine, Humans, Pathogen, Osteitis, Aged, Aged, 80 and over, ddc:616, Arthritis, Infectious, [SDV.GEN]Life Sciences [q-bio]/Genetics, Multidisciplinary, Computational Biology, Middle Aged, biology.organism_classification, Anti-Bacterial Agents, 3. Good health, Treatment Outcome, 030104 developmental biology, Metagenomics, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Metagenome, Medicine, Female, Bacteria
Abstract: International audience; Bone and joint infections (BJI) are severe infections that require a tailored and protracted antibiotic treatment. Yet, the diagnostic based on culturing samples lacks sensitivity, especially for hardly culturable bacteria. Metagenomic sequencing could potentially address those limitations. Here, we assessed the performances of metagenomic sequencing on 24 BJI samples for the identification of pathogens and the prediction of their antibiotic susceptibility. For monomicrobial samples in culture (n = 8), the presence of the pathogen was confirmed by metagenomics in all cases. For polymicrobial samples (n = 16), 32/55 bacteria (58.2%) were found at the species level (and 41/55 [74.5%] at the genus level). Conversely, 273 bacteria not found in culture were identified, 182 being possible pathogens and 91 contaminants. A correct antibiotic susceptibility could be inferred in 94.1% and 76.5% cases for monomicrobial and polymicrobial samples, respectively. Altogether, we found that clinical metagenomics applied to BJI samples is a potential tool to support conventional culture. Context. Bone and joint infections (BJI) are severe infections that affect a growing number of patients 1. Along with the surgical intervention, the microbiological diagnosis is a keystone of the management of BJI in (i) identifying the bacteria causing the infection and (ii) assessing their susceptibility to antibiotics. Currently, this is achieved by culturing surgical samples on various media and conditions, together with a long time of incubation to recover fastidiously-growing bacteria that can be involved in BJI. Still, some bacteria will not grow under these conditions because of extreme oxygen sensitivity, a prior antibiotic intake or metabolic issues (e.g. quiescent bacteria in chronic infections). Consequently, the antibiotic treatment may not span all the bacteria involved in the infection, which can favour the relapse and the need for a new surgery. Clinical metagenomics refers to the concept of sequencing all the DNA (i.e. all the genomes) present in a clinical sample with the purpose of identifying pathogens and inferring their antibiotic susceptibility pattern 2. This new, culture-independent method takes advantages of the thrilling development of next-generation sequenc-ing (NGS) technologies since the mid-2000s. The NGS platforms typically yield thousands to millions of reads (sequences of size ranging from 100 bp to a few kbp), which virtually enables to recover the sequences of all the genes present in the sample, yet in a disorganised fashion. Substantial bio-informatics efforts are thereby needed to reconstruct and reorder the original sequences in genomes, and are referred to as the assembly process. Hence, various information such as the taxonomic identification of the present species, antibiotic resistance determinants (ARDs), mutations (as compared to a reference genome or sequence), single nucleotide variants (SNVs, for clonality assessment) and virulence genes can be determined. Clinical metagenomics is an emerging field in medicine. So far, a few attempts to use metagenomics on clinical samples have been performed (on urines 3, 4 , cerebrospinal fluid or brain biopsy 5, 6 , blood 7 and skin granuloma 8) likely because of the high price of metagenomics and the complexity of the management of sequence data for clinical microbiologists. To the best of our knowledge, metagenomics has never been applied to BJI samples.
Published: 2017
Full Text: View/download PDF

138. Pseudomonas aeruginosa ExlA and Serratia marcescens ShlA trigger cadherin cleavage by promoting calcium influx and ADAM10 activation

