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4. Isoniazid-monoresistant tuberculosis in France: Risk factors, treatment outcomes and adverse events

Author

Bouchaud, O., Billard-Pomares, T., Carbonnelle, E., Mechaï, F., Nunes, H., Pellan, M., Morin, A.-S., Dumesnil, C., Dumoulin, J., Roux, A.-L., Jachym, M., le Du, D., Marigot-Outtandy, D., Abgrall, S., Chambrin, V., Guillet, C., Fantin, B., Galy, A., Decousser, J.-W., Lelièvre, J.D., Gallien, S., Nebbad-Lechani, B., Deconinck, L., Bulifon, S., Fortineau, N., Wyplosz, B., Cohen, F., Lemaitre, N., Crestani, B., Grall, N., Pierre-Audigier, C., Rioux, C., Yazdanpanah, Y., Le Jeunne, C., Morand, P., Roche, N., Pavie, J., Loulergue, P., Delcey, V., Lecorché, E., Munier, A.-L., Mougari, F., Sellier, P., Bille, E., Ferroni, A., Guéry, R., Hummel, A., Lourenco, J., Aubry, A., Bonnet, I., Caumes, E., Londner, C., Morel, F., Lacombe, K., Lalande, V., Meynard, J.-L., Veziris, N., De Castro, N., Denis, B., Lafaurie, M., Molina, J.-M., Canestri, A., Lassel, L., Pialoux, G., Verdet, C., Nardi, A.-L., Gominet, M., Catherinot, E., Bachir, Marwa, Guglielmetti, Lorenzo, Tunesi, Simone, Billard-Pomares, Typhaine, Chiesi, Sheila, Jaffré, Jérémy, Langris, Hugo, Pourcher, Valérie, Schramm, Frédéric, Lemaître, Nadine, and Robert, Jérôme

Published
2021
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9. Combined Bacterial Meningitis and Infective Endocarditis: When Should We Search for the Other When Either One is Diagnosed?

Author

Béraud, Guillaume, Tubiana, Sarah, Erpelding, Marie-Line, Le Moing, Vincent, Chirouze, Catherine, Gorenne, Isabelle, Manchon, Pauline, Tattevin, Pierre, Vernet, Veronique, Varon, Emmanuelle, Hoen, Bruno, Duval, Xavier, Obadia, J., Leport, C., Poyart, C., Revest, M., Selton-Suty, C., Strady, C., Vandenesch, F., Bernard, Y., Chocron, S., Plesiat, P., Abouliatim, I., de Place, C., Donnio, P., Alla, F., Carteaux, J., Doco-Lecompte, T., Lion, C., Aissa, N., Baehrel, B., Jaussaud, R., Nazeyrollas, P., Cambau, E., Iung, B., Nataf, P., Chidiac, C., Celard, M., Delahaye, F., Aumaître, H., Frappier, J., Oziol, E., Sotto, A., Sportouch, C., Bouvet, A., Bes, M., Abassade, P., Abrial, E., Acar, C., Alexandra, J., Amireche, N., Amrein, D., Andre, P., Appriou, M., Arnould, M., Atoui, A., Aziza, F., Baille, N., Bajolle, N., Battistella, P., Baumard, S., Ben Ali, A., Bertrand, J., Bialek, S., Bois Grosse, M., Boixados, M., Borlot, F., Bouchachi, A., Bouche, O., Bouchemal, S., Bourdon, J., Brasme, L., Bruntz, J., Cailhol, J., Caplan, M.P., Carette, B., Cartry, O., Cazorla, C., Chamagne, H., Champagne, H., Chanques, G., Chevalier, B., Chometon, F., Christophe, C., Colin de Verdiere, N., Daneluzzi, V., David, L., Danchin, N., de Lentdecker, P., Delcey, V., Deleuze, P., Deroure, B., Descotes-Genon, V., Didier Petit, K., Dinh, A., Doat, V., Duchene, F., Duhoux, F., Dupont, M., Ederhy, S., Epaulard, O., Evest, M., Faucher, J., Fauveau, E., Ferry, T., Fillod, M., Floch, T., Fraisse, T., Frapier, J., Freysz, L., Fumery, B., Gachot, B., Gallien, S., Garcon, P., Gaubert, A., Genoud, J., Ghiglione, S., Godreuil, C., Gandjbakhch, I., Grentzinger, A., Groben, L., Gherissi, D., Hagege, A., Hammoudi, N., Heliot, F., Henry, P., Houriez, P., Hustache-Mathieu, L., Huttin, O., Imbert, S., Jaureguiberry, S., Kaaki, M., Konate, A., Kuhn, J., Kural Menasche, S., Lafitte, A., Lafon, B., Lanternier, F., Le Chenault, V., Lechiche, C., Lefevre Thibaut, S., Lefort, A., Lemoine, J., Lepage, L., Lepousé, C., Leroy, J., Lesprit, P., Letranchant, L., Loncar, G., Lorentz, C., Magnin-Poull, I., Makinson, A., Man, H., Mansouri, M., Marçon, O., Maroni, J., Masse, V., Maurier, F., Mechaï, F., Merceron, O., Messika-Zeitoun, D., Metref, Z., Meyssonnier, V., Mezher, C., Micheli, S., Monsigny, M., Mouly, S., Mourvillier, B., Nallet, O., Nazerollas, P., Noel, V., Payet, B., Pelletier, A., Perez, P., Petit, J., Philippart, F., Piet, E., Plainvert, C., Popovic, B., Porte, J., Pradier, P., Ramadan, R., Richemond, J., Rodermann, M., Roncato, M., Roigt, I., Ruyer, O., Saada, M., Schwartz, J., Simon, M., Simorre, B., Skalli, S., Spatz, F., Sudrial, J., Tartiere, L., Terrier de La Chaize, A., Thiercelin, M., Thomas, D., Thomas, M., Toko, L., Tournoux, F., Tristan, A., Trouillet, J., Tual, L., Verdier, F., Vernet Garnier, V., Vidal, V., Weyne, P., Wolff, M., Wynckel, A., Zannad, N., Zinzius, P., Ploy, M.-C., Caron, F., Bollaert, P.-E., Gaillot, O., Taha, M.-K., Bonacorsi, S., Lecuit, M., Gravet, A., Frachet, B., Debroucker, T., Levy-Bruhl, D., Raffi, F., Preau, M., Anguel, N., Argaud, L., Arista, S., Armand-Lefevre, L., Balavoine, S., Baraduc, R., Barnaud, G., Bernard, L., Bernars, G., Bertei, D., Bessede, E., Billard Pomares, T., Biron, C., Bland, S., Boileau, J., Boubeau, P., Bourdon, S., Bousquet, A., Boyer, S., Bozorg-Grayeli, A., Bret, L., Bretonniere, C., Bricaire, F., Brocas, E., Brun, M., Buret, J., Burucoa, C., Cabalion, J., Cabon, M., Camuset, G., Canevet, C., Carricajo, A., Castan, B., Caumes, E., Cazanave, C., Chabrol, A., Challan-Belval, T., Chanteperdrix-Marillier, V., Chaplain, C., Charlier-Woerther, C., Chaussade, H., Clair, B., Colot, J., Conil, J.-M., Cordel, H., Cormier, P., Cousson, J., Cronier, P., Cua, E., Dao-Dubremetz, A., Dargere, S., Degand, N., Dekeyser, S., Delaune, D., Denes, E., Dequin, P.-F., Descamps, D., Descloux, E., Desmaretz, J.-L., Diehl, J.-L., Dimet, J., Escaut, L., Fabe, C., Faibis, F., Flateau, C., Fonsale, N., Forestier, E., Fortineau, N., Gagneux-Brunon, A., Garandeau, C., Garcia, M., Garot, D., Gaudry, S., Goehringer, F., Gregoire-Faucher, V., Grosset, M., Gubavu, C., Gueit, I., Guelon, D., Guimard, T., Guinard, J., Hadou, T., Helene, J.-P., Henard, S., Henry, B., Hochart, A.-C., Illes, G., Jaffuel, S., Jarrin, I., Jaureguy, F., Joseph, C., Juvin, M.-E., Kayal, S., Kerneis, S., Lacassin, F., Lamaury, I., Lanotte, P., Laurens, E., Laurichesse, H., Le Brun, C., Le Turnier, P., Lecuyer, H., Ledru, S., Legrix, C., Lemaignen, A., Lemble, C., Lemee, L., Lesens, O., Levast, M., Lhommet, C., Males, S., Malpote, E., Martin-Blondel, G., Marx, M., Masson, R., Matray, O., Mbadi, A., Mellon, G., Merens, A., Meyohas, M.-C., Michon, A., Mootien Yoganaden, J., Morquin, D., Mrozek, N., Nguyen, S., Nguyen, Y., Ogielska, M., Page, B., Patrat-Delon, S., Patry, I., Pechinot, A., Picot, S., Pierrejean, D., Piroth, L., Plassart, C., Plessis, P., Portel, L., Poubeau, P., Poupard, M., Prazuck, T., Quaesaet, L., Ramanantsoa, A., Rapp, C., Raskine, L., Raymond, J., Riche, A., Robaday-Voisin, S., Robin, F., Romaszko, J.-P., Rousseau, F., Roux, A.-L., Royer, C., Salmon, D., Saroufim, C., Schmit, J.-L., Sebire, M., Segonds, C., Sivadon-Tardy, V., Soismier, N., Son, O., Sunder, S., Suy, F., Tande, D., Tankovic, J., Valin, N., van Grunderbeeck, N., Verdon, R., Vergnaud, M., Vernet-Garnier, V., Vidal, M., Vitrat, V., Vittecoq, D., Vuotto, F., Laouenan, C., Marcault, E., Mentre, F., Pasquet, B., Roy, C., Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Université Sorbonne Paris Nord, Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Intercommunal de Créteil (CHIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and The AEPEI IE cohort was funded by a research grant from the French Ministry of Health (PHRC 2007), grants from the Société Française de Cardiologie, the European Society of Clinical Microbiology and Infectious Diseases, and Novartis France. The sponsor was Délégation à la Recherche Clinique et au Développement, Centre Hospitalier Universitaire de Besançon. The COMBAT cohort was funded by Assistance Publique—Hôpitaux de Paris, Inserm, The French Society of Infectious Diseases (SPILF), and Pfizer Laboratory. It was also supported by the Observatoire de la Resistance du Pneumocoque (ORP) and Santé Publique France. The sponsor of the study and the funding sources had no role in study design, data collection, data analysis, data interpretation or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit it for publication. The Rapid Service Fee was funded by the University Hospital of Poitiers, to which the corresponding author is affiliated.

