Descriptor: "MESH: Anti-Bacterial Agents" - Searchworks@Jio Institute Digital Library Search Results

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498 results on '"MESH: Anti-Bacterial Agents"'

1. Daptomycin Physiology-Based Pharmacokinetic Modeling to Predict Drug Exposure and Pharmacodynamics in Skin and Bone Tissues

Author: Romain Garreau, Damien Montange, Antoine Grillon, François Jehl, Tristan Ferry, Laurent Bourguignon, Sylvain Goutelle, Hospices Civils de Lyon (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), Laboratoire de Pharmacologie Clinique et Toxicologie [CHRU Besancon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), CHU Strasbourg, 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), 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), Institut des Sciences Pharmaceutiques et Biologiques (ISPB), Université de Lyon-Université de Lyon, 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), and 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)
Subjects: Pharmacology, MESH: Microbial Sensitivity Tests, MESH: Humans, MESH: Staphylococcal Infections / drug therapy, MESH: Daptomycin / pharmacology, Microbial Sensitivity Tests, Staphylococcal Infections, MESH: Bone and Bones, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bone and Bones, Anti-Bacterial Agents, Daptomycin, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Anti-Bacterial Agents, Humans, Pharmacology (medical), MESH: Staphylococcal Infections / microbiology
Abstract: International audience; Background and objective: Daptomycin has been recommended in the treatment of bone and joint infection. Previous work showed that the approved dosage of daptomycin may be insufficient to achieve optimal exposure in patients with bone and joint infection. However, those studies assumed that bone exposure was similar to steady-state daptomycin-free plasma concentrations. We sought to establish a physiologically based pharmacokinetic (PBPK) model of daptomycin to describe the dynamics of daptomycin disposition in bone and skin tissue.Methods: a PBPK model of daptomycin was built using PK-Sim®. Daptomycin concentrations in plasma and bone were obtained from three previously published studies. Physicochemical drug characteristics, mass balance, anthropometrics, and experimental data were used to build and refine the PBPK model. Internal validation of the PBPK model was performed using the usual diagnostic plots. The final PBPK model was then used to run simulations with doses of 6, 8, 10, and 12 mg/kg/24 h. Pharmacokinetic profiles were simulated in 1.000 subjects and the probabilities of target attainment for the area under the concentration-time curve over the bacterial minimum inhibitory concentration were computed in blood, skin, and bone compartments.Results: the final model showed a good fit of all datasets with an absolute average fold error between 0.5 and 2 for all pharmacokinetic quantities in blood, skin and bone tissues. Results of dosing simulations showed that doses ≥10 mg/kg should be used in the case of bacteremia caused by Staphylococcus aureus with a minimum inhibitory concentration >0.5 mg/L or Enterococcus faecalis with a minimum inhibitory concentration >1 mg/L, while doses ≥12 mg/kg should be used in the case of bone and joint infection or complicated skin infection. When considering a lower minimum inhibitory concentration, doses of 6-8 mg/kg would likely achieve a sufficient success rate. However, in the case of infections caused by E. faecalis with a minimum inhibitory concentration >2 mg/L, a higher dosage and combination therapy would be necessary to maximize efficacy.Conclusions: we developed the first daptomycin PBPK/pharmacodynamic model for bone and joint infection, which confirmed that a higher daptomycin dosage is needed to optimize exposure in bone tissue. However, such higher dosages raise safety concerns. In this setting, therapeutic drug monitoring and model-informed precision dosing appear necessary to ensure the right exposure on an individual basis.
Published: 2022

2. Influence of the healthcare pathway on the outcome of patients with infective endocarditis

Author: Florent Arregle, Nicolas Iline, Roch Giorgi, Mary Philip, Sandrine Hubert, Frederique Gouriet, Jean Paul Casalta, Frédéric Collart, Alberto Riberi, Hélène Martel, Sébastien Renard, Laurence Camoin, Anne Claire Casalta, Hubert Lepidi, Didier Raoult, Michel Drancourt, Gilbert Habib, Département de Cardiologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Biostatistique et technologies de l'information et de la communication (BioSTIC) - [Hôpital de la Timone - APHM] (BiosTIC ), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Département de Chirurgie Cardiaque [Hôpital de la Timone - APHM], and Hôpital de la Timone [CHU - APHM] (TIMONE)
Subjects: MESH: Endocarditis, MESH: Humans, Endocarditis, Referral centre, MESH: Delivery of Health Care, MESH: Retrospective Studies, Endocarditis, Bacterial, General Medicine, Critical Care and Intensive Care Medicine, MESH: Prospective Studies, Anti-Bacterial Agents, [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, MESH: Anti-Bacterial Agents, Humans, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Hospital Mortality, Prospective Studies, MESH: Endocarditis, Bacterial, MESH: Hospital Mortality, Mortality, Cardiology and Cardiovascular Medicine, Delivery of Health Care, Retrospective Studies, Healthcare pathway
Abstract: Aims To determine the prognosis of patients treated for infective endocarditis (IE) according to their healthcare pathway. To assess how the ESC guidelines are implemented concerning the performance of transoesophageal echocardiography, the use of antibiotic therapy, and the performance of valve surgery; and to compare the epidemiological profile of IE according to the type of centres in which the patients are hospitalized. Methods and results In a prospective multicentric study including 22 hospitals in the South-East of France, 342 patients were classified into three groups according to their healthcare pathway: 119 patients diagnosed and taken care entirely in a reference centre or hospital with cardiac surgery [Referral Center (RC) group], 111 patients diagnosed and initially taken care in a non-RC (NRC), then referred in a centre including cardiac surgery [transferred to the Referral Center (TRC) group] and 112 patients totally taken care in the NRC (NRC group). One-year mortality was 26% (88 deaths) and was not significantly different between Groups 1 and 2 (20 vs. 21%, P = 0.83). Patients in the NRC group had a higher mortality (37%) compared with patients in the RC and TRC groups (P Conclusion Prognosis of patients with IE is influenced by their healthcare pathway. Patients treated exclusively in NRC have a worse prognosis than patients treated in referral or surgical centres.
Published: 2022

3. Intermittent antibiotic treatment of bacterial biofilms favors the rapid evolution of resistance

Author: Masaru Usui, Yutaka Yoshii, Stanislas Thiriet-Rupert, Jean-Marc Ghigo, Christophe Beloin, Rakuno Gakuen University, Génétique des Biofilms - Genetics of Biofilms, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the French National Research Agency (ANR), project EvolTolAB (ANR-18-CE13-0010), by the French government’s Investissement d’Avenir Program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant n°ANR-10-LABX-62-IBEID) and by the Fondation pour la Recherche Médicale (grant DEQ20180339185). S.T.-R was supported by the French National Research Agency (ANR), project EvolTolAB (ANR-18-CE13-0010)., ANR-18-CE13-0010,EvoTolAB,Evolution et dynamique de dissémination de la tolérance aux antibiotiques dans les biofilms(2018), and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: MESH: Escherichia coli, MESH: Anti-Bacterial Agents, [SDV]Life Sciences [q-bio], MESH: Drug Resistance, Bacterial, Medicine (miscellaneous), MESH: Aminoglycosides, MESH: Biofilms, General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology
Abstract: The rise of antibiotic resistance in bacterial pathogens is a major health concern and the determinants of this emergence are actively studied. By contrast, although biofilms are an important cause of infections due to their high tolerance to a broad range of antimicrobials, much less is known on the development of antibiotic resistance within the biofilm environment, an issue potentially aggravating the current antibiotic crisis. Here, we compared the occurrence of resistance mutations in pathogenic Escherichia coli planktonic and biofilm populations exposed to clinically relevant cycles of lethal treatments with the aminoglycoside antibiotic amikacin. This experimental evolution approach revealed that mutations in sbmA and fusA are rapidly selected in biofilm but not in planktonic populations. The apparition of these bona fide resistance —and not tolerance— mutations is favored by the biofilm preexisting tolerance and high mutation rate. Moreover, we showed that while fusA mutations displayed a high fitness cost in planktonic conditions, these mutations were maintained in biofilms, a phenomenon further possibly amplified by the selection of fimH mutations favoring biofilm formation itself. Our study therefore provides new insights into the dynamic evolution of antibiotic resistance in biofilms, which could lead to clinically practical antibiotic regimen limiting biofilm-associated infections, while mitigating the emergence of worrisome antibiotic resistance mutations.
Published: 2023

4. Comparison of 8 versus 15 days of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia in adults: a randomized, controlled, open-label trial

Author: Adrien, Bouglé, Sophie, Tuffet, Laura, Federici, Marc, Leone, Antoine, Monsel, Thomas, Dessalle, Julien, Amour, Claire, Dahyot-Fizelier, François, Barbier, Charles-Edouard, Luyt, Olivier, Langeron, Bernard, Cholley, Julien, Pottecher, Tarik, Hissem, Jean-Yves, Lefrant, Benoit, Veber, Matthieu, Legrand, Alexandre, Demoule, Pierre, Kalfon, Jean-Michel, Constantin, Alexandra, Rousseau, Tabassome, Simon, Arnaud, Foucrier, Nora, Soussi, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Sud Francilien, Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre d'investigation clinique Biothérapie [CHU Pitié-Salpêtrière] (CIC-BTi), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Pharmacologie des anti-infectieux et antibiorésistance (PHAR2), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), CHU Strasbourg, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Initial MAnagement and prevention of acute orGan failures IN critically ill patiEnts (IMAGINE), Université de Montpellier (UM), CHU Rouen, Normandie Université (NU), Hôpital Lariboisière-Fernand-Widal [APHP], Hôpital Louis Pasteur [Chartres], CHU Clermont-Ferrand, Centre de Ressources Biologiques APHP-SU (PASS-CRB-APHP-SU), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Hôpital Beaujon [AP-HP]
Subjects: Adult, MESH: Humans, Survival, Pneumonia, Ventilator-Associated, MESH: Adult, MESH: Pneumonia, Ventilator-Associated, Antibiotic therapy, Critical Care and Intensive Care Medicine, Respiration, Artificial, Anti-Bacterial Agents, Ventilator-associated pneumonia, Intensive Care Units, Recurrence, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Anti-Bacterial Agents, MESH: Intensive Cate Units, MESH: Pseudomonas aeruginosa, Pseudomonas aeruginosa, Humans, MESH: Respiration, Artificial
Abstract: International audience; Purpose: Duration of antibiotic therapy for ventilator-associated pneumonia (VAP) due to non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA) remains uncertain. We aimed to assess the non-inferiority of a short duration of antibiotics (8 days) vs. prolonged antibiotic therapy (15 days) in VAP due to PA (PA-VAP).Methods: We conducted a nationwide, randomized, open-labeled, multicenter, non-inferiority trial to evaluate optimal duration of antibiotic treatment in PA-VAP. Eligible patients were adults with diagnosis of PA-VAP and randomly assigned in 1:1 ratio to receive a short-duration treatment (8 days) or a long-duration treatment (15 days). A pre-specified analysis was used to assess a composite endpoint combining mortality and PA-VAP recurrence rate during hospitalization in the intensive care unit (ICU) within 90 days.Results: The study was stopped after 24 months due to slow inclusion rate. In intention-to-treat population (n = 186), the percentage of patients who reached the composite endpoint was 25.5% (N = 25/98) in the 15-day group versus 35.2% (N = 31/88) in the 8-day group (difference 9.7%, 90% confidence interval (CI) -1.9%-21.2%). The percentage of recurrence of PA-VAP during the ICU stay was 9.2% in the 15-day group versus 17% in the 8-day group. The two groups had similar median days of mechanical ventilation, of ICU stay, number of extra pulmonary infections and acquisition of multidrug-resistant (MDR) pathogens during ICU stay.Conclusions: Our study failed to show the non-inferiority of a short duration of antibiotics in the treatment of PA-VAP, compared to a long duration. The short duration strategy may be associated to an increase of PA-VAP recurrence. However, the lack of power limits the interpretation of this study.
Published: 2022

5. Adenosine-Dependent Activation Mechanism of Prodrugs Targeting an Aminoacyl-tRNA Synthetase

Author: Guillaume Hoffmann, Madalen Le Gorrec, Emeline Mestdach, Stephen Cusack, Loïc Salmon, Malene Ringkjøbing Jensen, Andrés Palencia, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de RMN à très hauts champs de Lyon (CRMN), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), European Molecular Biology Laboratory [Grenoble] (EMBL), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-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)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)
Subjects: Colloid and Surface Chemistry, MESH: Humans, MESH: Leucine-tRNA Ligase, MESH: Anti-Bacterial Agents, [SDV]Life Sciences [q-bio], General Chemistry, MESH: Amino Acyl-tRNA Synthetases, MESH: Prodrugs, MESH: Adenosine, Biochemistry, Catalysis
Abstract: Prodrugs have little or no pharmacological activity and are converted to active drugs in the body by enzymes, metabolic reactions, or through human-controlled actions. However, prodrugs promoting their chemical bioconversion without any of these processes have not been reported before. Here, we present an enzyme-independent prodrug activation mechanism by boron-based compounds (benzoxaboroles) targeting leucyl-tRNA synthetase (LeuRS), including an antibiotic that recently has completed phase II clinical trials to cure tuberculosis. We combine nuclear magnetic resonance spectroscopy and X-ray crystallography with isothermal titration calorimetry to show that these benzoxaboroles do not bind directly to their drug target LeuRS, instead they are prodrugs that activate their bioconversion by forming a highly specific and reversible LeuRS inhibition adduct with ATP, AMP, or the terminal adenosine of the tRNALeu. We demonstrate how the oxaborole group of the prodrugs cyclizes with the adenosine ribose at physiological concentrations to form the active molecule. This bioconversion mechanism explains the remarkably good druglike properties of benzoxaboroles showing efficacy against radically different human pathogens and fully explains the mechanism of action of these compounds. Thus, this adenosine-dependent activation mechanism represents a novel concept in prodrug chemistry that can be applied to improve the solubility, permeability and metabolic stability of challenging drugs.
Published: 2023

6. Evaluation of ceftolozane-tazobactam susceptibility on a French nationwide collection of Enterobacterales

Author: Agnès B. Jousset, Sandrine Bernabeu, Cécile Emeraud, Rémy A. Bonnin, Alexandra Lomont, Jean Ralph Zahar, Audrey Merens, Christophe Isnard, Nathalie Soismier, Eric Farfour, Vincent Fihman, Nicolas Yin, Olivier Barraud, Hervé Jacquier, Anne-Gaëlle Ranc, Frédéric Laurent, Stéphane Corvec, Louise Ruffier d'Epenoux, Emmanuelle Bille, Nicolas Degand, Chloé Plouzeau, Thomas Guillard, Vincent Cattoir, Asaf Mizrahi, Antoine Grillon, Frédéric Janvier, Cécile Le Brun, Marlène Amara, Mathilda Bastide, Alban Lemonnier, Laurent Dortet, Centre National de Référence Associé de la Résistance aux Antibiotiques [Hôpital Bicêtre AP-HP] (CNRARA/Service de Microbiologie), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Microbiologie [Hôpital Bicêtre AP-HP] (UBH : Unité de Bactériologie-Hygiène), Service de bactériologie-Virologie-Hygiène [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Dynamique Microbienne associée aux Infections Urinaires et Respiratoires (DYNAMICURE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHI Créteil, Hôpital Foch [Suresnes], CHU Henri Mondor, Institut Gustave Roussy (IGR), CHU Limoges, Centre d'Investigation Clinique de Limoges (CIC1435), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM), Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Immunology and New Concepts in ImmunoTherapy (INCIT), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Service de bactériologie et hygiène hospitalière [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Bactériologie [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital Archet 2 [Nice] (CHU), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Bactériologie et Hygiène Hospitalière [Rennes], CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-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 ), Groupe Hospitalier Paris Saint-Joseph (hpsj), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Virulence Bactérienne Précoce : fonctions cellulaires et contrôle de l'infection aigüe et subaigüe, Université de Strasbourg (UNISTRA), Plateau technique de microbiologie, Laboratoire de bactériologie, Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg ), Hopital d'instruction des armées Sainte-Anne [Toulon] (HIA), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Biologie [CH Versailles], Centre Hospitalier de Versailles André Mignot (CHV), This work was partially supported by MSD and bioMérieux., Pecqueret, Valérie, and CHU Henri Mondor [Créteil]
Subjects: Microbiology (medical), MESH: Escherichia coli, Ceftolozane-tazobactam, [SDV]Life Sciences [q-bio], Immunology, MESH: Tazobactam, MESH: Pseudomonas Infections, MESH: beta-Lactamases, Microbiology, MESH: Prospective Studies, [SDV] Life Sciences [q-bio], MESH: Enterobacteriaceae, carbapenemase, MESH: Cephalosporins, Enterobacterales, ESBL, MESH: Anti-Bacterial Agents, MESH: Pseudomonas aeruginosa, Immunology and Allergy, epidemiology, France, MIC
Abstract: International audience; Objectives: Ceftolozane-tazobactam (C/T) proved its efficacy for the treatment of infections caused by non-carbapenemase producing Pseudomonas aeruginosa and Enterobacterales. Here, we aimed to provide susceptibility data on large series of Enterobacterales since the revision of EUCAST categorization breakpoints in 2020.Methods: First, C/T susceptibility was determined on characterized Enterobacterales resistant to 3rd generation cephalosporins (3GC) (ESBL production or different levels of AmpC overexpression) (n=213) and carbapenem resistant Enterobacterales (CRE) (n=259) including 170 carbapenemase producers (CPE). Then, 1,632 consecutive clinical Enterobacterales responsible for infection were prospectively collected in 23 French hospitals. C/T susceptibility was determined by Etest® (biomérieux) and broth microdilution (BMD) (Sensititre™, Thermo Scientific) to perform method comparison.Results: Within the collection isolates, 88% of 3GC resistant strains were susceptible to C/T, with important variation depending on the resistance mechanism: 93% vs 13% susceptibility for CTX-M and SHV-ESBL producers, respectively. Only 20% of the CRE were susceptible to C/T. Among CPE, 80 % of OXA-48-like producers were susceptible to C/T, whereas all metallo-β-lactamase producers were resistant. The prospective study revealed that 95.6% of clinical isolates were susceptible to C/T. Method comparison performed on these 1,632 clinical isolates demonstrated 99 % of categorization agreement between MIC to C/T determined by Etest® compared to BMD (reference) and only 74% of essential agreement.Conclusion: Overall, C/T showed good activity against wild-type Enterobacterales, AmpC producers and ESBL-producing E. coli but is less active against ESBL-producing K. pneumoniae and CRE. Etest® led to an underestimation of the MICs in comparison to BMD.
Published: 2023