Author: Ina Attrée, Philippe Huber, Stéphanie Bouillot, Benoît Béganton, Emeline Reboud, Sabine Patot, Pathogenèse bactérienne et réponses cellulaires (PBRC), Biologie du Cancer et de l'Infection (BCI ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), ANR-15-CE11-0018,HemoPseudo,Pneumonie hémorragique à Pseudomonas aeruginosa : étude de nouvelles stratégies de virulence(2015), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Serratia, Cell, Cell Membranes, Toxicology, Pathology and Laboratory Medicine, Cell junction, Epithelium, Mice, Hemolysin Proteins, ADAM10 Protein, Animal Cells, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Medicine and Health Sciences, Toxins, lcsh:QH301-705.5, Inbred BALB C, Serratia marcescens, Mice, Inbred BALB C, Microscopy, Microscopy, Confocal, medicine.diagnostic_test, Virulence, Blotting, Cadherins, Transmembrane protein, Cell biology, Bacterial Pathogens, medicine.anatomical_structure, Medical Microbiology, Confocal, Pseudomonas aeruginosa, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Cellular Structures and Organelles, Pathogens, Cellular Types, Anatomy, Western, Research Article, lcsh:Immunologic diseases. Allergy, Virulence Factors, Proteolysis, Immunology, Toxic Agents, Blotting, Western, Bacterial Toxins, Biology, Microbiology, 03 medical and health sciences, Enzyme activator, Enterobacteriaceae, Bacterial Proteins, Pseudomonas, Virology, Genetics, medicine, Cell Adhesion, Humans, Animals, Secretion, Molecular Biology, Microbial Pathogens, Bacteria, Cadherin, Host Cells, Organisms, Biology and Life Sciences, Endothelial Cells, Epithelial Cells, Cell Biology, Intracellular Membranes, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Enzyme Activation, Cytosol, 030104 developmental biology, Biological Tissue, lcsh:Biology (General), Parasitology, Calcium, lcsh:RC581-607, Gram-Negative Bacterial Infections, Viral Transmission and Infection
Abstract: Pore-forming toxins are potent virulence factors secreted by a large array of bacteria. Here, we deciphered the action of ExlA from Pseudomonas aeruginosa and ShlA from Serratia marcescens on host cell-cell junctions. ExlA and ShlA are two members of a unique family of pore-forming toxins secreted by a two-component secretion system. Bacteria secreting either toxin induced an ExlA- or ShlA-dependent rapid cleavage of E-cadherin and VE-cadherin in epithelial and endothelial cells, respectively. Cadherin proteolysis was executed by ADAM10, a host cell transmembrane metalloprotease. ADAM10 activation is controlled in the host cell by cytosolic Ca2+ concentration. We show that Ca2+ influx, induced by ExlA or ShlA pore formation in the plasma membrane, triggered ADAM10 activation, thereby leading to cadherin cleavage. Our data suggest that ADAM10 is not a cellular receptor for ExlA and ShlA, further confirming that ADAM10 activation occurred via Ca2+ signalling. In conclusion, ExlA- and ShlA-secreting bacteria subvert a regulation mechanism of ADAM10 to activate cadherin shedding, inducing intercellular junction rupture, cell rounding and loss of tissue barrier integrity., Author summary Pore-forming toxins are the most widespread toxins delivered by pathogenic bacteria and are required for full virulence. Pore-forming toxins perforate membranes of host cells for intracellular delivery of bacterial factors, for bacterial escape from phagosomes or in order to kill cells. Loss of membrane integrity, especially the plasma membrane, has broad implications on cell and tissue physiology. Here, we show that two members of a unique family of pore-forming toxins, secreted by Pseudomonas aeruginosa and Serratia marcescens, have the capacity to disrupt cell-cell junctions of epithelial and endothelial cells, hence breaching two major tissue barriers.
Published: 2017
Full Text: View/download PDF

139. Variable performance of four commercial chromogenic media for detection of methicillin-resistant Staphylococcus aureus isolates harbouring mecC

Author: Elizabeth Dickson, Robert Hill, Anders Rhod Larsen, Michèle Bes, Bruno Pichon, Robert Skov, Angela Kearns, Mark A. Holmes, Camille Kolenda, Christopher Teale, Frédéric Laurent, Céline Dupieux, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Reference des Staphylocoques, Université de Lyon, Statens Serum Institut [Copenhagen], Public Health England [London], Department of Veterinary Medicine, University of Cambridge, Cambridge, UK, Scottish Microbiology Reference Laboratories, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and University of Cambridge [UK] (CAM)
Subjects: 0301 basic medicine, Microbiology (medical), Methicillin-Resistant Staphylococcus aureus, Staphylococcus aureus, 030106 microbiology, Chromogenic media, medicine.disease_cause, Sensitivity and Specificity, Microbiology, 03 medical and health sciences, Medicine, Animals, Humans, Mass Screening, Pharmacology (medical), Bacteriological Techniques, business.industry, Chromogenic, mecC, General Medicine, biochemical phenomena, metabolism, and nutrition, Methicillin resistance, Staphylococcal Infections, equipment and supplies, bacterial infections and mycoses, Methicillin-resistant Staphylococcus aureus, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Culture Media, Europe, 030104 developmental biology, Infectious Diseases, Chromogenic Compounds, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Epidemiological surveillance, [SDV.IMM]Life Sciences [q-bio]/Immunology, business
Abstract: International audience; In this study, the performances of four methicillin-resistant Staphylococcus aureus (MRSA) chromogenic screening media were compared for detecting mecC-positive MRSA. Using 111 clinical isolates representative of the various mecC-MRSA clones in Europe, chromID\textregistered MRSA (bioMérieux) and BrillianceTM MRSA 2 (Oxoid Ltd.) showed higher sensitivity (99.1% and 97.3%, respectively) than BBLTM CHROMagar\textregistered MRSA II (BD Diagnostics) and MRSASelectTM (Bio-Rad) (79.3% and 63.1%, respectively) (P \textless0.0001). These findings have important implications for effective public health diagnostics and epidemiological surveillance of MRSA.
Published: 2017
Full Text: View/download PDF