Subjects
Microbiology (medical), Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Echocardiography, Austrian syndrome, Staphylococcus, [SDV]Life Sciences [q-bio], Bacterial meningitis, Streptococcus, Infective endocarditis
Abstract

International audience; Introduction: We aimed to describe patients with coexisting infective endocarditis (IE) and bacterial meningitis (BM).Methods: We merged two large prospective cohorts, an IE cohort and a BM cohort, with only cases of definite IE and community-acquired meningitis. We compared patients who had IE and BM concurrently to patients with IE only and BM only.Results: Among the 1030 included patients, we identified 42 patients with IE-BM (4.1%). Baseline characteristics of patients with IE-BM were mostly similar to those of patients with IE, but meningitis was the predominant presentation at admission (39/42, 92.3%). Causative pathogens were predominantly Streptococcus pneumoniae (18/42, 42.9%) and Staphylococcus aureus (14/42, 33.3%). All pneumococcal IE were associated with BM (18/18). BM due to oral and group D streptococci, Streptococcus agalactiae, and S. aureus were frequently associated with IE (14/30, 46.7%). Three-month mortality was 28.6% in patients with IE-BM, 20.5% in patients with IE, and 16.6% in patients with BM.Conclusions: Patients with pneumococcal IE or altered mental status during IE must be investigated for BM. Patients with S. aureus, oral and group D streptococcal or enterococcal BM, or unfavorable outcome in pneumococcal meningitis would benefit from an echocardiography. Patients with the dual infection have the worst prognosis. Their identification is mandatory to initiate appropriate treatment.

Published
2022
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11. Isoniazid-monoresistant tuberculosis in France: Risk factors, treatment outcomes and adverse events

Author

Bachir, Marwa, primary, Guglielmetti, Lorenzo, additional, Tunesi, Simone, additional, Billard-Pomares, Typhaine, additional, Chiesi, Sheila, additional, Jaffré, Jérémy, additional, Langris, Hugo, additional, Pourcher, Valérie, additional, Schramm, Frédéric, additional, Lemaître, Nadine, additional, Robert, Jérôme, additional, Bouchaud, O., additional, Billard-Pomares, T., additional, Carbonnelle, E., additional, Mechaï, F., additional, Nunes, H., additional, Pellan, M., additional, Morin, A.-S., additional, Dumesnil, C., additional, Dumoulin, J., additional, Roux, A.-L., additional, Jachym, M., additional, le Du, D., additional, Marigot-Outtandy, D., additional, Abgrall, S., additional, Chambrin, V., additional, Guillet, C., additional, Fantin, B., additional, Galy, A., additional, Decousser, J.-W., additional, Lelièvre, J.D., additional, Gallien, S., additional, Nebbad-Lechani, B., additional, Deconinck, L., additional, Bulifon, S., additional, Fortineau, N., additional, Wyplosz, B., additional, Cohen, F., additional, Lemaitre, N., additional, Crestani, B., additional, Grall, N., additional, Pierre-Audigier, C., additional, Rioux, C., additional, Yazdanpanah, Y., additional, Le Jeunne, C., additional, Morand, P., additional, Roche, N., additional, Pavie, J., additional, Loulergue, P., additional, Delcey, V., additional, Lecorché, E., additional, Munier, A.-L., additional, Mougari, F., additional, Sellier, P., additional, Bille, E., additional, Ferroni, A., additional, Guéry, R., additional, Hummel, A., additional, Lourenco, J., additional, Aubry, A., additional, Bonnet, I., additional, Caumes, E., additional, Londner, C., additional, Morel, F., additional, Lacombe, K., additional, Lalande, V., additional, Meynard, J.-L., additional, Veziris, N., additional, De Castro, N., additional, Denis, B., additional, Lafaurie, M., additional, Molina, J.-M., additional, Canestri, A., additional, Lassel, L., additional, Pialoux, G., additional, Verdet, C., additional, Nardi, A.-L., additional, Gominet, M., additional, and Catherinot, E., additional

Published
2021
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25. Characterization of a P1-like bacteriophage encoding an SHV-2 extended-spectrum β-lactamase from an Escherichia coli strain

Author

Billard-Pomares, T., Fouteau, S., Jacquet, M.E., Roche, D., Barbe, V., Castellanos, M., Bouet, J.Y., Cruveiller, S., Médigue, C., Blanco, J., Clermont, E., Denamur, E., Branger, C., Laboratoire de microbiologie et génétique moléculaires (LMGM), Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2014

26. Pulmonary tuberculosis: Evaluation of current diagnostic strategy

Author

Gressens, S.B., Billard-Pomares, T., Leboité, H., Cruaud, P., Bouchaud, O., Carbonnelle, E., and Méchaï, F.