7. Genome-wide screen in human plasma identifies multifaceted complement evasion of Pseudomonas aeruginosa

Author: Manon Janet-Maitre, Stéphane Pont, Frerich M. Masson, Serena Sleiman, Julian Trouillon, Mylène Robert-Genthon, Benoît Gallet, Chantal Dumestre-Perard, Sylvie Elsen, Christine Moriscot, Bart W. Bardoel, Suzan H. M. Rooijakkers, François Cretin, Ina Attrée, Groupe Pathogenèse Bactérienne et Réponses Cellulaires / Bacterial Pathogenesis and Cellular Responses Group (IBS-PBRC), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-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)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-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)-Université Grenoble Alpes (UGA), Groupe Microscopie Electronique et Méthodes (IBS-MEM), Integrated Structural Biology Grenoble (ISBG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), University Medical Center [Utrecht], Laboratoire d'Immunologie, and CHU Grenoble
Subjects: MESH: Humans, MESH: Anti-Bacterial Agents, [SDV]Life Sciences [q-bio], Virology, MESH: Pseudomonas aeruginosa, MESH: Complement System Proteins, Immunology, MESH: Complement Membrane Attack Complex, Genetics, Parasitology, Molecular Biology, Microbiology
Abstract: Pseudomonas aeruginosa, an opportunistic Gram-negative pathogen, is a leading cause of bacteremia with a high mortality rate. We recently reported that P. aeruginosa forms a persister-like sub-population of evaders in human plasma. Here, using a gain-of-function transposon sequencing (Tn-seq) screen in plasma, we identified and validated previously unknown factors affecting bacterial persistence in plasma. Among them, we identified a small periplasmic protein, named SrgA, whose expression leads to up to a 100-fold increase in resistance to killing. Additionally, mutants in pur and bio genes displayed higher tolerance and persistence, respectively. Analysis of several steps of the complement cascade and exposure to an outer-membrane-impermeable drug, nisin, suggested that the mutants impede membrane attack complex (MAC) activity per se. Electron microscopy combined with energy-dispersive X-ray spectroscopy (EDX) revealed the formation of polyphosphate (polyP) granules upon incubation in plasma of different size in purD and wild-type strains, implying the bacterial response to a stress signal. Indeed, inactivation of ppk genes encoding polyP-generating enzymes lead to significant elimination of persisting bacteria from plasma. Through this study, we shed light on a complex P. aeruginosa response to the plasma conditions and discovered the multifactorial origin of bacterial resilience to MAC-induced killing.
Published: 2023
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8. Biofilm Formation by Staphylococcus aureus in the Specific Context of Cystic Fibrosis

Author: Vincent Jean-Pierre, Agathe Boudet, Pauline Sorlin, Quentin Menetrey, Raphaël Chiron, Jean-Philippe Lavigne, Hélène Marchandin, Hydrosciences Montpellier (HSM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Virulence Bactérienne et Infections Chroniques (VBIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Pathogènes Hydriques Santé Environnement (PHySE ), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and This review was written with a grant for research by Nîmes University Hospital (NîmAO2018.02).
Subjects: Staphylococcus aureus, MESH: Humans, Biofilm, [SDV]Life Sciences [q-bio], Organic Chemistry, MESH: Cystic Fibrosis / complacations, General Medicine, MESH: Biofilms, Catalysis, Cystic fibrosis, Computer Science Applications, Inorganic Chemistry, Anti-biofilm, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Anti-Bacterial Agents, MESH: Child, MESH: Staphylococcal infections, MESH: Staphylococcus aureus / physiology, [CHIM]Chemical Sciences, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Physical and Theoretical Chemistry, Multispecies biofilm, Molecular Biology, Spectroscopy
Abstract: International audience; Staphylococcus aureus is a major human pathogen whose characteristics support its success in various clinical settings including Cystic Fibrosis (CF). In CF, S. aureus is indeed the most commonly identified opportunistic pathogen in children and the overall population. S. aureus colonization/infection, either by methicillin-susceptible or methicillin-resistant strains, will become chronic in about one third of CF patients. The persistence of S. aureus in CF patients’ lungs, despite various eradication strategies, is favored by several traits in both host and pathogen. Among the latter, living in biofilm is a highly protective way to survive despite deleterious environmental conditions, and is a common characteristic shared by the main pathogens identified in CF. This is why CF has earned the status of a biofilm-associated disease for several years now. Biofilm formation by S. aureus, and the molecular mechanisms governing and regulating it, have been extensively studied but have received less attention in the specific context of CF lungs. Here, we review the current knowledge on S. aureus biofilm in this very context, i.e., the importance, study methods, molecular data published on mono- and multi-species biofilm and anti-biofilm strategies. This focus on studies including clinical isolates from CF patients shows that they are still under-represented in the literature compared with studies based on reference strains, and underlines the need for such studies. Indeed, CF clinical strains display specific characteristics that may not be extrapolated from results obtained on laboratory strains.; Staphylococcus aureus est un agent pathogène humain majeur dont les caractéristiques soutiennent son succès dans divers contextes cliniques, y compris la fibrose kystique (FK). Dans la mucoviscidose, S. aureus est en effet l'agent pathogène opportuniste le plus couramment identifié chez les enfants et la population générale. La colonisation/infection à S. aureus, soit par des souches sensibles à la méthicilline, soit par des souches résistantes à la méthicilline, deviendra chronique chez environ un tiers des patients atteints de mucoviscidose. La persistance de S. aureus dans les poumons des patients atteints de mucoviscidose, malgré diverses stratégies d'éradication, est favorisée par plusieurs traits à la fois chez l'hôte et chez l'agent pathogène. Parmi ces derniers, vivre dans un biofilm est un moyen hautement protecteur de survivre malgré des conditions environnementales délétères, et est une caractéristique commune partagée par les principaux agents pathogènes identifiés dans la mucoviscidose. C'est pourquoi la mucoviscidose a obtenu depuis plusieurs années le statut de maladie associée au biofilm. La formation de biofilm par S. aureus et les mécanismes moléculaires qui le régissent et le régulent ont été largement étudiés mais ont reçu moins d'attention dans le contexte spécifique des poumons FK. Ici, nous passons en revue les connaissances actuelles sur le biofilm de S. aureus dans ce contexte précis, c'est-à-dire l'importance, les méthodes d'étude, les données moléculaires publiées sur le biofilm mono- et multi-espèces et les stratégies anti-biofilm. Cette focalisation sur les études incluant des isolats cliniques de patients atteints de mucoviscidose montre qu'ils sont encore sous-représentés dans la littérature par rapport aux études basées sur des souches de référence, et souligne la nécessité de telles études. En effet, les souches cliniques de mucoviscidose présentent des caractéristiques spécifiques qui ne peuvent être extrapolées à partir des résultats obtenus sur des souches de laboratoire.
Published: 2022

9. Combined Structural Analysis and Molecular Dynamics Reveal Penicillin-Binding Protein Inhibition Mode with β-Lactones

Author: Parker L. Flanders, Carlos Contreras-Martel, Nathaniel W. Brown, Joshua D. Shirley, Alexandre Martins, Kelsie N. Nauta, Andréa Dessen, Erin E. Carlson, Elizabeth A. Ambrose, University of Minnesota, Minneapolis, USA, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-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)-Université Grenoble Alpes (UGA), Grenoble Instruct-ERIC center (ISBG, UAR 3518 CNRS-CEA-UGA-EMBL), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), and ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010)
Subjects: MESH: Penicillin-Binding Proteins, [SDV]Life Sciences [q-bio], General Medicine, Molecular Dynamics Simulation, beta-Lactams, Ligands, Biochemistry, Article, Anti-Bacterial Agents, Lactones, Streptococcus pneumoniae, Bacterial Proteins, MESH: beta-Lactams, MESH: Anti-Bacterial Agents, MESH: Ligands, Penicillin-Binding Proteins, Molecular Medicine, MESH: Molecular Dynamics Simulation, MESH: Bacterial Proteins, MESH: Lactones, MESH: Streptococcus pneumoniae
Abstract: International audience; β-Lactam antibiotics comprise one of the most widely used therapeutic classes to combat bacterial infections. This general scaffold has long been known to inhibit bacterial cell wall biosynthesis by inactivating penicillin-binding proteins (PBPs); however, bacterial resistance to β-lactams is now widespread, and new strategies are urgently needed to target PBPs and other proteins involved in bacterial cell wall formation. A key requirement in the identification of strategies to overcome resistance is a deeper understanding of the roles of the PBPs and their associated proteins during cell growth and division, such as can be obtained with the use of selective chemical probes. Probe development has typically depended upon known PBP inhibitors, which have historically been thought to require a negatively charged moiety that mimics the C-terminus of the PBP natural peptidoglycan substrate, d-Ala-d-Ala. However, we have identified a new class of β-lactone-containing molecules that interact with PBPs, often in an isoform-specific manner, and do not incorporate this C-terminal mimetic. Here, we report a series of structural biology experiments and molecular dynamics simulations that we utilized to evaluate specific binding modes of this novel PBP inhibitor class. In this work, we obtained
Published: 2022

10. Molecular Mechanisms Involved in Pseudomonas aeruginosa Bacteremia

Author: Stéphane Pont, Manon Janet-Maitre, Eric Faudry, François Cretin, Ina Attrée, Groupe Pathogenèse Bactérienne et Réponses Cellulaires / Bacterial Pathogenesis and Cellular Responses Group (IBS-PBRC), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-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)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)
Subjects: Virulence determinants, MESH: Humans, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Complement, MESH: Pseudomonas Infections, Bacteremia, Type III secretion system, MESH: Anti-Bacterial Agents, Transmigration, MESH: Pseudomonas aeruginosa, MESH: Complement Membrane Attack Complex, MESH: Bacteremia, MESH: Phylogeny, Membrane attack complex (MAC), MESH: Virulence Factors
Abstract: International audience; Bloodstream infections (BSI) with Pseudomonas aeruginosa account for 8.5% of all BSIs, their mortality rate, at about 40%, is the highest among causative agents. For this reason and due to its intrinsic and acquired resistance to antibiotics, P. aeruginosa represents a threat to public health systems. From the primary site of infection, often the urinary and respiratory tracts, P. aeruginosa uses its arsenal of virulence factors to cross both epithelial and endothelial barriers, ultimately reaching the bloodstream. In this chapter, we review the main steps involved in invasion and migration of P. aeruginosa into blood vessels, and the molecular mechanisms governing bacterial survival in blood. We also review the lifestyle of P. aeruginosa "on" and "in" host cells. In the context of genomic and phenotypic diversity of laboratory strains and clinical isolates, we underline the need for more standardized and robust methods applied to host-pathogen interaction studies, using several representative strains from distinct phylogenetic groups before drawing general conclusions. Finally, our literature survey reveals a need for further studies to complete our comprehension of the complex interplay between P. aeruginosa and the immune system in the blood, specifically in relation to the complement system cascade(s) and the Membrane Attack Complex (MAC), which play crucial roles in counteracting P. aeruginosa BSI.
Published: 2022

11. The cnf1 gene is associated with an expanding Escherichia coli ST131 H30Rx/C2 subclade and confers a competitive advantage for gut colonization

Author: Landry L. Tsoumtsa Meda, Luce Landraud, Serena Petracchini, Stéphane Descorps-Declere, Emeline Perthame, Marie-Anne Nahori, Laura Ramirez Finn, Molly A. Ingersoll, Rafael Patiño-Navarrete, Philippe Glaser, Richard Bonnet, Olivier Dussurget, Erick Denamur, Amel Mettouchi, Emmanuel Lemichez, Vougny, Marie-Christine, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, Identification de biomarqueurs sanguins prédictifs des infections uriniaires récidivantes et développement d'immunothérapies préventives personnalisées - - PredictUTI2017 - ANR-17-CE17-0014 - AAPG2017 - VALID, Colonisation des tissus et resevoirs infectieux des ExPEC induits par CNF1, nouvelle voie thérapeutique - - ExPECtation2021 - ANR-21-CE15-0006 - AAPG2021 - VALID, Toxines bactériennes - Bacterial Toxins, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Inflammation et immunité des muqueuses - Mucosal Inflammation and Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Écologie et Évolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre National de Référence de la Résistance aux Antibiotiques [CHU Clermont-Ferrand] (CNR), CHU Clermont-Ferrand, Yersinia, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Fondation ARC [PJA 20191209650], Ligue Nationale contre le Cancer Subvention de Recherche Scientifique [RS20/75-63], Fondation pour la Recherche Médicale (Equipe FRM 2016, DEQ20161136698)., We thank François-Xavier WEILL for fruitful discussions. The plasmids pKOBEG and p3xFlag-CmR CNF1 wildtype were kindly provided by Jean-Marc GHIGO and Petra DERSCH, respectively., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-17-CE17-0014,PredictUTI,Identification de biomarqueurs sanguins prédictifs des infections uriniaires récidivantes et développement d'immunothérapies préventives personnalisées(2017), and ANR-21-CE15-0006,ExPECtation,Colonisation des tissus et resevoirs infectieux des ExPEC induits par CNF1, nouvelle voie thérapeutique(2021)
Subjects: rho GTP-Binding Proteins, Microbiology (medical), ST131, [SDV.IMM] Life Sciences [q-bio]/Immunology, Virulence Factors, UTI, Bacterial Toxins, MESH: beta-Lactamases, Microbiology, beta-Lactamases, MESH: Gastrointestinal Microbiome, Drug Resistance, Multiple, Bacterial, MESH: Anti-Bacterial Agents, Escherichia coli, Humans, Escherichia coli Infections, MESH: Escherichia coli Infections, MESH: Virulence Factors, ExPEC, MESH: Humans, MESH: Escherichia coli, Escherichia coli Proteins, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH: Drug Resistance, Multiple, Bacterial, colonization, MESH: rho GTP-Binding Proteins, CNF1, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Anti-Bacterial Agents, Gastrointestinal Microbiome, rho GTPases, Infectious Diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, gastrointestinal tract
Abstract: Epidemiological projections point to acquisition of ever-expanding multidrug resistance (MDR) byiEscherichia coli/i, a commensal of the digestive tract and a source of urinary tract pathogens. Bioinformatics analyses of a large collection ofiE. coli/igenomes from EnteroBase, enriched in clinical isolates of worldwide origins, suggest the Cytotoxic Necrotizing Factor 1 (CNF1)-toxin encoding gene,icnf1/i, is preferentially distributed in four common sequence types (ST) encompassing the pandemiciE. coli/iMDR lineage ST131. This lineage is responsible for a majority of extraintestinal infections that escape first-line antibiotic treatment, with known enhanced capacities to colonize the gastrointestinal tract. Statistical projections based on this dataset point to a global expansion oficnf1/i-positive multidrug-resistant ST131 strains from subcladeiH/i30Rx/C2, accounting for a rising prevalence oficnf1/i-positive strains in ST131. Despite the absence of phylogeographical signals,icnf1/i-positive isolates segregated into clusters in the ST131-iH/i30Rx/C2 phylogeny, sharing a similar profile of virulence factors and the sameicnf1/iallele. The suggested dominant expansion oficnf1/i-positive strains in ST131-iH/i30Rx/C2 led us to uncover the competitive advantage conferred byicnf1/ifor gut colonization to the clinical strain EC131GY ST131-iH/i30Rx/C2 versusicnf1/i-deleted isogenic strain. Complementation experiments showed that colon tissue invasion was compromised in the absence of deamidase activity on Rho GTPases by CNF1. Hence, gut colonization factor function oficnf1/iwas confirmed for another clinical strain ST131-iH/i30Rx/C2. In addition, functional analysis of theicnf1/i-positive clinical strain EC131GY ST131-iH/i30Rx/C2 and aicnf1/i-deleted isogenic strain showed no detectable impact of the CNF1 gene on bacterial fitness and inflammation during the acute phase of bladder monoinfection. Together these data argue for an absence of role of CNF1 in virulence during UTI, while enhancing gut colonization capacities of ST131-iH/i30Rx/C2 and suggested expansion oficnf1/i-positive MDR isolates in subclade ST131-iH/i30Rx/C2.
Published: 2022

12. Risk factors for therapeutic failure in the management of post-operative peritonitis: a post hoc analysis of the DURAPOP trial

Author: Karim Asehnoune, Sebastien Pease, Philippine Eloy, Alexandre Mignon, Marina Esposito-Farèse, Pascal Raclot, Sami Jaber, Joel Cousson, Soizic Gergaud, Hervé Dupont, Marc Beaussier, Josette Gally, Claude Girard, Melanie Levrard, Claude Meistelman, Gilles Blasco, Jean-Francois Payen, Philippe Gouin, Nathalie Grall, Olivier Collanges, Paer Abback, Thomas Lescot, Sigismond Lasocki, Thomas Gaillard, Sebastien Pily-Floury, Antoine Tesniere, Gaëtan Plantefève, Jean-François Georger, Benoit Veber, Philippe Montravers, Christian Auboyer, Marie-Christine Herault, Florent Wallet, Jean-François Perrier, Regis Bronchard, Yazine Mahjoub, Alain Lepape, Vincent Piriou, Thierry Floch, Emmanuel Samain, Emmanuel Weiss, Thomas Clavier, Mathieu Desmard, Philippe Seguin, Candice Tassin, Yoann Launey, Nouria Belhadj-Tahar, Raphaël Cinotti, Olivier Pajot, Guillaume Besch, Catherine Paugam, Boris Jung, Jean-Marc Delay, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, CHU Rouen, Normandie Université (NU), CHU Pontchaillou [Rennes], Hôpital Beaujon [AP-HP], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), CHU Amiens-Picardie, Université de Picardie Jules Verne (UPJV), DURAPOP trial group: Philippe Montravers, Regis Bronchard, Mathieu Desmard, Herve Dupont, Melanie Levrard, Yazine Mahjoub, Sigismond Lasocki, Soizic Gergaud, Thomas Gaillard, Gaetan Plantefeve, Olivier Pajot, Gilles Blasco, Emmanuel Samain, Guillaume Besch, Sebastien Pily-Floury, Catherine Paugam, Sebastien Pease, Paer Abback, Claude Girard, Jean-Francois Payen, Marie-Christine Herault, Sami Jaber, Boris Jung, Jean-Marc Delay, Josette Gally, Claude Meistelman, Jean-François Perrier, Karim Asehnoune, Raphael Cinotti, Antoine Tesniere, Alexandre Mignon, Thomas Lescot, Nouria Belhadj-Tahar, Marc Beaussier, Alain Lepape, Vincent Piriou, Florent Wallet, Candice Tassin, Joel Cousson, Pascal Raclot, Thierry Floch, Philippe Seguin, Yoann Launey, Benoit Veber, Philippe Gouin, Thomas Clavier, Christian Auboyer, Olivier Collanges, Jean-François Georger, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Simplification des soins chez les patients complexes - UR UPJV 7518 (SSPC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and MORNET, Dominique
Subjects: medicine.medical_treatment, [SDV]Life Sciences [q-bio], Penicillanic Acid, Logistic regression, 0302 clinical medicine, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, Pharmacology (medical), 030212 general & internal medicine, MESH: Penicillanic Acid, Prospective Studies, Original Research, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, AcademicSubjects/MED00290, Piperacillin, Tazobactam Drug Combination, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Piperacillin/tazobactam, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine.drug, Microbiology (medical), MESH: Piperacillin, medicine.medical_specialty, MESH: Peritonitis, Peritonitis, Tazobactam, 03 medical and health sciences, Internal medicine, MESH: Anti-Bacterial Agents, Post-hoc analysis, medicine, AcademicSubjects/MED00740, Humans, Renal replacement therapy, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Pharmacology, Piperacillin, MESH: Humans, business.industry, 030208 emergency & critical care medicine, medicine.disease, Comorbidity, MESH: Prospective Studies, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business, AcademicSubjects/MED00230
Abstract: Background Therapeutic failure is a frequent issue in the management of post-operative peritonitis. Objectives A post hoc analysis of the prospective, multicentre DURAPOP trial analysed the risk factors for failures in post-operative peritonitis following adequate source control and empirical antibiotic therapy in critically ill patients. Patients and methods Overall failures assessed post-operatively between Day 8 and Day 45 were defined as a composite of death and/or surgical and/or microbiological failures. Risk factors for failures were assessed using logistic regression analyses. Results Among the 236 analysed patients, overall failures were reported in 141 (59.7%) patients, including 30 (12.7%) deaths, 81 (34.3%) surgical and 95 (40.2%) microbiological failures. In the multivariate analysis, the risk factors associated with overall failures were documented piperacillin/tazobactam therapy [adjusted OR (aOR) 2.10; 95% CI 1.17–3.75] and renal replacement therapy on the day of reoperation (aOR 2.96; 95% CI 1.05–8.34). The risk factors for death were age (aOR 1.08 per year; 95% CI 1.03–1.12), renal replacement therapy on reoperation (aOR 3.95; 95% CI 1.36–11.49) and diabetes (OR 6.95; 95% CI 1.34–36.03). The risk factors associated with surgical failure were documented piperacillin/tazobactam therapy (aOR 1.99; 95% CI 1.13–3.51), peritoneal cultures containing Klebsiella spp. (aOR 2.45; 95% CI 1.02–5.88) and pancreatic source of infection (aOR 2.91; 95% CI 1.21–7.01). No specific risk factors were identified for microbiological failure. Conclusions Our data suggest a predominant role of comorbidities, the severity of post-operative peritonitis and possibly of documented piperacillin/tazobactam treatment on the occurrence of therapeutic failures, regardless of their type.
Published: 2021