140. Clinical value of the antibiofilmograma and contribution of biofilm formation capacity for the management of bone and joint infections due to staphylococcus

Author: TASSE, Jason, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Frédéric Laurent, Thierry Bernardi, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Staphylococcus aureus, CMI, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Antibiotics, Biofilm, IOA, PJIs, MIC, biochemical phenomena, metabolism, and nutrition, Antibiotiques, CMIb, BMIC
Abstract: In the context of Bone and Joint Infections (BJIs), the orthopedic devices are preferential surface for microorganisms to adhere and form biofilm associated with high rates of failures and relapses. Within biofilm, bacteria are protected from the host immune response and are able to survive in the presence of high concentration of antibiotics. The standard Minimal Inhibitory Concentration (MIC) informs on the antibiotic susceptibility of planktonic bacteria, but is not suited for biofilm. The company BioFilm Control developed a new test named AntibiofilmogramÂ® which measures early-stage biofilm growth in presence of antibiotics, and provides a biofilm Minimal Inhibitory Concentration (bMIC). The aim of my PhD research was first to take part in the demonstration of the clinical value of this new test for Staphylococcus aureus BJIs. We established a prospective collection of data and strains and realized the first in vitro assays. Our results for cloxacillin were confirmed in an in vivo model of catheter-associated infection. Second, we characterized the biofilm formation capacity of various clinical isolates based on the AntibiofilmogramÂ® resistance profile. We showed that the biofilm formation capacity is correlated with clonal lineage. Finally, we were able to develop a new method of washing and quantifying biofilms for microplate system using steam. This simple approach preserves the biofilm integrity and lead to highly reproducible data; Dans le cadre d'infections ostéo-articulaire (IOA), l'utilisation de matériels étrangers peut, en cas de contamination, aboutir à la formation d'un biofilm associé à un risque plus important d'échec du traitement et de récidive. Les bactéries sous forme de biofilm sont en effet protégées de l'action du système immunitaire et ont une tolérance plus importante aux antibiotiques. A l'heure actuelle, l'activité des antibiotiques est déterminée par la CMI (Concentration Minimale Inhibitrice), mais cette valeur ne tient pas compte de la forme sessile des bactéries. C'est pourquoi, la société BioFilm Control a développé un nouveau test, l'AntibiofilmogrammeÂ®, permettant de déterminer la CMI biofilm (CMIb) reflétant la capacité préventive des antibiotiques sur l'installation des microorganismes en biofilm. L'objectif de ma thèse a été dans un premier temps de participer à la démonstration de la valeur clinique de ce nouveau test dans le cadre des IOA à Staphylococcus aureus. Nous avons pu mettre en place un recueil prospectif et réaliser les premiers essais in vitro. Nos résultats obtenus pour la cloxacillin ont pu par la suite Ãªtre confirmés sur un modèle in vivo d'infection sur matériel. Dans un second temps, nous avons pu caractériser la capacité de formation de biofilm des souches cliniques en fonction des profils de résistance obtenus en AntibiofilmogrammeÂ®. Nous avons pu mettre en évidence des profils différents liés à la clonalité des souches. Enfin, nous avons pu mettre au point une nouvelle méthode de rinçage et de quantification des biofilms pour les modèles en microplaque via l'utilisation de vapeur. Cette approche simple améliore grandement la reproductibilité des résultats et préserve l'intégrité structurelle des biofilms
Published: 2017

141. The RNA targetome of Staphylococcus aureus non-coding RNA RsaA: impact on cell surface properties and defense mechanisms