Abstract

•Systematic use of fibroscopy procedure among acid-fast negative patients is pivotal in reducing time to diagnosis, especially when using molecular testing.•Tuberculosis diagnosis algorithms can be optimized to fit peculiar epidemiological settings in developed countries, and predefined diagnosis protocols could be developed in such centers.•A high suspicion score of tuberculosis could drive the reasoned use of molecular testing in such settings.

Published
2024
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27. Optimization of Mycobacterium tuberculosis DNA processing prior to whole genome sequencing.

Author

Dziri S, Marin J, Quagliaro P, Genestet C, Dumitrescu O, Carbonnelle E, and Billard-Pomares T

Subjects
Solvents, Humans, Microbial Viability drug effects, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis enzymology, DNA, Bacterial genetics, Whole Genome Sequencing, Octoxynol, Genome, Bacterial
Abstract

The process of whole genome sequencing of the Mycobacterium tuberculosis complex is dependent on complete the inactivation of the strain and subsequent DNA extraction. The objective of this study was to optimise the two steps. Firstly, the efficacy of Triton X-100 as a solvent for the inactivation step was evaluated. This solvent has been demonstrated to be effective in killing bacteria and is less toxic than the previously employed chloroform. For the extraction step, two lysis methods were evaluated: enzymatic (B1 protocol) and mechanical (B2 protocol). For whole genome sequencing, the Nextera XT DNA library preparation protocol was performed for both the B1 and B2 protocols. Subsequently, each library was subjected to whole-genome sequencing. The results demonstrated that heat lysis inactivation with Triton was effective, with no bacteria remaining viable following this treatment. The enzymatic and mechanical extraction protocols yielded comparable results in terms of DNA quantity and quality. The sequencing results showed that there was no significant difference in read depths between the two protocols. In conclusion, for MTBC strains, we recommend the use of our Triton inactivation method, which meets biosafety expectations., Competing Interests: Declaration of competing interest I am writing to submit the manuscript entitled “Optimization of Mycobacterium tuberculosis DNA processing prior to Whole Genome Sequencing” by Samira Dziri, Julie Marin, Pauline Quagliaro, Charlotte Genestet, Oana Dumitrescu, Etienne Carbonnelle and Typhaine Billard-Pomares for consideration as an original article in Tuberculosis. We are unaware of any competing interests associated with this publication, and there has been no significant financial support for this work that could have influenced its outcome. As the corresponding author, I confirm that the manuscript has been read and approved for submission by all the named authors. We hope that you will find our manuscript suitable for publication and look forward to hearing from you in due course., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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28. Extensive buruli ulcer in a patient returning from Mali and Senegal.

Author

Bohelay G, Guyot A, Billard-Pomares T, Marsollier L, Caux F, and Carbonnelle E

Subjects
Humans, Mali, Senegal, Male, Travel, Mycobacterium ulcerans isolation & purification, Adult, Buruli Ulcer drug therapy, Buruli Ulcer diagnosis
Abstract

no abstract requested for correspondance items., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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29. Towards the reconstruction of a global TB history using a new pipeline "TB-Annotator".

Author

Senelle G, Sahal MR, La K, Billard-Pomares T, Marin J, Mougari F, Bridier-Nahmias A, Carbonnelle E, Cambau E, Refrégier G, Guyeux C, and Sola C

Subjects
Humans, Animals, Phylogeny, Genome-Wide Association Study, Computational Biology, Mycobacterium tuberculosis genetics, Tuberculosis diagnosis, Tuberculosis genetics, Tuberculosis epidemiology
Abstract

Mycobacterium tuberculosis complex (MTBC) has a population structure consisting of 9 human and animal lineages. The genomic diversity within these lineages is a pathogenesis factor that affects virulence, transmissibility, host response, and antibiotic resistance. Hence it is important to develop improved information systems for tracking and understanding the spreading and evolution of genomes. We present results obtained thanks to a new informatics platform for computational biology of MTBC, that uses a convenience sample from public/private SRAs, designated as TB-Annotator. Version 1 was a first interactive graphic-based web tool based on 15,901 representative genomes. Version 2, still interactive, is a more sophisticated database, developed using the Snakemake Workflow Management System (WMS) that allows an unsupervised global and scalable analysis of the content of the USA National Center for Biotechnology Information Short Read Archives database. This platform analyzes nucleotide variants, the presence/absence of genes, known regions of difference and detect new deletions, the insertion sites of mobile genetic elements, and allows phylogenetic trees to be built, imported in a graphical interface and interactively analyzed between the data and the tree. The objective of TB-Annotator is triple: detect recent epidemiological links, reconstruct distant phylogeographical histories as well as perform more complex phenotypic/genotypic Genome-Wide Association Studies (GWAS). In this paper, we compare the various taxonomic SNPs-based labels and hierarchies previously described in recent reference papers for L1, and present a comparative analysis that allows identification of alias and thus provides the basis of a future unifying naming scheme for L1 sublineages. We present a global phylogenetic tree built with RAxML-NG, and one on L2; at the time of writing, we characterized about 200 sublineages, with many new ones; a detail tree for Modern L2 and a hierarchical scheme allowing to facilitate L2 lineage assignment are also presented., Competing Interests: Declaration of competing interest None declared., (Copyright © 2023. Published by Elsevier Ltd.)

Published
2023
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30. Performances of bioinformatics tools for the analysis of sequencing data of Mycobacterium tuberculosis complex strains.

Author

Quagliaro P, Dziri S, Magdoud El Alaoui F, Saint Louis P, de Pontual L, Marin J, Carbonnelle E, and Billard-Pomares T

Subjects
Humans, Microbial Sensitivity Tests, Antitubercular Agents therapeutic use, Computational Biology methods, Whole Genome Sequencing methods, Mycobacterium tuberculosis genetics
Abstract

Whole-genome sequencing of Mycobacterium tuberculosis complex (MTBC) strains is a rapidly growing tool to obtain results regarding the resistance and phylogeny of the strains. We evaluated the performances of two bioinformatics tools for the analysis of whole-genome sequences of MTBC strains. Two hundred and twenty-seven MTBC strains were isolated and whole-genome sequenced at the laboratory of Avicenne Hospital between 2015 and 2021. We investigated the resistance and susceptibility status of strains using two online tools, Mykrobe and PhyResSE. We compared the genotypic and phenotypic resistance results obtained by drug susceptibility testing. Unlike with the Mykrobe tool, sequencing quality data were obtained using PhyResSE: average coverage of 98% and average depth of 119X. We found a similar concordance between phenotypic and genotypic results when determining susceptibility to first-line anti-tuberculosis drugs (95%) with both tools. The sensitivity and specificity of each tool compared to the phenotypic method were respectively 72% [52-87] and 98% [96-99] for Mykrobe and 76% [57-90] and 97% [94-99] for PhyResSE. Mykrobe and PhyResSE were easy to use and efficient. These platforms are accessible to people not trained in bioinformatics and constitute a complementary approach to phenotypic methods for the study of MTBC strains., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Published
2023
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31. Prevalence and risk factors for carriage of extended-spectrum β-lactamase-producing enterobacteriaceae in rehabilitation wards in France.

