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84 results on '"Elisabeth Chachaty"'

1. Mycobacterium mucogenicum bacteremia: major role of clinical microbiologists

Author

Maxime Pradier, Anne Boucher, Olivier Robineau, Elisabeth Chachaty, Agnès Meybeck, and Eric Senneville

Subjects
Mycobacterium mucogenicum, Rapidly growing mycobacteria, Bacteremia, Catheter-related infection, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Introduction Mycobacterium mucogenicum is a rare but emerging cause of infections, especially in immunocompromised patients. Case presentation We describe a new case of M. mucogenicum catheter-related bloodstream infection in a 34-year-old woman with ovarian cancer. M. mucogenicum was at first considered as a contaminant, and susceptibility testing was not performed. Usual susceptibility of M. mucogenicum motivated prescription of clarithromycin and moxifloxacin. Finally, our isolate was confirmed susceptible to both drugs. Clinical outcome was favorable with no relapse of infection after antibiotics discontinuation despite concomitant chemotherapy. Conclusion Our case illustrates the need for a clinician-microbiologist dialogue in case of suspected M. mucogenicum infection to avoid delaying appropriate management.

Published
2018
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2. Clonal Population of Flucytosine-Resistant Candida tropicalis from Blood Cultures, Paris, France

Author

Marie Desnos-Ollivier, Stéphane Bretagne, Claire Bernède, Vincent Robert, Dorothée Raoux, Elisabeth Chachaty, Elisabeth Forget, Claire Lacroix, and Françoise Dromer

Subjects
Candida tropicalis, candidemia, flucytosine, antifungal drug resistance, polymorphic microsatellite markers, multilocus sequence typing, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Candida tropicalis is a diploid ascomycetes yeast responsible for 4%–24% of candidemia. Resistance to flucytosine is rarely described for this species but was observed for 45 (35%) of 130 C. tropicalis isolates recovered from blood cultures in the Paris area in a 4-year survey. The aims of this study were to test the hypothesis that the flucytosine-resistant isolates could represent a subgroup and to determine the relationship between epidemiologic and genomic data. Epidemiologic data and gene sequences were analyzed, and molecular typing was performed. Our results suggest that a clone of flucytosine-resistant isolates, associated with malignancies and a lower mortality than that for other C. tropicalis isolates, is widespread in the Paris area. We propose the analysis of 2 polymorphic microsatellite markers coupled with URA3 sequencing to track the clone.

Published
2008
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3. Mathematical modeling of bacterial kinetics to predict the impact of antibiotic colonic exposure and treatment duration on the amount of resistant enterobacteria excreted.

Author

Thu Thuy Nguyen, Jeremie Guedj, Elisabeth Chachaty, Jean de Gunzburg, Antoine Andremont, and France Mentré

Subjects
Biology (General), QH301-705.5
Abstract

Fecal excretion of antibiotics and resistant bacteria in the environment are major public health threats associated with extensive farming and modern medical care. Innovative strategies that can reduce the intestinal antibiotic concentrations during treatments are in development. However, the effect of lower exposure on the amount of resistant enterobacteria excreted has not been quantified, making it difficult to anticipate the impact of these strategies. Here, we introduce a bacterial kinetic model to capture the complex relationships between drug exposure, loss of susceptible enterobacteria and growth of resistant strains in the feces of piglets receiving placebo, 1.5 or 15 mg/kg/day ciprofloxacin, a fluoroquinolone, for 5 days. The model could well describe the kinetics of drug susceptible and resistant enterobacteria observed during treatment, and up to 22 days after treatment cessation. Next, the model was used to predict the expected amount of resistant enterobacteria excreted over an average piglet's lifetime (150 days) when varying drug exposure and treatment duration. For the clinically relevant dose of 15 mg/kg/day for 5 days, the total amount of resistant enterobacteria excreted was predicted to be reduced by 75% and 98% when reducing treatment duration to 3 and 1 day treatment, respectively. Alternatively, for a fixed 5-days treatment, the level of resistance excreted could be reduced by 18%, 33%, 57.5% and 97% if 3, 5, 10 and 30 times lower levels of colonic drug concentrations were achieved, respectively. This characterization on in vivo data of the dynamics of resistance to antibiotics in the colonic flora could provide new insights into the mechanism of dissemination of resistance and can be used to design strategies aiming to reduce it.

Published
2014
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4. Pullulation bactérienne gastrique : une observation histologique inhabituelle, à ne pas méconnaître

Author

Rita Bou Farah, Natacha Joyon, Elisabeth Chachaty, Valentine Langlois, and Jean-Yves Scoazec

Subjects
0301 basic medicine, medicine.medical_specialty, business.industry, medicine.medical_treatment, digestive, oral, and skin physiology, Reflux, medicine.disease, Gastroenterology, digestive system diseases, Pathology and Forensic Medicine, Pathogenesis, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Immune system, 030220 oncology & carcinogenesis, Internal medicine, medicine, Adenocarcinoma, Medical history, Gastritis, medicine.symptom, business, Dysbiosis, Colectomy
Abstract

Gastric bacterial overgrowth is a rare situation, which may be associated with short- and long-term complications. It must be known from pathologists, since it might be detected incidentally at histological examination of gastric biopsies. We report here the case of a 74-year old woman, obese, without significant medical history, apart from a gastro-esophageal reflux treated by the long-term administration of proton pump inhibitors (PPI). In this patient, gastric bacterial overgrowth was detected at histological examination of gastric biopsies performed after colectomy for left colon adenocarcinoma. Large clusters of small, round, "coccoid" bacteria were present in the gastric mucus. Their characteristics were suggestive of enterobacteria. Bacterial proliferation was associated with severe and diffuse lesions of active gastritis. The course was rapidly unfavorable, and the patient rapidly deceased with multiple infections and multi-organ failure. In our observation, the pathogenesis of gastric bacterial overgrowth was probably multifactorial. It might have been facilitated by long-term PPI treatment and obesity, which are known risk factors, and promoted, in the post-operative setting, by multiple infections and immune failure. Our observation underlines that gastric bacterial overgrowth might be associated with severe gastritis, which might justify antibiotherapy. Other consequences of prolonged gastric dysbiosis cannot be excluded, such as the promotion of neoplastic lesions.

Published
2021
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5. Development and stability of an oral suspension of procarbazine in pediatrics

Author

Elisabeth Chachaty, Lionel Tortolano, François Lemare, Sandra Raimbault, Pamela Bravo, Thomas Fleury, Louis Bertin, Maxime Annereau, and Antoine Pinon

Subjects
Pediatrics, medicine.medical_specialty, business.industry, Pharmaceutical Science, 02 engineering and technology, 021001 nanoscience & nanotechnology, Procarbazine, 030226 pharmacology & pharmacy, Dosage form, 03 medical and health sciences, 0302 clinical medicine, medicine, Pediatric oncology, 0210 nano-technology, business, medicine.drug
Abstract

Many drugs used in pediatric oncology are not labeled and adapted for pediatric use, such as caps of procarbazine to treat gliomas in children under 6 years old. Indeed, pediatric patients present difficulties to swallow these caps and it can lead to major observance problems. To provide a solution to this situation, we propose the development of an oral procarbazine suspension. Suspension was produced from the commercial capsules powder of procarbazine 50 mg, mixed with excipients, specifically selected for children. The physical and chemical stability of this presentation was assessing with a specific RP-HPLC method and degradation products were study in forced degradation conditions according to the French and the European recommendations. A 10 mg/mL suspension was formulated and divided into single-dose syringes, in order to secure administration. We formulated a new dosage form of procarbazine to ensure an accurate and safe dose for children administration.

Published
2019
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6. Thyroid nocardiosis: Case report and review of the literature

Author

Rocco Collarino, Bertrand Gachot, Violaine Esnault, Elisabeth Chachaty, Mathias Pouillon, Benjamin Wyplosz, Stéphane Jauréguiberry, and Sebastian Wittnebel

Subjects
Transplantation, medicine.medical_specialty, biology, medicine.diagnostic_test, business.industry, Brain biopsy, Thyroid, Nocardiosis, Nocardia, 030230 surgery, biology.organism_classification, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Bronchoalveolar lavage, medicine.anatomical_structure, medicine, 030211 gastroenterology & hepatology, Sampling (medicine), Radiology, Abscess, business, Nocardia farcinica
Abstract

Disseminated nocardiosis is a rare but growing concern in immunocompromised patients. Typical localizations include the lung, brain and/or soft tissues, but laboratory confirmation of nocardiosis usually requires sampling of infected organs by invasive procedures such as bronchoalveolar lavage or brain biopsy. We report a case of disseminated nocardiosis occurring in a hematopoietic stem-cell transplant recipient, with clinical lung and brain localizations. Examination of the thyroid gland was suggestive of a unilateral abscess. A culture of thyroid pus sampled by fine-needle aspiration was positive for Nocardia farcinica and therefore avoided a more invasive procedure. The patient recovered after a six-month antibiotic therapy without thyroid surgery. We reviewed other ten cases of thyroid nocardiosis published in the medical literature. Among the ten cases of disseminated nocardiosis established during the patient's lifetime including ours, six (60%) were asymptomatic and seven (70 %) were confirmed by culture of the aspiration of thyroid pus. When disseminated nocardiosis is suspected, systematic examination for a thyroid abscess may help establish a microbiological diagnosis and prevent further invasive procedures.

Published
2021
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7. Scedosporiosis/lomentosporiosis observational study (SOS): Clinical significance of Scedosporium species identification

Author

Boris Melloni, Benoit Roze, Lilia Hasseine, Jacques-Olivier Bay, Laurence Delhaes, Dominique Toubas, Gaelle Guillerm, Xavier Iriart, Thomas Similowski, Valérie Letscher-Bru, Liana Carausu, Adela Angoulvant, Eric Caumes, Marie-Elisabeth Bougnoux, Yves Leprince, Taieb Chouaki, Cécile Molucon-Chabrot, Eric Dannaoui, Hervé Dutronc, Youssef El-Samad, Florent Morio, Morgane Mourguet, Alexandre Alanio, Berengere Gruson, Pierre Cahen, Stéphane Ranque, Anne Boullié, Julie Bonhomme, Violaine Noel, Françoise Dromer, Elisabeth Chachaty, Felipe Suarez, Beate Heym, François Bissuel, Cécile Jensen, Jean-Pierre Gangneux, Emmanuelle Mouchon, Philippe Zann, Patricia Mariani, Bernard Bouteille, Véronique Leflon-Guibout, Dea Garcia-Hermoso, Anne Scemla, Stéphane Blanche, Agnes Lefort, Dorothée Raoux-Barbot, Didier Bronnimann, Olivier Lortholary, Matthieu Revest, Fanny Lanternier, Philippe Poirier, Luc Quaesaet, Marie Machouart, Françoise Botterel-Chartier, Viviane Queyrel-Moranne, Thomas Perpoint, Anne De Tinteniac, Pascale Penn, Ana Presedo, Marie Balsat, Anne Huynh, Lelia Escaut, Noémie Gadaud, Antoine Huguenin, Martine Gari-Toussaint, Sophie Brun, Jean-Marie Forel, Blandine Rammaert, Nicole Desbois, Alain Delmer, Valérie Moal, Arnaud Fekkar, Damien Hoinard, Elizabeth Rivaud, Delphine Lancement, Laurence Pougnet, Valérie Zeller, Jacques Grill, Florence Pasquier, Fabrice Larosa, Jean-François Papon, Nina Arakelyan-Laboure, Thomas Daix, Catherine Cordonnier, Nicolas Limal, Patrick Lutz, Laurence Maulin, Céline Nourrisson, Stéphane Bretagne, Françoise Uettwiller, Florence Ader, Céline Dieval, Nicolas Traversier, Sophie Bayle, Sorya Belaz, Frédéric Villega, Flore Sicre De Fontbrune, Didier Poisson, Olivier Moquet, Guillaume Martin-Blondel, Kamel Laribi, Delphine Horeau-Langlard, Gilles Nevez, Stéphanie Branger, Audrey Hessel, Philippe Herman, Jérémie Orain, Emilie Catherinot, Frédéric Mechai, Cristina Audoly, Frédéric Gabriel, Jean-François Velly, Caroline Fritz, Muriel Alvarez, Romain Guillemain, Pascal Turlure, Grégoire Leclerc, Frederic Pene, Lionel Mannone, Frédéric Grenouillet, Yoann Prevot, Louis-Jean Couderc, Isabelle Degasne, Giovanna Ingenuo, Joséphine Dorin, Florence Persat, Pierre-Marie Roger, Nathalie Brieu, David Boutoille, Pierre Frange, Nicolas Paleiron, Christophe Joubert, Laurent Hustache-Mathieu, Raoul Herbrecht, Frédéric Janvier, Lenaïg Le Clech, Cécile Gautier, Joelle Guitard, Nicolas Durrleman, Romain Guery, Stéphane De Botton, Sophie Cassaing, Marine Paul, Rachel Brault, Claire Briere-Bellier, Catherine Kauffmann-Lacroix, Nicolas Engrand, Audrey Berric, Hôpital Henri Mondor, Diane Bouvry, André Paugam, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Victor Segalen - Bordeaux 2, Université Paris Cité (UPCité), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP), 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), Centre Hospitalier du Pays d'Aix, CHU Amiens-Picardie, The National Reference Center for Invasive Mycoses and Antifungals is supported in part by Santé Publique France and Institut Pasteur., Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Pasteur [Paris], and Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP]

Subjects
Adult, Male, medicine.medical_specialty, Antifungal Agents, Adolescent, LOMENTOSPORA PROLIFICANS, Lomentospora prolificans, Microbial Sensitivity Tests, Neutropenia, Scedosporium sp, Scedosporium, Young Adult, 03 medical and health sciences, Scedosporium species, Internal medicine, Humans, Medicine, Clinical significance, Child, Mycological Typing Techniques, scedosporiosis, Phylogeny, Fungemia, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged, Retrospective Studies, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, 030306 microbiology, business.industry, Infant, Newborn, Infant, Scedosporium apiospermum, General Medicine, Middle Aged, medicine.disease, cardiovascular localization, 3. Good health, Infectious Diseases, Child, Preschool, outcome, Female, Observational study, France, business, Invasive Fungal Infections
Abstract

International audience; Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes. We retrospectively studied cases of invasive scedosporiosis in France from 2005 through 2017 based on isolates characterized by polyphasic approach. We recorded 90 cases, mainly related to Scedosporium apiospermum (n = 48), S. boydii/S. ellipsoideum (n = 20), and Lomentospora prolificans (n = 14). One-third of infections were disseminated, with unexpectedly high rates of cerebral (41%) and cardiovascular (31%) involvement. In light of recent Scedosporium taxonomic revisions, we aimed to study the clinical significance of Scedosporium species identification and report for the first time contrasting clinical presentations between infections caused S. apiospermum, which were associated with malignancies and cutaneous involvement in disseminated infections, and infections caused by S. boydii, which were associated with solid organ transplantation, cerebral infections, fungemia, and early death. The clinical presentation of L. prolificans also differed from that of other species, involving more neutropenic patients, breakthrough infections, fungemia, and disseminated infections. Neutropenia, dissemination, and lack of antifungal prescription were all associated with 3-month mortality. Our data support the distinction between S. apiospermum and S. boydii and between L. prolificans and Scedosporium sp. Our results also underline the importance of the workup to assess dissemination, including cardiovascular system and brain. Lay Summary Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes.

Published
2020
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8. Paradoxical High-Level Spiramycin Resistance and Erythromycin Susceptibility Due to 23S rRNA Mutation in Streptococcus constellatus

Author

Christophe Isnard, François Guérin, Elisabeth Chachaty, Vincent Cattoir, Michel Auzou, Jean-Christophe Giard, Agathe Capitaine, Paul-Louis Woerther, Université de Caen Normandie - UFR Santé (UNICAEN Santé), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Service de Microbiologie [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de bactériologie, virologie, hygiène [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut Gustave Roussy (IGR), Groupe de Recherche sur l'Adaptation Microbienne (GRAM 2.0), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Unité de Recherche Risques Microbiens (U2RM), CHU Pontchaillou [Rennes], Centre National de Référence de la Résistance aux Antibiotiques [CHU Rennes] (CNR), 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 ), 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 Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), and Mzembaba, Sandy

Subjects
Microbiology (medical), Streptococcus milleri group, medicine.drug_class, Immunology, medicine.disease_cause, Microbiology, Streptococcus constellatus, 03 medical and health sciences, Ribosomal protein, 23S ribosomal RNA, Streptococcus pneumoniae, medicine, 030304 developmental biology, Pharmacology, 0303 health sciences, Lincosamides, biology, ARMS qPCR, 030306 microbiology, Spiramycin, Broth microdilution, A2062C, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 23S rRNA mutation, Streptococcus milleri, MLS resistance, medicine.drug
Abstract

International audience; Objectives: The aim of the study was to characterize phenotypically and genotypically an uncommon mechanism of resistance to macrolides, lincosamides, and streptogramins (MLS) in a Streptococcus milleri group clinical isolate.Materials and Methods: The isolate UCN96 was recovered from an osteoradionecrosis wound, and was identified using the matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and the partial sequencing of the sodA gene. Antimicrobial susceptibility testing were carried out by the disk diffusion method and minimal inhibitory concentrations (MICs) were determined by the broth microdilution technique. PCR screening was performed for MLS resistance genes described in Gram-positive bacteria. Specific mutations in the ribosomal proteins L3-, L4-, and L22-encoding genes were also screened and those in domain V of the 23S rRNA gene (rrl). The number of mutated copies of the rrl gene was determined using amplification-refractory mutation system quantitative-polymerase chain reaction (qPCR) analysis.Results: The clinical isolate UCN96 was unambiguously identified as Streptococcus constellatus. It was susceptible to all macrolides and lincosamides (ML) antibiotics except spiramycin (MIC >256 mg/L) while it was also resistant to streptogramins. Screening for all acquired resistance genes was negative and no mutation was found in genes coding for L3, L4, and L22 ribosomal proteins. Of interest, a single mutation, A2062C (according to Escherichia coli numbering), was detected in the domain V of 23S rRNA.Conclusion: Mutations at the position 2062 of 23S rRNA have been detected once in Streptococcus pneumoniae, and not yet in other Streptococcus spp. This mechanism is very likely uncommon in Gram-positive bacteria because different copies of 23S rRNA operons should be mutated for development of such a resistance pattern.

