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1. Modeling SARS-CoV-2 viral kinetics and association with mortality in hospitalized patients from the French COVID cohort

Author

Néant, N. (Nadège), Lingas, G. (Guillaume), Le Hingrat, Q. (Quentin), Ghosn, J. (Jade), Engelmann, I. (Ilka), Lepiller, Q. (Quentin), Gaymard, A. (Alexandre), Ferré, V. (Virginie), Hartard, C. (Cédric), Plantier, J-C. (Jean-Christophe), Thibault, V. (V.), Marlet, J. (Julien), Montes, B. (Brigitte), Bouiller, K. (Kevin), Lescure, F-X. (François-Xavier), Timsit, J-F. (Jean-François), Faure, E. (Emmanuel), Poissy, J. (Julien), Chidiac, C. (Christian), Raffi, F. (François), Kimmoun, A. (Antoine), Etienne, M. (Manuel), Richard, J-C. (Jean-Christophe), Tattevin, P. (Pierre), Garot, D. (Denis), Le Moing, V. (Vincent), Bachelet, D. (Delphine), Tardivon, C. (Coralie), Duval, X. (Xavier), Yazdanpanah, Y. (Yazdan), Mentré, F. (France), Laouénan, C. (Cédric), Visseaux, B. (Benoit), Guedj, J. (Jérémie), plantier, 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, Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), 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), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement (LCPME), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHU Pontchaillou [Rennes], Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Service d'anesthésie - réanimation chirurgicale [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et tropicales [CHU Lyon] (hôpital de la Croix-Rousse), Hôpital de la Croix-Rousse [CHU Lyon], Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service des Maladies Infectieuses et Tropicales [Hôpital Charles Nicolle, Rouen], Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), 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), 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), 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 ), Service de Médecine Intensive et Réanimation [Tours], Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Département d’Epidémiologie, de Biostatistique et de Recherche Clinique [AP-HP Hôpital Bichat - Claude Bernard] (DEBRC), 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), The study has received financial support from the National Research Agency (ANR) through the ANR-Flash call for COVID-19 (Grant ANR-20-COVI-0018) and the Bill and Melinda Gates Foundation under Grant Agreement INV-017335. The French cohort was supported by the REACTing consortium and by a grant from the French Ministry of Health (Grant PHRC 20-0424). The funders had no role in the study design, in the collection, analysis, and interpretation of data, in the writing of the report, and in the decision to submit the article for publication., ANR-20-COVI-0018,TheraCoV,Dynamique virale au niveau individuel et populationnel : implications pour l'optimisation des stratégies antivirales(2020), Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène, Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-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), HAL UR1, Admin, Dynamique virale au niveau individuel et populationnel : implications pour l'optimisation des stratégies antivirales - - TheraCoV2020 - ANR-20-COVI-0018 - COVID-19 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), 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), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Unité de Glycobiologie Structurale et Fonctionnelle (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Lille, CNRS, Infection, Anti-microbiens, Modélisation, Evolution [IAME (UMR_S_1137 / U1137)], Pathogenèse virale du diabète de type 1 - ULR 3610, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) [CEF2P / CARCINO], Centre Hospitalier Régional Universitaire de Besançon [CHRU Besançon], Centre hospitalier universitaire de Nantes [CHU Nantes], Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement [LCPME], Morphogénèse et antigénicité du VIH et du virus des Hépatites [MAVIVH - U1259 Inserm - CHRU Tours ], CHU Montpellier, Laboratoire Chrono-environnement (UMR 6249) [LCE], Service des maladies infectieuses et tropicales, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF], Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Centre d’Investigation Clinique de Nantes [CIC Nantes], Défaillance Cardiovasculaire Aiguë et Chronique [DCAC], Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] [INI-CRCT], French-Clinical Research Infrastructure Network - F-CRIN [Paris] [Cardiovascular & Renal Clinical Trialists - CRCT ], Service des maladies infectieuses et tropicales [Rouen], Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé [CREATIS], ARN régulateurs bactériens et médecine [BRM], Centre Hospitalier Régional Universitaire de Tours [CHRU Tours], Département d'épidémiologie, biostatistique et recherche clinique, and Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique [CIC 1425]

Subjects
Male, 0301 basic medicine, Medical Sciences, viruses, MESH: Hospitalization, Antibodies, Viral, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Nasopharynx, Epidemiology, MESH: COVID-19, Prospective Studies, 030212 general & internal medicine, MESH: Models, Theoretical, Prospective cohort study, MESH: Aged, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, MESH: Kinetics, Mortality rate, Biological Sciences, Viral Load, Prognosis, viral dynamics, 3. Good health, Hospitalization, Survival Rate, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: RNA, Viral, Cohort, RNA, Viral, Female, France, MESH: Viral Load, Viral load, medicine.medical_specialty, MESH: Survival Rate, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, MESH: Prognosis, 03 medical and health sciences, Internal medicine, medicine, Humans, MESH: SARS-CoV-2, education, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Survival rate, Aged, MESH: Humans, SARS-CoV-2, business.industry, COVID-19, Models, Theoretical, mortality, MESH: Male, MESH: Nasopharynx, MESH: Prospective Studies, MESH: France, Kinetics, 030104 developmental biology, business, MESH: Female, MESH: Antibodies, Viral, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Significance A detailed characterization of viral load kinetics and its association with disease evolution is key to understand the virus pathogenesis, identify high-risk patients, and design better treatment strategies. We here analyze the mortality and the virological information collected in 655 hospitalized patients, including 284 with longitudinal measurements, and we build a mathematical model of virus dynamics and survival. We predict that peak viral load occurs 1 d before symptom onset, on average, and that dynamics of decline after peak is slower in older patients. Viral load dynamics after hospital admission is an independent predictor of the risk of death, suggesting that prolonged viral shedding of high quantities of virus is associated with poor outcome in this population., The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown. We analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort. The model predicted a median peak viral load that coincided with symptom onset. Patients with age ≥65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients (P < 10−4). In multivariate analysis, the risk factors associated with mortality were age ≥65 y, male gender, and presence of chronic pulmonary disease (hazard ratio [HR] > 2.0). Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 1.31, P < 10−3). Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality. A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 2.0 and 2.9 d in patients of age

Published
2021

2. The impact of transoesophageal echocardiography in elderly patients with infective endocarditis

Author

N’cho-Mottoh, Marie-Paule B, Erpelding, Marie-Line, Roubaud Baudron, Claire, Delahaye, François, Fraisse, Thibaut, Dijos, Marina, Ennezat, Pierre Vladimir, Fluttaz, Arnaud, Richard, Benjamin, Beaufort, Corinne, Nazeyrollas, Pierre, Brasselet, Camille, Pineau, Olivier, Tattevin, Pierre, Curlier, Elodie, Iung, Bernard, Forestier, Emmanuel, Selton-Suty, Christine, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Bordeaux [Bordeaux], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Alès-Cévennes (CHAC), CHU Grenoble, Centre Hospitalier Métropole Savoie [Chambéry], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Intercommunal Villeneuve-Saint-Georges (CHIV), 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 ), CHU Pointe-à-Pitre/Abymes [Guadeloupe], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Cardiologie [CHRU Nancy], and The initial research project ELDERL-IE, from which these data were analysed, was supported by a grant of the 'Fondation Coeur et Recherche' (France) in 2013.

Subjects
Elderly, Transoesophageal echocardiography, [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, General Medicine, Infective endocarditis, Cardiology and Cardiovascular Medicine, Geriatric assessment
Abstract

International audience; BACKGROUND: Infective endocarditis (IE) increasingly involves older patients. Geriatric status may influence diagnostic and therapeutic decisions. AIM: To describe transoesophageal echocardiography (TEE) use in elderly IE patients, and its impact on therapeutic management and mortality. METHODS: A multicentre prospective observational study (ELDERL-IE) included 120 patients aged ≥75 years with definite or possible IE: mean age 83.1±5.0; range 75-101 years; 56 females (46.7%). Patients had an initial comprehensive geriatric assessment, and 3-month and 1-year follow-up. Comparisons were made between patients who did or did not undergo TEE. RESULTS: Transthoracic echocardiography revealed IE-related abnormalities in 85 patients (70.8%). Only 77 patients (64.2%) had TEE. Patients without TEE were older (85.4±6.0 vs. 81.9±3.9 years; P=0.0011), had more comorbidities (Cumulative Illness Rating Scale-Geriatric score 17.9±7.8 vs. 12.8±6.7; P=0.0005), more often had no history of valvular disease (60.5% vs. 37.7%; P=0.0363), had a trend toward a higher Staphylococcus aureus infection rate (34.9% vs. 22.1%; P=0.13) and less often an abscess (4.7% vs. 22.1%; P=0.0122). Regarding the comprehensive geriatric assessment, patients without TEE had poorer functional, nutritional and cognitive statuses. Surgery was performed in 19 (15.8%) patients, all with TEE, was theoretically indicated but not performed in 15 (19.5%) patients with and 6 (14.0%) without TEE, and was not indicated in 43 (55.8%) patients with and 37 (86.0%) without TEE (P=0.0006). Mortality was significantly higher in patients without TEE. CONCLUSIONS: Despite similar IE features, surgical indication was less frequently recognized in patients without TEE, who less often had surgery and had a poorer prognosis. Cardiac lesions might have been underdiagnosed in the absence of TEE, hampering optimal therapeutic management. Advice of geriatricians should help cardiologists to better use TEE in elderly patients with suspected IE.

Published
2023

3. In vivo daptomycin efficacy against experimental vancomycin-resistant Enterococcus faecium endocarditis

Author

Sophie Reissier, Idir Ghout, Laurent Massias, Azzam Saleh-Mghir, Anne-Claude Crémieux, Clara Sinel, Vincent Cattoir, François Guérin, Infection et inflammation chronique ( 2IC ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), CHU Caen, ARN régulateurs bactériens et médecine ( BRM ), 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 ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Ambroise Paré, Unité de Recherche Risques Microbiens ( U2RM ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Ministere de l'Enseignement Superieur et de la Recherche [EA4655], Infection et inflammation (2I), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), ARN régulateurs bactériens et médecine (BRM), 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)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Ambroise Paré [AP-HP], Unité de Recherche Risques Microbiens (U2RM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), and 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 )

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Enterococcus faecium, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Daptomycin, In vivo, Mutant strain, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Internal medicine, medicine, High doses, Endocarditis, Animals, Pharmacology (medical), 030212 general & internal medicine, Gram-Positive Bacterial Infections, Vancomycin resistant Enterococcus faecium, Pharmacology, biology, business.industry, Vancomycin Resistance, Endocarditis, Bacterial, medicine.disease, biology.organism_classification, Bacterial Load, 3. Good health, Anti-Bacterial Agents, Disease Models, Animal, Infectious Diseases, Treatment Outcome, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infective endocarditis, Female, Rabbits, business, medicine.drug
Abstract

International audience; Objectives - Daptomycin has become a first-line therapeutic option for vancomycin-resistant Enterococcus faecium infective endocarditis (IE). Although high doses (≥8 mg/kg) are often recommended, optimal doses, particularly for strains with MICs close to the susceptibility breakpoint (4 mg/L), are still debated.Methods - Daptomycin efficacy at doses equivalent to 8 mg/kg daptomycin (DAP8) and 12 mg/kg daptomycin (DAP12) in humans was evaluated in a rabbit model of aortic valve IE induced by 108 cfu of E. faecium reference strain Aus0004 (daptomycin MIC = 2 mg/L) or its in vitro mutant strain Mut4 (daptomycin MIC = 4 mg/L). Treatment began 48 h post-inoculation and lasted 5 days.Results - With Aus0004, the median log10 cfu/g of vegetations was significantly lower after DAP8 and DAP12 versus controls [6.05 (n = 12) and 2.15 (n = 10) versus 9.14 (n = 11), respectively; P Conclusions - DAP12 was the most successful strategy against IE due to a WT E. faecium strain (daptomycin MIC = 2 mg/L). To treat IE strains with MIC = 4 mg/L, DAP8 or DAP12 monotherapy was poorly effective with the risk of resistant mutant emergence. Reassessment of the daptomycin susceptibility breakpoint for enterococci seems necessary.

Published
2018

4. Selective recovery of RNAs from bacterial pathogens after their internalization by human host cells

Author

Simon Raynaud, Brice Felden, Hélène Le Pabic, ARN régulateurs bactériens et médecine ( BRM ), 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 ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Fondation pour la Recherche Medicale [FDM40912], Inserm, Agence Nationale pour la Recherche (ANR) [ANR-15-CE12-0003-01], Fondation pour la Recherche Medicale (FRM) [DBF20160635724], 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 ), ANR-15-CE12-0003,sRNA-FIT,Adaptation par ARN régulateurs chez Staphylococcus aureus(2015), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
0301 basic medicine, Salmonella typhimurium, Staphylococcus aureus, Lysis, Bacterial and prokaryotic RNAs, media_common.quotation_subject, Cell Culture Techniques, zirconium beads, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, General Biochemistry, Genetics and Molecular Biology, Microbiology, Cell Line, Transcriptome, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene expression, Humans, Internalization, Molecular Biology, Gene, media_common, Osteoblasts, biology, Host-pathogen interactions, Chemistry, Macrophages, RNA, RNA expression, Gene Expression Regulation, Bacterial, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bacterial & prokaryotic RNAs, RNA, Bacterial, 030104 developmental biology, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Biological Assay, RNA extraction, Zirconium, Bacteria, Selective RNA purification, Bacterial internalization
Abstract

International audience; Selective RNA extractions are required when studying bacterial gene expression within complex mixtures of pathogens and human cells, during adhesion, internalization and survival within the host. New technologies should be developed and implemented to enrich the amount of bacterial RNAs since the majority of RNAs are from the eukaryotic host cells, requiring high read depth coverage to capture the bacterial transcriptomes in dual-RNAseq studies. This will improve our understanding about bacterial adaptation to the host cell defenses, and about how they will adapt to an intracellular life. Here we present an RNA extraction protocol to selectively enrich the lowest bacterial RNA fraction from a mixture of human and bacterial cells, using zirconium beads, with minimal RNA degradation. Zirconium beads have higher capacity to extract bacterial RNAs than glass beads after pathogen internalization. We optimized the beads size and composition for an optimal bacterial lysis and RNA extraction. The protocol was validated on two human cell lines, differentiated macrophages and osteoblasts, with either Gram-positive (Staphylococcus aureus) or -negative (Salmonella typhimurium) bacteria. Relative to other published protocols, yield of total RNA recovery was significantly improved, while host cell infection was performed with a lower bacterial inoculum. Within the host, bacterial RNA recovery yields were about sixfold lower than an RNA extraction from pure bacteria, but the quality of the RNA recovered was essentially similar. Bacterial RNA recovery was more efficient for S. aureus than for S. typhimurium, probably due to their higher protection by the Gram-positive cell walls during the early step of eukaryotic cell lysis. These purified bacterial RNAs allow subsequent genes expression studies in the course of host cell-bacteria interactions.

Published
2018

5. The use of TNF-α antagonists in tuberculosis to control severe paradoxical reaction or immune reconstitution inflammatory syndrome: a case series and literature review

Author

Lucas Armange, Adèle Lacroix, Paul Petitgas, Cédric Arvieux, Caroline Piau-Couapel, Patrice Poubeau, Matthieu Revest, Pierre Tattevin, CHU Pontchaillou [Rennes], CHU Saint-Pierre, 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 ), and None

Subjects
Microbiology (medical), TNF-α antagonists, Infectious Diseases, tuberculosis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, General Medicine, infliximab, paradoxical reaction, immune reconstitution inflammatory syndrome
Abstract

International audience; Paradoxical reaction (PR) and immune reconstitution inflammatory syndrome (IRIS) are common complications of tuberculosis treatment. Corticosteroids are first-line treatment for severe PR or IRIS, particularly neurological. We report four cases of severe PR or IRIS during tuberculosis treatment who required TNF-α antagonists, and identified 20 additional cases through literature review. They were 14 women and 10 men, with a median age of 36 years (interquartile range, 28-52). Twelve were immunocompromised before tuberculosis: untreated HIV infection (n=6), or immunosuppressive treatment (TNF-α antagonists, n=5; tacrolimus, n=1). Tuberculosis was mostly neuromeningeal (n=15), pulmonary (n=10), lymph node (n=6), and miliary (n=6), multi-susceptible in 23 cases. PR or IRIS started after a median time of 6 weeks (IQR, 4-9) following anti-tuberculosis treatment start, and consisted primarily of tuberculomas (n=11), cerebral vasculitis (n=8), and lymphadenitis (n=6). First-line treatment of PR or IRIS was high-dose corticosteroids in 23 cases. TNF-α antagonists were used as salvage treatment in all cases, with infliximab (n=17), thalidomide (n=6), and adalimumab (n=3). All patients improved, but 6 had neurological sequelae, and 4 had TNF-α antagonist-related severe adverse events. TNF-α antagonists are safe and effective as salvage or corticosteroid-sparing therapeutic for severe PR or IRIS during tuberculosis treatment.

Published
2023

6. Which trial do we need? Aminopenicillin-gentamicin versus aminopenicillin-ceftriaxone for Enterococcus faecalis endocarditis

Author

Luque-Paz, David, Cuervo, Guillermo, Miró, José M, Tattevin, Pierre, 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 ), CHU Pontchaillou [Rennes], University of Barcelona, and JMM received a personal 80:20 research grant from Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–23. This work was not funded.

Subjects
Microbiology (medical), [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, General Medicine
Abstract

International audience; No abstract available

Published
2023

7. When eukaryotes and prokaryotes look alike: the case of regulatory RNAs

Author

Brice Felden, Luc Paillard, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), ARN régulateurs bactériens et médecine (BRM), 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)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Sante et de la Recherche Medicale, University of Rennes 1, Centre National de la Recherche Scientifique and The French National Research Agency., ANR-15-CE12-0003,sRNA-FIT,Adaptation par ARN régulateurs chez Staphylococcus aureus(2015), 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 )-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Tramonti, Pierre, Adaptation par ARN régulateurs chez Staphylococcus aureus - - sRNA-FIT2015 - ANR-15-CE12-0003 - AAPG2015 - VALID, 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 ), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), ARN régulateurs bactériens et médecine ( BRM ), 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 ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and ANR-15-CE12-0003-02,sRNA-FIT

Subjects
0301 basic medicine, 030106 microbiology, Computational biology, Biology, regulatory RNA, Microbiology, Genome, RNA mechanism, 03 medical and health sciences, RNA interference, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, CRISPR, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Epigenetics, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, Regulation of gene expression, RNA biogenesis, Eukaryota, RNA-mediated adaptive immunity, epigenetic control, Long non-coding RNA, RNA silencing, 030104 developmental biology, Infectious Diseases, Gene Expression Regulation, Prokaryotic Cells, RNA function, RNA, gene regulation, Biogenesis
Abstract

International audience; The discovery that all living entities express many RNAs beyond mRNAs, tRNAs and rRNAs has been a surprise in the past two decades. In fact, regulatory RNAs (regRNAs) are plentiful, and we report stunning parallels between their mechanisms and functions in prokaryotes and eukaryotes. For instance, prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats) defense systems are functional analogs to eukaryotic RNA interference processes that preserve the cell against foreign nucleic acid elements. Regulatory RNAs shape the genome in many ways: by controlling mobile element transposition in both domains, via regulation of plasmid counts in prokaryotes, or by directing epigenetic modifications of DNA and associated proteins in eukaryotes. RegRNAs control gene expression extensively at transcriptional and post-transcriptional levels, with crucial roles in fine-tuning cell environmental responses, including intercellular interactions. Although the lengths, structures and outcomes of the regRNAs in all life kingdoms are disparate, they act through similar patterns: by guiding effectors to target molecules or by sequestering macromolecules to hamper their functions. In addition, their biogenesis processes have a lot in common. This unifying vision of regRNAs in all living cells from bacteria to humans points to the possibility of fruitful exchanges between fundamental and applied research in both domains.

Published
2017

8. Regulatory RNAs in bacteria: From identification to function

Author

Brice Felden, Philippe Bouloc, ARN régulateurs bactériens et médecine ( BRM ), 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 ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), 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 ), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), 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 )-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
0301 basic medicine, Regulation of gene expression, [SDV.GEN]Life Sciences [q-bio]/Genetics, biology, RNA, Gene Expression Regulation, Bacterial, Computational biology, Regulatory Sequences, Ribonucleic Acid, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, General Biochemistry, Genetics and Molecular Biology, RNA, Bacterial, 03 medical and health sciences, 030104 developmental biology, Regulatory sequence, Animals, Humans, Identification (biology), [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Molecular Biology, Bacteria, Function (biology), Introductory Journal Article
Abstract

International audience; Editorial: The discovery that RNA functions extend beyond their roles as messengers of DNA information and key components of the translation machinery has shaken up the RNA field...

Published
2017

9. Diffusion of amoxicillin into heart valves from infective endocarditis patients

Author

Sébastien Lalanne, François Guérin, Erwan Flécher, Vincent Cattoir, Nicolas Nesseler, Matthieu Revest, Marie-Clémence Verdier, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 ), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and This work was supported by the Rennes Clinical Investigation Center

Subjects
Pharmacology, Microbiology (medical), Infectious Diseases, [SDV]Life Sciences [q-bio], Pharmacology (medical)
Abstract

Objectives Amoxicillin is the drug of choice in the management of streptococcal and enterococcal infective endocarditis (IE) but little is known regarding amoxicillin diffusion into infected heart valves. Herein, we assessed amoxicillin valvular distribution and related pharmacokinetic/pharmacodynamic (PK/PD) target attainment in IE patients undergoing heart valve surgery. Patients and methods In this 2-year prospective study, patients with IE treated by continuous infusion of amoxicillin and undergoing a surgical valve replacement were included. Both amoxicillin plasma and tissue concentrations were measured the day of surgery. Amoxicillin concentration in plasma and crushed heart valves were measured by a validated liquid chromatography method coupled with ultra-violet and tandem mass spectrometry, respectively. MIC and MBC of amoxicillin were determined for all available isolates. The rate of achievement of PK/PD efficacy parameters were assessed. Results Twenty-two heart valves were removed from 20 patients. Bacterial aetiology was streptococcal (n = 17) and enterococcal (n = 3). Amoxicillin mean daily dose was 12 ± 3 g/24 h, mean plasma concentration was 29 ± 21 mg/L (n = 15), mean tissue concentration was 23 ± 15 mg/L (n = 22). Median diffusion rate was 62%. Patients reached a plasma concentration target >4XCMI (n = 13). Tissue concentrations were bactericidal for all streptococcal IE but not for enterococcal IE. Conclusions Amoxicillin intravalvular measurements in IE treated patients showed significant penetration into the infectious site. These data are reassuring that in situ bactericidal concentrations can be largely achieved in the management of streptococcal IE and support the need for combination antibiotic therapy for enterococcal IE.

