Search

Your search keyword '"Comets, Emmanuelle"' showing total 9 results
Start Over Author "Comets, Emmanuelle" Topic antibiotics
9 results on '"Comets, Emmanuelle"'

1. Ciprofloxacin population pharmacokinetics during long-term treatment of osteoarticular infections.

Author

Zahr, Noël, Urien, Saik, Aubry, Alexandra, Chauvin, Charlotte, Comets, Emmanuelle, Llopis, Benoit, Tissot, Nadine, Noe, Gaëlle, Fourniols, Eric, Jaureguiberry, Stéphane, Bleibtreu, Alexandre, Funck-Brentano, Christian, Hospital, the Centre de Référence pour le traitement des Infections Ostéo-Articulaires Complexes (CRIOAC) Pitié-Salpêtrière, and Centre de Référence pour le traitement des Infections Ostéo-Articulaires Complexes (CRIOAC) Pitié-Salpêtrière Hospital

Subjects
CIPROFLOXACIN, PHARMACOKINETICS, TANDEM mass spectrometry, STAPHYLOCOCCAL diseases, BLOOD volume, ADULTS, DIET in disease, ANTIBIOTICS, RETROSPECTIVE studies, RIFAMPIN
Abstract

Background: Ciprofloxacin is an antibiotic used in osteoarticular infections owing to its very good bone penetration. Very few pharmacokinetic data are available in this population.Objectives: To investigate oral ciprofloxacin population pharmacokinetics in adult patients treated for osteoarticular infections and propose guidance for more effective dosing.Methods: A retrospective population-pharmacokinetic analysis was performed on 92 consecutive hospitalized patients in the orthopaedic department. Ciprofloxacin plasma samples were obtained on one or two occasions during treatment. Plasma concentration was measured using ultra-performance liquid chromatography system coupled with tandem mass spectrometry. Data analysis was performed using a non-linear mixed-effect approach via Monolix 2019R2.Results: A total of 397 plasma samples were obtained with 11.5% and 41.6% of patients being below the therapeutic target for Gram-negative and staphylococcal infections, respectively. Ciprofloxacin pharmacokinetics were best described by a two-compartment model with a first-order absorption. Ciprofloxacin apparent plasma clearances and volumes of distribution were dependent on patients' fat-free mass according to the allometric rule. Elimination clearance was also positively related to renal function through the modification of diet in renal disease equation (MDRD) and rifampicin co-administration. When patients are co-treated with rifampicin, ciprofloxacin dosage should be increased by 50% to 60%.Conclusions: This study showed that free-fat mass was a better size predictor than total body weight for ciprofloxacin clearance and volumes terms. Moreover, both MDRD and rifampicin status were significant predictors of individual ciprofloxacin clearance. Our study suggests that individual adjustment of ciprofloxacin dose in osteoarticular infections with less-susceptible bacteria might be indicated to reach required efficacy targets. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

2. The Use of Translational Modelling and Simulation to Develop Immunomodulatory Therapy as an Adjunct to Antibiotic Treatment in the Context of Pneumonia.

Author

Michelet, Robin, Ursino, Moreno, Boulet, Sandrine, Franck, Sebastian, Casilag, Fiordiligie, Baldry, Mara, Rolff, Jens, van Dyk, Madelé, Wicha, Sebastian G., Sirard, Jean-Claude, Comets, Emmanuelle, Zohar, Sarah, Kloft, Charlotte, and Sanjuán, Victor Mangas

Subjects
RESPIRATORY infections, PNEUMONIA, ANTIBIOTICS, SIMULATION methods & models, DRUG resistance in bacteria, GENETIC translation
Abstract