13. A comprehensive resource for Bordetella genomic epidemiology and biodiversity studies

Author: Sébastien Bridel, Valérie Bouchez, Bryan Brancotte, Sofia Hauck, Nathalie Armatys, Annie Landier, Estelle Mühle, Sophie Guillot, Julie Toubiana, Martin C. J. Maiden, Keith A. Jolley, Sylvain Brisse, Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre national de Référence de la Coqueluche et autres Bordetelloses - National Reference Center for Whooping Cough and other Bordetella infections (CNR), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, University of Oxford, Collection de l'Institut Pasteur (CIP), Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Zoology [Oxford], This work was supported financially by the French Government’s Investissement d’Avenir program Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID). BIGSdb development is funded by a Wellcome Trust Biomedical Resource grant (218205/Z/19/Z). This work used the computational and storage services provided by the IT Department at Institut Pasteur. The National Reference Center for Whooping Cough and other Bordetella Infections is supported by Institut Pasteur and Santé publique France (Public Health France)., We thank Julien Guglielmini and Alexis Criscuolo (Bioinformatics and Biostatistics HUB in Institut Pasteur) for help with the BIGSdb-Pasteur database configuration and for advice regarding bioinformatics analyses., and ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010)
Subjects: Whooping Cough, Bordetella, virulence factors, General Physics and Astronomy, Bordetella bronchiseptica, Bordetella pertussis, MESH: Biodiversity, General Biochemistry, Genetics and Molecular Biology, MESH: Bordetella pertussis, taxonomy, MESH: Anti-Bacterial Agents, Drug Resistance, Bacterial, MESH: Drug Resistance, Bacterial, Animals, Humans, MESH: Animals, antimicrobial resistance, MESH: Phylogeny, Phylogeny, MESH: Humans, Multidisciplinary, MESH: Genomics, Biodiversity, Genomics, General Chemistry, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Anti-Bacterial Agents, diagnostic markers, phylogenetic diversity, Macrolides, MESH: Macrolides
Abstract: The genus Bordetella includes bacteria that are found in the environment and/or associated with humans and other animals. A few closely related species, including Bordetella pertussis, are human pathogens that cause diseases such as whooping cough. Here, we present a large database of Bordetella isolates and genomes and develop genotyping systems for the genus and for the B. pertussis clade. To generate the database, we merge previously existing databases from Oxford University and Institut Pasteur, import genomes from public repositories, and add 83 newly sequenced B. bronchiseptica genomes. The public database currently includes 2582 Bordetella isolates and their provenance data, and 2085 genomes (https://bigsdb.pasteur.fr/bordetella/). We use core-genome multilocus sequence typing (cgMLST) to develop genotyping systems for the whole genus and for B. pertussis, as well as specific schemes to define antigenic, virulence and macrolide resistance profiles. Phylogenetic analyses allow us to redefine evolutionary relationships among known Bordetella species, and to propose potential new species. Our database provides an expandable resource for genotyping of environmental and clinical Bordetella isolates, thus facilitating evolutionary and epidemiological research on whooping cough and other Bordetella infections.
Published: 2022

14. A Qualitative Method for Learning Medical Expert Reasoning

Author: Karima Sedki, Jean-Baptiste Lamy, Rosy Tsopra, Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), This work was supported by Agence Nationale de Sécurité du Médicament et des Produits de santé (ANSM). [AAP 2016- RaMiPA Project - Reasoning for a better antibiotic prescrip-tion - Dr Rosy TSOPRA]., TSOPRA, Rosy, École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE)
Subjects: [SDV] Life Sciences [q-bio], CPGs, MESH: Anti-Bacterial Agents, [SDV]Life Sciences [q-bio], Preferences learning, Learning, MESH: Learning, [INFO]Computer Science [cs], [INFO] Computer Science [cs], Experts reasoning, Problem Solving, Anti-Bacterial Agents, MESH: Problem Solving
Abstract: International audience; The aim of this paper is to propose a qualitative method for learning a model that represents the closest possible experts reasoning and strategies to provide recommendations of antibiotics. The learned model contains an integrity constraint and a preference formula. The former indicates the features that an antibiotic should have to be recommended. The later indicates the rank of recommendation of an antibiotic.
Published: 2022

15. Analysis of Haemophilus species in patients with respiratory tract infections in Yaoundé, Cameroon

Author: Ariane Nzouankeu, Muhamed-Kheir Taha, Eva Hong, Ala-Eddine Deghmane, Eric-Walter Pefura-Yone, Aude Terrade, Véronique Penlap Beng, Marie-Christine Fonkoua, Serges Tchatchouang, Richard Njouom, Mélanie Denizon, Suzie Moyo Tetang Ndiang, Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), Centre National de Référence des Méningocoques et Haemophilus influenzae - National Reference Center Meningococci and Haemophilus influenzae (CNR), Institut Pasteur [Paris], Université de Yaoundé I, Centre Hospitalier Essos [Yaoundé, Cameroun], Jamot hospital, This work was supported by the United States Department of Health and Human Services [grant number 6 DESP060001-01-01], the Institut Pasteur and the Institut Pasteur International Network (RIIP) through Traineeship Grants Calmette and Yersin., and Institut Pasteur [Paris] (IP)
Subjects: Male, 0301 basic medicine, Serotype, MESH: Drug Resistance, Microbial, Antibiotic resistance, Antibiotics, MESH: beta-Lactamases, Quinolones, Polymerase Chain Reaction, 0302 clinical medicine, MESH: Child, Ampicillin, Cameroon, 030212 general & internal medicine, Child, Respiratory Tract Infections, MESH: Microbial Sensitivity Tests, Respiratory tract infections, Drug Resistance, Microbial, General Medicine, Anti-Bacterial Agents, 3. Good health, Ciprofloxacin, Infectious Diseases, Child, Preschool, Female, MESH: Haemophilus Infections, medicine.drug, Microbiology (medical), MESH: Mutation, Haemophilus Infections, Adolescent, Respiratory tract infection, medicine.drug_class, 030106 microbiology, Microbial Sensitivity Tests, Biology, beta-Lactamases, lcsh:Infectious and parasitic diseases, Microbiology, 03 medical and health sciences, MESH: Anti-Bacterial Agents, Haemophilus, Haemophilus species, medicine, Humans, lcsh:RC109-216, MESH: Adolescent, MESH: Humans, MESH: Quinolones, MESH: Child, Preschool, typing, MESH: Polymerase Chain Reaction, MESH: Haemophilus influenzae, MESH: Cameroon, biology.organism_classification, rpoB, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Haemophilus influenzae, MESH: Male, Typeing, Whole genome sequencing, MESH: Respiratory Tract Infections, Mutation, MESH: Ampicillin, MESH: Female
Abstract: Objectives: To identifyHaemophilus species and characterise the antimicrobial susceptibility of isolates from patients with respiratory tract infections (RTIs) in Cameroon. Methods: Isolates (n = 95) were from patients with RTIs obtained from two hospitals in Yaoundé, Cameroon. Isolates were identified by biochemical assay, a polymerase chain reaction (PCR)-based method, matrix-assisted laser desorption ionization-time of flight (MALDI-TOF), and whole genome sequencing. Antibiotic minimum inhibitory concentrations were determined by E-test. Results: Haemophilus influenzae (H. influenzae) was the most prevalent species, varying from 76.8 to 84.2% according to the different methods. The isolates were mainly non-typeable (n = 70, 96%). Three H. influenzae isolates were capsulated (b, e and f). The isolates were genetically diverse and 40 unique sequence types were identified, including 11 new ones. Resistance to ampicillin was observed among 52 of 94 (55.3%), and 14 of the 52 (26.9%) produced TEM-1 β-lactamase. PBP3 mutations occurred in 40 of 52 (76.9%) ampicillin-resistant isolates. Eleven isolates were chloramphenicol-resistant, with eight of 10 (80%) producing chloramphenicol acetyltransferase. Four Haemophilus isolates were rifampicin-resistant, with two mutations in rpoB gene. Five isolates were ciprofloxacin-resistant and harboured mutations in the quinolone-resistance-determining regions of gyrA and parC genes. Conclusion: TheH. influenzae isolates were highly diverse and showed high levels of antibiotic resistance. H. influenzae serotype b is still circulating in the post-vaccination era.
Published: 2020

16. First report of meningococcal ciprofloxacin resistance in Greece due to invasive isolates of the sequence type ST-3129

Author: Ioanna Magaziotou, Athanasia Xirogianni, Ala-Eddine Deghmane, Georgina Tzanakaki, Anastasia Papandreou, Muhamed-Kheir Taha, Theano Georgakopoulou, National Meningitis Reference Laboratory, National School of Public Health Athens, Department of Epidemiological Surveillance and Intervention of the National Public Health Organization (NPHO), Infections Bactériennes Invasives, Institut Pasteur [Paris], The study was funded through the annual financial support from the National Public Health Organization (EODY)., and Institut Pasteur [Paris] (IP)
Subjects: Male, 0301 basic medicine, Antibiotics, Ciprofloxacin resistance, Neisseria meningitidis, MESH: Meningococcal Infections, medicine.disease_cause, 0302 clinical medicine, Medical microbiology, Ciprofloxacin, MESH: Child, 030212 general & internal medicine, Child, Greece, General Medicine, MESH: Infant, Anti-Bacterial Agents, 3. Good health, MESH: Multilocus Sequence Typing, Infectious Diseases, MESH: Young Adult, Child, Preschool, Female, Microbiology (medical), Susceptibility testing, medicine.medical_specialty, Adolescent, medicine.drug_class, 030106 microbiology, Multi locus sequence typing, Biology, Serogroup, MESH: Neisseria meningitidis, Microbiology, Young Adult, 03 medical and health sciences, MESH: Anti-Bacterial Agents, Drug Resistance, Bacterial, MESH: Drug Resistance, Bacterial, medicine, Humans, MESH: Ciprofloxacin, Greek island, MESH: Adolescent, MESH: Humans, MESH: Child, Preschool, Infant, Outbreak, MESH: Serogroup, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, Meningococcal Infections, MESH: Greece, MESH: Female, WGS, Multilocus Sequence Typing
Abstract: International audience; A local outbreak caused by Neisseria meningitidis occurred in the migration camp in the Greek island of Lesbos during January-February 2020 (4 of 5 cases). In total, 5 samples positive for N. meningitidis were further investigated for sero-/genogroup, PorA, and WGS analysis. MenB was found among 3 cases, while in two cases, MenY was identified. WGS analysis and antibiotic susceptibility testing on the 2 culture positive MenB samples showed the new ST-3129, ciprofloxacin-resistant clone was circulating among the immigrants in the aforementioned camp. This is the first report of ciprofloxacin resistance in Greece.
Published: 2020

17. Are the recommendations for post-operative antibiotics in patients with grade I or II acute calculous cholecystitis being applied in clinical practice?

Author: Marc Pocard, Jean-Christophe Paquet, Jean-Jacques Tuech, Karem Slim, J. Dembinski, Orlane Guérin, Francis Navarro, François Mauvais, Jean-Luc Faucheron, Jean-Marc Regimbeau, Chirurgie digestive [CHU Amiens], CHU Amiens-Picardie, Service de Chirurgie Digestive et Hépatobiliaire [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Groupe Hospitalier Nord Essonne [Longjumeau], Service de chirurgie digestive [CHU Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de chirurgie digestive (Centre Hospitalier de Beauvais), Centre Hospitalier de Beauvais, Centre Hospitalier Universitaire [Grenoble] (CHU), and Université de Picardie Jules Verne (UPJV)
Subjects: MESH: Cholecystectomy, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, Cholecystitis, Acute, Antibiotics, 030230 surgery, MESH: Length of Stay, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, MESH: Postoperative Period, MESH: Anti-Bacterial Agents, MESH: Postoperative Complications, medicine, Clinical endpoint, Humans, Cholecystectomy, In patient, Postoperative Period, Post operative, 10. No inequality, Retrospective Studies, MESH: Treatment Outcome, MESH: Humans, Hepatology, business.industry, Gastroenterology, MESH: Cholecystitis, Acute, MESH: Retrospective Studies, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Perioperative, Length of Stay, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Anti-Bacterial Agents, 3. Good health, Surgery, Clinical Practice, Treatment Outcome, MESH: Cholecystectomy, Laparoscopic, Cholecystectomy, Laparoscopic, 030220 oncology & carcinogenesis, Cholecystitis, business
Abstract: Background There is a level-1 evidence indicating that postoperative antibiotics are unnecessary following cholecystectomy for grade I or II acute calculous cholecystitis (ACC). We wanted to evaluate the applications of this recommendation in clinical practice four years after the original publication in ABCAL-participating centers. Methods A retrospective analysis of patients operated for grade I or II ACC from January to December 2016 in ABCAL-participating centers was performed. Inclusion criteria were the same as for the ABCAL-study. The primary endpoint was the postoperative antibiotic administration rate. The secondary endpoints were postoperative outcomes. Results Of the 283 patients included, 64% received postoperative antibiotics. Only 19% received antibiotics after POD1. The perioperative outcomes were similar between those that did or did not receive antibiotics after POD1. The median [range] length of stay was significantly shorter in patients who did not receive postoperative antibiotics (4 days [1–20]) compared to the others (6 days [1–50], p > 0.001). Conclusion Despite strong recommendations included in the Tokyo 2018 guidelines, the results of the ABCAL-study are poorly applied even if the absence of postoperative antibiotics has no impact on morbidity. It is important to stress that postoperative antibiotics are not necessary after cholecystectomy for grade I or II ACC.
Published: 2020

18. The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study

Author: Roberts, Jason, Joynt, Gavin, Lee, Anna, Choi, Gordon, Bellomo, Rinaldo, Kanji, Salmaan, Mudaliar, M Yugan, Peake, Sandra, Stephens, Dianne, Taccone, Fabio Silvio, Ulldemolins, Marta, Valkonen, Miia Maaria, Agbeve, Julius, Baptista, João, Bekos, Vasileios, Boidin, Clement, Brinkmann, Alexander, Buizen, Luke, Castro, Pedro, Cole, C Louise, Creteur, Jacques, de Waele, Jan, Deans, Renae, Eastwood, Glenn, Escobar, Leslie, Gomersall, Charles, Gresham, Rebecca, Jamal, Janattul Ain, Kluge, Stefan, König, Christina, Koulouras, Vasilios, Lassig-Smith, Melissa, Laterre, Pierre-Francois, Lei, Katie, Leung, Patricia, Lefrant, Jean-Yves, Llauradó-Serra, Mireia, Martin-Loeches, Ignacio, Mat Nor, Mohd Basri, Ostermann, Marlies, Parker, Suzanne, Rello, Jordi, Roberts, Darren, Roberts, Michael, Richards, Brent, Rodríguez, Alejandro, Roehr, Anka, Roger, Claire, Seoane, Leonardo, Sinnollareddy, Mahipal, Sousa, Eduardo, Soy, Dolors, Spring, Anna, Starr, Therese, Thomas, Jane, Turnidge, John, Wallis, Steven, Williams, Tricia, Wittebole, Xavier, Zikou, Xanthi, Paul, Sanjoy, Lipman, Jeffrey, Andresen, Max, Baltazar, Sónia, Barbar, Saber, Costa, Eulália, Durand, Dominique, Freitas, Ricardo, Frey, Otto, Guerra Valero, Yarmarly, Haughton, Margaret, Koeberer, Andreas, Kollef, Marin, Klein, Kerenaftali, Mehta, Ravindra, Mckenzie, Cathy, Muller, Laurent, Nair, Priya, Nayyar, Vineet, Ordóñez Mejia, Jenny, Panagou, Georgia-Laura, Paxton, Jody, Peck, Leah, Samanta, Mayukh, Vincent, Jean-Louise, Wan, Ruth, Young, Helen, University of Southern Queensland (USQ), Royal Brisbane & Women's Hospital [Brisbane, Australia] (RBWH), Princess Alexandra Hospital, Brisbane, SMARRT Study, ANZICS Clinical Trials Group, The Chinese University of Hong Kong [Hong Kong], Austin Hospital [Melbourne], Austin Health, The Ottawa Hospital, The Ottawa Hospital Research Institute, Centre for Rehabilitation Research and Development, 505 Smyth Road, Ottawa, ON, Canada, K1H 8M2., Westmead Hospital [Sydney], The University of Sydney, The Queen Elizabeth Hospital (TQEH), University of Adelaide, Monash University [Melbourne], Royal Darwin Hospital, Flinders University [Adelaide, Australia], National Critical Care and Trauma Response Centre (Darwin) (NCCTRC), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Corporació Sanitària Parc Taulí, Barcelona Biomedical Research Park (PRBB), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, QIMR Berghofer Medical Research Institute, Centro Hospitalar e Universitário [Coimbra], Athens Naval Hospital, University of Queensland [Brisbane], 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), Hospices Civils de Lyon (HCL), Kliniken Landkreis Heidenheim, Melbourne EpiCentre, The Royal Melbourne Hospital, Hospital Clínic de Barcelona (ICMiD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Nepean Hospital, Ghent University Hospital, Universidad de Santiago de Chile [Santiago] (USACH), University of Sydney and Nepean Hospital, Hospital Tengku Ampuan Afzan (HTAA), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University Hospital of Ioannina, Royal Brisbane & Women's Hospital, Cliniques universitaires St Luc [Bruxelles], Guy's and St Thomas' Hospital [London], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Universitat Internacional de Catalunya [Barcelona] (UIC), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, International Islamic University Malaysia [Kuala Lumpur], Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of South Australia [Adelaide], Basil Hetzel Institute (BHI), Translational Research Institute (TRI), Gold Coast University Hospital, University Hospital of Tarragona 'Joan XXIII', University Rovirai Virgili de Tarragona (URV), Ochsner Medical Center, The Queen Elizabeth Hospital, Hospital Clínic de Barcelona, Roberts, Jason A., Joynt, Gavin M., Lee, Anna, Choi, Gordon, Roberts, Michael S., Sinnollareddy, Mahipal, and Lipman, Jeffrey
Subjects: 0301 basic medicine, Continuous renal replacement therapy, medicine.medical_treatment, continuous renal replacement therapy, Antibiotics, urologic and male genital diseases, MESH: Meropenem, 030226 pharmacology & pharmacy, law.invention, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Prospective Studies, pharmacokinetic, extended daily dialysis, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Extended daily dialysis, Intensive care unit, Anti-Bacterial Agents, 3. Good health, Renal Replacement Therapy, Infectious Diseases, MESH: Critical Illness, Vancomycin, beta-lactam, medicine.drug, MESH: Piperacillin, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, Critical Illness, Beta-lactam, 030106 microbiology, Pharmacokinetic, Meropenem, 03 medical and health sciences, MESH: Anti-Bacterial Agents, Internal medicine, Intensive care, medicine, Humans, Trough Concentration, Dosing, Renal replacement therapy, Piperacillin, MESH: Humans, business.industry, MESH: Prospective Studies, renal clearance, MESH: Renal Replacement Therapy, business, Renal clearance
Abstract: Background The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. Methods We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. Results We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4–8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35–65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9–18.8), piperacillin was 78.6 mg/L (49.5–127.3), tazobactam was 9.5 mg/L (6.3–14.2), and vancomycin was 14.3 mg/L (11.6–21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. Conclusions In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.
Published: 2020