Author: Tomasini, Arnaud, Moreau, Karen, Chicher, Johana, Geissmann, Thomas, Vandenesch, François, Romby, Pascale, Marzi, Stefano, Caldelari, Isabelle, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Plateforme Protéomique Strasbourg - Esplanade (IBMC / CNRS FRC1589 / UNIV Strasbourg), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Moléculaire et Cellulaire [Strasbourg] (IBMC), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), and ANR-16-CE11-0007,RIBOSTAPH,La traduction et son contrôle chez Staphylococcus aureus: conséquences sur la virulence et la réponse aux stress(2016)
Subjects: Staphylococcus aureus, RNA, Untranslated, Binding Sites, Base Sequence, Proteome, Messenger, Bacterial, Untranslated, Membrane Proteins, Gene Expression Regulation, Bacterial, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, RNA, Bacterial, Bacterial Proteins, Gene Expression Regulation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, [SDV.IMM]Life Sciences [q-bio]/Immunology, RNA Interference, RNA, Messenger, Transcriptome
Abstract: International audience; The virulon of Staphyloccocus aureus is controlled by intricate connections between transcriptional and post-transcriptional regulators including proteins and small non-coding RNAs (sRNAs). Many of the sRNAs regulate gene expression through base-pairings with mRNAs. However, characterization of the direct sRNA targets in Gram-positive bacteria remained a difficult challenge. Here, we have applied and adapted the MS2-affinity purification approach coupled to RNA sequencing (MAPS) to determine the targetome of RsaA sRNA of S. aureus, known to repress the synthesis of the transcriptional regulator MgrA. Several mRNAs were enriched with RsaA expanding its regulatory network. Besides mgrA, several of these mRNAs encode a family of SsaA-like enzymes involved in peptidoglycan metabolism and the secreted anti-inflammatory FLIPr protein. Using a combination of in vivo and in vitro approaches, these mRNAs were validated as direct RsaA targets. Quantitative differential proteomics of wild-type and mutant strains corroborated the MAPS results. Additionally, it revealed that RsaA indirectly activated the synthesis of surface proteins supporting previous data that RsaA stimulated biofilm formation and favoured chronic infections. All together, this study shows that MAPS could also be easily applied in Gram-positive bacteria for identification of sRNA targetome.
Published: 2017
Full Text: View/download PDF

142. Disseminated actinomycosis treated with clindamycin

Author: Bouttefroy, S., Faure Conter, C., Tristan, A., VALOUR, Florent, Perpoint, T., Reix, P., Thiesse, P., Dijoud, F., Catho, G., Service de Pneumologie Pédiatrique [Hôpital Femme Mère Enfant - CHU de Lyon], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-lyon, Institut d'hématologie et d'oncologie pédiatrique [CHU - HCL] (IHOPe), Hospices Civils de Lyon (HCL), Centre de Biologie et Pathologie Est (CBPE), Hospices Civils de Lyon (HCL)-Centre National de Référence des Légionelles, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Léon Bérard [Lyon], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Delayed Diagnosis, Biopsy, Clindamycin, Magnetic Resonance Imaging, Long-Term Care, Actinomycosis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Diagnosis, Differential, Pulmonary Alveoli, Diagnosis, Differential, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, Child
Abstract: International audience; Actinomycosis is a rare bacterial disease caused by Actinomyces spp., an anaerobic bacteria from the oropharynx, digestive, and female genital tracts. Initial clinical presentation often mimics malignancy, which can lead to a delay in diagnosis. Cervico-facial, genitourinary, digestive, and respiratory features are the most frequent. Few cases are reported in children and risk factors are not well known in this population. We report on the case of an 8-year-old boy with disseminated actinomycosis with cervico-facial, pulmonary, and bone involvement caused by Actinomyces israelii. The infiltrative appearance initially suggested malignancy and the patient was started on chemotherapy for presumed histiocytosis. Evaluation of subsequent tissue samples demonstrated the presence of filamentous structures consistent with fungal or filamentous bacterial infection. Prolonged culture yielded the correct diagnosis. The patient had a severe allergic reaction to piperacillin/tazobactam and was therefore transitioned to clindamycin to complete a 9-month course. This treatment, which has not been reported in children, led to a favorable clinical, biological, and radiological response, with a good clinical tolerance.
Published: 2017
Full Text: View/download PDF