Published
2020
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9. Epidemiological investigation for grouped cases of Trichosporon asahii using whole genome and IGS1 sequencing

Author

N. Brieu, B. Sendid, E. Sitterle, Frédéric Gabriel, I. Poilane, D. Moissenet, Christine Aznar, V. Blanc, N. Traversier, M. Sasso, N. Godineau, O. Eloy, Corinne Maufrais, Danièle Maubon, H. Rabérin, C. Lawrence, P. Mariani, P. Cahen, C. Bonnal, B. Bouteille, M. Cornet, F. Moriot, B. Heym, Elisabeth Chachaty, Dominique Toubas, M. Nicolas, Sophie Cassaing, A. Paugam, S. Picot, E. Moalic, Adela Angoulvant, Loïc Favennec, Françoise Dromer, M. Gari‐toussaint, Marc Pihet, Taieb Chouaki, Magalie Pierre Demar, Frédéric Grenouillet, N. Fauchet, L. Collet, Frédéric Dalle, Marie-Elisabeth Bougnoux, Céline Nourrisson, Marie Desnos-Ollivier, O. Faure, Françoise Botterel, C. Nabet, N. Bourgeois, E. Bailly, Dorothée Quinio, Alexandre Alanio, O. Mouquet, S. Brun, S. Bland, Julie Bonhomme, Jean-Pierre Gangneux, Stéphane Ranque, Philippe Poirier, N. Desbois, Florence Persat, Anne-Pauline Bellanger, H. Piarroux, E. Forget, L. Lachaux, V. Bru, Laurence Millon, A. Minoza, C. Kauffman, L. Hasseine, Martine Wallon, A.L. Roux, D. Poisson, S. Bonacorsi, Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre d'Informatique pour la Biologie, Institut Pasteur [Paris], Laboratoire de Parasitologie-Mycologie (CHU d'Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Laboratoire Hospitalo-Universitaire de Parasitologie-Mycologie, Coordination Régionale de la lutte contre le Virus de L'Immunodéficience Humaine (COREVIH)-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Université des Antilles (UA), Observatoires Régionaux du Pneumocoque, Partenaires INRAE, Université de Picardie Jules Verne (UPJV), Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement - CNRS - UBFC (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 Brest (CHRU Brest), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Laboratoire de Parasitologie-Mycologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx ), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Laboratoire de parasitologie [Pointe-à-Pitre], CHU Pointe-à-Pitre/Abymes [Guadeloupe], Ecosystemes Amazoniens et Pathologie Tropicale (EPat), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Guyane (UG), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Sud Saint Pierre [Ile de la Réunion], Centre Hospitalier de Versailles André Mignot (CHV), Hôpital Huriez, CHU Limoges, Hospices Civils de Lyon (HCL), Institut de parasitologie et mycologie médicale, Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Service de Maladies Infectieuses et Tropicales [Fort-de-France, Martinique], CHU Fort de France-CHU de la Martinique [Fort de France]-Hôpital Pierre Zobda-Quitman [CHU de la Martinique], CHU de la Martinique [Fort de France], Hydrosciences Montpellier (HSM), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Nice (CHU Nice), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie-Mycologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Hôpital Delafontaine, Centre Hospitalier de Saint-Denis [Ile-de-France], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Hôpital universitaire Bichat, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hopital Saint-Louis [AP-HP] (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Curie [Paris], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Laboratoire Chrono-environnement (UMR 6249) (LCE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service de Parasitologie et Mycologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
0301 basic medicine, Adult, Male, Antifungal Agents, Adolescent, Genotype, Genotyping Techniques, [SDV]Life Sciences [q-bio], 030106 microbiology, Single-nucleotide polymorphism, Dermatology, Trichosporon asahii, Biology, Genome, DNA, Ribosomal, 030207 dermatology & venereal diseases, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Trichosporonosis, medicine, Humans, Child, DNA, Fungal, Mycological Typing Techniques, Genotyping, Phylogeny, ComputingMilieux_MISCELLANEOUS, Aged, Genetics, Voriconazole, Whole genome sequencing, Whole Genome Sequencing, Basidiomycota, Haplotype, Infant, General Medicine, Sequence Analysis, DNA, Middle Aged, medicine.disease, 3. Good health, Infectious Diseases, Child, Preschool, Female, France, Genome, Fungal, medicine.drug
Abstract

BACKGROUND Trichosporonosis is a rare invasive infection in humans mainly due to Trichosporon asahii, and especially recovered from patients having haematological malignancy. Since 2012, IGS1 region sequencing is used as a genotyping method to distinguish isolates, with high frequency of one haplotype worldwide and a geographic specificity for some haplotypes. OBJECTIVES We compared the IGS1 genotyping method and whole genome sequencing (WGS) to study the relationship between clinical isolates involved in two grouped cases in France. METHODS IGS1 sequencing and antifungal susceptibility testing were performed for 54 clinical isolates. Clinical data for 28 isolates included in surveillance programs were analysed. Whole genome was sequenced for 32 clinical isolates and the type strain. RESULTS All isolates were intrinsically resistant to flucytosine, while voriconazole had the most potent in vitro activity. The majority of the isolates was recovered from patients with haematological malignancies (42.86%), with a high proportion of children (

Published
2020
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10. [Gastric bacterial overgrowth: An unusual histological observation, not to be overlooked]

Author

Valentine, Langlois, Natacha, Joyon, Rita Bou, Farah, Elisabeth, Chachaty, and Jean-Yves, Scoazec

Subjects
Risk Factors, Gastritis, Humans, Female, Proton Pump Inhibitors, Aged
Abstract

Gastric bacterial overgrowth is a rare situation, which may be associated with short- and long-term complications. It must be known from pathologists, since it might be detected incidentally at histological examination of gastric biopsies. We report here the case of a 74-year old woman, obese, without significant medical history, apart from a gastro-esophageal reflux treated by the long-term administration of proton pump inhibitors (PPI). In this patient, gastric bacterial overgrowth was detected at histological examination of gastric biopsies performed after colectomy for left colon adenocarcinoma. Large clusters of small, round, "coccoid" bacteria were present in the gastric mucus. Their characteristics were suggestive of enterobacteria. Bacterial proliferation was associated with severe and diffuse lesions of active gastritis. The course was rapidly unfavorable, and the patient rapidly deceased with multiple infections and multi-organ failure. In our observation, the pathogenesis of gastric bacterial overgrowth was probably multifactorial. It might have been facilitated by long-term PPI treatment and obesity, which are known risk factors, and promoted, in the post-operative setting, by multiple infections and immune failure. Our observation underlines that gastric bacterial overgrowth might be associated with severe gastritis, which might justify antibiotherapy. Other consequences of prolonged gastric dysbiosis cannot be excluded, such as the promotion of neoplastic lesions.

Published
2020

11. Paradoxical High-Level Spiramycin Resistance and Erythromycin Susceptibility due to 23S rRNA Mutation in

Author

Agathe, Capitaine, Paul-Louis, Woerther, Michel, Auzou, Elisabeth, Chachaty, François, Guérin, Jean-Christophe, Giard, Vincent, Cattoir, and Christophe, Isnard

Subjects
Genotype, Streptogramins, Superoxide Dismutase, Streptococcus milleri Group, Microbial Sensitivity Tests, Real-Time Polymerase Chain Reaction, Streptococcus constellatus, Anti-Bacterial Agents, Erythromycin, RNA, Ribosomal, 23S, Phenotype, Bacterial Proteins, Drug Resistance, Bacterial, Spiramycin, Humans, Macrolides, Lincosamides
Published
2020

12. Mycobacterium mucogenicum bacteremia: major role of clinical microbiologists

Author

Eric Senneville, Olivier Robineau, Agnès Meybeck, Elisabeth Chachaty, Anne Boucher, M. Pradier, Centre Hospitalier de Tourcoing, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Gustave Roussy (IGR), Département de soins aigus [Gustave Roussy] (DSA), CHU Lille, Université de Lille, METRICS : Evaluation des technologies de santé et des pratiques médicales - ULR 2694, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 [METRICS], and Institut Gustave Roussy [IGR]

Subjects
0301 basic medicine, Adult, Catheter-related infection, Bacteremia, Mycobacterium mucogenicum, Rapidly growing mycobacteria, medicine.medical_specialty, medicine.drug_class, 030106 microbiology, Antibiotics, Case Report, Microbial Sensitivity Tests, Carcinoma, Ovarian Epithelial, Macrolide Antibiotics, lcsh:Infectious and parasitic diseases, Diagnosis, Differential, 03 medical and health sciences, Immunocompromised Host, Pharmacotherapy, Medical microbiology, Professional Role, Moxifloxacin, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Clarithromycin, Internal medicine, medicine, Humans, lcsh:RC109-216, Ovarian Neoplasms, Mycobacterium Infections, biology, business.industry, Clinical Laboratory Techniques, Nontuberculous Mycobacteria, biology.organism_classification, medicine.disease, 3. Good health, Anti-Bacterial Agents, Infectious Diseases, Catheter-Related Infections, Female, business, medicine.drug
Abstract

International audience; BACKGROUND: Mycobacterium mucogenicum is a rare but emerging cause of infections, especially in immunocompromised patients.METHODS: We describe a new case of M. mucogenicum catheter-related bloodstream infection in a 34-year-old woman with ovarian cancer. M. mucogenicum was at first considered as a contaminant, and susceptibility testing was not performed. Usual susceptibility of M. mucogenicum motivated prescription of clarithromycin and moxifloxacin. Finally, our isolate was confirmed susceptible to both drugs. Clinical outcome was favorable with no relapse of infection after antibiotics discontinuation despite concomitant chemotherapy.CONCLUSIONS: Our case illustrates the need for a clinician-microbiologist dialogue in case of suspected M. mucogenicum infection to avoid delaying appropriate management.

Published
2019
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13. Eggerthella lenta bacteremia in solid tumor cancer patients: Pathogen or witness of frailty?

Author

Elisabeth Chachaty, Sami Antoun, Paul-Louis Woerther, and Mansouria Merad

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, 030106 microbiology, Population, Bacteremia, Eggerthella lenta, Disease, Microbiology, Gastroenterology, Immunocompromised Host, 03 medical and health sciences, Peritoneum, Risk Factors, Neoplasms, Internal medicine, medicine, Humans, education, Pathogen, Aged, Retrospective Studies, education.field_of_study, Frailty, business.industry, Cancer, Immunosuppression, Middle Aged, medicine.disease, Survival Analysis, Surgery, Actinobacteria, 030104 developmental biology, Infectious Diseases, medicine.anatomical_structure, Female, business
Abstract

Eggerthella lenta is increasingly found in patients with severe comorbidities. Because oncologic patients are exposed to emerging pathogens, we aimed to describe the factors associated with E. lenta bacteremia in this immunosuppressed population. Oncology patients with blood cultures positive for E. lenta were retrospectively recorded from 2009 to 2015. Socio-demographic and medical/biological data as well as potential risk factors and mortality were recorded and analyzed. Twenty-three patients were included. Gastro intestinal (GI) and gynecological cancers were reported in 12/23 (52%) and 7/23 cases (30%), respectively. Eleven/23 patients (48%) had metastatics lesions and 6/23 (26%) had peritoneal carcinomatosis. No associated tissue infection was found in 14/23 cases (61%). Blood cultures yielded at least one other species in addition to E. lenta in 10/23 cases (43%). Mortality associated with E. lenta bacteremia was 22% (5/23). E. lenta bacteremia often occurred in patients with advanced cancer disease without documented infection. In most of the cases, intestinal obstruction and/or isolated fever were the only recorded symptoms. In these cases, the damages of intestinal barrier induced by the cancer and/or its specific treatments may be the cause of bacterial translocation.

Published
2017
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14. Ventilator-associated pneumonia and bloodstream infections in intensive care unit cancer patients: a retrospective 12-year study on 3388 prospectively monitored patients

Author

Elisabeth Chachaty, Federico Rotolo, Muriel Wartelle, François Blot, Jean-Pierre Pignon, Y. Hicheri, M. Mons, Bertrand Gachot, and Annabelle Stoclin

Subjects
Male, medicine.medical_specialty, Critical Illness, Bacteremia, Healthcare-associated infections, law.invention, Cohort Studies, Catheter-associated infections, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, Neoplasms, Sepsis, Epidemiology, medicine, Humans, Ventilator-associated pneumonia, Cumulative incidence, Intensive care unit, 030212 general & internal medicine, Aged, Monitoring, Physiologic, Retrospective Studies, Cross Infection, business.industry, Incidence (epidemiology), Incidence, Pneumonia, Ventilator-Associated, Middle Aged, bacterial infections and mycoses, medicine.disease, Confidence interval, Catheter, Pneumonia, Intensive Care Units, Oncology, Risk factors, 030220 oncology & carcinogenesis, Catheter-Related Infections, Female, Original Article, business
Abstract

Purpose Some publications suggest high rates of healthcare-associated infections (HAIs) and of nosocomial pneumonia portending a poor prognosis in ICU cancer patients. A better understanding of the epidemiology of HAIs in these patients is needed. Methods A retrospective analysis of all the patients hospitalized for ≥ 48 h during a 12-year period in the 12-bed ICU of the Gustave Roussy hospital, monitored prospectively for ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) and for use of medical devices. Results During 3388 first stays in the ICU, 198 cases of VAP and 103 primary, 213 secondary, and 77 catheter-related BSIs were recorded. The VAP rate was 24.5/1000 ventilator days (95% confidence interval [CI] 21.2–28.0); the catheter-related BSI rate was 2.3/1000 catheter days (95% CI 1.8–2.8). The cumulative incidence during the first 25 days of exposure was 58.8% (95% CI 49.1–66.6%) for VAP, 8.9% (95% CI, 6.2–11.5%) for primary, 15.1% (95% CI 11.6–18.5%) for secondary and 5.0% (95% CI 3.2–6.8%) for catheter-related BSIs. VAP or BSIs were not associated with a higher risk of ICU mortality. Conclusions This is the first study to report HAI rates in a large cohort of critically ill cancer patients. Although both the incidence of VAP and the rate of BSI are higher than in general ICU populations, this does not impact patient outcomes. The occurrence of device-associated infections is essentially due to severe medical conditions in patients and to the characteristics of malignancy. Electronic supplementary material The online version of this article (10.1007/s00520-019-04800-6) contains supplementary material, which is available to authorized users.

Published
2018

15. A Long-Term Study of the Diversity of OXA-48-Like Carbapenemase-Producing Bacterial Strains in Infected Patients and Carriers

Author

Paul-Louis Woerther, Sébastien Forget, Elisabeth Chachaty, Taha Jardak, Dominique Decré, Inès Ben Hassine, Guillaume Arlet, Centre d'Immunologie et de Maladies Infectieuses (CIMI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Microbiology (medical), Klebsiella pneumoniae, Hospital setting, 030106 microbiology, Immunology, Gene Expression, Microbial Sensitivity Tests, medicine.disease_cause, Microbiology, beta-Lactam Resistance, beta-Lactamases, 03 medical and health sciences, Plasmid, polycyclic compounds, medicine, Escherichia coli, Humans, Gene, Escherichia coli Infections, Phylogeny, ComputingMilieux_MISCELLANEOUS, Pharmacology, biology, Escherichia coli Proteins, Genetic Variation, Carbapenemase producing, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, DNA Fingerprinting, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Hospitals, 3. Good health, Anti-Bacterial Agents, Klebsiella Infections, Multiple drug resistance, Isoenzymes, Long term learning, Carbapenems, Carrier State, bacteria, France, Plasmids
Abstract

Since their emergence at the beginning of the century, OXA-48 carbapenemases have spread in the community and in hospitals. To assess the diversity of OXA-48-producing bacterial strains and plasmids in the hospital setting, we studied the strains isolated from patients in three hospitals in the Paris area.All possible OXA-48-like strains were included in the study. OXA-48-like and extended-spectrum beta-lactamase-encoding genes were identified, and fingerprinting analysis was performed for all Escherichia coli and Klebsiella pneumoniae strains. The backbones and close genetic environments of blaOverall, 68 strains from 30 patients were studied. These strains belonged to seven different enterobacterial species. OXA-48, OXA-204, and OXA-401 were identified in 62, 3, and 3 isolates, respectively. Additional broad-spectrum beta-lactamases were identified in 34% (23/68) of the strains. The strain diversity was high between and within patients. Identical patterns were observed only within individual patients or among epidemiologically related patients. Plasmid mapping was performed in the 62 OXA-48-producing strains and the 3 OXA-405-producing strains, resulting in the identification of 5 different patterns.Because of their ability to transfer between strains, OXA-48 carbapenemases have a high risk of dissemination and may become endemic in France.

Published
2018
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16. Protection of the Human Gut Microbiome From Antibiotics

Author

Jean de Gunzburg, Violaine Augustin, Amine Ghozlane, Laurence Armand-Lefevre, Xavier Duval, Antoine Andremont, Frédérique Sablier-Gallis, Sean Kennedy, Annie Ducher, Marina Varastet, Loubna Alavoine, Nicolas Pons, Elisabeth Chachaty, Florence Levenez, Charles Burdet, Etienne Ruppé, Da Volterra [Paris, France], MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Institut Gustave Roussy (IGR), Département de soins aigus [Gustave Roussy] (DSA), The randomized clinical trial was sponsored by Da Volterra (Paris) and funded in part by the European Union Seventh Framework Programme (FP7-HEALTH-2011-single-stage) under grant agreement number 282004, EvoTAR. Additional funding was from the Metagenopolis grant ANR-11-DPBS-0001, and from BPIFrance under the NOSOBIO collaborative program., We thank M. Ghidi and M. N. Bouverne (Da Volterra), as well as C. Féger (Emibiothech) for coordination and management of the clinical study, E. Arcaraz, E. Desmartin, A. Toutin, T. Mezzasalma, and C. Toutin (Amatsi Group) for the development and validation of bioanalytical methods, and for performing the fecal and plasma pharmacokinetic analyses, I. Wieder and C. Bourseau for performing the phenotypic microbiological analyses, Prof A. Dufour for biopharmacological analysis, P. Clerson (Orgamétrie) for statistical analysis of the clinical data, N. Galleron and B. Quinquis (Metagenopolis) for generating sequencing data, and P. Leonard (Metagenopolis) for informatics support., ANR-11-DPBS-0001,MGP,MetaGenoPolis(2011), European Project: 282004,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,EVOTAR(2011), Kennedy, Sean, Démonstrateurs - MetaGenoPolis - - MGP2011 - ANR-11-DPBS-0001 - DPBS - VALID, Evolution and Transfer of Antibiotic Resistance - EVOTAR - - EC:FP7:HEALTH2011-10-01 - 2015-09-30 - 282004 - VALID, de Gunzburg, Jean, Ghozlane, Amine, Ducher, Annie, Mentré, France, and Andremont, Antoine

Subjects
0301 basic medicine, Male, Antibiotics, Moxifloxacin, microbiome, MESH: Anti-Bacterial Agents/administration & dosage, MESH: Feces/chemistry, Pharmacology, antibiotics, law.invention, Feces, MESH: Aged, 80 and over, Randomized controlled trial, law, Immunology and Allergy, heterocyclic compounds, MESH: Healthy Volunteers, fluoroquinolones, MESH: Charcoal/administration & dosage, MESH: Gastrointestinal Microbiome/drug effects, MESH: Treatment Outcome, Aged, 80 and over, MESH: Aged, 0303 health sciences, MESH: Middle Aged, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Microbiota, Gastrointestinal Microbiome, MESH: Feces/microbiology, Middle Aged, Healthy Volunteers, 3. Good health, Anti-Bacterial Agents, Diarrhea, Infectious Diseases, Treatment Outcome, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Young Adult, Charcoal, MESH: Anti-Bacterial Agents/analysis, Female, medicine.symptom, MESH: Metagenomics, medicine.drug, Adult, medicine.drug_class, 030106 microbiology, Médecine humaine et pathologie, Biology, Microbiology, 03 medical and health sciences, Major Articles and Brief Reports, Young Adult, medicine, Humans, Microbiome, Adverse effect, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, Aged, Clostridium difficile, MESH: Humans, 030306 microbiology, business.industry, MESH: Adult, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, MESH: Moxifloxacin/analysis, MESH: Male, Clinical trial, MESH: Microbiota/drug effects, Regimen, 030104 developmental biology, Immunology, Human health and pathology, Metagenomics, MESH: Moxifloxacin/administration & dosage, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

In a phase 1 clinical study, coadministration of the adsorbent-based DAV132 product together with the fluoroquinolone antibiotic moxifloxacin, while not affecting the plasma concentrations of the antibiotic, reduced by >99% exposure of the intestinal microbiota to the moxifloxacin., Background Antibiotics are life-saving drugs but severely affect the gut microbiome with short-term consequences including diarrhea and selection of antibiotic-resistant bacteria. Long-term links to allergy and obesity are also suggested. We devised a product, DAV132, and previously showed its ability to deliver a powerful adsorbent, activated charcoal, in the late ileum of human volunteers. Methods We performed a randomized controlled trial in 28 human volunteers treated with a 5-day clinical regimen of the fluoroquinolone antibiotic moxifloxacin in 2 parallel groups, with or without DAV132 coadministration. Two control goups of 8 volunteers each receiving DAV132 alone, or a nonactive substitute, were added. Results The coadministration of DAV132 decreased free moxifloxacin fecal concentrations by 99%, while plasmatic levels were unaffected. Shotgun quantitative metagenomics showed that the richness and composition of the intestinal microbiota were largely preserved in subjects co-treated with DAV132 in addition to moxifloxacin. No adverse effect was observed. In addition, DAV132 efficiently adsorbed a wide range of clinically relevant antibiotics ex vivo. Conclusions DAV132 was highly effective to protect the gut microbiome of moxifloxacin-treated healthy volunteers and may constitute a clinical breakthrough by preventing adverse health consequences of a wide range of antibiotic treatments. Clinical Trials Registration NCT02176005.