The treatment of respiratory tract infections is threatened by the emergence of bacterial resistance. Immunomodulatory drugs, which enhance airway innate immune defenses, may improve therapeutic outcome. In this concept paper, we aim to highlight the utility of pharmacometrics and Bayesian inference in the development of immunomodulatory therapeutic agents as an adjunct to antibiotics in the context of pneumonia. For this, two case studies of translational modelling and simulation frameworks are introduced for these types of drugs up to clinical use. First, we evaluate the pharmacokinetic/pharmacodynamic relationship of an experimental combination of amoxicillin and a TLR4 agonist, monophosphoryl lipid A, by developing a pharmacometric model accounting for interaction and potential translation to humans. Capitalizing on this knowledge and associating clinical trial extrapolation and statistical modelling approaches, we then investigate the TLR5 agonist flagellin. The resulting workflow combines expert and prior knowledge on the compound with the in vitro and in vivo data generated during exploratory studies in order to construct high-dimensional models considering the pharmacokinetics and pharmacodynamics of the compound. This workflow can be used to refine preclinical experiments, estimate the best doses for human studies, and create an adaptive knowledge-based design for the next phases of clinical development. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

3. Type I Interferon in Children with Viral or Bacterial Infections

Author

Nina Droz, Philippe Rebaud, Etienne Javouhey, Sylvie Pons, Karen Brengel-Pesce, Antoine Ouziel, Romain Basmaci, Sophie Trouillet-Assant, Lucille Boisselier, Alexandre Belot, Yves Gillet, Sébastien Viel, BIOMERIEUX, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de référence des rhumatismes inflammatoires et maladies autoimmunes systémiques rares de l'enfant [Paris] (RAISE), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Pédiatrique [Lyon], Hospices Civils de Lyon (HCL)-Hôpital Femme-Mère-Enfant-Centre de référence des maladies rénales rares, CH de Villefranche-sur-Saône, 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, Service de Pédiatrie-Urgences [Hopital Louis Mourier - APHP, Colombes], Hôpital Louis Mourier - AP-HP [Colombes], Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Antoine Study Group: Marine Mommert, Audrey Guichard, François Bartolo, Laurence Generenaz, Alexandre Pachot, Claire Capella, Laure Hees, Ellia Mezgueldi, Chadia Toumi, Coralie Bouchiat-Sarabi, Jean-Sebastien Casalegno, Aurelie Portefaix, Romain Deshayes de Cambronne, Magali Perret, Comets, Emmanuelle, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3)

Subjects
Male, 0301 basic medicine, Pediatric emergency, Fever, emergency department, medicine.drug_class, Clinical Biochemistry, Antibiotics, Alpha interferon, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Interferon, Interferon α, Humans, Medicine, Prospective Studies, febrile children, 030203 arthritis & rheumatology, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Pediatric Emergency Medicine, business.industry, Biochemistry (medical), Infant, Newborn, bacterial infection, Infant, Interferon-alpha, Bacterial Infections, Emergency department, Serum concentration, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, 030104 developmental biology, Virus Diseases, Child, Preschool, Interferon Type I, Immunology, Etiology, Female, viral infection, Emergency Service, Hospital, business, Biomarkers, medicine.drug
Abstract

Background Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years. Distinguishing between bacterial and viral infections etiologies in febrile patients remains challenging. We hypothesized that specific host biomarkers for viral infections, such as type I-interferon (IFN), could help clinicians’ decisions and limit antibiotic overuse. Methods Paxgene tubes and serum were collected from febrile children (n = 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the Nanostring® technology and plasma IFN-α quantified by digital ELISA technology. Results Serum concentrations of IFN-α were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P 0.91 for both) between viral and bacterial infection in febrile children, compared to C-reactive protein (0.83). Conclusions IFN-α is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-α femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse. Clinical Trials Registration clinicaltrials.gov (NCT03163628).