Published
2022

10. Progressive multifocal leukoencephalopathy: epidemiology and spectrum of predisposing conditions

Author

Marine Joly, Cécile Conte, Charles Cazanave, Vincent Le Moing, Pierre Tattevin, Pierre Delobel, Agnès Sommet, Guillaume Martin-Blondel, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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 ), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV]Life Sciences [q-bio], epidemiology, Neurology (clinical), JC virus, progressive multifocal leukoencephalopathy
Abstract

Population-based data on the epidemiology of progressive multifocal leukoencephalopathy, its predisposing conditions and mortality rate are lacking, although such data are crucial to raise awareness among clinicians and to lay foundations for future therapeutic trials in immunomodulating therapies. In our study, patients were identified by interrogating the French national healthcare reimbursement database from 1 January 2008 to 31 December 2017, using progressive multifocal leukoencephalopathy International Classification of Diseases code and a patient’s selection algorithm. Overall incidence rate, 1-year all-cause mortality rate and survival patterns were calculated, and factors associated with death were identified using a multivariate Cox proportional hazards regression model. Our cohort is the largest to date, comprising 584 patients with incident progressive multifocal leukoencephalopathy. The overall incidence in France from 2010 to 2017 was stable during the study period at 0.11 per 100 000 person-years, 95% confidence interval [0.10–0.12]. Predisposing diseases were HIV infection (43.7%), followed by haematological malignancies (21.9%), chronic inflammatory diseases (20.2%), solid organ transplantation (4.3%), solid neoplasm (4.1%) and primary immune deficiency (1.5%). The 1-year mortality rate was 38.2%, with a 95% confidence interval (34.2–42.2). In multivariate analysis, factors independently associated with death were older age [adjusted hazard ratio 0.33 (0.20–0.53) for patients aged 20 to 40 compared with patients aged over 60], male gender [adjusted hazard ratio 0.73 (0.54–0.99) for females compared with males] and predisposing immunosuppressive disease, with the highest risk for solid neoplasms [adjusted hazard ratio 4.34 (2.25–8.37)], followed by haematological malignancies [adjusted hazard ratio 3.13 (1.85–5.30)] and HIV infection [adjusted hazard ratio 1.83 (1.12–3.00)], compared with chronic inflammatory diseases. Immune reconstitution inflammatory syndrome was notified in 7.0% of patients. In conclusion, incidence of progressive multifocal leukoencephalopathy is stable in France, and HIV infection remains the main predisposing disease. This large-size cohort uncovers a higher risk of mortality for male patients compared to females, and the worst prognosis for patients with solid neoplasm, while prognosis in patients with haematological malignancies appeared less dismal than in previous studies.

Published
2022

11. Non-HACEK gram-negative bacilli endocarditis: a multicentre retrospective case-control study

Author

Sébillotte, M, Boutoille, David, Declerck, Charles, Talarmin, Jean-Philippe, Lemaignen, Adrien, Piau, Caroline, Revest, Matthieu, Tattevin, Pierre, Gousseff, Marie, CHU Pontchaillou [Rennes], Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), 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 ), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), and None

Subjects
Endocarditis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, gram-negative bacilli, Escherichia coli, intravenous drug use, healthcare-associated
Abstract

International audience; BACKGROUND: Infective endocarditis (IE) caused by non-HACEK gram-negative bacilli (GNB) is poorly characterised and may be emerging as a consequence of medical progress. METHODS: We performed an observational retrospective case-control study. Cases were non-HACEK GNB IE, definite or possible (modified Duke criteria), diagnosed in adults between 2007 and 2020 in six French referral hospitals. Two controls were included for each case (IE due to other bacteria, matched by sites and diagnosis date). RESULTS: Non-HACEK GNB were identified in 2.4% (77/3230) of all IE during the study period, with a mean age of 69.2 ± 14.6 years, and a large male predominance (53/77, 69%). Primary pathogens were Escherichia coli (n = 33), Klebsiella sp. (n = 12) and Serratia marcescens (n = 9), including eight (10%) multidrug-resistant GNB. Compared to controls (n = 154: 43% Streptococcus sp., 41% Staphylococcus sp. and 12% Enterococcus sp.), non-HACEK GNB IE were independently associated with intravenous drug use (IVDU, 8% vs. 2%, p = .003), active neoplasia (15% vs. 6%, p = .009), haemodialysis (9% vs. 3%, p = .007) and healthcare-associated IE (36% vs. 18%, p = .002). Urinary tract was the main source of infection (n = 25, 33%) and recent invasive procedures were reported in 29% of cases. Non-HACEK GNB IE were at lower risk of embolism (31% vs. 47%, p = .002). One-year mortality was high (n = 28, 36%). Comorbidities, particularly malignant hemopathy and cirrhosis, were associated with increased risk of death. CONCLUSIONS: Non-HACEK GNB are rarely responsible for IE, mostly as healthcare-associated IE in patients with complex comorbidities (end-stage renal disease, neoplasia), or in IVDUs.

Published
2023

12. Influenza vaccine coverage among healthcare workers: A cluster analysis from a cross-sectional survey

Author

Saade, Anastasia, Rasoloarivalona, Fanjanirina, Poinsignon, Jean, Garlantezec, Ronan, Tattevin, Pierre, Paris, Christophe, École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), 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 ), and None

Subjects
[SDV]Life Sciences [q-bio], Healthcare workers, Hesitancy, Vaccine, Influenza
Abstract

International audience; OBJECTIVES: Influenza vaccination is recommended for healthcare workers (HCWs). However, in a 1500-bed tertiary care university hospital in France, influenza vaccine coverage among HCWs was 23% in 2017. PATIENTS AND METHODS: We performed a cross-sectional study between 05/09/2018 and 25/09/2018 among HCWs, randomly selected independent of their vaccination status, to estimate influenza vaccination coverage rate during the 2017-2018 season, and explore factors influencing vaccination, using a questionnaire. Multivariable regression analysis to assess factors associated with vaccine uptake and hierarchical clustering on principal components to identify HCW profiles regarding factors influencing vaccine uptake, were performed after multiple imputation. RESULTS: 977 HCWs were included (68% participation rate), primarily females (84%), nurses (38%) of 18-39 years old. Influenza vaccination coverage rate reached 33[30-36]%. Frequent vaccination (aOR 39.27[21.52-74.51]) and personal/family medical history of influenza (aOR 3.33[1.16-10.02]) were independently associated with vaccination. In HCWs’ patterns of influenza vaccination status, three clusters were identified: 1) (n = 438) mostly vaccinated (70%); 2) (n = 507) most unvaccinated (97%); and 3) (n = 32) unvaccinated HCWs lacking knowledge on influenza and influenza vaccine. Among the 148 (15%) HCWs reluctant to receive the vaccine the following year, 23 (16%) received it for the 2017-2018 season, while 125 (84%) did not, mostly stating they had doubts about the vaccine (82%). CONCLUSION: This work identifies determinants of vaccine uptake and highlights HCWs profiles associated with factors influencing vaccination and a subgroup of HCWs flexible about having the vaccine during the upcoming seasonal campaign. This result opens up perspectives toward improved vaccination coverage among HCWs.

Published
2023

13. Pneumococcal vaccination coverage at the initiation of chronic dialysis, and its association with mortality during the first year

Author

Élodie Pierre, Adélaïde Pladys, Sahar Bayat-Makoei, Pierre Tattevin, Cécile Vigneau, CHU Pontchaillou [Rennes], Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), Recherche sur les services et le management en santé (RSMS), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département Méthodes quantitatives en santé publique (METIS), 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 ), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and None

Subjects
End-stage renal disease, Infectious Diseases, Pneumococcal vaccination, General Veterinary, General Immunology and Microbiology, Public Health, Environmental and Occupational Health, Molecular Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Mortality, Dialysis, Vaccination coverage
Abstract

International audience; Objectives: Pneumococcal immunization is recommended in dialysis patients. We aimed to estimate pneumococcal vaccination coverage among patients who initiate dialysis in France, and its association with mortality. Methods: Data were extracted from two prospective national databases, merged using a deterministic linkage method: renal epidemiology and information network (REIN) registry, which includes all patients on dialysis and kidney transplants recipients in France, and the national health insurance information system (SNIIRAM) which collects individual data on health expenditure reimbursement, including vaccines. We enrolled all patients who initiated chronic dialysis in 2015. Data on health status at dialysis initiation, dialysis modalities, and pneumococcal vaccine prescribed from 2 years before to 1 year after dialysis start were collected. Univariate and multivariate Cox proportional hazard models were used to assess one-year all-cause mortality. Results: Among the 8,294 incident patients included, 1,849 (22.3 %) received at least one pneumococcal vaccine before (n = 542, 6.5 %), or after (n = 1,307, 15.8 %) dialysis start, as follows: 13-valent pneumococcal conjugated vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23), n = 938 (50.7 %); only PPSV23, n = 650 (35.1 %); or only PCV13, n = 261 (14.1 %). Vaccinated patients were younger (mean, 66.5 ± 14.8 years vs. 69.0 ± 14.9 years, P ≤ 0.001), more likely to suffer from glomerulonephritis (17.0 % vs. 11.0 %, P ≤ 0.001), and less likely to start dialysis in emergency (27.2 % vs. 31.1 %, P = 0.001). On multivariate analysis, patients who received PCV13 and PPSV23, or only PCV13 were less likely to die (respectively, HR = 0.37; 95 %CI 0.28–0.51, and HR = 0.35; 95 %CI 0.19–0.65). Conclusions: Pneumococcal immunization with PCV13 followed by PPSV23, or with PCV13 alone, but not with PPSV23 alone, is independently associated with decreased one year-mortality in patients who start dialysis.

Published
2023

14. Differential response to antibiotic therapy in staphylococcal infective endocarditis: contribution of an ex vivo model

Author

Sébastien Lalanne, Vincent Cattoir, François Guerin, Marie-Clémence Verdier, Matthieu Revest, 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 ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], and This work was supported by Inserm, UMR_S 1230 ‘Bacterial Regulatory RNAs and Medicine’ Rennes 1 University, and Rennes clinical investigation center.

Subjects
Pharmacology, Microbiology (medical), Infectious Diseases, [SDV]Life Sciences [q-bio], Pharmacology (medical)
Abstract

Objectives Staphylococcal infective endocarditis (IE) remains a hard-to-treat infection with high mortality. Both the evaluation of new innovative therapies and research on alternative models mimicking human IE are therefore urgently needed to improve the prognosis of patients with diagnosed IE. Dalbavancin is a novel anti-staphylococcal lipoglycopeptide but there are limited data supporting its efficacy on biofilm infections. This antibiotic could be an alternative to current therapies for the medical treatment of IE but it needs to be further evaluated. Methods Here we developed an original ex vivo model of Staphylococcus aureus IE on human heart valves and assessed biofilm formation on them. After validating the model, the efficacy of two antistaphylococcal antibiotics, vancomycin and dalbavancin, was compared by measuring and visualizing their respective ability to inhibit and eradicate late-formed biofilm. Results Determination of the minimum biofilm inhibitory (MbIC) and eradicating (MbEC) concentrations in our ex vivo model identified dalbavancin as a promising drug with much lower MbIC and MBEC than vancomycin (respectively Conclusions These data highlight a strong bactericidal effect of dalbavancin, particularly on an infected heart valve compared with vancomycin. Dalbavancin could be a realistic alternative treatment for the management of staphylococcal IE.

Published
2023

15. Temocillin Resistance in the Enterobacter cloacae Complex Is Conferred by a Single Point Mutation in BaeS, Leading to Overexpression of the AcrD Efflux Pump

Author

François Guérin, François Gravey, Sophie Reissier, Malo Penven, Charlotte Michaux, Simon Le Hello, Vincent Cattoir, 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 ), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), 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), and The three-year doctoral contract of François Gravey was funded by a grant from the Normandy Region

Subjects
Pharmacology, BaeSR, MdtABCD, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, E. asburiae, ECC, Pharmacology (medical), AcrD
Abstract

International audience; The Enterobacter cloacae complex (ECC) has become a major opportunistic pathogen with antimicrobial resistance issues. Temocillin, an "old" carboxypenicillin that is remarkably stable toward beta-lactamases, has been used as an alternative for the treatment of multidrug-resistant ECC infections. Here, we aimed at deciphering the never-investigated mechanisms of temocillin resistance acquisition in Enterobacterales. By comparative genomic analysis of two clonally related ECC clinical isolates, one susceptible (Temo_S [MIC of 4 mg/L]) and the other resistant (Temo_R [MIC of 32 mg/L]), we found that they differed by only 14 single-nucleotide polymorphisms, including one nonsynonymous mutation (Thr175Pro) in the two-component system (TCS) sensor histidine kinase BaeS. By site-directed mutagenesis in Escherichia coli CFT073, we demonstrated that this unique change in BaeS was responsible for a significant (16-fold) increase in temocillin MIC. Since the BaeSR TCS regulates the expression of two resistance-nodulation-cell division (RND)-type efflux pumps (namely, AcrD and MdtABCD) in E. coli and Salmonella, we demonstrated by quantitative reverse transcription-PCR that mdtB, baeS, and acrD genes were significantly overexpressed (15-, 11-, and 3-fold, respectively) in Temo_R. To confirm the role of each efflux pump in this mechanism, multicopy plasmids harboring mdtABCD or acrD were introduced into either Temo_S or the reference strain E. cloacae subsp. cloacae ATCC 13047. Interestingly, only the overexpression of acrD conferred a significant increase (from 8- to 16-fold) of the temocillin MIC. Altogether, we have shown that temocillin resistance in the ECC can result from a single BaeS alteration, likely resulting in the permanent phosphorylation of BaeR and leading to AcrD overexpression and temocillin resistance through enhanced active efflux. The Enterobacter cloacae complex (ECC) has become a major opportunistic pathogen with antimicrobial resistance issues. Temocillin, an "old" carboxypenicillin that is remarkably stable toward beta-lactamases, has been used as an alternative for the treatment of multidrug-resistant ECC infections.

Published
2023

16. Amoxicillin therapeutic drug monitoring for endocarditis: a comparative study (EI-STAB)

Author

Marie Dorel, Robin Albert, Audrey Le Bot, Leila Caillault, Sébastien Lalanne, Pierre Tattevin, Marie-Clémence Verdier, Adrien Lemaignen, Matthieu Revest, CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), 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 ), and None

Subjects
Microbiology (medical), Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Enterocococcus, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV]Life Sciences [q-bio], [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Amoxicillin, Streptococcus, Pharmacology (medical), General Medicine, Infective endocarditis, Therapeutic drug monitoring
Abstract

International audience; Introduction - International guidelines recommend high doses of β-lactams for most cases of infective endocarditis (IE). Therapeutic drug monitoring (TDM) is increasingly used to adjust β-lactam dose based on plasma concentrations, although there are no comparative studies to support this practice. The benefit of amoxicillin TDM during IE was evaluated. Methods - An observational, retrospective, cohort study of adults treated with high-dose amoxicillin for enterococcal or streptococcal IE was conducted in two referral centers. Patients with, or without TDM were compared. The primary outcome was mean daily amoxicillin dose. Results - A total of 206 cases of streptococcal (n=140, 68%) or enterococcal (n=66, 32%) IE were included. IE occurred on prosthetic valves in 77 (37%) cases, and on intracardiac devices in 28 (14%) cases. Aortic valve was involved in 136 (66%) cases. There were 154 men (75%), mean age was 70 ± 14 years, valve surgery was performed in 81/206 (39%) patients, and in-hospital mortality was 8% (17/206). All patients in the TDM group and most patients in the group without TDM received amoxicillin as continuous infusion. Amoxicillin TDM was performed for 114 patients (55.3%), with a mean of 4.7 ± 2.3 measures per patient, a mean plasma steady-state concentration of 41.2 ± 19 mg/L, most (82/114, 72%) being within the therapeutic target (20-80 mg/L). Mean amoxicillin dose was lower in patients with TDM (10.0 ± 3.3 g/day) than those without TDM (11.3 ± 2.0 g/day) (P=0.003). Conclusion - Amoxicillin TDM was associated with a reduction in daily doses, with no impact on adverse events and prognosis. Individualized treatment of IE through TDM may contribute to decreased use of antibiotics.

Published
2023

17. Empirical Treatment in Acute Bacterial Meningitis: a Plea for High Doses of Cefotaxime or Ceftriaxone

Author

Paul Le Turnier, Pierre Tattevin, Emmanuelle Varon, Xavier Duval, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], 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 ), CHU Henri Mondor [Créteil], Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], 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), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord

Subjects
Pharmacology, Streptococcus pneumoniae, Infectious Diseases, cephalosporin, meningitis, Pharmacology (medical), [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Abstract

International audience

Published
2023

18. Encephalitis in travellers: A prospective multicentre study

Author

Picard, Léa, Mailles, Alexandra, Fillâtre, Pierre, Tattevin, Pierre, Stahl, Jean-Paul, CHU Pontchaillou [Rennes], Santé publique France - French National Public Health Agency [Saint-Maurice, France], ESCMID [Basel], CHU de Saint-Brieuc, 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 ), Université Grenoble Alpes (UGA), and French Infectious Diseases Society (Société de pathologie infectieuse de langue française, SPILF)

Subjects
arbovirus, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, prevention, travellers, Encephalitis, General Medicine, herpes simplex virus
Abstract

Background As the epidemiology of encephalitis varies from one country to another, international travel may be an important clue for the diagnostic workout of this puzzling disease. Methods We performed an ancillary study using the ENCEIF prospective cohort conducted in 62 clinical sites in France from 2016 to 2019. All cases of encephalitis in adults that fulfilled a case definition derived from the International Encephalitis Consortium were included. Travellers were defined as patients who spent at least one night in a foreign country within the last six months. Results Of the 494 encephalitis patients enrolled, 69 (14%) were travellers. As compared to non-travellers, they were younger (median age, 48 years [interquartile range, 36–69] vs 66 [49–76], P Conclusion The two primary causes of encephalitis in travellers are arboviruses and HSV. Empirical treatment of encephalitis in travellers must include acyclovir. Pre-travel advice and vaccination may decrease the risk of encephalitis in travellers.

Published
2023

19. Cefotaxime resistance in bile samples is an independent predictor of deep infectious complications after pancreaticoduodenectomy in patients with endoprosthesis

Author

Fabien Robin, Marie Livin, Damien Bergeat, Haitham Triki, Elodie Gaignard, Marine Cailleaux, Vincent Cattoir, Karim Boudjema, Pierre Tattevin, Laurent Sulpice, CHU Pontchaillou [Rennes], Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 ), Chemistry, Oncogenesis, Stress and Signaling (COSS), and Jonchère, Laurent

Subjects
[SDV] Life Sciences [q-bio], pancreatoduodenectomy, bacteriobilia, Hepatology, complications, [SDV]Life Sciences [q-bio], Surgery, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, endoprosthesis, infection
Abstract

International audience; Background Bacteriobilia may increase the rate of deep infectious complications (DIC) after pancreaticoduodenectomy. To better adjust prophylactic and empirical antibacterial treatment, we aimed to characterize bacteriobilia in patients with preoperative endoprosthesis, and its association with postoperative DIC. Methods All patients who underwent pancreaticoduodenectomy in our center between 2010 and 2019 were included. The association between microbiological findings from bile samples, and postoperative DIC was analyzed, and we compared microbiology data between 2010-2014 and 2015-2019 periods. Results We enrolled 578 patients (median age 67 years [59-72], 58.7% males), of whom 220 (38.1%) had preoperative biliary endoprosthesis, with 197 (89.5%) positive preoperative bile samples pathogens were Enterobacterales, enterococci, and Candida albicans. The incidence of DIC was similar in patients with or without endoprosthesis (20.4% vs 17.8%, P = .352). Bacterial isolates collected during 2015-2019 were more resistant to cefotaxime than those recovered from 2010-2014 (45.5% vs 25.5%, P = .009). The only independent risk factor for DIC in patients with endoprosthesis was cefotaxime resistance in bile (hazard ratio 3.027 [1.115-8.216], P = .03). Conclusions The incidence of DIC is high after pancreaticoduodenectomy, with or without endoprosthesis, despite routine postoperative treatment. Cefotaxime resistance, the only independent predictor of DIC in patients with endoprosthesis, has increased over time. Hence, cefotaxime may no longer be an appropriate empirical treatment.

Published
2023

20. Characteristics, management, and outcomes of patients with infectious encephalitis requiring intensive care: A prospective multicentre observational study

Author

Pierre Fillatre, Alexandra Mailles, Jean Paul Stahl, Pierre Tattevin, Sophie Abgrall, Laurent Argaud, Xavier Argemi, Guillaume Baille, Aurélie Baldolli, Sarah Benghanem, Kevin Bertrand, Julien Biberon, Charlotte Biron, Geneviève Blanchet Fourcade, Mathieu Blot, Elisabeth Bothelo-Nevers, Frédéric Bourdain, David Boutoille, Hélène Brasme, Cédric Bruel, Fabrice Bruneel, Rodolphe Buzele, Emmanuel Canet, Etienne Canoui, Philippe Casenave, Bernard Castan, Charles Cazanave, Céline Cazorla, Pascal Chavanet, Catherine Chirouze, Tomasz Chroboczek, Johan Courjon, Daniel Da Silva, Thomas De Broucker, Arnaud De La Blanchardiere, Etienne De Montmollin, Eric Denes, Colin Deschanvres, Aurélien Dinh, Olivier Epaulard, Emmanuel Forestier, Thibaut Fraisse, Benjamin Gaborit, Amandine Gagneux-Brunon, Nicolas Gaillard, Arnaud Galbois, Mathieu Godement, François Goehringer, Pascale Goubin, Simon Gravier, Valentin Greigert, Isabelle Gueit, Thomas Guimard, Carole Henry, Maxime Hentzien, Pierre Jaquet, Fanny Jomier, Snejana Jurici, Solen Kerneis, Morgane Le Bras, Marion Le Marechal, Gwenael Le Moal, Paul Le Turnier, Anne-Sophie Lecompte, Raphael Lecomte, Stéphanie Lejeune, François-Xavier Lescure, Olivier Lesieur, Philippe Lesprit, Guillaume Louis, Rafael Mahieu, Alain Makinson, Guillaume Marc, Alexandre Maria, Nathalie Marin, Guillaume Martin-Blondel, Martin Martinot, Alexandre Mas, Philippe Mateu, Morgan Matt, Laurence Maulin, Frédéric Mechai, Eugénie Mutez, Jérémie Orain, Anne Pachart, Nathalie Pansu, Solene Patrat-Delon, Patricia Pavese, Hélène Pelerin, Véronique Pelonde-Erimée, Isabelle Pierre, Emilie Piet, Diane Ponscarme, Dimitri Psimaras, Mathilde Puges, Jean Reignier, Mathilde Reveillon Istin, Sylvain Rheims, Aurélie Richard-Mornas, Vincent Roubeau, Yvon Ruch, Isabelle Runge, Hélène Savini, Romain Sonneville, Jean-Marie Turmel, Louise Tyvaert, Marc-Olivier Vareil, Magali Vidal-Roux, Virginie Vitrat, Adrien Wang, Heidi Wille, Mathieu Zuber, Laurent Almoyna-Martinez, Jean-Louis Herrmann, Jérome Honnorat, Patrice Morand, France Roblot, Jean-Paul Stahl, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Santé publique France - French National Public Health Agency [Saint-Maurice, France], Centre Hospitalier Universitaire [Grenoble] (CHU), 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 ), and This work was supported by the French Infectious Diseases Society (Société de pathologie infectieuse de langue française, SPILF).

Subjects
Frailty, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV]Life Sciences [q-bio], Encephalitis, Intensive care unit, Functional outcome, Herpes simplex virus, Critical Care and Intensive Care Medicine
Abstract

International audience; PURPOSE: Infectious encephalitis (IE) is a severe disease which requires intensive care unit (ICU) admission in up to 50% of cases. We aimed to describe characteristics, management and outcomes of IE patients who required ICU admission. MATERIALS AND METHODS: Ancillary study focusing on patients with ICU admission within the ENCEIF cohort, a French prospective observational multicentre study. The primary criteria for outcome was the functional status at hospital discharge, categorized using the Glasgow outcome scale (GOS). Logistic regression model was used to identify risk factors for poor outcome, defined as a GOS ≤ 3. RESULTS: We enrolled 198 ICU patients with IE. HSV was the primary cause (n = 72, 36% of all IE, 53% of IE with microbiological documentation). Fifty-two patients (26%) had poor outcome at hospital discharge, including 22 deaths (11%). Immunodeficiency, supratentorial focal signs on admission, lower cerebrospinal fluid (CSF) white cells count (2 days were independent predictors of poor outcome. CONCLUSION: HSV is the primary cause of IE requiring ICU admission. IE patients admitted in ICU have a poor prognosis with 11% of in-hospital mortality and 15% of severe disabilities in survivors at discharge.