Published
2018
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17. Invasive cutaneous infection due to Scopulariopsis brevicaulis unsuccessfully treated with high-dose micafungin in a neutropenic patient

Author

Linda Mahjoubi, Stéphane de Botton, Daniela Gavril, Jean-Baptiste Micol, Elisabeth Chachaty, Bertrand Gachot, Christophe Willekens, Aïcha Ben Lakhdar, Paul-Louis Woerther, and Emilie Routier

Subjects
0301 basic medicine, Microbiology (medical), Antifungal, medicine.medical_specialty, Antifungal Agents, Neutropenia, medicine.drug_class, 030106 microbiology, Echinocandins, Immunocompromised Host, Lipopeptides, 03 medical and health sciences, Pharmacotherapy, Onychomycosis, medicine, Dermatomycoses, Humans, Aged, Foot Dermatoses, Acute leukemia, business.industry, Micafungin, Scopulariopsis brevicaulis, General Medicine, medicine.disease, Dermatology, Surgery, Neutropenic patient, Treatment Outcome, Infectious Diseases, Scopulariopsis, Female, business, Febrile neutropenia, medicine.drug
Abstract

Scopulariopsis brevicaulis onychomycosis with local cutaneous invasion was diagnosed in an acute leukemia patient and unsuccessfully treated with high-dose micafungin, based on antifungal susceptibility testing. This case should alert clinicians to the possible severe evolution of onychomycosis in neutropenic patients and suggests that surgery should be preferred in such a situation.

Published
2016
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18. Differential time to positivity of central and peripheral blood cultures is inaccurate for the diagnosis of Staphylococcus aureus long-term catheter-related sepsis

Author

Hanène Bouzidi, Bertrand Gachot, Aurélie Emirian, Antoine Marty, François Blot, Elisabeth Chachaty, and Agnès Laplanche

Subjects
0301 basic medicine, Microbiology (medical), Catheter related sepsis, Adult, Male, medicine.medical_specialty, Staphylococcus aureus, Time Factors, medicine.medical_treatment, 030106 microbiology, medicine.disease_cause, Sensitivity and Specificity, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Time to positivity, Aged, Retrospective Studies, business.industry, General Medicine, Middle Aged, Staphylococcal Infections, medicine.disease, Peripheral blood, Peripheral, Catheter, Infectious Diseases, Blood Culture, Catheter-Related Infections, Female, business, Central venous catheter
Abstract

Differential time to positivity of cultures of blood drawn simultaneously from central venous catheter and peripheral sites is widely used to diagnose catheter-related bloodstream infections without removing the catheter. However, the accuracy of this technique for some pathogens, such as Staphylococcus aureus, is debated in routine practice.In a 320-bed reference cancer centre, the charts of patients with at least one blood culture positive for S. aureus among paired blood cultures drawn over a six-year period were studied retrospectively. Microbiological data were extracted from the prospectively compiled database of the microbiology unit. Data concerning the 149 patients included were reviewed retrospectively by independent physicians blinded to the absolute and differential times to positivity, in order to establish or refute the diagnosis of catheter-related sepsis. Due to missing data, 48 charts were excluded, so 101 cases were actually analysed. The diagnosis was established in 62 cases, refuted in 15 cases and inconclusive in the remaining 24 cases.For the 64 patients with both central and peripheral positive blood cultures, the differential positivity time was significantly greater for patients with catheter-related bloodstream infections due to S. aureus (P0.02). However, because of the high number of false-negative cases, the classic cut-off limit of 120 min showed 100% specificity but only 42% sensitivity for the diagnosis of catheter-related bloodstream infection due to S. aureus.These results strongly suggest that despite its high specificity, the differential time to positivity may not be reliable to rule out catheter-related bloodstream infection due to S. aureus.

Published
2017

19. Modalités de prise en charge des neutropénies fébriles chez les patients traités pour une néoplasie solide dans le service d’urgence de cancérologie Gustave-Roussy et leurs impacts économiques

Author

Bertrand Gachot, Isabelle Borget, Elisabeth Chachaty, Mansouria Merad, Mario Di Palma, Arif Alibay, and Sami Antoun

Subjects
Gynecology, Cancer Research, medicine.medical_specialty, Oncology, business.industry, Medicine, Radiology, Nuclear Medicine and imaging, Hematology, General Medicine, business, Outpatient management
Abstract

Resume Introduction La neutropenie febrile (NF) est une complication severe de la chimiotherapie. Si l’hospitalisation est recommandee pour les patients avec une NF a haut risque (HR) de complications, la prise en charge des NF a faible risque reste mal codifiee. Methodes Etude prospective observationnelle chez les patients avec une tumeur solide consultant aux urgences pour un episode de NF. Les donnees demographiques, cliniques, biologiques, le score de MASCC et les couts ont ete collectes. Resultats Cent trente-sept episodes de NF survenus chez 128patients ont ete analyses. L’hospitalisation de ces patients a ete decidee sur des parametres clinicobiologiques: 26NF (19%) ont ete pris en charge en ambulatoire strict (tous ces patients avaient un MASCC ≥ 21); 111 (81%) ont ete hospitalises: 37episodes ont ete consideres a risque eleve de complications (tous avaient un MASCC Conclusion Cette etude a permis de montrer certaines limites au score de MASCC (groupe RI). Certains patients hospitalises selon nos criteres clinicobiologiques avec un score de MASCC les classant a HR n’ont pas presente de complications. Malgre les limites methodologiques, notre etude a permis l’evaluation des couts et des difficultes du choix des prises en charge de la NF post-chimiotherapie

Published
2014
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20. Factors influencing posaconazole plasmatic concentrations in patients presenting with acute myeloid leukemia

Author

Elisabeth Chachaty, Benjamin Wyplosz, Eliane M. Billaud, Vianney Poinsignon, Isabelle Borget, Bertrand Gachot, P.-Y. Desplanques, R. Burlacu, Florence Netzer, Jean-Baptiste Micol, H. Boussion, and S. de Botton

Subjects
Adult, Male, medicine.medical_specialty, Posaconazole, Antifungal Agents, medicine.medical_treatment, Pharmacology, Neutropenia, Gastroenterology, Feeding difficulty, Young Adult, Internal medicine, Blood plasma, Aspergillosis, Humans, Medicine, In patient, Aged, Retrospective Studies, Chemotherapy, business.industry, Myeloid leukemia, Induction chemotherapy, Middle Aged, Triazoles, medicine.disease, Leukemia, Myeloid, Acute, Infectious Diseases, Female, Drug Monitoring, business, medicine.drug
Abstract

The effectiveness of posaconazole (PSZ) prophylaxis on invasive fungal infections, in patients presenting with acute myeloid leukemia (AML), seems to be correlated to its blood plasma concentration. Our goal was to identify the risk factors for underdosing.We retrospectively reviewed the records of patients treated for AML treated with PSZ, during a 2-year period. Assays500ng/mL were considered as under dosed.Fifty-nine assays (43 patients) were performed during induction (n=22) or consolidation (n=37) chemotherapy. PSZ treatment was initiated within a median of 3 days before neutropenia with a first assay performed at 8 days (3-28). The median PSZ blood plasma concentration was 375ng/mL (200-1900). Forty-one (69%) treatment were maintained until the end of neutropenia. One patient presented with candidemia, 9 with possible invasive aspergillosis, without any significant association with underdosing. The univariate analysis showed that co-administration of proton pump inhibitors (PPIs) (P=0.01) and cause of hospitalization (induction chemotherapy vs consolidation, P=0.008) were associated with underdosing, contrary to feeding difficulties (P=0.07) and digestive disorders (P=0.5). The multivariate analysis confirmed the impact of PPI use (P=0.01) and the cause of hospitalization (P=0.003).This study highlights the major impact of PPI administration on PSZ blood plasma levels and stresses the risk of non-effective prophylaxis during induction treatment of AML.

Published
2014
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21. Trends in Human Fecal Carriage of Extended-Spectrum β-Lactamases in the Community: Toward the Globalization of CTX-M

Author

Elisabeth Chachaty, Antoine Andremont, Paul-Louis Woerther, and Charles Burdet

Subjects
Microbiology (medical), Pediatrics, medicine.medical_specialty, Internationality, Epidemiology, Hospitalized patients, Reviews, Developing country, World Health Organization, beta-Lactamases, Disease Outbreaks, Feces, Globalization, Enterobacteriaceae, Environmental health, Pandemic, medicine, Humans, Disease Reservoirs, General Immunology and Microbiology, business.industry, β lactamases, Enterobacteriaceae Infections, Public Health, Environmental and Occupational Health, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, Community-Acquired Infections, Infectious Diseases, Carriage, Carrier State, business, Fecal carriage
Abstract

SUMMARY In the last 10 years, extended-spectrum β-lactamase-producing enterobacteria (ESBL-E) have become one of the main challenges for antibiotic treatment of enterobacterial infections, largely because of the current CTX-M enzyme pandemic. However, most studies have focused on hospitalized patients, though today it appears that the community is strongly affected as well. We therefore decided to devote our investigation to trends in ESBL-E fecal carriage rates and comprehensively reviewed data from studies conducted on healthy populations in various parts of the world. We show that (i) community ESBL-E fecal carriage, which was unknown before the turn of the millennium, has since increased significantly everywhere, with developing countries being the most affected; (ii) intercontinental travel may have emphasized and globalized the issue; and (iii) CTX-M enzymes, especially CTX-M-15, are the dominant type of ESBL. Altogether, these results suggest that CTX-M carriage is evolving toward a global pandemic but is still insufficiently described. Only a better knowledge of its dynamics and biology will lead to further development of appropriate control measures.

Published
2013
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22. Prevalence of mupirocin resistance among invasive coagulase-negative staphylococci and methicillin-resistant Staphylococcus aureus (MRSA) in France: emergence of a mupirocin-resistant MRSA clone harbouring mupA

Author

Richard Bonnet, Hélène Jean-Pierre, Anne-Sophie Bourrel, J. Etienne, Y. Rio, Jacques Tankovic, M. Biendo, Elisabeth Chachaty, Jean-Winoc Decousser, Véronique Vernet-Garnier, Julien Potier, Nejla Aissa, Alain Lozniewski, Alain Fiacre, Marie-Hélène Nicolas-Chanoine, Frédéric Laurent, Patrice Nordmann, F. Girard-Pipau, Jean-Philippe Lavigne, C. Plouzeau-Jayle, Christian Cattoen, François Vandenesch, Vincent Cattoir, Florence Doucet-Populaire, C. Eloy, Jocelyne Caillon, François Caron, T. Roussel-Gaillard, François Jehl, J. Texier-Maugein, Max Maurin, Laurent Bret, Grégoire Aubert, M. Archambaud, Marie-Cécile Ploy, C. Loiez-Durocher, Isabelle Patry, Gerard Lina, H. Courtade, C. Buisson-Touati, H. Rostane, G. Blanchard-Marche, Nicolas Fortineau, Roland Leclercq, Nadège Bourgeois-Nicolaos, Philippe Morand, Marine Desroches, Frédéric Robin, Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Bactéries, Pathogènes et Santé (UBaPS), Faculté de Pharmacie, Université Paris-Sud - Paris 11 (UP11)-Université Paris-Sud - Paris 11 (UP11), CHU Henri Mondor, Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), 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)-CHU Limoges, Service de Bactériologie, Virologie, Hygiène [CHU Limoges], CHU Limoges, and Novartis, France

Subjects
DNA, Bacterial, Microbiology (medical), Staphylococcus, Mupirocin, Microbial Sensitivity Tests, Biology, Staphylococcal infections, medicine.disease_cause, Polymerase Chain Reaction, Microbiology, law.invention, 03 medical and health sciences, chemistry.chemical_compound, Bacterial Proteins, law, Drug Resistance, Bacterial, medicine, Pharmacology (medical), Prospective Studies, Polymerase chain reaction, 030304 developmental biology, Lyon clone, Pharmacology, Molecular Epidemiology, 0303 health sciences, 030306 microbiology, Broth microdilution, Nuclear Proteins, invasive staphylococci, Staphylococcal Infections, Microarray Analysis, medicine.disease, Methicillin-resistant Staphylococcus aureus, Anti-Bacterial Agents, Electrophoresis, Gel, Pulsed-Field, 3. Good health, Molecular Typing, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, chemistry, Staphylococcus aureus, [SDV.IMM]Life Sciences [q-bio]/Immunology, decolonization, lipids (amino acids, peptides, and proteins), France, Coagulase
Abstract

OBJECTIVES Mupirocin is the cornerstone of decolonization regimens, a successful strategy to prevent healthcare-associated staphylococcal infections. Several recent studies have reported alarming results: (i) an extending reservoir of mupA, the ancestral mobile resistance gene, among coagulase-negative staphylococci (CoNS); (ii) the emergence of a new resistance gene (mupB); and (iii) a growing number of mupirocin-resistant methicillin-resistant Staphylococcus aureus (MRSA), including highly pathogenic clones. We performed a nationwide prospective study in France to detect such trends among invasive staphylococci. METHODS Between October 2011 and February 2012, 367 MRSA and 708 CoNS invasive isolates were collected from 37 hospitals and analysed centrally. Mupirocin MICs were determined using the broth microdilution method. mupA/B PCR was performed for resistant isolates (MIC >1 mg/L). Genetic relatedness between mupirocin-resistant MRSA isolates was determined by PFGE analysis and related isolates were tested by microarray. RESULTS Among MRSA isolates 2.2% (n = 8) were classified as mupirocin resistant; 1.4% (n = 5) showing low-level resistance (MIC ≤256 mg/L) and 0.8% (n = 3) high-level resistance (MIC >256 mg/L). Only the latter isolates carried mupA. A clonal relationship was identified between two mupA-negative MRSA from the same hospital and three mupA-positive MRSA from three distant towns; these three isolates belonged to the Lyon clone. Mupirocin resistance was identified in 10.3% of CoNS, mainly highly resistant mupA-positive isolates (5.6%). The mupB gene was not detected in mupirocin-resistant MRSA or CoNS. CONCLUSIONS This first large national study indicates the need for thorough epidemiological monitoring and a stewardship programme to prevent and detect mupirocin resistance in staphylococci.

Published
2013
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23. Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study