19. Harmonisation of in-silico next-generation sequencing based methods for diagnostics and surveillance

Author: Nunez-Garcia, J., AbuOun, M., Storey, N., Brouwer, M.S., Delgado-Blas, J.F., Mo, S.S., Ellaby, N., Veldman, K.T., Haenni, M., Châtre, P., Madec, J.Y., Hammerl, J.A., Serna, C., Getino, M., La Ragione, R., Naas, T., Telke, A.A., Glaser, P., Sunde, M., Gonzalez-Zorn, B., Ellington, M.J., Anjum, M.F., Animal and Plant Health Agency [Addlestone, UK] (APHA), Wageningen BioVeterinary Research, Wageningen University and Research [Wageningen] (WUR), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Norwegian Veterinary Institute [Oslo], Public Health England [London], Unité Antibiorésistance et Virulence Bactériennes (AVB), Laboratoire de Lyon [ANSES], Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), German Federal Institute for Risk Assessment [Berlin] (BfR), University of Surrey (UNIS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Écologie et Évolution de la Résistance aux Antibiotiques / Ecology and Evolution of Antibiotics Resistance (EERA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Saclay-Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and European Project: 773830, H2020-SFS-2017-1 ,One Health EJP(2018)
Subjects: ARDIG, Microbial Sensitivity Tests, Antimicrobial resistance, Next generation sequencing, MESH: Anti-Bacterial Agents, MESH: Drug Resistance, Bacterial, Drug Resistance, Bacterial, Escherichia coli, Life Science, Humans, MESH: High-Throughput Nucleotide Sequencing, Escherichia coli Infections, MESH: Escherichia coli Infections, Host Pathogen Interaction & Diagnostics, MESH: Microbial Sensitivity Tests, Multidisciplinary, MESH: Escherichia coli, Bacteriologie, Computational Biology, High-Throughput Nucleotide Sequencing, Bacteriology, Bacteriology, Host Pathogen Interaction & Diagnostics, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Host Pathogen Interactie & Diagnostiek, Anti-Bacterial Agents, Bacteriologie, Host Pathogen Interactie & Diagnostiek, MESH: Computational Biology
Abstract: Improvements in cost and speed of next generation sequencing (NGS) have provided a new pathway for delivering disease diagnosis, molecular typing, and detection of antimicrobial resistance (AMR). Numerous published methods and protocols exist, but a lack of harmonisation has hampered meaningful comparisons between results produced by different methods/protocols vital for global genomic diagnostics and surveillance. As an exemplar, this study evaluated the sensitivity and specificity of five well-established in-silico AMR detection software where the genotype results produced from running a panel of 436 Escherichia coli were compared to their AMR phenotypes, with the latter used as gold-standard. The pipelines exploited previously known genotype–phenotype associations. No significant differences in software performance were observed. As a consequence, efforts to harmonise AMR predictions from sequence data should focus on: (1) establishing universal minimum to assess performance thresholds (e.g. a control isolate panel, minimum sensitivity/specificity thresholds); (2) standardising AMR gene identifiers in reference databases and gene nomenclature; (3) producing consistent genotype/phenotype correlations. The study also revealed limitations of in-silico technology on detecting resistance to certain antimicrobials due to lack of specific fine-tuning options in bioinformatics tool or a lack of representation of resistance mechanisms in reference databases. Lastly, we noted user friendliness of tools was also an important consideration. Therefore, our recommendations are timely for widespread standardisation of bioinformatics for genomic diagnostics and surveillance globally.
Published: 2022

20. The AAA+ ATPase RavA and its binding partner ViaA modulate E. coli aminoglycoside sensitivity through interaction with the inner membrane

Author: Jan Felix, Ladislav Bumba, Clarissa Liesche, Angélique Fraudeau, Fabrice Rébeillé, Jessica Y. El Khoury, Karine Huard, Benoit Gallet, Christine Moriscot, Jean-Philippe Kleman, Yoan Duhoo, Matthew Jessop, Eaazhisai Kandiah, Frédéric Barras, Juliette Jouhet, Irina Gutsche, Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-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)-Université Grenoble Alpes (UGA), Institute of Microbiology of the Czech Academy of Sciences [Prague, Czech Republic] (MBU / CAS), Czech Academy of Sciences [Prague] (CAS), LIPID, Physiologie cellulaire et végétale (LPCV), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), Adaptation au stress et Métabolisme chez les entérobactéries - Stress adaptation and metabolism in enterobacteria (SAMe), Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Integrated Structural Biology Grenoble (ISBG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Nanobody Generation Platform de laboratoire AFMB (Marseille, France), Plateformes de Grenoble Instruct-ERIC center (ISBG, UAR 3518 CNRS-CEA-UGA-EMBL), LIPANG (Lipid analysis in Grenoble) hebergé par LPCV (UMR 5168 CNRS-CEA-INRAE-UGA), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010), European Project: 647784,H2020,ERC-2014-CoG,Chap4Resp(2015), European Project: 789385,RespViRALI, and European Project: LX22NPO5103
Subjects: MESH: Gentamicins, General Physics and Astronomy, MESH: Escherichia coli Proteins, General Biochemistry, Genetics and Molecular Biology, Membrane Lipids, Fumarates, MESH: Anti-Bacterial Agents, Escherichia coli, MESH: Adenosine Triphosphatases, MESH: Fumarates, Phospholipids, Adenosine Triphosphatases, MESH: Phospholipids, Multidisciplinary, MESH: Humans, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], MESH: Escherichia coli, Escherichia coli Proteins, MESH: Aminoglycosides, General Chemistry, Anti-Bacterial Agents, Oxygen, MESH: ATPases Associated with Diverse Cellular Activities, Aminoglycosides, ATPases Associated with Diverse Cellular Activities, MESH: Membrane Lipids, Gentamicins, MESH: Oxygen
Abstract: Enteric bacteria have to adapt to environmental stresses in the human gastrointestinal tract such as acid and nutrient stress, oxygen limitation and exposure to antibiotics. Membrane lipid composition has recently emerged as a key factor for stress adaptation. The E. coli ravA-viaA operon is essential for aminoglycoside bactericidal activity under anaerobiosis but its mechanism of action is unclear. Here we characterise the VWA domain-protein ViaA and its interaction with the AAA+ ATPase RavA, and find that both proteins localise at the inner cell membrane. We demonstrate that RavA and ViaA target specific phospholipids and subsequently identify their lipid-binding sites. We further show that mutations abolishing interaction with lipids restore induced changes in cell membrane morphology and lipid composition. Finally we reveal that these mutations render E. coli gentamicin-resistant under fumarate respiration conditions. Our work thus uncovers a ravA-viaA-based pathway which is mobilised in response to antibiotics under anaerobiosis and has a major impact on cell membrane regulation.
Published: 2022

21. Environmental contamination in a high-income country (France) by antibiotics, antibiotic-resistant bacteria, and antibiotic resistance genes: Status and possible causes

Author: Marisa Haenni, Christophe Dagot, Olivier Chesneau, Delphine Bibbal, Jérôme Labanowski, Michèle Vialette, Damien Bouchard, Fabrice Martin-Laurent, Louisiane Calsat, Sylvie Nazaret, Fabienne Petit, Anne-Marie Pourcher, Anne Togola, Morgane Bachelot, Edward Topp, Didier Hocquet, Laboratoire de Lyon [ANSES], Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Collection de l'Institut Pasteur (CIP), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Innovations Thérapeutiques et Résistances (InTheRes), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Chimie des Milieux et Matériaux de Poitiers (IC2MP), Université de Poitiers-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Anses ANMV (Anses ANMV), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Agroécologie [Dijon], Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Direction de l'Evaluation des Risques (DER), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Morphodynamique Continentale et Côtière (M2C), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Milieux Environnementaux, Transferts et Interactions dans les hydrosystèmes et les Sols (METIS), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Optimisation des procédés en Agriculture, Agroalimentaire et Environnement (UR OPAALE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), Agriculture and Agri-Food Canada, Saskatoon Research Centre, Agriculture and Agri-Food (AAFC), University of Western Ontario (UWO), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), This document was prepared thanks to the collective expert assessment, carried out by the Anses expert working group ‘Antimicrobial resistance and the environment’ (ANSES opinion 2016-SA-0252), chaired by Morgane Bachelot and whose active contributors are co-authors of this publication., Togola, Anne, Institut Pasteur [Paris], AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Agriculture and Agri-Food [Ottawa] (AAFC), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Agence nationale du médicament vétérinaire (ANMV), and École Pratique des Hautes Études (EPHE)
Subjects: [SDE] Environmental Sciences, MESH: Drug Resistance, Microbial, Antibiotic resistance, MESH: One Health, 010501 environmental sciences, Wastewater, 01 natural sciences, MESH: Waste Water, 03 medical and health sciences, Rivers, MESH: Anti-Bacterial Agents, Drug Resistance, Bacterial, Animals, GE1-350, One Health, 030304 developmental biology, 0105 earth and related environmental sciences, General Environmental Science, Environmental antibiotic concentrations, 0303 health sciences, Bacteria, Aquatic environment, [SDV.EE.IEO] Life Sciences [q-bio]/Ecology, environment/Symbiosis, 6. Clean water, Anti-Bacterial Agents, 3. Good health, Environmental sciences, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, Terrestrial environment, 13. Climate action, [SDE]Environmental Sciences, Organic waste product, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, [CHIM.OTHE]Chemical Sciences/Other, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract: This document was prepared thanks to the collective expert assessment, carried out by the Anses expert working group ‘Antimicrobial resistance and the environment’ (ANSES opinion 2016-SA-0252), chaired by Morgane Bachelot and whose active contributors are co-authors of this publication.; International audience; Antimicrobial resistance (AMR) is a major global public health concern, shared by a large number of human and animal health actors. Within the framework of a One Health approach, actions should be implemented in the environmental realm, as well as the human and animal realms. The Government of France commissioned a report to provide policy and decision makers with an evidential basis for recommending or taking future actions to mitigate AMR in the environment. We first examined the mechanisms that underlie the emergence and persistence of antimicrobial resistance in the environment. This report drew up an inventory of the contamination of aquatic and terrestrial environments by AMR and antibiotics, anticipating that the findings will be representative of some other high-income countries. Effluents of wastewater treatment plants were identified as the major source of contamination on French territory, with spreading of organic waste products as a more diffuse and incidental contamination of aquatic environments. A limitation of this review is the heterogeneity of available data in space and time, as well as the lack of data for certain sources.Comparing the French Measured Environmental Concentrations (MECs) with predicted no effect concentrations (PNECs), fluoroquinolones and trimethoprim were identified as representing high and medium risk of favoring the selection of resistant bacteria in treated wastewater and in the most contaminated rivers. All other antibiotic molecules analyzed (erythromycin, clarithromycin, azithromycin, tetracycline) were at low risk of resistance selection in those environments. However, the heterogeneity of the data available impairs their full exploitation. Consequently, we listed indicators to survey AMR and antibiotics in the environment and recommended the harmonization of sampling strategies and endpoints for analyses.Finally, the objectives and methods used for the present work could comprise a useful example for how national authorities of countries sharing common socio-geographic characteristics with France could seek to better understand and define the environmental dimension of AMR in their particular settings.
Published: 2022

22. Aeromonas: the multifaceted middleman in the One Health world

Author: Sandrine Baron, Brigitte Lamy, Olivier Barraud, Centre méditerranéen de médecine moléculaire (C3M), 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), Laboratoire de Bactériologie [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital Archet 2 [Nice] (CHU), Medical Research Council Centre for Molecular Bacteriology and Infection [Londres, Royaume-Uni] (MRC CMBI), Imperial College London, Laboratoire de Ploufragan-Plouzané-Niort [ANSES], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-OmégaHealth (ΩHealth), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), and Duborgel, Françoise
Subjects: Microbiology (medical), [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], MESH: Aeromonas, business.industry, [SDV.OT] Life Sciences [q-bio]/Other [q-bio.OT], Genetic transfer, MESH: One Health, Aquaculture, Biology, biology.organism_classification, Microbiology, Anti-Bacterial Agents, Biotechnology, Human health, Infectious Diseases, One Health, Aeromonas, MESH: Anti-Bacterial Agents, Animals, MESH: Aquaculture, business, Antibiotic resistance genes
Abstract: International audience; Aeromonas is at the interface of all the One Health components and represents an amazingly sound test case in the One Health approach, from economic loss in aquaculture tochallenges related to antibiotic-resistant bacteria selected from the environment. In human health, infections following leech therapy is an outstanding example of such One Health challenges. Aeromonads are not only ubiquitous environmental bacteria, able to rapidly colonize and cause opportunistic infections in humans and animals, they are also capable of promoting interactions and gene exchanges between the One Health components. This makes this genus a key amplifier of genetic transfer, especially of antibiotic resistance genes.
Published: 2022

23. Optimization of 1,2,4-Triazole-3-thiones toward Broad-Spectrum Metallo-β-lactamase Inhibitors Showing Potent Synergistic Activity on VIM- and NDM-1-Producing Clinical Isolates

Author: Alice Legru, Federica Verdirosa, Yen Vo-Hoang, Giusy Tassone, Filippo Vascon, Caitlyn A. Thomas, Filomena Sannio, Giuseppina Corsica, Manuela Benvenuti, Georges Feller, Rémi Coulon, Francesca Marcoccia, Savannah Rowane Devente, Ezeddine Bouajila, Catherine Piveteau, Florence Leroux, Rebecca Deprez-Poulain, Benoît Deprez, Patricia Licznar-Fajardo, Michael W. Crowder, Laura Cendron, Cecilia Pozzi, Stefano Mangani, Jean-Denis Docquier, Jean-François Hernandez, Laurent Gavara, Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Università degli Studi di Siena = University of Siena (UNISI), Università degli Studi di Padova = University of Padua (Unipd), Miami University [Ohio] (MU), Université de Liège, Médicaments et molécules pour agir sur les Systèmes Vivants - U 1177 (M2SV), 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, Hydrosciences Montpellier (HSM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: MESH: Microbial Sensitivity Tests, MESH: Humans, Inhibitors, [SDV]Life Sciences [q-bio], MESH: beta-Lactamases, Thiones, Microbial Sensitivity Tests, Metallo β-lactamase, beta-Lactamases, Anti-Bacterial Agents, Triazole-thione, Antibiotics, MESH: Anti-Bacterial Agents, Carbapenem resistant enterobacteriaceae, MESH: HeLa Cells, Drug Discovery, [CHIM]Chemical Sciences, Molecular Medicine, Humans, MESH: Thiones, beta-Lactamase Inhibitors, MESH: beta-Lactamase Inhibitors, HeLa Cells
Abstract: International audience; Metallo-β-lactamases (MBLs) contribute to the resistance of Gram-negative bacteria to carbapenems, last-resort antibiotics at hospital, and MBL inhibitors are urgently needed to preserve these important antibacterial drugs. Here, we describe a series of 1,2,4-triazole-3-thione-based inhibitors displaying an α-amino acid substituent, which amine was mono- or disubstituted by (hetero)aryl groups. Compounds disubstituted by certain nitrogen-containing heterocycles showed submicromolar activities against VIM-type enzymes and strong NDM-1 inhibition (Ki = 10-30 nM). Equilibrium dialysis, native mass spectrometry, isothermal calorimetry (ITC), and X-ray crystallography showed that the compounds inhibited both VIM-2 and NDM-1 at least partially by stripping the catalytic zinc ions. These inhibitors also displayed a very potent synergistic activity with meropenem (16- to 1000-fold minimum inhibitory concentration (MIC) reduction) against VIM-type- and NDM-1-producing ultraresistant clinical isolates, including Enterobacterales and Pseudomonas aeruginosa. Furthermore, selected compounds exhibited no or moderate toxicity toward HeLa cells, favorable absorption, distribution, metabolism, excretion (ADME) properties, and no or modest inhibition of several mammalian metalloenzymes.
Published: 2022