Author

Grall-Zahar I, Rucly S, Billard-Pomares T, Gasnier-Besnardeau K, Al Mouft O, Zahar JR, and Zirnhelt I

Subjects
Humans, Female, Aged, Prevalence, beta-Lactamases, Prospective Studies, Carrier State epidemiology, Carrier State microbiology, Feces microbiology, Enterobacteriaceae, Hospitals, Escherichia coli, Risk Factors, Enterobacteriaceae Infections drug therapy, Enterobacteriaceae Infections epidemiology
Abstract

Objectives: Extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-PE) are a major public health concern worldwide. Little is known about the prevalence of ESBL-PE colonization in rehabilitation wards in France. Our aim was to determine the prevalence of ESBL-PE colonization in rehabilitation wards in the Parisian area and to identify potential risk factors for ESBL-PE carriage., Patients and Methods: This one-day prospective study was performed in three rehabilitation wards in Paris, France, between September 1, 2016, and June 26, 2017. Rectal samples were collected for microbial analysis from patients who were present at 8am and all isolates recovered were identified by mass spectrometry. The presence of ESBL-PE was confirmed using a double-disk synergy test according to EUCAST recommendations. Risk factors for colonization were determined by univariate and multivariate analyses., Results: A total of 136 patients were analyzed (50.7% of female patients; median age 71 years). Twenty-eight patients (20.6%) were colonized with ESBL-PE on the day of sampling. Escherichia coli was identified in 15 (50%) cases and Klebsiella pneumoniae in six (20%). None of the variables studied was significantly associated with a higher risk of ESBL-PE colonization. However, there was a tendency for a higher risk of ESBL-PE colonization with dementia (OR = 6.116 [95%CI: 0.92-40.57]; p = 0.06) and diabetes with complications (OR = 2.853 [95%CI: 1-8.16]; p = 0.05)., Conclusions: Patients in rehabilitation wards showed a high rate of ESBL-PE colonization (21%). Continuous monitoring of antibiotic resistance among potentially pathogenic bacteria, including ESBL-PE, is crucial as colonized patients represent an important reservoir for transmission after discharge outside the hospital setting., (Copyright © 2022. Published by Elsevier Masson SAS.)

Published
2022
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32. Use of Whole-Genome Sequencing to Explore Mycobacterium tuberculosis Complex Circulating in a Hotspot Department in France.

Author

Billard-Pomares T, Marin J, Quagliaro P, Méchaï F, Walewski V, Dziri S, and Carbonnelle E

Abstract

The Seine-Saint-Denis is the French metropolitan department with the highest incidence of tuberculosis (TB). Our aim was to explore epidemiological and phylogenetic characteristics of TB strains in this hotspot department. We performed WGS on 227 strains of Mycobacterium tuberculosis complex isolated from patients at the Avicenne Hospital from 2016 to 2021 and randomly selected to represent the clinical diversity of French TB localization. Clinical and demographic data were recorded for each TB patient. The mean age of patients was 36 years old. They came from Africa (44%), Asia (27%), Europe (26%) and America (3%). Strains isolated from extrapulmonary samples were associated with Asian patients, whereas strains isolated from pulmonary samples were associated with European patients. We observed a high level of lineage diversity in line with the known worldwide diversity. Interestingly, lineage 3 was associated with lymph node TB. Additionally, the sensitivity of WGS for predicting resistance was 100% for rifampicin, isoniazid and ethambutol and 66.7% for pyrazinamide. The global concordance with drug-susceptibility testing using the phenotypic approach was 97%. In microbiology laboratories, WGS turns out to be an essential tool for better understanding local TB epidemiology, with direct access to circulating lineage identification and to drug susceptibilities to first- and second-line anti-TB drugs.

Published
2022
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33. Molecular detection of isoniazid monoresistance improves tuberculosis treatment: A retrospective cohort in France.

Author

Bachir M, Guglielmetti L, Tunesi S, Billard-Pomares T, Chiesi S, Jaffré J, Langris H, Pourcher V, Schramm F, Lemaître N, and Robert J

Subjects
Antitubercular Agents pharmacology, Antitubercular Agents therapeutic use, Humans, Isoniazid pharmacology, Isoniazid therapeutic use, Microbial Sensitivity Tests, Retrospective Studies, Mycobacterium tuberculosis genetics, Tuberculosis diagnosis, Tuberculosis drug therapy, Tuberculosis, Multidrug-Resistant diagnosis, Tuberculosis, Multidrug-Resistant drug therapy
Abstract

Objectives: Isoniazid-monoresistant tuberculosis (HR-TB) requires early diagnosis and adapted treatment to achieve optimal outcomes. The primary aim of the study was to assess the impact of the implementation of rapid diagnostic tests on HR-TB treatment in France., Methods: We designed a retrospective multicentre study including consecutive HR-TB patients diagnosed in 2016 and 2017. Implementation of a molecular assay detecting isoniazid resistance directly on a clinical sample was recorded. The association between early implementation of such assays and adequate treatment was assessed by a multivariable Cox proportional hazards model., Results: Overall, 99 HR-TB patients were included from 20 University Hospitals. Among all smear-positive HR-TB patients, only 26% beneficiated from early molecular HR detection. This detection was independently associated with shorter time to adequate treatment (HR = 2.0 [1.1-3.8], p = 0.03)., Conclusion: In our study, molecular detection of HR on an initial sample was independently associated with earlier treatment adaptation., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Published
2022
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34. Temocillin susceptibility among Enterobacterales strains recovered from blood culture in France.

Author

Farfour E, Si Larbi AG, Cattoir V, Corvec S, Guillard T, Grillon A, Isnard C, Mérens A, Degand N, Billard-Pomares T, Fournier D, Bille E, Le Brun C, Plouzeau C, Flevin E, Yin N, Woerther PL, Lourtet J, Lesprit P, and Le Monnier A

Subjects
Dose-Response Relationship, Drug, Enterobacteriaceae Infections epidemiology, France epidemiology, Humans, Microbial Sensitivity Tests, Anti-Bacterial Agents pharmacology, Drug Resistance, Bacterial, Enterobacteriaceae drug effects, Enterobacteriaceae Infections microbiology, Penicillins pharmacology
Abstract

Temocillin is used for several years in some European countries but, only since 2015 in France. We assessed the susceptibility of Enterobacterales strains isolated from blood culture 1 year before (2014) and 2 years after (2017) its use in France. 1,387 strains were included by 17 clinical laboratories located throughout France: 363 in 2014 and 1,024 in 2017. The rate of resistance to temocillin was 4.6% and 26.7% in 3rd generation cephalosporin (3GC) susceptible and resistant strains respectively. Cephalosporinase-overproducer (COPE) strains were significantly more resistant to temocillin (37.7%) than ESBL-producer (ESBL-PE) (23.5%) (P < 0.01). The rate of temocillin resistance was correlated to the number of inactive beta-lactams. The rate of resistance to temocillin trend to increase from 13.9% in 2014 to 23.9% in 2017 (P < 0.01). Temocillin remains highly active against Enterobacterales but the trend in resistance should be assessed over time., Competing Interests: Competing interest The temocillin Etest strips (bioMérieux, Lyon, France) were provided without charge by Eumedica pharmaceutical., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
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35. A recurrent lung abscess caused by delayed diagnosis of unique co-infection with Abiotrophia defectiva.