Author

Odile Fremin-Batteux, Juliette Clarissou-Philippe, Benoît Jauhlac, Severine Guyetand, Jacques Gasnault, Corinne Haioun, Liamine Aissaoui, Marie-Christine Pages, Marie-Pierre Fos, Christian Rose, Didier Hubert, Marie-Rose Rothe, N. Bouziges, Benoît Huc, François Devianne, Sabine Bidart, Anne Forest, Kevin Bertrand, Mohamed Eldeghedy, Annick Verhaeghe, Caroline Malderet, Anne Bertrou, Bernard Guerquin, Catherine Duche, Muriel Archambaud, Rabea Cotteret, Olivier Toullalan, Yves Devaux, Smail Bergheul, Valérie Sivadon-Tardy, Pierre-Gilles Merville, Geneviève Blanchard-Marche, Didier Raoult, Bernard Hory, Florence Richardin, Evelyne Belle, Mohamed Menouar, K Guitteaud, Mohamad Mohty, Ambroise Montcriol, Max Laurin, Aurélia Picard, Jean-Paul Mira, Marie-Charlotte Chopin, Richard Bonnet, Michel Wolff, Sébastien Maillez, Jeanne Maugein, Véronique Leblond, Nicola Walid, Bernard Gauche, Mathieu Evillard, Hassen Jeddi, Anne Bourlet, Isabelle Grawey, Thierry Jault, Sandrine Hiret, Valerie Gaborieau, Véronique Boin-Gay, An Kim, Thierry Constans, Jean-François Gaide, Martine Giraud, Eric Meaudre Desgouttes, Alain Fur, Abdallah Maakaroun, Olivier Matray, Bertrand Maubert, Frédérique Péchinot, Aurelie Garbi, Claire Delbrouck, Benoît Grandclerc, Vincent Cadiergue, Hervé Lécuyer, Bernadette Grignon, Thierry Bensaid, Nicole Constantin, Yannick Chevalier, Hassène Rahmani, Thierry Levent, Joelle Desliers, Florence Van de Velde, Xavier Adhoute, Clara Andriau, Christophe Charasse, Rémi Vatan, Benoît Martha, Alain Lecis, Didier Albert, Romain Jacobs, Hélène Lefranc, Christian Martin, Nasseur Rezgui, Bertrand Pigeon, Catherine Le Henaff, Dominique Cassignard, Françoise Cotes, Eric Pujade Lauraine, Jean-François Gattault, Nicole Ferreira-Maident, Noémie Jourde-Chiche, Hélène Garrec, Olivier Darchen, Carole Schwebel, Marie-Christine Bezian, Patrick Daoud, Tsouria Becaid, Simone Laluque, David Broche, Christine Boisselier, Pascale Martres, Sarah Hammami, Brigitte Olivier, Jean-Marie Nkunzimana, Eric Monlun, Isabelle Marterl-Lafay, Marion Carboni, Marie-Françoise Mattei, Sandrine Castelin, Isabelle Barillot, Marie-Noelle Cufi, Thomas Kaiser, Catherine Herry, Pascal Hutin, Jean-Pierre Bronowicki, Bernard Branger, Pierre Thomas, Elie Zagdoun, Anne Goquelin, Ziad Assaf, Ingrid Croquet, Bruno Pozzetto, Thomas Similowski, Anne-Isabelle Briere, Marie-Thérèse Albertini, Mariam Blaka, Christelle Tassot, Anne Gaschet, Jean-Philippe Lavigne, Antoine Pujol, Philippe Colombat, Edouard Devaud, Hana Talabani-Boizot, François Barière, Anne-Marie Cordier, Philippe Gueudet, Georges Simon, Anne-Sophie Lipovac, Françoise Bandaly, Anne Beauplet-Lepage, Sylvie Prince, Charlotte Jouzel, Jean-Luc Deboutin, Patrick Zavadil, Louis Puybasset, Marie-Cécile Petit, Loïc Guillevin, Kamel Touati, Christophe Ntalu Nkato, Sylvie Carette, Jacques Vaucel, Chantal Delasalle, Marine Gross Goupil, Laurent Gutmann, Christiane Payen, Annick Barboteau, Firouzé Bani-Sadr, Christophe Legendre, Philippe Roulier, Elie Azria, Ibrahim Farah, Isabelle Rouquette-Vincent, Anne-Sophie Erena-Penet, Philippe Labadie, Eric Josien, Aicha Derragui, Mathieu Legrand, Odile Beyne-Rauzy, Jean-Marc Nabholtz, Marie-Joelle Demarcq, Olivier Garosi, Michel Deiber, Fabrice Chaix, Bertrand Souweine, Anne Collignon, Gisèle Renard, Mickael Jego, Gilles Bernardin, Anne Allart, Jocelyn Barrier, Marc Vasse, Philippe Ménager, Marc Wurmser, Abderkader Ouazir, Olivier Gontieron, Yvon Berland, Sébastien Trouiller, David Leysenne, Christophe Ozanon, Fanny Autret, Tahar Saghi, Loïc Dopeux, Sophie Benoit-Coustou, T. Fraisse, Christine Maillard, Karine Nikodijevic, Georges Kaltenbach, Angéline Jamet, Philippe Aucher, Julie Bottero, Marie-Claude Piffaut, Marianne Besnard, Florence Courillon, Marie Bonfils, Christine Ghevaert, Marie Destors, Eliette Jeanmaire, Franck Zerbib, Manuel-Luis Gameiro, T Prazuck, Laurent Mandin, Olivier Guisset, Marguerite Fines, Toufik Feddal, Agnès Jouffret, Louis Mesnard, Thomas Bourrée, Hasinrina Razafimahefa, Sylvestre Tigaud, Vincent Estève, Philippe Malherbe, Jean-Michel Salord, Pascal Adam, Bertrand Rozec, Michel Fuillet, Olivier Lemenand, Denis Quinsat, Ana Danalaché, Véronique Vialette, François Brosset, Patrick Messner Pellenc, Nicolas Heisel, Edouard Girard, Régine Martin, Olivier Garesslin, Catherine Mille, Alexandre Gascon, Marc Nicolino, Laurence Mouly, Claire Fabre, Bénédicte Ponceau, Marie-Etiennette Emeriau, Pascal Cathebras, Bérangère Bernardaud, Michèle Pérouse de Montclos, O. Arsene, Karine Grenet, Yazdan Yazdanpanah, Sten De Witte, Anne Scemla, Laurence Bouillet, Christophe Burucoa, Vincent Loffeier, Séverine Visentin, Luc Desfrere, Miloud Arabi, Frédérique Costa, Sylvie Lechat, Ali Chekroun, Raymond Ruimy, Marie, Jérôme Bizet, Xavier Nassif, Baihas Dib, Patrick Bert-Marcaz, Laurent Martin Lefèvre, Nicholas Sedillot, Blandine Cattier, Emilie Boidin, Daniel Sondag, Aude Bourrouillou, Alain Noirot, Franck Desemerie, Fréderic Heluwaert, Catherine Tamalet, Marc G. Berger, Jean-Daniel Lelièvre, Dominique Perotin, Abdelkader Bemrah, Alain Lozniewski, Bernard Borstein, Hanna Eid, Diana Suatean, Virginie Mignaut, Jean-Claude N'guyen, Valérie Le Goff, Laurent Teillet, Christophe Rolland, Gwenaël Alfonsi, Florence Lachenal, Philippe Bossi, Yves Botreau, Florence Doucet Populaire, Henry Jardel, Nicolas Gallo, Elias Jabre-Sikias, Michel Dupon, Hélène Brihier, Isabelle Patry, Alexandre Leclercq, Bernadette Tourrand, Christophe Roussel, Jean-Emmanuel Kurtz, Bénédicte Paindaveine, Simon Elhadad, Richard Sanchez, Eric Sgro, Pierre Berger, Valérie Murbach, Anne Holstein, Florence Martin, Taoufik Merabet, Amélie Benbara, Milagros Ferreyra, Laure Esposito, Pierre Delobel, Antoine Andremont, Marc Bourlière, Carole-Anne Boudy, Jean-Baptiste Gaulthier, Laurent Tacchini, Olivier Marpeau, Sonia Tesseydre, Marie-Pierre Coulhon, Nathalie Hodee, Marie-Chrsitine Conroy, Pierre Weinbreck, Roland Leclercq, Laurent Souply, Christian Bidault, Annie Elbez, Marie-Annick Lebreton, Patrick Brisou, Agnès Ferroni, Jean-Louis Pourriat, Nadia Anguel, Christian Noel, Philippe Jouvencel, Eric Pichard, Xavier Martin, Mathieu Coste, Pierre Zuber, Catherine Neuwirth, Jean-Pierre Hacot, Paul Aye, Jérôme Guinard, Yves Pean, Jean-Christophe Dengo, Fabrice Petassou, Didier Viole, Thierry Messiaen, Jean Beytout, Philippe Petitjean, Ferdinand Savare, Patrice Cuvillier, Sophie Coignard, Hélène Anglaret, Nassim Kamar, Elisabeth Chachaty, Karine Guimard, Louis Braem, Hacene Fezoui, Pierre Martin, Jean-Paul Viard, Claire Larroche, Nicolai Claudiu-Plesa, Thierry Benoit-Cattin, Olivier Moquet, Thierry Pasdeloup, David Rosay, Rodolphe Jean, Jean-Bernard Mariette, Marc Debouverie, Hervé Peltier, Mustapha Terki, Jacques Daleas, Valérie Dattin-Dorrière, Michel Vergnaud, Emmanuel Grimprel, Sylvène Rosselli, Jean-Marc Didier, Pierre Faurie, Luc Frimat, Aziza Mandjee, Sabine Etchemendy, Pierre Tissières, Jean Nakhleh, Sylvie Mariette, Christian Perronne, Bruno Carbonne, Nathalie Houssiaux-Maisonneuve, Tristan Ferry, S Beague, Anthony Sebban, Marie-Thérèse Hili, Jean-Michel De Kermadec, Lucien Brasme, Gilles Blaison, Caroline Garandeau, Jean-Pierre Sollet, Laurent Tronchon, Thierry Samson, Julien Gesquière, Nicolas Ettahar, Alain Créange, Etienne Laurens, Véronique Equy, Fréderic Bart, Bernard Bouffandeau, Christine Vaillant, Valerie Pesque, Jean-Marc Lalot, Marc Levy, Michel Kaidomar, Mihaela Saplacan, Sterenn Yvenou, Marie-Isabelle Steibach, Emmanuelle Cambau, Agnès Riche, François Fourrier, François Raffi, Mélissa Lalu, Henri Bérard, Danielle Clave, Jean-Claude Mouries, Martine Porcheron, Jean Cabalion, Richard Lamarca, Nathalie Canu, Jean-Baptiste Roseau, Annabelle Stoclin, Luca Luminitan Elena Lupean, Rémi Gebeile, Celia Salanoubat, Carole Marmouset, Pierre Bigot, Anne-Laure Breton, Pierre Kalfon, Colette Vincent, Sophie Marty, Olivier Tandonnet, Alexis Redor, Xavier Valette, Ourida Aoudia, Jacques-Arnaud Seyrig, Bertrand Beaune, Hugues Aumaitre, Georges Pinon, Yann Leveneur, Sylvie Charachon, Raoul Herbrecht, Henriette de Valk, Gary David, Julien Pouyanne, Marc Dommergues, Majed Al Chaar, Véronique Blanc-Amrane, Pascale Guillarmé Grossmann, Bruno Abraham, Yves Morel, Philippe Suel, Denis Sautereau, Olivier Guilloy, Tu Anh Tran, Frédéric Laurent, Zahir Amoura, Jacques-Olivier Bay, Zoubida Elharie-Heraux, Joyce Sibony-Prat, Bernard Guillois, Dominique Rohmer-Heitz, Audrey Barrelet, Jérémie Courouble, Jean-Paul Herry, Daniel Vittecoq, Annie Vermesch-Langlin, Jean Auroux, Claude Aubert, Thierry Harvey, Ghislaine Lamoine-Gimet, J. Riahi, Florence Soraudeau, Bachar Al-Jalaby, Caroline Périsson, Khélifa Ayouz, Florence Cardot, François Maillet, Alain Goux, Théophile Magna, Bertille de Barbeyrac, Adrien May, Dominique Andreotti, Olivier Jonquet, Hélène Dumouchel, Didier Thibaud, Philippe Morlat, Pascal Chevalet, Pascal Ancelin, Guy Chambreuil, Cécile Le Boterff, Anne Ceriez, Olivier Detante, B Pangon, Claude C.A. Bernard, Vincent Cailleaux Pierre-Etienne Cailleux, Jordi Miatello, Pierre-Yves le Berruyer, Sylvain Kouaho, Michel Briaud, Hélène Delaby, Patrick Herbecq, Christine Segonds, Véronique Jault, Pascale Brunel, Christine Dussopt, Jean Thore, Jean-Marc Thouret, Jean-Marc Kerleau, François Le Baron, Slavius Matica, Sophie Leautez-Nainville, Matthieu Pecquet, Laurent Bret, Yacine Sedjelmaci, Pierre Metton, Habiboulaye Diallo, Jany Rey Zermati, Arnaud Delahaye, Hélène Chaussade, Laurent Mandelbrot, Emilie Bessede, Olivier Casanovas, Paul Pierrot, Annick Legras, Dominique Lauque, Hélène Gatti, Jean Catineau, Ebutu Likose, Gilles Capellier, Eric Kibbrecht, Freddy Thibaut, Patrick Valadier, Chantal Lemble, Joël Gaudelus, Joelle Mellier, Joëlle Brochen, Emmanuel Gascou, Stéphane Bonacorsi, Stéphanie Bannier, Bruno Fantin, Didier Raffenot, Valérie Revel, Hakim Amroun, Huguette Negrery, Anne-Laure Fauchais, Paul Mercury, Michel Chuzeville, Christian Zumbo, Nicolas Després, Pascal Roblot, Jérôme Pasche, Jean Claude Boufetteau, Jocelyne Caillon, Julien Boileau, V. Rabier, Benjamin Manéglier, Emilie Jourdes, Franck Ceppa, Christine Recule, Nicolas Degand, Benoît Henry, Thierry Baranger, Dominique Pateron, Agnès Pélaquier, Gérard Bouchet, Hélène Fiette, Ozel Guiden, Dana Ranta, Etienne Ruppé, Nabil Chiouk, Jacques Breuil, Dominique Leduc, Véronique Loustaud, Hervé Métenier, Michel Durand, Isabelle Mahé, Leila Karaoui, Marie-José Collus, Mehran Monchi, Olivier Belmonte, Romain Blondet, Jacques Thierry, Karine Humbert, Gilles Salama, Marie-Noelle Heurtaux, Cécile Goujard, Bruno Sivery, Martial Boisseau, Redouane Dahoumane, Pierre Delour, Christian Niels Meyer, Anne Faudon-Gibelin, Gérard Poulain, Roger-Charles Luciani, J.-C. Souquet, Olivier Grossi, François Vandenesch, Sylvain Mermont, Jacques Bronner, Sonia Dahan, Paul Marzouk, Pascal Pouedras, Noureddine Djafari, François-Xavier Caroli-Bosc, Jean-François Dessin, Brigitte Gruffat, Armelle Morin-Fatome, Sylvie Thoinet, Bano Konate, Jean-Winoc Decousser, Claire Poyart, Patrick Plessis, Olivier Millet, Vincent Cattoir, Françoise Geffroy, Manica Vasseur, Pierre Carli, Isabelle Citony, Christian Richard, Nicolas Sigur, Patrick Marthelet, Luwawu Mbimba, Pierre Feugier, Philippe Sauder, Hama Djerad, Evelyne Bourgerette, Hanen Chahtour, Adrien Lemaignen, Dominique Bechade, Patrick Ochocki, Antoine Vieillard Baron, Dominique Astruc, Marie-Pierre Moiton, Nicolas Dubois, Sylvie Ledru, Corinne Seknazi, Hélène Poupet, Jean-Philippe Brieux, Gérard Barthélémy, Aihem Yehia, Louis-Jean Couderc, Ahmed, Françoise Rigaux, Yohann N'guyen, Philippe Bethery, Damien Corberand, Etienne Auvray, Paul-Louis Woerther, Christian Combe, Sophie Delesalle, Jean-Marie Piala, Faraj Al Freijat, Philippe Juvin, Malcolm Lemyze, Hyacine Rey, Claire Larible, Noel Milpied, Lémia Zgarni, Julia Gaillard, Agnès Juven, Paola Otean, Adrien Melis, André Pechinot, Olivier Bouchaud, Olivier Chassin, Pierre Hausfater, Asma Trabelsi-Jnifen, Vincent Grobost, Didier Lemery, Pierre Soury, Françoise Brevet, Jacques Tankovic, Dominique Sansot, Jean Louis Salomon, Charlotte Cordonnier, Brigitte Lamy, Antoine Maisonneuve, Dominique Pressac, Claude Rémy, Rodolphe Sobesky, Stéphanie Cognet, Pierre Cougoul, Didier Jan, Dominique Perrotin, Cécile Hombrouk-Alet, Thierry André, Gilbert Pochmalicki, Serge Girard, Vincent Zerr, Guillaume Cadiot, Claudine Lasbasses, Michel Slama, Abderrazak El Yamani, Sophie Brovedani, Jean Armengaud, Romain Hernu, Géraldine Mascade, Aurélien Lorléa'ch, Ali Akkari, Mathieu Tourdjman, Christopher Payan, Eric Jullian, Nathalie Fonsale, Frédéric Riehl, Paul Strock, Geneviève Grise, Philippe Mottaz, Christian Floriot, Marie-Noëlle Ungeheuer, Denis Caillot, Arnaud Chalvon-Demersay, Catherine Branger, Stanislas Bruley des Varannes, Marc Paccalin, Marie-Pierre Danjean, Alexandre Mebazaa, Xavier Brunet, Roland De Varax, Laurence Delhoustal, Sophie Haro, Bruno Chabanon-Pouget, Isabelle Goidin, Dominique Chudersky, Corinne Costes, Delphine Chatellier, Maud Gelez, Damien Dassant, Pascal Joly, Jean-Michel Arnal, Zakaria Hamitou, Philippe Rondepierre, Carole Pignon, Valérie Crombe, Amanda Lopes, Chrystelle Kemenar, Olivia Raulin, Anne-Cécile Hochart, Sandrine Gérart Pons, Valérie Zeller, Guillermo Reyes Ortega, Mathilde Guérin, Audrey Migraine Bouvagnet, Florence Eboue, Isabelle Loury-Lariviere, Sophie Leotard, Suzanne Lima, Marie Kassis, Jean-Luc Donay, Jean-Pierre Audié, Guillaume Cartron, Arnaud Ribier, Fanny Buron, Mirela Tuca, Marius Semenescu, Arnaud Serre, Vincent Quentin, Denise Bouyssou-Destriau, Violaine Bresson, Christine Chandesris Joséphine Chapalain-Cagnon, Eric Cua, Henri Courtade, François Bénézit, Sébastien Lamache, Philippe Bonnefoy, Francis Schneider, Richard Monarchi, Adeline Schendel, Paramasiven Mootien, Ghislaine Gardes, Pierre-François Westeel, Jean-François Magny, François Caron, Jocelyn Michon, Didier Eyer, Isabelle Ronda, Pierre-Yves Robillard, Frédéric Renou, Anna Faucher, Jean-Robert Harlé, Anne Debernardi, Grégory Akerman, Benoît Fontenel, Pierre Hourdebaigt-Larrusse, Marie-Noëlle Adam, Aude Lessene, Abdelkader Hrichi, François Blot, Athéna Le Pierres, Romain Lemarie, Françoise Granier, Véronique Tardy, Marc Gatfosse, Pierre-Marie Roger, François Goupil, Saïd Aberrane, Franck Bernardi, Isabelle Plantier, Nathalie Funakoshi, Jean-Gilles Delecalle, Patricia Barbut, Jacques Reynes, Christophe Roy, Sophie Perreve, Michel Garre, David Ribes, Cyrille Ede, Jean-Claude Dausset, Francis Duchene, Jean Caussin, Michelle Becker-Schneider, Gilles Berthelot, Damien Dupont, Jean-Michel Gillot, Aurélie Messager, Jean-Marie Pannecouck, Jean-Christian Roussel, Alain Reynaud, Sylvie Cariou, Anne Dao, François Guillemot, Martin Martinot, Patrick Casali, Anne-Sophie Poirier, Aissa Kerchache, Necera Sakek, Eric Porthault, Christophe Decoene, Chantal Ache-Papillon, Brigitte Bicais, Jean-Claude Feugier, Thierry Masseron, Charles Marty-Ane, Daniele Goldgran Toledano, Jean-Christophe Dubus, Damien du Cheyron, Dominique Decré, Jean-Loup Pennaforte, Ahmed Tigaizin, Bernard Vache, Eric Oswald, Claire Moulinoux, Anne-Christine Jaouen, Caroline Charlier, Anne-Laure Virlouvet, Ali Kara, Jean-Luc Sicsic, Sylvie Goffart, Mathieu Zuber, Claudine Fèbre, Olivier Lortholary, Mathieu Dupont, Annie Vessieres, Thierry Helvadjian, Thomas Signouret, Cedric Daupin, Sandrine Essouri, Jean-Louis Jacob, Pascal Boileau, Caroline Blazejewski, Quentin Lepiller, Juan-Pablo Maureira, Eddy Lebas, Christophe Deschamps, Amévi Ananivi, Clovis Foguem, Daniel Adoue, Abdourahim Chamouine, Alain Michault, Bruno Guérin, Olivier Baud, Clara Vinci, Thierry Weitten, Jean-Marc Eychene, Marie Froidure, Julien Obiols, Patricia Roussellier, Marc Lecuit, André Cabié, Saskia Foucart, Karim Belhadj, Michel Cingotti, Bruno Dumoulard, Jean Puyhardy, Etienne Danquechin Dorval, Lucile Mendes-Martin, Enrique Casalino, Luc Jarrige, Fabien Lambiotte, Philippe Masson, Mohammed Mansouria, Pierre Thouvenot, Katy Jeannot, Martine Nyunga, Valérie Macci, Florent Masia, Claire Briere de la Hosseraye, Wassila Anteur, André Sommabère, Marie-Claude Germain, Isabelle Arnault, Bernard Carbonelle, Philippe Devos, Daniel Protar, Tiphaine Gaillart, Ludovic Lassel, Laurence Hamou-Plotkine, David Trystram, Thierry Bureau, Olivier Collard, Fanny Vuotto, Sophie Malhiere, Frederique Canis, Gillles Plainfosse, Catherine Lechiche, Bertrand Lassere, Martine Chouraqui, Jean Baptiste Michot, Fethi Radhouane-Khanjari, Carole Barbier, Pascal Bonitchi, Abdelaziz Benkhelil, Odile Salmon, Laurent Damaj Gandhi, Bertrand Minguet, Michel Wagner, Odile Falguières, Zahr-Eddine Ali Chaouche, Eric Zaoui, Isabelle Guichard, Bernard Huttin, Apollinaire Karirisi, Gaël Cinquetti, Christophe Plane, Lionel Rostaing, Yanne Henry-Andrieu, Daniel Re, Virginie Verrier, Pascal Bolot, Michel De Biasi, Laurence Vrigneaud, Mathilde Turpin, Marie-Claude Demachy, Etienne Roussel, Michèle Blancs, Olivier Join-Lambert, Yves Ville, Thierry Granger, Gilles Hilbert, Virginie Medeau, Daniel Villers, Benoit Pilmis, François Gouraud, Emmanuel Ardiet, Catherine Heyraud-Blanchet, Alain Devidas, Hélène Dieye, Julie Cremniter, Jean-François Bergmann, Rozenn Le Berre, Virginie Leguen, Daniel Royer, Gilles Le Maout, Christian Harou, Sylvie Gabriel-Soléan, Yves Regouby, Martine Pestel-Caron, Patrick Brunet, David Boutoille, Emmanuelle Bonnin, Patrice Coulon, Marc Sullice, Marianne Barbieux, Gilles Cambonie, Joëlle Tricoire, Marie-Nadège Bachelier, Delphine Briend, Céline Ramanantsoa, Nathalie Bednarek, Didier Lebreton, Julien Lagrandeur, Damien M'Bey, Philippe Audeguy, Elie Saliba, Lena Damaj, Hassan Fallouh, Pascal Couturier, Fabrice Prévost, Yves Domart, Marie-Odile Lafforgue, Anne Le Du, C. Beuscart, Pierre Guillet, Fabrice Larrazet, Marie-Hélène Hausermann, Henri Robert, Nicolas Fanjaud, François Goehringer, Thomas Bachelot Philippe Badia, Jean-Michel Coulaud, Cristel Fissore Magdelein, Renaud Defebvre, Anne-Sohie Moreau, Johan Courjon, Gilles Salles, Michel Mialon, Silvia Iacobelli, Emmanuelle Bille, Marie-Christine Barbier, Yves Aubard, Patrice Badila, Jean-Philippe Rasigade, Alban Deroux, Evelyne Lecaillon-Thibon, Michel Godin, Abdelmajid Djeffal, Viorica Badurescu, Meriem Canitrot, Pierre Blanchard, Antoine Legros, Laurence Got, Françoise Duluc, Mylène M. Maury, Gilles Dassieu, Nordine Khodeir, Jean-Marie Duez, Mathieu Morincomme, Jérôme Lacroix, Mathieu Revest, Koffi Blewoussi, Isabelle Barazer, Françoise Poitevin, Camille Seignovert, Stéphanie Honore Bouakline, Anne Heidt, Brigitte Malbruny, Julien Desblache, Christian Cattoen, Eric Jaunait, Bruno Chaminade, Claude Bazin, Jonathan Chelly, Anne Pottier, Alain Schmitt, Alain Tissot, Karim Dadoun, P. Rebattu, Claudine Contamin, Arnaud Guerard, Nathalie Ravet, Sandrine Khalifa-Thellier, Marlène Chatron, Gaëlle Dörr, Hélène Biessy, Emmanuel Forestier, Bruno Devaux, Jean-Jacques Grelaud, Xavier Tchenio, Marie-Cécile Ploy, Jérémie Violette, Michèle Burdin, Lionel Falchero, Dominique Jacomy, Jean-Christophe Rozé, Damien Labarriere, Stéphane Leroux, Corinne Meregnani, Assia Ferhat Carre, Paul Orode, Jean-Gabriel Paul, Catherine Godon, Agnès Vinay, Régine Barraduc, Dominique Dallay, Alexandre Ampère, Anne-Gaelle Kervegant, Guillaume Louart, Dominique Beal Ardisson, Francoise Leonetti, Jean-Yves Baril, Stéphanie Haiat, Bincy Darre, Jérôme Bay, Yvan Gauthier, Sylvie Radenne, Pierre-Yves Gueugniaud, Philippe Ravaud, Luc Landraud, Guillaume Ranchon, Loïc Chimot, Véronique Duval, Ilhem Agha-Mir, Sabine Camiade, Estelle Wafo, Jean-Patrick Laporte, Mariam Roncato-Saberane, Camille Bron, Patrice Laudat, Samir Kennouche, Nawel Afroukh, Dominique Neri, Hakim Kherouf, Yoar Hichri, Pierre-Edouard Bollaert, Gwenaelle Vary, Denis Castaing, Christine Lefort, Sébastien Rouget, René Robert, Christelle Guillet-Caruba, Catherine Simonin, Alain Vighetto, Severine Cabasson, Alain Brusset, Alexandra Doloy, Christel Cherlet, Ahmed Rouidi, Marina Salvucci, Réginald Pordes, René-Gilles Patrigeon, Emmanuelle Dupre-Narlet, Jacques Minet, Fethi Taleb, Anne-Marie Colingorski, Tahar Hadou, Sylvain Diamantis, Isabelle Glorieux, Thierry May, Jean-Claude Colombani, Anne Berth-Farges, Nicole Desplaces, Renaud de Tayrac, Elisabeth Walter, Fabienne Lorge, Pascal Reboul, Nathalie Dournon, Laurence Estépa, Marie-Lina Toubia, Mathilde Flahault, Thierry Delacour, Dominique Hurel, Hélinoro Andriamaneo, Cécile Bébéar, Denis Grasset, Miloud Serier, Oléna Orléva, Nadine Dubroca, Hervé Gentilhomme, Jean-Luc Baudel, Isabelle Lavenu, Salim Smati, Carlo Saroufim, Eric Placidi, Albert Sotto, Benoît Libeau, Hélène Leroy, François Golfier, Christophe Dollon, Laurence Desnoulez, Eric Barre, Daniel Cohen, Pascal Priollet, Thierry Marsepoil, Benoît Lionnet, Jacques Tebib, Pascale Penn, Antoine Bouissou, Christian Roth, Olivier Martinet, Anna Schmitt, Nathalie Fruleux, Fouzia Radaoui, Jean-Marc Lessinger, Virginie Morando, Jean-Jacques Maillet, Christophe Fruchart, François Boué, François Goffinet, Franck Lellouche, Martin Demarchi, Alain Geissler, Jean-Charles Picaud, David Assouline, Patricia Brazille, Philippe Guimier, Marie-Françoise Dabysing, Bruno Delpeuch, Vanessa Tran, Guy Gengembre, Delphine Deligne, Dominique Vodovar, Yvan Touze, Sabrina Parent, Anne Decoster, Camille Dewitte, Emmanuel Weiss, Thierry Lambert, Thomas Guimard, Vincent Caille, Claude Guérin, Françoise Evreux, Geneviève Barjon, Basile Ondze, Damien Fournier, Olivia Bandin, Sophie Mignart, Henri Demontclos, Didier Perez, Jacques Croize, Nicole Desbois-Nogard, Guenièvre Imbert, Clarisse Dupin, Khalid Ridah, Marie-Christine Varin, Guillaume Arlet, Edith De Clareuil, Marie-Line Eustache, Patricia Le Pimpec, Louise Fortin, Eugène Ngami, Fabrice Mihout, Cecilia Esnault, Vincent Bouden, Véronique Annaix, Yves Poinsignon, Aurélien Lorchleac'h, Jean-Marc Degreff, Marie Garofano, Renaud Mesnage, Anne-Marie Roque-Afonso, Alain Chevailler, Stéphane Hominal, Thierry Charbonnier, Adrianna Bildea, Fabien Fily, Benjamin Davido, Emmanuel Rassiat, Assi Assi, Stéphanie Brunet, Hervé Jacquier, Catherine Claise, Annie Durand, Yannick Monceau, Pierre Blanc, Jean-Marie Sire, Yves Sucin, Jean-Pierre Zarski, Nathalie Bronet, Ingrid Lafon, Philippe Rey, Jacques Markarian, Eric Sennevile, Olivier Wink, Guilène Barnaud, Anne-Sophie Peultier, Sabine Taylor, Rim Savatier, Patrick Valayer, Claude Negrier, Selim Jennane, Edouard Begon, Laura Hyerle, Delphine Bridoux, Claire Daurel, Benoît Dalle, Mathilde Lescat, Philippe Stolidi, Elodie Perrodeau, Xavier Heches, Pierre Castelnau, Philippe Bray, Jean-Claude Texier, Serge Rossignol, Maud Brung-Lefebvre, Jean-François Subra, Jean-Marie Delarbre, Morgane Schneerson, Guyro Jang, Mona Mehri, Nathalie Landgraf, Pierre-Marie Girard, Armand Goll, Zaineb Bekguesmia, Christophe Clement, Michel Collet, Vincent Maze, Amine Benjelloul, Solène Durliat-Ellie, Vincent Letouzey, François Schmitt, Valérie Martinez, Sarah Watson, Abderrezak Bouasria, François Barbier, Raphael Lauretta, Mirana Razafimahery, Cristina Sirbu, Patrick Malherbe, Anne Wuillai, Ludovic Lesecq, Philippe Gaudard, Serge Houssaye, Jacques Monsegu, Gilles Rival, Chantal Chaplain, Jean-Didier Grangé, Oana Zamfiri, Florence Nguyen-Khac, Marc Portneuf, Jean-Michel Pawlotsky, Delphine Bonnet, Laurent Traissac, Sophie Hamon-Charles, Didier Dreyfuss, Louis Bernard, Laurence Detourmignies, Olivier Martineau, François Pettinelli, Marc Zandecki, Michel Dreyfus, Alain Chapelle, Sébastien Sabbat, Anne-Sophie Labussiere, Jean-Louis Gaillard, Chloé Plouzeau-Jayle, Patrick Zoveda, Véronique Leflon, Marie Levy, Aurélie Labé, Bruno Soulie, Raoul Jacques Bensaude, Hecham Moussa, Sylviane Catteu, Nathalie Biron, Loïc Masson, Georges Mourad, Nejla Aissa, Dragos Ciocan, Hubert De Boysson, Jean-Luc Bouyer, Patrick Yeni, Thierry-Pascal Zame, Caroline Thomas, François Cavalié, Laurence Koulmann, Christophe Rioux, Olivier Barraud, François Bricaire, Marguerite Le Poulain, Marie-Noelle Noulard, René Thomas, Guy Semet, Laurent Mosser, Olivier Marret, Brigitte Rivière, Vincent Jarlier, Jean-Philippe Coindre, Marc Villemain, Martin Pierre, Yacine Benkaci, Philippe Chiron, Hoang Vu-Thien, Jérôme Gournay, Andrea Labaune-Kiss, Brigitte Lauzanne, Fanny Lemercier, Souad Silhadi, Imad Kansau, Christophe Poncelet, Olivier Baldesi, Francis Thuet, Olivier Leroy, Aurore Lamberet, Camille Petit Hoang, Sophie Micheli, Ayman Abokasem, Hakima Nesrine, Pierre Lureau, Christian Chidiac, Vincent Piriou, Fabien Zoulim, Dieudonné Nicobaharaye, Anne Tixier, Isabelle Matheron, Soumeth Abasse, Victoria Cacheux, Serge Herson, Christine Fuhrmann, Olivier Proost, Bernard Bedock, Olivier Rogeaux, Mostapha Hajjar, Anne Reverseau, René Courcol, Françoise Carmagnol, Yves Guénard, Céline Ménard, Bouchra Lamia, Bruno Lemmens, Damien Bouhour, L. Lequen, Gaëlle Baty, Cédric Bouet, Dominique Guerrot, Stéphane Blanc, Catherine Chirouze, Anne-Hélène Reboux, A. Vachée, Gregory Taurin, Myriam Mein-Bottini, Jean-Pierre Belot, Alain Lafeuillade, Patricia Gabez-Therou, Philippe Labrousse, Bernard Jarrousse, Philippe Noto, Vincent Brunot, Philippe Condominas, Marion Challier, Béatrice Berçot, Delphine Anuset, Mélanie Daval Cote, François Bernasconi, Y. Costa, Chandrah Goburdhun, Bernard Gressier, Alban Michaud-herbst, Franck Charlier, Moussa Hecham, Luc Boulain, Hélène Corneloup, Alix Greder Belan, Nicolas Boussekey, Claire-Antoinette Dupuy, Yannick Rouquet, Benoit Renard, Benifla Jl, Etienne Javouhey, Michèle Granier, Marie-Christine Jaffarbandjee, Emilie Piet, Benoît Bergues, Claire Malbrunot, Catherine Tiry, Philippe Mérigot, Mouna Ben Soltana, Chantal Roure Sobas, Florian Radenac, Yves Thomas, Agathe Blaise, Sylvie De Martino, Laurence Legout, Gabriel Choukroun, Jean-François Muir, Peggy Dupretz, Patrick Dupont, François Guichart, Julie Jean, Jean-Michel Descamps, Bernard Kittschke, Anne Gruson, Gerard Viquesnel, Marie Keller, Pascal Chavanet, Françis Vallet, Yvan Vaschalde, Jean-Luc Hanouz, Gerard Lina, Françoise Loison, Simon Vincent, Jean-Paul Thellier, Moncef Afi, Dominique Zagozda, Hélène Sokeng-Affoule, Marc Le Bideau, Jean-François Loriferne, Alain Gravet, Sophie Deprecq, Tarik Naceur, Severine Mielczarek, René-Jean Bensadoun, Bernard Karkous, Yves Bléher, Jocelyne Poulain, Véronique Goulet, Laurence Nicolet, Sophie Arista, Antônio Lúcio Teixeira, Jean-François Schved, Laurent Nicolet, Claire Lecomte, Faiza Benddif-Fin, Michel Aumersier, Laurence Burc-Struxiano, Maxime Thouvenin, Samia Harbi, Mathieu Detave, Catherine Rebeyrotte, Jean-Paul Kisterman, Bruno Berdin, Pascal Vincent, Laurent Argaud, Elisabeth Parisi-Duchene, Geneviève Julienne, Fernanda Farto-Bensasson, Georges-Fabrice Blum, Sad Gaizi, Tali-Anne Szwebel, Raphaël Lepeule, Marie-Thérèse Climas, Anne-Françoise Dillies, Amar Boudhane, Umberto Simeoni, Pierre-François Dequin, Gérard Oliviero, Alain Gourlaouen, Caroline Piau, Marie-France Lutz-Murphy, Benoît Claude, Jean-Paul Aubry, Nadine Dubosc-Marchenay, Kamilla Chraibi, Emmanuelle Heusse, Sylvain Le Chevallier, Nathalie Brieu, Farid Sifaoui, Lorraine Letranchant, Hélène Durox, Jean-Pierre Lagasse, Adel Ghedira, Xavier Roubert, Fatma Magdoud, Hélène Jean-Pierre, Etienne Carbonelle, Olivier Dereeper, Lionel Carbillon, Christophe Billy, Mélanie Roblin, Marie-José Kodzin, Philippe Niel, Solène Makdessi, Matteo Vassallo, Maryse Archambaud, Fabian Haccourt, Didier Blaise, Stéphane Bourgeois, Elena Marcu, Charles Kubiak, Brisse Castel, François Guinet, Marie Pouzoullic, Frédérique Nathan-Bonnet, Vincent Gendrin, Céline Becherrawy, Aline Secher, Pierre Abgueguen, Clarence Eloy, Jean-Marc Tourani, Frédéric Klapczynski, Bernard Montmasson, Philippe Real, Joanna Pofelski, Yves Welker, Karim Krechiem, Eric Caumes, Martine Elena-Daumas, Christophe Saigne, Gilles Hittinger, Chantal Delesalle, Jonathan Messika, Fabrice Lesage, Daniela Pop, Daniel Coetmeur, Renato Colamarino, Chetaou Mahaza, Patrick Plésiat, Isabelle Fredenucci, Mylène Baret, Guy Mager, Pascale Chavel, Isabelle Labourdette, Anne-Claude Menguy, Nicolas Fortineau, Ludovic Le Sec, Valérie Gauduchon, Francis Barraud, Nicolas Letellier, Didier Vincent, Janine Frey, Philippe Riegel, Michel Pavic, Jean-Luc Fabre, Jean-Pierre Fauchart, Alain Goudeau, Stéphanie Husson-Wetzel, Philippe Eymerit, Mohamed Camara, Nathalie Seta, Elisabeth Carole Ngo Bell, Philippe Repellin, Laurent Alric, Vincent Leroy, Françoise Delisle Mizon, Jean-Philippe Emond, Marie-Françoise Borie, Lise Crémet, Wladimir Chelle, Elisabeth Brottier-Mancini, Bernard Garrigues, Claire Letellier, Loïc Geffray, Frédéric Méchaï, Julien Bador, Benoit Guery, Alain-Charles Fouilhoux, Corinne Dagada, Pierre Duhaut, Julien Goustille, Arnaud Sément, Francis Carcenac, Isabelle Girard-Buttaz, Claire Chapuzet, Fabienne Jouatte, Bruno Riou, Fabrice Hayoun, Chloé Di Meglio, Youssef Ali, Michel Leneveu, Nathalie Montagne, Yves Garcera, Audrey Moustache, Pierre-Eric Danin, Geneviève Le Lay, Dominique Courouge-Dorcier, Isabelle Worcel, Emmanuel Morelon, Vincent Pestre, Jean-Pierre Vilque, Jean-Christophe Paquet, Lucien Bodson, Anne-Marie Forest, Fabrice Pierre, Christian Pommier, Fabien Dutasta, Pierre Fournel, Stéphanie Courtois, Elodie Dubois, Serge Vanden Einjden, Patrick Honderlick, Pascal Richette, Fabienne Tamion, Véronique Chassy, Richard Megbemado, Anne-Marie Le Reste, Bernard Simian, Henri Osman, Anthony Texier, Badih Ayach, François Simon, Jean-Michel Filloux, Béatrice Dubourdieu, Jean-Claude Semet, Sarah Kubab, Tawfiq Henni, Patrick Dudeffant, Delphine Hequet, Olivier Mimoz, Marc Auburtin, Amélie Chabrol, Mickael Bonnan, Caroline Léonnet, Claire Wintenberger, Serge Ilunga, Patrice Lanba, Sophie Rosello, Alexandre Damage, Flore Bouche, Michel Thibault, Frederic Faibis, Chantal Dhennain, Jean-Philippe Talarmin, Armelle Lamour, Remi Boussier, Fabien Garnier, Marie-Laure Brival, Nourredine Hedjem, Philippe Vande-perre, Raphaël Coint, Jean-Claude Reveil, Eva Weinbronn, Emmanuelle Lavalard, Alexandra Fille, Françoise Le Turdu, Lionel Leroux, Jean-Yves Lefrant, Jean Berthet, Radia Bouaziz, Alain Ravaud, Sylvaine Rousseau, Yacine Merrouche, Alain Le Coustumier, Bertrand Guider, Gisèle Dewulf, Jean-Marc Faucheux, Jacques Piquet, Franck Leibinger, Charles Cerf, Robin Stephan, Jean-Philippe Redonnet, Jean-Paul Stahl, Ella Dzeing, Simona Pavel, Guy Vernet, Ghada Hatem, Samer Kayal, Jacques Deschamps, Dominique Descamps, Marion Levast, Marc Bouiller, Sylvie Dargere, Claire Dingremont, Stéphane Gaudry, François Maillot, Sylvie Odent, Nathalie Cervantes, Hélène Zanaldi, Laurence Gachassin, Olivier Ruyer, David Patin, Benoît Cazenave, Pascal Jacquier, Michelle Boyer, Béatrice Berteaux, Virginie Zarrouk, Jacques Bor, Isabelle Legoff, Hélène Albinet, Florence Rousseau, Gilles Pialoux, Guenaelle Salaun-Beretta, Alexandra Moura, Véronique Vernet Garnier, Didier Lepelletier, Pierre-Alexandre Hauss, Joëlle Belaisch-Amart, Didier Lepeletier, Jacob Xavier, Aline Nare, Annie Motard-Picheloup, Alain Améri, Bertrand Lioger, Jean-Valère Malfuson, 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), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Département de Médecine interne [Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Biologie des Infections - Biology of Infection, Service de Gynécologie et Obstétrique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources (ICAReB), Institut Pasteur [Paris] (IP), Infectious Disease Department [Saint Maurice], Agence Nationale de la Santé Publique [Saint-Maurice] (ANSP), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, MONALISA study group, Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency., ROZIER, marie-Claire, CHU Necker - Enfants Malades [AP-HP], Centre National de Référence Listeria - Biologie des Infections (CNRL), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), CHU Pitié-Salpêtrière [APHP], Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre National de Référence Listeria - Biologie des Infections ( CNRL ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre collaborateur de l'OMS (CCOMS) des Listeria ( CCOMS ), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité ( CRESS (U1153 / UMR_A 1125) ), Institut National de la Recherche Agronomique ( INRA ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie ( UPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Lariboisière, Biologie des Infections, Institut Pasteur [Paris]-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Investigation Clinique et d’Accès aux Ressources Biologiques (Plate-forme) - Clinical Investigation and Access to BioResources ( ICAReB ), Agence Nationale de la Santé Publique [Saint-Maurice] ( ANSP ), Assistance Publique - Hôpitaux de Paris, Assistance publique - Hôpitaux de Paris (AP-HP), Université Paris Descartes - Paris 5 ( UPD5 ), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)