24. Fate of Sulfonamides and Tetracyclines in Meat during Pan Cooking

Author: Planche, Christelle, Chevolleau, Sylvie, Noguer-Meireles, Maria-Hélèna, Jouanin, Isabelle, Mompelat, Sophie, ratel, jérémy, Verdon, Eric, Engel, Erwan, Debrauwer, Laurent, Qualité des Produits Animaux (QuaPA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Fougères - ANSES, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), ANR-12-ALID-0004,SOMEAT,Sécurité sanitaire des viandes issues de l'agriculture biologique(2012), PLANCHE, Christelle, and Systèmes Alimentaires Durables - Sécurité sanitaire des viandes issues de l'agriculture biologique - - SOMEAT2012 - ANR-12-ALID-0004 - ALID - VALID
Subjects: radiolabeling, cooking, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, MESH: Heterocyclic Compounds, MESH: Tetracyclines, MESH: Sulfonamides, beef meat, tetracyclines, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, degradation products, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, sulfonamides, MESH: Anti-Bacterial Agents, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Although antimicrobials are generally found in trace amounts in meat, the human health risk they bear cannot be ignored. With the ultimate aim of making a better assessment of consumer exposure, this study explored the effects of pan cooking on sulfonamides and tetracyclines in meat. Screening of these antimicrobials in cooked meat was first performed by the European Union Reference Laboratory on the basis of HPLC-MS/MS analyses. A proof of concept approach using radiolabeling was then carried out on the most cooking-sensitive antimicrobial—sulfamethoxazole—to assess if a thermal degradation could explain the observed cooking losses. Degradation products were detected thanks to separation by HPLC and monitoring by online radioactivity detection. HPLC-Orbitrap HRMS analyses completed by 1D and 2D NMR experiments allowed the structural characterization of these degradation compounds. This study revealed that cooking could induce significant antimicrobial losses of up to 45% for sulfamethoxazole. Six potential degradation products of 14C-sulfamethoxazole were detected in cooked meat, and a thermal degradation pattern was proposed. This study highlights the importance of considering the cooking step in chemical risk assessment procedures and its impact on the level of chemical contaminants in meat and on the formation of potentially toxic breakdown compounds.
Published: 2022

25. Intestinal Bacteriophage Therapy: Looking for Optimal Efficacy

Author: Chloé Latour, Quentin Lamy-Besnier, François Javaudin, Laurent Debarbieux, Microbiotes, Hôtes, Antibiotiques et Résistances bactériennes (MiHAR) (MiHAR), Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Service des Urgences [CHU Nantes], Hôtel-Dieu de Nantes, Centre Hospitalier Centre Bretagne [Pontivy] (CHCB Pontivy), Bactériophage, bactérie, hôte - Bacteriophage, bacterium, host, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This research was supported by funding to L.D. from ANR-20-CE92-0048. Q.L.-B. is funded by École Doctorale FIRE-Program Bettencourt., We thank Pierre Chauvet for help with the illustrations and Patrick Lane (ScEYEnce Studios) for graphical enhancement., and ANR-20-CE92-0048,PhaStGut,Etude des mécanismes de la coexistence stable entre bactériophages et bactéries et de ses conséquences sur la fonction du microbiote intestinal(2020)
Subjects: Microbiology (medical), Epidemiology, medicine.drug_class, Antibiotics, Disease, Review, enteric pathogens, MESH: Phage Therapy, MESH: Gastrointestinal Microbiome, Microbiology, Bacteriophage, Animal model, MESH: Anti-Bacterial Agents, medicine, Animals, Humans, Bacteriophages, MESH: Animals, Phage Therapy, MESH: Bacteriophages, MESH: Humans, General Immunology and Microbiology, biology, Bacteria, Public Health, Environmental and Occupational Health, intestinal colonization, biology.organism_classification, Treatment efficacy, Anti-Bacterial Agents, Gastrointestinal Microbiome, MESH: Bacteria, Infectious Diseases, Bacteriophage Therapy, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Intestinal bacteria, gastrointestinal infection
Abstract: International audience; Several human intestinal microbiota studies suggest that bacteriophages, viruses infecting bacteria, play a role in gut homeostasis. Currently, bacteriophages are considered a tool to precisely engineer the intestinal microbiota, but they have also attracted considerable attention as a possible solution to fight against bacterial pathogens resistant to antibiotics. These two applications necessitate bacteriophages to reach and kill their bacterial target within the gut environment. Unfortunately, exploitable clinical data in this field are scarce. Here, we review the administration of bacteriophages to target intestinal bacteria in mammalian experimental models. While bacteriophage amplification in the gut was often confirmed, we found that in most studies, it had no significant impact on the load of the targeted bacteria. In particular, we observed that the outcome of bacteriophage treatments is linked to the behavior of the target bacteria toward each animal model. Treatment efficacy ranges from poor in asymptomatic intestinal carriage to high in intestinal disease. This broad range of efficacy underlines the difficulties to reach a consensus on the impact of bacteriophages in the gut and calls for deeper investigations of key parameters that influence the success of such interventions before launching clinical trials.
Published: 2021

26. Design of a Visual Interface for Comparing Antibiotics Using Rainbow Boxes

Author: Rosy TSOPRA, Shérazade Kinouani, Alain Venot, Marie-Christine Jaulent, Catherine Duclos, Jean-Baptiste Lamy, Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, and Université Paris 13 (UP13)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: MESH: Humans, Clinical Decision Support System, education, Usability, Visual analytics, MESH: Urinary Tract Infections, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Anti-Bacterial Agents, Antibiotic prescription, Physicians, MESH: Anti-Bacterial Agents, Urinary Tract Infections, Computer Graphics, Humans, MESH: Physicians, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Computer Graphics
Abstract: International audience; Non-optimal prescriptions of antibiotics have a negative impact on patients and population. Clinical practice guidelines are not always followed by doctors because the rationale of the recommendations is not always clear and can be difficult to understand. In this paper, we propose a new approach consisting in presenting the properties of antibiotics for allowing doctors to compare them and choose the most appropriate one. For that, we used and extended rainbow boxes, a new technique for overlapping set visualization. We tested our approach on 11 clinical situations related to urinary infections, and assessed the simplicity, the interest and utility with 11 doctors. 10 of them found that this approach was interesting and useful in clinical practice. Further studies are needed to confirm this preliminary work.
Published: 2021

27. Interplay between Bacterial Clones and Plasmids in the Spread of Antibiotic Resistance Genes in the Gut: Lessons from a Temporal Study in Veal Calves

Author: Jean-Yves Madec, Méril Massot, Bénédicte Condamine, Marisa Haenni, Pierre Châtre, Olivier Clermont, Véronique Métayer, Erick Denamur, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Unité Antibiorésistance et Virulence Bactériennes (AVB), Laboratoire de Lyon [ANSES], Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Lyon-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), INTERBEV (Protocol N° SECU-15-31), La Fondation pour la Recherche Médicale to M.M. (grant number FDM20150633309), La Fondation pour la Recherche Médicale to E.D. (équipe FRM 2016, grant number DEQ20161136698), ANR-16-JPEC-0004,TransComp-ESC-R,Genomic approach to transmission and compartmentalization of extended-spectrum cephalosporin resistance in Enterobacteriaceae from animals and humans(2016), and European Project: 773830, H2020-SFS-2017-1 ,One Health EJP(2018)
Subjects: clone (Java method), Context (language use), Biology, medicine.disease_cause, Applied Microbiology and Biotechnology, beta-Lactamases, Microbiology, 03 medical and health sciences, Plasmid, MESH: Plasmids, plasmid, MESH: Anti-Bacterial Agents, MESH: Drug Resistance, Bacterial, Drug Resistance, Bacterial, Escherichia coli, medicine, Animals, Colonization, Gene, Genotyping, 030304 developmental biology, clone, MESH: Red Meat, 2. Zero hunger, 0303 health sciences, Ecology, MESH: Escherichia coli, Public and Environmental Health Microbiology, 030306 microbiology, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Anti-Bacterial Agents, Clone Cells, Red Meat, Carriage, ESBL, Cattle, veal calves, Plasmids, Food Science, Biotechnology
Abstract: International audience; Intestinal carriage of extended spectrum b-lactamase (ESBL)-producing Escherichia coli is a frequent, increasing, and worrying phenomenon, but little is known about the molecular scenario and the evolutionary forces at play. We screened 45 veal calves, known to have high prevalence of carriage, for ESBL-producing E. coli on 514 rectal swabs (one randomly selected colony per sample) collected over 6 months. We characterized the bacterial clones and plasmids carrying bla ESBL genes with a combination of genotyping methods, whole genome sequencing, and conjugation assays. One hundred and seventy-three ESBL-producing E. coli isolates [bla CTX-M-1 (64.7%), bla CTX-M-14 (33.5%), or bla CTX-M-15 (1.8%)] were detected, belonging to 32 bacterial clones, mostly of phylogroup A. Calves were colonized successively by different clones with a trend in decreasing carriage. The persistence of a clone in a farm was significantly associated with the number of calves colonized. Despite a high diversity of E. coli clones and bla CTX-M-carrying plasmids, few bla CTX-M gene/plasmid/chromosomal background combinations dominated, due to (i) efficient colonization of bacterial clones and/or (ii) successful plasmid spread in various bacterial clones. The scenario "clone versus plasmid spread" depended on the farm. Thus, epistatic interactions between resistance genes, plasmids, and bacterial clones contribute to optimize fitness in specific environments. IMPORTANCE The gut microbiota is the epicenter of the emergence of resistance. Considerable amount of knowledge on the molecular mechanisms of resistance has been accumulated, but the ecological and evolutionary forces at play in nature are less studied. In this context, we performed a field work on temporal intestinal carriage of extended spectrum b-lactamase (ESBL)-producing Escherichia coli in veal farms. Veal calves are animals with one of the highest levels of ESBL producing E. coli fecal carriage, due to early high antibiotic exposure. We were able to show that calves were colonized successively by different ESBL-producing E. coli clones, and that two main scenarios were at play in the spread of bla CTX-M genes among calves: efficient colonization of several calves by a few bacterial clones and successful plasmid spread in various bacterial clones. Such knowledge should help develop new strategies to fight the emergence of antibiotic-resistance.
Published: 2021

28. Les urgences infectieuses en urologie

Author: E, Seizilles de Mazancourt, M, Vallée, A, Sotto, C, Le Goux, A, Dihn, A, Therby, R, Boissier, P H, Savoie, J A, Long, F, Bruyere, Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Virulence bactérienne et maladies infectieuses (VBMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service d'urologie [CH René Dubos Pontoise], Centre Hospitalier René Dubos [Pontoise], CIT-IT Garches, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Versailles André Mignot (CHV), Aix Marseille Université (AMU), Assistance Publique - Hôpitaux de Marseille (APHM), Hopital d'instruction des armées Sainte-Anne [Toulon] (HIA), Service d'urologie [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Service d'urologie [Tours], and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau
Subjects: Male, Pyélonéphrite, Urology, MESH: Urinary Tract Infections, Urgence, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Infection urinaire, MESH: Emergencies, MESH: Anti-Bacterial Agents, Humans, MESH: Ecosystem, Infections urinaires associées aux soins, Ecosystem, Aged, Infection urinaire masculine, MESH: Aged, Bacterial prostatitis, Urinary tract infection, MESH: Humans, Pyelonephritis, Candidurie, MESH: Urology, MESH: Male, Anti-Bacterial Agents, Urosepsis, Sepsis urinaire, Health related urinary infection, Urinary Tract Infections, Emergency, Candiduria, Emergencies
Abstract: International audience; Objective: To report the nature, diagnosis and therapeutic strategy of infectious emergencies in urology.Material and methods: Bibliographic research from Pubmed, Embase, and Google scholar in July 2021. A synthesis of the guidelines of national infectious diseases societies.Results: Urosepsis and complicated urinary tract infection have a standardized definition. Diagnosis and therapeutic strategy are presented for upper tract urinary infection, male urinary infection, healthcare associated urinary infection, symptomatic canduria and urinary infections of the elderly. Appropriate antibiotherapy should be tailored to the degree of severity, bacterial ecosystem, patient characteristics et localization of the infection.Conclusion: Urinary infections can be critical and require immediate care. Knowledge of the guidelines and of appropriate diagnosis and therapeutics strategy improve care which should be rapidly applied, and collegial.; ObjectifRapporter la nature, les stratégies diagnostiques et thérapeutiques des urgences infectieuses en urologie.Matériel et méthodeRecherche bibliographique à partir de Pubmed, Embase et Google Scholar en juillet 2021. Synthèse des recommandations nationales du comité d’infectiologie de l’AFU (CIAFU) et de la Société de Pathologies Infectieuses de Langue Française (SPILF).RésultatsL’urosepsis et sepsis urinaire grave répondent à des critères diagnostiques stricts. La prise en charge infectieuse diagnostique et thérapeutique des pyélonéphrites graves, infections urinaires masculines graves, infections urinaires associées aux soins, candiduries symptomatiques et infections urinaires chez la personne âgée sont décrites. L’antibiothérapie doit être adaptée à la gravité, l’écologie bactérienne, aux particularités du patient et au site d’infection.ConclusionLes infections urinaires peuvent être graves et nécessitent une prise en charge en urgence. La connaissance des recommandations et des stratégies diagnostiques et thérapeutiques adaptées aux diverses présentations permet une optimisation de la prise en charge qui doit être la plus rapide possible, et collégiale.
Published: 2021

29. Voatriafricanines A and B, Trimeric Vobasine-Aspidosperma-Aspidosperma Alkaloids from Voacanga africana

Author: Jérôme Vanheuverzwijn, Franck Meyer, Augustin Ephrem Nkengfack, Véronique Fontaine, Jean-François Gallard, Pierre Le Pogam, Erwan Poupon, Mehdi A. Beniddir, Karine Leblanc, Pierre Mkounga, Zhiyu Zhou, Somia Rharrabti, Hugues Fouotsa, Guillaume Bernadat, Alain Meli Lannang, Biomolécules : Conception, Isolement, Synthèse (BioCIS), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-CY Cergy Paris Université (CY), UniversitÃ© de YaoundÃ© I - UY1 (CAMEROON), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Transfrontalière BioEcoAgro - UMR 1158 (BioEcoAgro), Université d'Artois (UA)-Université de Liège-Université de Picardie Jules Verne (UPJV)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Faculté de Pharmacie [Bruxelles] (ULB), and Université libre de Bruxelles (ULB)
Subjects: medicine.drug_class, Stereochemistry, Monoterpene, MESH: Molecular Structure, Pharmaceutical Science, MESH: Voacanga, 010402 general chemistry, Antimycobacterial, 01 natural sciences, Homonuclear molecule, Analytical Chemistry, MESH: Anti-Bacterial Agents, Immunologie, Drug Discovery, medicine, [CHIM]Chemical Sciences, MESH: Phytochemicals, Pharmacology, biology, 010405 organic chemistry, Hydrogen bond, Chemistry, Organic Chemistry, Biologie moléculaire, MESH: Cameroon, biology.organism_classification, 0104 chemical sciences, MESH: Indole Alkaloids, Voacanga africana, Complementary and alternative medicine, Heteronuclear molecule, Intramolecular force, Aspidosperma, Molecular Medicine, Biologie cellulaire, Microbiologie et protistologie [bacteriol.virolog.mycolog.], MESH: Plant Bark
Abstract: International audience; Voatriafricanines A and B (1 and 2), the first examples of vobasine-aspidosperma-aspidosperma monoterpene trisindole alkaloids, were isolated from the stem barks of Voacanga africana, guided by a molecular networking strategy. Their structures, including absolute configurations, were elucidated by spectroscopic methods and ECD calculations. Compounds 1 and 2 possess intramolecular hydrogen bonding, sufficiently robust to transfer homonuclear and heteronuclear magnetizations. Compound 1 exhibited potent antimycobacterial activity with no discernible cytotoxic activity.
Published: 2021

30. Microbiome-pathogen interactions drive epidemiological dynamics of antibiotic resistance: A modeling study applied to nosocomial pathogen control

Author: Smith, DR, Temime, L, Opatowski, L, Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Paris Cité (UPCité), The work was supported directly by internal resources from the French National Institute for Health and Medical Research, the Institut Pasteur, the Conservatoire National des Arts et Métiers, and the University of Versailles–Saint-Quentin-en-Yvelines / University of Paris-Saclay. This study received funding from the French Government’s ‘Investissement d’Avenir’ program, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (Grant ANR-10-LABX-62- IBEID). DS is supported by a Canadian Institutes of Health Research Doctoral Foreign Study Award (Funding Reference Number 164263) and all authors are supported by the French government through its National Research Agency project SPHINX-17-CE36-0008-01., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-17-CE36-0008,SPHINx,Diffusion de pathogènes au sein des réseaux de soins : une étude de modélisation(2017), Bertram, Marie-Liesse, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, and Diffusion de pathogènes au sein des réseaux de soins : une étude de modélisation - - SPHINx2017 - ANR-17-CE36-0008 - AAPG2017 - VALID
Subjects: MESH: Drug Resistance, Microbial, QH301-705.5, Science, global health, antibiotics, K. pneumoniae, MESH: Anti-Bacterial Agents, microbiota, Humans, MESH: Microbiota, human, Biology (General), MESH: Models, Theoretical, Cross Infection, MESH: Humans, Bacteria, E. coli, MESH: Cross Infection, Drug Resistance, Microbial, Models, Theoretical, S. aureus, within-host interactions, Anti-Bacterial Agents, MESH: Bacteria, Epidemiology and Global Health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Medicine, epidemiology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Other, C. difficile, ecology, Research Article
Abstract: International audience; The human microbiome can protect against colonization with pathogenic antibiotic-resistant bacteria (ARB), but its impacts on the spread of antibiotic resistance are poorly understood. We propose a mathematical modeling framework for ARB epidemiology formalizing within-host ARB-microbiome competition, and impacts of antibiotic consumption on microbiome function. Applied to the healthcare setting, we demonstrate a trade-off whereby antibiotics simultaneously clear bacterial pathogens and increase host susceptibility to their colonization, and compare this framework with a traditional strain-based approach. At the population level, microbiome interactions drive ARB incidence, but not resistance rates, reflecting distinct epidemiological relevance of different forces of competition. Simulating a range of public health interventions (contact precautions, antibiotic stewardship, microbiome recovery therapy) and pathogens ( Clostridioides difficile , methicillin-resistant Staphylococcus aureus , multidrug-resistant Enterobacteriaceae) highlights how species-specific within-host ecological interactions drive intervention efficacy. We find limited impact of contact precautions for Enterobacteriaceae prevention, and a promising role for microbiome-targeted interventions to limit ARB spread.
Published: 2021

31. Generating High-Resolution Hi-C Contact Maps of Bacteria

Author: Charlotte Cockram, Agnès Thierry, Régulation spatiale des Génomes - Spatial Regulation of Genomes, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This research was supported by funding to Romain Koszul from the Agence Nationale pour la Recherche (HiResBac ANR-15-CE11-0023-03) and from the European Research Council under the Horizon 2020 program (ERC grant agreement: 771813)., We thank Romain Koszul and the members of the RSG lab for insightful discussions regarding the development of this protocol., ANR-15-CE11-0023,HiResBaCS,Structure des chromosomes bactériens revélée a haute résolution(2015), and European Project: 771813,ERC-2017-COG,SynarchiC(2018)
Subjects: Chromosome conformation capture, biology, Bacteria, Computer science, [SDV]Life Sciences [q-bio], Resolution (electron density), High resolution, Computational biology, Bacterial genome size, biology.organism_classification, Genome organization, MESH: Gram-Positive Bacteria, MESH: Bacteria, MESH: Software, Chromosome (genetic algorithm), Hi-C, MESH: Anti-Bacterial Agents, MESH: Gram-Negative Bacteria, MESH: Chromosomes, Prokaryotes, 3C, Genomic organization
Abstract: International audience; During the past decade, Chromosome Conformation Capture (3C/Hi-C)-based methods have been used to probe the 3D structure and organization of bacterial genomes, revealing fundamental aspects of chromosome dynamics. However, the current protocols are expensive, inefficient, and limited in their resolution. Here we present a simple, cost-effective Hi-C approach that is readily applicable to a range of Gram-positive and Gram-negative bacteria.
Published: 2021