Published
2023

21. Delay between COVID-19 complete vaccination and SARS-CoV-2 infection among healthcare workers

Author

Anastasia Saade, Leo Cha, Emilie Tadié, Bruno Jurado, Alix Le Bihan, Pauline Baron-Latouche, Christine Febreau, Vincent Thibault, Ronan Garlantezec, Pierre Tattevin, Christophe Paris, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Pontchaillou, Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [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 ), This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., and Jonchère, Laurent

Subjects
COVID-19 Vaccines, General Veterinary, General Immunology and Microbiology, SARS-CoV-2, Health Personnel, SARS-CoV-2 infection, [SDV]Life Sciences [q-bio], Vaccination, Complete vaccination, Public Health, Environmental and Occupational Health, virus diseases, COVID-19, [SDV] Life Sciences [q-bio], Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, ChAdOx1 nCoV-19, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Healthcare workers, Molecular Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Vaccine, BNT162 Vaccine
Abstract

International audience; OBJECTIVES: Healthcare workers (HCWs), at increased risk of coronavirus disease 2019 (COVID-19) were among the primary targets for vaccination, which became mandatory for them on September 15th, 2021 in France. In November they were confronted to the fifth COVID-19 wave despite excellent vaccine coverage. We aimed to estimate the incidence of SARS-CoV-2 infection after complete vaccination among HCWs with different vaccination schemes, and its determinants. METHODS: We enrolled all HCWs in the university hospital of Rennes, France who had received complete vaccination (two doses of COVID-19 vaccine). The delay from last vaccination dose to SARS-CoV-2 infection was computed.Fitted mixed Cox survival model with a random effect applied to exposure risk periods to account for epidemic variation was used to estimate the determinants of SARS-CoV-2 infection after complete vaccination. RESULTS: Of the 6674 (82%) HCWs who received complete vaccination (36% BNT162b2, 29% mRNA-1273, and 34% mixed with ChAdOx1 nCoV-19) and were prospectively followed-up for a median of 7.0 [6.3-8.0] months, 160 (2.4%) tested positive for SARS-CoV-2 by RT-PCR. Incidence density of SARS-CoV-2 infection after complete vaccination was 3.39 [2.89-3.96] infections per 1000 person-month. Median time from vaccine completion to SARS-CoV-2 infection was 5.5 [3.2-6.6] months. Using fitted mixed Cox regression with the delay as a time-dependent variable and random effect applied to exposure risk periods, age (P

Published
2022

22. Epidemiological Changes and Improvement in Outcomes of Infective Endocarditis in Europe in the Twenty-First Century: An International Collaboration on Endocarditis (ICE) Prospective Cohort Study (2000-2012)

Author

Ambrosioni, Juan, Hernández-Meneses, Marta, Mangoni, Emanuele, Tattevin, Pierre, Olaison, Lars, Freiberger, Tomas, Hurley, John, Hannan, Margaret M., Chu, Vivian, Hoen, Bruno, Moreno, Asunción, Cuervo, Guillermo, Llopis, Jaume, Miró, José M, University of Barcelona, Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, 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 ), University of Gothenburg (GU), Masaryk University [Brno] (MUNI), Mater Misericordiae University Hospital (The Mater Hospital), Duke University [Durham], Groupe de recherche sur l'apprentissage, l'innovation et la connaissance dans les organisations (GRAICO), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], and None

Subjects
Microbiology (medical), Europe, Infectious Diseases, Epidemiology, [SDV]Life Sciences [q-bio], Cardiac surgery, Infective endocarditis, Mortality
Abstract

International audience; INTRODUCTION: Infective endocarditis (IE) has undergone important changes in its epidemiology worldwide. METHODS: The study aimed to compare IE epidemiological features and outcomes according to predefined European regions and between two different time periods in the twenty-first century. RESULTS: IE cases from 13 European countries were included. Two periods were considered: 2000-2006 and 2008-2012. Two European regions were considered, according to the United Nations geoscheme for Europe: Southern (SE) and Northern-Central Europe (NCE). Comparisons were performed between regions and periods. A total of 4195 episodes of IE were included, 2113 from SE and 2082 from NCE; 2787 cases were included between 2000 and 2006 and 1408 between 2008 and 2012. Median (IQR) age was 63.7 (49-74) years and 69.4% were males. Native valve IE (NVE), prosthetic valve IE (PVE), and device-related IE were diagnosed in 68.3%, 23.9%, and 7.8% of cases, respectively; 52% underwent surgery and 19.3% died during hospitalization. NVE was more prevalent in NCE, whereas device-related IE was more frequent in SE. Higher age, acute presentation, hemodialysis, cancer, and diabetes mellitus all were more prevalent in the second period. NVE decreased and PVE and device-related IE both increased in the second period. Surgical treatment also increased from 48.7% to 58.4% (p

Published
2023

23. Prevalence of Post-Acute COVID-19 Symptoms Twelve Months after Hospitalisation in Participants Retained in Follow-up: Analyses Stratified by Gender from a Large Prospective Cohort

Author

Ghosn, Jade, Bachelet, Delphine, Livrozet, Marine, Cervantes-Gonzalez, Minerva, Poissy, Julien, Goehringer, François, Gandonniere, Charlotte Salmon, Maillet, Mylène, Bani-Sadr, Firouzé, Martin-Blondel, Guillaume, Tattevin, Pierre, Launay, Odile, Surgers, Laure, Dudoignon, Emmanuel, Liegeon, Geoffroy, Zucman, David, Joseph, Cédric, Senneville, Eric, Yelnik, Cécile, Roger, Pierre-Marie, Faure, Karine, Gousseff, Marie, Cabié, André, Duval, Xavier, Chirouze, Catherine, Laouénan, Cedric, 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, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CArdiovasculaire Rénal Transplantation nEurovasculaire [Paris] (DMU CARTE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire de Reims (CHU Reims), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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 ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Foch [Suresnes], Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Gustave Dron [Tourcoing], European Atherosclerosis Society [Göteborg, Sweden] (EAS), CHU Pointe-à-Pitre/Abymes [Guadeloupe], Université des Antilles - UFR des sciences médicales Hyacinthe Bastaraud (UA UFR SM), Université des Antilles (UA), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], CHU de la Martinique [Fort de France], Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM), F-CRIN, Innovative clinical research network in vaccinology (I-REIVAC), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), 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), The French COVID cohort is funded by the REACTing (REsearch & ACtion emergING infectious diseases) consortium, by a grant of the French Ministry of Health (PHRC n°20-0424), and by the ORCHESTRA project which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement N°101016167. The funders had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and decision to submit the manuscript for publication., DESSAIVRE, Louise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Services des Maladies Infectieuses et Tropicales [CHU Saint-Antoine], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Emerging infectious diseases, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Moderate to severe COVID-19, SARS-CoV-2, Cohort, Post-acute COVID-19 symptoms, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Objectives - Persistent post-acute coronavirus disease 2019 (COVID-19) symptoms (PACSs) have been reported up to 6 months after hospital discharge. Herein we assessed the symptoms that persisted 12 months (M12) after admission for COVID-19 in the longitudinal prospective national French coronavirus disease cohort. Methods - Hospitalized patients with a confirmed virological diagnosis of COVID-19 were enrolled. Follow-up was planned until M12 after admission. Associations between persistence of ≥3 PACSs at M12 and clinical characteristics at admission were assessed through logistic regression according to gender. Results - We focused on participants enrolled between 24 January 2020 and 15 July 2020, to allow M12 follow-up. The M12 data were available for 737 participants. Median age was 61 years, 475 (64%) were men and 242/647 (37%) were admitted to intensive care units during the acute phase. At M12, 27% (194/710) of the participants had ≥3 persistent PACS, mostly fatigue, dyspnoea and joint pain. Among those who had a professional occupation before the acute phase, 91 out of 339 (27%) were still on sick leave at M12. Presence of ≥3 persistent PACS was associated with female gender, both anxiety and depression, impaired health-related quality of life and Medical Muscle Research Council Scale

Published
2023

24. Borréliose de Lyme

Author

Raffetin, Alice, Hansmann, Yves, Sauvat, Léo, Shramm, Frédéric, Tattevin, Pierre, Baux, Elisabeth, Patrat-Delon, Solène, Centre Hospitalier Intercommunal Villeneuve-Saint-Georges (CHIV), CHU Strasbourg, CHU Louise Michel [Clermont-Ferrand], CHU Clermont-Ferrand, 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 ), and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)

Subjects
Lyme Disease, [SDV]Life Sciences [q-bio], Borrelia Infections
Abstract

National audience; LYME BORRELIOSIS. Lyme borreliosis (LB) is the most common vector-borne disease in the Northern Hemisphere, caused by the bacterium Borrelia burgdorferi sensu lato, transmitted to humans by a bite of ticks Ixodes. Prevention is based on simple measures to evict ticks, and on their rapid extractionin the event of a bite. The diagnosis of LB is based on 3 arguments: an exposure to tick bites; clinically compatible symptoms (cutaneous, neurological or rheumatological manifestations, +/- functional symptoms such as fatigue or polyarthromyalgia), evolving in 3 stages (early localized or erythema migrans, early or late disseminated LB); a positive two-tier serological test (ELISA +/- Western-Blot). Serology can be negative for the first 6 weeks, without excluding the diagnosis. Since serology can remain positive for life, evolution is only evaluated clinically. LB treatment is mainly based on doxycycline for 14 to 28 days, depending on the clinical stage and manifestations, without demonstrated interest in prolonging it, even if symptoms persist. Nonetheless their management is crucial as often responsible for medical wandering. Attentive listening to the patient is essential. The prognosis of LB in the medium-term is favorable, especially if they beneficiate of an early management.; La borréliose de Lyme est la principale zoonose vectorielle en France. Elle est due à la bactérie Borrelia burgdorferi sensu lato, transmise lors d’une piqûre de tique infectée du genre Ixodes. Son diagnostic repose sur un trépied diagnostique, parfois incomplet. La prévention consiste en la protection contre les piqûres de tiques, et leur extraction rapide en cas de piqûre. Le traitement repose principalement sur la doxycycline.

Published
2023

25. Striking differences in weight gain after cART initiation depending on early or advanced presentation: Results from the ANRS CO4 FHDH cohort

Author

Sophie Grabar, Valérie Potard, Lionel Piroth, Sophie Abgrall, Louis Bernard, Clotilde Allavena, Fabienne Caby, Pierre de Truchis, Claudine Duvivier, Patricia Enel, Christine Katlama, Marie-Aude Khuong, Odile Launay, Sophie Matheron, Giovanna Melica, Hugues Melliez, Jean-Luc Meynard, Juliette Pavie, Laurence Slama, Sylvie Bregigeon, Pierre Tattevin, Jacqueline Capeau, Dominique Costagliola, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pneumologie [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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, Université de Tours (UT), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Victor Dupouy, Hôpital Raymond Poincaré [Garches], Université Paris-Saclay, CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), Centre Médical de l'Institut Pasteur (CMIP), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Assistance Publique - Hôpitaux de Marseille (APHM), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), CHU Pitié-Salpêtrière [AP-HP], Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Hôpital Cochin [AP-HP], CIC Cochin Pasteur (CIC 1417), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital Henri Mondor, Hôpital de Riaumont [Lievin], Hôpital Hôtel-Dieu [Paris], Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), 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 ), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], The ANRS CO4 FHDH is supported by the ANRS-MIE (Agence Nationale de Recherche sur le Sida et les hépatites virales-Maladies Infectieuse Emergentes), INSERM (Institut National de la Santé et de la Recherche Médicale) and the French Ministry of Health. The funders had no role in the study design, data collection, data analysis and interpretation, or writing of the report., Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Pasteur [Paris] (IP), CHU Henri Mondor, Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and GRABAR, SOPHIE

Subjects
Pharmacology, Microbiology (medical), Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.CAN]Life Sciences [q-bio]/Cancer, Pharmacology (medical)
Abstract

BackgroundMany studies have reported weight gain in ART-naive people living with HIV (PWH) initiating an integrase strand-transfer inhibitor-based regimen. We studied the impact of early or advanced presentation and that of individual drugs in PWH initiating combined ART (cART) between 2012 and 2018.MethodsFrom the French Hospital Database HIV cohort, we assessed factors associated with a weight gain ≥10%, weight change after cART initiation or BMI increase ≥5 kg/m2 up to 30 months. The analyses were conducted overall, and among PWH with early (primary infection or CD4 >350/mm3 and viral load ResultsAt 30 months, 34.5% (95% CI: 33.5–35.6) of the 12 773 PWH had a weight gain ≥10%, with 20.9% (95% CI: 19.6–22.2) among the 5794 with early presentation and 63.1% (95% CI: 60.9–65.3) among the 3106 with advanced presentation. Weight gain was 2.8 kg (95% CI: 2.0–3.7) for those with early presentation and 9.7 kg (95% CI: 8.4–11.1) for those with advanced presentation. Most weight gain occurred in the first 12 months. Underweight and obese PWH were at significantly higher risk of a BMI increase ≥5 kg/m2 than normal-weight PWH. Results differed within classes and by outcome. Raltegravir and dolutegravir were consistently associated with greater weight gain than the other third agents. Tenofovir alafenamide was also associated with higher weight gain than tenofovir disoproxil or abacavir.ConclusionsAfter initiating cART, PWH with early presentation exhibited a small weight gain, whereas it was large among those with advanced presentation. The choice of ART should account for the risk of weight gain, especially for PWH who present with advanced disease and/or are obese.

Published
2023

26. Synergistic Activity of Pep16, a Promising New Antibacterial Pseudopeptide against Multidrug-Resistant Organisms, in Combination with Colistin against Multidrug-Resistant Escherichia coli, In Vitro and in a Murine Peritonitis Model

Author

Samuel Chosidow, Bruno Fantin, Irène Nicolas, Jean-Baptiste Mascary, Françoise Chau, Valérie Bordeau, Marie-Clemence Verdier, Pierre Rocheteau, Francois Guérin, Vincent Cattoir, Victoire de Lastours, 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, Olgram, 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 ), CHU Pontchaillou [Rennes], and This study was supported by internal funding from 'IAME' and from the 'Fondation pour la Recherche Médicale' (Equipe FRM 2016, Grant Number DEQ20161136698).

Subjects
Microbiology (medical), antimicrobial peptides, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Escherichia coli, Pharmacology (medical), colistin, multiresistance, murine models, General Pharmacology, Toxicology and Pharmaceutics, Biochemistry, Microbiology
Abstract

International audience; Colistin is a drug of last resort to treat extreme drug-resistant Enterobacterales, but is limited by dose-dependent toxicity and the emergence of resistance. A recently developed antimicrobial pseudopeptide, Pep16, which acts on the cell membrane, may be synergistic with colistin and limit the emergence of resistance. We investigated Pep16 activity against Escherichia coli with varying susceptibility to colistin, in vitro and in a murine peritonitis model. Two isogenic derivatives of E. coli CFT073 (susceptible and resistant to colistin) and 2 clinical isolates (susceptible (B119) and resistant to colistin (Af31)) were used. Pep16 activity, alone and in combination with colistin, was determined in vitro (checkerboard experiments, time-kill curves, and flow cytometry to investigate membrane permeability). Toxicity and pharmacokinetic analyses of subcutaneous Pep16 were performed in mice, followed by the investigation of 10 mg/kg Pep16 + 10 mg/kg colistin (mimicking human concentrations) in a murine peritonitis model. Pep16 alone was inactive (MICs = 32-64 mg/L; no bactericidal effect). A concentration-dependent bactericidal synergy of Pep16 with colistin was evidenced on all strains, confirmed by flow cytometry. In vivo, Pep16 alone was ineffective. When Pep16 and colistin were combined, a significant decrease in bacterial counts in the spleen was evidenced, and the combination prevented the emergence of colistin-resistant mutants, compared to colistin alone. Pep16 synergizes with colistin in vitro, and the combination is more effective than colistin alone in a murine peritonitis by reducing bacterial counts and the emergence of resistance. Pep16 may optimize colistin use, by decreasing the doses needed, while limiting the emergence of colistin-resistant mutants.

Published
2023

27. Diagnostic stewardship in infectious diseases: a continuum of antimicrobial stewardship in the fight against antimicrobial resistance

Author

Johnny Zakhour, Sara F Haddad, Anthony Kerbage, Heiman Wertheim, Pierre Tattevin, Andreas Voss, Serhat Ünal, Abdoul Salam Ouedraogo, Souha S Kanj, American University of Beirut Faculty of Medicine and Medical Center (AUB), Mayo Clinic [Rochester], Radboud University Medical Center [Nijmegen], 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 ), University Medical Center Groningen [Groningen] (UMCG), Faculty of Medicine [Hacettepe University], and Hacettepe University = Hacettepe Üniversitesi

Subjects
Microbiology (medical), All institutes and research themes of the Radboud University Medical Center, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pharmacology (medical), Novel diagnostics in Infectious Diseases, General Medicine, Antimicrobial stewardship, Multidisciplinary teams, Diagnostic stewardship
Abstract

Contains fulltext : 293869.pdf (Publisher’s version ) (Open Access) Antimicrobial resistance (AMR) has been exacerbated by the inappropriate use of diagnostics, leading to excessive prescription of antimicrobials, and is an imminent threat to global health. Diagnostic stewardship (DS) is an auxiliary to antimicrobial stewardship (AMS) and comprises ordering the right tests, for the right patient, at the right time. It also promotes the judicious use of rapid and novel molecular diagnostic tools to enable the initiation of proper antibiotic therapy, while avoiding excessive use of broad-spectrum antibiotics. Proper interpretation of test results is crucial to avoid overdiagnosis and excessive healthcare costs. Although many rapid diagnostic tools have been developed with a high diagnostic yield, they are often limited by accessibility, cost, and lack of knowledge regarding their use. Careful consideration of clinical signs and symptoms with knowledge of the local epidemiology are essential for DS. This enables appropriate interpretation of microbiological results. Multidisciplinary teams that include well trained professionals should cooperate to promote DS. Challenges and barriers to the implementation of DS are mostly caused by scarcity of resources and lack of trained personnel and, most importantly, lack of knowledge. The lack of resources is often due to absence of awareness of the impact that good medical microbiology diagnostic facilities and expertise can have on the proper use of antibiotics. 01 juli 2023

Published
2023

28. Mortality in hepatitis C virus-cured vs. hepatitis C virus-uninfected people with HIV: a matched analysis in the ANRS CO4 FHDH cohort

Author

Requena, Maria-Bernarda, Grabar, Sophie, Lanoy, Emilie, Pialoux, Gilles, Billaud, Eric, Duvivier, Claudine, Merle, Philippe, Piroth, Lionel, Tattevin, Pierre, Salmon, Dominique, Weiss, Laurence, Costagliola, Dominique, Lacombe, Karine, Épidémiologie clinique des maladies virales chroniques [iPLesp] (CLEPIVIR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), 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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), 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), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 ), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Sidaction

Subjects
direct-acting antiviral agents, HIV/Hepatitis C coinfection, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, sustained virologic response, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, mortality
Abstract

International audience; Objective: It is unknown whether HCV-cured people with HIV (PWH) without cirrhosis reached the same mortality risk as HCV-uninfected PWH. We aimed to compare mortality in PWH cured of HCV by direct-acting antivirals (DAAs) to mortality in individuals with HIV monoinfection. Design: Nationwide hospital cohort. Methods: HIV-controlled participants without cirrhosis and HCV-cured by DAAs started between 09/2013 and 09/2020, were matched on age (±5 years), sex, HIV transmission group, AIDS status, and BMI (±1 kg/m 2) to up to ten participants with a virally suppressed HIV monoinfection followed at the time of HCV cure ± 6 months. Poisson regression models with robust variance estimates were used to compare mortality in both groups after adjusting for confounders. Results: The analysis included 3961 HCV-cured PWH (G1) and 33 872 HCV-uninfected PWH (G2). Median follow-up was 3.7 years in G1 (interquartile range (IQR): 2.0-4.6), and 3.3 years in G2. Median age was 52.0 years (IQR: 47.0–56.0), and 29 116 (77.0%) were men. There were 150 deaths in G1 (adjusted incidence rate (aIR): 12.2/1000 person-years) and 509 (aIR: 6.3/1000 person-years) in G2, with an incidence rate ratio (IRR): 1.9 [95%CI, 1.4–2.7]. The risk remained elevated 12 months post HCV cure (IRR: 2.4 [95%CI, 1.6–3.5]). Non-AIDS/nonliver-related malignancy was the most common cause of death in G1 (28 deaths).Conclusions: Despite HCV cure and HIV viral suppression, after controlling on factors related to mortality, DAA-cured PWH without cirrhosis remain at higher risk of all-cause mortality than people with HIV monoinfection. A better understanding of the determinants of mortality is needed in this population.

Published
2023

29. Simple purification and characterization of soluble and homogenous ABC-F translation factors from Enterococcus faecium

Author

Demay, Fanny, Hallier, Marc, Georgeault, Sylvie, Com, Emmanuelle, Cattoir, Vincent, Goude, Renan, Gillet, Reynald, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), 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 ), Infrastructures en Biologie Santé et Agronomie, IBiSA, Fondation pour la Recherche Médicale, FRM, (FRM EQU202203014663), Conseil Régional de Bretagne, and Université de Rennes 1

Subjects
ABC-F protein, Antibiotic resistance, SUMO, [SDV]Life Sciences [q-bio], Heparin chromatography, Ni-NTA chromatography
Abstract

International audience; The family of ATP-binding cassette F proteins (ABC-F) is mainly made up of cytosolic proteins involved in regulating protein synthesis, and they are often part of a mechanism that confers resistance to ribosome-targeting antibiotics. The existing literature has emphasized the difficulty of purifying these recombinant proteins because of their very low solubility and stability. Here, we describe a rapid and efficient three-step purification procedure that allows for the production of untagged ABC-F proteins from Enterococcus faecium in the heterologous host Escherichia coli. After four purified ABC-F proteins were produced using this protocol, their biological activities were validated by in vitro experiment. In conclusion, our study provides an invaluable tool for obtaining large amounts of untagged and soluble ABC-F proteins that can then be used for in vitro experiments. © 2023 Elsevier Inc.