143. Rapid detection and evolutionary analysis of Legionella pneumophila serogroup 1 sequence type 47

Author: Laura Gomez-Valero, M. Mentasti, Carmen Buchrieser, Baharak Afshar, Sophia David, Timothy G. Harrison, S. Jarraud, P. Cassier, Christophe Ginevra, Anthony Underwood, Vicki Chalker, Jerome Etienne, Julian Parkhill, Public Health England [London], Centre National de Référence Legionella, The Wellcome Trust Sanger Institute [Cambridge], Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), European Programme for Public Health Microbiology Training (EUPHEM), European Centre for Disease Prevention and Control [Stockholm, Sweden] (ECDC), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and European Centre for Disease Prevention and Control (ECDC)
Subjects: 0301 basic medicine, Microbiology (medical), Legionella, Evolution, 030106 microbiology, Biology, Real-Time Polymerase Chain Reaction, Serogroup, Genome, Legionella pneumophila, Polymorphism, Single Nucleotide, Sensitivity and Specificity, Evolution, Molecular, 03 medical and health sciences, Genetic, Phylogenetics, ST47, Humans, Typing, Legionella pneumophila Serogroup 1, Polymorphism, Phylogeny, ST62, Comparative genomics, Genetics, Recombination, Genetic, Phylogenetic tree, Bacterial, Molecular, General Medicine, Sequence Analysis, DNA, Single Nucleotide, DNA, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Recombination, Molecular Typing, 030104 developmental biology, Infectious Diseases, PCR, L.~pneumophila, ST109, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Sequence Analysis, Genome, Bacterial, WGS
Abstract: International audience; OBJECTIVES: Legionella pneumophila serogroup 1 (Lp1) sequence type 47 is the leading cause of legionellosis in north-western Europe, but, surprisingly, it is rarely isolated from environmental samples. Comparative genomics was applied to develop a PCR assay and to better understand the evolution of this strain. METHODS: Comparative analysis of 36 genomes representative of the Lp species was used to identify specific PCR targets, which were then evaluated in silico on 545 sequenced genomes and in~vitro on 436 Legionella strains, 106 respiratory samples, and three environmental samples from proven ST47 sources. Phylogenetic analyses were performed to understand the evolution of ST47. RESULTS: The gene LPO\₁073 was characterized as being 100% conserved in all 129 ST47 genomes analysed. A real-time PCR designed to detect LPO\₁073 was positive for all 110 ST47 strains tested and agreed with culture and typing results previously obtained for 106 respiratory samples. The three environmental samples were also positive. Surprisingly, 26 of the 44 ST109 strains tested among 342 non-ST47 strains scored positive for LPO\₁073. SNP-based phylogenetic analysis was undertaken to understand this result: the PCR-positive ST109 genomes were almost identical to ST47 genomes, with the exception of a recombined region probably acquired by ST47 from a ST62(-like) strain. CONCLUSION: The genomic analysis allowed the design of a highly specific PCR assay for rapid detection of ST47 strains. Furthermore, it allowed us to uncover the evolution of ST47 strains from ST109 by homologous recombination with ST62. We hypothesize that this recombination generated the leading cause of legionellosis in north-western Europe.
Published: 2017
Full Text: View/download PDF

144. Strain-specific estimation of epidemic success provides insights into the transmission dynamics of tuberculosis

Author: Gérard Carret, Véronique Jacomo, Oana Dumitrescu, Ghislaine Blasquez, Gerard Lina, Maxime Barbier, Jean-Philippe Rasigade, Isabelle Fredenucci, Jean-Pierre Flandrois, Sandrine Boisset, Anne Carricajo, Philip Supply, Michèle Pérouse de Montclos, Thierry Wirth, Catherine Pichat, Anne-Sophie Ronnaux-Baron, Christine Godin-Benhaim, Florence Ader, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Comité Départemental d’Hygiène Sociale - CLAT69 [Lyon), Agence régionale de santé Auvergne Rhône Alpes (ARS), Laboratoire de Bactériologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Eurofins Biomnis, Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Tuberculosis, Genotype, Minisatellite Repeats, Biology, Article, law.invention, 03 medical and health sciences, law, Risk Factors, Epidemiology, medicine, Humans, Aged, Estimation, Multidisciplinary, Sputum, Genetic Variation, Mycobacterium tuberculosis, Middle Aged, medicine.disease, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, 030104 developmental biology, Minisatellite, Transmission (mechanics), Haplotypes, Cohort, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, Demography
Abstract: The transmission dynamics of tuberculosis involves complex interactions of socio-economic and, possibly, microbiological factors. We describe an analytical framework to infer factors of epidemic success based on the joint analysis of epidemiological, clinical and pathogen genetic data. We derive isolate-specific, genetic distance-based estimates of epidemic success, and we represent success-related time-dependent concepts, namely epidemicity and endemicity, by restricting analysis to specific time scales. The method is applied to analyze a surveillance-based cohort of 1,641 tuberculosis patients with minisatellite-based isolate genotypes. Known predictors of isolate endemicity (older age, native status) and epidemicity (younger age, sputum smear positivity) were identified with high confidence (P
Published: 2017
Full Text: View/download PDF