Subjects
Bacteremia/epidemiology/mortality, 0301 basic medicine, Male, Pediatrics, bacteraemia, Infectious Disease Transmission, [SDV]Life Sciences [q-bio], Bacteremia, France/epidemiology, Infant, Newborn, Diseases, Foodborne Diseases, Meningoencephalitis, Pregnancy, Risk Factors, Vertical, Medicine, Listeriosis, Prospective Studies, Pregnancy Complications, Infectious, Prospective cohort study, ddc:618, diabetes, alcoholism, Hazard ratio, Foodborne Diseases/microbiology, immuno suppressive therapies, Prognosis, 3. Good health, [SDV] Life Sciences [q-bio], Hospitalization, Infectious Diseases, isolates, Population Surveillance, Female, France, Listeria monocytogenes/classification/isolation & purification, Cohort study, Adult, medicine.medical_specialty, 030106 microbiology, Notifiable disease, Listeriosis/diagnosis/epidemiology/microbiology, Context (language use), macromolecular substances, 03 medical and health sciences, Humans, study, Aged, [ SDV ] Life Sciences [q-bio], business.industry, Public health, cirrhosis, Infant, Newborn, Infant, Diseases/epidemiology/microbiology, HIV, Mandatory Reporting, Newborn, medicine.disease, Listeria monocytogenes, infection, Infectious Disease Transmission, Vertical, Pregnancy Complications, Infectious/epidemiology/microbiology, Meningoencephalitis/epidemiology/microbiology/mortality, Observational study, business, prognostic, mellitus
Abstract

International audience; Evidence before this study We searched PubMed on June 30, 2016, for English-language cohort studies published since Jan 1, 1980, of patients with invasive listeriosis worldwide with the keywords " listeria " , " listeriosis " , " maternal " , and " neurolisteriosis ". Studies had to include epidemiological or clinical data on listeriosis. All clinical forms of infection were included (bacteraemia, neurolisteriosis, and maternal–neonatal infection). Host risk factors for listeriosis have been well identified, but the clinical features and prognostic factors of the disease are based on retrospective studies compiling heterogeneous data or random collected cases. Furthermore, no clinical trial has ever been done and medical management is not evidence based. Added value of the study Our study is the first prospective clinical study focusing on all forms of invasive listeriosis. The study is based on a national mandatory system that allowed the nearly complete capture of microbiologically proven cases. The study shows a higher burden of listeriosis than reported before: more than 80% of infected mothers experienced major fetal or neonatal complications (fetal loss, very high prematurity, early or late onset disease); only 39% of patients with neurolisteriosis survived and fully recovered. The study provides important new data to improve management and predict outcome in listeriosis, such as determination of the time window for fetal losses (

Published
2016
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24. Discontinuation of empirical antibiotic therapy in neutropenic acute myeloid leukaemia patients with fever of unknown origin: is it ethical?