Published
2023

30. Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19

Author

Kartsonaki, Christiana, Baillie, J Kenneth, Barrio, Noelia García, Baruch, Joaquín, Beane, Abigail, Blumberg, Lucille, Bozza, Fernando, Broadley, Tessa, Burrell, Aidan, Carson, Gail, Citarella, Barbara Wanjiru, Dagens, Andrew, Dankwa, Emmanuelle A, Donnelly, Christl A, Dunning, Jake, Elotmani, Loubna, Escher, Martina, Farshait, Nataly, Goffard, Jean-Christophe, Gonçalves, Bronner P, Hall, Matthew, Hashmi, Madiha, Sim Lim Heng, Benedict, Ho, Antonia, Jassat, Waasila, Pedrera Jiménez, Miguel, Laouenan, Cedric, Lissauer, Samantha, Martin-Loeches, Ignacio, Mentré, France, Merson, Laura, Morton, Ben, Munblit, Daniel, Nekliudov, Nikita A, Nichol, Alistair D, Singh Oinam, Budha Charan, Ong, David, Panda, Prasan Kumar, Petrovic, Michele, Pritchard, Mark G, Ramakrishnan, Nagarajan, Ramos, Grazielle Viana, Roger, Claire, Sandulescu, Oana, Semple, Malcolm G, Sharma, Pratima, Sigfrid, Louise, Somers, Emily C, Streinu-Cercel, Anca, Taccone, Fabio, Vecham, Pavan Kumar, Kumar Tirupakuzhi Vijayaraghavan, Bharath, Wei, Jia, Wils, Evert-Jan, Ci Wong, Xin, Horby, Peter, Rojek, Amanda, Olliaro, Piero L, ISARIC Clinical Characterisation Group: Ali Abbas, Sheryl Ann Abdukahil, Nurul Najmee Abdulkadir, Ryuzo Abe, Laurent Abel, Lara Absil, Subhash Acharya, Andrew Acker, Elisabeth Adam, Diana Adrião, Saleh Al Ageel, Shakeel Ahmed, Kate Ainscough, Eka Airlangga, Tharwat Aisa, Ali Ait Hssain, Younes Ait Tamlihat, Takako Akimoto, Ernita Akmal, Eman Al Qasim, Razi Alalqam, Angela Alberti, Tala Al-Dabbous, Senthilkumar Alegesan, Cynthia Alegre, Marta Alessi, Beatrice Alex, Kévin Alexandre, Abdulrahman Al-Fares, Huda Alfoudri, Imran Ali, Adam Ali, Naseem Ali Shah, Kazali Enagnon Alidjnou, Jeffrey Aliudin, Qabas Alkhafajee, Clotilde Allavena, Nathalie Allou, Aneela Altaf, João Alves, Rita Alves, João Melo Alves, Maria Amaral, Nur Amira, Phoebe Ampaw, Roberto Andini, Claire Andréjak, Andrea Angheben, François Angoulvant, Séverine Ansart, Sivanesen Anthonidass, Massimo Antonelli, Carlos Alexandre Antunes de Brito, Ardiyan Apriyana, Yaseen Arabi, Irene Aragao, Francisco Arancibia, Carolline Araujo, Antonio Arcadipane, Patrick Archambault, Lukas Arenz, Jean-Benoît Arlet, Christel Arnold-Day, Lovkesh Arora, Rakesh Arora, Elise Artaud-Macari, Diptesh Aryal, Angel Asensio, Muhammad Ashraf, Namra Asif, Mohammad Asim, Jean Baptiste Assie, Amirul Asyraf, Anika Atique, A M Udara Lakshan Attanyake, Johann Auchabie, Hugues Aumaitre, Adrien Auvet, Laurène Azemar, Cecile Azoulay, Benjamin Bach, Delphine Bachelet, Claudine Badr, Nadia Baig, J Kevin Baird, Erica Bak, Agamemnon Bakakos, Nazreen Abu Bakar, Andriy Bal, Mohanaprasanth Balakrishnan, Valeria Balan, Firouzé Bani-Sadr, Renata Barbalho, Nicholas Yuri Barbosa, Wendy S Barclay, Saef Umar Barnett, Michaela Barnikel, Helena Barrasa, Audrey Barrelet, Cleide Barrigoto, Marie Bartoli, Mustehan Bashir, Romain Basmaci, Muhammad Fadhli Hassin Basri, Denise Battaglini, Jules Bauer, Diego Fernando Bautista Rincon, Denisse Bazan Dow, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Aleksandr Beljantsev, David Bellemare, Anna Beltrame, Beatriz Amorim Beltrão, Marine Beluze, Nicolas Benech, Lionel Eric Benjiman, Dehbia Benkerrou, Suzanne Bennett, Luís Bento, Jan-Erik Berdal, Delphine Bergeaud, Hazel Bergin, José Luis Bernal Sobrino, Giulia Bertoli, Lorenzo Bertolino, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Amar Bhatt, Krishna Bhavsar, Claudia Bianco, Farah Nadiah Bidin, Moirangthem Bikram Singh, Felwa Bin Humaid, Mohd Nazlin Bin Kamarudin, François Bissuel, Patrick Biston, Laurent Bitker, Jonathan Bitton, Pablo Blanco-Schweizer, Catherine Blier, Frank Bloos, Mathieu Blot, Filomena Boccia, Laetitia Bodenes, Alice Bogaarts, Debby Bogaert, Anne-Hélène Boivin, Pierre-Adrien Bolze, François Bompart, Aurelius Bonfasius, Diogo Borges, Raphaël Borie, Hans Martin Bosse, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, Sabelline Bouchez, Dounia Bouhmani, Damien Bouhour, Kévin Bouiller, Laurence Bouillet, Camile Bouisse, Anne-Sophie Boureau, John Bourke, Maude Bouscambert, Aurore Bousquet, Jason Bouziotis, Bianca Boxma, Marielle Boyer-Besseyre, Maria Boylan, Axelle Braconnier, Cynthia Braga, Timo Brandenburger, Filipa Brás Monteiro, Luca Brazzi, Patrick Breen, Dorothy Breen, Kathy Brickell, Shaunagh Browne, Alex Browne, Nicolas Brozzi, Marjolein Brusse-Keizer, Nina Buchtele, Christian Buesaquillo, Polina Bugaeva, Marielle Buisson, Danilo Buonsenso, Erlina Burhan, Ingrid G Bustos, Denis Butnaru, André Cabie, Susana Cabral, Eder Caceres, Cyril Cadoz, Mia Callahan, Kate Calligy, Jose Andres Calvache, João Camões, Valentine Campana, Paul Campbell, Josie Campisi, Cecilia Canepa, Mireia Cantero, Pauline Caraux-Paz, Sheila Cárcel, Chiara Simona Cardellino, Sofia Cardoso, Filipe Cardoso, Filipa Cardoso, Nelson Cardoso, Simone Carelli, Nicolas Carlier, Thierry Carmoi, Gayle Carney, Inês Carqueja, Marie-Christine Carret, François Martin Carrier, Ida Carroll, Maire-Laure Casanova, Mariana Cascão, Siobhan Casey, José Casimiro, Bailey Cassandra, Silvia Castañeda, Nidyanara Castanheira, Guylaine Castor-Alexandre, Henry Castrillón, Ivo Castro, Ana Catarino, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Giulio Giovanni Cavalli, Alexandros Cavayas, Adrian Ceccato, Minerva Cervantes-Gonzalez, Anissa Chair, Catherine Chakveatze, Adrienne Chan, Meera Chand, Christelle Chantalat Auger, Jean-Marc Chapplain, Julie Chas, Allegra Chatterjee, Mobin Chaudry, Jonathan Samuel Chávez Iñiguez, Anjellica Chen, Yih-Sharng Chen, Matthew Pellan Cheng, Antoine Cheret, Thibault Chiarabini, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Catherine Chirouze, Davide Chiumello, Sung-Min Cho, Bernard Cholley, Marie-Charlotte Chopin, Ting Soo Chow, Yock Ping Chow, Hiu Jian Chua, Jonathan Chua, Jose Pedro Cidade, José Miguel Cisneros Herreros, Anna Ciullo, Jennifer Clarke, Emma Clarke, Rolando Claure-Del Granado, Sara Clohisey, Perren J Cobb, Cassidy Codan, Caitriona Cody, Alexandra Coelho, Megan Coles, Gwenhaël Colin, Michael Collins, Sebastiano Maria Colombo, Pamela Combs, Marie Connor, Anne Conrad, Sofía Contreras, Elaine Conway, Graham S Cooke, Mary Copland, Hugues Cordel, Amanda Corley, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Andrea Cortegiani, Grégory Corvaisier, Emma Costigan, Camille Couffignal, Sandrine Couffin-Cadiergues, Roxane Courtois, Stéphanie Cousse, Rachel Cregan, Charles Crepy D'Orleans, Cosimo Cristella, Sabine Croonen, Gloria Crowl, Jonathan Crump, Claudina Cruz, Juan Luis Cruz Berm, Jaime Cruz Rojo, Marc Csete, Ailbhe Cullen, Matthew Cummings, Gerard Curley, Elodie Curlier, Colleen Curran, Paula Custodio, Ana da Silva Filipe, Charlene Da Silveira, Al-Awwab Dabaliz, Darren Dahly, Heidi Dalton, Jo Dalton, Seamus Daly, Nick Daneman, Corinne Daniel, Jorge Dantas, Frédérick D'Aragon, Menno de Jong, Gillian de Loughry, Diego de Mendoza, Etienne De Montmollin, Rafael Freitas de Oliveira França, Ana Isabel de Pinho Oliveira, Rosanna De Rosa, Cristina De Rose, Thushan de Silva, Peter de Vries, Jillian Deacon, David Dean, Alexa Debard, Marie-Pierre Debray, Nathalie DeCastro, William Dechert, Lauren Deconninck, Romain Decours, Eve Defous, Isabelle Delacroix, Eric Delaveuve, Karen Delavigne, Nathalie M Delfos, Ionna Deligiannis, Andrea Dell'Amore, Christelle Delmas, Pierre Delobel, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Dominique Deplanque, Pieter Depuydt, Mehul Desai, Diane Descamps, Mathilde Desvallées, Santi Dewayanti, Pathik Dhanger, Alpha Diallo, Sylvain Diamantis, André Dias, Juan Jose Diaz, Priscila Diaz, Rodrigo Diaz, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Jérôme Dimet, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Félix Djossou, Annemarie B Docherty, Helen Doherty, Arjen M Dondorp, Andy Dong, Maria Donnelly, Sean Donohue, Yoann Donohue, Chloe Donohue, Peter Doran, Céline Dorival, Eric D'Ortenzio, James Joshua Douglas, Renee Douma, Nathalie Dournon, Triona Downer, Joanne Downey, Mark Downing, Tom Drake, Aoife Driscoll, Murray Dryden, Claudio Duarte Fonseca, Vincent Dubee, François Dubos, Alexandre Ducancelle, Toni Duculan, Susanne Dudman, Abhijit Duggal, Paul Dunand, Mathilde Duplaix, Emanuele Durante-Mangoni, Lucian Durham, Bertrand Dussol, Juliette Duthoit, Xavier Duval, Anne Margarita Dyrhol-Riise, Sim Choon Ean, Marco Echeverria-Villalobos, Siobhan Egan, Carla Eira, Mohammed El Sanharawi, Subbarao Elapavaluru, Brigitte Elharrar, Jacobien Ellerbroek, Philippine Eloy, Tarek Elshazly, Iqbal Elyazar, Isabelle Enderle, Tomoyuki Endo, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Mariano Esperatti, Hélène Esperou, Marina Esposito-Farese, João Estevão, Manuel Etienne, Nadia Ettalhaoui, Anna Greti Everding, Mirjam Evers, Marc Fabre, Isabelle Fabre, Amna Faheem, Arabella Fahy, Cameron J Fairfield, Zul Fakar, Komal Fareed, Pedro Faria, Ahmed Farooq, Hanan Fateena, Arie Zainul Fatoni, Karine Faure, Raphaël Favory, Mohamed Fayed, Niamh Feely, Laura Feeney, Jorge Fernandes, Marília Andreia Fernandes, Susana Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Sílvia Ferreira, Isabel Ferreira, Benigno Ferreira, Ricard Ferrer-Roca, Nicolas Ferriere, Céline Ficko, Claudia Figueiredo-Mello, William Finlayson, Juan Fiorda, Thomas Flament, Clara Flateau, Tom Fletcher, Letizia Lucia Florio, Deirdre Flynn, Claire Foley, Jean Foley, Victor Fomin, Tatiana Fonseca, Patricia Fontela, Simon Forsyth, Denise Foster, Giuseppe Foti, Erwan Fourn, Robert A Fowler, Marianne Fraher, Diego Franch-Llasat, John F Fraser, Christophe Fraser, Marcela Vieira Freire, Ana Freitas Ribeiro, Caren Friedrich, Ricardo Fritz, Stéphanie Fry, Nora Fuentes, Masahiro Fukuda, G Argin, Valérie Gaborieau, Rostane Gaci, Massimo Gagliardi, Jean-Charles Gagnard, Amandine Gagneux-Brunon, Sérgio Gaião, Linda Gail Skeie, Phil Gallagher, Carrol Gamble, Yasmin Gani, Arthur Garan, Rebekha Garcia, Julia Garcia-Diaz, Esteban Garcia-Gallo, Navya Garimella, Denis Garot, Valérie Garrait, Basanta Gauli, Nathalie Gault, Aisling Gavin, Anatoliy Gavrylov, Alexandre Gaymard, Johannes Gebauer, Eva Geraud, Louis Gerbaud Morlaes, Nuno Germano, Praveen Kumar Ghisulal, Jade Ghosn, Marco Giani, Jess Gibson, Tristan Gigante, Morgane Gilg, Elaine Gilroy, Guillermo Giordano, Michelle Girvan, Valérie Gissot, Daniel Glikman, Petr Glybochko, Eric Gnall, Geraldine Goco, François Goehringer, Siri Goepel, Jin Yi Goh, Jonathan Golob, Rui Gomes, Kyle Gomez, Joan Gómez-Junyent, Marie Gominet, Alicia Gonzalez, Patricia Gordon, Isabelle Gorenne, Laure Goubert, Cécile Goujard, Tiphaine Goulenok, Margarite Grable, Jeronimo Graf, Edward Wilson Grandin, Pascal Granier, Giacomo Grasselli, Christopher A Green, Courtney Greene, William Greenhalf, Segolène Greffe, Domenico Luca Grieco, Matthew Griffee, Fiona Griffiths, Ioana Grigoras, Albert Groenendijk, Anja Grosse Lordemann, Heidi Gruner, Yusing Gu, Jérémie Guedj, Martin Guego, Dewi Guellec, Anne-Marie Guerguerian, Daniela Guerreiro, Romain Guery, Anne Guillaumot, Laurent Guilleminault, Maisa Guimarães de Castro, Thomas Guimard, Marieke Haalboom, Daniel Haber, Hannah Habraken, Ali Hachemi, Amy Hackmann, Nadir Hadri, Fakhir Haidri, Sheeba Hakak, Adam Hall, Sophie Halpin, Jawad Hameed, Ansley Hamer, Raph L Hamers, Rebecca Hamidfar, Terese Hammond, Lim Yuen Han, Rashan Haniffa, Kok Wei Hao, Hayley Hardwick, Ewen M Harrison, Janet Harrison, Samuel Bernard Ekow Harrison, Alan Hartman, Mohd Shahnaz Hasan, Junaid Hashmi, Muhammad Hayat, Ailbhe Hayes, Leanne Hays, Jan Heerman, Lars Heggelund, Ross Hendry, Martina Hennessy, Aquiles Henriquez-Trujillo, Maxime Hentzien, Jaime Hernandez-Montfort, Andrew Hershey, Liv Hesstvedt, Astarini Hidayah, Eibhilin Higgins, Dawn Higgins, Rupert Higgins, Rita Hinchion, Samuel Hinton, Hiroaki Hiraiwa, Haider Hirkani, Hikombo Hitoto, Yi Bin Ho, Alexandre Hoctin, Isabelle Hoffmann, Wei Han Hoh, Oscar Hoiting, Rebecca Holt, Jan Cato Holter, Juan Pablo Horcajada, Koji Hoshino, Ikram Houas, Catherine L Hough, Stuart Houltham, Jimmy Ming-Yang Hsu, Jean-Sébastien Hulot, Stella Huo, Abby Hurd, Iqbal Hussain, Samreen Ijaz, Hajnal-Gabriela Illes, Patrick Imbert, Mohammad Imran, Rana Imran Sikander, Aftab Imtiaz, Hugo Inácio, Carmen Infante Dominguez, Yun Sii Ing, Elias Iosifidis, Mariachiara Ippolito, Sarah Isgett, Tiago Isidoro, Nadiah Ismail, Margaux Isnard, Junji Itai, Daniel Ivulich, Danielle Jaafar, Salma Jaafoura, Julien Jabot, Clare Jackson, Nina Jamieson, Victoria Janes, Pierre Jaquet, Coline Jaud-Fischer, Stéphane Jaureguiberry, Jeffrey Javidfar, Denise Jaworsky, Florence Jego, Anilawati Mat Jelani, Synne Jenum, Ruth Jimbo-Sotomayor, Ong Yiaw Joe, Ruth N Jorge García, Cédric Joseph, Mark Joseph, Swosti Joshi, Mercé Jourdain, Philippe Jouvet, Hanna Jung, Anna Jung, Dafsah Juzar, Ouifiya Kafif, Florentia Kaguelidou, Neerusha Kaisbain, Thavamany Kaleesvran, Sabina Kali, Alina Kalicinska, Smaragdi Kalomoiri, Muhammad Aisar Ayadi Kamaluddin, Zul Amali Che Kamaruddin, Nadiah Kamarudin, Paul Kambiya, Kavita Kamineni, Darshana Hewa Kandamby, Chris Kandel, Kong Yeow Kang, Darakhshan Kanwal, Pratap Karpayah, Todd Karsies, Daisuke Kasugai, Anant Kataria, Kevin Katz, Aasmine Kaur, Christy Kay, Hannah Keane, Seán Keating, Pulak Kedia, Claire Kelly, Yvelynne Kelly, Andrea Kelly, Niamh Kelly, Aoife Kelly, Sadie Kelly, Maeve Kelsey, Ryan Kennedy, Kalynn Kennon, Maeve Kernan, Younes Kerroumi, Sharma Keshav, Imrana Khalid, Osama Khalid, Antoine Khalil, Coralie Khan, Irfan Khan, Quratul Ain Khan, Sushil Khanal, Abid Khatak, Amin Khawaja, Krish Kherajani, Michelle E Kho, Saye Khoo, Ryan Khoo, Denisa Khoo, Nasir Khoso, Khor How Kiat, Yuri Kida, Peter Kiiza, Beathe Kiland Granerud, Anders Benjamin Kildal, Jae Burm Kim, Antoine Kimmoun, Detlef Kindgen-Milles, Alexander King, Nobuya Kitamura, Paul Klenerman, Rob Klont, Gry Kloumann Bekken, Stephen R Knight, Robin Kobbe, Chamira Kodippily, Malte Kohns Vasconcelos, Sabin Koirala, Mamoru Komatsu, Caroline Kosgei, Arsène Kpangon, Karolina Krawczyk, Vinothini Krishnan, Sudhir Krishnan, Oksana Kruglova, Deepali Kumar, Ganesh Kumar, Mukesh Kumar, Dinesh Kuriakose, Ethan Kurtzman, Demetrios Kutsogiannis, Galyna Kutsyna, Konstantinos Kyriakoulis, Marie Lachatre, Marie Lacoste, John G Laffey, Marie Lagrange, Fabrice Laine, Olivier Lairez, Sanjay Lakhey, Antonio Lalueza, Marc Lambert, François Lamontagne, Marie Langelot-Richard, Vincent Langlois, Eka Yudha Lantang, Marina Lanza, Cédric Laouénan, Samira Laribi, Delphine Lariviere, Stéphane Lasry, Sakshi Lath, Naveed Latif, Odile Launay, Didier Laureillard, Yoan Lavie-Badie, Andy Law, Teresa Lawrence, Cassie Lawrence, Minh Le, Clément Le Bihan, Cyril Le Bris, Georges Le Falher, Lucie Le Fevre, Quentin Le Hingrat, Marion Le Maréchal, Soizic Le Mestre, Gwenaël Le Moal, Vincent Le Moing, Hervé Le Nagard, Paul Le Turnier, Ema Leal, Marta Leal Santos, Todd C Lee, James Lee, Jennifer Lee, Heng Gee Lee, Biing Horng Lee, Yi Lin Lee, Su Hwan Lee, Gary Leeming, Laurent Lefebvre, Bénédicte Lefebvre, Benjamin Lefevre, Sylvie LeGac, Jean-Daniel Lelievre, François Lellouche, Adrien Lemaignen, Véronique Lemee, Anthony Lemeur, Gretchen Lemmink, Ha Sha Lene, Jenny Lennon, Rafael León, Marc Leone, Michela Leone, Quentin Lepiller, François-Xavier Lescure, Olivier Lesens, Mathieu Lesouhaitier, Amy Lester-Grant, Bruno Levy, Yves Levy, Claire Levy-Marchal, Katarzyna Lewandowska, Erwan L'Her, Gianluigi Li Bassi, Janet Liang, Ali Liaquat, Geoffrey Liegeon, Wei Shen Lim, Kah Chuan Lim, Chantre Lima, Lim Lina, Bruno Lina, Andreas Lind, Maja Katherine Lingad, Guillaume Lingas, Sylvie Lion-Daolio, Keibun Liu, Marine Livrozet, Patricia Lizotte, Antonio Loforte, Navy Lolong, Leong Chee Loon, Diogo Lopes, Dalia Lopez-Colon, Jose W Lopez-Revilla, Anthony L Loschner, Paul Loubet, Bouchra Loufti, Guillame Louis, Silvia Lourenco, Lara Lovelace-Macon, Lee Lee Low, Marije Lowik, Jia Shyi Loy, Jean Christophe Lucet, Carlos Lumbreras Bermejo, Carlos M Luna, Olguta Lungu, Liem Luong, Nestor Luque, Dominique Luton, Nilar Lwin, Ruth Lyons, Olavi Maasikas, Oryane Mabiala, Moïse Machado, Gabriel Macheda, Hashmi Madiha, Guillermo Maestro de la Calle, Rafael Mahieu, Sophie Mahy, Ana Raquel Maia, Lars S Maier, Mylène Maillet, Thomas Maitre, Maximilian Malfertheiner, Nadia Malik, Paddy Mallon, Fernando Maltez, Denis Malvy, Victoria Manda, Laurent Mandelbrot, Frank Manetta, Julie Mankikian, Edmund Manning, Aldric Manuel, Ceila Maria Sant Ana Malaque, Flávio Marino, Daniel Marino, Samuel Markowicz, Charbel Maroun Eid, Ana Marques, Catherine Marquis, Brian Marsh, Laura Marsh, Megan Marshal, John Marshall, Celina Turchi Martelli, Dori-Ann Martin, Emily Martin, Guillaume Martin-Blondel, Martin Martinot, Alejandro Martin-Quiros, João Martins, Ana Martins, Nuno Martins, Caroline Martins Rego, Gennaro Martucci, Olga Martynenko, Eva Miranda Marwali, Marsilla Marzukie, David Maslove, Sabina Mason, Sobia Masood, Basri Mat Nor, Moshe Matan, Meghena Mathew, Daniel Mathieu, Mathieu Mattei, Romans Matulevics, Laurence Maulin, Michael Maxwell, Javier Maynar, Thierry Mazzoni, Natalie Mc Evoy, Lisa Mc Sweeney, Colin McArthur, Anne McCarthy, Aine McCarthy, Colin McCloskey, Rachael McConnochie, Sherry McDermott, Sarah E McDonald, Aine McElroy, Samuel McElwee, Victoria McEneany, Allison McGeer, Chris McKay, Johnny McKeown, Kenneth A McLean, Paul McNally, Bairbre McNicholas, Elaine McPartlan, Edel Meaney, Cécile Mear-Passard, Maggie Mechlin, Maqsood Meher, Omar Mehkri, Ferruccio Mele, Luis Melo, Kashif Memon, Joao Joao Mendes, Ogechukwu Menkiti, Kusum Menon, Alexander J Mentzer, Emmanuelle Mercier, Noémie Mercier, Antoine Merckx, Mayka Mergeay-Fabre, Blake Mergler, António Mesquita, Roberta Meta, Osama Metwally, Agnès Meybeck, Dan Meyer, Alison M Meynert, Vanina Meysonnier, Amina Meziane, Mehdi Mezidi, Céline Michelanglei, Isabelle Michelet, Efstathia Mihelis, Vladislav Mihnovit, Hugo Miranda-Maldonado, Nor Arisah Misnan, Tahira Jamal Mohamed, Nik Nur Eliza Mohamed, Asma Moin, David Molina, Elena Molinos, Brenda Molloy, Mary Mone, Agostinho Monteiro, Claudia Montes, Giorgia Montrucchio, Shona C Moore, Sarah Moore, Lina Morales Cely, Lucia Moro, Catherine Motherway, Ana Motos, Hugo Mouquet, Clara Mouton Perrot, Julien Moyet, Caroline Mudara, Aisha Kalsoom Mufti, Ng Yong Muh, Dzawani Muhamad, Jimmy Mullaert, Fredrik Müller, Karl Erik Müller, Syed Muneeb, Nadeem Munir, Laveena Munshi, Aisling Murphy, Lorna Murphy, Marlène Murris, Srinivas Murthy, Himed Musaab, Himasha Muvindi, Gugapriyaa Muyandy, Dimitra Melia Myrodia, Farah Nadia Mohd-Hanafiah, Dave Nagpal, Alex Nagrebetsky, Mangala Narasimhan, Nageswaran Narayanan, Rashid Nasim Khan, Alasdair Nazerali-Maitland, Nadège Neant, Holger Neb, Erni Nelwan, Raul Neto, Emily Neumann, Pauline Yeung Ng, Wing Yiu Ng, Anthony Nghi, Duc Nguyen, Orna Ni Choileain, Niamh Ni Leathlobhair, Prompak Nitayavardhana, Stephanie Nonas, Nurul Amani Mohd Noordin, Marion Noret, Nurul Faten Izzati Norharizam, Lisa Norman, Alessandra Notari, Mahdad Noursadeghi, Karolina Nowicka, Adam Nowinski, Saad Nseir, Jose I Nunez, Nurnaningsih Nurnaningsih, Dwi Utomo Nusantara, Elsa Nyamankolly, Fionnuala O Brien, Annmarie O Callaghan, Annmarie O'Callaghan, Giovanna Occhipinti, Derbrenn OConnor, Max O'Donnell, Tawnya Ogston, Takayuki Ogura, Tak-Hyuk Oh, Sophie O'Halloran, Katie O'Hearn, Shinichiro Ohshimo, Agnieszka Oldakowska, João Oliveira, Larissa Oliveira, Jee Yan Ong, Wilna Oosthuyzen, Anne Opavsky, Peter Openshaw, Saijad Orakzai, Claudia Milena Orozco-Chamorro, Jamel Ortoleva, Javier Osatnik, Linda O'Shea, Miriam O'Sullivan, Siti Zubaidah Othman, Nadia Ouamara, Rachida Ouissa, Eric Oziol, Maïder Pagadoy, Justine Pages, Mario Palacios, Amanda Palacios, Massimo Palmarini, Giovanna Panarello, Hem Paneru, Lai Hui Pang, Mauro Panigada, Nathalie Pansu, Aurélie Papadopoulos, Rachael Parke, Melissa Parker, Briseida Parra, Taha Pasha, Jérémie Pasquier, Bruno Pastene, Fabian Patauner, Drashti Patel, Mohan Dass Pathmanathan, Luís Patrão, Patricia Patricio, Juliette Patrier, Lisa Patterson, Rajyabardhan Pattnaik, Mical Paul, Christelle Paul, Jorge Paulos, William A Paxton, Jean-François Payen, Kalaiarasu Peariasamy, Giles J Peek, Florent Peelman, Nathan Peiffer-Smadja, Vincent Peigne, Mare Pejkovska, Paolo Pelosi, Ithan D Peltan, Rui Pereira, Daniel Perez, Luis Periel, Thomas Perpoint, Antonio Pesenti, Vincent Pestre, Lenka Petrou, Ventzislava Petrov-Sanchez, Frank Olav Pettersen, Gilles Peytavin, Scott Pharand, Michael Piagnerelli, Walter Picard, Olivier Picone, Maria de Piero, Carola Pierobon, Djura Piersma, Carlos Pimentel, Raquel Pinto, Catarina Pires, Isabelle Pironneau, Lionel Piroth, Ayodhia Pitaloka, Riinu Pius, Laurent Plantier, Hon Shen Png, Julien Poissy, Ryadh Pokeerbux, Maria Pokorska-Spiewak, Sergio Poli, Georgios Pollakis, Diane Ponscarme, Jolanta Popielska, Diego Bastos Porto, Andra-Maris Post, Douwe F Postma, Pedro Povoa, Diana Póvoas, Jeff Powis, Sofia Prapa, Sébastien Preau, Christian Prebensen, Jean-Charles Preiser, Anton Prinssen, Gamage Dona Dilanthi Priyadarshani, Lucia Proença, Sravya Pudota, Oriane Puéchal, Bambang Pujo Semedi, Mathew Pulicken, Gregory Purcell, Luisa Quesada, Vilmaris Quinones-Cardona, Víctor Quirós González, Else Quist-Paulsen, Mohammed Quraishi, Maia Rabaa, Christian Rabaud, Ebenezer Rabindrarajan, Aldo Rafael, Marie Rafiq, Gabrielle Ragazzo, Mutia Rahardjani, Rozanah Abd Rahman, Ahmad Kashfi Haji Ab Rahman, Arsalan Rahutullah, Fernando Rainieri, Giri Shan Rajahram, Pratheema Ramachandran, Ahmad Afiq Ramli, Blandine Rammaert, Asim Rana, Rajavardhan Rangappa, Ritika Ranjan, Christophe Rapp, Aasiyah Rashan, Thalha Rashan, Ghulam Rasheed, Menaldi Rasmin, Indrek Rätsep, Cornelius Rau, Tharmini Ravi, Ali Raza, Andre Real, Stanislas Rebaudet, Sarah Redl, Brenda Reeve, Attaur Rehman, Liadain Reid, Dag Henrik Reikvam, Renato Reis, Jordi Rello, Jonathan Remppis, Martine Remy, Hongru Ren, Hanna Renk, Anne-Sophie Resseguier, Matthieu Revest, Oleksa Rewa, Luis Felipe Reyes, Tiago Reyes, Maria Ines Ribeiro, Antonia Ricchiuto, David Richardson, Denise Richardson, Laurent Richier, Siti Nurul Atikah Ahmad Ridzuan, Jordi Riera, Ana L Rios, Asgar Rishu, Patrick Rispal, Karine Risso, Maria Angelica Rivera Nuñez, Nicholas Rizer, Chiara Robba, André Roberto, Stephanie Roberts, David L Robertson, Olivier Robineau, Ferran Roche-Campo, Paola Rodari, Simão Rodeia, Bernhard Roessler, Pierre-Marie Roger, Emmanuel Roilides, Juliette Romaru, Roberto Roncon-Albuquerque, Mélanie Roriz, Manuel Rosa-Calatrava, Michael Rose, Dorothea Rosenberger, Nurul Hidayah Mohammad Roslan, Andrea Rossanese, Matteo Rossetti, Bénédicte Rossignol, Patrick Rossignol, Stella Rousset, Carine Roy, Benoît Roze, Desy Rusmawatiningtyas, Clark D Russell, Maria Ryan, Maeve Ryan, Steffi Ryckaert, Aleksander Rygh Holten, Isabela Saba, Sairah Sadaf, Musharaf Sadat, Valla Sahraei, Maximilien Saint-Gilles, Pranya Sakiyalak, Nawal Salahuddin, Leonardo Salazar, Jodat Saleem, Gabriele Sales, Stéphane Sallaberry, Charlotte Salmon Gandonniere, Hélène Salvator, Olivier Sanchez, Angel Sanchez-Miralles, Vanessa Sancho-Shimizu, Gyan Sandhu, Zulfiqar Sandhu, Pierre-François Sandrine, Marlene Santos, Shirley Sarfo-Mensah, Bruno Sarmento Banheiro, Iam Claire E Sarmiento, Benjamine Sarton, Ankana Satya, Sree Satyapriya, Rumaisah Satyawati, Egle Saviciute, Parthena Savvidou, Yen Tsen Saw, Justin Schaffer, Tjard Schermer, Arnaud Scherpereel, Marion Schneider, Stephan Schroll, Michael Schwameis, Gary Schwartz, Brendan Scicluna, Janet T Scott, James Scott-Brown, Nicholas Sedillot, Tamara Seitz, Jaganathan Selvanayagam, Mageswari Selvarajoo, Caroline Semaille, Rasidah Bt Senian, Eric Senneville, Claudia Sepulveda, Filipa Sequeira, Tânia Sequeira, Ary Serpa Neto, Pablo Serrano Balazote, Ellen Shadowitz, Syamin Asyraf Shahidan, Mohammad Shamsah, Anuraj Shankar, Shaikh Sharjeel, Catherine A Shaw, Victoria Shaw, Ashraf Sheharyar, Rohan Shetty, Rajesh Mohan Shetty, Haixia Shi, Nisreen Shiban, Mohiuddin Shiekh, Nobuaki Shime, Hiroaki Shimizu, Keiki Shimizu, Sally Shrapnel, Pramesh Sundar Shrestha, Shubha Kalyan Shrestha, Hoi Ping Shum, Nassima Si Mohammed, Ng Yong Siang, Jeanne Sibiude, Atif Siddiqui, Piret Sillaots, Catarina Silva, Rogério Silva, Maria Joao Silva, Wai Ching Sin, Dario Sinatti, Punam Singh, Budha Charan Singh, Pompini Agustina Sitompul, Karisha Sivam, Vegard Skogen, Sue Smith, Benjamin