32. A Web Interface for Antibiotic Prescription Recommendations in Primary Care: User-Centered Design Approach

Author: Ronni Madar, Adrien Ugon, Damir Ivanković, Rosy Tsopra, Université Sorbonne Paris Nord, ESIEE Paris, Systèmes Electroniques (SYEL), LIP6, Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Amsterdam [Amsterdam] (UvA), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École pratique des hautes études (EPHE), and TSOPRA, Rosy
Subjects: 020205 medical informatics, [SDV]Life Sciences [q-bio], 02 engineering and technology, 0302 clinical medicine, antibiotic, 0202 electrical engineering, electronic engineering, information engineering, Medicine, 030212 general & internal medicine, Practice Patterns, Physicians', Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], usability, MESH: User-Centered Design, clinical decision support system, Prescriptions, Medical emergency, Public aspects of medicine, RA1-1270, User interface, clinical practice guidelines, MESH: Prescriptions, medicine.medical_specialty, Computer applications to medicine. Medical informatics, education, R858-859.7, Health Informatics, [INFO] Computer Science [cs], Clinical decision support system, MESH: Primary Health Care, Likert scale, 03 medical and health sciences, primary care, MESH: Anti-Bacterial Agents, Humans, [INFO]Computer Science [cs], visualization, User-centered design, Original Paper, MESH: Humans, Primary Health Care, business.industry, Public health, Usability, medicine.disease, Antibiotic misuse, Decision Support Systems, Clinical, Readability, MESH: Practice Patterns, Physicians', MESH: Decision Support Systems, Clinical, business, User-Centered Design
Abstract: Background Antibiotic misuse is a serious public health problem worldwide. National health authorities release clinical practice guidelines (CPGs) to guide general practitioners (GPs) in their choice of antibiotics. However, despite the large-scale dissemination of CPGs, GPs continue to prescribe antibiotics that are not recommended as first-line treatments. This nonadherence to recommendations may be due to GPs misunderstanding the CPGs. A web interface displaying antibiotic prescription recommendations and their justifications could help to improve the comprehensibility and readability of CPGs, thereby increasing the adoption of recommendations regarding antibiotic treatment. Objective This study aims to design and evaluate a web interface for antibiotic prescription displaying both the recommended antibiotics and their justifications in the form of antibiotic properties. Methods A web interface was designed according to the same principles as e-commerce interfaces and was assessed by 117 GPs. These GPs were asked to answer 17 questions relating to the usefulness, user-friendliness, and comprehensibility and readability of the interface, and their satisfaction with it. Responses were recorded on a 4-point Likert scale (ranging from “absolutely disagree” to “absolutely agree”). At the end of the evaluation, the GPs were allowed to provide optional, additional free comments. Results The antibiotic prescription web interface consists of three main sections: a clinical summary section, a filter section, and a recommended antibiotics section. The majority of GPs appreciated the clinical summary (90/117, 76.9%) and filter (98/117, 83.8%) sections, whereas 48.7% (57/117) of them reported difficulty reading some of the icons in the recommended antibiotics section. Overall, 82.9% (97/117) of GPs found the display of drug properties useful, and 65.8% (77/117) reported that the web interface improved their understanding of CPG recommendations. Conclusions The web interface displaying antibiotic recommendations and their properties can help doctors understand the rationale underlying CPG recommendations regarding antibiotic treatment, but further improvements are required before its implementation into a clinical decision support system.
Published: 2021

33. Highly Resistant Cholera Outbreak Strain in Zimbabwe

Author: Andrew Tarupiwa, Anthony M. Smith, Sekesai Mtapuri-Zinyowera, François-Xavier Weill, Portia Manangazira, Tapfumanei Mashe, Prosper Chonzi, Daryl Domman, Isaac K. Phiri, Masindi Ramudzulu, Elisabeth Njamkepo, Kudzai P.E. Masunda, Ministry of Health and Child Care [Harare], The University of New Mexico [Albuquerque], Beatrice Road Infectious Diseases Hospital [Harare, Zimbabwé], Bactéries pathogènes entériques (BPE), Institut Pasteur [Paris] (IP), National Institute for Communicable Diseases [Johannesburg] (NICD), and Institut Pasteur [Paris]
Subjects: DNA, Bacterial, Zimbabwe, Drug resistance, 030204 cardiovascular system & hematology, MESH: Genome, Bacterial, medicine.disease_cause, Genome, Cholera outbreak, Disease Outbreaks, 03 medical and health sciences, 0302 clinical medicine, Cholera, MESH: Cholera, Phylogenetics, MESH: Anti-Bacterial Agents, Drug Resistance, Bacterial, MESH: Drug Resistance, Bacterial, medicine, Humans, 030212 general & internal medicine, MESH: Disease Outbreaks, MESH: Phylogeny, Vibrio cholerae, Phylogeny, ComputingMilieux_MISCELLANEOUS, MESH: Humans, business.industry, Strain (biology), Outbreak, General Medicine, MESH: DNA, Bacterial, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Virology, Anti-Bacterial Agents, 3. Good health, MESH: Zimbabwe, business, Genome, Bacterial, MESH: Vibrio cholerae
Abstract: Highly Resistant Cholera Outbreak Strain in Zimbabwe Whole genomes of 11 Vibrio cholerae O1 isolates from the 2018–2019 outbreak in Zimbabwe were sequenced to investigate the determinants of antimi...
Published: 2020

34. Whole genome sequencing reveals resemblance between ESBL-producing and carbapenem resistant Klebsiella pneumoniae isolates from Austrian rivers and clinical isolates from hospitals

Author: Rainer Hartl, Heidrun Kerschner, Burkhard Springer, Sieglinde Sorschag, Franz Allerberger, Sarah Lepuschitz, Norbert Inreiter, Simone Schill, Steliana Huhulescu, Sylvain Brisse, Werner Ruppitsch, Robert L. Mach, Anna Stoeger, Shiva Pekard-Amenitsch, Austrian Agency for Health and Food Safety (AGES), Vienna University of Technology (TU Wien), Ordensklinikum Linz Elisabethinen, Klinikum Klagenfurt am Wörthersee, Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris] (IP), Universität für Bodenkultur Wien = University of Natural Resources and Life [Vienne, Autriche] (BOKU), This work was partially funded by a grant to S.L. by the Austrian Society for Antimicrobial Chemotherapy (ÖGACH). Part of the sequencing-work was supported financially by the MedVetKlebs project, a component of the One Health European Joint Programme, which has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No 773830., We thank the team of curators of the Institut Pasteur MLST and whole genome MLST databases for curating the data and making them publicly available at http://bigsdb.pasteur.fr/., European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health)(2018), Institut Pasteur [Paris], University of Natural Resources and Life Sciences (BOKU), and European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health EJP)(2018)
Subjects: Veterinary medicine, 010504 meteorology & atmospheric sciences, MESH: beta-Lactamases, Pilot Projects, Drug resistance, 010501 environmental sciences, 01 natural sciences, Surface-water, MESH: Carbapenems, Drug Resistance, Multiple, Bacterial, MESH: Bacterial Proteins, Waste Management and Disposal, Antiinfective agent, Surveillance, Multiresistance Anthropogenic pollution Surface-water Surveillance Whole-genome sequencing, MESH: Hospitals, Pollution, Hospitals, 6. Clean water, Subtyping, Anti-Bacterial Agents, 3. Good health, MESH: Multilocus Sequence Typing, Austria, MESH: Whole Genome Sequencing, Environmental Engineering, Anthropogenic pollution, Locus (genetics), [SDV.BID]Life Sciences [q-bio]/Biodiversity, Biology, beta-Lactamases, MESH: Rivers, Antibiotic resistance, Bacterial Proteins, Rivers, MESH: Anti-Bacterial Agents, Environmental Chemistry, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Typing, Multiresistance, 0105 earth and related environmental sciences, Whole genome sequencing, Whole-genome sequencing, Bacteria, Whole Genome Sequencing, MESH: Drug Resistance, Multiple, Bacterial, MESH: Pilot Projects, Multiple drug resistance, MESH: Bacteria, Carbapenems, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Austria, Multilocus Sequence Typing
Abstract: International audience; In 2016, the Austrian Agency for Health and Food Safety started a pilot project to investigate antimicrobial resistance in surface water. Here we report on the characterisation of carbapenem resistant and ESBL-producing K. pneumoniae isolates from Austrian river water samples compared to 95 clinical isolates recently obtained in Austrian hospitals. Ten water samples were taken from four main rivers, collected upstream and downstream of major cities in 2016. For subtyping and comparison, public core genome multi locus sequence typing (cgMLST) schemes were used. The presence of AMR genes, virulence genes and plasmids was extracted from whole genome sequence (WGS) data. In total three ESBL-producing strains and two carbapenem resistant strains were isolated. WGS based comparison of these five water isolates to 95 clinical isolates identified three clusters. Cluster 1 (ST11) and cluster 2 (ST985) consisted of doublets of carbapenem resistant strains (one water and one clinical isolate each). Cluster 3 (ST405) consisted of three ESBL-producing strains isolated from one water sample and two clinical specimens. The cities, in which patient isolates of cluster 2 and 3 were collected, were in concordance with the water sampling locations downstream from these cities. The genetic concordance between isolates from river water samples and patient isolates raises concerns regarding the release of wastewater treatment plant effluents into surface water. From a public health perspective these findings demand attention and strategies are required to minimize the spread of multiresistant strains to the environment.
Published: 2019

35. Pertussis epidemiology in Tunisian infants and children and characterization of Bordetella pertussis isolates: results of a 9-year surveillance study, 2007 to 2016

Author: Sylvain Brisse, Ikram Ben Fraj, Amel Kechrid, Nicole Guiso, Hanen Smaoui, Sophie Guillot, Valérie Bouchez, Université de Tunis El Manar (UTM), Béchir Hamza Children's Hospital, Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris], Centre National de Référence de la Coqueluche et autres bordetelloses (CNR), This work received no specific grant from any funding agency. The French National Reference Center is supported financially by Institut Pasteur and Public Health France., and Institut Pasteur [Paris] (IP)
Subjects: Male, 0301 basic medicine, Bordetella pertussis, Whooping Cough, Bordetella, [SDV]Life Sciences [q-bio], Polymerase Chain Reaction, MESH: Bordetella pertussis, MESH: Genotype, Nasopharynx, MESH: Child, Genotype, MESH: Cough, Medicine, Prospective Studies, Child, Bordetella holmesii, MESH: Immunoblotting, biology, pertussis, Incidence (epidemiology), MESH: Infant, Newborn, MESH: Bronchi, General Medicine, MESH: Whooping Cough, MESH: Infant, Anti-Bacterial Agents, 3. Good health, Trachea, Phenotype, Child, Preschool, surveillance, Female, epidemiology, Pertactin, MESH: Tunisia, Microbiology (medical), Tunisia, Immunoblotting, 030106 microbiology, Bronchi, MESH: Phenotype, Microbiology, Bordetella parapertussis, MESH: Cyanosis, 03 medical and health sciences, MESH: Anti-Bacterial Agents, Humans, Genotyping, Cyanosis, MESH: Humans, business.industry, MESH: Child, Preschool, Infant, Newborn, Infant, MESH: Polymerase Chain Reaction, biology.organism_classification, MESH: Male, MESH: Nasopharynx, MESH: Prospective Studies, 030104 developmental biology, Cough, genotyping, business, MESH: Female, MESH: Trachea
Abstract: International audience; Purpose. Pertussis remains a public health concern in most countries. Our study aimed to prospectively explore the epidemiology of pertussis in the Tunis area of Tunisia between 2007 and 2016, and to characterize the virulence-associated genes of the collected Bordetella pertussis isolates.Methodology. Infants and children hospitalized at the Children’s Hospital of Tunis, Tunisia, between 2007 and 2016 for suspicion of pertussis were enrolled in the study. Culture and real-time PCR (qPCR) assays targeting IS481, IS1001, recA, H-IS1001 and ptxP were used to confirm the pertussis diagnosis. Phenotypic and genotypic characterization of recovered isolates was performed.Results/Key findings. A total of 1844 children were included in the study. Overall, 306 children (16.6 %) with Bordetella infection were confirmed by qPCR. Among them, 265 (86.6 %) were confirmed as having B. pertussis (IS481+, ptxP+, H-IS1001−), 18 (5.9 %) as having Bordetella parapertussis (IS481−, IS1001+) and 11 (3.6 %) as having Bordetella spp. (IS481+, ptxP−, H-IS1001−). No Bordetella holmesii (IS481+, IS1001−, H-IS1001+) was identified. The estimated pertussis incidence in the Tunis area was 134/100 000 in children aged less than 5 years. Two epidemic peaks were observed in 2009 and 2014. Ten B. pertussis isolates were cultured and characterized. Deficiency in pertactin expression was not observed, and genotyping of the isolates revealed a predominant allelic profile: ptxP3-ptxA1-prn2-fim2-1-fim3-2.Conclusion. This study demonstrated that pertussis is still present as a cyclical disease in Tunisia, despite high primo-vaccination coverage with a pertussis whole-cell vaccine. The predominant genotype of Tunisian B. pertussis isolates is similar to isolates circulating in countries using the acellular vaccine.
Published: 2019

36. Population pharmacokinetics of daptomycin in patients with bone and joint infection: minimal effect of rifampicin co-administration and confirmation of a sex difference

Author: Garreau, Romain, Bricca, Romain, Gagnieu, Marie-Claude, Roux, Sandrine, Conrad, Anne, Bourguignon, Laurent, Ferry, Tristan, Goutelle, Sylvain, Valour, Florent, Perpoint, Thomas, Miailhes, Patrick, Ader, Florence, Becker, Agathe, Triffault-Fillit, Claire, Pouderoux, Cécile, Benech, Nicolas, Chauvelot, Pierre, Perry, Marielle, Daoud, Fatiha, Lippman, Johanna, Braun, Evelyne, Chidiac, Christian, Servien, Elvire, Lustig, Sébastien, Batailler, Cécile, Gunst, Stanislas, Schmidt, Axel, Malatray, Matthieu, Sappey-Marinier, Elliot, Fessy, Michel-Henry, Viste, Anthony, Besse, Jean-Luc, Chaudier, Philippe, Louboutin, Lucie, Ode, Quentin, van Haecke, Adrien, Mercier, Marcelle, Belgaid, Vincent, Walch, Arnaud, Martres, Sébastien, Trouillet, Franck, Barrey, Cédric, Mojallal, Ali, Brosset, Sophie, Hanriat, Camille, Person, Hélène, Sigaux, Nicolas, Céruse, Philippe, Fuchsmann, Carine, Aubrun, Frédéric, Dziadzko, Mikhail, Macabéo, Caroline, Laurent, Frederic, Beraud, Laetitia, Roussel-Gaillard, Tiphaine, Dupieux, Céline, Kolenda, Camille, Josse, Jérôme, Brevet, Marie, Trecourt, Alexis, Craighero, Fabien, Boussel, Loic, Pialat, Jean-Baptiste, Morelec, Isabelle, Tod, Michel, Mabrut, Eugénie, Hospices Civils de Lyon (HCL), Lyon Bone and Joint Infection Study Group (BJI), Hôpital Nord-Ouest de Villefranche-sur-Saône, 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, Institut des Sciences Pharmaceutiques et Biologiques (ISPB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, 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 (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), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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 Claude Bernard Lyon 1 (UCBL)
Subjects: Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Population, MESH: Daptomycin, 03 medical and health sciences, 0302 clinical medicine, Daptomycin, Pharmacokinetics, MESH: Drug Monitoring, Internal medicine, MESH: Anti-Bacterial Agents, medicine, polycyclic compounds, Humans, Pharmacology (medical), 030212 general & internal medicine, Dosing, education, Pharmacology, Volume of distribution, Sex Characteristics, education.field_of_study, MESH: Humans, medicine.diagnostic_test, business.industry, Drug interaction, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, bacterial infections and mycoses, MESH: Rifampin, MESH: Male, Anti-Bacterial Agents, Infectious Diseases, Therapeutic drug monitoring, Female, Drug Monitoring, Rifampin, business, MESH: Female, Rifampicin, medicine.drug, MESH: Sex Characteristics
Abstract: Background Daptomycin is increasingly used in the treatment of bone and joint infection (BJI), but its pharmacokinetics (PK) and dosage requirements have not been thoroughly investigated in this indication. Daptomycin may be co-administered with rifampicin, which raises questions about a potential drug interaction. Objectives To investigate the population PK and dosage requirements of daptomycin in patients with BJI, and examine the influence of rifampicin co-administration. Methods A population approach was used to analyse PK data from patients who received daptomycin in our regional reference for BJI. We examined the influence of available covariates, including rifampicin co-administration on daptomycin PK. Simulations performed with the final model investigated the influence of dosages and covariates on PTA for both efficacy and safety. Results A total of 1303 daptomycin concentrations from 183 patients were analysed. A two-compartment model best described the data. Significant intra-individual variability was observed. Daptomycin clearance was influenced by renal function and sex, with females having a 26% lower typical clearance than males. Central volume of distribution (V1) was influenced by body weight, age, sex and rifampicin co-administration. Typical V1 was 11% lower in patients who were co-administered rifampicin. In PK/PD simulations, sex influenced the probability of AUC24/MIC target attainment, while rifampicin had a marginal effect. Conclusions A daptomycin dosage of 8 mg/kg/24 h in women and 10 mg/kg/24 h in men should optimize efficacy but may lead to excessive trough concentrations in many patients, especially in women. Therapeutic drug monitoring appears necessary for precision dosing of daptomycin.
Published: 2021

37. Contribution of Nanomaterials to the Development of Electrochemical Aptasensors for the Detection of Antimicrobial Residues in Food Products