145. Vertebral B-cell lymphoma mimicking a Pott's disease in a man aged 63 years coming back from Tunisia

Author: Christian Chidiac, Tristan Ferry, C Peyron, Cécile Pouderoux, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Radiologie [Hôpital de la Croix-Rousse - HCL], Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, medicine.medical_specialty, Lymphoma, B-Cell, Tunisia, Anorexia, Disease, Article, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, medicine.artery, Diabetes mellitus, Weight Loss, medicine, Back pain, Humans, Medical history, Spondylitis, ComputingMilieux_MISCELLANEOUS, Psoas Muscles, 030222 orthopedics, Aorta, business.industry, General Medicine, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Surgery, Radiography, Back Pain, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tuberculosis, Spinal, medicine.symptom, business, Polyneuropathy, 030217 neurology & neurosurgery
Abstract: We report the case of a man aged 63 years, a native from Tunisia, whose medical history was marked by diabetes treated with insulin (complicated with inferior limbs polyneuropathy), an ischaemic heart disease, a peripheral arterial disease and a smoking-related chronic obstructive pulmonary disease. His mother might have had pulmonary tuberculosis. He was retired since 2 years and shared his life between Tunisia and France. He had mechanical back pain since several years, but since 3 months, his back pain awakened him at night and was accompanied with loss of weight and anorexia. There was no fever or night sweats. In Tunisia, he underwent a CT scan showing a retroperitoneal mass infiltrating the left psoas and the left renal artery close to the aorta with the erosion of the L2 cortical and spondylitis (figure 1A, B). There was also regional necrotic lymphadenopathy. The patient decided to return to France and was hospitalised in our infectious …
Published: 2017
Full Text: View/download PDF

146. In vitro activity of ceftobiprole on 440 Staphylococcus aureus strains isolated from bronchopulmonary infections

Author: C. Bouveyron, François Vandenesch, L. Delouere, Frédéric Laurent, Gerard Lina, Michèle Bes, Anne Tristan, Oana Dumitrescu, Hélène Meugnier, Elisabeth Hodille, Centre National de Reference des Staphylocoques, Université de Lyon, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Lung Diseases, Staphylococcus aureus, Céftobiprole, 030106 microbiology, Ceftobiprole, Tigecycline, Microbial Sensitivity Tests, medicine.disease_cause, Staphylococcal infections, Ceftaroline fosamil, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pneumonia, Staphylococcal, medicine, polycyclic compounds, Humans, 030212 general & internal medicine, Céftaroline, business.industry, Bronchial Diseases, Pneumonia, biochemical phenomena, metabolism, and nutrition, Staphylococcal Infections, medicine.disease, bacterial infections and mycoses, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Infections broncho-pulmonaires, 3. Good health, Anti-Bacterial Agents, Cephalosporins, Infectious Diseases, chemistry, Linezolid, Bronchopulmonary infections, Staphylococcal, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Vancomycin, bacteria, [SDV.IMM]Life Sciences [q-bio]/Immunology, Daptomycin, business, medicine.drug
Abstract: Objective We assessed the in vitro activity of ceftobiprole on 440 Staphylococcus aureus clinical strains isolated from bronchopulmonary infections (2010–2014). Methods S . aureus isolates were characterized for methicillin resistance, PVL status, and clonal complex. All isolates were tested for minimal inhibitory concentrations (MIC) determination by broth microdilution method for ceftobiprole, ceftaroline fosamil, and comparator antibiotics (linezolid, tigecycline, vancomycin, and daptomycin). Results A total of 325 (74%) strains were methicillin-susceptible S . aureus (MSSA) and 115 (26%) were methicillin-resistant S . aureus (MRSA); 105 (24%) S . aureus strains were PVL-positive, including 35.2% (37/105) MRSA and 64.8% (68/105) MSSA. Ceftobiprole was highly active against S . aureus with MIC 90 of 1 mg/L, MICs ranging between 0.12 and 4 mg/L (only one resistant strain, MIC of 4 mg/L). MIC 50 and MIC 90 were twice lower in MSSA than MRSA. Moreover, PVL + MRSA were slightly more susceptible to ceftobiprole (MIC 50 of 0.5 mg/L and MIC 90 of 1 mg/L) than PVL − MRSA (MIC 50 and MIC 90 of 1 mg/L). The ceftobiprole-resistant strain was also resistant to ceftaroline fosamil and presented the D239L mutation in PBP2A. The comparator antibiotics were equally active on the strains tested, with MIC 90 of 0.5 mg/L for ceftaroline fosamil, tigecycline, and daptomycin; 1 mg/L for vancomycin; and 2 mg/L for linezolid. Conclusions Our results suggest that ceftobiprole is highly active against S . aureus and is an effective alternative to vancomycin or linezolid in the management of staphylococcal pneumonia. However, close monitoring of isolates should be maintained to prevent resistant strain diffusion.
Published: 2017
Full Text: View/download PDF