Smood, Coilin Smyth, Michelle Smyth, Morgane Snacken, Dominic So, Tze Vee Soh, Joshua Solomon, Tom Solomon, Agnès Sommet, Rima Song, Tae Song, Jack Song Chia, Michael Sonntagbauer, Azlan Mat Soom, Alberto Sotto, Edouard Soum, Marta Sousa, Ana Chora Sousa, Maria Sousa Uva, Vicente Souza-Dantas, Alexandra Sperry, Elisabetta Spinuzza, B P Sanka Ruwan Sri Darshana, Shiranee Sriskandan, Sarah Stabler, Thomas Staudinger, Stephanie-Susanne Stecher, Trude Steinsvik, Ymkje Stienstra, Birgitte Stiksrud, Eva Stolz, Amy Stone, Adrian Streinu-Cercel, David Stuart, Ami Stuart, Decy Subekti, Gabriel Suen, Jacky Y Suen, Asfia Sultana, Charlotte Summers, Dubravka Supic, Deepashankari Suppiah, Magdalena Surovcová, Suwarti Suwarti, Andrey Svistunov, Sarah Syahrin, Konstantinos Syrigos, Jaques Sztajnbok, Konstanty Szuldrzynski, Shirin Tabrizi, Lysa Tagherset, Shahdattul Mawarni Taib, Ewa Talarek, Sara Taleb, Jelmer Talsma, Renaud Tamisier, Maria Lawrensia Tampubolon, Kim Keat Tan, Yan Chyi Tan, Taku Tanaka, Hiroyuki Tanaka, Hayato Taniguchi, Huda Taqdees, Arshad Taqi, Coralie Tardivon, Pierre Tattevin, M Azhari Taufik, Hassan Tawfik, Richard S Tedder, Tze Yuan Tee, João Teixeira, Sofia Tejada, Marie-Capucine Tellier, Sze Kye Teoh, Vanessa Teotonio, François Téoulé, Pleun Terpstra, Olivier Terrier, Nicolas Terzi, Hubert Tessier-Grenier, Adrian Tey, Alif Adlan Mohd Thabit, Anand Thakur, Zhang Duan Tham, Suvintheran Thangavelu, Vincent Thibault, Simon-Djamel Thiberville, Benoît Thill, Jananee Thirumanickam, Shaun Thompson, Emma C Thomson, David Thomson, Surain Raaj Thanga Thurai, Ryan S Thwaites, Paul Tierney, Vadim Tieroshyn, Peter S Timashev, Jean-François Timsit, Noémie Tissot, Jordan Zhien Yang Toh, Maria Toki, Kristian Tonby, Sia Loong Tonnii, Margarida Torres, Antoni Torres, Rosario Maria Torres Santos-Olmo, Hernando Torres-Zevallos, Michael Towers, Tony Trapani, Théo Treoux, Cécile Tromeur, Ioannis Trontzas, Tiffany Trouillon, Jeanne Truong, Christelle Tual, Sarah Tubiana, Helen Tuite, Jean-Marie Turmel, Lance C W Turtle, Anders Tveita, Pawel Twardowski, Makoto Uchiyama, P G Ishara Udayanga, Andrew Udy, Roman Ullrich, Alberto Uribe, Asad Usman, Timothy M Uyeki, Cristinava Vajdovics, Piero Valentini, Luís Val-Flores, Amélie Valran, Stijn Van de Velde, Marcel van den Berge, Machteld Van der Feltz, Job van der Palen, Paul van der Valk, Nicky Van Der Vekens, Peter Van der Voort, Sylvie Van Der Werf, Laura van Gulik, Jarne Van Hattem, Carolien van Netten, Frank van Someren Greve, Ilonka van Veen, Hugo Van Willigen, Noémie Vanel, Henk Vanoverschelde, Pooja Varghese, Michael Varrone, Shoban Raj Vasudayan, Charline Vauchy, Shaminee Veeran, Aurélie Veislinger, Sebastian Vencken, Sara Ventura, Annelies Verbon, James Vickers, José Ernesto Vidal, César Vieira, Deepak Vijayan, Joy Ann Villanueva, Judit Villar, Pierre-Marc Villeneuve, Andrea Villoldo, Gayatri Vishwanathan, Benoit Visseaux, Hannah Visser, Chiara Vitiello, Harald Vonkeman, Fanny Vuotto, Suhaila Abdul Wahab, Noor Hidayu Wahab, Nadirah Abdul Wahid, Marina Wainstein, Wan Fadzlina Wan Muhd Shukeri, Chih-Hsien Wang, Steve Webb, Katharina Weil, Tan Pei Wen, Sanne Wesselius, T Eoin West, Murray Wham, Bryan Whelan, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Surya Otto Wijaya, Keith Wille, Suzette Willems, Virginie Williams, Calvin Wong, Yew Sing Wong, Teck Fung Wong, Natalie Wright, Gan Ee Xian, Lim Saio Xian, Kuan Pei Xuan, Ioannis Xynogalas, Siti Rohani Binti Mohd Yakop, Masaki 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Munblit, Daniel, Nekliudov, Nikita A, Nichol, Alistair D, Singh Oinam, Budha Charan, Ong, David, Panda, Prasan Kumar, Petrovic, Michele, Pritchard, Mark G, Ramakrishnan, Nagarajan, Ramos, Grazielle Viana, Roger, Claire, Sandulescu, Oana, Semple, Malcolm G, Sharma, Pratima, Sigfrid, Louise, Somers, Emily C, Streinu-Cercel, Anca, Taccone, Fabio, Vecham, Pavan Kumar, Kumar Tirupakuzhi Vijayaraghavan, Bharath, Wei, Jia, Wils, Evert-Jan, Ci Wong, Xin, Horby, Peter, Rojek, Amanda, Olliaro, Piero L, ISARIC Clinical Characterisation Group: Ali Abbas, Sheryl Ann Abdukahil, Nurul Najmee Abdulkadir, Ryuzo Abe, Laurent Abel, Lara Absil, Subhash Acharya, Andrew Acker, Elisabeth Adam, Diana Adrião, Saleh Al Ageel, Shakeel Ahmed, Kate Ainscough, Eka Airlangga, Tharwat Aisa, Ali Ait Hssain, Younes Ait Tamlihat, Takako Akimoto, Ernita Akmal, Eman Al Qasim, Razi Alalqam, Angela Alberti, Tala Al-Dabbous, Senthilkumar Alegesan, Cynthia Alegre, Marta Alessi, Beatrice Alex, Kévin Alexandre, Abdulrahman Al-Fares, Huda Alfoudri, Imran Ali, Adam Ali, Naseem Ali Shah, Kazali Enagnon Alidjnou, Jeffrey Aliudin, Qabas Alkhafajee, Clotilde Allavena, Nathalie Allou, Aneela Altaf, João Alves, Rita Alves, João Melo Alves, Maria Amaral, Nur Amira, Phoebe Ampaw, Roberto Andini, Claire Andréjak, Andrea Angheben, François Angoulvant, Séverine Ansart, Sivanesen Anthonidass, Massimo Antonelli, Carlos Alexandre Antunes de Brito, Ardiyan Apriyana, Yaseen Arabi, Irene Aragao, Francisco Arancibia, Carolline Araujo, Antonio Arcadipane, Patrick Archambault, Lukas Arenz, Jean-Benoît Arlet, Christel Arnold-Day, Lovkesh Arora, Rakesh Arora, Elise Artaud-Macari, Diptesh Aryal, Angel Asensio, Muhammad Ashraf, Namra Asif, Mohammad Asim, Jean Baptiste Assie, Amirul Asyraf, Anika Atique, A M Udara Lakshan Attanyake, Johann Auchabie, Hugues Aumaitre, Adrien Auvet, Laurène Azemar, Cecile Azoulay, Benjamin Bach, Delphine Bachelet, Claudine Badr, Nadia Baig, J Kevin Baird, Erica Bak, Agamemnon Bakakos, Nazreen Abu Bakar, Andriy Bal, Mohanaprasanth Balakrishnan, Valeria Balan, Firouzé Bani-Sadr, Renata Barbalho, Nicholas Yuri Barbosa, Wendy S Barclay, Saef Umar Barnett, Michaela Barnikel, Helena Barrasa, Audrey Barrelet, Cleide Barrigoto, Marie Bartoli, Mustehan Bashir, Romain Basmaci, Muhammad Fadhli Hassin Basri, Denise Battaglini, Jules Bauer, Diego Fernando Bautista Rincon, Denisse Bazan Dow, Alexandra Bedossa, Ker Hong Bee, Husna Begum, Sylvie Behilill, Albertus Beishuizen, Aleksandr Beljantsev, David Bellemare, Anna Beltrame, Beatriz Amorim Beltrão, Marine Beluze, Nicolas Benech, Lionel Eric Benjiman, Dehbia Benkerrou, Suzanne Bennett, Luís Bento, Jan-Erik Berdal, Delphine Bergeaud, Hazel Bergin, José Luis Bernal Sobrino, Giulia Bertoli, Lorenzo Bertolino, Simon Bessis, Sybille Bevilcaqua, Karine Bezulier, Amar Bhatt, Krishna Bhavsar, Claudia Bianco, Farah Nadiah Bidin, Moirangthem Bikram Singh, Felwa Bin Humaid, Mohd Nazlin Bin Kamarudin, François Bissuel, Patrick Biston, Laurent Bitker, Jonathan Bitton, Pablo Blanco-Schweizer, Catherine Blier, Frank Bloos, Mathieu Blot, Filomena Boccia, Laetitia Bodenes, Alice Bogaarts, Debby Bogaert, Anne-Hélène Boivin, Pierre-Adrien Bolze, François Bompart, Aurelius Bonfasius, Diogo Borges, Raphaël Borie, Hans Martin Bosse, Elisabeth Botelho-Nevers, Lila Bouadma, Olivier Bouchaud, Sabelline Bouchez, Dounia Bouhmani, Damien Bouhour, Kévin Bouiller, Laurence Bouillet, Camile Bouisse, Anne-Sophie Boureau, John Bourke, Maude Bouscambert, Aurore Bousquet, Jason Bouziotis, Bianca Boxma, Marielle Boyer-Besseyre, Maria Boylan, Axelle Braconnier, Cynthia Braga, Timo Brandenburger, Filipa Brás Monteiro, Luca Brazzi, Patrick Breen, Dorothy Breen, Patrick Breen, Kathy Brickell, Shaunagh Browne, Alex Browne, Nicolas Brozzi, Marjolein Brusse-Keizer, Nina Buchtele, Christian Buesaquillo, Polina Bugaeva, Marielle Buisson, Danilo Buonsenso, Erlina Burhan, Ingrid G Bustos, Denis Butnaru, André Cabie, Susana Cabral, Eder Caceres, Cyril Cadoz, Mia Callahan, Kate Calligy, Jose Andres Calvache, João Camões, Valentine Campana, Paul Campbell, Josie Campisi, Cecilia Canepa, Mireia Cantero, Pauline Caraux-Paz, Sheila Cárcel, Chiara Simona Cardellino, Sofia Cardoso, Filipe Cardoso, Filipa Cardoso, Nelson Cardoso, Simone Carelli, Nicolas Carlier, Thierry Carmoi, Gayle Carney, Inês Carqueja, Marie-Christine Carret, François Martin Carrier, Ida Carroll, Maire-Laure Casanova, Mariana Cascão, Siobhan Casey, José Casimiro, Bailey Cassandra, Silvia Castañeda, Nidyanara Castanheira, Guylaine Castor-Alexandre, Henry Castrillón, Ivo Castro, Ana Catarino, François-Xavier Catherine, Paolo Cattaneo, Roberta Cavalin, Giulio Giovanni Cavalli, Alexandros Cavayas, Adrian Ceccato, Minerva Cervantes-Gonzalez, Anissa Chair, Catherine Chakveatze, Adrienne Chan, Meera Chand, Christelle Chantalat Auger, Jean-Marc Chapplain, Julie Chas, Allegra Chatterjee, Mobin Chaudry, Jonathan Samuel Chávez Iñiguez, Anjellica Chen, Yih-Sharng Chen, Matthew Pellan Cheng, Antoine Cheret, Thibault Chiarabini, Julian Chica, Suresh Kumar Chidambaram, Leong Chin Tho, Catherine Chirouze, Davide Chiumello, Sung-Min Cho, Bernard Cholley, Marie-Charlotte Chopin, Ting Soo Chow, Yock Ping Chow, Hiu Jian Chua, Jonathan Chua, Jose Pedro Cidade, José Miguel Cisneros Herreros, Anna Ciullo, Jennifer Clarke, Emma Clarke, Rolando Claure-Del Granado, Sara Clohisey, Perren J Cobb, Cassidy Codan, Caitriona Cody, Alexandra Coelho, Megan Coles, Gwenhaël Colin, Michael Collins, Sebastiano Maria Colombo, Pamela Combs, Marie Connor, Anne Conrad, Sofía Contreras, Elaine Conway, Graham S Cooke, Mary Copland, Hugues Cordel, Amanda Corley, Sabine Cornelis, Alexander Daniel Cornet, Arianne Joy Corpuz, Andrea Cortegiani, Grégory Corvaisier, Emma Costigan, Camille Couffignal, Sandrine Couffin-Cadiergues, Roxane Courtois, Stéphanie Cousse, Rachel Cregan, Charles Crepy D'Orleans, Cosimo Cristella, Sabine Croonen, Gloria Crowl, Jonathan Crump, Claudina Cruz, Juan Luis Cruz Berm, Jaime Cruz Rojo, Marc Csete, Ailbhe Cullen, Matthew Cummings, Gerard Curley, Elodie Curlier, Colleen Curran, Paula Custodio, Ana da Silva Filipe, Charlene Da Silveira, Al-Awwab Dabaliz, Darren Dahly, Heidi Dalton, Jo Dalton, Seamus Daly, Nick Daneman, Corinne Daniel, Jorge Dantas, Frédérick D'Aragon, Menno de Jong, Gillian de Loughry, Diego de Mendoza, Etienne De Montmollin, Rafael Freitas de Oliveira França, Ana Isabel de Pinho Oliveira, Rosanna De Rosa, Cristina De Rose, Thushan de Silva, Peter de Vries, Jillian Deacon, David Dean, Alexa Debard, Marie-Pierre Debray, Nathalie DeCastro, William Dechert, Lauren Deconninck, Romain Decours, Eve Defous, Isabelle Delacroix, Eric Delaveuve, Karen Delavigne, Nathalie M Delfos, Ionna Deligiannis, Andrea Dell'Amore, Christelle Delmas, Pierre Delobel, Corine Delsing, Elisa Demonchy, Emmanuelle Denis, Dominique Deplanque, Pieter Depuydt, Mehul Desai, Diane Descamps, Mathilde Desvallées, Santi Dewayanti, Pathik Dhanger, Alpha Diallo, Sylvain Diamantis, André Dias, Juan Jose Diaz, Priscila Diaz, Rodrigo Diaz, Kévin Didier, Jean-Luc Diehl, Wim Dieperink, Jérôme Dimet, Vincent Dinot, Fara Diop, Alphonsine Diouf, Yael Dishon, Félix Djossou, Annemarie B Docherty, Helen Doherty, Arjen M Dondorp, Andy Dong, Maria Donnelly, Sean Donohue, Yoann Donohue, Chloe Donohue, Peter Doran, Céline Dorival, Eric D'Ortenzio, James Joshua Douglas, Renee Douma, Nathalie Dournon, Triona Downer, Joanne Downey, Mark Downing, Tom Drake, Aoife Driscoll, Murray Dryden, Murray Dryden, Claudio Duarte Fonseca, Vincent Dubee, François Dubos, Alexandre Ducancelle, Toni Duculan, Susanne Dudman, Abhijit Duggal, Paul Dunand, Mathilde Duplaix, Emanuele Durante-Mangoni, Lucian Durham, Bertrand Dussol, Juliette Duthoit, Xavier Duval, Anne Margarita Dyrhol-Riise, Sim Choon Ean, Marco Echeverria-Villalobos, Siobhan Egan, Carla Eira, Mohammed El Sanharawi, Subbarao Elapavaluru, Brigitte Elharrar, Jacobien Ellerbroek, Philippine Eloy, Tarek Elshazly, Iqbal Elyazar, Isabelle Enderle, Tomoyuki Endo, Chan Chee Eng, Ilka Engelmann, Vincent Enouf, Olivier Epaulard, Mariano Esperatti, Hélène Esperou, Marina Esposito-Farese, João Estevão, Manuel Etienne, Nadia Ettalhaoui, Anna Greti Everding, Mirjam Evers, Marc Fabre, Isabelle Fabre, Amna Faheem, Arabella Fahy, Cameron J Fairfield, Zul Fakar, Komal Fareed, Pedro Faria, Ahmed Farooq, Hanan Fateena, Arie Zainul Fatoni, Karine Faure, Raphaël Favory, Mohamed Fayed, Niamh Feely, Laura Feeney, Jorge Fernandes, Marília Andreia Fernandes, Susana Fernandes, François-Xavier Ferrand, Eglantine Ferrand Devouge, Joana Ferrão, Mário Ferraz, Sílvia Ferreira, Isabel Ferreira, Benigno Ferreira, Ricard Ferrer-Roca, Nicolas Ferriere, Céline Ficko, Claudia Figueiredo-Mello, William Finlayson, Juan Fiorda, Thomas Flament, Clara Flateau, Tom Fletcher, Letizia Lucia Florio, Deirdre Flynn, Claire Foley, Jean Foley, Victor Fomin, Tatiana Fonseca, Patricia Fontela, Simon Forsyth, Denise Foster, Giuseppe Foti, Erwan Fourn, Robert A 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Srinivas Murthy, Himed Musaab, Himasha Muvindi, Gugapriyaa Muyandy, Dimitra Melia Myrodia, Farah Nadia Mohd-Hanafiah, Dave Nagpal, Alex Nagrebetsky, Mangala Narasimhan, Nageswaran Narayanan, Rashid Nasim Khan, Alasdair Nazerali-Maitland, Nadège Neant, Holger Neb, Erni Nelwan, Raul Neto, Emily Neumann, Pauline Yeung Ng, Wing Yiu Ng, Anthony Nghi, Duc Nguyen, Orna Ni Choileain, Niamh Ni Leathlobhair, Prompak Nitayavardhana, Stephanie Nonas, Nurul Amani Mohd Noordin, Marion Noret, Nurul Faten Izzati Norharizam, Lisa Norman, Alessandra Notari, Mahdad Noursadeghi, Karolina Nowicka, Adam Nowinski, Saad Nseir, Jose I Nunez, Nurnaningsih Nurnaningsih, Dwi Utomo Nusantara, Elsa Nyamankolly, Fionnuala O Brien, Annmarie O Callaghan, Annmarie O'Callaghan, Giovanna Occhipinti, Derbrenn OConnor, Max O'Donnell, Tawnya Ogston, Takayuki Ogura, Tak-Hyuk Oh, Sophie O'Halloran, Katie O'Hearn, Shinichiro Ohshimo, Agnieszka Oldakowska, João Oliveira, Larissa Oliveira, Jee Yan Ong, Wilna Oosthuyzen, Anne 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Gilles Peytavin, Scott Pharand, Michael Piagnerelli, Walter Picard, Olivier Picone, Maria de Piero, Carola Pierobon, Djura Piersma, Carlos Pimentel, Raquel Pinto, Catarina Pires, Isabelle Pironneau, Lionel Piroth, Ayodhia Pitaloka, Riinu Pius, Laurent Plantier, Hon Shen Png, Julien Poissy, Ryadh Pokeerbux, Maria Pokorska-Spiewak, Sergio Poli, Georgios Pollakis, Diane Ponscarme, Jolanta Popielska, Diego Bastos Porto, Andra-Maris Post, Douwe F Postma, Pedro Povoa, Diana Póvoas, Jeff Powis, Sofia Prapa, Sébastien Preau, Christian Prebensen, Jean-Charles Preiser, Anton Prinssen, Gamage Dona Dilanthi Priyadarshani, Lucia Proença, Sravya Pudota, Oriane Puéchal, Bambang Pujo Semedi, Mathew Pulicken, Gregory Purcell, Luisa Quesada, Vilmaris Quinones-Cardona, Víctor Quirós González, Else Quist-Paulsen, Mohammed Quraishi, Maia Rabaa, Christian Rabaud, Ebenezer Rabindrarajan, Aldo Rafael, Marie Rafiq, Gabrielle Ragazzo, Mutia Rahardjani, Rozanah Abd Rahman, Ahmad Kashfi Haji Ab Rahman, Arsalan Rahutullah, Fernando Rainieri, Giri Shan Rajahram, Pratheema Ramachandran, Ahmad Afiq Ramli, Blandine Rammaert, Asim Rana, Rajavardhan Rangappa, Ritika Ranjan, Christophe Rapp, Aasiyah Rashan, Thalha Rashan, Ghulam Rasheed, Menaldi Rasmin, Indrek Rätsep, Cornelius Rau, Tharmini Ravi, Ali Raza, Andre Real, Stanislas Rebaudet, Sarah Redl, Brenda Reeve, Attaur Rehman, Liadain Reid, Liadain Reid, Dag Henrik Reikvam, Renato Reis, Jordi Rello, Jonathan Remppis, Martine Remy, Hongru Ren, Hanna Renk, Anne-Sophie Resseguier, Matthieu Revest, Oleksa Rewa, Luis Felipe Reyes, Tiago Reyes, Maria Ines Ribeiro, Antonia Ricchiuto, David Richardson, Denise Richardson, Laurent Richier, Siti Nurul Atikah Ahmad Ridzuan, Jordi Riera, Ana L Rios, Asgar Rishu, Patrick Rispal, Karine Risso, Maria Angelica Rivera Nuñez, Nicholas Rizer, Chiara Robba, André Roberto, Stephanie Roberts, David L Robertson, Olivier Robineau, Ferran Roche-Campo, Paola Rodari, Simão Rodeia, Bernhard Roessler, Pierre-Marie Roger, 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Scherpereel, Marion Schneider, Stephan Schroll, Michael Schwameis, Gary Schwartz, Brendan Scicluna, Janet T Scott, James Scott-Brown, Nicholas Sedillot, Tamara Seitz, Jaganathan Selvanayagam, Mageswari Selvarajoo, Caroline Semaille, Rasidah Bt Senian, Eric Senneville, Claudia Sepulveda, Filipa Sequeira, Tânia Sequeira, Ary Serpa Neto, Pablo Serrano Balazote, Ellen Shadowitz, Syamin Asyraf Shahidan, Mohammad Shamsah, Anuraj Shankar, Shaikh Sharjeel, Catherine A Shaw, Victoria Shaw, Ashraf Sheharyar, Rohan Shetty, Rajesh Mohan Shetty, Haixia Shi, Nisreen Shiban, Mohiuddin Shiekh, Nobuaki Shime, Hiroaki Shimizu, Keiki Shimizu, Sally Shrapnel, Pramesh Sundar Shrestha, Shubha Kalyan Shrestha, Hoi Ping Shum, Nassima Si Mohammed, Ng Yong Siang, Jeanne Sibiude, Atif Siddiqui, Piret Sillaots, Catarina Silva, Rogério Silva, Maria Joao Silva, Wai Ching Sin, Dario Sinatti, Punam Singh, Budha Charan Singh, Pompini Agustina Sitompul, Karisha Sivam, Vegard Skogen, Sue Smith, Benjamin Smood, Coilin Smyth, Michelle Smyth, Michelle Smyth, Morgane Snacken, Dominic So, Tze Vee Soh, Joshua Solomon, Tom Solomon, Agnès Sommet, Rima Song, Tae Song, Jack Song Chia, Michael Sonntagbauer, Azlan Mat Soom, Alberto Sotto, Edouard Soum, Marta Sousa, Ana Chora Sousa, Maria Sousa Uva, Vicente Souza-Dantas, Alexandra Sperry, Elisabetta Spinuzza, B P Sanka Ruwan Sri Darshana, Shiranee Sriskandan, Sarah Stabler, Thomas Staudinger, Stephanie-Susanne Stecher, Trude Steinsvik, Ymkje Stienstra, Birgitte Stiksrud, Eva Stolz, Amy Stone, Adrian Streinu-Cercel, David Stuart, Ami Stuart, Decy Subekti, Gabriel Suen, Jacky Y Suen, Asfia Sultana, Charlotte Summers, Dubravka Supic, Deepashankari Suppiah, Magdalena Surovcová, Suwarti Suwarti, Andrey Svistunov, Sarah Syahrin, Konstantinos Syrigos, Jaques Sztajnbok, Konstanty Szuldrzynski, Shirin Tabrizi, Lysa Tagherset, Shahdattul Mawarni Taib, Ewa Talarek, Sara Taleb, Jelmer Talsma, Renaud Tamisier, Maria Lawrensia Tampubolon, Kim Keat Tan, Yan Chyi Tan, Taku Tanaka, Hiroyuki Tanaka, Hayato Taniguchi, Huda Taqdees, Arshad Taqi, Coralie Tardivon, Pierre Tattevin, M Azhari Taufik, Hassan Tawfik, Richard S Tedder, Tze Yuan Tee, João Teixeira, Sofia Tejada, Marie-Capucine Tellier, Sze Kye Teoh, Vanessa Teotonio, François Téoulé, Pleun Terpstra, Olivier Terrier, Nicolas Terzi, Hubert Tessier-Grenier, Adrian Tey, Alif Adlan Mohd Thabit, Anand Thakur, Zhang Duan Tham, Suvintheran Thangavelu, Vincent Thibault, Simon-Djamel Thiberville, Benoît Thill, Jananee Thirumanickam, Shaun Thompson, Emma C Thomson, David Thomson, Surain Raaj Thanga Thurai, Ryan S Thwaites, Paul Tierney, Vadim Tieroshyn, Peter S Timashev, Jean-François Timsit, Noémie Tissot, Jordan Zhien Yang Toh, Maria Toki, Kristian Tonby, Sia Loong Tonnii, Margarida Torres, Antoni Torres, Rosario Maria Torres Santos-Olmo, Hernando Torres-Zevallos, Michael Towers, Tony Trapani, Théo Treoux, Cécile Tromeur, Ioannis Trontzas, Tiffany Trouillon, Jeanne Truong, Christelle Tual, Sarah Tubiana, Helen Tuite, Jean-Marie Turmel, Lance C W Turtle, Anders Tveita, Pawel Twardowski, Makoto Uchiyama, P G Ishara Udayanga, Andrew Udy, Roman Ullrich, Alberto Uribe, Asad Usman, Timothy M Uyeki, Cristinava Vajdovics, Piero Valentini, Luís Val-Flores, Amélie Valran, Stijn Van de Velde, Marcel van den Berge, Machteld Van der Feltz, Job van der Palen, Paul van der Valk, Nicky Van Der Vekens, Peter Van der Voort, Sylvie Van Der Werf, Laura van Gulik, Jarne Van Hattem, Carolien van Netten, Frank van Someren Greve, Ilonka van Veen, Hugo Van Willigen, Noémie Vanel, Henk Vanoverschelde, Pooja Varghese, Michael Varrone, Shoban Raj Vasudayan, Charline Vauchy, Shaminee Veeran, Aurélie Veislinger, Sebastian Vencken, Sara Ventura, Annelies Verbon, James Vickers, José Ernesto Vidal, César Vieira, Deepak Vijayan, Joy Ann Villanueva, Judit Villar, Pierre-Marc Villeneuve, Andrea Villoldo, Gayatri Vishwanathan, Benoit Visseaux, Hannah Visser, Chiara Vitiello, Harald Vonkeman, Fanny Vuotto, Suhaila Abdul Wahab, Noor Hidayu Wahab, Nadirah Abdul Wahid, Marina Wainstein, Wan Fadzlina Wan Muhd Shukeri, Chih-Hsien Wang, Steve Webb, Katharina Weil, Tan Pei Wen, Sanne Wesselius, T Eoin West, Murray Wham, Bryan Whelan, Nicole White, Paul Henri Wicky, Aurélie Wiedemann, Surya Otto Wijaya, Keith Wille, Suzette Willems, Virginie Williams, Calvin Wong, Yew Sing Wong, Teck Fung Wong, Natalie Wright, Gan Ee Xian, Lim Saio Xian, Kuan Pei Xuan, Ioannis Xynogalas, Siti Rohani Binti Mohd Yakop, Masaki Yamazaki, Yazdan Yazdanpanah, Nicholas Yee Liang Hing, Cécile Yelnik, Chian Hui Yeoh, Stephanie Yerkovich, Toshiki Yokoyama, Hodane Yonis, Obada Yousif, Saptadi Yuliarto, Akram Zaaqoq, Marion Zabbe, Kai Zacharowski, Masliza Zahid, Maram Zahran, Nor Zaila Binti Zaidan, Maria Zambon, Miguel Zambrano, Alberto Zanella, Konrad Zawadka, Nurul Zaynah, Hiba Zayyad, Alexander Zoufaly, David Zucman, University of Oxford, 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, 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 ), This work was made possible by the UK Foreign, Commonwealth and Development Office, Wellcome (215091/Z/18/Z, 205228/Z/16/Z, 220757/Z/20/Z), Bill & Melinda Gates Foundation (OPP1209135), UK Medical Research Council Clinical Research Training Fellowship (MR/V001671/1), the philanthropic support of the donors to the University of Oxford’s COVID-19 Research Response Fund, CIHR Coronavirus Rapid Research Funding Opportunity (OV2170359) and the co-ordination in Canada by Sunnybrook Research Institute, endorsement of the Irish Critical Care—Clinical Trials Group, co-ordination in Ireland by the Irish Critical Care—Clinical Trials Network at University College Dublin and funding by the Health Research Board of Ireland (CTN-2014–12), the Rapid European COVID-19 Emergency Response research (RECOVER) (H2020 project 101003589) and European Clinical Research Alliance on Infectious Diseases (ECRAID) (965313), the COVID clinical management team, AIIMS, Rishikesh, India, the COVID-19 Clinical Management team, Manipal Hospital Whitefield, Bengaluru, India, Cambridge NIHR Biomedical Research Centre, the dedication and hard work of the Groote Schuur Hospital Covid ICU Team, support by the Groote Schuur nursing and University of Cape Town registrar bodies co-ordinated by the Division of Critical Care at the University of Cape Town, the Liverpool School of Tropical Medicine and the University of Oxford, the dedication and hard work of the Norwegian SARS-CoV-2 study team, the Research Council of Norway (grant no. 312780) and a philanthropic donation from Vivaldi Invest A/S owned by Jon Stephenson von Tetzchner, Imperial NIHR Biomedical Research Centre, the Comprehensive Local Research Networks of which PJMO is an NIHR Senior Investigator (NIHR201385), Innovative Medicines Initiative Joint Undertaking under Grant Agreement No. 115523 COMBACTE, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007– 2013) and EFPIA companies, in-kind contribution, the French COVID cohort (NCT04262921) is sponsored by INSERM and is funded by the REACTing (REsearch & ACtion emergING infectious diseases) consortium and by a grant of the French Ministry of Health (PHRC n 20–0424), Stiftungsfonds zur Förderung der Bekämpfung der Tuberkulose und anderer Lungenkrankheiten of the City of Vienna (project no. APCOV22BGM), Italian Ministry of Health ‘Fondi Ricerca corrente–L1P6’ to IRCCS Ospedale Sacro Cuore–Don Calabria, Australian Department of Health grant (3273191), Gender Equity Strategic Fund at University of Queensland, Artificial Intelligence for Pandemics (A14PAN) at University of Queensland, the Australian Research Council Centre of Excellence for Engineered Quantum Systems (EQUS, CE170100009), the Prince Charles Hospital Foundation, Australia, grants from Instituto de Salud Carlos III, Ministerio de Ciencia, Spain, Brazil, National Council for Scientific and Technological Development (scholarship no. 303953/2018–7), the Firland Foundation, Shoreline, Washington, USA, a grant from foundation Bevordering Onderzoek Franciscus, the South Eastern Norway Health Authority and the Research Council of Norway, and preparedness work conducted by the Short PeRiod IncideNce sTudy of Severe Acute Respiratory Infection. Data and Material provision was supported by grants from the National Institute for Health Research (NIHR, award CO-CIN-01), the Medical Research Council (MRC, and grant MC_PC_19059) and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with PHE (award no. 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award no. 200927), Liverpool Experimental Cancer Medicine Centre (grant no. C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award no. IS-BRC-1215–20013) and NIHR Clinical Research Network providing infrastructure support.