Author: Gaudin, Valérie, Laboratoire de Fougères - ANSES, and Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)
Subjects: Veterinary drugs, Antibiotique, Food safety, Détection, lcsh:Biochemistry, Aaptacapteur électrochimique, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, MESH: Anti-Bacterial Agents, [SDV.IDA]Life Sciences [q-bio]/Food engineering, antimicrobial residues, Nanotechnology, lcsh:QD415-436, Nanotechnologie, MESH: Nanotechnology, Sécurité des aliments, nanomaterials, MESH: Optical Imaging, Antibiotic, Electrochemical aptasensor, Médicament vétérinaire, aptasensors, Residues, electrochemical, Nanomaterial, Analyse, food products, Detection, Antimicrobial, Antimicrobien, Résidus, Nanomatériau, Analysis, MESH: Biosensing Techniques
Abstract: International audience; The detection of antimicrobial residues in food products of animal origin is of utmost importance. Indeed antimicrobial residues could be present in animal derived food products because of animal treatments for curative purposes or from illegal use. The usual screening methods to detect antimicrobial residues in food are microbiological, immunological or physico-chemical methods. The development of biosensors to propose sensitive, cheap and quick alternatives to classical methods is constantly increasing. Aptasensors are one of the major trends proposed in the literature, in parallel with the development of immunosensors based on antibodies. The characteristics of electrochemical sensors (i.e., low cost, miniaturization, and portable instrumentation) make them very good candidates to develop screening methods for antimicrobial residues in food products. This review will focus on the recent advances in the development of electrochemical aptasensors for the detection of antimicrobial residues in food products. The contribution of nanomaterials to improve the performance characteristics of electrochemical aptasensors (e.g., Sensitivity, easiness, stability) in the last ten years, as well as signal amplification techniques will be highlighted.
Published: 2021

38. Immediate flare-up–like reaction of skin tests to betalactams with lymphangitis during drug provocation test

Author: Anca Mirela Chiriac, Maria De Filippo, Pascal Demoly, Jean-Luc Bourrain, Omar Ali Al Ali, Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Fondazione IRCCS Policlinico San Matteo [Pavia], Università di Pavia, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM), CCSD, Accord Elsevier, Università degli Studi di Pavia = University of Pavia (UNIPV), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Drug, MESH: Drug Hypersensitivity, medicine.medical_specialty, media_common.quotation_subject, MESH: Pharmaceutical Preparations, Provocation test, Lymphangitis, beta-Lactams, Beta-lactam, Drug Hypersensitivity, 030207 dermatology & venereal diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, MESH: Skin Tests, MESH: beta-Lactams, MESH: Anti-Bacterial Agents, Immunology and Allergy, Flare up, Medicine, Humans, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, ComputingMilieux_MISCELLANEOUS, media_common, Skin Tests, MESH: Humans, business.industry, MESH: Lymphangitis, medicine.disease, Dermatology, 3. Good health, Anti-Bacterial Agents, 030228 respiratory system, chemistry, Pharmaceutical Preparations, business, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology
Abstract: International audience; No abstract available
Published: 2021

39. A targeted ultra performance liquid chromatography – Tandem mass spectrometric assay for tyrosine and metabolites in urine and plasma: Application to the effects of antibiotics on mice

Author: Dumas, Marc-Emmanuel, Letertre, Marine, Myridakis, Antonis, Whiley, Luke, Camuzeaux, Stéphane, Lewis, Matthew, Chappell, Katie, Thaikkatil, Annie, Nicholson, Jeremy, Swann, Jonathan, Wilson, Ian, Letertre, Marine P.M., Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK, Imperial College London - National Heart and Lung Institute, Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Imperial College London, Institute for Women's Health [London], University College London Hospitals (UCLH), Department of Surgery and Cancer [Londres, Royaume-Uni], Biomolecular Medicine, Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK., Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Electrospray, Clinical Biochemistry, Urine, 030226 pharmacology & pharmacy, 01 natural sciences, Biochemistry, High-performance liquid chromatography, Analytical Chemistry, MESH: Tyrosine, MESH: Linear Models, Cresols, Mice, chemistry.chemical_compound, 0302 clinical medicine, Limit of Detection, Tandem Mass Spectrometry, Liquid chromatography–mass spectrometry, Metabolites, MESH: Animals, Tyrosine, Chromatography, High Pressure Liquid, Dansyl Compounds, Mice, Inbred BALB C, Dansyl chloride, General Medicine, Anti-Bacterial Agents, MESH: Reproducibility of Results, MESH: Cresols, Female, Glucuronide, P-cresol conjugates, MESH: Mice, Inbred BALB C, MESH: Limit of Detection, MESH: Gastrointestinal Microbiome, Tyrosinemia, 03 medical and health sciences, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Quantification, MESH: Anti-Bacterial Agents, Biofluids, medicine, Animals, MESH: Chromatography, High Pressure Liquid, MESH: Mice, MESH: Dansyl Compounds, Chromatography, 010401 analytical chemistry, Reproducibility of Results, MESH: Tandem Mass Spectrometry, Cell Biology, medicine.disease, Gastrointestinal Microbiome, 0104 chemical sciences, chemistry, Linear Models, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Tyrosine plays a key role in mammalian biochemistry and defects in its metabolism (e.g., tyrosinemia, alkaptonuria etc.) have significant adverse consequences for those affected if left untreated. In addition, gut bacterially-derived p-cresol and its metabolites are of interest as a result of various effects on host xenobiotic metabolism. A fit-for-purpose quantitative ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay was developed to target and quantify tyrosine and eleven metabolites in urine and plasma. Dansylation, using dansyl chloride, was used to improve chromatographic and mass spectral properties for tyrosine and nine phenolic metabolites, with detection using positive electrospray ionisation (ESI). The sulfate and glucuronide conjugates of p-cresol, where the phenol group was blocked, were quantified intact, using negative ESI via polarity switching during the same run. Sample preparation for urine and plasma involved deproteinization by solvent precipitation (of acetonitrile:isopropyl alcohol (1:1 v/v)) followed by in situ dansylation in 96 well plates. To minimize sample and solvent usage, and maximize sensitivity, analysis was performed using microbore reversed-phase gradient UPLC on a C8 phase with a 7.5 min. cycle time. The coefficients of variation obtained were
Published: 2021

40. Revisiting the cardiovascular risk of hydroxychloroquine in RA

Author: Guillaume Padern, Yves-Marie Pers, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Herrada, Anthony, and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: 0301 basic medicine, Time Factors, MESH: Hydroxychloroquine, Azithromycin, Arthritis, Rheumatoid, 0302 clinical medicine, Anti-Infective Agents, Cardiac toxicity, Medicine, MESH: COVID-19, News & Views, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, MESH: Arthritis, Rheumatoid, Anti-Bacterial Agents, 3. Good health, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Cardiovascular Diseases, MESH: Heart Disease Risk Factors, Rheumatoid arthritis, Drug Therapy, Combination, Drug therapy, Safety, Hydroxychloroquine, medicine.drug, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MESH: Anti-Infective Agents, Antimalarials, 03 medical and health sciences, Rheumatology, Internal medicine, MESH: Anti-Bacterial Agents, MESH: Azithromycin, Humans, MESH: SARS-CoV-2, 030203 arthritis & rheumatology, MESH: Humans, MESH: Sulfasalazine, SARS-CoV-2, business.industry, Adverse effects, MESH: Safety, MESH: Time Factors, COVID-19, MESH: Cardiovascular Diseases, medicine.disease, bacterial infections and mycoses, MESH: Antimalarials, COVID-19 Drug Treatment, Sulfasalazine, MESH: Drug Therapy, Combination, 030104 developmental biology, Heart Disease Risk Factors, business
Abstract: International audience; Cardiac toxicity can be induced by hydroxychloroquine, especially when used in combination with azithromycin. Interest in hydroxychloroquine and azithromycin as potential therapies for COVID-19 has renewed concerns about the possible cardiovascular risk these drugs present to patients with rheumatoid arthritis.
Published: 2020

41. Risk factors for the abundance of antimicrobial resistance genes aph(3')-III, erm(B), sul2 and tet(W) in pig and broiler faeces in nine European countries

Author: Yang, Dongsheng, Heederik, Dick J J, Mevius, Dik J, Scherpenisse, Peter, Luiken, Roosmarijn E C, Van Gompel, Liese, Skarżyńska, Magdalena, Wadepohl, Katharina, Chauvin, Claire, Van Heijnsbergen, Eri, Wouters, Inge M, Greve, Gerdit D, Jongerius-Gortemaker, Betty G M, Tersteeg-Zijderveld, Monique, Zając, Magdalena, Wasyl, Dariusz, Juraschek, Katharina, Fischer, Jennie, Wagenaar, Jaap A, Smit, Lidwien A M, Schmitt, Heike, IRAS OH Epidemiology Microbial Agents, Faculteit Diergeneeskunde, dIRAS RA-I&I RA, Klinische infectiologie en microb. lab., dI&I I&I-4, dIRAS RA-I&I I&I, LS IRAS EEPI GRA (Gezh.risico-analyse), One Health Microbieel, IRAS OH Epidemiology Microbial Agents, Faculteit Diergeneeskunde, dIRAS RA-I&I RA, Klinische infectiologie en microb. lab., dI&I I&I-4, dIRAS RA-I&I I&I, LS IRAS EEPI GRA (Gezh.risico-analyse), One Health Microbieel, Institute for Risk Assessment Sciences [Utrecht, The Netherlands] (IRAS), Utrecht University [Utrecht], Wageningen BioVeterinary Research, Wageningen University and Research [Wageningen] (WUR), National Veterinary Research Institute [Pulawy, Pologne] (NVRI), Tierärztliche Hochschule Hannover, Laboratoire de Ploufragan-Plouzané-Niort [ANSES], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), German Federal Institute for Risk Assessment [Berlin] (BfR), Research at the National Veterinary Research Institute (PIWet), Poland, was supported by the Polish Ministry of Science: No. 3173/7PR/2014/2.D.Y. was also funded by the China Scholarships Council (No.201709110149), and European Project: 613754,EC:FP7:KBBE,FP7-KBBE-2013-7-single-stage,EFFORT(2013)
Subjects: Microbiology (medical), Farms, Epidemiology, Bioinformatica & Diermodellen, Swine, animal diseases, MESH: Anti-Infective Agents, Drug Resistance, Anti-Bacterial Agents/pharmacology, Feces, Anti-Infective Agents, MESH: Risk Factors, Risk Factors, MESH: Anti-Bacterial Agents, Bio-informatics & Animal models, MESH: Drug Resistance, Bacterial, Drug Resistance, Bacterial, Life Science, Animals, Pharmacology (medical), MESH: Animals, Epidemiology, Bio-informatics & Animal models, MESH: Farms, MESH: Swine, Epidemiologie, Pharmacology, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, MESH: Chickens, Bacterial, MESH: Feces, Anti-Infective Agents/pharmacology, Anti-Bacterial Agents, Infectious Diseases, Epidemiologie, Bioinformatica & Diermodellen, Chickens
Abstract: Objectives The occurrence and zoonotic potential of antimicrobial resistance (AMR) in pigs and broilers has been studied intensively in past decades. Here, we describe AMR levels of European pig and broiler farms and determine the potential risk factors. Methods We collected faeces from 181 pig farms and 181 broiler farms in nine European countries. Real-time quantitative PCR (qPCR) was used to quantify the relative abundance of four antimicrobial resistance genes (ARGs) [aph(3′)-III, erm(B), sul2 and tet(W)] in these faeces samples. Information on antimicrobial use (AMU) and other farm characteristics was collected through a questionnaire. A mixed model using country and farm as random effects was performed to evaluate the relationship of AMR with AMU and other farm characteristics. The correlation between individual qPCR data and previously published pooled metagenomic data was evaluated. Variance component analysis was conducted to assess the variance contribution of all factors. Results The highest abundance of ARG was for tet(W) in pig faeces and erm(B) in broiler faeces. In addition to the significant positive association between corresponding ARG and AMU levels, we also found on-farm biosecurity measures were associated with relative ARG abundance in both pigs and broilers. Between-country and between-farm variation can partially be explained by AMU. Different ARG targets may have different sample size requirements to represent the overall farm level precisely. Conclusions qPCR is an efficient tool for targeted assessment of AMR in livestock-related samples. The AMR variation between samples was mainly contributed to by between-country, between-farm and within-farm differences, and then by on-farm AMU.
Published: 2022

42. Safety and Efficacy of Fidaxomicin and Vancomycin in Children and Adolescents with Clostridioides (Clostridium) difficile Infection: A Phase 3, Multicenter, Randomized, Single-blind Clinical Trial (SUNSHINE)

Author: Claudia Fortuny, Arnaud Petit, Samantha Bosis, Elodie Incera, Bartosz Korczowski, Krisztina Kalocsai, Daniel Bradford, Joost Melis, Stefan Lazar, Rob van Maanen, Rodney Croos-Dabrera, Joshua Wolf, St Jude Children's Research Hospital, Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet [Budapest, Hungary], Hospital Sant Joan de Déu [Barcelona], Universitat de Barcelona (UB), Victor Babeş University of Medicine and Pharmacy (UMFT), Università degli Studi di Milano [Milano] (UNIMI), Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Rzeszow University (RU Poland), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Astellas Pharma B.V. [Leiden, the Netherlands], Astellas Pharma Development [Northbrook, IL, USA], Gestionnaire, Hal Sorbonne Université, Università degli Studi di Milano = University of Milan (UNIMI), Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Microbiology (medical), MESH: Clostridioides difficile, medicine.medical_specialty, medicine.drug_class, MESH: Clostridium Infections, [SDV]Life Sciences [q-bio], 030106 microbiology, Antibiotics, vancomycin, MESH: Clostridioides, 03 medical and health sciences, MESH: Vancomycin, 0302 clinical medicine, Internal medicine, MESH: Anti-Bacterial Agents, MESH: Child, Medicine, Fidaxomicin, 030212 general & internal medicine, Adverse effect, MESH: Treatment Outcome, MESH: Adolescent, MESH: Aged, MESH: Humans, business.industry, MESH: Clostridium, fidaxomicin, MESH: Fidaxomicin, MESH: Child, Preschool, MESH: Adult, MESH: Aminoglycosides, Clostridium difficile, 16. Peace & justice, MESH: Single-Blind Method, Confidence interval, 3. Good health, [SDV] Life Sciences [q-bio], Clinical trial, Infectious Diseases, pediatric, Clostridioides difficile infection, Vancomycin, business, Clostridioides, medicine.drug
Abstract: Background Fidaxomicin, a narrow-spectrum antibiotic approved for Clostridioides (Clostridium) difficile infection (CDI) in adults, is associated with lower rates of recurrence than vancomycin; however, pediatric data are limited. This multicenter, investigator-blind, phase 3, parallel-group trial assessed the safety and efficacy of fidaxomicin in children. Methods Patients aged Results Of 148 patients randomized, 142 were treated (30 Conclusions Compared with vancomycin, fidaxomicin was well tolerated and demonstrated significantly higher rates of GC in children and adolescents with CDI. Clinical Trials Registration NCT02218372
Published: 2020

43. Genomic background of the Klebsiella pneumoniae NDM-1 outbreak in Poland, 2012–18

Author: Mariusz Krawczyk, Radosław Izdebski, Sylvain Brisse, P Urbanowicz, Marek Gniadkowski, M Sitkiewicz, National Medicines Institute - Narodowy Instytut Leków [Warsaw] (NIL), Genomed S.A. [Warsaw], Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris], This work was partially financed by: (i) grants 2017/01/X/NZ7/00220 and 2018/31/B/NZ7/04002 from the Polish National Science Centre, and (ii) SPUB MIKROBANK from the Polish Ministry of Science and Higher Education. In addition, a 2017 French Government Scholarship from the French Embassy in Poland was given to R.I. to visit the Brisse lab., and Institut Pasteur [Paris] (IP)
Subjects: Klebsiella pneumoniae, MESH: Klebsiella pneumoniae, MESH: beta-Lactamases, Yersiniabactin, Disease Outbreaks, chemistry.chemical_compound, Plasmid, Genotype, Pharmacology (medical), MESH: Disease Outbreaks, Clade, Bulgaria, MESH: Phylogeny, Phylogeny, Genetics, 0303 health sciences, MESH: Microbial Sensitivity Tests, Phylogenetic tree, Greece, MESH: Genomics, Genomics, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, MESH: Klebsiella Infections, MESH: Multilocus Sequence Typing, MESH: Bulgaria, MESH: Poland, Plasmids, Microbiology (medical), Microbial Sensitivity Tests, [SDV.BID]Life Sciences [q-bio]/Biodiversity, Biology, beta-Lactamases, 03 medical and health sciences, MESH: Plasmids, MESH: Anti-Bacterial Agents, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Pharmacology, MESH: Humans, 030306 microbiology, Outbreak, biology.organism_classification, Klebsiella Infections, chemistry, MESH: Greece, Multilocus sequence typing, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Poland, Multilocus Sequence Typing
Abstract: Objectives To characterize genomes of Klebsiella pneumoniae ST11 NDM-1 responsible for a countrywide outbreak in Poland and compare them phylogenetically with other Polish and international ST11 strains. Methods Seventy-one carbapenemase-producing K. pneumoniae ST11 isolates from Poland, including 66 representatives of the NDM-1 epidemic from 2012–18, were sequenced using Illumina MiSeq. Additionally, three outbreak isolates were also sequenced using MinION. The clonality and phylogenetic analysis was done by core-genome MLST and SNP approaches. Resistomes, virulomes, K/O antigens and plasmid replicons were screened for. The detailed plasmid analysis was based on full assemblies using Oxford Nanopore Technologies data. Results Chromosomes of the outbreak isolates formed an essentially homogeneous cluster (though accumulating SNPs gradually with time), differing remarkably from other Polish NDM-1/-5-, KPC-2- or OXA-48-producing K. pneumoniae ST11 strains. The cluster belonged to a clade with 72 additional isolates identified worldwide, including closely related NDM-1 producers from several countries, including organisms from Bulgaria and Greece. All these had KL24 and O2v1 antigens and the chromosomal yersiniabactin locus YbST230 residing in the ICEKp11 element. The specific blaNDM-1-carrying Tn125 transposon derivative, named Tn125A, was located in IncFII/pKPX-1- and/or IncR-like plasmids; however, the IncRs rearranged extensively during the outbreak, contributing to highly dynamic plasmid profiles and resistomes. Conclusions The K. pneumoniae ST11 NDM-1 genotype that has been expanding in Poland since 2012 is largely monoclonal and represents a novel international high-risk lineage that is also spreading in other countries.
Published: 2020

44. Characterization of Clostridium Perfringens Isolates Collected from Three Agricultural Biogas Plants over a One-Year Period