Author

Onorati I, Guiraudet P, Billard-Pomares T, and Martinod E

Subjects
Endocarditis, Endocarditis, Bacterial diagnosis, Endocarditis, Bacterial microbiology, Gram-Positive Bacterial Infections diagnosis, Gram-Positive Bacterial Infections microbiology, Humans, Lung microbiology, Lung Abscess diagnosis, Lung Abscess microbiology, Male, Middle Aged, Tomography, X-Ray Computed, Abiotrophia isolation & purification, Coinfection, Delayed Diagnosis adverse effects, Endocarditis, Bacterial etiology, Gram-Positive Bacterial Infections etiology, Lung diagnostic imaging, Lung Abscess etiology
Abstract

We report the case of a lung abscess due to Prevotella baroniae with a co-infection by Abiotrophia defective, which is a 'nutritionally variant streptococci' (NVS), in a 48-year-old patient. The delayed diagnosis of this co-infection led to multiple failures of medical treatment and need for surgery. Pathogenicity of these bacteria is well known, particularly in endocarditis, but not in lung infection. In pulmonary abscesses, co-infection with NVS is difficult to detect. It may explain some medical treatment failures. This case highlights the importance to systematically search for and consider NVS in such clinical contexts., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Published
2020
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36. Molecular identification of Actinomadura madurae isolated from a patient originally from Algeria; observations from a case report.

Author

Izri A, Aljundi M, Billard-Pomares T, Fofana Y, Marteau A, Ferreira TG, Brun S, Caux F, and Akhoundi M

Subjects
Actinomadura, Algeria ethnology, DNA, Ribosomal genetics, Emigrants and Immigrants, Foot pathology, Humans, Male, Middle Aged, Mycetoma ethnology, Mycetoma microbiology, Paris, Treatment Outcome, Actinobacteria genetics, Actinobacteria isolation & purification, Anti-Bacterial Agents therapeutic use, Mycetoma diagnosis, Mycetoma drug therapy, Trimethoprim, Sulfamethoxazole Drug Combination therapeutic use
Abstract

Background: Mycetoma is a chronic granulomatous subcutaneous infection caused by anaerobic pseudofilamentous bacteria or fungi. It is commonly prevalent in tropical and subtropical countries. Men are more susceptible to the disease due to greater participation in agricultural works. Mycetoma commonly involves lower extremities, wherein untreated cases lead to aggressive therapeutic choices, such as amputation of the affected body organs and consequently lifelong disability., Case Presentation: In this report, we present the rare case of a 58-year-old man, originally from Algeria with a left foot chronic tumefaction of 5 years. In the initial clinical examination, mycetoma was diagnosed based on tumefaction and the presence of multiple sinuses with the emission of white grains. The latter was observed via direct examination. The histopathological analysis demonstrated an actinomycetoma caused by bacteria, as the etiological agent. Imaging showed a bone involvement with osteolysis at the levels of 2nd to 4th metatarsal diaphysis. The mycological and bacterial cultures were both negative. For an accurate diagnosis, the obtained grains were subjected to molecular analysis, targeting the 16S-rDNA gene. Molecular identification yielded Actinomadura madurae as the causal agent, and 800/160 mg of trimethoprim/sulfamethoxazole was prescribed twice a day for 1 year, as a treatment., Conclusion: Considering low information about this disease, especially in non-endemic areas, it is of high importance to enhance the knowledge and awareness of clinicians and healthcare providers, in particular in the countries with immigration issues.

Published
2020
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37. Fatal Legionella pneumophila serogroup 1 pleural empyema: A case report.

Author

Maillet F, Bonnet N, Billard-Pomares T, El Alaoui Magdoud F, and Tandjaoui-Lambiotte Y

Abstract

Background: Legionella pneumophila ( L. pneumophila ) is a gram-negative intracellular bacillus composed of sixteen different serogroups. It is mostly known to cause pneumonia in individuals with known risk factors as immunocompromised status, tobacco use, chronic organ failure or age older than 50 years. Although parapneumonic pleural effusion is frequent in legionellosis, pleural empyema is very uncommon. In this study, we report a case of fatal pleural empyema caused by L. pneumophila serogroup 1 in an 81-year-old man with multiple risk factors., Case Summary: An 81-year-old man presented to the emergency with a 3 wk dyspnea, fever and left chest pain. His previous medical conditions were chronic lymphocytic leukemia, diabetes mellitus, chronic kidney failure, hypertension and hyperlipidemia, without tobacco use. Chest X-ray and comouted tomography-scan confirmed a large left pleural effusion, which puncture showed a citrine exudate with negative standard bacterial cultures. Despite intravenous cefotaxime antibiotherapy, patient's worsening condition after 10 d led to thoracocentesis and evacuation of 2 liters of pus. The patient progressively developed severe hypoxemia and multiorgan failure occurred. The patient was treated by antibiotherapy with cefepime and amikacin and with adequate symptomatic shock treatment, but died of uncontrolled sepsis. The next day, cultures of the surgical pleural liquid samples yielded L. pneumophila serogroup 1, consistent with the diagnosis of pleural legionellosis., Conclusion: L. pneumophila should be considered in patients with multiple risk factors and undiagnosed pleural empyema unresponsive to conventional antibiotherapy., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)

Published
2019
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38. Specialization of small non-conjugative plasmids in Escherichia coli according to their family types.

Author

Branger C, Ledda A, Billard-Pomares T, Doublet B, Barbe V, Roche D, Médigue C, Arlet G, and Denamur E

Subjects
Databases, Genetic, Evolution, Molecular, Gene Frequency, Phylogeny, Plasmids classification, Plasmids genetics, Species Specificity, Escherichia coli genetics, Plasmids metabolism
Abstract

We undertook a comprehensive comparative analysis of a collection of 30 small (<25 kb) non-conjugative Escherichia coli plasmids previously classified by the gene sharing approach into 10 families, as well as plasmids found in the National Center for Biotechnology Information (NCBI) nucleotide database sharing similar genomic sequences. In total, 302 mobilizable (belonging to 2 MOB rep and 5 MOB RNA families) and 106 non-transferable/relaxase-negative (belonging to three ReL RNA families) plasmids were explored. The most striking feature was the specialization of the plasmid family types that was not related to their transmission mode and replication system. We observed a range of host strain specificity, from narrow E. coli host specificity to broad host range specificity, including a wide spectrum of Enterobacteriaceae . We found a wide variety of toxin/antitoxin systems and colicin operons in the plasmids, whose numbers and types varied according to the plasmid family type. The plasmids carried genes conferring resistance spanning almost all of the antibiotic classes, from those to which resistance developed early, such as sulphonamides, to those for which resistance has only developed recently, such as colistin. However, the prevalence of the resistance genes varied greatly according to the family type, ranging from 0 to 100 %. The evolutionary history of the plasmids based on the family type core genes showed variability within family nucleotide divergences in the range of E. coli chromosomal housekeeping genes, indicating long-term co-evolution between plasmids and host strains. In rare cases, a low evolutionary divergence suggested the massive spread of an epidemic plasmid. Overall, the importance of these small non-conjugative plasmids in bacterial adaptation varied greatly according to the type of family they belonged to, with each plasmid family having specific hosts and genetic traits.

Published
2019
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39. Using SNOMED-CT to Help the Transition from Microbiological Data to ICD-10 Sepsis Codes.

Author

Ternois I, Billard-Pomares T, Carbonelle E, Franchinard L, and Duclos C

Subjects
Humans, International Classification of Diseases, Sepsis, Systematized Nomenclature of Medicine
Abstract

Assigning ICD-10 code of sepsis in regard of a pathogenic bacterium found in an haemoculture requires knowledge of microbiology because of the difference of granularity. The aim of this paper is to automate this coding thanks to the use of SNOMED-CT. A dichotomous classification of bacteria causing sepsis has been generated in respect of ICD-10. Our algorithm follows this and explores SNOMED-CT to assign the right ICD-10 code of the sepsis. Applied to a list of 164 bacteria, the system has an error rate of 1.22 %.