Published
2020

4. Treatment and Outcomes of Children with Febrile Urinary Tract Infection due to Extended Spectrum Beta-lactamase-producing Bacteria in Europe: TOO CUTE Study

Author

Ana Isabel Valdivielso Martínez, Mike Sharland, Tina Plankar Srovin, Maia De Luca, Eleni Vergadi, Ángela Gómez Manzanares, Alasdair Bamford, Romain Basmaci, Ana Maria Oliveira Brett, Julia Bielicki, John Kopsidas, Andrew Riordan, Yingfen Hsia, Elise Aguadisch, Marion Caseris, Elias Iosifidis, Tim Planche, Konstantinos Vazouras, Laura Folgori, Rimante Cerkauskiene, University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Universidad de Málaga [Málaga] = University of Málaga [Málaga], St George's, University of London, The Stavros Niarchos Foundation [Athens, Greece], Queen's University [Belfast] (QUB), University of Milan, University Children's Hospital [Basel, Switzerland]], Service de Pédiatrie-Urgences [Hopital Louis Mourier - APHP, Colombes], Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK], Universidade de Coimbra [Coimbra], Hôpital Robert Debré, Vilnius University [Vilnius], Children's Hospital Bambino Gesù IRCCS [Rome], Aristotle University of Thessaloniki, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), St George's Hospital Medical School [London], Liverpool Women's NHS Foundation Trust, University of Crete [Heraklion] (UOC), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, Comets, Emmanuelle, Università degli Studi di Milano = University of Milan (UNIMI), Great Ormond Street Hospital for Children NHS Foundation Trust [London, UK] (GOSHC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord

Subjects
Microbiology (medical), Male, medicine.medical_specialty, Combination therapy, Urinalysis, Adolescent, medicine.drug_class, Urinary system, Antibiotics, Urine, Drug resistance, beta-Lactamases, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, 030225 pediatrics, Internal medicine, Drug Resistance, Bacterial, Medicine, Humans, 030212 general & internal medicine, Child, Retrospective Studies, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], medicine.diagnostic_test, Pyelonephritis, business.industry, Infant, Newborn, Infant, Retrospective cohort study, Bacterial Infections, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, Anti-Bacterial Agents, Infectious Diseases, Treatment Outcome, Child, Preschool, Pediatrics, Perinatology and Child Health, Urinary Tract Infections, Epsilonproteobacteria, Female, business
Abstract

Background: \ud The prevalence of extended-spectrum beta-lactamase producing Εnterobacteriaceae (ESBL-PE) is increasing globally. ESBL-PE are an important cause of urinary tract infections (UTIs) in children. We aimed to characterize the clinical presentation, treatment and outcomes of childhood UTI caused by ESBL-PE in Europe.\ud \ud Methods: \ud Multicenter retrospective cohort study. Children 0 to 18 years of age with fever, positive urinalysis and positive urine culture for an ESBL-PE uropathogen, seen in a participating hospital from January 2016 to July 2017, were included.\ud \ud Main Outcome Measures: \ud Primary outcome measure: day of defervescence was compared between (1) initial microbiologically effective treatment (IET) versus initial microbiologically ineffective treatment (IIT) and (2) single initial antibiotic treatment versus combined initial antibiotic treatment. Secondary outcome measures: Clinical and microbiological failure of initial treatment.\ud \ud Results: \ud We included 142 children from 14 hospitals in 8 countries. Sixty-one children had IET and 77 IIT. There was no statistical difference in time to defervescence for effective/ineffective groups (P = 0.722) and single/combination therapy groups (P = 0.574). Two out of 59 (3.4%) and 4/66 (6.1%) patients exhibited clinical failure during treatment (P = 0.683) when receiving IET or IIT, respectively. Eight of 51 (15.7%) receiving IET and 6/58 (10.3%) receiving IIT patients (P = 0.568) had recurring symptoms/signs suggestive of a UTI. Recurrence of a UTI occurred 15.5 days (interquartile range, 9.0–19.0) after the end of treatment.\ud \ud Conclusions: \ud Time to defervescence and clinical failure did not differ between IET/IIT groups. Non-carbapenem beta-lactam antibiotics may be used for the empiric treatment of ESBL febrile UTIs, until susceptibility testing results become available.