Author: Derongs, Lorine, Druilhe, Céline, Ziebal, Christine, Le Maréchal, Caroline, Pourcher, Anne-Marie, Optimisation des procédés en Agriculture, Agroalimentaire et Environnement (UR OPAALE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Ploufragan-Plouzané-Niort [ANSES], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and ADEME (grant number 1606C0022)
Subjects: MESH: Clostridium perfringens, Clostridium perfringens, MESH: Clostridium Infections, MESH: Manure, mesophilic anaerobic digestion, lcsh:R, lcsh:Medicine, C. perfringens, biochemical phenomena, metabolism, and nutrition, antimicrobial susceptibility, toxinotypes, MESH: Anti-Bacterial Agents, manure, digestate, [SDE]Environmental Sciences, MESH: Biofuels
Abstract: Digestate produced by agricultural biogas plants (BGPs) may contain pathogenic bacteria. Among them, Clostridium perfringens deserves particular attention due to its ability to grow under anaerobic conditions and persist in amended soil. The aim of this study was to examine the potential pathogenicity and the antimicrobial resistance of C. perfringens in manure and digestate collected from three agricultural biogas plants (BGPs). A total of 157 isolates (92 from manure, 65 from digestate) were screened for genes encoding seven toxins (cpa, cpb, etx, iapcpe, netB, and cpb2). The 138 cpa positive isolates were then screened for tetA(P), tetB(P), tet(M), and erm(Q) genes and tested for antimicrobial susceptibility. The toxinotypes identified in both manure and digestate were type A (78.3% of the isolates), type G (16.7%), type C (3.6%), and type D (1.4%), whereas none of the isolates were type F. Moreover, half of the isolates carried the cpb2 gene. The overall prevalence of tetA(P) gene alone, tetA(P)-tetB(P) genes, and erm(Q) gene was 31.9, 34.8, and 6.5%, respectively. None of the isolates harbored the tet(M) gene. Multiple antimicrobial resistant isolates were found in samples that were collected from all the manure and digestates. Among them, 12.3% were highly resistant to some of the antibiotics tested, especially to clindamycin (MIC &ge, 16 &micro, g/mL) and tilmicosin (MIC &gt, 64 &micro, g/mL). Some isolates were highly resistant to antibiotics used in human medicine, including vancomycin (MIC &gt, 8 &micro, g/mL) and imipenem (MIC &gt, g/mL). These results suggest that digestate may be a carrier of the virulent and multidrug resistant C. perfringens.
Published: 2020
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45. Identifying Experts Reasoning in Antibiotic Treatment with Preference Learning

Author: Sedki, Karima, Lakrafli, Chaymae, Lamy, Jean-Baptiste, Tsopra, Rosy, Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Université Sorbonne Nouvelle - Paris 3 - Institut des Hautes Études de l'Amérique latine (USN IHEAL), Université Sorbonne Nouvelle - Paris 3, Centre Hospitalier Universitaire [Rennes], Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Primary Health Care, MESH: Anti-Bacterial Agents, Preferences learning, Learning, MESH: Learning, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Clinical Practice Guidelines, Experts reasoning, MESH: Primary Health Care, Problem Solving, MESH: Problem Solving, Anti-Bacterial Agents
Abstract: International audience; The aim of this paper is to propose an approach based on preference learning for building a model that represents the closest possible experts reasoning to provide recommendations. We apply this method to antibiotherapy in primary care. The preference model was learned from the recommendations and from a database describing the domain.
Published: 2020

46. Trends in antimicrobial resistance among Escherichia coli from defined infections in humans and animals

Author: Jean-Yves Madec, Clémence Bourély, Nathalie Jarrige, Jocelyne Caillon, Claire Chauvin, Géraldine Cazeau, Thomas Coeffic, Marisa Haenni, Eric Jouy, Agnès Leblond, S. Thibaut, École Nationale des Services Vétérinaires (ENSV), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Unité Mixte de Recherche d'Épidémiologie des maladies Animales et zoonotiques (UMR EPIA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MedQual network, Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Lyon [ANSES], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Unité Epidémiologie, Santé et Bien-être (EPISABE), Laboratoire de Ploufragan-Plouzané-Niort [ANSES], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and Unité Antibiorésistance et Virulence Bactériennes
Subjects: 0301 basic medicine, Microbiology (medical), Veterinary medicine, Food-producing animals, Swine, medicine.drug_class, MESH: Dog Diseases, [SDV]Life Sciences [q-bio], 030106 microbiology, Cephalosporin, Antibiotics, Microbial Sensitivity Tests, Drug resistance, Cat Diseases, medicine.disease_cause, Poultry, 03 medical and health sciences, Dogs, Antibiotic resistance, Antibiogram, MESH: Anti-Bacterial Agents, Drug Resistance, Bacterial, medicine, Escherichia coli, Animals, Humans, Pharmacology (medical), Dog Diseases, Escherichia coli Infections, MESH: Escherichia coli Infections, Pharmacology, MESH: Microbial Sensitivity Tests, biology, Resistance (ecology), medicine.diagnostic_test, MESH: Cat Diseases, biology.organism_classification, Anti-Bacterial Agents, 3. Good health, 030104 developmental biology, Infectious Diseases, Cats, Antibiotic use, Cattle, Bacteria
Abstract: Objectives To characterize and compare resistance trends in clinical Escherichia coli isolates from humans, food-producing animals (poultry, cattle and swine) and pets (dogs and cats). Methods Antibiogram results collected between January 2014 and December 2017 by MedQual [the French surveillance network for antimicrobial resistance (AMR) in bacteria isolated from the community] and RESAPATH (the French surveillance network for AMR in bacteria from diseased animals) were analysed, focusing on resistance to antibiotics of common interest to human and veterinary medicine. Resistance dynamics were investigated using generalized additive models. Results In total, 743 637 antibiograms from humans, 48 170 from food-producing animals and 7750 from pets were analysed. For each antibiotic investigated, the resistance proportions of isolates collected from humans were of the same order of magnitude as those from food-producing animals or pets. However, resistance trends in humans differed from those observed in pets and food-producing animals over the period studied. For example, resistance to third-generation cephalosporins and fluoroquinolones was almost always below 10% for both humans and animals. However, in contrast to the notable decreases in resistance observed in both food-producing animals and pets, resistance in humans decreased only slightly. Conclusions Despite several potential biases in the data, the resistance trends remain meaningful. The strength of the parallel is based on similar data collection in humans and animals and on a similar statistical methodology. Resistance dynamics seemed specific to each species, reflecting different antibiotic-use practices. These results advocate applying the efforts already being made to reduce antibiotic use to all sectors and all species, both in human and veterinary medicine.
Published: 2020

47. Genome-based insights into the resistomes and mobilomes of two Providencia rettgeri strains isolated from wound infections in Madagascar

Author: Jean-Marc Collard, Lovasoa Ramparany, Pierrette Landrie Simo Tchuinte, Elisoa Ratsima, Frédérique Randrianirina, Mamitina Alain Noah Rabenandrasana, Vincent Enouf, Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Pasteur International Bioresources network (PIBNet), Institut Pasteur [Paris] (IP), This study was conducted during a postdoctoral internship supported by a Postdoctoral Grant CALMETTE and YERSIN from the Institute Pasteur Department of International Affairs., and Institut Pasteur [Paris]
Subjects: 0301 basic medicine, Antimicrobial resistance, MESH: Genome, Bacterial, Genome, MESH: Madagascar, 0302 clinical medicine, Plasmid, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Resistance, Multiple, Bacterial, Providencia rettgeri, Immunology and Allergy, MESH: Genomic Islands, 030212 general & internal medicine, Insertion sequence, MESH: Phylogeny, MESH: High-Throughput Nucleotide Sequencing, Phylogeny, Wound infections, Genetics, MESH: Microbial Sensitivity Tests, biology, High-Throughput Nucleotide Sequencing, QR1-502, Anti-Bacterial Agents, Gene cassette, Horizontal gene transfer, MESH: Whole Genome Sequencing, Plasmids, Microbiology (medical), MESH: Interspersed Repetitive Sequences, Gene Transfer, Horizontal, Genomic Islands, 030106 microbiology, Immunology, Microbial Sensitivity Tests, Providencia, MESH: Providencia, Microbiology, 03 medical and health sciences, MESH: Plasmids, Intensive care, MESH: Anti-Bacterial Agents, Madagascar, MESH: Spain, MESH: United States, MESH: Wound Infection, Humans, Intensive care unit, MESH: Humans, Whole Genome Sequencing, MESH: Drug Resistance, Multiple, Bacterial, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, United States, MESH: Gene Transfer, Horizontal, Interspersed Repetitive Sequences, Spain, Wound Infection, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Mobile genetic elements, Genome, Bacterial
Abstract: Objectives A molecular analysis was performed of two Providencia rettgeri (P. rettgeri) strains (Pr 297 and Pr 269) collected in 2007 and 2009 from wound swabs of patients admitted to the intensive care units at Joseph Ravoangy Andrianavalona hospital and the Military Hospital in Antananarivo, Madagascar. Methods The two P. rettgeri isolates were subjected to susceptibility testing. Whole genome sequencing was performed to characterise the antibiotic resistance genes, genomic islands and mobilomes (integrons, plasmids and insertion sequences). Results All isolates were found to be multidrug-resistant. Antibiotic-resistant genes described were amongst eight different classes of antimicrobial agents. Thirty insertion sequences and twelve genomic islands were predicted in each genome. Class 1 and class 2 integrons were found in both genomes, with gene cassette regions encompassing arr-2 - cmlA5 - blaOXA-10 - ant (3”)-Ia and dfrA1 - sat2 - ant (3”)-Ia – orfX, respectively. IncA/C2, ColM and ColE1-like plasmids were described harbouring blaCMY-30, qnrD and aac(6’)-Ib-cr4 genes, respectively. Phylogenetic analysis showed that Pr 297 and Pr 269 isolates were genetically identical and clustered with P. rettgeri strains described in the USA and Spain. Conclusions It is believed that this is the first molecular characterisation of wound infection pathogens from Madagascan patients and the first description of P. rettgeri co-producing CMY-30, OXA-10 and AAC(6’)-Ib-cr4 enzymes. The diversity of the resistance determinants and mobile genetic elements was probably due to extensive horizontal gene transfer events, highlighting the need to conduct further molecular monitoring studies to understand the genomic plasticity of resistant bacteria in Madagascan hospitals.
Published: 2020

48. Antimicrobial susceptibility profiles of anaerobic bacteria, isolated from human clinical specimens, within different European and surrounding countries. A joint ESGAI study

Author: A.C.M. Veloo, H. Bahar Tokman, H. Jean-Pierre, Y. Dumont, S. Jeverica, R. Lienhard, A. Novak, A. Rodloff, V. Rotimi, I. Wybo, E. Nagy, on behalf of the ESGAI study group, University Medical Center Groningen [Groningen] (UMCG), Cerrahpasa Faculty of Medicine, Istanbul University, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), University of Ljubljana, ADMed Microbiologie [La Chaux‑de‑Fonds, Switzerland], University of Split, University Hospital Leipzig, Kuwait University, Vrije Universiteit Brussel (VUB), University of Szeged [Szeged], Brussels Heritage Lab, Clinical sciences, Microbiology and Infection Control, Clinical Biology, and İÜC, Cerrahpaşa Tıp Fakültesi, Temel Tıp Bilimleri Bölümü
Subjects: Veterinary medicine, Bacteria, Anaerobic/classification, Antibiotics, Peptoniphilus, MESH: Bacteria, Anaerobic, ESGAI study, 0303 health sciences, MESH: Microbial Sensitivity Tests, biology, Kuwait/epidemiology, Bacterial Infections, 3. Good health, Anti-Bacterial Agents, Europe, Infectious Diseases, Kuwait, Anaerobic bacteria, medicine.drug, food.ingredient, medicine.drug_class, MESH: Bacterial Infections, Resistance profile, Eggerthella lenta, Microbial Sensitivity Tests, Microbiology, Anti-Bacterial Agents/pharmacology, Europe/epidemiology, 03 medical and health sciences, Bacteria, Anaerobic, food, MESH: Anti-Bacterial Agents, Drug Resistance, Bacterial, MESH: Drug Resistance, Bacterial, medicine, resistance profile, antibiotics, anaerobic bacteria, Europe, ESGAI study, Humans, Etest, 030304 developmental biology, MESH: Humans, 030306 microbiology, BACTEROIDES, Clindamycin, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Metronidazole, METRONIDAZOLE, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Kuwait, MESH: Europe, Bacteroides, Bacterial Infections/epidemiology, ANTIBIOTIC SUSCEPTIBILITY, RESISTANCE
Abstract: bahar tokman, hrisi/0000-0002-2205-5120 WOS:000525325200020 PubMed ID: 31634565 Objectives: Studies on the antimicrobial susceptibility profile of anaerobic bacteria are underrepresented in the literature. Within this study we aim to give an extensive overview of the differences in antimicrobial susceptibility profiles between different European and surrounding countries. Methods: Minimal inhibitory concentration (MIC) data of different antibiotics were collected from 10 participating laboratories, representing an equal number of countries. All MIC's were determined using Etest, according to the protocol used by the participating laboratory. Anaerobic genera represented by at least 10 clinical isolates were included in the study. Results: Each country tested different antibiotics, sometimes depending on the kind of infection and/or the anaerobic species isolated. All countries tested clindamycin and metronidazole. Resistance rates differed remarkably between the different countries. Especially in Kuwait, resistance was high for all tested antibiotics. Unexpected metronidazole resistance was observed for Finegoldia magna isolates, Peptoniphilus isolates and Eggerthella lenta isolates. Conclusions: Due to the extensive differences in antimicrobial susceptibility profile of anaerobic bacteria isolated within different countries, we strongly recommend to perform this kind of study on a regular basis. (C) 2019 The Authors. Published by Elsevier Ltd.
Published: 2020

49. AntibioGame® A serious game for teaching medical students about antibiotic use

Author: Samuel Cohen, Frédéric Méchaï, Rosy Tsopra, Manon Cabal, Olivier Bouchaud, Karima Sedki, Jean-Baptiste Lamy, Mélanie Courtine, David Eap, Laboratoire Traitement du Signal et de l'Image (LTSI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Sorbonne Paris Nord, Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Université Paris 13 (UP13), Sorbonne Université (SU), Service de maladies infectieuses et tropicales [CHU Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Agence Nationale de Sécurité du Médicament et des Produits de Santé, Jonchère, Laurent, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and École Pratique des Hautes Études (EPHE)
Subjects: Male, Serious games, Students, Medical, 020205 medical informatics, [SDV]Life Sciences [q-bio], E-learning (theory), General Practice, 02 engineering and technology, Serious game, E-learning, 0302 clinical medicine, MESH: Students, Medical, Antibiotics, MESH: General Practice, 0202 electrical engineering, electronic engineering, information engineering, 030212 general & internal medicine, MESH: Teaching, media_common, Education, Medical, 4. Education, MESH: Clinical Decision-Making, Disease Management, Primary care, Anti-Bacterial Agents, MESH: Young Adult, Infectious diseases, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Psychology, Adult, media_common.quotation_subject, MESH: Education, Medical, Clinical Decision-Making, education, Health Informatics, MESH: Video Games, MESH: Disease Management, MESH: Primary Health Care, Likert scale, Education, 03 medical and health sciences, Young Adult, MESH: Anti-Bacterial Agents, Humans, Learning, [INFO]Computer Science [cs], Quality (business), Antibiotic use, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Medical education, MESH: Humans, Primary Health Care, business.industry, Teaching, ComputingMilieux_PERSONALCOMPUTING, Usability, MESH: Adult, MESH: Male, Video Games, Medical team, MESH: Learning, business, MESH: Female, human activities
Abstract: International audience; Introduction - Measures for controlling antimicrobial resistance are urgently required. We describe here AntibioGame®, a serious game for improving the training of medical students in antibiotic use in primary care. Objective - We aimed to design a serious game for antibiotics teaching and to evaluate its usability and playability by medical students. Methods - We used various gamification techniques (e.g. use of mascots, avatars, rewards, leader board) and cartoon graphics in the design of AntibioGame®. This game implements clinical case templates built from a list of learning goals defined by a medical team through an analysis of clinical practice guidelines. The game was evaluated by asking medical students to rate their satisfaction and the usability and playability of the game on an electronic form and through group discussions. The electronic form was derived from the MEEGA + scale, a five-point Likert scale including 32 items for assessing both usability and playability. Results - AntibioGame® is a case-based game in which students play the role of a doctor meeting patients in consultation and helping other health professionals to solve their problems, as in real life. The scenarios are realistic and cover situations frequently encountered in primary care. The 57 medical students enrolled found the game attractive, usable, fun, and appropriate for learning. Game quality was considered "good" (score = 60 on the MEEGA + scale). All the students said they would recommend the game, 96 % liked it and 81 % would use it for revision. Conclusion - AntibioGame® is a promising tool for improving knowledge in antibiotic prescription that could easily be included in multifaceted programs for training medical students.
Published: 2020

50. Highly efficient and stable FeIIFeIII LDH carbon felt cathode for removal of pharmaceutical ofloxacin at neutral pH

Author: Mehmet A. Oturan, Marc Cretin, Mikhael Bechelany, Nihal Oturan, Weilu Yang, Minghua Zhou, Jinan University [Guangzhou], Nankai University (NKU), Laboratoire Géomatériaux et Environnement (LGE ), Université Gustave Eiffel, Institut Européen des membranes (IEM), and Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)
Subjects: Ofloxacin, MESH: Hydrogen-Ion Concentration, Environmental Engineering, Surface catalysis, Health, Toxicology and Mutagenesis, Radical, Kinetics, Inorganic chemistry, 0211 other engineering and technologies, MESH: Carbon, 02 engineering and technology, 010501 environmental sciences, Electrochemistry, 01 natural sciences, Catalysis, law.invention, chemistry.chemical_compound, Heterogeneous electro-Fenton, Reaction rate constant, law, MESH: Anti-Bacterial Agents, MESH: Electrolysis, Environmental Chemistry, Waste Management and Disposal, 0105 earth and related environmental sciences, Reusability, 021110 strategic, defence & security studies, MESH: Iron, Chemistry, [SDE.IE]Environmental Sciences/Environmental Engineering, MESH: Electrodes, Pollution, Cathode, MESH: Hydroxides, MESH: Water Pollutants, Chemical, Hydroxide, Fe(II)Fe(III) LDH-CF, MESH: Ofloxacin, Leaching (metallurgy), [CHIM.OTHE]Chemical Sciences/Other
Abstract: International audience; The traditional electro-Fenton (EF) has been facing major challenges including narrow suitable range of pH and non-reusability of catalyst. To overcome these drawbacks we synthesized FeIIFeIII-layered double hydroxide modified carbon felt (FeIIFeIII LDH-CF) cathode via in situ solvo-thermal process. Chemical composition and electrochemical characterization of FeIIFeIII LDH-CF were tested and analyzed. The apparent rate constant of decay kinetics of ofloxacin (OFC) with FeIIFeIII LDH-CF (0.18 min-1) at pH 7 was more than 3 times higher than that of homogeneous EF (0.05 min-1) at pH 3 with 0.1 mM Fe2+ under same current density (9.37 mA cm-2). Also, a series of experiments including evolution of solution pH, iron leaching, OFC removal with trapping agent and quantitative detection of hydroxyl radicals (OH) were conducted, demonstrating the dominant role of OH generated by surface catalyst via ≡ FeII/FeIII on LDH cathode for degradation of organics as well contributing to high efficiency and good stability at neutral pH. Besides, formation and evolution of aromatic intermediates, carboxylic acids and inorganic ions (F-, NH4+ and NO3-) were identified by High-Performance Liquid chromatography, Gas Chromatography-Mass Spectrometry and ionic chromatography analyses. These findings allowed proposing a plausible degradation pathway of OFC by OH generated in the heterogeneous EF process.
Published: 2020

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