Author

Bertrand Gachot, David Ghez, Claude Chahine, Florence Netzer, S. de Botton, Paul-Louis Woerther, Elisabeth Chachaty, François Blot, M. Merad, C. Dufour, and Jean-Baptiste Micol

Subjects
Adult, Male, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, Antibiotics, Neutropenia, Acute myeloid leukaemia, Empirical antibiotic therapy, Antibiotic resistance, Internal medicine, hemic and lymphatic diseases, medicine, Humans, neutropenia, Fever of unknown origin, Intensive care medicine, Aged, Septic shock, business.industry, General Medicine, Middle Aged, bacterial resistance, medicine.disease, Anti-Bacterial Agents, Discontinuation, Leukemia, Myeloid, Acute, Treatment Outcome, Infectious Diseases, Withholding Treatment, fever of unknown origin, Female, antibiotic discontinuation, Myeloid leukaemia, business
Abstract

Based on recommendations of the ECIL-4, we prospectively evaluated discontinuation of empirical antibiotic therapy in high-risk neutropenic acute myeloid leukaemia patients with fever of unknown origin. Seven patients (median neutropenia duration 30 days) were included. Four of them remained afebrile but quickly recovered from neutropenia. The other three had rapid recurrent fever. Two of these three patients had bacteraemia with susceptible strains and one of them was transferred to the ICU for septic shock. Median duration of sparing of antibiotics for the seven patients was 3 days (2–4). Because of these limited results the study was stopped.

Published
2014
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25. Clonal Population of Flucytosine-Resistant Candida tropicalis from Blood Cultures, Paris, France

Author

Stéphane Bretagne, Elisabeth Chachaty, Vincent Robert, Elisabeth Forget, Marie Desnos-Ollivier, Dorothée Raoux, Claire Lacroix, Françoise Dromer, and Claire Bernède

Subjects
Microbiology (medical), URA3, Antifungal Agents, Time Factors, Genotype, Epidemiology, flucytosine, Clone (cell biology), Drug Resistance, lcsh:Medicine, multilocus sequence typing, Drug resistance, Microbiology, Flucytosine, lcsh:Infectious and parasitic diseases, Candida tropicalis, Drug Resistance, Fungal, Risk Factors, medicine, Polymorphic Microsatellite Marker, Humans, lcsh:RC109-216, Fungemia, biology, Research, molecular typing, candidemia, lcsh:R, Candidiasis, antifungal drug resistance, biology.organism_classification, medicine.disease, Infectious Diseases, Fungal, Phenotype, Multilocus sequence typing, France, polymorphic microsatellite markers, medicine.drug, Microsatellite Repeats
Abstract

Such isolates are widespread around clinical centers and are associated with malignancies that cause fewer deaths than other C. tropicalis isolates., Candida tropicalis is a diploid ascomycetes yeast responsible for 4%–24% of candidemia. Resistance to flucytosine is rarely described for this species but was observed for 45 (35%) of 130 C. tropicalis isolates recovered from blood cultures in the Paris area in a 4-year survey. The aims of this study were to test the hypothesis that the flucytosine-resistant isolates could represent a subgroup and to determine the relationship between epidemiologic and genomic data. Epidemiologic data and gene sequences were analyzed, and molecular typing was performed. Our results suggest that a clone of flucytosine-resistant isolates, associated with malignancies and a lower mortality than that for other C. tropicalis isolates, is widespread in the Paris area. We propose the analysis of 2 polymorphic microsatellite markers coupled with URA3 sequencing to track the clone.

Published
2008

26. DAV132, an Adsorbent-Based Product, Protects the Gut Microbiome and Prevents Clostridium difficile Infections During Moxifloxacin Treatments

Author

Jean De Gunzburg, Amine Ghozlane, Annie Ducher, Xavier Duval, Etienne Ruppé, Mark Pulse, Caroline Chilton, Laurence Armand-Lefevre, Elisabeth Chachaty, Sakina Sayah-Jeanne, Joël Doré, Emmanuelle Le Chatelier, Florence Levenez, Sean Kennedy, Nicolas Pons, William Weiss, Mark Wilcox, France Mentré, Antoine Andremont, Stanislav Dusko Ehrlich, Da Volterra [Paris, France], MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), AP-HP - Hôpital Bichat - Claude Bernard [Paris], 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), University of Leeds, 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, Institut Gustave Roussy (IGR), Département de soins aigus [Gustave Roussy] (DSA), Leeds Teaching Hospitals NHS Trust, Infectious Diseases Society of America, hiv medicine association, Kennedy, Sean, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord

Subjects
2. Zero hunger, medicine.medical_specialty, business.industry, Medical school, clostridium difficile infections, Claude bernard, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Clostridium difficile infections, Gut microbiome, 3. Good health, Surgery, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Oncology, Health science, medicine, intestinal bacteria, moxifloxacin, business, Humanities, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology
Abstract

International audience; Background. During antibiotic treatments, antibiotics reach the colon and alter the microbiome, resulting in emergence and dissemination of resistant bacteria, antibiotic-associated diarrhea (AAD) and occurrence of Clostridium difficile (Cd) infections (CDI). We developed an oral adsorbent-based product, DAV132, to be co-administered with antibiotics in order to prevent these effects. We report here the results of protection of the microbiome in human volunteers treated with oral moxifloxacin (MOX), and protection against CDI in vitro in a human gut model (HGM) and in vivo in experimental hamsters.Methods. Four groups (MOX [400 mg OD for 5 days], MOX + DAV132 [7.5 g TID for 7 days], DAV132, or control) of healthy volunteers (n = 44) were included in a randomized clinical trial. Feces were collected at screening, daily from D1 to D9 and at D12, D16, D23, D30, D37 and plasma PK assayed at D1and5. Metagenomic analyses were done by shotgun sequencing at screening, D3, D6, D9, D16 and D37. The effect of DAV132 on MOX was also assessed in a HGM inoculated with Cd spores (ribotype 027, MOX MIC 32 mg/L); bacterial counts, toxin production and MOX concentrations were measured over time. MOX dosed hamsters were inoculated with 104 spores of a non-epidemic Cd (TcdA + , TcdB + , cdtB−) and treated ±DAV132. Mortality and Cd counts were assessed over time.Results. In humans, DAV132 was well tolerated and decreased free fecal MOX by > 99% compared to MOX alone: ratio of mean LogAUCD1-D16 = 0.0093 (95% CI 0.0061-0.0144), p = 0.03 × 10−16; MOX plasma PK was not changed significantly. Alterations of the fecal microbiome observed with MOX were prevented. In the HGM, DAV protected the microbiota and prevented Cd overgrowth and toxin production. Hamsters were fully protected by DAV against MOX-induced CDI (dose dependent), with decreased free fecal MOX and Cd counts.Conclusion. DAV132 protects humans against fecal microbiome disruption after oral MOX treatment, without altering its plasma PK. In vitro results in HGM and in vivo results in hamsters suggest that DAV132 should be protective against antibiotic-induced CDI. These results warrant further clinical development of DAV132 to protect the intestinal microbiota, and so prevent AAD and CDI, in patients receiving oral or parenteral antibiotics.

Published
2015
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27. Enterococcus hirae and Barnesiella intestinihominis Facilitate Cyclophosphamide-Induced Therapeutic Immunomodulatory Effects

Author

Vichnou Poirier-Colame, Silvia C. Formenti, Alexander M. M. Eggermont, Christophe Isnard, Elisabeth Chachaty, Didier Raoult, Maria Paula Roberti, Harry Sokol, Patricia Lepage, Encouse B. Golden, David Enot, Ivo G. Boneca, Guido Kroemer, Laurence Zitvogel, Nicolas Jacquelot, Mutsa Tatenda Madondo, Mathias Chamaillard, Jean-Charles Soria, Caroline Flament, Philip Rosenstiel, Marie Vétizou, Takahiro Yamazaki, Romain Daillère, Antoine Roux, Sylvie Rusakiewicz, Sonia Becharef, Vincent Cattoir, Nadine Waldschmitt, Bertrand Routy, Paul Louis Woerther, Magdalena Plebanski, Eric Tartour, Lionel Apetoh, Philippe Langella, Connie P.M. Duong, Ludger Johannes, Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 Recherche Risques Microbiens (U2RM), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Département d'oncologie médicale [Centre Georges-François Leclerc], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Plateforme de métabolomique, Direction de la recherche [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Apoptose, cancer et immunité (U848), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biologie [CHU HEGP], 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 Gustave Roussy (IGR), Université Paris Descartes - Paris 5 (UPD5), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S 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)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chimie biologique des membranes et ciblage thérapeutique (CBMCT - UMR 3666 / U1143), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Microbiologie, Département de biologie et pathologie médicales [Gustave Roussy], Université Paris-Saclay, Department Radiation Oncology (Weill Cornell Medicine), Weill Medical College of Cornell University [New York], Monash University [Clayton], Unabhängiges Landeszentrum für Datenschutz Schleswig-Holstein [Kiel, Germany] (ULD), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), 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, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall (BGPB), Institut Pasteur [Paris] (IP), La Ligue contre le cancer, Ligue Nationale contre le Cancer (Equipes labellisees), European Research Council Advanced Investigator Grant, Fondation pour la Recherche Medicale (FRM), Institut National du Cancer (INCa), Fondation de France, LabEx Immuno-Oncology, SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), SIRIC, Paris Alliance of Cancer Research Institutes (PACRI), ISREC, Swiss Bridge Foundation, NIH [R01 CA161879], FRM [DEQ20130326475], INCa [Plbio-2012-106], Agence Nationale de la Recherche [ANR- 13-BSV3-0014-01], Association pour la Recherche contre le cancer [PGA120140200851], Ministere de l'enseignement superieur et de la recherche, Institut de veille sanitaire (InVS), Interreg IVA France (Manche) - Angleterre (Risk Manche), Anti-Cancer Fund, Monash PhD Scholarship, NHMRC SRF Award, DFG CE Inflammation at Interfaces, European Union's FP7 [305564, SFB1182 TP C2], Service de Gastroentérologie et nutrition [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), 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), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), 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 National de la Recherche Scientifique (CNRS), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie-Université Paris Descartes - Paris 5 (UPD5), Institut Hospitalier Universitaire Méditerranée Infection (IHU AMU), Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 ( CIIL ), Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -IFR142-Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Unité de Recherche Risques Microbiens ( U2RM ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Centre d'Investigation Clinique en Biotherapie des cancers ( CIC 1428 , CBT 507 ), Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), MICrobiologie de l'ALImentation au Service de la Santé humaine ( MICALIS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Apoptose, cancer et immunité ( U848 ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Institut Gustave Roussy ( IGR ), Université Paris Descartes - Paris 5 ( UPD5 ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Chimie biologique des membranes et ciblage thérapeutique ( CBMCT - UMR 3666 / U1143 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Unabhängiges Landeszentrum für Datenschutz Schleswig-Holstein [Kiel, Germany] ( ULD ), Institut Hospitalier Universitaire Méditerranée Infection ( IHU AMU ), 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 ), and Biologie et Génétique de la Paroi bactérienne

Subjects
0301 basic medicine, Richness, Nod2 Signaling Adaptor Protein, medicine.disease_cause, Mice, 0302 clinical medicine, Enterococcus hirae, NOD2, Neoplasms, Intestine, Small, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Gut Microbiota, Cancer, biology, 3. Good health, Immunosurveillance, Infectious Diseases, 030220 oncology & carcinogenesis, Barnesiella intestinihominis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Immunotherapy, medicine.symptom, Infection, medicine.drug, Cyclophosphamide, Colon, Immunology, Translocation, Inflammation, 03 medical and health sciences, Interferon-gamma, Immune system, Monitoring, Immunologic, medicine, Animals, Immunologic Factors, Antitumor Immunity, Bacteria, Dendritic Cells, Th1 Cells, medicine.disease, biology.organism_classification, Mice, Inbred C57BL, 030104 developmental biology, Intestinal Microbiota, Ovarian cancer, Immunologic Memory
Abstract

International audience; The efficacy of the anti-cancer immunomodulatory agent cyclophosphamide (CTX) relies on intestinal bacteria. How and which relevant bacterial species are involved in tumor immunosurveillance, and their mechanism of action are unclear. Here, we identified two bacterial species, Enterococcus hirae and Barnesiella intestinihominis that are involved during CTX therapy. Whereas E. hirae translocated from the small intestine to secondary lymphoid organs and increased the intratumoral CD8/ Treg ratio, B. intestinihominis accumulated in the colon and promoted the infiltration of IFN-gamma-producing gamma delta Tau cells in cancer lesions. The immune sensor, NOD2, limited CTX-induced cancer immunosurveillance and the bioactivity of these microbes. Finally, E. hirae and B. intestinihominis specific-memory Th1 cell immune responses selectively predicted longer progression-free survival in advanced lung and ovarian cancer patients treated with chemo-immunotherapy. Altogether, E. hirae and B. intestinihominis represent valuable ''oncomicrobiotics'' ameliorating the efficacy of the most common alkylating immunomodulatory compound.

Published
2015
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28. Monitoring antibiotic-resistant enterobacteria faecal levels is helpful in predicting antibiotic susceptibility of bacteraemia isolates in patients with haematological malignancies

Author

Paul-Louis Woerther, Cécile Angebault, Elisabeth Chachaty, Jean-Baptiste Micol, Sylvain Pilorge, Bertrand Gachot, Florence Pasquier, Jean-Henri Bourhis, and Stéphane de Botton

Subjects
Microbiology (medical), Adult, Male, medicine.medical_specialty, Neutropenia, Adolescent, medicine.drug_class, Antibiotics, Bacteremia, Drug resistance, Microbial Sensitivity Tests, Microbiology, beta-Lactam Resistance, beta-Lactamases, Feces, Young Adult, Antibiotic resistance, Enterobacteriaceae, Internal medicine, Positive predicative value, Drug Resistance, Bacterial, Medicine, Humans, Aged, Retrospective Studies, business.industry, Enterobacteriaceae Infections, Retrospective cohort study, General Medicine, Middle Aged, bacterial infections and mycoses, medicine.disease, Antimicrobial, Surgery, Anti-Bacterial Agents, Carriage, Carbapenems, Hematologic Neoplasms, Female, business
Abstract

Delay of active antimicrobial therapy in haematological patients with Gram-negative bacilli bacteraemia during profound neutropenia exposes them to increased morbidity and mortality. The digestive tract is the main source of enterobacteria causing bacteraemia in these patients. We thus evaluated the usefulness of broad-spectrum beta-lactam resistant enterobacteria (BSBL-RE) faecal shedding assessment in forecasting the susceptibility to BSBLs of the strains isolated from blood cultures. From 2002 to 2011, neutropenic haematological patients with bacteraemia caused by enterobacteria who had a stool culture during the previous 7 days were retrospectively included. BSBL-RE intestinal carriers were compared with non-carriers in terms of clinical and microbiological criteria. One hundred and four patients were included and 16 of them (15.4 %) were BSBL-RE carriers. Multivariate analysis showed that BSBL-RE carriage was independently associated with BSBL-RE identified in blood cultures (P

Published
2015

29. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota

Author

Elisabeth Chachaty, Alexander M.M. Eggermont, Vichnou Poirier-Colame, Jérôme Nigou, Antoine Roux, Gérard Eberl, Caroline Robert, Nicolas Jacquelot, Caroline Flament, Laurence Zitvogel, Franck Carbonnel, Silvia C. Formenti, Guido Kroemer, Didier Raoult, Paul Louis Woerther, Nadine Waldschmitt, David Enot, Marie Vétizou, Jonathan M. Pitt, Sonia Becharef, Romain Daillère, Christina Mateus, Sascha Cording, Paule Opolon, Sridhar Mani, Connie P.M. Duong, Nathalie Chaput, Bertrand Routy, Takahiro Yamazaki, Patricia Lepage, Ivo G. Boneca, Marion Bérard, Mathias Chamaillard, Florent Ginhoux, Sylvie Rusakiewicz, Maria Paula Roberti, Andreas Schlitzer, Encouse B. Golden, Université Paris-Sud - Paris 11 (UP11), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, 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), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sorbonne Paris Cité (USPC), New York University [New York] (NYU), NYU System (NYU), Microenvironnement et Immunité - Microenvironment and Immunity, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Albert Einstein College of Medicine [New York], Animalerie centrale (Plate-forme), Institut Pasteur [Paris] (IP), Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Pôle de biologie, 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), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Université de la Méditerranée - Aix-Marseille 2, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Hôpital Bicêtre, La Ligue contre le cancer, ARC, Ligue Nationale contre le Cancer (Equipes labelisees), Agence Nationale pour la Recherche (ANR AUTOPH), Agence Nationale pour la Recherche (ANR, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), ProdInra, Migration, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Adoptive cell transfer, Skin Neoplasms, medicine.medical_treatment, T-Lymphocytes, [SDV]Life Sciences [q-bio], B7-H1 Antigen, Mice, Cancer immunotherapy, Bacteroides, Innate, CTLA-4 Antigen, Melanoma, Cancer, Aged, 80 and over, Multidisciplinary, Host, Antibodies, Monoclonal, hemic and immune systems, Fecal Microbiota Transplantation, Middle Aged, 3. Good health, Anti-Bacterial Agents, [SDV] Life Sciences [q-bio], Intestines, medicine.anatomical_structure, Female, Immunotherapy, Adult, T cell, T-Cells, chemical and pharmacologic phenomena, Biology, Article, Polysaccharides, medicine, Germ-Free Life, Animals, Humans, Antibody, Aged, Molecule, medicine.disease, Ipilimumab, Blockade, Gastrointestinal Microbiome, Transplantation, Mice, Inbred C57BL, CTLA-4, Immunology, Dysbiosis, Bifidobacterium, Immunologic Memory, Model
Abstract

International audience; Antibodies targeting CTLA-4 have been successfully used as cancer immunotherapy. We find that the antitumor effects of CTLA-4 blockade depend on distinct Bacteroides species. In mice and patients, Tcell responses specific for B. thetaiotaomicron or B. fragilis were associated with the efficacy of CTLA-4 blockade. Tumors in antibiotic-treated or germ-free mice did not respond to CTLA blockade. This defect was overcome by gavage with B. fragilis, by immunization with B. fragilis polysaccharides, or by adoptive transfer of B. fragilis-specific T cells. Fecal microbial transplantation from humans to mice confirmed that treatment of melanoma patients with antibodies against CTLA-4 favored the outgrowth of B. fragilis with anticancer properties. This study reveals a key role for Bacteroidales in the immunostimulatory effects of CTLA-4 blockade.

Published
2015
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30. Single-step polymerase chain reaction for combined gene detection and epidemiological typing in three bacterial models

Author

Elisabeth Chachaty, Farida Hilali, Antoine Andremont, and Patrick Saulnier

Subjects
Staphylococcus aureus, Bacterial Toxins, Clostridium difficile toxin A, Biology, medicine.disease_cause, Polymerase Chain Reaction, Microbiology, law.invention, Enterotoxins, law, Genotype, Escherichia coli, Genetics, medicine, Typing, Molecular Biology, Polymerase chain reaction, Southern blot, Superantigens, Clostridioides difficile, Cytotoxins, Escherichia coli Proteins, Toxic shock syndrome toxin, Molecular biology, Bacterial Typing Techniques, Random Amplified Polymorphic DNA Technique, RAPD, Genes, Bacterial
Abstract

We describe a new polymerase chain reaction (PCR) for combined gene detection and epidemiological typing (COGEDET), which allows bacterial typing and gene detection in a one-step assay. This assay, in which target gene-specific primers are used under low-stringency annealing conditions, was evaluated on 32 Staphylococcus aureus strains using toxic shock syndrome toxin 1 (tst) primers, 30 Clostridium difficile strains using toxin A (toxA) primers, and 30 Escherichia coli strains using cytotoxic necrotizing factor (cnf) primers. Typing performances with COGEDET were compared to those of conventional random amplification polymorphic DNA (RAPD), and gene detection performances, to those of conventional PCR followed by Southern blot hybridization. Concordances between conventional PCR/Southern blot and COGEDET were 96.9, 100 and 96.7% for the detection of the tst, toxA and cnf genes, respectively. Discriminatory indexes for the conventional RAPD and COGEDET techniques were similar in the three bacterial species tested. These results show that the COGEDET assay can replace two separate assays for typing and genes detection respectively, thus saving both technicians' time and reagents.