Published
2020

5. Ceftriaxone and cefotaxime have similar effects on the intestinal microbiota in human volunteers treated by standard-dose regimens

Author

Charles Burdet, Nathalie Grall, Morgane Linard, Antoine Andremont, Khadija Bourabha, Loubna Alavoine, Camille d’Humières, Erick Denamur, Mélanie Magnan, Michèle Benhayoun, Antoine Bridier-Nahmias, Olivier Tenaillon, L. Massias, Sarah Tubiana, Xavier Duval, Olivier Clermont, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Département d'épidémiologie, biostatistique et recherche clinique, 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), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie et virologie moléculaire (PVM (UMR_7151)), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), CIC1425 Bichat [AP-HP Hôpital Bichat - Claude Bernard] (INSERM), 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)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital universitaire Robert-Debré [Paris], Service de pharmacie, Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Comets, Emmanuelle

Subjects
Adult, Male, intestinal microbiota, medicine.medical_specialty, Cefotaxime, Adolescent, medicine.drug_class, cefotaxime, Antibiotics, Cephalosporin, Gastroenterology, Feces, Young Adult, 03 medical and health sciences, Pharmacokinetics, RNA, Ribosomal, 16S, Internal medicine, Gram-Negative Bacteria, medicine, Humans, Pharmacology (medical), Volunteer, 030304 developmental biology, Pharmacology, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], biology, 030306 microbiology, business.industry, Ceftriaxone, Middle Aged, biology.organism_classification, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Healthy Volunteers, Anti-Bacterial Agents, Cephalosporins, Gastrointestinal Microbiome, 3. Good health, Infectious Diseases, Enterococcus, 16S rRNA gene profiling, Female, Gram-Negative Bacterial Infections, business, pharmacokinetics, medicine.drug
Abstract

Ceftriaxone has a higher biliary elimination than cefotaxime (40% versus 10%), which may result in a more pronounced impact on the intestinal microbiota. We performed a monocenter, randomized open-label clinical trial in 22 healthy volunteers treated by intravenous ceftriaxone (1 g/24 h) or cefotaxime (1 g/8 h) for 3 days. We collected fecal samples for phenotypic analyses, 16S rRNA gene profiling, and measurement of the antibiotic concentration and compared the groups for the evolution of microbial counts and indices of bacterial diversity over time. Plasma samples were drawn at day 3 for pharmacokinetic analysis. The emergence of 3rd-generation-cephalosporin-resistant Gram-negative enteric bacilli (Enterobacterales), Enterococcus spp., or noncommensal microorganisms was not significantly different between the groups. Both antibiotics reduced the counts of total Gram-negative enteric bacilli and decreased the bacterial diversity, but the differences between the groups were not significant. All but one volunteer from each group exhibited undetectable levels of antibiotic in feces. Plasma pharmacokinetic endpoints were not correlated to alteration of the bacterial diversity of the gut. Both antibiotics markedly impacted the intestinal microbiota, but no significant differences were detected when standard clinical doses were administered for 3 days. This might be related to the similar daily amounts of antibiotics excreted through the bile using a clinical regimen. (This study has been registered at ClinicalTrials.gov under identifier NCT02659033.)

Published
2019

6. Antibiotic-induced dysbiosis predicts mortality in an animal model of Clostridium difficile infection

Author

Charles Burdet, Sakina Sayah-Jeanne, Thu Thuy Nguyen, Perrine Hugon, Frédérique Sablier-Gallis, Nathalie Saint-Lu, Tanguy Corbel, Stéphanie Ferreira, Mark Pulse, William Weiss, Antoine Andremont, France Mentré, Jean de Gunzburg, Service de Biostatistique [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), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Da Volterra, 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)-Université Paris Diderot - Paris 7 (UPD7), Genoscreen, UNT Health Science Center [Fort Worth, USA], University of North Texas (UNT), Emergence de la résistance bactérienne in vivo (EA3964), Université Paris Diderot - Paris 7 (UPD7), Transduction du signal et oncogénèse, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), and Comets, Emmanuelle