147. Ribosomal Mutations Conferring Macrolide Resistance in Legionella pneumophila

Author: Françoise Forey, Ghislaine Descours, Sophie Jarraud, Jerome Etienne, Joelle Chastang, Nathalie Jacotin, Christophe Ginevra, Gerard Lina, Elisabeth Kay, Patricia Doublet, Pathogenèse des légionelles- Legionella pathogenesis (LegioPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Legionella, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Ribosomal Proteins, Lineage (genetic), 030106 microbiology, Drug Resistance, Erythromycin, Microbial Sensitivity Tests, ribosomal mutations, Azithromycin, medicine.disease_cause, Legionella pneumophila, Microbiology, resistance, 03 medical and health sciences, Antibiotic resistance, Bacterial Proteins, Ribosomal protein, 23S ribosomal RNA, Mechanisms of Resistance, Drug Resistance, Bacterial, medicine, Protein Isoforms, Pharmacology (medical), Pharmacology, Ribosomal, Mutation, biology, Bacterial, High-Throughput Nucleotide Sequencing, 23S rRNA, macrolide, Ribosomal RNA, biology.organism_classification, 23S, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Anti-Bacterial Agents, Clone Cells, RNA, Ribosomal, 23S, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.drug
Abstract: Monitoring the emergence of antibiotic resistance is a recent issue in the treatment of Legionnaires' disease. Macrolides are recommended as first-line therapy, but resistance mechanisms have not been studied in Legionella species. Our aim was to determine the molecular basis of macrolide resistance in L. pneumophila . Twelve independent lineages from a common susceptible L. pneumophila ancestral strain were propagated under conditions of erythromycin or azithromycin pressure to produce high-level macrolide resistance. Whole-genome sequencing was performed on 12 selected clones, and we investigated mutations common to all lineages. We reconstructed the dynamics of mutation for each lineage and demonstrated their involvement in decreased susceptibility to macrolides. The resistant mutants were produced in a limited number of passages to obtain a 4,096-fold increase in erythromycin MICs. Mutations affected highly conserved 5-amino-acid regions of L4 and L22 ribosomal proteins and of domain V of 23S rRNA (G2057, A2058, A2059, and C2611 nucleotides). The early mechanisms mainly affected L4 and L22 proteins and induced a 32-fold increase in the MICs of the selector drug. Additional mutations related to 23S rRNA mostly occurred later and were responsible for a major increase of macrolide MICs, depending on the mutated nucleotide, the substitution, and the number of mutated genes among the three rrl copies. The major mechanisms of the decreased susceptibility to macrolides in L. pneumophila and their dynamics were determined. The results showed that macrolide resistance could be easily selected in L. pneumophila and warrant further investigations in both clinical and environmental settings.
Published: 2017
Full Text: View/download PDF

148. Implant-associated ESBL-Klebsiella pneumonia producing small colony variant bone and joint infection in a healthy 40-year-old man