Published
2006
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31. Durée de péremption des solutions de morphine et de la péthidine présentées dans des dispositifs pour analgésie autocontrôlée : étude de stabilité physicochimique et microbiologique

Author

Elisabeth Chachaty, Lionel Mercier, Angelo Paci, Philippe Bourget, and Isabelle Laville

Subjects
Preservative, business.industry, Analgesic, General Medicine, Shelf life, High-performance liquid chromatography, Pethidine, chemistry.chemical_compound, Solvent evaporation, chemistry, Anesthesia, Morphine, Medicine, business, medicine.drug, Pseudomorphine
Abstract

Morphine and meperidine in Patient-Controlled Analgesic devices are commonly used to treat chronic pain patients. These devices deliver a programmed amount of drug and allow self-administration by the patient depending on the pain. In our department of pharmacy, 300 devices were manufactured in 2003. The aim of this study was to assess their shelf-life. The devices were filled aseptically and without preservatives with 1 and 40 mg/ml morphine solution and 5 and 20 mg/ml meperidine and stored over 30 days at room temperature and protected from light. Culture assay of the solutions showed that they remained sterile for 30 days. No turbidity of any solutions from samples collected twice a week was noticed. pH and osmolarity remained constant. Drug concentrations were determined using stability indicating HPLC method, as we showed that degradation products can be separated from the drugs. Little loss of meperidine occurred within 21 days (

Published
2005
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32. Intérêt de l’amplification génique à l’aide d’amorces universelles dans le diagnostic des infections fongiques chez le patient immunodéprimé

Author

Bertrand Gachot, Elisabeth Chachaty, Sami Antoun, M. Merad, Olivier Adam, O. Casiraghi, and Jean-Henri Bourhis

Subjects
General Medicine, Biology, Molecular biology
Abstract

Resume Le diagnostic microbiologique des infections fongiques profondes est rendu difficile par la faible sensibilite des techniques d’isolement en culture des champignons a partir des tissus infectes. Nous avons evalue l’interet diagnostique de l’amplification genique de portions de la region contenant les genes codant pour l’ARN ribosomal suivi du sequencage de l’ADN amplifie pour detecter et identifier les champignons a partir de biopsies tissulaires. Cette technique nous a permis d’identifier l’agent responsable d’une infection fongique profonde chez trois malades. Dans deux cas, ils s’agissaient de patients suspects de candidose hepatosplenique et pour lesquels la presence de Candida albicans a ete detectee a partir de biopsies hepatiques. Le troisieme cas est celui d’une patiente prise en charge pour un thymome et presentant une osteite du manubrium a Scedosporium apiospermum .

Published
2004
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33. Épidémiologie et résistance aux antibiotiques de Streptococcus pneumoniae en Île de France en 2001

Author

N Lucet, F. Faibis, C Dupeyron, C Gallet, D Mathieu, C Chaplain, Elisabeth Chachaty, A. Fremaux, G Otterbein, C. Benoit, J C Decotte, J Pollet, F Le Manach, A Mangeol, A. Artigou, B. Hacquard, D. Demontrond, E Cambau, M.C. Demachy, F Cousinard, B Ferre, C Malbrunot, A Dublanchet, T. Rabenja, M Hornstein, A Farges, P Legrand, C Spicq, I Poilane, P Cormier, A Cecille, P. Guiet, F. Pateyron, and M.J. Galanti

Subjects
Gynecology, medicine.medical_specialty, Infectious Diseases, Ile de france, business.industry, β lactams, medicine, Benzylpénicilline, business, Antibacterial agent
Abstract

Resume Objectif. – Evaluer le niveau de resistance aux antibiotiques du pneumocoque en Ile de France. Methode. – En 2001, 637 souches cliniques de pneumocoque ont ete etudiees a partir de 32 laboratoires de microbiologie. Resultats. – Cinquante et un pour cent des souches ont ete isolees chez les enfants de moins de 15 ans et 49 % chez les adultes. Chez l'enfant 76 % des souches provenaient de pus d'oreille, 20 % d'hemocultures ; chez l'adulte la plupart des souches (92 %) provenaient d'hemocultures. Le pourcentage de pneumocoque de sensibilite diminuee a la penicilline G est globalement de 61 %, plus eleve chez l'enfant (73 %) que chez l'adulte (50 %). Parmi les souches de moindre sensibilite, 21,8 % sont resistantes a la penicilline (CMI > 1 mg/l). La sensibilite diminuee a l'amoxicilline et au cefotaxime concerne respectivement 38 et 17 % des souches. Les souches resistantes a ces deux molecules (CMI > 2 mg/l) sont rares 2,6 et 0,4 % respectivement. Parmi les autres antibiotiques, les taux de resistance sont de 63 % pour l'erythromycine, 47 % pour le cotrimoxazole, 40 % pour les tetracyclines et 23 % pour le chloramphenicol. Les serogroupes les plus frequents sont les serogroupes 19 et 14, respectivement 23 et 18 %. Les serotypes contenus dans le vaccin heptavalent couvrent 90 % des souches isolees chez l'enfant de moins de deux ans. Conclusion. – Les taux de resistance a la penicilline sont plus particulierement eleves dans les pus d'oreille chez l'enfant (76 %).

Published
2004
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34. Treatment with Piperacillin‐Tazobactam and False‐PositiveAspergillusGalactomannan Antigen Test Results for Patients with Hematological Malignancies

Author

Jean-Henri Bourhis, Fanny Wilquin, Elisabeth Chachaty, Anne Auperin, Bertrand Gachot, and Olivier Adam

Subjects
Microbiology (medical), medicine.medical_specialty, Hematology, business.industry, Aspergillus Galactomannan Antigen Test, Aspergillosis, medicine.disease, Tazobactam, Gastroenterology, Galactomannan, chemistry.chemical_compound, Infectious Diseases, chemistry, Internal medicine, Piperacillin/tazobactam, Immunology, polycyclic compounds, Medicine, business, Antibacterial agent, medicine.drug, Piperacillin
Abstract

We report the occurrence of a high rate of false-positive test results during the surveillance of hematology patients for galactomannan (GM) antigenemia. Among 218 patients surveyed from June 2002 through June 2003, 42 (19.3%) had > or =1 serum sample positive for GM (optical density index, >1.5). Of these patients, 38 had no additional evidence of invasive aspergillosis, and, therefore, their test results were considered to be false-positives. Case-control analysis showed that treatment with piperacillin-tazobactam was the only risk factor significantly associated with receiving false-positive test results. When tested for GM antigen, 3 of 4 piperacillin-tazobactam batches had positive results. Physicians should be aware of the possible interference of treatment with piperacillin-tazobactam when interpreting the results of the GM assay.

Published
2004
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35. [Modalities of management of cancer patients with febrile neutropenia in the oncology emergency unit of Gustave-Roussy and their related costs]

Author

Isabelle, Borget, Sami, Antoun, Elisabeth, Chachaty, Bertrand, Gachot, Arif, Alibay, Mario, Di Palma, and Mansouria, Merad

Subjects
Adult, Male, Ceftriaxone, Antineoplastic Agents, Cancer Care Facilities, Middle Aged, Amoxicillin-Potassium Clavulanate Combination, Risk Assessment, Anti-Bacterial Agents, Hospitalization, Young Adult, Ciprofloxacin, Neoplasms, Ambulatory Care, Humans, Female, France, Prospective Studies, Emergency Service, Hospital, Aged, Febrile Neutropenia
Abstract

Febrile neutropenia (FN) is a severe chemotherapy side effect. Hospitalization is recommended for FN episode of high-risk (HR) of complications. Management of FN at lower risk of complications remains unclear.This is a prospective observation study in patients with solid tumors admitted to the emergency department FN. Collected data included demographics, clinical, biological, therapeutic costs, MASCC score and complications.Hundred and thirty-seven consecutive FN were recorded in 128 patients. Twenty-six FN (19%) were managed at home (all of them had a MASCC score ≥ 21); 111 (81%) were treated at hospital of which 37 NF were at HR of complications based on clinical and biological parameters (all of them had a MASCC score21) and for 74 of them the admission could be discussed (MASCC20 or ≥ 20). This group of patients was considerate with intermediate risk (IR). All IR patients were treated with the same antibiotics than outpatients, i.e. ceftriaxone in 36 cases (49%) or amoxicillin/clavulanic acid and ciprofloxacin in 38 cases (51%). For these 74 cases, any severe complication was recorded. Antibiotics were adapted for only 12% of these patients according to bacteriology results.This study showed the limits of the MASCC score. We did not observe any severe complications in patients admitted to the hospital according to clinical and biological parameters and with the high risk score MASCC. This study had some methodological bias but it allowed us to estimate the cost of the different ways of management and the difficulties to decide the hospitalization in FN.

Published
2014

36. Mechanisms and risk factors for infection of pulmonary artery catheters and introducer sheaths in cancer patients admitted toan intensive care unit

Author

Gérard Nitenberg, Elisabeth Chachaty, Bruno Raynard, François Blot, Sami Antoun, and J.L. Bourgain

Subjects
Male, Microbiology (medical), medicine.medical_specialty, Percutaneous, endocrine system diseases, medicine.medical_treatment, education, Bacteremia, law.invention, Catheters, Indwelling, Risk Factors, law, Neoplasms, health services administration, medicine.artery, medicine, Humans, Prospective Studies, Internal jugular vein, business.industry, Pulmonary artery catheter, food and beverages, General Medicine, Middle Aged, medicine.disease, Intensive care unit, humanities, Surgery, Intensive Care Units, Catheter, Infectious Diseases, Catheterization, Swan-Ganz, Pulmonary artery, Wound Infection, Introducer sheath, Female, business
Abstract

Pulmonary artery catheters (PACs) are typically inserted for short periods, and the extra-luminal route is assumed to be the overriding source of contamination and/or infection. Our aim was to assess the incidence of PAC and introducer colonization in cancer patients, and to study the mechanisms and risk factors for infection. Patients with a Swan-Ganz catheter admitted to an intensive care unit were prospectively analyzed over 14 months. As soon they were no longer necessary, PACs and introducer sheaths were removed and cultured. We recorded the mean duration of placement, the number of times PACs were handled and the site of insertion. Seventy-nine catheters were inserted in 68 patients. The median (range) duration was three days (0-10) for PACs, and 3.6 days (0-18) for introducers. PAC and/or percutaneous introducer sheath colonization was diagnosed in seven patients (8.9%), but in only one case were both colonized. Colonization rates were 15.5 per 1000 days for PACs and 14.1 per 1000 days for introducers. Introducers were mainly colonized before the 5th day, while PACs were mainly colonized after the 5th day. No PAC or introducer-related local infection or bacteraemia was diagnosed. Colonization was more frequent on catheters inserted into the internal jugular vein. The colonization rate was 5% for PACs and introducers. Our findings suggest that contamination of introducers and PACs may be dissociated and could result from either extraluminal or endoluminal colonization. As three of four PAC colonizations occurred after 5 days, the duration of catheter placement should be considered important. There was little clinical impact of microbial colonization.

Published
2001
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37. Infections à Bacillus et immunodépression, à propos de deux cas

Author

Jean-Ralph Zahar, Sami Antoun, Gérard Nitenberg, Elisabeth Chachaty, and H. Farhat

Subjects
Bacillus (shape), Infectious Diseases, Bacillaceae, biology, business.industry, fungi, Oncology hematology, bacteria, Medicine, biology.organism_classification, business, Bacillales, Microbiology
Abstract

Resume Objectif Les bacteries du genre Bacillus sont des bacilles Gram positif de l’environnement. L’isolement d’une bacterie du genre Bacillus est tres souvent considere comme un contaminant. En effet, les infections a Bacillus spp. sont rares et surviennent chez des patients frequemment immunodeprimes. Bacillus cereus est l’espece la plus frequemment responsable d’infection notamment de toxi-infections alimentaires, toutefois d’autres especes peuvent etre responsables de syndrome infectieux grave. Patients et methodes Nous rapportons deux observations d’infections severes bacteriemiques a Bacillus , toutes deux survenues chez des patients immunodeprimes admis en reanimation. Il s’agissait de deux especes rarement decrites a ce jour, l’une a Bacillus macerans et l’autre a Bacillus pumilus . Conclusion L’isolement de Bacillus spp. a partir d’hemocultures lors d’un syndrome infectieux, notamment chez des patients d’oncohematologie, temoigne d’une infection potentiellement grave.

Published
2008
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38. Intercontinental travels of patients and dissemination of plasmid-mediated carbapenemase KPC-3 associated with OXA-9 and TEM-1

Author

Elisabeth Chachaty, François Blot, Guillaume Arlet, Laurent Dortet, Irina Radu, and Valérie Gautier

Subjects
Adult, Male, Microbiology (medical), Internationality, Tetracycline, Microbial Sensitivity Tests, Biology, medicine.disease_cause, beta-Lactamases, Enterococcus faecalis, Microbiology, Plasmid, Antibiotic resistance, Bacterial Proteins, medicine, Humans, Pharmacology (medical), Streptococcus gallolyticus, Pharmacology, Travel, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Erythromycin resistance, Infectious Diseases, Streptococcus pyogenes, Enterobacter cloacae, Plasmids, medicine.drug
Abstract

1. Tsai JC, Hsueh PR, Chen HJ et al. The erm(T) gene is flanked by IS1216V in inducible erythromycin-resistant Streptococcus gallolyticus subsp. pasteurianus. Antimicrob Agents Chemother 2005; 49: 4347–50. 2. Brenciani A, Ojo KK, Monachetti A et al. Distribution and molecular analysis of mef(A)-containing elements in tetracycline-susceptible and -resistant Streptococcus pyogenes clinical isolates with effluxmediated erythromycin resistance. J Antimicrob Chemother 2004; 54: 991–8. 3. Ng LK, Martin I, Alfa M et al. Multiplex PCR for the detection of tetracycline resistant genes. Mol Cell Probes 2001; 15: 209–15. 4. Teng LJ, Hsueh PR, Wang YH et al. Determination of Enterococcus faecalis groESL full-length sequence and application for species identification. J Clin Microbiol 2001; 39: 3326–31. 5. Perreten V, Schwarz F, Cresta L et al. Antibiotic resistance spread in food. Nature 1997; 389: 801–2.

Published
2007
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39. Mucosal immunogenicity elicited in mice by oral vaccination with phosphorylcholine encapsulated in poly (d,l-lactide-co-glycolide) microspheres

Author

Antoine Andremont, Elisabeth Chachaty, Khadija Allaoui-Attarki, Sophie Pecquet, Sylvine Trolle, Patrick Couvreur, and Elias Fattal

Subjects
Polymers, Ratón, Phosphorylcholine, medicine.medical_treatment, Administration, Oral, Biocompatible Materials, Thyroglobulin, Mice, chemistry.chemical_compound, Drug Delivery Systems, Immune system, Polylactic Acid-Polyglycolic Acid Copolymer, Antigen, Oral administration, Phosphatidylcholine, Animals, Medicine, Lactic Acid, Immunity, Mucosal, Mice, Inbred BALB C, Vaccines, General Veterinary, General Immunology and Microbiology, business.industry, Immunogenicity, Public Health, Environmental and Occupational Health, Molecular biology, Microspheres, Infectious Diseases, chemistry, Immunology, Molecular Medicine, Female, business, Polyglycolic Acid
Abstract

Poly(D,L-lactide-co-glycolide) microspheres loaded with phosphorylcholine linked to thyroglobulin (PC-Thyr) as protein carrier were prepared. The entrapment efficiency reached 80% when the initial protein:polymer ratio was 1:8. Ninety-four percent of the loaded microspheres had a diameteror = 10 microns. The encapsulation process did not alter PC-Thyr absorbance nor PC antigenic reactivity. Oral administration of these microspheres induced a specific IgA response in intestinal, pulmonary and vaginal secretions, as well as a strong specific systemic immune response in female Balb/c mice. This suggests the need to explore further the potential ability of PC-Thyr loaded microspheres to protect against infections caused by PC-bearing microorganisms which invade or colonize different mucosal sites.

Published
1998
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40. Use of molecular typing to investigate bacterial translocation from the intestinal tract in malnourished children with Gram-negative bacteremia

Author

Abder-Rahman Bsoul, Elisabeth Chachaty, Mohammad Youssef, Abdallah Al Shurman, and Antoine Andremont

Subjects
Microbiology (medical), education.field_of_study, Gram-negative bacteria, biology, Population, Chromosomal translocation, malnutrition, General Medicine, medicine.disease, biology.organism_classification, Enterobacteriaceae, Microbiology, Malnutrition, Infectious Diseases, Bacterial translocation, Bacteremia, Immunology, medicine, Typing, bacteremia, education, Feces
Abstract

Objective To investigate whether translocation of intestinal Enterobacteriaceae was a likely source of bacteremia in children of 2 years or less hospitalized for fever and moderate malnutrition. Methods Blood and fecal cultures were obtained from 198 such children admitted in the Princess Basma Hospital (Irbid, Jordan). Enterobacteriaceae isolated from blood cultures were compared with those present in fecal cultures by genomic typing using pulsed-field gel electrophoresis. The characteristics of children whose blood and fecal strain typing patterns were not distinguishable, i.e. with documented translocation, were compared to those of children without documented translocation. Results Bacterial translocation was documented in 12 of 19 children (63%) with Enterobacteriaceae bacteremia for whom paired blood and fecal strains were available for genomic typing, and was thus the major source of these bacteremias. The clinical or biological signs of malnutrition were not significantly more pronounced in the bacteremic children with documented translocation than in those without. Conclusions We demonstrated that bacterial translocation from the intestinal tract was the most common source of Gram-negative bacteremia in the population studied.

Published
1998
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41. [Untitled]

Author

Antoine Andremont, Elisabeth Chachaty, Marie-Estelle Page-Clisson, Patrick Couvreur, and Huguette Pinto-Alphandary

Subjects
Pharmacology, Salmonella, Organic Chemistry, Pharmaceutical Science, macromolecular substances, Mononuclear phagocyte system, biochemical phenomena, metabolism, and nutrition, Biology, bacterial infections and mycoses, medicine.disease_cause, Microbiology, Ciprofloxacin, Targeted drug delivery, In vivo, Colistin, medicine, Molecular Medicine, Pharmacology (medical), Drug carrier, Biotechnology, medicine.drug, Antibacterial agent
Abstract

Purpose. We have investigated the efficacy of colistin and ciprofloxacin, free or bound to polyalkylcyanoacrylate nanoparticles, for the targeting and eradication of Salmonella persisting in the organs of the mononuclear phagocyte system.