Published
2019
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40. The Arginine Deiminase Operon Is Responsible for a Fitness Trade-Off in Extended-Spectrum-β-Lactamase-Producing Strains of Escherichia coli.

Author

Billard-Pomares T, Clermont O, Castellanos M, Magdoud F, Royer G, Condamine B, Fouteau S, Barbe V, Roche D, Cruveiller S, Médigue C, Pognard D, Glodt J, Dion S, Rigal O, Picard B, Denamur E, and Branger C

Subjects
Animals, England, Escherichia coli Infections microbiology, France, Humans, Mice, Microbial Sensitivity Tests methods, Phylogeny, Plasmids genetics, Urinary Tract Infections microbiology, Escherichia coli genetics, Hydrolases genetics, Operon genetics, beta-Lactamases genetics
Abstract

We previously identified an operon involved in an arginine deiminase (ADI) pathway ( arc operon) on a CTX-M-producing plasmid from an O102-ST405 strain of Escherichia coli As the ADI pathway was shown to be involved in the virulence of various Gram-positive bacteria, we tested whether the ADI pathway could be involved in the epidemiological success of extended-spectrum-β-lactamase (ESBL)-producing E. coli strains. We studied two collections of human E. coli isolated in France ( n  = 493) and England ( n  = 1,509) and show that the prevalence of the arc operon (i) is higher in ESBL-producing strains (12.1%) than in nonproducers (2.5%), (ii) is higher in CTX-M-producing strains (16%) than in other ESBL producers (3.5%), and (iii) increased over time in ESBL-producing strains from 0% before 2000 to 43.3% in 2011 to 2012. The arc operon, found in strains from various phylogenetic backgrounds, is carried by IncF plasmids (85%) or chromosomes (15%) in regions framed by numerous insertion sequences, indicating multiple arrivals. Competition experiments showed that the arc operon enhances fitness of the strain in vitro in lysogeny broth with arginine. In vivo competition experiments showed that the arc operon is advantageous for the strain in a mouse model of urinary tract infection (UTI), whereas it is a burden in a mouse model of intestinal colonization. In summary, we have identified a trait linked to CTX-M-producing strains that is responsible for a trade-off between two main E. coli lifestyles, UTI and gut commensalism. This trait alone cannot explain the wide spread of ESBLs in E. coli but merits epidemiological surveillance., (Copyright © 2019 American Society for Microbiology.)

Published
2019
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41. Proposition of a safe Mycobacterium tuberculosis complex denaturation method that does not compromise the integrity of DNA for whole-genome sequencing.

Author

Billard-Pomares T, Bleibtreu A, Walewski V, Dziri S, Barbat A, Zahar JR, Cruaud P, and Carbonnelle E

Subjects
Bacteriological Techniques, Chloroform pharmacology, Ethanol pharmacology, Humans, Laboratory Infection prevention & control, Mycobacterium tuberculosis drug effects, Specimen Handling methods, DNA, Bacterial analysis, Microbial Viability drug effects, Mycobacterium tuberculosis genetics, Safety Management methods, Tuberculosis microbiology, Whole Genome Sequencing methods
Abstract

Whole-genome sequencing plays now a leading role in epidemiologic studies of tuberculosis. DNA extraction of Mycobacterium tuberculosis complex (MTBC) requires complete inactivation of the strains, to be handled for further molecular procedures. In this study we compared two chloroform-based denaturation methods (one with a step of heat killing, one without) to a traditional heat inactivation method. Our results showed that 40% of the strains of MTBC treated by the traditional protocol resulted in a positive culture whereas no culture was observed with the two chloroform-based protocols. The DNA extracts obtained with chloroform-based protocols preparation were successfully used for whole-genome sequencing. We recommend inactivation with our rapid and efficient denaturation method using chloroform without heat killing which met our expectations and biosecurity requirements., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Published
2019
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42. Pneumonia-Specific Escherichia coli with Distinct Phylogenetic and Virulence Profiles, France, 2012-2014.

Author

La Combe B, Clermont O, Messika J, Eveillard M, Kouatchet A, Lasocki S, Corvec S, Lakhal K, Billard-Pomares T, Fernandes R, Armand-Lefevre L, Bourdon S, Reignier J, Fihman V, de Prost N, Bador J, Goret J, Wallet F, Denamur E, and Ricard JD

Subjects
Anti-Bacterial Agents pharmacology, Drug Resistance, Bacterial, Escherichia coli drug effects, Escherichia coli pathogenicity, Escherichia coli Infections history, France epidemiology, Genes, Bacterial, History, 21st Century, Humans, Microbial Sensitivity Tests, Molecular Typing, Pneumonia, Bacterial history, Public Health Surveillance, Serogroup, Virulence Factors genetics, Escherichia coli classification, Escherichia coli genetics, Escherichia coli Infections epidemiology, Escherichia coli Infections microbiology, Phylogeny, Pneumonia, Bacterial epidemiology, Pneumonia, Bacterial microbiology, Virulence genetics
Abstract

In a prospective, nationwide study in France of Escherichia coli responsible for pneumonia in patients receiving mechanical ventilation, we determined E. coli antimicrobial susceptibility, phylotype, O-type, and virulence factor gene content. We compared 260 isolates with those of 2 published collections containing commensal and bacteremia isolates. The preponderant phylogenetic group was B2 (59.6%), and the predominant sequence type complex (STc) was STc73. STc127 and STc141 were overrepresented and STc95 underrepresented in pneumonia isolates compared with bacteremia isolates. Pneumonia isolates carried higher proportions of virulence genes sfa/foc, papGIII, hlyC, cnf1, and iroN compared with bacteremia isolates. Virulence factor gene content and antimicrobial drug resistance were higher in pneumonia than in commensal isolates. Genomic and phylogenetic characteristics of E. coli pneumonia isolates from critically ill patients indicate that they belong to the extraintestinal pathogenic E. coli pathovar but have distinguishable lung-specific traits.

Published
2019
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43. Oropharyngeal Bacterial Colonization after Chlorhexidine Mouthwash in Mechanically Ventilated Critically Ill Patients.

Author

La Combe B, Mahérault AC, Messika J, Billard-Pomares T, Branger C, Landraud L, Dreyfuss D, Dib F, Massias L, and Ricard JD

Subjects
Aged, Anti-Infective Agents, Local analysis, Anti-Infective Agents, Local pharmacology, Chlorhexidine analysis, Chlorhexidine pharmacology, Colony Count, Microbial, Critical Care, Enterobacteriaceae drug effects, Female, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Pneumonia, Ventilator-Associated microbiology, Pneumonia, Ventilator-Associated prevention & control, Prospective Studies, Saliva chemistry, Streptococcus drug effects, Anti-Infective Agents, Local therapeutic use, Bacteria drug effects, Chlorhexidine therapeutic use, Critical Illness, Mouthwashes therapeutic use, Oropharynx microbiology, Respiration, Artificial
Abstract