Subjects
Male, Epidemiology, MESH: Hospitalization, MESH: Proportional Hazards Models, MESH: Risk Factors, Risk Factors, MESH: Child, cohort study, MESH: COVID-19, Humans, MESH: SARS-CoV-2, Child, Proportional Hazards Models, MESH: Humans, MESH: Middle Aged, SARS-CoV-2, COVID-19, risk of death, General Medicine, Middle Aged, co-morbidities, symptoms, treatments, MESH: Male, Hospitalization, Intensive Care Units, MESH: Intensive Care Units, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, COVID-19/therapy
Abstract

Background We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. Methods The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). Results Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. Conclusions Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.

Published
2023

31. Recent Trends in Antimicrobial Resistance among Anaerobic Clinical Isolates

Author

Reissier, Sophie, Penven, Malo, Guerin, Francois, Cattoir, Vincent, 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 ), CHU Pontchaillou [Rennes], and None

Subjects
metronidazole, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, evolution, β-lactams, anaerobes, antimicrobial resistance, clindamycin
Abstract

International audience; Anaerobic bacteria are normal inhabitants of the human commensal microbiota and play an important role in various human infections. Tedious and time-consuming, antibiotic susceptibility testing is not routinely performed in all clinical microbiology laboratories, despite the increase in antibiotic resistance among clinically relevant anaerobes since the 1990s. β-lactam and metronidazole are the key molecules in the management of anaerobic infections, to the detriment of clindamycin. β-lactam resistance is usually mediated by the production of β-lactamases. Metronidazole resistance remains uncommon, complex, and not fully elucidated, while metronidazole inactivation appears to be a key mechanism. The use of clindamycin, a broad-spectrum anti-anaerobic agent, is becoming problematic due to the increase in resistance rate in all anaerobic bacteria, mainly mediated by Erm-type rRNA methylases. Second-line anti-anaerobes are fluoroquinolones, tetracyclines, chloramphenicol, and linezolid. This review aims to describe the up-to-date evolution of antibiotic resistance, give an overview, and understand the main mechanisms of resistance in a wide range of anaerobes. © 2023 by the authors.

Published
2023

32. Heart transplantation as salvage treatment of intractable infective endocarditis

Author

Pierre Tattevin, Patricia Muñoz, Asuncion Moreno, Guillaume Hékimian, François Delahaye, Xavier Duval, María Ángeles Castel, Barbara Hasse, Natalia Jaramillo, Josip Vincelj, Dannah Wray, Silvia Limonta, María Carmen Fariñas, Carlos A. Mestres, Jose M. Miro, 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 ), Instituto de Salud Carlos III [Madrid] (ISC), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hospices Civils de Lyon (HCL), Universität Zürich [Zürich] = University of Zurich (UZH), Medical University of South Carolina [Charleston] (MUSC), and Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

Subjects
Microbiology (medical), Infectious Diseases, General Immunology and Microbiology, infective endocarditis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, salvage treatment, General Medicine, peri-annular abscess, Cardiac surgery, heart transplantation
Abstract

International audience; BackgroundFor infective endocarditis (IE) with extensive perivalvular lesions or end-stage cardiac failure, heart transplantation (HT) may be the last resort.MethodsWe retrospectively collected all cases of HT for IE within the International Collaboration on Endocarditis (ICE) network.ResultsBetween 1991 and 2021, 20 patients (5 women, 15 men), median age 50 years [interquartile range, 29-61], underwent HT for IE in Spain (n = 9), France (n = 6), Switzerland (n = 2), Colombia, Croatia, and USA (n = 1). IE affected prosthetic (n = 10), and native valves (n = 10), primarily aortic (n = 11) and mitral (n = 6). The main pathogens were oral streptococci (n = 8), Staphylococcus aureus (n = 5), and Enterococcus faecalis (n = 2). The major complications included heart failure (n = 18), peri-annular abscess (n = 10), and prosthetic valve dehiscence (n = 4). Eighteen patients had previous cardiac surgery for this episode of IE, and four were on circulatory support before HT (left ventricular assist-device and extra-corporeal membrane oxygenation, 2 patients each). The median time interval between first symptoms of IE and HT was 44.5 days [22-91.5]. The main post-HT complication was acute rejection (n = 6). Seven patients died (35%), four during the first month post-HT. Thirteen (81%) of the 16 patients discharged from the hospital survived with a median follow-up of 35.5 months [4-96.5] after HT, and no relapse of IE.ConclusionsIE is not an absolute contraindication for HT: Our case series and the literature review support that HT may be considered as a salvage treatment in highly-selected patients with intractable IE.