Subjects
Male, 0301 basic medicine, medicine.drug_class, Moxifloxacin, 030106 microbiology, Antibiotics, Microbiology, 03 medical and health sciences, Subcutaneous injection, Cricetinae, medicine, Animals, Pharmacology (medical), Colonization, Mechanisms of Action: Physiological Effects, Feces, 030304 developmental biology, Pharmacology, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Mesocricetus, Clostridioides difficile, 030306 microbiology, business.industry, Clindamycin, Clostridium difficile, medicine.disease, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Anti-Bacterial Agents, Gastrointestinal Microbiome, 3. Good health, 030104 developmental biology, Infectious Diseases, Clostridium Infections, Dysbiosis, business, medicine.drug
Abstract

BackgroundAntibiotic disruption of the intestinal microbiota favors colonization byClostridium difficile. Using a charcoal-based adsorbent to decrease intestinal antibiotic concentrations, we studied the relationship between antibiotic concentrations in feces and the intensity of dysbiosis, and quantified the link between this intensity and mortality.MethodsWe administered either moxifloxacin (n=70) or clindamycin (n=60) to hamsters by subcutaneous injection from day 1 (D1) to D5, and challenged them with aC. difficiletoxigenic strain at D3. Hamsters received various doses of a charcoal-based adsorbent, DAV131A, to modulate intestinal antibiotic concentrations. Gut dysbiosis was evaluated at D0and D3using diversity indices determined from 16S rRNA gene profiling. Survival was monitored until D16. We analyzed the relationship between fecal antibiotic concentrations and dysbiosis at the time ofC. difficilechallenge and studied their capacity to predict subsequent death of the animals.ResultsIncreasing doses of DAV131A reduced fecal concentrations of both antibiotics, lowered dysbiosis and increased survival from 0% to 100%. Mortality was related to the level of dysbiosis (p−5for the change of Shannon index in moxifloxacin-treated animals and p−9in clindamycin-treated animals). The Shannon diversity index and unweighted UniFrac distance best predicted death, with areas under the ROC curve of 0.89 [95%CI, 0.82;0.95] and 0.95 [0.90;0.98], respectively.ConclusionsAltogether, moxifloxacin and clindamycin disrupted the diversity of the intestinal microbiota with a dependency to the DAV131A dose; mortality afterC. difficilechallenge was related to the intensity of dysbiosis in a similar manner with the two antibiotics.

Published
2018

7. Protection of hamsters from mortality by reducing fecal moxifloxacin concentration with DAV131A in a model of moxifloxacin-induced Clostridium difficile colitis

Author

Charles Burdet, Sakina Sayah-Jeanne, Thu Thuy Nguyen, Christine Miossec, Nathalie Saint-Lu, Mark Pulse, William Weiss, Antoine Andremont, France Mentré, Jean de Gunzburg, Département d’Epidémiologie, de Biostatistique et de Recherche Clinique [AP-HP Hôpital Bichat - Claude Bernard] (DEBRC), 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), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Da Volterra, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), UNT Health Science Center [Fort Worth, USA], University of North Texas (UNT), Laboratoire de bactériologie, 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 Diderot - Paris 7 (UPD7), and Comets, Emmanuelle