What We Already Know About This Topic: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Oropharyngeal care with chlorhexidine to prevent ventilator-associated pneumonia is currently questioned, and exhaustive microbiologic data assessing its efficacy are lacking. The authors therefore aimed to study the effect of chlorhexidine mouthwash on oropharyngeal bacterial growth, to determine chlorhexidine susceptibility of these bacteria, and to measure chlorhexidine salivary concentration after an oropharyngeal care., Methods: This observational, prospective, single-center study enrolled 30 critically ill patients under mechanical ventilation for over 48 h. Oropharyngeal contamination was assessed by swabbing the gingivobuccal sulcus immediately before applying 0.12% chlorhexidine with soaked swabs, and subsequently at 15, 60, 120, 240, and 360 min after. Bacterial growth and identification were performed, and chlorhexidine minimal inhibitory concentration of recovered pathogens was determined. Saliva was collected in 10 patients, at every timepoint, with an additional timepoint after 30 min, to measure chlorhexidine concentration., Results: Two hundred fifty bacterial samples were analyzed and identified 48 pathogens including Streptococci (27.1%) and Enterobacteriaceae (20.8%). Oropharyngeal contamination before chlorhexidine mouthwash ranged from 10 to 10 colony-forming units (CFU)/ml in the 30 patients (median contamination level: 2.5·10 CFU/ml), and remained between 8·10 (lowest) and 3·10 CFU/ml (highest count) after chlorhexidine exposure. These bacterial counts did not decrease overtime after chlorhexidine mouthwash (each minute increase in time resulted in a multiplication of bacterial count by a coefficient of 1.001, P = 0.83). Viridans group streptococci isolates had the lowest chlorhexidine minimal inhibitory concentration (4 [4 to 8] mg/l); Enterobacteriaceae isolates had the highest ones (32 [16 to 32] mg/l). Chlorhexidine salivary concentration rapidly decreased, reaching 7.6 [1.8 to 31] mg/l as early as 60 min after mouthwash., Conclusions: Chlorhexidine oropharyngeal care does not seem to reduce bacterial oropharyngeal colonization in critically ill ventilated patients. Variable chlorhexidine minimal inhibitory concentrations along with low chlorhexidine salivary concentrations after mouthwash could explain this ineffectiveness, and thus question the use of chlorhexidine for ventilator-associated pneumonia prevention.

Published
2018
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44. Extended-spectrum β-lactamase-encoding genes are spreading on a wide range of Escherichia coli plasmids existing prior to the use of third-generation cephalosporins.

Author

Branger C, Ledda A, Billard-Pomares T, Doublet B, Fouteau S, Barbe V, Roche D, Cruveiller S, Médigue C, Castellanos M, Decré D, Drieux-Rouze L, Clermont O, Glodt J, Tenaillon O, Cloeckaert A, Arlet G, and Denamur E

Subjects
Animals, Anti-Bacterial Agents therapeutic use, Cephalosporins therapeutic use, Cluster Analysis, Escherichia coli classification, Escherichia coli enzymology, Escherichia coli isolation & purification, Genes, Bacterial, Humans, Phylogeny, Plasmids classification, Sequence Analysis, DNA, Escherichia coli genetics, Plasmids genetics, beta-Lactamases genetics
Abstract

To understand the evolutionary dynamics of extended-spectrum β-lactamase (ESBL)-encoding genes in Escherichia coli, we undertook a comparative genomic analysis of 116 whole plasmid sequences of human or animal origin isolated over a period spanning before and after the use of third-generation cephalosporins (3GCs) using a gene-sharing network approach. The plasmids included 82 conjugative, 22 mobilizable and 9 non-transferable plasmids and 3 P-like bacteriophages. ESBL-encoding genes were found on 64 conjugative, 6 mobilizable, 2 non-transferable plasmids and 2 P1-like bacteriophages, indicating that these last three types of mobile elements also play a role, albeit modest, in the diffusion of the ESBLs. The network analysis showed that the plasmids clustered according to their genome backbone type, but not by origin or period of isolation or by antibiotic-resistance type, including type of ESBL-encoding gene. There was no association between the type of plasmid and the phylogenetic history of the parental strains. Finer scale analysis of the more abundant clusters IncF and IncI1 showed that ESBL-encoding plasmids and plasmids isolated before the use of 3GCs had the same diversity and phylogenetic history, and that acquisition of ESBL-encoding genes had occurred during multiple independent events. Moreover, the blaCTX-M-15 gene, unlike other CTX-M genes, was inserted at a hot spot in a blaTEM-1-Tn2 transposon. These findings showed that ESBL-encoding genes have arrived on wide range of pre-existing plasmids and that the successful spread of blaCTX-M-15 seems to be favoured by the presence of well-adapted IncF plasmids that carry a Tn2-blaTEM-1 transposon.

Published
2018
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45. Decreased susceptibility to chlorhexidine affects a quarter of Escherichia coli isolates responsible for pneumonia in ICU patients.

Author

La Combe B, Bleibtreu A, Messika J, Fernandes R, Clermont O, Branger C, Billard-Pomares T, Barnaud G, Magdoud F, Eveillard M, Kouatchet A, Lasocki S, Asfar P, Corvec S, Lakhal K, Armand-Lefevre L, Wolff M, Timsit JF, Bourdon S, Reignier J, Martin S, Fihman V, de Prost N, Bador J, Charles PE, Goret J, Boyer A, Wallet F, Jaillette E, Nseir S, Landraud L, Ruimy R, Danin PE, Dellamonica J, Cremniter J, Frat JP, Jauréguy F, Clec'h C, Decré D, Maury E, Dreyfuss D, Denamur E, and Ricard JD

Subjects
Humans, Intensive Care Units, Microbial Sensitivity Tests, Anti-Bacterial Agents pharmacology, Chlorhexidine pharmacology, Drug Resistance, Bacterial, Escherichia coli drug effects, Pneumonia drug therapy, Pneumonia microbiology
Published
2018
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46. Diagnosis in France of a Non-Toxigenic tox Gene-Bearing Strain of Corynebacterium diphtheriae in a Young Male Back From Senegal.

Author

Billard-Pomares T, Rouyer C, Walewski V, Badell-Ocando E, Dumas M, Zumelzu C, Jaureguy F, Brisse S, Caux F, Bouchaud O, and Carbonnelle E

Abstract

Cutaneous diphtheria is uncommon in Europe. In this study, we report a case of imported cutaneous infection due to a non-toxigenic but tox gene-bearing (NTTB) strain of Corynebacterium diphtheriae . The NTTB strains are recognized as emerging pathogens across Europe, and physicians and bacteriologists should be aware of the circulation of these strains.

Published
2017
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47. Fatal transfusion-transmitted infection due to Citrobacter koseri.

Author

Hauser L, Menasie S, Bonacorsi S, Raoult L, AitOubelli N, Belloy M, Avran D, Beyloune A, Simonet M, Billard-Pomares T, Pangon B, and Bierling P

Abstract

Background: Transfusion-transmitted bacterial infection (TTBI) is still one of the most feared complications of blood transfusion., Case Report: We report a fatal case involving an 8-year-old child with congenital dyskeratosis complicated by severe aplastic anemia who was regularly transfused with platelet (PLT) concentrates for 5 years. The patient received an apheresis PLT concentrate (APC) on Day 0 due to thrombocytopenia complicated by mucocutaneous hemorrhage. Thirty minutes after the start of the transfusion, bradycardia and dyspnea appeared, quickly followed by chills, nausea, vomiting, headache, and hyperthermia. TTBI was suspected and the patient was immediately treated with intravascular antibiotherapy. On Day 3, the patient developed severe acute respiratory distress syndrome leading to death on Day 7. Patient blood cultures and APC cultures were both positive for Citrobacter koseri., Results: The donor was a 19-year-old woman. She had previously given blood. No infectious symptom was reported during the medical interviews before and after the donation and no postdonation information was received. On the day of the donation (Day -2), her white blood cell count was 5.83 × 10 9 /L. She came back on Day 8 to undergo additional tests. The cultures from blood, stool, urine, the skin of the inside of the elbow at the point of needle insertion, and ear samples were all negative for C. koseri. However, a nasal sample was positive for C. koseri., Conclusion: The isolates from the donor's blood cultures, the APC bag, the attached tube, and the donor's nasal sample all gave identical profiles; they were thus identified as the same strain and the TTBI was confirmed., (© 2016 AABB.)