Published
2023

33. 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

34. Use of the quantitative antibiogram method for assessing nosocomial transmission of ESBL-producing Enterobacterales in a French hospital

Author

A. Morin-Le Bihan, K. Le Neindre, L. Dejoies, C. Piau, P-Y. Donnio, G. Ménard, 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 ), and None

Subjects
Microbiology (medical), Klebsiella pneumoniae, lactamase, Infectious Diseases, Cross -transmission event, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Escherichia coli, Quantitative antibiogram, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, Extended -spectrum b, Pulsed -field gel electrophoresis
Abstract

International audience; Background: Extended-spectrum beta-lactamase-producing Enterobacterales (eESBL) have high prevalence in hospitals, but real-time monitoring of nosocomial acquisition through conventional typing methods is challenging. Moreover, patient-to-patient transmission varies between the main species, namely Escherichia coli and Klebsiella pneumoniae, which draws into question the relevance of applying identical preventive measures.Aim: To detect eESBL cross-transmission events (CTEs) using the quantitative antibiogram (QA) method in combination with epidemiological data (combined QA method), and to determine the effectiveness of standard or contact precautions for eESBL species. Methods: First, a validation set was used to compare the relevance of the combined QA method with a combination of pulsed-field gel electrophoresis and epidemiological data (combined PFGE method). Next, a 4-year retrospective analysis was conducted to detect eESBL CTEs in hospitalized patients. Two species were screened - ESBL E. coli (ESBL-Ec) and ESBL K. pneumoniae (ESBL-Kp). During the study, standard precautions alone were applied to patients with ESBL-Ec, whereas contact precautions were applied for patients with ESBL-Kp. Findings: As a proof of concept, use of the combined QA method and the combined PFGE method for the detection of CTEs gave identical results for E. coli, and similar results for at least 75% of K. pneumoniae. Overall, 722 patients with ESBL-Ec isolates and 280 patients with ESBL-Kp isolates were included in the retrospective analysis. Nine and 23 CTEs were identified for E. coli and K. pneumoniae, respectively, involving 20 (2.7%) and 36 (12.8%) patients, respectively.Conclusion: The combined QA method constitutes a rapid tool for epidemiological surveillance to detect CTEs. In the study hospital, standard precautions are sufficient to prevent acquisition of ESBL-Ec, whereas contact precautions must be implemented to prevent acquisition of ESBL-Kp.

Published
2023

35. The Association Between Antibiotic Use and Outcome Among Metastatic Melanoma Patients Receiving Immunotherapy

Author

Florence Poizeau, Sandrine Kerbrat, Frédéric Balusson, Pierre Tattevin, Matthieu Revest, Vincent Cattoir, David Luque-Paz, Thierry Lesimple, Marc Pracht, Monica Dinulescu, David Russo, Emmanuel Oger, Alain Dupuy, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), 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 ), Centre Eugène Marquis (CRLCC), This work was supported by the Ligue Contre le Cancer ([French] League Against Cancer) (PhD grant to FP)., and Chard-Hutchinson, Xavier

Subjects
Cancer Research, [SDV]Life Sciences [q-bio], Neoplasms, Second Primary, [SDV.CAN]Life Sciences [q-bio]/Cancer, Articles, Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, Dysbiosis, Humans, Immunologic Factors, Immunotherapy, Immune Checkpoint Inhibitors, Melanoma, Retrospective Studies
Abstract

Background Several observational studies have reported a decreased response to immune checkpoint inhibitors (ICI) following antibiotic use. ICI activity has been hypothesized to be impaired by antibiotic-induced gut dysbiosis. Methods Patients with advanced melanoma receiving an anti-PD-1 antibody as a first-line therapy between 2015 and 2017 in France were selected using the French Health Insurance database. We compared overall survival and time-to-treatment discontinuation according to antibiotic exposure in the 3 months prior to the initiation of anti-PD-1 antibody. To disentangle a causal effect of antibiotics from a confounding bias, we balanced characteristics of patients exposed and nonexposed to antibiotics using an overlap weighting method based on a propensity score. We also evaluated a control cohort of patients with advanced melanoma receiving first-line targeted therapy, as there is no rationale for decreased efficacy of targeted therapy following antibiotic treatment. Results The anti-PD-1 antibody cohort comprised 2605 individuals. Antibiotic exposure in the 3 months prior to anti-PD-1 antibody initiation was not associated with shorter overall survival (weighted hazard ratio = 1.01, 95% confidence interval = 0.88 to 1.17) or time-to-treatment discontinuation (weighted hazard ratio = 1.00, 95% confidence interval = 0.89 to 1.11). Consistent results were observed when the time frame of antibiotics was narrowed to 1 month prior to anti-PD-1 initiation or when exposure was restricted to antibiotics leading to more profound gut dysbiosis. Similar results were observed in the targeted therapy cohort. Conclusions In a large cohort of advanced melanoma patients, we showed that antibiotic use preceding anti-PD-1 antibody was not associated with worse outcome. Physicians should not delay immunotherapy for patients who have recently received antibiotics.

Published
2022

36. Changing profile of encephalitis: Results of a 4-year study in France

Author

A. Mailles, X. Argemi, C. Biron, P. Fillatre, T. De Broucker, R. Buzelé, A. Gagneux-Brunon, I. Gueit, C. Henry, S. Patrat-Delon, A. Makinson, E. Piet, H. Wille, M.O. Vareil, O. Epaulard, M. Martinot, P. Tattevin, J.P. Stahl, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Yves le Foll, Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], CHU Rouen, Normandie Université (NU), CHU Pontchaillou [Rennes], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Le CHCB, Centre Hospitalier de la Côte Basque, Centre Hospitalier Universitaire [Grenoble] (CHU), CH Colmar, ARN régulateurs bactériens et médecine (BRM), 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 )-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), This study was funded by the French Infectious Diseases Society (Société de pathologie de langue française)., Centre Hospitalier de la Côte Basque (CHCB), and 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 )

Subjects
Adult, Etiology, Epidemiology, [SDV]Life Sciences [q-bio], Cohort, Hospitals, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Encephalitis, Humans, France, Prospective Studies, 030212 general & internal medicine, 030217 neurology & neurosurgery, Outcome
Abstract

International audience; CONTEXT: In 2007, we performed a nationwide prospective study to assess the epidemiology of encephalitis in France. We aimed to evaluate epidemiological changes 10years later. METHODS: We performed a 4-year prospective cohort study in France (ENCEIF) from 2016 to 2019. Medical history, comorbidities, as well as clinical, biological, imaging, and demographic data were collected. For the comparison analysis, we selected similar data from adult patients enrolled in the 2007 study. We used Stata statistical software, version 15 (Stata Corp). Indicative variable distributions were compared using Pearson’s Chi(2) test, and means were compared using Student’s t-test for continuous variables. RESULTS: We analyzed 494 cases from 62 hospitals. A causative agent was identified in 65.7% of cases. Viruses represented 81.8% of causative agents, Herpesviridae being the most frequent (63.6%). Arboviruses accounted for 10.8%. Bacteria and parasites were responsible for respectively 14.8% and 1.2% of documented cases. Zoonotic infections represented 21% of cases. When comparing ENCEIF with the 2007 cohort (222 adults patients from 59 hospitals), a higher proportion of etiologies were obtained in 2016-2019 (66% vs. 53%). Between 2007 and 2016-2019, the proportions of Herpes simplex virus and Listeria encephalitis cases remained similar, but the proportion of tuberculosis cases decreased (P=0.0001), while tick-borne encephalitis virus (P=0.01) and VZV cases (P=0.03) increased. In the 2016-2019 study, 32 causative agents were identified, whereas only 17 were identified in the 2007 study. CONCLUSION: Our results emphasize the need to regularly perform such studies to monitor the evolution of infectious encephalitis and to adapt guidelines.

Published
2022

37. Prospective cohort of COVID-19 patients requiring hospital admission in Douala, Cameroon

Author

Tchamgoué, S, Ntep Eboko, M, Makamté, A, Ngagnia, A, Talla-Mba, F, Nitcheu Wendi, O, Kafando, E, Tengang, B, Sandjon, J P, Tattevin, P, Université de Douala, Hôpital Laquintinie [Douala, Cameroun], 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 ), and None

Subjects
Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, COVID-19, Cameroon, prognosis, mechanical ventilation, intensive care unit
Abstract

International audience; OBJECTIVES: To report characteristics and outcome of COVID-19 patients who required hospital admission in sub-Saharan Africa clinics with no access to invasive mechanical ventilation. METHODS: Between April and June 2021, documented COVID-19 patients with SaO(2) 6L/min. CT scan demonstrated extended lesions (>50%) in 50/61 cases (82%). Most patients received dexamethasone (n=64, 96%), heparin (n=64, 96%), chloroquine/azithromycin (n=59, 88%), and broad-spectrum antibiotics (n=59, 88%). Sixteen patients died (24%), after a median of 11.5 days [7.5-15.5] post-admission. CONCLUSIONS: Despite the lack of invasive mechanical ventilation, 76% of COVID-19 patients survived.

Published
2023

38. Osteosynthesis-associated infection of the lower limbs by multidrug-resistant and extensively drug-resistant Gram-negative bacteria: a multicentre cohort study

Author

Giannitsioti, Efthymia, Salles, Mauro José, Mavrogenis, Andreas, Rodriguez-Pardo, Dolors, Los-Arcos, Ibai, Ribera, Alba, Ariza, Javier, Toro, María Dolores, Nguyen, Sophie, Senneville, Eric, Bonnet, Eric, Chan, Monica, Pasticci, Maria Bruna, Petersdorf, Sabine, Benito, Natividad, Connell, Nuala, Blanco García, Antonio, Skaliczki, Gábor, Tattevin, Pierre, Kocak Tufan, Zeliha, Pantazis, Nikolaos, Megaloikonomos, Panayiotis D., Papagelopoulos, Panayiotis, Soriano, Alejandro, Papadopoulos, Antonios, the ESGIAI collaborators study group, National and Kapodistrian University of Athens (NKUA), 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 ), Salles, Mauro José, Pasticci, Maria Bruna, Benito, Natividad, O' Connell, Nuala, Skaliczki, Gábor, Pantazis, Nikolaos, Megaloikonomos, Panayiotis D ., and Soriano, Alejandro

Subjects
[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Original Full-Length Article, Orthopedics and Sports Medicine, Surgery
Abstract

[Purpose] The purpose of this study was the clinical and therapeutic assessment of lower-limb osteosynthesis-associated infection (OAI) by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), which have been poorly studied to date., [Methods] A prospective multicentre observational study was conducted on behalf of ESGIAI (the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Implant-Associated Infections). Factors associated with remission of the infection were evaluated by multivariate and Cox regression analysis for a 24-month follow-up period., [Results] Patients ( n=57 ) had a history of trauma (87.7 %), tumour resection (7 %) and other bone lesions (5.3 %). Pathogens included Escherichia coli ( n=16 ), Pseudomonas aeruginosa ( n=14 ; XDR 50 %), Klebsiella spp. ( n=7 ), Enterobacter spp. ( n=9 ), Acinetobacter spp. ( n=5 ), Proteus mirabilis ( n=3 ), Serratia marcescens ( n=2 ) and Stenotrophomonas maltophilia ( n=1 ). The prevalence of ESBL (extended-spectrum β -lactamase), fluoroquinolone and carbapenem resistance were 71.9 %, 59.6 % and 17.5 % respectively. Most patients ( n=37 ; 64.9 %) were treated with a combination including carbapenems ( n=32 ) and colistin ( n=11 ) for a mean of 63.3 d. Implant retention with debridement occurred in early OAI (66.7 %), whereas the infected device was removed in late OAI (70.4 %) ( p=0.008 ). OAI remission was achieved in 29 cases (50.9 %). The type of surgery, antimicrobial resistance and duration of treatment did not significantly influence the outcome. Independent predictors of the failure to eradicate OAI were age >60 years (hazard ratio, HR, of 3.875; 95 % confidence interval, CI95 %, of 1.540-9.752; p=0.004 ) and multiple surgeries for OAI (HR of 2.822; CI95 % of 1.144-6.963; p=0.024 )., [Conclusions] Only half of the MDR/XDR GNB OAI cases treated by antimicrobials and surgery had a successful outcome. Advanced age and multiple surgeries hampered the eradication of OAI. Optimal therapeutic options remain a challenge.

Published
2022

39. Staphylococcus aureus endocarditis: Identifying prognostic factors using a method derived from morbidity and mortality conferences

Author

Benjamin Lefèvre, Antoine Legoff, Mathilde Boutrou, François Goehringer, Willy Ngueyon-Sime, Catherine Chirouze, Matthieu Revest, Véronique Vernet Garnier, Xavier Duval, François Delahaye, Vincent Le Moing, Christine Selton-Suty, Laura Filippetti, Bruno Hoen, Nelly Agrinier, Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service des maladies infectieuses, Hopital Andree Rosemond, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), 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), 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 ), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], 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), 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 Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Cardiologie [CHRU Nancy], Université de Lorraine, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CIC Hôpital Bichat, 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)-UFR de Médecine, and Association pour l’Etude et la Prévention de l’Endocardite Infectieuse (AEPEI)

Subjects
Staphylococcus aureus, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, morbidity and mortality conference method, infective endocarditis, [SDV]Life Sciences [q-bio], morbidity and mortality, prognostic factors, conference method, General Medicine, survival, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

ObjectivesLethality of Staphylococcus aureus (Sa) infective endocarditis (IE) is high and might be due to yet unidentified prognostic factors. The aim of this study was to search for new potential prognostic factors and assess their prognostic value in SaIE.Materials and methodsWe used a two-step exploratory approach. First, using a qualitative approach derived from mortality and morbidity conferences, we conducted a review of the medical records of 30 patients with SaIE (15 deceased and 15 survivors), randomly extracted from an IE cohort database (NCT03295045), to detect new factors of possible prognostic interest. Second, we collected quantitative data for these factors in the entire set of SaIE patients and used multivariate Cox models to estimate their prognostic value.ResultsA total of 134 patients with modified Duke definite SaIE were included, 64 of whom died during follow-up. Of the 56 candidate prognostic factors identified at the first step, 3 had a significant prognostic value in multivariate analysis: the prior use of non-steroidal anti-inflammatory drugs [aHR 3.60, 95% CI (1.59–8.15), p = 0.002]; the non-performance of valve surgery when indicated [aHR 1.85, 95% CI (1.01–3.39), p = 0.046]; and the decrease of vegetation size on antibiotic treatment [aHR 0.34, 95% CI (0.12–0.97), p = 0.044].ConclusionWe identified three potential SaIE prognostic factors. These results, if externally validated, might eventually help improve the management of patients with SaIE.

Published
2022

40. Cerebral nocardiosis in a patient treated with pembrolizumab: a first case report

Author

Petitgas, Paul, Lesouhaitier, Mathieu, Boukthir, Sarrah, Cattoir, Vincent, Tattevin, Pierre, Bénézit, François, CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Université de Rennes - Faculté de Médecine (UR Médecine), Université de Rennes (UR), 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 ), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and No financial support was received for this study

Subjects
Nocardiosis, IRAE, [SDV]Life Sciences [q-bio], Case report, Pembrolizumab
Abstract

International audience; ackground: Checkpoints inhibitors (CPIs) are increasingly used for the treatment of several malignancies. The most common side effects are Immune Related Adverse Events, while infectious complications are rare, especially cerebral nocardiosis.Case presentation: Here, we report the first clinical case of a cerebral nocardiosis revealed after seizure in a patient treated by pembrolizumab for a metastatic lung cancer, in the absence of any additional immunosuppressive therapy or risk factors for cerebral nocardiosis. The extended evaluation including a brain CT-scan did not reveal any lesion before pembrolizumab. Nevertheless, the 3-month delay between the start of Pembrolizumab and the diagnosis of cerebral nocardiosis suggests that the infection occurred prior to the CPI. Unfortunately, the patient died during treatment for cerebral nocardiosis, while the lung cancer tumor mass had decreased by 80% after the sixth cycle of pembrolizumab.Conclusions: This case report emphasizes that clinicians should consider diagnoses other than metastasis in a patient with a brain mass and metastatic cancer treated with CPI, such as opportunistic infections or IRAE.

Published
2022

41. Treatment of Herpes Simplex Virus Type 2 Meningitis: A Survey Among Infectious Diseases Specialists in France, Sweden, Australia, and Denmark

Author

Jacob Bodilsen, Pierre Tattevin, Steven Y C Tong, Pontus Naucler, Henrik Nielsen, gomspace [Aalborg], Aalborg University Hospital, ESCMID [Basel], Pôle de Formation des Professionnels de Santé du Centre hospitalier de Rennes (PFPS), 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 ), Mercer Australia [Melbourne], The Royal Melbourne Hospital, University of Melbourne, Division of Infectious Diseases [Stockholm, Sweden] (Department of Medicine Solna), Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], and None

Subjects
Infectious Diseases, Oncology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, meningitis, survey, trial, HSV-2, management
Abstract

Background We aimed to describe attitudes toward treatment of herpes simplex virus type 2 (HSV-2) meningitis and prioritize future trials. Methods This was a self-administered online survey of HSV-2 meningitis treatment among infectious diseases (ID) specialists in France, Sweden, Australia, and Denmark. Results A total of 223 ID specialists (45% female) from France (36%), Denmark (24%), Sweden (21%), and Australia (19%) participated in the survey, primarily from university hospitals (64%). The estimated overall response rate was 11% and ranged from 6% (Australia) to 64% (Denmark). Intravenous (IV) acyclovir followed by oral valacyclovir was the favored treatment in 110 of 179 (61%), whereas monotherapy with either IV acyclovir or oral valacyclovir was used by 35 of 179 (20%) and 34 of 179 (19%), respectively. The median total duration was reported to be 7 days (interquartile range, 7–10 days) regardless of antiviral regimen. Immunocompromise influenced decisions on antiviral treatment in 110 of 189 (58%) of respondents, mainly by prolonged total duration of treatment (36/110 [33%]), prolonged IV administration (31/110 [28%]), and mandatory antiviral treatment (25/110 [23%]). Treatment with acyclovir/valacyclovir versus placebo and comparison of acyclovir versus valacyclovir were assigned the highest prioritization scores for future randomized controlled trials on HSV-2 meningitis. Conclusions Perceptions of indications for as well as type and duration of antiviral treatment varied substantially among ID specialists.

Published
2022

42. Reply to Cuervo et al. and Horinouchi et al

Author

Pierre Danneels, Jean-François Hamel, Adrien Lemaignen, Vincent Cattoir, Vincent Dubée, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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 ), and Sante publique France

Subjects
Microbiology (medical), Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV]Life Sciences [q-bio]
Abstract

International audience

Published
2022

43. Exploring Cluster-Dependent Antibacterial Activities and Resistance Pathways of NOSO-502 and Colistin against Enterobacter cloacae Complex Species

Author

Lucile Pantel, François Guérin, Marine Serri, François Gravey, Jessica Houard, Kelly Maurent, Marie Attwood, Alan Noel, Alasdair MacGowan, Emilie Racine, Vincent Cattoir, Maxime Gualtieri, Nosopharm, 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 ), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), 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), Southmead Hospital [Bristol, UK], and This work was partially performed within the framework of IMI’s GNA-NOW Program.

Subjects
CrrAB two-component-system, Pharmacology, Colistin, hetero-resistance, Enterobacter cloacae complex, PhoPQ, Microbial Sensitivity Tests, Anti-Bacterial Agents, Klebsiella pneumoniae, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Bacterial Proteins, mechanism of resistance, Enterobacter cloacae, Drug Resistance, Bacterial, Humans, NOSO-502, Pharmacology (medical), KexD efflux pump
Abstract

International audience; The Enterobacter cloacae complex (ECC) is a group of diverse environmental and clinically relevant bacterial species associated with a variety of infections in humans. ECC have emerged as one of the leading causes of nosocomial infections worldwide. The purpose of this paper is to evaluate the activity of NOSO-502 and colistin (CST) against a panel of ECC clinical isolates, including different Hoffmann's clusters strains, and to investigate the associated resistance mechanisms. NOSO-502 is the first preclinical candidate of a novel antibiotic class, the odilorhabdins (ODLs). MIC50 and MIC90 of NOSO-502 against ECC are 1 mu g/mL and 2 mu g/mL, respectively, with a MIC range from 0.5 mu g/mL to 32 mu g/mL. Only strains belonging to clusters XI and XII showed decreased susceptibility to both NOSO-502 and CST while isolates from clusters I, II, IV, and IX were only resistant to CST. To understand this phenomenon, E. cloacae ATCC 13047 from cluster XI was chosen for further study. Results revealed that the two-component system Ea_01761-ECL_01762 (ortholog of CrrAB from Klebsiella pneumoniae) induces NOSO-502 hetero-resistance by expression regulation of the Ea_01758 efflux pump component (ortholog of KexD from K. pneumoniae) which could compete with AcrB to work with the multidrug efflux pump proteins AcrA and TolC. In E. cloacae ATCC 13047, CST-hetero-resistance is conferred via modification of the lipid A by addition of 4-amino-4-deoxy-L-arabinose controlled by PhoPQ. We identified that the response regulator Ea_01761 is also involved in this resistance pathway by regulating the expression of the Ea_01760 membrane transporter.

Published
2022

44. sRNA-controlled iron sparing response in Staphylococci

Author

Rodrigo H Coronel-Tellez, Mateusz Pospiech, Maxime Barrault, Wenfeng Liu, Valérie Bordeau, Christelle Vasnier, Brice Felden, Bruno Sargueil, Philippe Bouloc, Cibles Thérapeutiques et conception de médicaments (CiTCoM - UMR 8038), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Center for Agricultural Water Research in China, China Agricultural University (CAU), 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 ), CNRS/Universite Paris-Saclay, INSERM / Universite Rennes 1, 'Agence Nationale de la Recherche' (ANR) [ANR-15-CE12-0003-01], 'Fondation pour la Recherche Medicale' (FRM) [DBF20160635724], ANR [ANR-19-CE45-0023-02, ANR-19-CE12-0006-01], CNRS, Universite de Paris, 'Consejo Nacional de Ciencia y Tecnologia' (CONACyT) [ANRS-A02019-2 ECTZ108689], Agence Nationale de la Recherche contre le SIDA fellowship [ANRS-A02019-2 ECTZ108689], ANR-15-CE12-0003,sRNA-FIT,Adaptation par ARN régulateurs chez Staphylococcus aureus(2015), ANR-19-CE45-0023,PaRNAssus,Décrypter les architectures complexes d'ARN par sondage et interactions(2019), ANR-19-CE12-0006,RRARE,ARN Régulateurs et Résistance aux Antibiotiques(2019), Jonchère, Laurent, Adaptation par ARN régulateurs chez Staphylococcus aureus - - sRNA-FIT2015 - ANR-15-CE12-0003 - AAPG2015 - VALID, Décrypter les architectures complexes d'ARN par sondage et interactions - - PaRNAssus2019 - ANR-19-CE45-0023 - AAPG2019 - VALID, and ARN Régulateurs et Résistance aux Antibiotiques - - RRARE2019 - ANR-19-CE12-0006 - AAPG2019 - VALID

Subjects
Staphylococcus aureus, Bacteria, Iron, Staphylococcus, [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Gene Expression Regulation, Bacterial, Mice, RNA, Bacterial, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Genetics, Animals, Humans, RNA, Small Untranslated, RNA, Messenger, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
Abstract

Staphylococcus aureus, a human opportunist pathogen, adjusts its metabolism to cope with iron deprivation within the host. We investigated the potential role of small non-coding RNAs (sRNAs) in dictating this process. A single sRNA, named here IsrR, emerged from a competition assay with tagged-mutant libraries as being required during iron starvation. IsrR is iron-repressed and predicted to target mRNAs expressing iron-containing enzymes. Among them, we demonstrated that IsrR down-regulates the translation of mRNAs of enzymes that catalyze anaerobic nitrate respiration. The IsrR sequence reveals three single-stranded C-rich regions (CRRs). Mutational and structural analysis indicated a differential contribution of these CRRs according to targets. We also report that IsrR is required for full lethality of S. aureus in a mouse septicemia model, underscoring its role as a major contributor to the iron-sparing response for bacterial survival during infection. IsrR is conserved among staphylococci, but it is not ortholog to the proteobacterial sRNA RyhB, nor to other characterized sRNAs down-regulating mRNAs of iron-containing enzymes. Remarkably, these distinct sRNAs regulate common targets, illustrating that RNA-based regulation provides optimal evolutionary solutions to improve bacterial fitness when iron is scarce.