Subjects
0301 basic medicine, Antibiotics, Quantitative Biology - Quantitative Methods, Gastroenterology, prevention, Moxifloxacin, Cricetinae, Pharmacology (medical), Quantitative Methods (q-bio.QM), Enterocolitis, Pseudomembranous, C. difficile infection, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Mortality rate, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 3. Good health, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Charcoal, moxifloxacin, Fluoroquinolones, medicine.drug, medicine.medical_specialty, medicine.drug_class, 030106 microbiology, Hamster, Clostridium Difficile Colitis, 03 medical and health sciences, Internal medicine, medicine, Animals, Experimental Therapeutics, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Feces, Pharmacology, Dose-Response Relationship, Drug, Clostridioides difficile, business.industry, mortality, Gastrointestinal Microbiome, Gastrointestinal Tract, Disease Models, Animal, Regimen, hamster animal model, Activated charcoal, FOS: Biological sciences, Clostridium Infections, Dysbiosis, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Lowering the gut exposure to antibiotics during treatments can prevent microbiota disruption. We evaluated the effects of an activated charcoal-based adsorbent, DAV131A, on the fecal free moxifloxacin concentration and mortality in a hamster model of moxifloxacin-induced Clostridium difficile infection. A total of 215 hamsters receiving moxifloxacin subcutaneously (day 1 [D 1 ] to D 5 ) were orally infected at D 3 with C. difficile spores. They received various doses (0 to 1,800 mg/kg of body weight/day) and schedules (twice a day [BID] or three times a day [TID]) of DAV131A (D 1 to D 8 ). Moxifloxacin concentrations and C. difficile counts were determined at D 3 , and mortality was determined at D 12 . We compared mortality rates, moxifloxacin concentrations, and C. difficile counts according to DAV131A regimen and modeled the links between DAV131A regimen, moxifloxacin concentration, and mortality. All hamsters that received no DAV131A died, but none of those that received 1,800 mg/kg/day died. Significant dose-dependent relationships between DAV131A dose and (i) mortality, (ii) moxifloxacin concentration, and (iii) C. difficile count were evidenced. Mathematical modeling suggested that (i) lowering the moxifloxacin concentration at D 3 , which was 58 μg/g (95% confidence interval [CI] = 50 to 66 μg/g) without DAV131A, to 17 μg/g (14 to 21 μg/g) would reduce mortality by 90%; and (ii) this would be achieved with a daily DAV131A dose of 703 mg/kg (596 to 809 mg/kg). In this model of C. difficile infection, DAV131A reduced mortality in a dose-dependent manner by decreasing the fecal free moxifloxacin concentration.

Published
2017

8. Phylogenetic, virulence and antibiotic resistance characteristics of commensal strain populations of Escherichia coli from community subjects in the Paris area in 2010 and evolution over 30 years

Author

Catherine Branger, Françoise Jauréguy, Camille Couffignal, Azucena Mora, Alain Eddi, Anne-Sophie Daubié, Ghizlane Dahbi, Méril Massot, Bertrand Picard, Erick Denamur, Jorge Blanco, Olivier Clermont, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratorio de Referencia de E. coli [Lugo, Spain] (LREC), Universidade de Santiago de Compostela [Spain] (USC ), Département de Médecine Générale - DMG [Paris] (Faculté de Médecine), Sorbonne Paris Cité-Université Paris Diderot - Paris 7 (UPD7), This work was partially supported by the grant CN2012/303(Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia and The European Regional Development Fund, ERDF)., The COLIVILLE Group. The COLIVILLE Group is composed of the following medical practitioners who were involved in the recruitment of subjects for the study: Monique Allouche, Jean-Pierre Aubert, Isabelle Aubin, Ghislaine Audran, Dan Baruch, Philippe Birembaux, Max Budowski, Emilie Chemla, Alain Eddi, Marc Frarier, Eric Galam, Julien Gelly, Serge Joly, Jean-François Millet, Michel Nougairede, Nadja Pillon, Guy Septavaux, Catherine Szwebel, Philippe Vellard, Raymond Wakim, Xavier Watelet and Philippe Zerr., and Comets, Emmanuelle

Subjects
0301 basic medicine, phylogroup, Paris, Time Factors, Genotype, medicine.drug_class, Virulence Factors, 030106 microbiology, Antibiotics, Virulence, Biology, medicine.disease_cause, Serogroup, Microbiology, Group A, Polymerase Chain Reaction, Article, 03 medical and health sciences, Feces, Antibiotic resistance, Drug Resistance, Bacterial, medicine, Escherichia coli, microbiota, Humans, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Gene, Phylogeny, Phylogenetic tree, O Antigens, Sequence Analysis, DNA, 3. Good health, Molecular Typing, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Streptomycin, commensal, medicine.drug
Abstract