Published
2016
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48. Five-year trends for ventilator-associated pneumonia: Correlation between microbiological findings and antimicrobial drug consumption.

Author

Fihman V, Messika J, Hajage D, Tournier V, Gaudry S, Magdoud F, Barnaud G, Billard-Pomares T, Branger C, Dreyfuss D, and Ricard JD

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Bacterial Infections epidemiology, Cohort Studies, Drug Utilization, Enterobacteriaceae isolation & purification, Female, Humans, Intensive Care Units, Male, Middle Aged, Pneumonia, Ventilator-Associated microbiology, Pseudomonas aeruginosa isolation & purification, Retrospective Studies, Staphylococcus aureus isolation & purification, Young Adult, Anti-Bacterial Agents therapeutic use, Bacterial Infections microbiology, Drug Resistance, Bacterial, Enterobacteriaceae drug effects, Pneumonia, Ventilator-Associated epidemiology, Pseudomonas aeruginosa drug effects, Staphylococcus aureus drug effects
Abstract

The epidemiology of multidrug-resistant bacteria (MDRB) has changed significantly in European healthcare settings, with a decrease in frequency of meticillin-resistant Staphylococcus aureus and an increase in extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Little is known about the effects of these changes on ventilator-associated pneumonia (VAP). A retrospective 5-year trend analysis of ICU antibiotic consumption and resistance in bacteria causing VAP was undertaken. Poisson regression analysis between complete microbiological data and antibiotic consumption was performed. In total, 252 episodes of VAP in 184 patients were identified between 2007 and 2011, from which 364 causal bacteria were isolated. Enterobacteriaceae isolation rates increased significantly over this period [from 6.64 to 10.52 isolates/1000 patient-days; P=0.006], mostly due to an increase in AmpC-producing Enterobacteriaceae (APE) (2.85-4.51 isolates/1000 patient-days; P=0.013), whereas the number of episodes due to S. aureus and Pseudomonas aeruginosa remained stable. A positive association was found between the increase in APE infections and an increase in past-year antibiotic consumption: amoxicillin/clavulanic acid (P=0.003), ceftazidime and cefepime (P=0.007), carbapenems (P=0.002), fluoroquinolones (P=0.012), macrolides (P=0.002) and imidazoles (P=0.004). No such association was found for the emergence of resistance in P. aeruginosa. These results indicate a change in the epidemiology of VAP, with Enterobacteriaceae exceeding P. aeruginosa and S. aureus. Moreover, a positive correlation was observed between antibiotic consumption and the incidence of potentially MDRB such as APE. No such correlation was found for ESBL-producing Escherichia coli and antibiotic-resistant P. aeruginosa., (Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Published
2015
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49. Characterization of a P1-like bacteriophage carrying an SHV-2 extended-spectrum β-lactamase from an Escherichia coli strain.

Author

Billard-Pomares T, Fouteau S, Jacquet ME, Roche D, Barbe V, Castellanos M, Bouet JY, Cruveiller S, Médigue C, Blanco J, Clermont O, Denamur E, and Branger C

Subjects
Base Sequence, Escherichia coli Infections drug therapy, Escherichia coli Infections microbiology, Humans, Molecular Sequence Data, Sequence Analysis, DNA, Chromosomes, Artificial, P1 Bacteriophage genetics, Escherichia coli drug effects, Escherichia coli genetics, beta-Lactamases genetics
Abstract

P1 bacteriophages lysogenize bacteria as independent plasmid-like elements. We describe here a P1-like bacteriophage, RCS47, carrying a blaSHV-2 gene, isolated from a clinical strain of Escherichia coli from phylogroup B1, and we report the prevalence of P1-like prophages in natural E. coli isolates. We found that 70% of the sequence of RCS47, a 115-kb circular molecule, was common to the reference P1 bacteriophage under GenBank accession no. AF234172.1, with the shared sequences being 99% identical. RCS47 had acquired two main foreign DNA fragments: a 9,636-bp fragment mobilized by two IS26 elements containing a blaSHV-2 gene, and an 8,544-bp fragment mobilized by two IS5 elements containing an operon encoding a dimethyl sulfoxide reductase. The reference P1 prophage plasmid replication gene belonged to the IncY incompatibility group, whereas that of RCS47 was from an unknown group. The lytic capacity of RCS47 and blaSHV-2 gene transduction, through the lysogenization of RCS47 in the recipient E. coli strains, were not demonstrated. The prevalence of P1-like prophages in various animal and human E. coli strain collections, as determined by the PCR detection of repL, the lytic replication gene, was 12.6%. No differences in the prevalences of these prophages were found between extended-spectrum β-lactamase (ESBL)-producing and non-ESBL-producing strains (P = 0.69), but this prevalence was lower in phylogroup B2 than in the other phylogroups (P = 0.008), suggesting epistatic interactions between P1 family phages and the genetic background of E. coli strains. P1-like phages are part of the mobile elements that carry antibiotic resistance. The high prevalence of P1-like prophages suggests their role may be underestimated., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Published
2014
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50. Risks of nonsteroidal antiinflammatory drugs in undiagnosed intensive care unit pneumococcal pneumonia: younger and more severely affected patients.

Author

Messika J, Sztrymf B, Bertrand F, Billard-Pomares T, Barnaud G, Branger C, Dreyfuss D, and Ricard JD

Subjects
APACHE, Adult, Age Factors, Aged, Community-Acquired Infections complications, Community-Acquired Infections drug therapy, Community-Acquired Infections mortality, Comorbidity, Contraindications, Female, Hospitalization, Humans, Inappropriate Prescribing adverse effects, Intensive Care Units, Male, Middle Aged, Noninvasive Ventilation, Pleural Effusion diagnosis, Pneumonia, Pneumococcal complications, Pneumonia, Pneumococcal mortality, Prospective Studies, Retrospective Studies, Risk, Streptococcus pneumoniae isolation & purification, Anti-Inflammatory Agents, Non-Steroidal, Pneumonia, Pneumococcal drug therapy
Abstract

Purpose: The purpose of this study is to investigate whether exposure to nonsteroidal antiinflammatory drugs (NSAIDs) at the early stage of severe pneumococcal community-acquired pneumonia (CAP) requiring intensive care unit (ICU) admission may affect its presentation and outcome., Material and Methods: Medical records of ICU adult patients (12-year period) with a pneumococcal CAP diagnosis were retrospectively analyzed according to previous NSAID exposure., Results: One hundred six confirmed pneumococcal CAP were identified, 20 received NSAIDs within 4 (2-6) days before admission. Nonsteroidal antiinflammatory drug-exposed patients were younger (43.3 vs 62.2 years; P < .0001), had less frequently at least one chronic comorbid condition (40% vs 75%; P = .003), had more often complicated pleural effusions (20% vs 2.3%; P = .01), and more frequent pleuropulmonary complications (odds ratio: 5.75 [1.97-16.76]). Nonsteroidal antiinflammatory drug patients required more often noninvasive ventilatory support (25% vs 4.6%; P = .003). Intensive care unit length of stay and mortality were similar., Conclusions: We report as severe pneumococcal pneumonia in young and healthy patients exposed to NSAIDs as in older, more comorbid, and nonexposed ones. Nonsteroidal antiinflammatory drug use may mask initial symptoms and delay antimicrobial therapy, thus predisposing to worse outcomes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Published
2014
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