Published
2022

45. Invasive pneumococcal infections in France: Changes from 2009 to 2021 in antibiotic resistance and serotype distribution of Streptococcus pneumoniae based on data from the French Regional Pneumococcal Observatories network

Author

Plainvert, C., Varon, E., Viriot, D., Kempf, M., Alauzet, C., Auger, G., Batah, J., Brieu, N., Cattoir, V., Cremniter, J., Culeux, C., Decousser, J.W., El Mniai, A., Goulard de Curraize, C., Gravet, A., Grelaud, C., Hamdad, F., Isnard, C., Labrunie, A., Lanotte, P., Laurens, C., Luce, S., Lemaitre, N., Patry, I., Pelloux, I., Peuchant, O., Ploy, M.C., Revillet, H., Robin, F., Ruimy, R., Vernet-Garnier, V., Wallet, F., Lévy-Bruhl, D., Danis, K., Centre national de Référence des Streptocoques (CNR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Cochin [AP-HP], Centre National de Référence des Pneumocoques (CNRP), Assistance Publique - Hôpitaux de Paris, Centre Hospitalier Intercommunal de Créteil (CHIC), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Université d'Angers (UA), Programme ATIP - Avenir, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Laboratoire de Bactériologie [CHU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pontchaillou [Rennes], Observatoires Régionaux du Pneumocoque, Partenaires INRAE, 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 ), Service de Microbiologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre Hospitalier Universitaire de Reims (CHU Reims), and This work was funded by Pfizer, Sanofi, GlaxoSmithKline, and bioMérieux laboratories.

Subjects
Serotype, Streptococcus pneumoniae, Infectious Diseases, French Regional Pneumococcal Observatories, Antimicrobial resistance, Invasive infection, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Objective: The 23 French Regional Pneumococcal Observatories (ORPs) analyzed antibiotic resistance and serotypes of Streptococcus pneumoniae strains isolated from invasive infections in France over a 12-year period.Methods: Between 2009 and 2021, the ORPs analyzed 19,319 strains, including 1,965 in children and 17,354 in adults. Strains were assessed for their resistance to penicillin G, amoxicillin and cefotaxime. Serotypes were identified in collaboration with the National Reference Centre.Results: During this period, the number of strains collected yearly decreased significantly. The decrease was particularly pronounced up until 2013, especially in children (-61.0%). However, penicillin non-susceptible strains (PNSPs) increased in children (24.7% in 2009 vs 45.0% in 2021, p < 0.0001) and in adults (27.1% in 2009 vs 31.3% in 2021, p < 0.05), as well as resistance (I + R) to amoxicillin (children: 12.5% in 2009 vs 19.4% in 2021, p < 0.05; adults: 13.4% in 2009 vs 14.5% in 2021, NS) and resistance (I + R) to cefotaxime (children: 8.0% in 2009 vs 13.1% in 2021, p < 0.05; adults: 7.1% in 2009 vs 11.9% in 2021, p < 0.0001). All in all, the proportion of strains belonging to serotypes present in the PCV13 vaccine has fallen sharply, from 64.8% in 2009 to 23.6 % in 2021. At the same time, serotypes such as 8, 10A, 11A, 15B/C and 9N, not included in PCV13, were increasing.Conclusion: During the study period, data collected by the network highlighted an increase of invasive PNSPs in children and non-vaccine serotypes. Surveillance of resistance and serotypes remains instrumental, particularly to monitor the evolution of vaccine efficacy.

Published
2022

46. Relationship between serotypes, disease characteristics and 30-day mortality in adults with invasive pneumococcal disease

Author

Benadji, Amine, Danis, Kostas, Brieu, Nathalie, Gaillat, Jacques, Mourvillier, Bruno, Bollaert, Pierre-Edouard, Gaillot, Olivier, Taha, Muhamed-Kheir, Bonacorsi, Stephane, Lecuit, Marc, Frachet, Bruno, Debroucker, Thomas, Levy Bruhl, Daniel, Preau, Marie, Anguel, Nadia, Argaud, Laurent, Arista, Sophie, Armand-Lefevre, Laurence, Balavoine, Stéphanie, Baraduc, Régine, Barnaud, Guilène, Béraud, Guillaume, Bernars, Georges, Bertei, Dominique, Bessede, Emilie, Billard Pomares, Typhaine, Biron, Charlotte, Bland, Stéphane, Boileau, Julien, Boubeau, Patrice, Bourdon, Sandra, Bousquet, Aurore, Boyer, Sophie, Bozorg-Grayeli, Alexis, Bretonniere, Cédric, Bricaire, François, Brocas, Elsa, Brun, Michel, Buret, Jennifer, Burucoa, Christophe, Cabalion, Jean, Cabon, Mathieu, Cambau, Emmanuelle, Camuset, Guillaume, Canevet, Christophe, Caron, François, Carricajo, Anne, Castan, Bernard, Caumes, Eric, Cazanave, Charles, Chabrol, Amélie, Challan-Belval, Thibaut, Chanteperdrix-Marillier, Vanessa, Chaplain, Chantal, Charlier-Woerther, Caroline, Chaussade, Hélène, Chirouze, Catherine, Clair, Bernard, Colot, Julien, Conil, Jean-Marie, Cordel, Hugues, Cormier, Philippe, Cousson, Joël, Cronier, Pierrick, Cua, Eric, Dao-Dubremetz, Anne, Dargere, Sylvie, Degand, Nicolas, Dekeyser, Sophie, Delaune, Deborah, Denes, Eric, Dequin, Pierre-Francois, Descamps, Diane, Descloux, Elodie, Desmaretz, Jean-Luc, Diehl, Jean-Luc, Dimet, Jérôme, Dinh, Aurélien, Duval, Xavier, Escaut, Lelia, Fabe, Claude, Faibis, Frédéric, Flateau, Clara, Fonsale, Nathalie, Fortineau, Nicolas, Gagneux-Brunon, Amandine, Garandeau, Caroline, Garcia, Magali, Garot, Denis, Gaudry, Stéphane, Goehringer, François, Gravet, Alain, Gregoire-Faucher, Valérie, Grosset, Marine, Gueit, Isabelle, Guelon, Dominique, Guimard, Thomas, Hadou, Tahar, Helene, Jean-Pierre, Henard, Sandrine, Henry, Benoit, Hochart, Anne-Cécile, Hoen, Bruno, Illes, Gabriela, Jaffuel, Sylvain, Jarrin, Irène, Jaureguy, Françoise, Joseph, Cédric, Juvin, Marie-Emmanuelle, Kayal, Samer, Kerneis, Solen, Lamaury, Isabelle, Laurens, Etienne, Laurichesse, Henri, Le Brun, Cécile, Le Moing, Vincent, Le Turnier, Paul, Lecuyer, Hervé, Ledru, Sylvie, Legrix, Céline, Lemaignen, Adrien, Lemble, Chantal, Lemee, Ludovic, Lesens, Olivier, Lhommet, Claire, Males, Silvija, Malpote, Edith, Martin-Blondel, Guillaume, Marx, Matthieu, Masson, Raphael, Matray, Olivier, Mbadi, Aurore, Mechai, Frédéric, Mellon, Guillaume, Merens, Audrey, Meyohas, Marie Caroline, Michon, Adrien, Mootien Yoganaden, Joy, Morquin, David, Mouly, Stéphane, Mrozek, Natacha, Nguyen, Sophie, Oziol, Eric, Page, Bernard, Patrat-Delon, Solène, Patry, Isabelle, Picot, Sandrine, Pierrejean, Denys, Piroth, Lionel, Plassart, Claire, Plessis, Patrice, Ploy, Marie-Cécile, Portel, Laurent, Poubeau, Patrice, Poupard, Marie, Poyart, Claire, Prazuck, Thierry, Quaesaet, Luc, Raffi, François, Ramanantsoa, Adriatsiferana, Rapp, Christophe, Raskine, Laurent, Raymond, Josette, Revest, Matthieu, Riche, Agnès, Robaday-Voisin, Stéphanie, Robin, Frédéric, Romaszko, Jean-Pierre, Rousseau, Florence, Roux, Anne-Laure, Royer, Cécile, Saada, Matthieu, Salmon, Dominique, Saroufim, Carlo, Schmit, Jean Luc, Sebire, Manuela, Segonds, Christine, Sivadon-Tardy, Valérie, Soismier, Nathalie, Son, Olivia, Sunder, Simon, Suy, Florence, Tande, Didier, Tankovic, Jacques, Valin, Nadia, van Grunderbeeck, Nicolas, Vandenesch, François, Varon, Emmanuelle, Verdon, Renaud, Vergnaud, Michel, Vidal, Magali, Vittecoq, Daniel, Vuotto, Fanny, Gorenne, Isabelle, Laouenan, Cédric, Marcault, Estelle, Mentre, France, Pasquet, Blandine, Roy, Carine, Tubiana, Sarah, Arsac, Philippe, Benoit, Martha, Bernard, Louis, Bissuel, François, Bret, Laurent, Brieu, Natalie, Burret, Jennifer, Carvalhoschneider, Claudia, Champagne, Hélène, Chapalain, Joséphine, Chardon, Hubert, Chavanet, Pascal, Ducruet, Judith, Epaulard, Olivier, Fabre, Marc, Fasquelle, Dominique, Forestier, Emmanuel, Galempoix, Jean-Marc, Gautier, Guillaume, de Curraize, Claire Goulard, Gracet, Alain, Gubavu, Camélia, Guinard, Jérôme, Habet, Tarik, Haudour, Aurélie, Henry, Caroline, Hombrouckalet, Cécile, Janssen, Céline, Kisteman, Jean-Paul, Lanotte, Philippe, Lartigue, Marie-Frédérique, Launois, Claire, Lebrun, Cécile, Legout, Laurence, Levast, Marion, Madoux, Yannick, Maulin, Laurence, Mestrallet, Stéphanie, Mohareb, Abdo, Mootien, Joy, Nguyen, Yohan, Noel, Franck, Ogielska, Maja, Ogier Desserrey, Agathe, Paleau, Anne, Pavel, Simona, Pechinot, André, Pelloux, Isabelle, Petillon, Camille, Petitprez, Hélène, Podac, Bianca, Poirot, Jerome, Ponceau, Bénédicte, Prieur, Nathalie, Recule, Christine, Saraceni, Orlando, Sartre, Jacques, Sifaoui, Farid, Simonin, Catherine, Strady, Christophe, Tellini, Charlotte, Texier, Anthony, Thouvenin, Maxime, Tixier, Anne, Tremeaux, Pauline, Verger, Pascale, Vernet-Garnier, Véronique, Verquin, Jean-Pierre, Vitrat, Virginie, Vray, Isabelle, Zamfir, Oana, Zucchini, Laure, Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], 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), 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), 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, 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), 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 ), CHU Pontchaillou [Rennes], CHI Créteil, 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), The COMBAT study was supported by the Assistance Publique Hopitaux de Paris, French Ministry of Health, Inserm, SPILF, and the Pfizer Pharmaceutical company, which also funded ORP. The study was endorsed by the following professional organizations: Association Pour l’enseignement de la Thérapeutique, Société de Pathologie Infectieuse de Langue Française, Société Française de Microbiologie, Société Nationale Française de Médecine Interne, Société de Réanimation de Langue Française, Société Française de Gérontologie, Société Française d’Anesthésie-Réanimation. The SIIP study was supported by (i) the Société de Pathologie Infectieuse de Langue Fran.aise (SPILF, the French Infectious Diseases Society), (ii) Santé Publique France (SpFrance, the French National Public Health Agency), (iii) the European Centre for Disease Prevention and Control (ECDC), and (iv) Pfizer. The Regional Observatories of Pneumococci (Observatoires Régionaux du Pneumocoque) were supported by Pfizer, BioMerieux, and Sanofi., and Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE)

Subjects
Adult, Microbiology (medical), Serotype, medicine.medical_specialty, Multivariate analysis, Adolescent, [SDV]Life Sciences [q-bio], 30-day mortality, Serogroup, medicine.disease_cause, Logistic regression, Pneumococcal Infections, Cohort Studies, Pneumococcal Vaccines, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Streptococcus pneumoniae, medicine, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Aged, 0303 health sciences, Meningitis, Pneumococcal, 030306 microbiology, business.industry, Mortality rate, Infant, Invasive pneumococcal disease, Pneumococcal vaccine, General Medicine, bacterial infections and mycoses, medicine.disease, 3. Good health, Infectious Diseases, business, Meningitis, Cohort study
Abstract

International audience; Purpose: Invasive pneumococcal disease (IPD) is responsible for substantial mortality and morbidity worldwide. We aimed to identify host and bacterial factors associated with 30-day mortality in 18-year-old patients hospitalized with IPD in France from 2013 to 2015.Methods: This study analyzed data collected from consecutives IPD cases included in two parallel multi-center cohort studies: COMBAT study (280 patients with pneumococcal community-acquired bacterial meningitis) and SIIP study (491 patients with non-meningitis IPD). Factors associated with 30-day mortality were identified using logistic regression.Results: Among the 771 enrolled patients (median age 66 years, IQR [52.0-79.7]), 592/767 (77.2%) had at least one chronic disease. Patients with meningitis were younger (60.2 vs 70.9 years; p < 0.001) and had fewer chronic diseases than those with non-meningitis IPD (73.3% vs 79.4%; p = 0.05). Non-vaccine serotypes were more frequent in meningitis patients than in those with other IPD (36.1% vs 23.1%; p < 0.001). The overall 30-day mortality was 16.7% and patients with concurrent meningitis and extra-cerebral IPD had the highest 30-day mortality rate (26.5%). On multivariate analyses, older age, history of malignant solid tumor, meningeal IPD and serotypes previously identified with high mortality potential were independently associated with 30-day mortality. Of the serotypes with high mortality potential, 80% were included in licensed (PCV13 or PPV23) vaccines.Conclusion: We observed an effect of both host factors and pneumococcal serotypes on 30-day mortality in IPD. This highlights the need for a focused strategy to vaccinate at-risk patients.Clinical trial: ClinicalTrial. Gov identification number: NCT01730690.

Published
2021

47. Lyme arthritis in Western Europe: a multicentre retrospective study

Author

Brigitte Degeilh, Xavier Guennic, Benoit Le Goff, Jean-David Albert, Clémence Corre, Guillaume Coiffier, Solène Patrat-Delon, Pierre Tattevin, Marine Ferreyra, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), CHU Pontchaillou [Rennes], Centre hospitalier Rene Pleven de Dinan, Centre hospitalier universitaire de Nantes (CHU Nantes), CHU de Saint-Brieuc, 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 ), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Adult, Male, Microbiology (medical), medicine.medical_specialty, [SDV]Life Sciences [q-bio], Lyme Arthritis, Polymerase Chain Reaction, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Borreliella, Borrelia burgdorferi Group, Interquartile range, Internal medicine, Borrelia, Synovial Fluid, medicine, Monoarthritis, Humans, Synovial fluid, Serologic Tests, Borrelia burgdorferi, Lyme borreliosis, Retrospective Studies, 030304 developmental biology, 030203 arthritis & rheumatology, Doxycycline, Lyme Disease, 0303 health sciences, biology, business.industry, Lyme arthritis, General Medicine, Middle Aged, Amoxicillin, bacterial infections and mycoses, medicine.disease, biology.organism_classification, Antibodies, Bacterial, Anti-Bacterial Agents, 3. Good health, Europe, Infectious Diseases, business, medicine.drug
Abstract

International audience; To characterize Lyme arthritis, with a focus on management, and outcome. Observational retrospective multicentre study in Western France, of all consecutive cases of Lyme arthritis, documented by Borrelia burgdorferi IgG on ELISA serological testing, confirmed by Western blot, with or without positive Borrelia PCR in synovial fluid, with no alternative diagnosis. We enrolled 52 patients (29 males), with a mean age of 43 +/- 19.4 years. Most patients had monoarthritis (n = 43, 82.7%), involving the knee (n = 51, 98.1%), with a median delay between symptoms onset and Lyme arthritis diagnosis of 5 months (interquartile range, 1.5-8). Synovial fluid analysis yielded median white cell count of 16,000/mm(3) (9230-40,500), and positive PCR in 16 cases (39%), for B. burgdorferi sensu stricto (n = 5), B. garinii (n = 5), B. afzelii (n = 3), and undetermined (n = 3). All patients received antibiotics, for a median duration of 28 days (21-30), with doxycycline (n = 44, 84.6%), ceftriaxone (n = 6, 11.5%), or amoxicillin (n = 2). Twelve patients (23.1%) also received intra-articular injection of glucocorticoids as first-line treatment. Of 47 patients with follow-up, 35 (74.5%) had complete resolution of Lyme arthritis. Lyme arthritis in Western Europe may be due to B. burgdorferi ss, B. afzelii, or B. garinii. Clinical presentation is similar to Lyme arthritis in North America (i.e. chronic knee monoarthritis), with low sensitivity of synovial fluid PCR (39%).

Published
2021

48. Maladie de Lyme : « la fin des controverses ? »

Author

Guillaume Coiffier, Pierre Tattevin, Centre Hospitalier Dinan/St Brieuc (CH Dinan/St Brieuc), CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), and 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 )

Subjects
030203 arthritis & rheumatology, 03 medical and health sciences, 0302 clinical medicine, Arthrite, Rheumatology, Recommandations, [SDV]Life Sciences [q-bio], Érythème migrant, 030212 general & internal medicine, Maladie de Lyme, Radiculite, 3. Good health
Abstract

National audience; La borréliose de Lyme est une maladie vectorielle à tiques présente largement dans l'hémisphère Nord. En France Métropolitaine, Ixodes ricinus est présent partout à l'exception du pourtour méditerranéen. La source de controverse repose sur l'existence ou non d'une forme chronique de la maladie de Lyme. Cette controverse n'est pas une particularité française : elle est rapportée à travers le monde entier. En France, en 2019, les 24 sociétés savantes représentatives des disciplines médicales les plus concernées par la maladie de Lyme, dont la Société française de rhumatologie et la Société de pathologie infectieuse de langue française, ont publié des recommandations concernant la prise en charge de la borréliose de Lyme, suite à une saisine du Directeur Général de la Santé. Ces recommandations sont en désaccord avec celles de la Haute Autorité de Santé sur un point principal : la désignation d'une nouvelle entité nosologique étiquetée « symptomatologie/syndrome polymorphe persistant après une possible piqûre de tique ». La création de ce nouveau syndrome risquait d'aggraver le phénomène d'ancrage, qui conduit à rattacher tous les symptômes à une possible piqûre de tique, sans envisager de diagnostics différentiels. Pourtant, la maladie de Lyme est bien étudiée. L’érythème migrant est la principale manifestation clinique. Une monoarthrite non septique non métabolique impliquant le genou ou une radiculite du membre inférieur estivale doit faire évoquer une maladie de Lyme. La sérologie de Lyme est fiable dans les formes tardives comme l'arthrite, tandis que la détection d'ADN borrelien par PCR dans le liquide synovial est inconstante. La sérologie peut en revanche être mise à défaut dans les formes précoces comme la radiculite. Le traitement repose sur la doxycycline pendant 14 jours dans les formes précoces (radiculite) ou 28 jours dans les formes tardives (arthrite). Une persistance ou récidive de l'arthrite après une antibiothérapie adaptée est possible. La prévalence d'un syndrome polyalgique diffus (fibromyalgie) au décours d'une maladie de Lyme ne semble pas être différente de celle de la population générale et n'est pas améliorée par une antibiothérapie prolongée, non recommandée.

Published
2021

49. Impact of Enterococcus faecalis endocarditis treatment on risk of relapse

Author

Danneels, Pierre, Hamel, Jean François, Picard, Léa, Rezig, Schéhérazade, Martinet, Pauline, Lorleac’h, Aurélien, Talarmin, Jean Philippe, Buzelé, Rodolphe, Guimard, Thomas, Le Moal, Gwenaël, Brochard-Libois, Julia, Beaudron, Aurélie, Letheulle, Julien, Codde, Cyrielle, Chenouard, Rachel, Boutoille, David, Lemaignen, Adrien, Bernard, Louis, Cattoir, Vincent, Dubée, Vincent, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Pontchaillou, Hôpital de la Cavale Blanche, Groupe Hospitalier Bretagne Sud (GHBS), Centre Hospitalier Intercommunal de Cornouaille (CHIC), CHU de Saint-Brieuc, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre hospitalier de Saint-Nazaire, Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier de Laval (CH Laval), CHU Limoges, Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique (CIC 0004 - Nantes), Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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 ), 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), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Pecqueret, Valérie

Subjects
Microbiology (medical), [SDV] Life Sciences [q-bio], Infectious Diseases, Drug Therapy, Endocarditis, E. faecalis, [SDV]Life Sciences [q-bio], Combination, Amoxicillin, Relapse
Abstract

Background Enterococcus faecalis infective endocarditis (EFIE) is characterized by a higher frequency of relapses than other infective endocarditis. The role of the treatment on its occurrence remains poorly understood. The aim of this study was to investigate whether the antibiotic regimen could impact the risk of relapse in EFIE. Materials This was a multicenter retrospective study of patients diagnosed with definite EFIE between 2015 and 2019 in 14 French hospitals. The primary endpoint was the occurrence of relapses within the year following endocarditis diagnosis. As death was a competing risk for relapse, Fine and Gray models were used for studying risk factors and impact of treatment. Results Of the 279 patients included, 83 (29.7%) received the amoxicillin-gentamicin (A-G) combination, 114 (40.9%) amoxicillin-ceftriaxone (A-C), 63 (22.6%) A-G and A-C (A-G/A-C) sequentially, 9 (3.2%) amoxicillin (A), and 10 received other treatments. One-year-relapse rate was 9.3% (26 patients). Relapse occurred after a median delay of 107 days from EFIE diagnosis; 6 occurred after 6 months, and 6 were diagnosed by blood cultures in asymptomatic patients. In multivariate analysis, surgery during treatment was a protective factor against one-year relapse and death. The cumulative incidence of relapse 1 year after endocarditis was 46.2% for patients treated with amoxicillin, 13.4% with A-G, 14.7% with A-C, and 4.3% with A-G/A-C (P≥.05 in multivariate analysis). Conclusions Relapses after treatment of EFIE are frequent, frequently asymptomatic, and may occur more than 6 months after the initial episode.

Published
2022

50. The intravenous vancomycin prescription practices of French infectious disease specialists: A cross-sectional observational study

Author

M, Lemaitre, A, Galy, V, de Lastours, P, Thill, P, Tattevin, A, Lefort, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Henri Mondor, 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, Centre Hospitalier Tourcoing, 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 ), CHU Pontchaillou [Rennes], Jonchère, Laurent, and CHU Henri Mondor [Créteil]

Subjects
Prescriptions, Infectious Diseases, Vancomycin, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Physicians, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Drug Monitoring, Clinical practice, Loading dose, Anti-Bacterial Agents
Abstract

International audience; INTRODUCTION: Vancomycin prescription modalities remain non-consensual. We examined and evaluated the vancomycin prescription habits of infectious disease specialists in France. METHODS: Through an anonymized online questionnaire sent to members of the French Infectious Diseases Society, detailed information on vancomycin prescription modalities was collected. RESULTS: Out of the 712 physicians contacted, 179 (25%) completed the questionnaire; 174 (97%) of them routinely prescribed intravenous vancomycin: 95 (55%) by continuous infusion only, 12 (7%) by intermittent infusion, while 67 (38%) used the two modalities. Among continuous administration users, 157 (97%) applied a loading dose of 15 mg/kg or less (n = 80, 49%), 20-25 mg/kg (n = 33, 20%), or 30 mg/kg or more (n = 45, 28%); 143 (88%) used a maintenance dosage of 30 mg/kg/day and 157 (97%) carried out drug monitoring. CONCLUSION: In France, infectious disease specialists favor continuous administration of vancomycin using a loading dose, with systematic monitoring of vancomycin serum concentrations.

Published
2022

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