Published
1998
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42. Serum 2-hydroxyglutarate production in IDH1- and IDH2-mutated de novo acute myeloid leukemia: a study by the Acute Leukemia French Association group

Author

Denis Caillot, Sébastien Forget, Marie-Hélène Courtier, Aline Renneville, Olivier Bernard, Cécile Pautas, Hervé Dombret, Serge Koscielny, Daniel Rabier, Véronique Saada, Nathalie Auger, Claude Preudhomme, Jean-Baptiste Micol, Maxime Janin, Cyril Quivoron, Laurianne Scourzic, Elena Mylonas, Chris Ottolenghi, Edwige Leclercq, Robert Barouki, Annelise Bennaceur-Griscelli, Virginie Penard-Lacronique, Stéphane de Botton, Elisabeth Chachaty, Frank Griscelli, Céline Berthon, and Eric Solary

Subjects
Adult, Male, Cancer Research, NPM1, Myeloid, IDH1, Neoplasm, Residual, Kaplan-Meier Estimate, IDH2, Sensitivity and Specificity, Mass Spectrometry, Glutarates, Predictive Value of Tests, Biomarkers, Tumor, Medicine, Humans, WT1 Proteins, Aged, Acute leukemia, business.industry, Myeloid leukemia, Nuclear Proteins, Stereoisomerism, Middle Aged, medicine.disease, Prognosis, Molecular biology, Minimal residual disease, Isocitrate Dehydrogenase, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Oncology, ROC Curve, Area Under Curve, Immunology, Mutation, Female, France, business, Nucleophosmin
Abstract

Purpose Mutated isocitrate dehydrogenases (IDHs) 1 and 2 produce high levels of 2-hydroxyglutarate (2-HG). We investigated whether, in acute myeloid leukemia (AML), serum 2-HG would predict the presence of IDH1/2 mutations at diagnosis and provide a marker of minimal residual disease (MRD). Patients and Methods Serum samples from 82 patients at diagnosis of de novo AML (IDH1/2 mutated, n = 53) and 68 patients without AML were analyzed for total 2-HG and its ratio of D to L stereoisomers by mass spectrometry. We measured 2-HG levels and molecular markers of MRD (WT1 and NPM1) in serial samples of 36 patients with IDH1/2 mutations after induction therapy. Results In patients with AML with IDH1/2 mutations, 2-HG serum levels were significantly higher than in patients with IDH1/2 wild type (P < .001). Area under the receiver operating characteristic curve was 99%. The optimum diagnostic cutoff between IDH1/2 mutated and normal was 2 μmol/L (sensitivity, 100%; specificity, 79%). Quantification of the D/L stereoisomers increased specificity (100%; 95% CI, 83% to 100%) compared with total 2-HG (P = .031). In patients with IDH2 R172 mutations, 2-HG levels were higher relative to those with other IDH1/2 mutations (P < .05). During follow-up, serum 2-HG levels showed strong positive correlation with WT1 and NPM1 (P < .001). After induction therapy, total 2-HG serum levels < 2 μmol/L were associated with better overall (P = .008) and disease-free survival (P = .005). Conclusion Serum 2-HG is a predictor of the presence of IDH1/2 mutations and outcome in these patients. Discrimination between D/L stereoisomers improved specificity.

Published
2013

43. Mathematical modeling of bacterial kinetics to predict the impact of antibiotic colonic exposure and treatment duration on the amount of resistant enterobacteria excreted

Author

Thu Thuy Nguyen, Jeremie Guedj, Elisabeth Chachaty, Jean de Gunzburg, Antoine Andremont, France Mentré, 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), Microbiologie, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Da Volterra [Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Bodescot, Myriam, and 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)

Subjects
medicine.drug_class, Colon, Swine, Antibiotics, Population Modeling, Drug resistance, Pharmacology, Biostatistics, Models, Biological, Excretion, Cellular and Molecular Neuroscience, Feces, Antibiotic resistance, Enterobacteriaceae, In vivo, Ciprofloxacin, Drug Resistance, Bacterial, Genetics, medicine, Animals, Molecular Biology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, lcsh:QH301-705.5, Ecology, Evolution, Behavior and Systematics, 2. Zero hunger, Ecology, biology, Biology and Life Sciences, Computational Biology, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, biology.organism_classification, Anti-Bacterial Agents, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, Kinetics, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Computational Theory and Mathematics, lcsh:Biology (General), Modeling and Simulation, Physical Sciences, Infectious Disease Modeling, Mathematics, Statistics (Mathematics), medicine.drug, Fluoroquinolones, Research Article
Abstract

Fecal excretion of antibiotics and resistant bacteria in the environment are major public health threats associated with extensive farming and modern medical care. Innovative strategies that can reduce the intestinal antibiotic concentrations during treatments are in development. However, the effect of lower exposure on the amount of resistant enterobacteria excreted has not been quantified, making it difficult to anticipate the impact of these strategies. Here, we introduce a bacterial kinetic model to capture the complex relationships between drug exposure, loss of susceptible enterobacteria and growth of resistant strains in the feces of piglets receiving placebo, 1.5 or 15 mg/kg/day ciprofloxacin, a fluoroquinolone, for 5 days. The model could well describe the kinetics of drug susceptible and resistant enterobacteria observed during treatment, and up to 22 days after treatment cessation. Next, the model was used to predict the expected amount of resistant enterobacteria excreted over an average piglet's lifetime (150 days) when varying drug exposure and treatment duration. For the clinically relevant dose of 15 mg/kg/day for 5 days, the total amount of resistant enterobacteria excreted was predicted to be reduced by 75% and 98% when reducing treatment duration to 3 and 1 day treatment, respectively. Alternatively, for a fixed 5-days treatment, the level of resistance excreted could be reduced by 18%, 33%, 57.5% and 97% if 3, 5, 10 and 30 times lower levels of colonic drug concentrations were achieved, respectively. This characterization on in vivo data of the dynamics of resistance to antibiotics in the colonic flora could provide new insights into the mechanism of dissemination of resistance and can be used to design strategies aiming to reduce it., Author Summary Fecal excretion of antibiotics and resistant bacteria in the environment are major public health threats associated with extensive farming. Innovative strategies that reduce the intestinal antibiotic concentrations during treatment are in development and could help prevent the dissemination of resistance. In order to anticipate the impact of these strategies, the effect of lower exposure on the amount of resistant enterobacteria excreted needs to be quantified precisely. Here, we introduce a bacterial kinetic model to capture the complex relationships between dosage regimen, antibiotic fecal concentrations, loss of susceptible enterobacteria and growth of resistant strains in the feces of piglets receiving different doses of ciprofloxacin for 5 days. We use this model to evaluate by simulation how much it would be necessary to reduce the antibiotic colonic concentration in order to prevent the expansion of antibiotic resistance. This approach provides new insights into the mechanism of dissemination of resistance during treatments and can be used to design strategies to reduce it.

Published
2013
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44. Oral DAV131, a charcoal-based adsorbent, inhibits intestinal colonization by β-lactam-resistant Klebsiella pneumoniae in cefotaxime-treated mice

Author

Thu Thuy Nguyen, Antoine Andremont, Laurent Massias, Nicolas Ducrot, Elisabeth Chachaty, Nathalie Grall, Jean de Gunzburg, and Sakina Sayah-Jeanne

Subjects
Cefotaxime, medicine.drug_class, Klebsiella pneumoniae, Antibiotics, Cephalosporin, Colony Count, Microbial, Administration, Oral, Colonisation resistance, Biology, beta-Lactam Resistance, Microbiology, Feces, Mice, medicine, polycyclic compounds, Animals, Pharmacology (medical), Colonization, Experimental Therapeutics, Pharmacology, Area under the curve, Drug Synergism, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, bacterial infections and mycoses, Anti-Bacterial Agents, Klebsiella Infections, Intestines, Infectious Diseases, Area Under Curve, Charcoal, Female, Adsorption, medicine.drug
Abstract

Antibiotics excreted into the intestinal tract, such as broad-spectrum cephalosporins, disrupt the indigenous microflora, affect colonization resistance (CR), and promote intestinal colonization by resistant bacteria. We tested whether oral DAV131, a charcoal-based adsorbent, would prevent colonization by a cefotaxime (CTX)-resistant Klebsiella pneumoniae strain (PUG-2) in CTX-treated mice. Mice received CTX, saline, CTX and DAV131, or saline and DAV131 for 3 days before oral challenge with 10 6 CFU of PUG-2. The fecal CTX concentrations and counts of PUG-2 were assayed. Fecal CTX disappeared when DAV131 was given concomitantly with CTX ( P < 0.05), and the area under the curve of PUG-2 fecal density was significantly reduced ( P < 0.01). In conclusion, reducing intestinal antibiotic exposure with DAV131 may reduce colonization by resistant strains during treatment compared to treatment with CTX only. This might open new possibilities for decreasing the impact of antibiotics on the intestinal microbiota during treatments.

Published
2013

45. O012: Can DAV132, a medical device targeting an adsorbent to the late ileum, decrease significantly the impact of antibiotics on the fecal microbiota?

Author

Elisabeth Chachaty, J. De Gunzburg, Nathalie Grall, A. Andremont, and Sakina Sayah-Jeanne

Subjects
Microbiology (medical), medicine.medical_specialty, Cefotaxime, medicine.drug_class, business.industry, Antibiotics, Cephalosporin, Public Health, Environmental and Occupational Health, Ileum, Drug resistance, Microbiology, Infectious Diseases, medicine.anatomical_structure, Medical microbiology, Levofloxacin, medicine, Oral Presentation, Pharmacology (medical), business, Feces, medicine.drug
Abstract

During antibiotic treatments a fraction of the dose impacts the intestinal microbiota, promoting spread of resistant bacteria (RB). Antibiotics can be inactivated by adsorption. DAV132 is an oral medical device to deliver an adsorbent in the late ileum. We investigated if DAV132 could reduce fecal antibiotics and RB excreted.

Published
2013
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46. Intravascular catheter-related bloodstream infection caused by Abiotrophia defectiva in a neutropenic child

Author

Bertrand Gachot, A. Emirian, Dominique Valteau-Couanet, Elisabeth Chachaty, N. Gaspar, and A. Phulpin-Weibel

Subjects
Microbiology (medical), Male, medicine.medical_specialty, Pathology, Neutropenia, Antineoplastic Agents, Microbiology, Immunocompromised Host, Catheters, Indwelling, Bloodstream infection, Internal medicine, Abiotrophia, Rare case, Drug Resistance, Bacterial, medicine, Endocarditis, Humans, Gram-Positive Bacterial Infections, Abiotrophia defectiva, biology, business.industry, General Medicine, medicine.disease, biology.organism_classification, Anti-Bacterial Agents, Histiocytosis, Histiocytosis, Langerhans-Cell, Intravascular catheter, Catheter-Related Infections, Child, Preschool, business
Abstract

Bacteraemia and endocarditis are the most frequently reported clinical infections due to Abiotrophia defectiva species. This species has been rarely implicated in infections in neutropenic patients. We report a rare case of long-term venous catheter-related infection caused by A. defectiva that occurred in a febrile child who had neutropenia and Langerhans’ cell histiocytosis.

Published
2013

47. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide

Author

Christina Pfirschke, Charles O. Elson, Marion Bérard, Florent Ginhoux, Nadine Cerf-Bensussan, Mikael J. Pittet, Fabiana Saccheri, Lionel Apetoh, François Ghiringhelli, Eric Vivier, Elisabeth Chachaty, Guido Kroemer, Paul Louis Woerther, Paule Opolon, Andreas Schlitzer, Valérie Gaboriau-Routhiau, Sophie Viaud, Chantal Bizet, Bernhard Ryffel, Patricia Lepage, Gérard Eberl, Nadia Yessaad, David Enot, Camilla Engblom, Ivo G. Boneca, Grégoire Mignot, Chantal Ecobichon, Romain Daillère, Dalil Hannani, Dominique Clermont, Joël Doré, Laurence Zitvogel, Takahiro Yamazaki, Université Paris-Sud - Paris 11 (UP11), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Apoptose, cancer et immunité (U848), Harvard Medical School [Boston] (HMS), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Microbiologie, Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Développement des Tissus Lymphoïdes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Animalerie centrale (Plate-forme), Institut Pasteur [Paris], Groupe Avenir, Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall (BGPB), Collection de l'Institut Pasteur (CIP), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, U989, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), IFR54 IRCIV, Institut de recherche intégrée en cancérologie, Laboratoire de Pathologie Expérimentale, Institut Gustave Roussy (IGR), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Immunologie et Neurogénétique Expérimentales et Moléculaires (INEM), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), University of Alabama at Birmingham [ Birmingham] (UAB), Apoptose, cancer et immunité (Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Paris, Université Paris Descartes - Paris 5 (UPD5), Groupe Avenir [Dijon], Programme ATIP - Avenir, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'Investigation Clinique en Biotherapie des cancers (CIC 1428 , CBT 507 ), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National du Cancer (INCa), la Ligue contre le cancer (LIGUE labelisee), SIRIC Socrates, LABEX, PACRI Onco-Immunology, European Research Council [202283], NIH [P01DK071176], ANR-11-PHUC-0002/11-PHUC-0002,PACRI,PACRI(2011), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-11-PHUC-0002,PACRI,Alliance Parisienne des Instituts de Recherche en Cancérologie(2011), ProdInra, Archive Ouverte, Pôle hospitalier Universitaire Cancer (PHUC) - Alliance Parisienne des Instituts de Recherche en Cancérologie - - PACRI2011 - ANR-11-PHUC-0002 - PHUC - VALID, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris-Sud - Paris 11 ( UP11 ), Immunologie des tumeurs et immunothérapie ( UMR 1015 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Apoptose, cancer et immunité ( U848 ), Harvard Medical School, Center for Systems Biology, Harvard University-Massachusetts General Hospital ( MGH ), Agency for Science, Technology and Research, Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale, Biologie et Génétique de la Paroi bactérienne, Collection de l'Institut Pasteur ( CIP ), MICrobiologie de l'ALImentation au Service de la Santé humaine ( MICALIS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, Institut National de la Santé et de la Recherche Médicale-Université Paris Descartes - Paris 5 ( UPD5 ), Institut Gustave Roussy ( IGR ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Immunologie et Neurogénétique Expérimentales et Moléculaires ( INEM ), Université d'Orléans ( UO ) -Centre National de la Recherche Scientifique ( CNRS ), The University of Alabama at Birmingham [ Birmingham] ( UAB ), Apoptose, cancer et immunité ( Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138 ), Institut Gustave Roussy ( IGR ) -Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Investigation Clinique en Biotherapie des cancers ( CIC 1428 , CBT 507 ), Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and ANR-11-PHUC-0002/11-PHUC-0002,PACRI,PACRI ( 2011 )

Subjects
Adoptive cell transfer, Cyclophosphamide, medicine.drug_class, Lymphoid Tissue, Gram-positive bacteria, [SDV]Life Sciences [q-bio], Antibiotics, Antineoplastic Agents, Gut flora, Gram-Positive Bacteria, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Neoplasms, Intestine, Small, medicine, Tumor Microenvironment, Germ-Free Life, Animals, 030304 developmental biology, 0303 health sciences, Multidisciplinary, biology, [ SDV ] Life Sciences [q-bio], Microbiota, biology.organism_classification, Adoptive Transfer, Small intestine, 3. Good health, Anti-Bacterial Agents, Intestines, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Lymphatic system, 030220 oncology & carcinogenesis, Bacterial Translocation, Immunology, Cancer research, Th17 Cells, Immunologic Memory, Immunosuppressive Agents, medicine.drug
Abstract

The Microbiota Makes for Good Therapy The gut microbiota has been implicated in the development of some cancers, such as colorectal cancer, but—given the important role our intestinal habitants play in metabolism—they may also modulate the efficacy of certain cancer therapeutics. Iida et al. (p. 967 ) evaluated the impact of the microbiota on the efficacy of an immunotherapy [CpG (the cytosine, guanosine, phosphodiester link) oligonucleotides] and oxaliplatin, a platinum compound used as a chemotherapeutic. Both therapies were reduced in efficacy in tumor-bearing mice that lacked microbiota, with the microbiota important for activating the innate immune response against the tumors. Viaud et al. (p. 971 ) found a similar effect of the microbiota on tumor-bearing mice treated with cyclophosphamide, but in this case it appeared that the microbiota promoted an adaptive immune response against the tumors.

Published
2013
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48. Infections chez les patients neutropéniques

Author

Elisabeth Chachaty, Bertrand Gachot, and François Blot

Abstract

Une neutropenie est definie par un chiffre de polynucleaires neutrophiles inferieur a 500/mm3 ou inferieur a 1000/mm3 avec une baisse attendue a moins de 500/mm3. Les episodes febriles (definis par une temperature ≥ 38,3 °C ou ≥ 38 °C pendant au moins 1 heure) sont tres frequents en cas de neutropenie chimio-induite : ils concernent entre 10 et 50 % des patients traites pour une tumeur solide, et plus de 80 % des patients pris en charge pour une hemopathie [1, 2]. Si ces episodes febriles sont non documentes dans plus de la moitie des cas, il est neanmoins connu depuis plusieurs decennies que, l’existence d’fune neutropenie est associee a un risque accru de complications infectieuses graves, avant tout bacteriennes et fongiques. De fait, la survenue d’fune fievre dans ce contexte doit conduire a commencer, en urgence, un traitement antibiotique empirique, l’evolution rapide vers un choc septique etant la regle en cas de bacteriemie, avec un pronostic alors tres sombre [3]. Parallelement a cette urgence therapeutique absolue, l’evolution de l’epidemiologie des infections a bacilles a Gram negatif en France et en Europe, avec banalisation des enterobacteries productrices de betalactamases a spectre elargi et emergence de souches productrices de carbapenemases, impose une utilisation particulierement raisonnee des antibiotiques dans ce contexte [4,5].

Published
2013
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49. Isospora belli infection in a patient with non-Hodgkin's lymphoma

Author

D. Resiere, J.M. Vantelon, Elisabeth Chachaty, P. Bourée, Gérard Nitenberg, and François Blot

Subjects
Adult, Male, Diarrhea, Microbiology (medical), medicine.medical_specialty, Isosporiasis, Antiprotozoal Agents, Mali, trimethoprim-sulfamethoxazole, Feces, immune system diseases, hemic and lymphatic diseases, Acute lymphocytic leukemia, Trimethoprim, Sulfamethoxazole Drug Combination, medicine, Animals, Humans, Immunodeficiency, Isospora, biology, Isospora belli, business.industry, Lymphoma, Non-Hodgkin, Non-Hodgkin's lymphoma, General Medicine, medicine.disease, biology.organism_classification, Dermatology, Lymphoma, Leukemia, Infectious Diseases, Immunology, France, medicine.symptom, business, immunodeficiency
Abstract

Isospora belli infection is frequent in patients with acquired immunodeficiency syndrome in tropical areas. It has also been reported in other immunodepressive diseases, such as lymphoblastic leukemia, adult T-cell leukemia, and Hodgkin's disease. To date, no case of non-Hodgkin's lymphoma-related isosporiasis has been reported in a non-HIV-infected patient. We describe a case of non-Hodgkin's lymphoma with chronic diarrhea due to I. belli. In Europe, I. belli can cause severe chronic diarrhea in patients with malignancies whose country of origin is in an endemic area. Trimethoprim-sulfamethoxazole can provide rapid and prolonged clinical and parasitologic cure.

Published
2003
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50. Correlation between fecal concentrations of ciprofloxacin and fecal counts of resistant Enterobacteriaceae in piglets treated with ciprofloxacin: toward new means to control the spread of resistance?

Author

A. Andremont, Carole Cambier, Elisabeth Chachaty, Thu Thuy Nguyen, Jean de Gunzburg, and Clarisse Huy

Subjects
Veterinary medicine, Swine, Biology, Body weight, Placebo, Drug Administration Schedule, Microbiology, Placebos, 03 medical and health sciences, Feces, Antibiotic resistance, fluids and secretions, Enterobacteriaceae, Ciprofloxacin, Mechanisms of Resistance, Drug Resistance, Bacterial, medicine, Animals, Pharmacology (medical), 030304 developmental biology, 2. Zero hunger, Pharmacology, 0303 health sciences, Fecal flora, Dose-Response Relationship, Drug, 030306 microbiology, biology.organism_classification, bacterial infections and mycoses, Bacterial Load, 3. Good health, Anti-Bacterial Agents, Resistant bacteria, Infectious Diseases, Animals, Newborn, Area Under Curve, medicine.drug
Abstract

We assessed in a piglet model the relationship between fecal ciprofloxacin concentrations and ciprofloxacin-resistant Enterobacteriaceae counts. Twenty-nine piglets were orally treated with placebo or with 1.5 or 15 mg ciprofloxacin/kg of body weight/day from day 1 (D1) to D5. Areas under the curve (AUC) of concentrations increased sharply with dose and correlated positively with AUC of resistant bacteria log counts between D1 and D9. Removing residual colonic quinolones could help to control the emergence of resistance in fecal flora.

Published
2012

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