International audience; It is important to study commensal populations of Escherichia coli because they appear to be the reservoir of both extra-intestinal pathogenic E. coli and antibiotic resistant strains of E. coli. We studied 279 dominant faecal strains of E. coli from 243 adults living in the community in the Paris area in 2010. The phylogenetic group and sub-group [sequence type complex (STc)] of the isolates and the presence of 20 virulence genes were determined by PCR assays. The O-types and the resistance to 18 antibiotics were assessed phenotypically. The B2 group was the most frequently recovered (34.0%), followed by the A group (28.7%), and other groups were rarer. The most prevalent B2 subgroups were II (STc73), IV (STc141), IX (STc95) and I (STc131) with 22.1%, 21.1%, 16.8% and 13.7%, respectively, of the B2 group strains. Virulence factors (VFs) were more common in B2 group than other strains. One or more resistance was found in 125 strains (44.8% of the collection) but only six (2.2% of the collection) were multiresistant; no extended-spectrum beta-lactamase-producing strain was isolated. The C phylogroup and clonal group A strains were the most resistant. No trade-off between virulence and resistance was evidenced. We compared these strains to collections of strains gathered in the same conditions 30 and 10 years ago. There has been a parallel and linked increase in the frequency of B2 group strains (from 9.4% in 1980 to 22.7% in 2000 and 34.0% in 2010) and of VFs. Antibiotic resistance also increased, from 22.6% of strains resistant to at least one antibiotic in 1980 to 31.8% in 2000 and 44.8% in 2010; resistance to streptomycin, however, remained stable. Commensal human E. coli populations have clearly evolved substantially over time, presumably reflecting changes in human practices, and particularly increasing antibiotic use.

Published
2016

9. Ciprofloxacin Dosage and Emergence of Resistance in Human Commensal Bacteria

Author

Bruno Fantin, Xavier Duval, Laurent Massias, Loubna Alavoine, Françoise Chau, Sylvie Retout, Antoine Andremont, France Mentré, Emergence de la résistance bactérienne in vivo (EA3964), Université Paris Diderot - Paris 7 (UPD7), Service de médecine interne, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Hôpital Bichat - Claude Bernard, Laboratoire de Toxicologie et Pharmacocinétique, Service de Pharmacie, 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), CNR « Résistance dans les flores commensales », Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Comets, Emmanuelle, and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Male, Nalidixic acid, medicine.drug_class, 030231 tropical medicine, Antibiotics, Microbial Sensitivity Tests, Drug resistance, Biology, Pharmacology, Article, Microbiology, Feces, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Ciprofloxacin, Levofloxacin, Drug Resistance, Bacterial, Escherichia coli, medicine, Humans, Immunology and Allergy, Saliva, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Antibacterial agent, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 030306 microbiology, Viridans Streptococci, biology.organism_classification, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Anti-Bacterial Agents, 3. Good health, Infectious Diseases, Pharynx, Female, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Bacteria, medicine.drug
Abstract

International audience; Background. Although optimization of the fluoroquinolone dosage increases the efficacy of this class of drugs against bacterial infections, its impact on the emergence of resistance in commensal bacteria is unknown. Methods. Six different 14-day dosages of oral ciprofloxacin were randomly assigned to 48 healthy volunteers. Individual pharmacokinetic and pharmacodynamic parameters combining antibiotic exposure in plasma, saliva, and stool specimens and ciprofloxacin minimum inhibitory concentrations (MICs) and mutant prevention concentrations against viridans group streptococci in the pharyngeal flora and Escherichia coli in the fecal flora were estimated. Their links with the emergence of resistance to nalidixic acid or ciprofloxacin in the fecal flora and to levofloxacin in the pharyngeal flora 7, 14, or 42 days after ciprofloxacin initiation were investigated. Results. Resistance emerged in the fecal and pharyngeal flora of 25% and 33% of the subjects, respectively, mainly when local concentrations of ciprofloxacin were less than the MIC. No variable that integrated pharmacokinetic data and pharmacodynamic parameters was found to differ significantly between the subjects in whom resistance emerged and those in whom it did not. Probabilities of the emergence of resistance were not significantly different across the different antibiotic dosages. Conclusions. Selection of resistant commensals during ciprofloxacin therapy is a frequent ecological side effect that is not preventable by dosage optimization. Trial registration. Clinical Trials.gov identifier: NCT00190151 .

Published
2009

Catalog

Books, media, physical & digital resources
See catalog results