Author: Ronde-Oustau, Cécile, Lustig, Sébastien, Dupieux, Céline, Ferry, Tristan, group, Lyon BJI Study, Les Hôpitaux Universitaires de Strasbourg (HUS), Service de Chirurgie Orthopédique [Centre Albert Trillat], Centre Albert Trillat [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre interrégional de référence Rhône-Alpes - Auvergne des infections ostéo-articulaires complexes, Laboratoire de Bactériologie de l'Hôpital de la Croix-Rousse, Hospices Civils de Lyon (HCL), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, Adult, medicine.medical_specialty, medicine.drug_class, 030106 microbiology, Antibiotics, Microbial Sensitivity Tests, Meropenem, Article, beta-Lactamases, 03 medical and health sciences, medicine, Humans, Tibia, Abscess, ComputingMilieux_MISCELLANEOUS, business.industry, Colistin, General Medicine, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Internal Fixators, 3. Good health, Surgery, Klebsiella Infections, Anti-Bacterial Agents, Klebsiella pneumoniae, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Thienamycins, Implant, Klebsiella pneumonia, business, medicine.drug
Abstract: A 40-year-old man underwent a bifocal fracture of the left leg in Senegal. An intramedullar rod was implanted to obtain consolidation. At 7 months, the patient was admitted to our institution as the distal fracture had not consolidated (figure 1A). There was no clinical sign of infection. A 1-stage exchange of the rod was performed. No abscess or suspected tissue was detectable during the surgery. Systematic peroperative test of samples were performed, and revealed Klebsiella pneumonia producing extended-spectrum β-lactamase (ESBL), and some colonies expressed the small colony variant (SCV) phenotype in the culture (with the same antibiotic susceptibility), which was also identified to be K. pneumonia (figure 1 B and C). An early new intervention was required due to local abscess formation, the rod was explanted, the tibia was immobilised with a cruro-pedal cast and negative pressure therapy on the skin defect was instaured. …
Published: 2017
Full Text: View/download PDF

149. The Role of Antibiotics in Modulating Virulence in Staphylococcus aureus

Author: Warren E. Rose, Oana Dumitrescu, Sylvain Goutelle, Gerard Lina, Elisabeth Hodille, Binh An Diep, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Wisconsin-Madison, Department of Medicine [San Francisco], University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Evaluation et modélisation des effets thérapeutiques, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), School of Pharmacy, University of Wisconsin, Madison, University of California [San Francisco] (UCSF), and University of California-University of California
Subjects: 0301 basic medicine, Microbiology (medical), Staphylococcus aureus, Epidemiology, medicine.drug_class, 030106 microbiology, Antibiotics, virulence factors, Virulence, antimicrobial agents, Review, Biology, medicine.disease_cause, Staphylococcal infections, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, medicine, Humans, Animals, Antiinfective agent, General Immunology and Microbiology, Public Health, Environmental and Occupational Health, Clindamycin, Staphylococcal Infections, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Anti-Bacterial Agents, 030104 developmental biology, Infectious Diseases, chemistry, Linezolid, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Exotoxin, medicine.drug
Abstract: SUMMARY Staphylococcus aureus is often involved in severe infections, in which the effects of bacterial virulence factors have great importance. Antistaphylococcal regimens should take into account the different effects of antibacterial agents on the expression of virulence factors and on the host's immune response. A PubMed literature search was performed to select relevant articles on the effects of antibiotics on staphylococcal toxin production and on the host immune response. Information was sorted according to the methods used for data acquisition (bacterial strains, growth models, and antibiotic concentrations) and the assays used for readout generation. The reported mechanisms underlying S. aureus virulence modulation by antibiotics were reviewed. The relevance of in vitro observations is discussed in relation to animal model data and to clinical evidence extracted from case reports and recommendations on the management of toxin-related staphylococcal diseases. Most in vitro data point to a decreased level of virulence expression upon treatment with ribosomally active antibiotics (linezolid and clindamycin), while cell wall-active antibiotics (beta-lactams) mainly increase exotoxin production. In vivo studies confirmed the suppressive effect of clindamycin and linezolid on virulence expression, supporting their utilization as a valuable management strategy to improve patient outcomes in cases of toxin-associated staphylococcal disease.
Published: 2017
Full Text: View/download PDF

150. Erratum

Author: Efthimia Lioliou, Pierre Fechter, Isabelle Caldelari, Brian C. Jester, Sarah Dubrac, Anne-Catherine Helfer, Sandrine Boisset, François Vandenesch, Pascale Romby, Thomas Geissmann, Architecture et Réactivité de l'ARN (ARN), Centre National de la Recherche Scientifique (CNRS)-Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie systémique et synthétique (ISSB), Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Biologie des Bactéries pathogènes à Gram-positif, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cell Biology, Molecular Biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience
Published: 2017
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

281 results on '"Pathogénie des Staphylocoques – Staphylococcal Pathogenesis"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources