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2. Immunomodulators for immunocompromised patients hospitalized for COVID-19: a meta-analysis of randomized controlled trials

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Hermine, Olivier, Mariette, Xavier, Ravaud, Philippe, Bureau, Serge, Dougados, Maxime, Resche-Rigon, Matthieu, Tharaux, Pierre-Louis, Tibi, Annick, Azoulay, Elie, Cadranel, Jacques, Emmerich, Joseph, Fartoukh, Muriel, Guidet, Bertrand, Humbert, Marc, Lacombe, Karine, Mahevas, Matthieu, Pene, Frédéric, Porcher, Raphaël, Pourchet-Martinez, Valerie, Schlemmer, Frédéric, Yazdanpanah, Yazdan, Baron, Gabriel, Perrodeau, Elodie, Vanhoye, Damien, Kedzia, Cécile, Demerville, Lauren, Gysembergh-Houal, Anne, Bourgoin, Alexandre, Raked, Nabil, Mameri, Lakhdar, Montlahuc, Claire, Biard, Lucie, Alary, St.phanie, Hamiria, Samir, Bariz, Thinhinane, Semri, Hala, Hai, Dhiaa Meriem, Benafla, Moustafa, Belloul, Mohamed, Vauboin, Pernelle, Flamand, Saskia, Pacheco, Claire, Walter-Petrich, Anouk, Stan, Emilia, Benarab, Souad, Nyanou, Corine, Charreteur, Robin, Dupre, Céline, Cardet, Kévin, Lehmann, Blandine, Baghli, Kamyl, Madelaine, Claire, D'Ortenzio, Eric, Puéchal, Oriane, Semaille, Caroline, Savale, Laurent, Harrois, Anatole, Figueiredo, Samy, Duranteau, Jacques, Anguel, Nadia, Pavot, Arthur, Monnet, Xavier, Richard, Christian, Teboul, Jean-Louis, Durand, Philippe, Tissieres, Pierre, Jevnikar, Mitja, Montani, David, Pavy, Stephan, Nocturne, Gaétane, Bitoun, Samuel, Noel, Nicolas, Lambotte, Olivier, Escaut, Lelia, Jauréguiberry, Stephane, Baudry, Elodie, Verny, Christiane, Lefevre, Edouard, Zaidan, Mohamad, Molinari, Domitille, Leprun, Gaël, Fourreau, Alain, Cylly, Laurent, Grimaldi, Lamiae, Virlouvet, Myriam, Meftali, Ramdane, Fabre, Soléne, Licois, Marion, Mamoune, Asmaa, Boudali, Yacine, Le Tiec, Clotilde, Verstuyft, Céline, Roques, Anne-Marie, Georgin-Lavialle, Sophie, Senet, Patricia, Pialoux, Gilles, Soria, Angele, Parrot, Antoine, François, Helene, Rozensztajn, Nathalie, Blin, Emmanuelle, Choinier, Pascaline, Camuset, Juliette, Rech, Jean-Simon, Canellas, Antony, Rolland-Debord, Camille, Lemarié, Nadege, Belaube, Nicolas, Nadal, Marine, Siguier, Martin, Petit-Hoang, Camille, Chas, Julie, Drouet, Elodie, Lemoine, Matthieu, Phibel, Audrey, Aunay, Lucie, Bertrand, Eliane, Ravato, Sylviane, Vayssettes, Marie, Adda, Anne, Wilpotte, Celine, Thibaut, Pélagie, Fillon, Julie, Debrix, Isabelle, Fellahi, Soraya, Bastard, Jean-Philippe, Lefévre, Guillaume, Gottenberg, Jacques-Eric, Hansmann, Yves, Blanc, Frédéric, Ohlmann-Caillard, Sophie, Castelain, Vincent, Chatelus, Emmanuel, Chatron, Eva, Collange, Olivier, Danion, François, De Blay, Frédéric, Diemunsch, Pierre, Diemunsch, Sophie, Felten, Renaud, Goichot, Bernard, Greigert, Valentin, Guffroy, Aurelien, Heger, Bob, Kaeuffer, Charlotte, Kassegne, Loic, Korganow, Anne Sophie, Le Borgne, Pierrick, Lefebvre, Nicolas, Mertes, Paul-Michel, Noll, Eric, Oberlin, Mathieu, Poindron, Vincent, Pottecher, Julien, Ruch, Yvon, Weill, François, Meyer, Nicolas, Andres, Emmanuel, Demonsant, Eric, Tayebi, Hakim, Nisand, Gabriel, Brin, Stéphane, Sublon, Cédric, Becker, Guillaume, Hutt, Anne, Martin, Tristan, Bayer, Sophie, Metzger, Catherine, Mekinian, Arsene, Abisror, Noémie, Adedjouma, Amir, Bollens, Diane, Bonneton, Marion, Bourcicaux, Nathalie, Bourrier, Anne, Thibault Chiarabiani, Maria Chauchard, Chopin, Doroth.e, Cohen, Jonathan, Devred, Ines, Donadille, Bruno, Fain, Olivier, Hariri, Geoffrey, Jachiet, Vincent, Ingliz, Patrick, Garnier, Marc, Gatfosse, Marc, Ghrenassia, Etienne, Gobert, Delphine, Krause le Garrec, Jessica, Landman, Cecilia, Lavillegrand, Jean Remy, Lefebvre, Benedicte, Mahevas, Thibault, Mazerand, Sandie, Meynard, Jean Luc, Morgand, Marjolaine, Ouaz.ne, Zineb, Pacanowski, Jerome, Riviere, S.bastien, Seksik, Philippe, Sokol, Harry, Soliman, Heithem, Valin, Nadia, Urbina, Thomas, McAvoy, Chloé, Miranda, Maria Pereira, Aratus, Gladys, Berard, Laurence, Simon, Tabassome, Nguyen, Anne Daguenel, Girault, Elise, Mayala-Kanda, Cl.mentine, Antignac, Marie, Leplay, Céline, Arlet, Jean-Benoit, Diehl, Jean-Luc, Bellenfant, Florence, Blanchard, Anne, Buffet, Alexandre, Cholley, Bernard, Fayol, Antoine, Flamarion, Edouard, Godier, Anne, Gorget, Thomas, Hamada, Sophie-Rym, Hauw-Berlemont, Caroline, Hulot, Jean-Sébastien, Lebeaux, David, Livrozet, Marine, Michon, Adrien, Neuschwander, Arthur, Pennet, Marie-Aude, Planquette, Benjamin, Ranque, Brigitte, Sanchez, Olivier, Volle, Geoffroy, Briois, Sandrine, Cornic, Mathias, Elisee, Virginie, Denis, Jesuthasan, Djadi-Prat, Juliette, Jouany, Pauline, Junquera, Ramon, Henriques, Mickael, Kebir, Amina, Lehir, Isabelle, Meunier, Jeanne, Patin, Florence, Paquet, Val.rie, Tréhan, Anne, Vigna, Véronique, Sabatier, Brigitte, Bergerot, Damien, Jouve, Charléne, Knosp, Camille, Lenoir, Olivia, Mahtal, Nassim, Resmini, Léa, Lescure, Xavier, Ghosn, Jade, Bachelard, Antoine, Rachline, Anne, Isernia, Valentina, Bao-chau, Phung, Vallois, Dorothée, Sautereau, Aurelie, Neukrich, Catherine, Dossier, Antoine, Borie, Raphaël, Crestani, Bruno, Ducrocq, Gregory, Steg, Philippe Gabriel, Dieude, Philippe, Papo, Thomas, Marcault, Estelle, Chaudhry, Marhaba, Da Silveira, Charléne, Metois, Annabelle, Mahenni, Ismahan, Meziani, Meriam, Nilusmas, Cyndie, Le Gac, Sylvie, Ndiaye, Awa, Louni, Fran.oise, Chansombat, Malikhone, Julia, Zelie, Chalal, Solaya, Chalal, Lynda, Kramer, Laura, Le Grand, Jeniffer, Ouifiya, Kafif, Piquard, Valentine, Tubiana, Sarah, Nguyen, Yann, Honsel, Vasco, Weiss, Emmanuel, Codorniu, Anais, Zarrouk, Virginie, de Lastours, Victoire, Uzzan, Matthieu, Gamany, Naura, Claveirole, Agathe, Navid, Alexandre, Fouque, Tiffanie, Cohen, Yonathan, Lupo, Maya, Gilles, Constance, Rahli, Roza, Louis, Zeina, Boutboul, David, Galicier, Lionel, Amara, Yaël, Archer, Gabrielle, Benattia, Amira, Bergeron, Anne, Bondeelle, Louise, de Castro, Nathalie, Clément, Melissa, Darmon, Michaël, Denis, Blandine, Dupin, Clairelyne, Feredj, Elsa, Feyeux, Delphine, Joseph, Adrien, Lenglin, Etienne, Le Guen, Pierre, Liégeon, Geoffroy, Lorillon, Gwenaël, Mabrouki, Asma, Mariotte, Eric, Martin de Frémont, Grégoire, Mirouse, Adrien, Molina, Jean-Michel, Peffault de Latour, Régis, Oksenhendler, Eric, Saussereau, Julien, Tazi, Abdellatif, Tudesq, Jean-Jacques, Zafrani, Lara, Brindele, Isabelle, Bugnet, Emmanuelle, Lebras, Karine Celli, Chabert, Julien, Djaghout, Lamia, Fauvaux, Catherine, Jegu, Anne Lise, Kozakiewicz, Ewa, Meunier, Martine, Tremorin, Marie-Thérèse, Davoine, Claire, Madelaine, Isabelle, Caillat-Zucman, Sophie, Delaugerre, Constance, Morin, Florence, Sène, Damien, Burlacu, Ruxandra, Chousterman, Benjamin, Mégarbanne, Bruno, Richette, Pascal, Riveline, Jean-Pierre, Frazier, Aline, Vicaut, Eric, Berton, Laure, Hadjam, Tassadit, Vazquez-Ibarra, Miguel Alejandro, Jourdaine, Clément, Tran, Olivia, Jouis, Véronique, Jacob, Aude, Smati, Julie, Renaud, Stéphane, Pernin, Claire, Suarez, Lydia, Semerano, Luca, Abad, Sébastien, nainous, Ruben B., Bonnet, Nicolas, Comparon, Celine, Cohen, Yves, Cordel, Hugues, Dhote, Robin, Dournon, Nathalie, Duchemann, Boris, Ebstein, Nathan, Gille, Thomas, Giroux-Leprieur, Benedicte, Goupil de Bouille, Jeanne, Nunes, Hilario, Oziel, Johanna, Roulot, Dominique, Sese, Lucile, ClaireTantet, Uzunhan, Yurdagul, Bloch-Queyrat, Coralie, Levy, Vincent, Messani, Fadhila, Rahaoui, Mohammed, Petit, Myléne, Brahmi, Sabrina, Rathoin, Vanessa, Rigal, Marthe, Costedoat-Chalumeau, Nathalie, Luong, Liem Binh, Hamou, Zakaria Ait, Benghanem, Sarah, Blanche, Philippe, Carlier, Nicolas, Chaigne, Benjamin, Gauzit, Remy, Joumaa, Hassan, Jozwiak, Mathieu, Lachétre, Marie, Lafoeste, Hélène, Launay, Odie, Legendre, Paul, Marey, Jonathan, Morbieu, Caroline, Palmieri, Lola-Jade, Szwebel, Tali-Anne, Abdoul, Hendy, Bruneau, Alexandra, Beclin-Clabaux, Audrey, Larrieu, Charly, Montanari, Pierre, Dufour, Eric, Clarke, Ada, Le Bourlout, Catherine, Marin, Nathalie, Menage, Nathalie, Saleh-Mghir, Samira, Cisse, Mamadou Salif, Cheref, Kahina, Guerin, Corinne, Zerbit, Jérémie, Michel, Marc, Gallien, Sébastien, Crickx, Etienne, Le Vavasseur, Benjamin, Kempf, Emmanuelle, Jaffal, Karim, Vindrios, William, Oniszczuk, Julie, Guillaud, Constance, Lim, Pascal, Fois, Elena, Melica, Giovanna, Matignon, Marie, Jalabert, Maud, Lelièvre, Jean-Daniel, Schmitz, David, Bourhis, Marion, Belazouz, Sylia, Languille, Laetitia, Boucle, Caroline, Cita, Nelly, Didier, Agnés, Froura, Fahem, Ledudal, Katia, Sadaoui, Thiziri, Thiemele, Alaki, Le Febvre De Bailly, Delphine, Verlinde, Muriel Carvhalo, Mayaux, Julien, Cacoub, Patrice, Saadoun, David, Vautier, Mathieu, Bugaut, Héléne, Benveniste, Olivier, Allenbach, Yves, Leroux, Gaëlle, Rigolet, Aude, Guillaume-Jugnot, Perrine, Domont, Fanny, Desbois, Anne Claire, Comarmond, Chloé, Champtiaux, Nicolas, Toquet, Segolene, Ghembaza, Amine, Vieira, Matheus, Maalouf, Georgina, Boleto, Goncalo, Ferfar, Yasmina, Corvol, Jean-Christophe, Louapre, C.line, Sambin, Sara, Mariani, Louise-Laure, Karachi, Carine, Tubach, Florence, Estellat, Candice, Gimeno, Linda, Martin, Karine, Bah, Aicha, Keo, Vixra, Ouamri, Sabrine, Messaoudi, Yasmine, Yelles, Nessima, Faye, Pierre, Cavelot, Sebastien, Larcheveque, Cecile, Annonay, Laurence, Benhida, Jaouad, Zahrate-Ghoul, Aida, Hammal, Soumeya, Belilita, Ridha, Charbonnier, Fanny, Aguilar, Claire, Alby-Laurent, Fanny, Burger, Carole, Campos-Vega, Clara, Chavarot, Nathalie, Fournier, Benjamin, Rouzaud, Claire, Vimpére, Damien, Elie, Caroline, Bakouboula, Prissile, Choupeaux, Laure, Granville, Sophie, Issorat, Elodie, Broissand, Christine, Alyanakian, Marie-Alexandra, Geri, Guillaume, Derridj, Nawal, Sguiouar, Naima, Meddah, Hakim, Djadel, Mourad, Chambrin-Lauvray, Héléne, Duclos-vallée, Jean-Charles, Saliba, Faouzi, Sacleux, Sophie-Caroline, Kounis, Ilias, Tamazirt, Sonia, Rudant, Eric, Michot, Jean-Marie, Stoclin, Annabelle, Colomba, Emeline, Pommeret, Fanny, Willekens, Christophe, Da Silva, Rosa, Dejean, Valérie, Mekid, Yasmina, Ben-Mabrouk, Ines, Netzer, Florence, Pradon, Caroline, Drouard, Laurence, Camara-Clayette, Valérie, Morel, Alexandre, Garcia, Gilles, Mohebbi, Abolfazl, Berbour, Férial, Dehais, Mélanie, Pouliquen, Anne-Lise, Klasen, Alison, Soyez-Herkert, Loren, London, Jonathan, Keroumi, Younes, Guillot, Emmanuelle, Grailles, Guillaume, El amine, Younes, Defrancq, Fanny, Fodil, Hanane, Bouras, Chaouki, Dautel, Dominique, Gambier, Nicolas, Dieye, Thierno, Bienvenu, Boris, Lancon, Victor, Lecomte, Laurence, Beziriganyan, Kristina, Asselate, Belkacem, Allanic, Laure, Kiouris, Elena, Legros, Marie-Héléne, Lemagner, Christine, Martel, Pascal, Provitolo, Vincent, Ackermann, Félix, Le Marchand, Mathilde, Chan Hew Wai, Aurélie, Fremont, Dimitri, Coupez, Elisabeth, Adda, Mireille, Duée, Frédéric, Bernard, Lise, Gros, Antoine, Henry, Estelle, Courtin, Claire, Pattyn, Anne, Guinot, Pierre-Grégoire, Bardou, Marc, Maurer, Agnes, Jambon, Julie, Cransac, Amélie, Pernot, Corinne, Mourvillier, Bruno, Marquis, Eric, Benoit, Philippe, Roux, Damien, Gernez, Coralie, Yelnik, Cécile, Poissy, Julien, Nizard, Mandy, Denies, Fanette, Gros, Helene, Mourad, Jean-Jacques, Sacco, Emmanuelle, Renet, Sophie, Ader, F., Yazdanpanah, Y., Mentre, F., Peiffer-Smadja, N., Lescure, F.X., Poissy, J., Bouadma, L., Timsit, J.F., Lina, B., Morfin-Sherpa, F., Bouscambert, M., Gaymard, A., Peytavin, G., Abel, L., Guedj, J., Andrejak, C., Burdet, C., Laouenan, C., Belhadi, D., Dupont, A., Alfaiate, T., Basli, B., Chair, A., Laribi, S., Level, J., Schneider, M., Tellier, M.C., Dechanet, A., Costagliola, D., Terrier, B., Ohana, M., Couffin-Cadiergues, S., Esperou, H., Delmas, C., Saillard, J., Fougerou, C., Moinot, L., Wittkop, L., Cagnot, C., Le Mestre, S., Lebrasseur-Longuet, D., Petrov-Sanchez, V., Diallo, A., Mercier, N., Icard, V., Leveau, B., Tubiana, S., Hamze, B., Gelley, A., Noret, M., D’Ortenzio, E., Puechal, O., Semaille, C., Welte, T., Paiva, J.A., Halanova, M., Kieny, M.P., Balssa, E., Birkle, C., Gibowski, S., Landry, E., Le Goff, A., Moachon, L., Moins, C., Wadouachi, L., Paul, C., Levier, A., Bougon, D., Djossou, F., Epelboin, L., Dellamonica, J., Marquette, C.H., Robert, C., Gibot, S., Senneville, E., Jean-Michel, V., Zerbib, Y., Chirouze, C., Boyer, A., Cazanave, C., Gruson, D., Malvy, D., Andreu, P., Quenot, J.P., Terzi, N., Faure, K., Chabartier, C., Le Moing, V., Klouche, K., Ferry, T., F, Valour, Gaborit, B., Canet, E., Le Turnier, P., Boutoille, D., Bani-Sadr, F., Benezit, F., Revest, M., Cameli, C., Caro, A., Um Tegue, MJ Ngo, Le Tulzo, Y., Laviolle, B., Laine, F., Thiery, G., Meziani, F., Hansmann, Y., Oulehri, W., Tacquard, C., Vardon-Bounes, F., Riu-Poulenc, B., Murris-Espin, M., Bernard, L., Garot, D., Hinschberger, O., Martinot, M., Bruel, C., Pilmis, B., Bouchaud, O., Loubet, P., Roger, C., Monnet, X., Figueiredo, S., Godard, V., Mira, J.P., Lachatre, M., Kerneis, S., Aboab, J., Sayre, N., Crockett, F., Lebeaux, D., Buffet, A., Diehl, J.L., Fayol, A., Hulot, J.S., Livrozet, M., Dessap, A Mekontso, Ficko, C., Stefan, F., Le Pavec, J., Mayaux, J., Ait-Oufella, H., Molina, J.M., Pialoux, G., Fartoukh, M., Textoris, J., Brossard, M., Essat, A., Netzer, E., Riault, Y., Ghislain, M., Beniguel, L., Genin, M., Gouichiche, L., Betard, C., Belkhir, L., Altdorfer, A., Centro, V Fraipont, Braz, S., Ribeiro, JM Ferreira, Alburqueque, R Roncon, Berna, M., Alexandre, M., Lamprecht, B., Egle, A., Greil, R., Joannidis, M., Patterson, Thomas F., Ponce, Philip O., Taylor, Barbara S., Patterson, Jan E., Bowling, Jason E., Javeri, Heta, Kalil, Andre C., Larson, LuAnn, Hewlett, Angela, Mehta, Aneesh K., Rouphael, Nadine G., Saklawi, Youssef, Scanlon, Nicholas, Traenkner, Jessica J., Trible, Ronald P., Jr., Walter, Emmanuel B., Ivey, Noel, Holland, Thomas L., Ruiz-Palacios, Guillermo M., Ponce de León, Alfredo, Rajme, Sandra, Hsieh, Lanny, Amin, Alpesh N., Watanabe, Miki, Lee, Helen S., Kline, Susan, Billings, Joanne, Noren, Brooke, Kim, Hyun, Bold, Tyler D., Tapson, Victor, Grein, Jonathan, Sutterwala, Fayyaz, Iovine, Nicole, Beattie, Lars K., Wakeman, Rebecca Murray, Shaw, Matthew, Jain, Mamta K., Mocherla, Satish, Meisner, Jessica, Luque, Amneris, Sweeney, Daniel A., Benson, Constance A., Ali, Farhana, Atmar, Robert L., El Sahly, Hana M., Whitaker, Jennifer, Falsey, Ann R., Branche, Angela R., Rozario, Cheryl, Pineda, Justino Regalado, Martinez-Orozco, José Arturo, Lye, David Chien, Ong, Sean WX., Chia, Po Ying, Young, Barnaby E., Sandkovsky, Uriel, Berhe, Mezgebe, Haley, Clinton, Dishner, Emma, Cantos, Valeria D., Kelley, Colleen F., Rebolledo Esteinou, Paulina A., Kandiah, Sheetal, Doernberg, Sarah B., Crouch, Pierre-Cedric B., Jang, Hannah, Luetkemeyer, Anne F., Dwyer, Jay, Cohen, Stuart H., Thompson, George R., 3rd, Nguyen, Hien H., Finberg, Robert W., Wang, Jennifer P., Perez-Velazquez, Juan, Wessolossky, Mireya, Jackson, Patrick E.H., Bell, Taison D., West, Miranda J., Taiwo, Babafemi, Krueger, Karen, Perez, Johnny, Pearson, Triniece, Paules, Catharine I., Julian, Kathleen G., Ahmad, Danish, Hajduczok, Alexander G., Arguinchona, Henry, Arguinchona, Christa, Erdmann, Nathaniel, Goepfert, Paul, Ahuja, Neera, Frank, Maria G., Wyles, David, Young, Heather, Oh, Myoung-don, Park, Wan Beom, Kang, Chang Kyung, Marconi, Vincent, Moanna, Abeer, Cribbs, Sushma, Harrison, Telisha, Kim, Eu Suk, Jung, Jongtak, Song, Kyoung-Ho, Kim, Hong Bin, Tan, Seow Yen, Shafi, Humaira, Chien, Jaime, Fong, Raymond KC., Murray, Daniel D., Lundgren, Jens, Nielsen, Henrik, Jensen, Tomas, Zingman, Barry S., Grossberg, Robert, Riska, Paul F., Yang, Otto O., Ahn, Jenny, Arias, Rubi, Rapaka, Rekha R., Hauser, Naomi, Campbell, James D., Short, William R., Tebas, Pablo, Baron, Jillian T., McLellan, Susan L.F., Blanton, Lucas S., Seashore, Justin B., Creech, C. Buddy, Rice, Todd W., Walker, Shannon, Thomsen, Isaac P., Lopez de Castilla, Diego, Van Winkle, Jason W., Riedo, Francis X., Pada, Surinder Kaur, Wang, Alvin DY., Lin, Li, Harkins, Michelle, Mertz, Gregory, Sosa, Nestor, Ann Chai, Louis Yi, Tambyah, Paul Anantharajah, Tham, Sai Meng, Archuleta, Sophia, Yan, Gabriel, Lindholm, David A., Markelz, Ana Elizabeth, Mende, Katrin, Mularski, Richard, Hohmann, Elizabeth, Torres-Soto, Mariam, Jilg, Nikolaus, Maves, Ryan C., Utz, Gregory C., George, Sarah L., Hoft, Daniel F., Brien, James D., Paredes, Roger, Mateu, Lourdes, Loste, Cora, Kumar, Princy, Thornton, Sarah, Mohanraj, Sharmila, Hynes, Noreen A., Sauer, Lauren M., Colombo, Christopher J., Schofield, Christina, Colombo, Rhonda E., Chambers, Susan E., Novak, Richard M., Wendrow, Andrea, Gupta, Samir K., Lee, Tida, Lalani, Tahaniyat, Holodniy, Mark, Chary, Aarthi, Huprikar, Nikhil, Ganesan, Anuradha, Ohmagari, Norio, Mikami, Ayako, Price, D. Ashley, Duncan, Christopher J.A., Dierberg, Kerry, Neumann, Henry J., Taylor, Stephanie N., Lacour, Alisha, Masri, Najy, Swiatlo, Edwin, Widmer, Kyle, Neaton, James D., Bessesen, Mary, Stephens, David S., Burgess, Timothy H., Uyeki, Timothy M., Walker, Robert, Marks, G. Lynn, Osinusi, Anu, Cao, Huyen, Cardoso, Anabela, de Bono, Stephanie, Schlichting, Douglas E., Chung, Kevin K., Ferreira, Jennifer L., Green, Michelle, Makowski, Mat, Wierzbicki, Michael R., Conrad, Tom M., El-Khorazaty, Jill Ann, Hill, Heather, Bonnett, Tyler, Gettinger, Nikki, Engel, Theresa, Lewis, Teri, Wang, Jing, Beigel, John H., Tomashek, Kay M., Ghazaryan, Varduhi, Beresnev, Tatiana, Nayak, Seema, Dodd, Lori E., Dempsey, Walla, Nomicos, Effie, Lee, Marina, Pikaart-Tautges, Rhonda, Elsafy, Mohamed, Jurao, Robert, Koo, Hyung, Proschan, Michael, Yokum, Tammy, Arega, Janice, Florese, Ruth, Voell, Jocelyn D., Davey, Richard, Serrano, Ruth C., Wiley, Zanthia, Phadke, Varun K., Goepfert, Paul A., Gomez, Carlos A., Sofarelli, Theresa A., Certain, Laura, Imlay, Hannah N., Wolfe, Cameron R., Ko, Emily R., Engemann, John J., Felix, Nora Bautista, Wan, Claire R., Elmor, Sammy T., Bristow, Laurel R., Harkins, Michelle S., Iovine, Nicole M., Elie-Turenne, Marie-Carmelle, Tapson, Victor F., Choe, Pyoeng Gyun, Mularski, Richard A., Rhie, Kevin S., Hussein, Rezhan H., Ince, Dilek, Winokur, Patricia L., Takasaki, Jin, Saito, Sho, McConnell, Kimberly, Wyles, David L., Sarcone, Ellen, Grimes, Kevin A., Perez, Katherine, Janak, Charles, Whitaker, Jennifer A., Rebolledo, Paulina A., Gharbin, John, Lambert, Allison A., Zea, Diego F., Bainbridge, Emma, Hostler, David C., Hostler, Jordanna M., Shahan, Brian T., Ling, Evelyn, Go, Minjoung, Hubbard, Fleesie A., Chakrabarty, Melony, Laguio-Vila, Maryrose, Walsh, Edward E., Guirgis, Faheem, Marconi, Vincent C., Madar, Christian, Borgetti, Scott A., Levine, Corri, Nock, Joy, Candiotti, Keith, Rozman, Julia, Dangond, Fernando, Hyvert, Yann, Seitzinger, Andrea, Cross, Kaitlyn, Pettibone, Stephanie, Nayak, Seema U., Deye, Gregory A., Siempos, Ilias I., Belhadi, Drifa, Veiga, Viviane Cordeiro, Cavalcanti, Alexandre Biasi, Branch-Elliman, Westyn, Papoutsi, Eleni, Gkirgkiris, Konstantinos, Xixi, Nikoleta A., and Kotanidou, Anastasia

Published
2024
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3. Normalization of eosinophil count is predictive of oxygen weaning over the course of COVID-19 infection among hospitalized adults during the first wave of 2020 pandemic

Author

Benjamin Davido, Karim Jaffal, Azzam Saleh-Mghir, Isabelle Vaugier, Stephane Bourlet, Pierre De Truchis, and Djillali Annane

Subjects
eosinophil count, COVID-19, normalization, oxygen, eosinopenia, oxygen weaning, Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundUnderstanding COVID-19 outcomes remains a challenge. While numerous biomarkers have been proposed for severity at admission, limited exploration exists for markers during the infection course, especially for the requirement of oxygen therapy. This study investigates the potential of eosinophil count normalization as a predictor for oxygen weaning during the initial wave of the pandemic.MethodsA retrospective study was conducted between March and April 2020 (first wave) among adults admitted directly to a medicine ward. Biological abnormalities, including lymphocyte count, eosinophil count, and C-reactive protein (CRP), were gathered daily during the first week of admission according to oxygen level. In case of worsening, oxygen level was censored at 15 L/min. The primary aim was to assess whether eosinophil count normalization predicts a subsequent decrease in oxygen requirements.ResultsOverall, 132 patients were admitted, with a mean age of 59.0 ± 16.3 years. Of the patients, 72% required oxygen, and 20.5% were admitted to the intensive care unit after a median delay of 48 hours. The median CRP at admission was 79 (26–130) mg/L, whereas the eosinophil count was 10 (0–60)/mm3. Eosinophil count normalization (≥100/mm3) by day 2 correlated significantly with decreased oxygen needs (

Published
2024
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4. Efficacy of Expired Antibiotics: A Real Debate in the Context of Repeated Drug Shortages

Author

Benjamin Davido, Hugues Michelon, Christel Mamona, Pierre de Truchis, Karim Jaffal, and Azzam Saleh-Mghir

Subjects
expired drugs, expiry date, antibiotic shortages, Therapeutics. Pharmacology, RM1-950
Abstract

This narrative review aims to discuss the main interest in and cautions associated with the use of expired antibiotics in the context of repeated shortages, notably in Europe. Articles concerning the topic of expiry dates related to antibiotic use were reviewed using keywords in the PubMed®/MEDLINE and Google Scholar databases to identify the most extensive evidence-based documentation. The present review evaluates the potential interest and efficacy of using expired drugs and their possible related adverse events. Overall, in the context of drug shortages, expiry dates could be safely extended for at least one year for most solid antibiotics (tablets or powder) used in daily clinical practice, as long as they are stored under the right conditions, in accordance with the summary of product characteristics.

Published
2024
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6. Sarilumab in adults hospitalised with moderate-to-severe COVID-19 pneumonia (CORIMUNO-SARI-1): An open-label randomised controlled trial

Author

Mariette, Xavier, Hermine, Olivier, Tharaux, Pierre-Louis, Resche-Rigon, Matthieu, Porcher, Raphael, Ravaud, Philippe, Bureau, Serge, Dougados, Maxime, Tibi, Annick, Azoulay, Elie, Cadranel, Jacques, Emmerich, Joseph, Fartoukh, Muriel, Guidet, Bertrand, Humbert, Marc, Lacombe, Karine, Mahevas, Matthieu, Pene, Frédéric, Pourchet-Martinez, Valérie, Schlemmer, Frédéric, Yazdanpanah, Yazdan, Baron, Gabriel, Perrodeau, Elodie, Vanhoye, Damien, Kedzia, Cécile, Demerville, Lauren, Gysembergh-Houal, Anne, Bourgoin, Alexandre, Dalibey, Sarah, Raked, Nabil, Mameri, Lakhdar, Alary, Stéphanie, Hamiria, Samir, Bariz, Thinhinane, Semri, Hala, Hai, Dhiaa Meriem, Benafla, Moustafa, Belloul, Mohamed, Vauboin, Pernelle, Flamand, Saskia, Pacheco, Claire, Walter-Petrich, Anouk, Stan, Emilia, Benarab, Souad, Nyanou, Corine, Montlahuc, Claire, Biard, Lucie, Charreteur, Robin, Dupré, Celine, Cardet, Kévin, Lehmann, Blandine, Baghli, Kamyl, Madelaine, Claire, D'Ortenzio, Eric, Puéchal, Oriane, Semaille, Caroline, Savale, Laurent, Harrois, Anatole, Figueiredo, Samy, Duranteau, Jacques, Anguel, Nadia, Pavot, Arthur, Monnet, Xavier, Richard, Christian, Teboul, Jean-Louis, Durand, Philippe, Tissieres, Pierre, Jevnikar, Mitja, Montani, David, Bulifon, Sophie, Jaïs, Xavier, Sitbon, Olivier, Pavy, Stéphan, Noel, Nicolas, Lambotte, Olivier, Escaut, Lelia, Jauréguiberry, Stéphane, Baudry, Elodie, Verny, Christiane, Noaillon, Mathilde, Lefèvre, Edouard, Zaidan, Mohamad, Le Tiec, Clotilde Le Tiec, Verstuyft, Céline, Roques, Anne-Marie, Grimaldi, Lamiae, Molinari, Domitille, Leprun, Gaël, Fourreau, Alain, Cylly, Laurent, Virlouvet, Myriam, Meftali, Ramdane, Fabre, Solène, Licois, Marion, Mamoune, Asmaa, Boudali, Yacine, Georgin-Lavialle, Sophie, Senet, Patricia, Pialoux, Gilles, Soria, Angèle, Parrot, Antoine, François, Hélène, Rozensztajn, Nathalie, Blin, Emmanuelle, Choinier, Pascaline, Camuset, Juliette, Rech, Jean-Simon, Canellas, Antony, Rolland-Debord, Camille, Lemarié, Nadège, Belaube, Nicolas, Nadal, Marine, Siguier, Martin, Petit-Hoang, Camille, Chas, Julie, Drouet, Elodie, Lemoine, Matthieu, Phibel, Audrey, Aunay, Lucie, Bertrand, Eliane, Ravato, Sylviane, Vayssettes, Marie, Adda, Anne, Wilpotte, Celine, Thibaut, Pélagie, Fillon, Julie, Debrix, Isabelle, Fellahi, Soraya, Bastard, Jean-Philippe, Lefèvre, Guillaume, Fallet, Vincent, Gottenberg, Jacques-Eric, Hansmann, Yves, Andres, Emmanuel, Bayer, Sophie, Becker, Guillaume, Blanc, Frédéric, Brin, Stéphane, Castelain, Vincent, Chatelus, Emmanuel, Chatron, Eva, Collange, Olivier, Danion, François, De Blay, Frédéric, Demonsant, Eric, Diemunsch, Pierre, Diemunsch, Sophie, Felten, Renaud, Goichot, Bernard, Greigert, Valentin, Guffroy, Aurélien, Heger, Bob, Hutt, Anne, Kaeuffer, Charlotte, Kassegne, Loic, Korganow, Anne Sophie, Le Borgne, Pierrick, Lefebvre, Nicolas, Martin, Tristan, Mertes, Paul Michel, Metzger, Catherine, Meyer, Nicolas, Nisand, Gabriel, Noll, Eric, Oberlin, Mathieu, Ohlmann-Caillard, Sophie, Poindron, Vincent, Pottecher, Julien, Ruch, Yvon, Sublon, Cédric, Tayebi, Hakim, Weill, François, Mekinian, Arsène, Abisror, Noémie, Jachiet, Vincent, Chopin, Dorothée, Fain, Olivier, Garnier, Marc, Krause le Garrec, Jessica, Morgand, Marjolaine, Pacanowski, Jerome, Urbina, Tomas, McAvoy, Chloe, Pereira, Maria, Aratus, Gladys, Berard, Laurence, Simon, Tabassome, Daguenel-Nguyen, Anne, Antignac, Marie, Leplay, Céline, Arlet, Jean-Benoit, Diehl, Jean-Luc, Bellenfant, Florence, Blanchard, Anne, Buffet, Alexandre, Cholley, Bernard, Fayol, Antoine, Flamarion, Edouard, Godier, Anne, Gorget, Thomas, Hamada, Sophie-Rym, Hauw-Berlemont, Caroline, Hulot, Jean-Sébastien, Lebeaux, David, Livrozet, Marine, Michon, Adrien, Neuschwander, Arthur, Penet, Marie-Aude, Planquette, Benjamin, Ranque, Brigitte, Sanchez, Olivier, Volle, Geoffroy, Briois, Sandrine, Cornic, Mathias, Elisee, Virginie, Jesuthasan, Denis, Djadi-Prat, Juliette, Jouany, Pauline, Junquera, Ramon, Henriques, Mickael, Kebir, Amina, Lehir, Isabelle, Meunier, Jeanne, Patin, Florence, Paquet, Valérie, Tréhan, Anne, Vigna, Véronique, Sabatier, Brigitte, Bergerot, Damien, Jouve, Charléne, Knosp, Camille, Lenoir, Olivia, Mahtal, Nassim, Resmini, Léa, Lescure, F-Xavier, Ghosn, Jade, BACHELARD, Antoine, BIRONNE, Timothee, BORIE, Raphael, BOUNHIOL, Agathe, BOUSSARD, Catherine, CHAUFFiER, Jeanne, CHALAL, Solaya, CHALAL, Lynda, CHANSOMBAT, Malikhone, CRESPIN, Paul, CRESTANI, Bruno, DACONCEICAO, Olivia, DECONINCK, Laurene, DIEUDE, Philippe, DOSSIER, Antoine, DUBERT, Marie, DUCROCQ, Greggory, FUENTES, Axelle, GERVAIS, Anne, GILBERT, Marie, ISERNIA, Valentina, ISMAEL, Sophie, JOLY, Veronique, JULIA, Zelie, LARIVEN, Sylvie, LE GAC, Sylvie, LE PLUART, Diane, LOUNI, Francoise, NDIAYE, Awa, PAPO, Thomas, PARISEY, Marion, PHUNG, Bao, POURBAIX, Annabelle, RACHLINE, Anne, RIOUX, Christophe, SAUTEREAU, Aurelie, STEG, Gabriel, TARHINI, Hassan, VALAYER, Simon, VALLOIS, Dorothee, VERMES, Paul, VOLPE, Thomas, Nguyen, Yann, Honsel, Vasco, Weiss, Emmanuel, Codorniu, Anaïs, Zarrouk, Virginie, De Lastours, Victoire, Uzzan, Matthieu, Olivier, Olivier, Rossi, Geoffrey, Gamany, Naura, Rahli, Roza, Louis, Zeina, Boutboul, David, Galicier, Lionel, Amara, Yaël, Archer, Gabrielle, Benattia, Amira, Bergeron, Anne, Bondeelle, Louise, De Castro, Nathalie, Clément, Melissa, Darmont, Michaël, Denis, Blandine, Dupin, Clairelyne, Feredj, Elsa, Feyeux, Delphine, Joseph, Adrien, Lengliné, Etienne, Le Guen, Pierre, Liégeon, Geoffroy, Lorillon, Gwenaël, Mabrouki, Asmaa, Mariotte, Eric, Martin de Frémont, Grégoire, Mirouse, Adrien, Molina, Jean-Michel, Peffault de Latour, Régis, Oksenhendler, Eric, Saussereau, Julien, Tazi, Abdellatif, Tudesq, Jean-Jacques, Zafrani, Lara, Brindele, Isabelle, Bugnet, Emmanuelle, Celli Lebras, Karine, Chabert, Julien, Djaghout, Lalia, Fauvaux, Catherine, Jegu, Anne Lise, Kozaliewicz, Ewa, Meunier, Martine, Tremorin, Marie-Thérèse, Davoine, Claire, Madeleine, Isabelle, Caillat-Zucman, Sophie, Delaugerre, Constance, Morin, Florence, SENE, Damien, BURLACU, Ruxandra, CHOUSTERMAN, Benjamin, MEGARBANE, Bruno, RICHETTE, Pascal, RIVELINE, Jean-Pierre, FRAZIER, Aline, VICAUT, Eric, BERTON, Laure, HADJAM, Tassadit, VASQUEZ-IBARRA, Miguel Alejandro, JOURDAINE, Clément, JACOB, Aude, SMATI, Julie, RENAUD, Stéphane, MANIVET, Philippe, PERNIN, Claire, SUAREZ, Lydia, Semerano, Luca, ABAD, Sebastien, Benainous, Ruben, Bloch Queyrat, Coralie, Bonnet, Nicolas, Brahmi, Sabrina, Cailhol, johann, Cohen, Yves, Comparon, Celine, Cordel, Hugues, Dhote, Robin, Dournon, Nathalie, Duchemann, Boris, Ebstein, Nathan, Giroux-Leprieur, Benedicte, Goupil de Bouille, Jeanne, Jacolot, Anne, Nunes, Hilario, Oziel, Johanna, Rathouin, Vanessa, Rigal, Marthe, Roulot, Dominique, Tantet, Claire, Uzunhan, Yurdagul, COSTEDOAT-CHALUMEAU, Nathalie, Ait Hamou, Zakaria, Benghanem, Sarah, BLANCHE, Philippe, CANOUI, Etienne, CARLIER, Nicolas, CHAIGNE, Benjamin, CONTEJEAN, Adrien, DUNOGUE, Bertrand, DUPLAND, Pierre, DUREL - MAURISSE, Aurélie, GAUZIT, Remy, JAUBERT, Paul, Joumaa, Hassan, Jozwiak, Mathieu, KERNEIS, Solen, LACHATRE, Marie, Lafoeste, Hélène, LEGENDRE, Paul, LUONG NGUYEN, Liem Binh, MAREY, Jonathan, MORBIEU, Caroline, MOUTHON, Luc, NGUYEN, Lee, Palmieri, Lola-Jade, REGENT, Alexis, SZWEBEL, Tali-Anne, TERRIER, Benjamin, GUERIN, Corinne, ZERBIT, Jérémie, CHEREF, Kahina, CHITOUR, Kamil, CISSE, Mamadou Salif, CLARKE, Ada, CLAVERE, Gaelle, DUSANTER, Isabelle, GAUDEFROY, Caroline, JALLOULI, Moez, KOLTA, Sami, LE BOURLOUT, Catherine, MARIN, Nathalie, MENAGE, Nathalie, MOORES, Alexandre, PEIGNEY, Isabelle, PIERRON, Cédric, SALEH-MGHIR, Samira, VALLET, Mathilde, MICHEL, Marc, MELICA, Giovanna, LELIEVRE, Jean-Daniel, FOIS, Elena, LIM, Pascal, MATIGNON, Marie, GUILLAUD, Constance, THIEMELE, Alaki, SCHMITZ, David, BOUHRIS, Marion, BELAZOUZ, Syllia, LANGUILLE, Laetitia, MEKONTSO-DESSAPS, Armand, SADAOUI, Thiziri, Mayaux, Julien, Cacoub, Patrice, Corvol, Jean-Christophe, Louapre, Céline, Sambin, Sara, Mariani, Louise-Laure, Karachi, Carine, Tubach, Florence, Estellat, Candice, Gimeno, Linda, Martin, Karine, Bah, Aïcha, Keo, Vixra, Ouamri, Sabrine, Messaoudi, Yasmine, Yelles, Nessima, Faye, Pierre, Cavelot, Sébastien, Larcheveque, Cecile, Annonay, Laurence, Benhida, Jaouad, Zahrate-Ghoul, Aida, Hammal, Soumeya, Belilita, Ridha, Lecronier, Marie, Beurton, Alexandra, Haudebourg, Luc, Deleris, Robin, Le Marec, Julien, Virolle, Sara, Nemlaghi, Safaa, Bureau, Côme, Mora, Pierre, De Sarcus, Martin, Clovet, Olivier, Duceau, Baptiste, Grisot, Paul Henri, Pari, Marie hélène, Arzoine, Jérémy, Clarac, Ulrich, Faure, Morgane, Delemazure, Julie, Decavele, Maxence, Morawiec, Elise, Demoule, Alexandre, Dres, Martin, Vautier, Mathieu, Allenbach, Yves, Benveniste, Olivier, Leroux, Gaelle, Rigolet, Aude, Guillaume-Jugnot, Perrine, Domont, Fanny, Desbois, Anne Claire, Comarmond, Cloé, Champtiaux, Nicolas, Toquet, Segolene, Ghembaza, Amine, Vieira, Matheus, Maalouf, Georgina, Boleto, Gonçalo, Ferfar, Yasmina, Charbonnier, Fanny, AGUILAR, Claire, ALBY-LAURENT, Fanny, ALYANAKIAN, Marie-Alexandra, BAKOUBOULA, Prissile, BROISSAND, Christine, BURGER, Carole, CAMPOS-VEGA, Clara, CHAVAROT, Nathalie, CHOUPEAUX, Laure, FOURNIER, Benjamin, GRANVILLE, Sophie, ISSORAT, Elodie, ROUZAUD, Claire, VIMPERE, Damien, Geri, Guillaume, Derridj, Nawal, Sguiouar, Naima, Meddah, Hakim, Djadel, Mourad, Chambrin-Lauvray, Helene, Duclos-Vallée, Jean-Charles, Saliba, Faouzi, Sacleux, Sophie-Caroline, Koumis, Ilias, Michot, Jean-Marie, Stoclin, Annabelle, Colomba, Emeline, Pommeret, Fanny, Willekens, Chistophe, Sakkal, Madona, Da Silva, Rosa, Dejean, Valérie, Mekid, Yasmina, Ben-Mabrouk, Ines, Pradon, Caroline, Drouard, Laurence, Camara-Clayette, Valérie, Morel, Alexandre, Garcia, Gilles, Mohebbi, Abolfazl, Berbour, Férial, Dehais, Mélanie, Pouliquen, Anne-Lise, Klasen, Alison, Soyez-Herkert, Loren, London, Jonathan, Keroumi, Younes, Guillot, Emmanuelle, Grailles, Guillaume, El Amine, Younes, Defrancq, Fanny, Fodil, Hanane, Bouras, Chaouki, Dautel, Dominique, Gambier, Nicolas, Dieye, Thierno, Razurel, Anaïs, Bienvenu, Boris, Lancon, Victor, Lecomte, Laurence, Beziriganyan, Kristina, Asselate, Belkacem, Allanic, Laure, Kiouris, Elena, Legros, Marie-Hélène, Lemagner, Christine, Martel, Pascal, Provitolo, Vincent, Ackermann, Félix, Le Marchand, Mathilde, Clan Hew Wai, Aurélie, Fremont, Dimitri, Coupez, Elisabeth, Adda, Mireille, Duée, Frédéric, Bernard, Lise, Gros, Antoine, Henry, Estelle, Courtin, Claire, Pattyn, Anne, Guinot, Pierre-Grégoire, Bardou, Marc, Maurer, Agnes, Jambon, Julie, Cransac, Amélie, Pernot, Corinne, Mourvillier, Bruno, Servettaz, Amélie, Deslée, Gaetan, Wynckel, Alain, Benoit, Philippe, Marquis, Eric, Roux, Damien, Gernez, Coralie, Yelnik, Cécile, Poissy, Julien, Nizard, Mandy, Denies, Fanette, Gros, Hélène, Mourad, Jean-Jacques, Sacco, Emmanuelle, and Renet, Sophie

Published
2022
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7. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial

Author

Tharaux, Pierre-Louis, Pialoux, Gilles, Pavot, Arthur, Mariette, Xavier, Hermine, Olivier, Resche-Rigon, Matthieu, Porcher, Raphael, Ravaud, Philippe, Bureau, Serge, Dougados, Maxime, Tibi, Annick, Azoulay, Elie, Cadranel, Jacques, Emmerich, Joseph, Fartoukh, Muriel, Guidet, Bertrand, Humbert, Marc, Lacombe, Karine, Mahevas, Matthieu, Pene, Frédéric, Pourchet-Martinez, Valérie, Schlemmer, Frédéric, Yazdanpanah, Yazdan, Baron, Gabriel, Perrodeau, Elodie, Vanhoye, Damien, Kedzia, Cécile, Demerville, Lauren, Gysembergh-Houal, Anne, Bourgoin, Alexandre, Dalibey, Sarah, Raked, Nabil, Mameri, Lakhdar, Alary, Stéphanie, Hamiria, Samir, Bariz, Thinhinane, Semri, Hala, Hai, Dhiaa Meriem, Benafla, Moustafa, Belloul, Mohamed, Vauboin, Pernelle, Flamand, Saskia, Pacheco, Claire, Walter-Petrich, Anouk, Stan, Emilia, Benarab, Souad, Nyanou, Corine, Montlahuc, Claire, Biard, Lucie, Charreteur, Robin, Dupré, Celine, Cardet, Kévin, Lehmann, Blandine, Baghli, Kamyl, Madelaine, Claire, D'Ortenzio, Eric, Puéchal, Oriane, Semaille, Caroline, Savale, Laurent, Harrois, Anatole, Figueiredo, Samy, Duranteau, Jacques, Anguel, Nadia, Monnet, Xavier, Richard, Christian, Teboul, Jean-Louis, Durand, Philippe, Tissieres, Pierre, Jevnikar, Mitja, Montani, David, Bulifon, Sophie, Jaïs, Xavier, Sitbon, Olivier, Pavy, Stéphan, Noel, Nicolas, Lambotte, Olivier, Escaut, Lelia, Jauréguiberry, Stéphane, Baudry, Elodie, Verny, Christiane, Noaillon, Mathilde, Lefèvre, Edouard, Zaidan, Mohamad, Le Tiec, Clotilde Le Tiec, Verstuyft, Céline Verstuyft, Roques, Anne-Marie, Grimaldi, Lamiae, Molinari, Domitille, Leprun, Gaël, Fourreau, Alain, Cylly, Laurent, Virlouvet, Myriam, Meftali, Ramdane, Fabre, Solène, Licois, Marion, Mamoune, Asmaa, Boudali, Yacine, Georgin-Lavialle, Sophie, Senet, Patricia, Soria, Angèle, Parrot, Antoine, François, Hélène, Rozensztajn, Nathalie, Blin, Emmanuelle, Choinier, Pascaline, Camuset, Juliette, Rech, Jean-Simon, Canellas, Antony, Rolland-Debord, Camille, Lemarié, Nadège, Belaube, Nicolas, Nadal, Marine, Siguier, Martin, Petit-Hoang, Camille, Chas, Julie, Drouet, Elodie, Lemoine, Matthieu, Phibel, Audrey, Aunay, Lucie, Bertrand, Eliane, Ravato, Sylviane, Vayssettes, Marie, Adda, Anne, Wilpotte, Celine, Thibaut, Pélagie, Fillon, Julie, Debrix, Isabelle, Fellahi, Soraya, Bastard, Jean-Philippe, Lefèvre, Guillaume, Fallet, Vincent, Gottenberg, Jacques-Eric, Hansmann, Yves, Andres, Emmanuel, Bayer, Sophie, Becker, Guillaume, Blanc, Frédéric, Brin, Stéphane, Castelain, Vincent, Chatelus, Emmanuel, Chatron, Eva, Collange, Olivier, Danion, François, De Blay, Frédéric, Demonsant, Eric, Diemunsch, Pierre, Diemunsch, Sophie, Felten, Renaud, Goichot, Bernard, Greigert, Valentin, Guffroy, Aurélien, Heger, Bob, Hutt, Anne, Kaeuffer, Charlotte, Kassegne, Loic, Korganow, Anne Sophie, Le Borgne, Pierrick, Lefebvre, Nicolas, Martin, Tristan, Mertes, Paul Michel, Metzger, Catherine, Meyer, Nicolas, Nisand, Gabriel, Noll, Eric, Oberlin, Mathieu, Ohlmann-Caillard, Sophie, Poindron, Vincent, Pottecher, Julien, Ruch, Yvon, Sublon, Cédric, Tayebi, Hakim, Weill, François, Mekinian, Arsène, Chopin, Dorothée, Fain, Olivier, Garnier, Marc, Krause le Garrec, Jessica, Morgand, Marjolaine, Pacanowski, Jerome, Urbina, Tomas, McAvoy, Chloe, Pereira, Maria, Aratus, Gladys, Berard, Laurence, Simon, Tabassome, Daguenel-Nguyen, Anne, Antignac, Marie, Leplay, Céline, Arlet, Jean-Benoit, Diehl, Jean-Luc, Bellenfant, Florence, Blanchard, Anne, Buffet, Alexandre, Cholley, Bernard, Fayol, Antoine, Flamarion, Edouard, Godier, Anne, Gorget, Thomas, Hamada, Sophie-Rym, Hauw-Berlemont, Caroline, Hulot, Jean-Sébastien, Lebeaux, David, Livrozet, Marine, Michon, Adrien, Neuschwander, Arthur, Penet, Marie-Aude, Planquette, Benjamin, Ranque, Brigitte, Sanchez, Olivier, Volle, Geoffroy, Briois, Sandrine, Cornic, Mathias, Elisee, Virginie, Jesuthasan, Denis, Djadi-Prat, Juliette, Jouany, Pauline, Junquera, Ramon, Henriques, Mickael, Kebir, Amina, Lehir, Isabelle, Meunier, Jeanne, Patin, Florence, Paquet, Valérie, Tréhan, Anne, Vigna, Véronique, Sabatier, Brigitte, Bergerot, Damien, Jouve, Charléne, Knosp, Camille, Lenoir, Olivia, Mahtal, Nassim, Resmini, Léa, Lescure, F-Xavier, Ghosn, Jade, BACHELARD, Antoine, BIRONNE, Timothee, BORIE, Raphael, BOUNHIOL, Agathe, BOUSSARD, Catherine, CHAUFFiER, Jeanne, CHALAL, Solaya, CHALAL, Lynda, CHANSOMBAT, Malikhone, CRESPIN, Paul, CRESTANI, Bruno, DACONCEICAO, Olivia, DECONINCK, Laurene, DIEUDE, Philippe, DOSSIER, Antoine, DUBERT, Marie, DUCROCQ, Greggory, FUENTES, Axelle, GERVAIS, Anne, GILBERT, Marie, ISERNIA, Valentina, ISMAEL, Sophie, JOLY, Veronique, JULIA, Zelie, LARIVEN, Sylvie, LE GAC, Sylvie, LE PLUART, Diane, LOUNI, Francoise, NDIAYE, Awa, PAPO, Thomas, PARISEY, Marion, PHUNG, Bao, POURBAIX, Annabelle, RACHLINE, Anne, RIOUX, Christophe, SAUTEREAU, Aurelie, STEG, Gabriel, TARHINI, Hassan, VALAYER, Simon, VALLOIS, Dorothee, VERMES, Paul, VOLPE, Thomas, Nguyen, Yann, Honsel, Vasco, Weiss, Emmanuel, Codorniu, Anaïs, Zarrouk, Virginie, De Lastours, Victoire, Uzzan, Matthieu, Olivier, Olivier, Rossi, Geoffrey, Gamany, Naura, Rahli, Roza, Louis, Zeina, Boutboul, David, Galicier, Lionel, Amara, Yaël, Archer, Gabrielle, Benattia, Amira, Bergeron, Anne, Bondeelle, Louise, De Castro, Nathalie, Clément, Melissa, Darmont, Michaël, Denis, Blandine, Dupin, Clairelyne, Feredj, Elsa, Feyeux, Delphine, Joseph, Adrien, Lengliné, Etienne, Le Guen, Pierre, Liégeon, Geoffroy, Lorillon, Gwenaël, Mabrouki, Asmaa, Mariotte, Eric, Martin de Frémont, Grégoire, Mirouse, Adrien, Molina, Jean-Michel, Peffault de Latour, Régis, Oksenhendler, Eric, Saussereau, Julien, Tazi, Abdellatif, Tudesq, Jean-Jacques, Zafrani, Lara, Brindele, Isabelle, Bugnet, Emmanuelle, Celli Lebras, Karine, Chabert, Julien, Djaghout, Lalia, Fauvaux, Catherine, Jegu, Anne Lise, Kozaliewicz, Ewa, Meunier, Martine, Tremorin, Marie-Thérèse, Davoine, Claire, Madeleine, Isabelle, Caillat-Zucman, Sophie, Delaugerre, Constance, Morin, Florence, SENE, Damien, BURLACU, Ruxandra, CHOUSTERMAN, Benjamin, MEGARBANE, Bruno, RICHETTE, Pascal, RIVELINE, Jean-Pierre, FRAZIER, Aline, VICAUT, Eric, BERTON, Laure, HADJAM, Tassadit, VASQUEZ-IBARRA, Miguel Alejandro, JOURDAINE, Clément, JACOB, Aude, SMATI, Julie, RENAUD, Stéphane, MANIVET, Philippe, PERNIN, Claire, SUAREZ, Lydia, Semerano, Luca, ABAD, Sebastien, Benainous, Ruben, Bloch Queyrat, Coralie, Bonnet, Nicolas, Brahmi, Sabrina, Cailhol, johann, Cohen, Yves, Comparon, Celine, Cordel, Hugues, Dhote, Robin, Dournon, Nathalie, Duchemann, Boris, Ebstein, Nathan, Giroux-Leprieur, Benedicte, Goupil de Bouille, Jeanne, Jacolot, Anne, Nunes, Hilario, Oziel, Johanna, Rathouin, Vanessa, Rigal, Marthe, Roulot, Dominique, Tantet, Claire, Uzunhan, Yurdagul, COSTEDOAT-CHALUMEAU, Nathalie, Ait Hamou, Zakaria, Benghanem, Sarah, BLANCHE, Philippe, CANOUI, Etienne, CARLIER, Nicolas, CHAIGNE, Benjamin, CONTEJEAN, Adrien, DUNOGUE, Bertrand, DUPLAND, Pierre, DUREL - MAURISSE, Aurélie, GAUZIT, Remy, JAUBERT, Paul, Joumaa, Hassan, Jozwiak, Mathieu, KERNEIS, Solen, LACHATRE, Marie, Lafoeste, Hélène, LEGENDRE, Paul, LUONG NGUYEN, Liem Binh, MAREY, Jonathan, MORBIEU, Caroline, MOUTHON, Luc, NGUYEN, Lee, Palmieri, Lola-Jade, REGENT, Alexis, SZWEBEL, Tali-Anne, TERRIER, Benjamin, GUERIN, Corinne, ZERBIT, Jérémie, CHEREF, Kahina, CHITOUR, Kamil, CISSE, Mamadou Salif, CLARKE, Ada, CLAVERE, Gaelle, DUSANTER, Isabelle, GAUDEFROY, Caroline, JALLOULI, Moez, KOLTA, Sami, LE BOURLOUT, Catherine, MARIN, Nathalie, MENAGE, Nathalie, MOORES, Alexandre, PEIGNEY, Isabelle, PIERRON, Cédric, SALEH-MGHIR, Samira, VALLET, Mathilde, MICHEL, Marc, MELICA, Giovanna, LELIEVRE, Jean-Daniel, FOIS, Elena, LIM, Pascal, MATIGNON, Marie, GUILLAUD, Constance, THIEMELE, Alaki, SCHMITZ, David, BOUHRIS, Marion, BELAZOUZ, Syllia, LANGUILLE, Laetitia, MEKONTSO-DESSAPS, Armand, SADAOUI, Thiziri, Mayaux, Julien, Cacoub, Patrice, Corvol, Jean-Christophe, Louapre, Céline, Sambin, Sara, Mariani, Louise-Laure, Karachi, Carine, Tubach, Florence, Estellat, Candice, Gimeno, Linda, Martin, Karine, Bah, Aïcha, Keo, Vixra, Ouamri, Sabrine, Messaoudi, Yasmine, Yelles, Nessima, Faye, Pierre, Cavelot, Sébastien, Larcheveque, Cecile, Annonay, Laurence, Benhida, Jaouad, Zahrate-Ghoul, Aida, Hammal, Soumeya, Belilita, Ridha, Lecronier, Marie, Beurton, Alexandra, Haudebourg, Luc, Deleris, Robin, Le Marec, Julien, Virolle, Sara, Nemlaghi, Safaa, Bureau, Côme, Mora, Pierre, De Sarcus, Martin, Clovet, Olivier, Duceau, Baptiste, Grisot, Paul Henri, Pari, Marie hélène, Arzoine, Jérémy, Clarac, Ulrich, Faure, Morgane, Delemazure, Julie, Decavele, Maxence, Morawiec, Elise, Demoule, Alexandre, Dres, Martin, Vautier, Mathieu, Allenbach, Yves, Benveniste, Olivier, Leroux, Gaelle, Rigolet, Aude, Guillaume-Jugnot, Perrine, Domont, Fanny, Desbois, Anne Claire, Comarmond, Cloé, Champtiaux, Nicolas, Toquet, Segolene, Ghembaza, Amine, Vieira, Matheus, Maalouf, Georgina, Boleto, Gonçalo, Ferfar, Yasmina, Charbonnier, Fanny, AGUILAR, Claire, ALBY-LAURENT, Fanny, ALYANAKIAN, Marie-Alexandra, BAKOUBOULA, Prissile, BROISSAND, Christine, BURGER, Carole, CAMPOS-VEGA, Clara, CHAVAROT, Nathalie, CHOUPEAUX, Laure, FOURNIER, Benjamin, GRANVILLE, Sophie, ISSORAT, Elodie, ROUZAUD, Claire, VIMPERE, Damien, Geri, Guillaume, Derridj, Nawal, Sguiouar, Naima, Meddah, Hakim, Djadel, Mourad, Chambrin-Lauvray, Helene, Duclos-Vallée, Jean-Charles, Saliba, Faouzi, Sacleux, Sophie-Caroline, Koumis, Ilias, Michot, Jean-Marie, Stoclin, Annabelle, Colomba, Emeline, Pommeret, Fanny, Willekens, Chistophe, Sakkal, Madona, Da Silva, Rosa, Dejean, Valérie, Mekid, Yasmina, Ben-Mabrouk, Ines, Pradon, Caroline, Drouard, Laurence, Camara-Clayette, Valérie, Morel, Alexandre, Garcia, Gilles, Mohebbi, Abolfazl, Berbour, Férial, Dehais, Mélanie, Pouliquen, Anne-Lise, Klasen, Alison, Soyez-Herkert, Loren, London, Jonathan, Keroumi, Younes, Guillot, Emmanuelle, Grailles, Guillaume, El Amine, Younes, Defrancq, Fanny, Fodil, Hanane, Bouras, Chaouki, Dautel, Dominique, Gambier, Nicolas, Dieye, Thierno, Razurel, Anaïs, Bienvenu, Boris, Lancon, Victor, Lecomte, Laurence, Beziriganyan, Kristina, Asselate, Belkacem, Allanic, Laure, Kiouris, Elena, Legros, Marie-Hélène, Lemagner, Christine, Martel, Pascal, Provitolo, Vincent, Ackermann, Félix, Le Marchand, Mathilde, Clan Hew Wai, Aurélie, Fremont, Dimitri, Coupez, Elisabeth, Adda, Mireille, Duée, Frédéric, Bernard, Lise, Gros, Antoine, Henry, Estelle, Courtin, Claire, Pattyn, Anne, Guinot, Pierre-Grégoire, Bardou, Marc, Maurer, Agnes, Jambon, Julie, Cransac, Amélie, Pernot, Corinne, Mourvillier, Bruno, Servettaz, Amélie, Deslée, Gaetan, Wynckel, Alain, Benoit, Philippe, Marquis, Eric, Roux, Damien, Gernez, Coralie, Yelnik, Cécile, Poissy, Julien, Nizard, Mandy, Denies, Fanette, Gros, Hélène, Mourad, Jean-Jacques, Sacco, Emmanuelle, and Renet, Sophie

Published
2021
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10. Case series of carbapenemase-producing Enterobacteriaceae osteomyelitis: Feel it in your bones

Author

B. Davido, L. Noussair, A. Saleh-Mghir, E. Salomon, F. Bouchand, M. Matt, C. Lawrence, T. Bauer, J.L. Herrmann, C. Perronne, J.L. Gaillard, M. Rottman, and A. Dinh

Subjects
Carbapenemase, Enterobacteriaceae, CPE, Osteomyelitis, Bone, Infection, Microbiology, QR1-502
Abstract

Objectives: Limited data have been reported regarding osteomyelitis due to carbapenemase-producing Enterobacteriaceae (CPE), including co-infections with extended-spectrum β-lactamase (ESBL)-producing micro-organisms. Methods: We conducted a retrospective study in a reference centre for bone and joint infections from 2011 to 2019 among patients infected with CPE. Results: Nine patients (mean age 46.8 ± 16.6 years), including three with infected implants, were identified. Infections were mostly polymicrobial (n = 8/9), including Staphylococcus aureus (n = 6/9). CPE were mainly OXA-48-type, associated with ESBL-producing Enterobacteriaceae (n = 8/9), of which 5/9 isolates were Klebsiella pneumoniae. Control of the infection was achieved in seven cases. Conclusions: CPE osteomyelitides are essentially polymicrobial and fluoroquinolone-resistant infections, highlighting the need for efficient surgery with implant removal.

Published
2020
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11. Normalization of eosinophil count is predictive of oxygen weaning over the course of COVID-19 infection among hospitalized adults during the first wave of 2020 pandemic.

Author

Davido, Benjamin, Jaffal, Karim, Saleh-Mghir, Azzam, Vaugier, Isabelle, Bourlet, Stephane, De Truchis, Pierre, and Annane, Djillali

Subjects
COVID-19 pandemic, COVID-19, EOSINOPHILS, LYMPHOCYTE count, INTENSIVE care units
Abstract

Background: Understanding COVID-19 outcomes remains a challenge. While numerous biomarkers have been proposed for severity at admission, limited exploration exists for markers during the infection course, especially for the requirement of oxygen therapy. This study investigates the potential of eosinophil count normalization as a predictor for oxygen weaning during the initial wave of the pandemic. Methods: A retrospective study was conducted between March and April 2020 (first wave) among adults admitted directly to a medicine ward. Biological abnormalities, including lymphocyte count, eosinophil count, and C-reactive protein (CRP), were gathered daily during the first week of admission according to oxygen level. In case of worsening, oxygen level was censored at 15 L/min. The primary aim was to assess whether eosinophil count normalization predicts a subsequent decrease in oxygen requirements. Results: Overall, 132 patients were admitted, with a mean age of 59.0 ± 16.3 years. Of the patients, 72% required oxygen, and 20.5% were admitted to the intensive care unit after a median delay of 48 hours. The median CRP at admission was 79 (26-130) mg/L, whereas the eosinophil count was 10 (0-60)/mm³. Eosinophil count normalization (=100/mm³) by day 2 correlated significantly with decreased oxygen needs (<2 L) with hazard ratio (HR) = 3.7 [1.1-12.9] (p = 0.04). Likewise, CRP < 80 mg/L was associated with reduced oxygen requirements (p < 0.001). Predictors, including underlying chronic respiratory disease, exhibited a trend toward a negative association (p = 0.06). Conclusion: The study highlights the relationship between eosinophil count and CRP, with implications for predicting oxygen weaning during COVID-19. Further research is warranted to explore the relevance of these biomarkers in other respiratory infections. [ABSTRACT FROM AUTHOR]

Published
2024
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12. Efficacy of ceftazidime/avibactam in various combinations for the treatment of experimental osteomyelitis in rabbits caused by OXA-48-/ESBL-producing Escherichia coli

Author

Benjamin Davido, Anne-Claude Crémieux, Isabelle Vaugier, Pierre De Truchis, Kamel Hamami, Frédéric Laurent, and Azzam Saleh-Mghir

Subjects
Pharmacology, Microbiology (medical), Infectious Diseases, Pharmacology (medical)
Abstract

Background While the treatment of ESBL-producing Enterobacterales osteomyelitis relies on carbapenems, the optimal regimen for OXA48 types remains unclear. We evaluated the efficacy of ceftazidime/avibactam in different combinations in an experimental model of OXA-48-/ESBL-producing Escherichia coli osteomyelitis. Methods E. coli pACYC184 is a clinical strain harbouring blaOXA-48 and blaCTX-M-15 inserts, with ‘increased exposure susceptibility’ to imipenem (MIC, 2 mg/L), gentamicin (MIC, 0.5 mg/L), colistin (MIC, 0.25 mg/L), ceftazidime/avibactam (MIC, 0.094 mg/L) and fosfomycin (MIC, 1 mg/L), and resistance to ceftazidime (MIC, 16 mg/L). Osteomyelitis was induced in rabbits by tibial injection of 2 × 108 cfu of OXA-48/ESBL E. coli. Treatment started 14 days later for 7 days in six groups: (1) control, (2) colistin 150.000 IU/kg subcutaneously (SC) q8h, (3) ceftazidime/avibactam 100/25 mg/kg SC q8h, (4) ceftazidime/avibactam + colistin, (5) ceftazidime/avibactam + fosfomycin 150 mg/kg SC q12h, (6) ceftazidime/avibactam + gentamicin 15 mg/kg intramuscularly (IM) q24h. Treatment was evaluated at Day 24 according to bone cultures. Results In vitro, time–kill curves of ceftazidime/avibactam in combination showed a synergistic effect. In vivo, compared with controls, rabbits treated with colistin alone had similar bone bacterial density (P = 0.50), whereas ceftazidime/avibactam alone or in combinations significantly decreased bone bacterial densities (P = 0.004 and P Conclusions In our model of E. coli OXA-48/ESBL osteomyelitis, ceftazidime/avibactam in combination was more effective than any single therapy, whatever the companion drug used (gentamicin or colistin or fosfomycin).

Published
2023
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13. Germs of thrones - spontaneous decolonization of Carbapenem-Resistant Enterobacteriaceae (CRE) and Vancomycin-Resistant Enterococci (VRE) in Western Europe: is this myth or reality?

Author

Benjamin Davido, Aurore Moussiegt, Aurélien Dinh, Frédérique Bouchand, Morgan Matt, Olivia Senard, Laurene Deconinck, Florence Espinasse, Christine Lawrence, Nicolas Fortineau, Azzam Saleh-Mghir, Silvia Caballero, Lelia Escaut, and Jérome Salomon

Subjects
Decolonization, Carbapenem-Resistant Enterobacteriaceae, Vancomycin-Resistant Enterococcus, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background In France, Carbapenem-Resistant Enterobacteriaceae (CRE) and Vancomycin-Resistant Enterococci (VRE) are considered as Extensively Drug-Resistant (XDR) bacteria. Their management requires reinforcement of hospital’s hygiene policies, and currently there is few consistent data concerning the spontaneous decolonization in XDR colonized patients. Our aim is to study the natural history of decolonization of XDR carriers over time in a hospital setting in a low prevalence country. Material and methods Retrospective multicenter study over 2 years (2015–2016) in 2 different tertiary care hospital sites and units having an agreement for permanent cohorting of such XDR carriers. We gathered the type of microorganisms, risk factors for colonization and rectal swabs from patient’s follow-up. We also evaluated patient care considering isolation precautions. Results We included 125 patients, aged 63+/−19y, including 72.8% of CRE (n = 91), 24.8% of VRE (n = 31) and 2.4% (n = 3) co-colonized with CRE and VRE. CRE were mainly E. coli (n = 54), K. pneumoniae (n = 51) and E. cloacae (n = 6). Mechanisms of resistance were mainly OXA-48 (n = 69), NDM-1 (n = 11), OXA-232 (n = 8) and KPC (n = 3). Prior antibiotic therapy was reported in 38.4% (n = 48) of cases. Conversely, 17.6% (n = 22) received antibiotics during follow-up. Spontaneous decolonization occurred within the first 30 days in 16.4% (n = 19/116) of cases and up to 48.2% after day-90 with a median follow-up of 96 days (0–974). We estimated that XDR carriage was associated with a larger care burden in 13.6% (n = 17) of cases, especially due to a prolongation of hospitalization of 32.5 days (15–300). Conclusions Our study shows that spontaneous decolonization is increasing over time (up to 48.2%). We can regret that only few patients underwent screening after 1 year, emphasizing the need for more monitoring and prospective studies.

Published
2018
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14. Efficacy of Expired Antibiotics: A Real Debate in the Context of Repeated Drug Shortages.

Author

Davido, Benjamin, Michelon, Hugues, Mamona, Christel, de Truchis, Pierre, Jaffal, Karim, and Saleh-Mghir, Azzam

Subjects
SCARCITY, ANTIBIOTICS, PRODUCT attributes, DRUGS
Abstract

This narrative review aims to discuss the main interest in and cautions associated with the use of expired antibiotics in the context of repeated shortages, notably in Europe. Articles concerning the topic of expiry dates related to antibiotic use were reviewed using keywords in the PubMed®/MEDLINE and Google Scholar databases to identify the most extensive evidence-based documentation. The present review evaluates the potential interest and efficacy of using expired drugs and their possible related adverse events. Overall, in the context of drug shortages, expiry dates could be safely extended for at least one year for most solid antibiotics (tablets or powder) used in daily clinical practice, as long as they are stored under the right conditions, in accordance with the summary of product characteristics. [ABSTRACT FROM AUTHOR]

Published
2024
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15. A novel antibacterial compound decreases MRSA biofilm formation without the use of antibiotics in a murine model.

Author

Bouloussa, Houssam, Durand, Zoe, Gibon, Emmanuel, Chen, Antonia F., Grant, Matthew, Saleh‐Mghir, Azzam, Mirza, Mohsin, Stutzman, Bradley, Vergari, Claudio, Yue, James, Anzala, Nelson, Bonnot, Dorian, Albac, Sandrine, Bouloussa, Othman, and Croisier, Delphine

Subjects
METHICILLIN-resistant staphylococcus aureus, BIOFILMS, SURGICAL site infections, ANTIBIOTICS assay, ANTIBIOTICS, MATERIALS science
Abstract

Despite significant advancements in material science, surgical site infection (SSI) rates remain high and prevention is key. This study aimed to demonstrate the in vivo safety and antibacterial efficacy of titanium implants treated with a novel broad‐spectrum biocidal compound (DBG21) against methicillin‐resistant Staphylococcus aureus (MRSA). Titanium (Ti) discs were covalently bound with DBG21. Untreated Ti discs were used as controls. All discs were implanted either untreated for 44 control mice or DBG21‐treated for 44 treated mice. After implantation, 1 × 107 colony forming units (CFU) of MRSA were injected into the operating site. Mice were killed at 7 and 14 days to determine the number of adherent bacteria (biofilm) on implants and in the peri‐implant surrounding tissues. Systemic and local toxicity were assessed. At both 7 and 14 days, DBG21‐treated implants yielded a significant decrease in MRSA biofilm (3.6 median log10 CFU [99.97%] reduction [p < 0.001] and 1.9 median log10 CFU [98.7%] reduction [p = 0.037], respectively) and peri‐implant surrounding tissues (2.7 median log10 CFU/g [99.8%] reduction [p < 0.001] and 5.6 median log10 CFU/g [99.9997%] reduction [p < 0.001], respectively). There were no significant differences between control and treated mice in terms of systemic and local toxicity. DBG‐21 demonstrated a significant decrease in the number of biofilm bacteria without associated toxicity in a small animal implant model of SSI. Preventing biofilm formation has been recognized as a key element of preventing implant‐related infections. [ABSTRACT FROM AUTHOR]

Published
2024
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20. 199. A novel and scalable antimicrobial surface modification technology to prevent and mitigate implant related surgical site infections: an in-vivo safety and efficacy study

Author

Houssam Bouloussa, Zoe Durand, Azzam Saleh-Mghir, Mohsin Mirza, Bradley Stutzman, Emmanuel Gibon, Claudio Vergari, Nelson Anzala, Dorian Bonnot, Othman Bouloussa, James J. Yue, Sandrine Albac, and Delphine Croisier

Subjects
Surgery, Orthopedics and Sports Medicine, Neurology (clinical)
Published
2022
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21. Phenol-Soluble Modulins Contribute to Early Sepsis Dissemination Not Late Local USA300-Osteomyelitis Severity in Rabbits.

Author

Benjamin Davido, Azzam Saleh-Mghir, Frédéric Laurent, Claire Danel, Florence Couzon, Laure Gatin, François Vandenesch, Jean-Philippe Rasigade, and Anne-Claude Crémieux

Subjects
Medicine, Science
Abstract

INTRODUCTION:In bone and joint infections (BJIs), bacterial toxins are major virulence factors: Panton-Valentine leukocidin (PVL) expression leads to severe local damage, including bone distortion and abscesses, while α-hemolysin (Hla) production is associated with severe sepsis-related mortality. Recently, other toxins, namely phenol-soluble modulins (PSMs) expressed by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain USA300 (LAC WT) were shown to have ex vivo intracellular cytotoxic activity after S. aureus invasion of osteoblasts, but their in vivo contribution in a relatively PVL-sensitive osteomyelitis model remains poorly elucidated. MATERIALS AND METHODS:We compared the outcomes of experimental rabbit osteomyelitises induced with pvl+hla+psms+ LAC WT and its isogenic Δpsm derivatives (LAC Δpsmα and LAC Δpsmαβhld) using an inoculum of 3 × 108 CFUs. Mortality, hematogenous spread (blood culture, spleen and kidney), lung and bone involvements were assessed in two groups (non-survivors of severe sepsis and survivors sacrificed on day (D) 14). RESULTS:Severe sepsis-related mortality tended to be lower for Δpsm derivatives (Kaplan-Meier curves, P = .06). Non-survivors' bone LAC-Δpsmα (6.9 log10 CFUs/g of bone, P = .04) or -Δpsmαβhld (6.86 log10 CFUs/g of bone, P = .014) densities were significantly higher than LAC WT (6.43 log10 CFUs/g of bone). Conversely, lung Δpsmαβhld CFUs were significantly lower than LAC WT (P = .04). LAC Δpsmα, Δpsmαβhld and WT induced similar bone damage in D14 survivors, with comparable bacterial densities (respectively: 5.89, 5.91, and 6.15 log10 CFUs/g of bone). Meanwhile, pulmonary histological scores of inflammation were significantly higher for LAC Δpsmα- and Δpsmαβhld-infected rabbits compared to LAC WT (P = .04 and .01, respectively) but with comparable lung bacterial densities. CONCLUSION:Our experimental results showed that deactivating PSM peptides significantly limited bacterial dissemination from bone during the early phase of infection, but did not affect local severity of USA300 rabbit osteomyelitis.

Published
2016
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22. Efficacy of ceftazidime/avibactam in various combinations for the treatment of experimental osteomyelitis in rabbits caused by OXA-48-/ESBL-producing Escherichia coli.

Author

Davido, Benjamin, Crémieux, Anne-Claude, Vaugier, Isabelle, Truchis, Pierre De, Hamami, Kamel, Laurent, Frédéric, and Saleh-Mghir, Azzam

Subjects
CEFTAZIDIME, ESCHERICHIA coli, OSTEOMYELITIS, RABBITS, BONE density, COLISTIN
Abstract

Background While the treatment of ESBL-producing Enterobacterales osteomyelitis relies on carbapenems, the optimal regimen for OXA48 types remains unclear. We evaluated the efficacy of ceftazidime/avibactam in different combinations in an experimental model of OXA-48-/ESBL-producing Escherichia coli osteomyelitis. Methods E. coli pACYC184 is a clinical strain harbouring bla OXA-48 and bla CTX-M-15 inserts, with 'increased exposure susceptibility' to imipenem (MIC, 2 mg/L), gentamicin (MIC, 0.5 mg/L), colistin (MIC, 0.25 mg/L), ceftazidime/avibactam (MIC, 0.094 mg/L) and fosfomycin (MIC, 1 mg/L), and resistance to ceftazidime (MIC, 16 mg/L). Osteomyelitis was induced in rabbits by tibial injection of 2 × 108 cfu of OXA-48/ESBL E. coli. Treatment started 14 days later for 7 days in six groups: (1) control, (2) colistin 150.000 IU/kg subcutaneously (SC) q8h, (3) ceftazidime/avibactam 100/25 mg/kg SC q8h, (4) ceftazidime/avibactam + colistin, (5) ceftazidime/avibactam + fosfomycin 150 mg/kg SC q12h, (6) ceftazidime/avibactam + gentamicin 15 mg/kg intramuscularly (IM) q24h. Treatment was evaluated at Day 24 according to bone cultures. Results In vitro , time–kill curves of ceftazidime/avibactam in combination showed a synergistic effect. In vivo , compared with controls, rabbits treated with colistin alone had similar bone bacterial density (P  = 0.50), whereas ceftazidime/avibactam alone or in combinations significantly decreased bone bacterial densities (P  = 0.004 and P  < 0.0002, respectively). Bone sterilization was achieved using ceftazidime/avibactam in combination with colistin (91%) or fosfomycin (100%) or gentamicin (100%) (P  < 0.0001), whereas single therapies were not different from controls. No ceftazidime/avibactam-resistant strains emerged in rabbits treated, regardless of the combination. Conclusions In our model of E. coli OXA-48/ESBL osteomyelitis, ceftazidime/avibactam in combination was more effective than any single therapy, whatever the companion drug used (gentamicin or colistin or fosfomycin). [ABSTRACT FROM AUTHOR]

Published
2023
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23. Efficacy of colistin alone and in various combinations for the treatment of experimental osteomyelitis due to carbapenemase-producing Klebsiella pneumoniae

Author

L. Gatin, Azzam Saleh-Mghir, Omar Aimer, Aurélien Dinh, Idir Ghout, Aurélie Jayol, Pierre Tattevin, Frédéric Laurent, Patrice Nordmann, William Mouton, Marie-Clémence Verdier, Anne-Claude Crémieux, Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Raymond Poincaré [AP-HP], 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), Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Reference des Staphylocoques, Université de Lyon, CHU Pontchaillou [Rennes], ARN régulateurs bactériens et médecine (BRM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Ambroise Paré [AP-HP], French National Agency, AAP-2013–055, Agence Nationale de Sécurité du Médicament, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
Microbiology (medical), Klebsiella pneumoniae, medicine.drug_class, [SDV]Life Sciences [q-bio], Antibiotics, Microbial Sensitivity Tests, Tigecycline, Pharmacology, Fosfomycin, Meropenem, 03 medical and health sciences, Drug Resistance, Multiple, Bacterial, Drug Resistance, Bacterial, polycyclic compounds, medicine, Animals, Pharmacology (medical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Antiinfective agent, Dose-Response Relationship, Drug, biology, Colistin, 030306 microbiology, business.industry, Drug Synergism, Osteomyelitis, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, biology.organism_classification, Anti-Bacterial Agents, Klebsiella Infections, 3. Good health, Disease Models, Animal, Carbapenem-Resistant Enterobacteriaceae, Infectious Diseases, bacteria, Drug Therapy, Combination, lipids (amino acids, peptides, and proteins), Gentamicin, Rabbits, business, medicine.drug
Abstract

ObjectivesIn a new experimental model of carbapenemase-producing Klebsiella pneumoniae osteomyelitis we evaluated the efficacy of colistin alone and in various combinations and examined the emergence of colistin-resistant strains and cross-resistance to host defence peptides (HDPs).MethodsKPC-99YC is a clinical strain with intermediate susceptibility to meropenem (MIC = 4 mg/L) and full susceptibility to gentamicin, colistin and tigecycline (MICs = 1 mg/L) and fosfomycin (MIC = 32 mg/L). Time–kill curves were performed at 4× MIC. Osteomyelitis was induced in rabbits by tibial injection of 2 × 108 cfu. Treatment started 14 days later for 7 days in seven groups: (i) control; (ii) colistin; (iii) colistin + gentamicin; (iv) colistin + tigecycline; (v) colistin + meropenem; (vi) colistin + meropenem + gentamicin; and (vii) colistin + fosfomycin.ResultsIn vitro, colistin was rapidly bactericidal, but regrowth occurred after 9 h. Combinations of colistin with meropenem or fosfomycin were synergistic, whereas combination with tigecycline was antagonistic. In vivo, colistin alone was not effective. Combinations of colistin with meropenem or fosfomycin were bactericidal (P ConclusionsIn this model, combinations of colistin plus meropenem, with or without gentamicin, or colistin plus fosfomycin were the only effective therapies. The combination of colistin and tigecycline should be administered with caution, as it may be antagonistic in vitro and in vivo.

Published
2019
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25. Emergence of daptomycin resistance in daptomycin-naïve rabbits with methicillin-resistant Staphylococcus aureus prosthetic joint infection is associated with resistance to host defense cationic peptides and mprF polymorphisms.

Author

Nagendra N Mishra, Soo-Jin Yang, Liang Chen, Claudette Muller, Azzam Saleh-Mghir, Sebastian Kuhn, Andreas Peschel, Michael R Yeaman, Cynthia C Nast, Barry N Kreiswirth, Anne-Claude Crémieux, and Arnold S Bayer

Subjects
Medicine, Science
Abstract

Previous studies of both clinically-derived and in vitro passage-derived daptomycin-resistant (DAP-R) Staphylococcus aureus strains demonstrated the coincident emergence of increased DAP MICs and resistance to host defense cationic peptides (HDP-R).In the present investigation, we studied a parental DAP-susceptible (DAP-S) methicillin-resistant Staphylococcus aureus (MRSA) strain and three isogenic variants with increased DAP MICs which were isolated from both DAP-treated and DAP-untreated rabbits with prosthetic joint infections. These strains were compared for: in vitro susceptibility to distinct HDPs differing in size, structure, and origin; i.e.; thrombin-induced platelet microbicidal proteins [tPMPs] and human neutrophil peptide-1 [hNP-1]; cell membrane (CM) phospholipid and fatty acid content; CM order; envelope surface charge; cell wall thickness; and mprF single nucleotide polymorphisms (SNPs) and expression profiles.In comparison with the parental strain, both DAP-exposed and DAP-naive strains exhibited: (i) significantly reduced susceptibility to each HDP (P

Published
2013
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27. Panton-valentine leukocidin enhances the severity of community-associated methicillin-resistant Staphylococcus aureus rabbit osteomyelitis.

Author

Anne-Claude Crémieux, Oana Dumitrescu, Gerard Lina, Christian Vallee, Jean-François Côté, Martine Muffat-Joly, Thomas Lilin, Jerome Etienne, François Vandenesch, and Azzam Saleh-Mghir

Subjects
Medicine, Science
Abstract

BACKGROUND: Extensive spread of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in the United States, and the concomitant increase in severe invasive staphylococcal infections, including osteomyelitis, in healthy children, has led to renewed interest in Panton-Valentine leukocidin (PVL). However, the pathogenetic role of PVL in staphylococcal infections remains controversial, possibly because it depends on the site of infection. METHODOLOGY/PRINCIPAL FINDINGS: We compared the course of experimental rabbit osteomyelitis due to the PVL-positive CA-MRSA strain USA 300 (LAC) and its PVL-negative isogenic derivative (LACDeltapvl), using a low and a high inoculum (8x10(5) and 4x10(8) CFU). With the low inoculum, bone infection was less frequent on day 7 (D7) and day 28 (D28) with LACDeltapvl than with LAC (respectively 12/19 and 18/19 animals, p = 0.042). With the high inoculum of both strains, all the animals were infected on D7 and the infection persisted on D28 in almost every case. However, tibial bacterial counts and the serum CRP concentration fell significantly between D7 and D28 with LACDeltapvl but not with LAC. Respectively 67% and 60% of LAC-infected rabbits had bone deformation and muscle/joint involvement on D7, compared to 0% and 7% of LACDeltapvl-infected rabbits (p = 0.001 and p = 0.005 respectively). Between D0 and D28, the anti-PVL antibody titer increased significantly only with the high inoculum of LAC. CONCLUSIONS/SIGNIFICANCE: PVL appears to play a role in the persistence and rapid local extension of rabbit osteomyelitis, in keeping with the greater severity of human bone infections due to PVL-positive S. aureus. The possible therapeutic implications of these findings are discussed.

Published
2009
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28. SARS-CoV-2 reinfections among hospital staff in the greater Paris area.

Author

Davido, Benjamin, Truchis, Pierre De, Lawrence, Christine, Annane, Djillali, Domart-Rancon, Martine, Gault, Elyanne, Saleh-Mghir, Azzam, Delarocque-Astagneau, Elisabeth, Gautier, Sylvain, De Truchis, Pierre, and Annane, Djilalli

Subjects
SARS-CoV-2, REINFECTION, MEDICAL personnel, HOSPITAL personnel, COVID-19, INFECTION
Published
2021
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29. A Graftable Quaternary Ammonium Biocidal Polymer Reduces Biofilm Formation and Ensures Biocompatibility of Medical Devices.

Author

Bouloussa, Houssam, Saleh‐Mghir, Azzam, Valotteau, Claire, Cherifi, Chahrazad, Hafsia, Narjes, Cohen‐Solal, Martine, Court, Charles, Crémieux, Anne‐Claude, and Humblot, Vincent

Subjects
SURFACE charges, MEDICAL equipment, X-ray photoelectron spectroscopy, BIOCOMPATIBILITY, METHICILLIN-resistant staphylococcus aureus, BIOFILMS, ANTIMICROBIAL polymers, OXAZOLIDINONES
Abstract

A quaternized polyvinylpyridine (Q‐PVP) polymer methanolic solution synthesized in a single step is used to covalently graft titanium surfaces. Q‐PVP is quaternized with varying N+/N ratios. 1 cm2 pure titanium plates are polished and activated. Treated samples are grafted by spin coating or dip‐coating (grafting‐to method). Surfaces are characterized by X‐ray photoelectron spectroscopy, polarization modulation reflection absorption IR spectroscopy, atomic force microscopy, scanning electron microscopy, and surface charge density calculation. Polymer leaching is assessed at 7 days. Biocompatibility is assessed on MC3T3 and L929 cells (MTT‐assay) and SEM. In vitro antibacterial activity is assessed on methicillin‐resistant Staphylococcus aureus (MRSA) at 1 and 24 h (37 °C in brain heart infusion) and at 7 days in a biofilm model. Polymers exceeding 31.3 ± 0.7% quaternization led to bactericidal surfaces. Bactericidal activity increased with surface cationic density. Surface cationic density and biocompatibility are inversely correlated. Polymers with 44.6 ± 1.2% quaternization are antibacterial and biocompatible. High‐density Q‐PVP inhibited MRSA biofilm formation. Q‐PVP is a promising candidate for antibacterial surface modification. Further in vivo studies are required. [ABSTRACT FROM AUTHOR]

Published
2021
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30. Efficacy of colistin alone and in various combinations for the treatment of experimental osteomyelitis due to carbapenemase-producing Klebsiella pneumoniae.

Author

Crémieux, Anne-Claude, Dinh, Aurélien, Nordmann, Patrice, Mouton, William, Tattevin, Pierre, Ghout, Idir, Jayol, Aurelie, Aimer, Omar, Gatin, Laure, Verdier, Marie-Clémence, Saleh-Mghir, Azzam, and Laurent, Frédéric

Subjects
KLEBSIELLA pneumoniae, FOSFOMYCIN, MEROPENEM, COLISTIN, GENTAMICIN, DRUG resistance in bacteria, OSTEOMYELITIS treatment, INVESTIGATIONAL therapies
Abstract

Objectives In a new experimental model of carbapenemase-producing Klebsiella pneumoniae osteomyelitis we evaluated the efficacy of colistin alone and in various combinations and examined the emergence of colistin-resistant strains and cross-resistance to host defence peptides (HDPs). Methods KPC-99YC is a clinical strain with intermediate susceptibility to meropenem (MIC = 4 mg/L) and full susceptibility to gentamicin, colistin and tigecycline (MICs = 1 mg/L) and fosfomycin (MIC = 32 mg/L). Time–kill curves were performed at 4× MIC. Osteomyelitis was induced in rabbits by tibial injection of 2 × 108 cfu. Treatment started 14 days later for 7 days in seven groups: (i) control; (ii) colistin; (iii) colistin + gentamicin; (iv) colistin + tigecycline; (v) colistin + meropenem; (vi) colistin + meropenem + gentamicin; and (vii) colistin + fosfomycin. Results In vitro , colistin was rapidly bactericidal, but regrowth occurred after 9 h. Combinations of colistin with meropenem or fosfomycin were synergistic, whereas combination with tigecycline was antagonistic. In vivo , colistin alone was not effective. Combinations of colistin with meropenem or fosfomycin were bactericidal (P <  0.001) and the addition of gentamicin enhanced the efficacy of colistin + meropenem (P =  0.025). Tigecycline reduced the efficacy of colistin (P =  0.007). Colistin-resistant strains emerged in all groups except colistin + fosfomycin and two strains showed cross-resistance to HDP LL-37. Conclusions In this model, combinations of colistin plus meropenem, with or without gentamicin, or colistin plus fosfomycin were the only effective therapies. The combination of colistin and tigecycline should be administered with caution, as it may be antagonistic in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Published
2019
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31. Activité de la daptomycine et émergence de résistance dans un modèle expérimental d’endocardite à Enterococcus faecium résistant à la vancomycine

Author

Clara Sinel, F. Guérin, Vincent Cattoir, L. Massias, S. Reissier, A Saleh-Mghir, Idir Ghout, and Anne-Claude Crémieux

Subjects
Infectious Diseases
Abstract

Introduction La daptomycine apparait comme un antibiotique de premiere ligne dans le traitement de l’endocardite infectieuse [EI] a enterocoques resistants a la vancomycine. De fortes doses sont necessaires, mais les posologies optimales, notamment pour traiter les souches d’Enterococcus faecium ayant une CMI proche du seuil de sensibilite (4 mg/L), ne sont pas connues. Materiels et methodes Dans un modele experimental d’EI chez le lapin, des posologies equivalentes a 8 et 12 mg/kg (DAP8 et DAP12) ont ete testees sur des souches d’E. faecium ayant des CMI de la daptomycine a 2 (souche Aus0004) et 4 mg/L (Mut4, mutant obtenu in vitro). Les numerations bacteriennes des vegetations ont ete comparees entre les differents groupes de traitement. Nous avons ensuite estime l’emergence de mutants resistants sur des milieux additionnes de daptomycine. Resultats Pour la souche Aus0004, DAP8 et DAP12 permettaient de reduire significativement la charge bacterienne des vegetations par rapport au groupe controle (6,05 et 2,15 vs 9,14 log10 CFU/g respectivement, p 0,999) et aucune ne permettait de steriliser les vegetations. Avec DAP8, 8,3 % des vegetations infectees par Aus0004 et 63,6 % des vegetations infectees par Mut4 presentaient des mutants resistants. Avec DAP12, 77,8 % des vegetations infectees par Mut4 presentaient des mutants resistants. Conclusion Une posologie de 12 mg/kg semble la plus adaptee dans le traitement des EI a E. faecium ayant une CMI de la daptomycine a 2 mg/L. Dans le traitement des EI dues a une souche ayant une CMI a 4 mg/L, la daptomycine en monotherapie entraine l’emergence de resistance. Une reevaluation de la concentration critique de sensibilite a la daptomycine pour les enterocoques semble necessaire.

Published
2017
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32. In vivo daptomycin efficacy against experimental vancomycin-resistant Enterococcus faecium endocarditis.

Author

Reissier, Sophie, Saleh-Mghir, Azzam, Guerin, François, Massias, Laurent, Ghout, Idir, Sinel, Clara, Cattoir, Vincent, and Cremieux, Anne-Claude

Subjects
*VANCOMYCIN, *ENTEROCOCCUS faecium, *ENDOCARDITIS, *DRUG resistance in bacteria, *COMORBIDITY
Abstract

Objectives: Daptomycin has become a first-line therapeutic option for vancomycin-resistant Enterococcus faecium infective endocarditis (IE). Although high doses (>8 mg/kg) are often recommended, optimal doses, particularly for strains with MICs close to the susceptibility breakpoint (4 mg/L), are still debated. Methods: Daptomycin efficacy at doses equivalent to 8 mg/kg daptomycin (DAP8) and 12 mg/kg daptomycin (DAP12) in humans was evaluated in a rabbit model of aortic valve IE induced by 108 cfu of E. faecium reference strain Aus0004 (daptomycin MIC = 2 mg/L) or its in vitro mutant strain Mut4 (daptomycin MIC = 4 mg/L). Treatment began 48 h post-inoculation and lasted 5 days. Results: With Aus0004, the median log10 cfu/g of vegetations was significantly lower after DAP8 and DAP12 versus controls [6.05 (n = 12) and 2.15 (n = 10) versus 9.14 (n = 11), respectively; P < 0.001], with DAP12 being more effective than DAP8 concerning vegetation bacterial load (P< 0.001) and percentages of sterile vegetations (100% versus 0%, respectively; P< 0.001). Daptomycin-resistant Aus0004 mutants were detected in 8.3% of DAP8-treated vegetations. With Mut4, the median logio cfu/g of vegetations was significantly lower after DAP8 and DAP12 versus controls [7.7 (n - 11) and 6.95 (n - 10) versus 9.59 (n - 11), respectively; P - 0.001 and P - 0.002], without any between-dose difference, but no vegetation was sterile. Moreover, 7 of 11 (63.6%) and 7 of 9 (77.8%) vegetations contained resistant mutants after DAP8 and DAP12, respectively. Conclusions: DAP12 was the most successful strategy against IE due to a WT E. faecium strain (daptomycin MIC - 2 mg/L). To treat IE strains with MIC - 4 mg/L, DAP8 or DAP12 monotherapy was poorly effective with the risk of resistant mutant emergence. Reassessment of the daptomycin susceptibility breakpoint for enterococci seems necessary. [ABSTRACT FROM AUTHOR]

Published
2018
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33. Phenol-Soluble Modulins Contribute to Early Sepsis Dissemination Not Late Local USA300-Osteomyelitis Severity in Rabbits.

Author

Davido, Benjamin, Saleh-Mghir, Azzam, Laurent, Frédéric, Danel, Claire, Couzon, Florence, Gatin, Laure, Vandenesch, François, Rasigade, Jean-Philippe, and Crémieux, Anne-Claude

Subjects
SEPSIS, OSTEOMYELITIS, PHENOLS, METHICILLIN-resistant staphylococcus aureus, SEVERITY of illness index, BACTERIAL toxins, LABORATORY rabbits
Abstract

Introduction: In bone and joint infections (BJIs), bacterial toxins are major virulence factors: Panton—Valentine leukocidin (PVL) expression leads to severe local damage, including bone distortion and abscesses, while α-hemolysin (Hla) production is associated with severe sepsis-related mortality. Recently, other toxins, namely phenol-soluble modulins (PSMs) expressed by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strain USA300 (LAC WT) were shown to have ex vivo intracellular cytotoxic activity after S. aureus invasion of osteoblasts, but their in vivo contribution in a relatively PVL-sensitive osteomyelitis model remains poorly elucidated. Materials and Methods: We compared the outcomes of experimental rabbit osteomyelitises induced with pvl+hla+psms+ LAC WT and its isogenic Δpsm derivatives (LAC Δpsmα and LAC Δpsmαβhld) using an inoculum of 3 × 108 CFUs. Mortality, hematogenous spread (blood culture, spleen and kidney), lung and bone involvements were assessed in two groups (non-survivors of severe sepsis and survivors sacrificed on day (D) 14). Results: Severe sepsis-related mortality tended to be lower for Δpsm derivatives (Kaplan—Meier curves, P = .06). Non-survivors’ bone LAC-Δpsmα (6.9 log10 CFUs/g of bone, P = .04) or -Δpsmαβhld (6.86 log10 CFUs/g of bone, P = .014) densities were significantly higher than LAC WT (6.43 log10 CFUs/g of bone). Conversely, lung Δpsmαβhld CFUs were significantly lower than LAC WT (P = .04). LAC Δpsmα, Δpsmαβhld and WT induced similar bone damage in D14 survivors, with comparable bacterial densities (respectively: 5.89, 5.91, and 6.15 log10 CFUs/g of bone). Meanwhile, pulmonary histological scores of inflammation were significantly higher for LAC Δpsmα- and Δpsmαβhld-infected rabbits compared to LAC WT (P = .04 and .01, respectively) but with comparable lung bacterial densities. Conclusion: Our experimental results showed that deactivating PSM peptides significantly limited bacterial dissemination from bone during the early phase of infection, but did not affect local severity of USA300 rabbit osteomyelitis. [ABSTRACT FROM AUTHOR]

Published
2016
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34. Influence of the pre-treatment duration of infection on the efficacies of various antibiotic regimens in experimental streptococcal endocarditis.

Author

Crémieux, Anne-Claude, Saleh-Mghir, Azzam, Vallois, Jean-Marie, Muffat-Joly, Martine, Devine, Catherine, Pocidalo, Jean-Jacques, Carbon, Claude, Crémieux, A C, Saleh-Mghir, A, Vallois, J M, Muffat-Joly, M, Devine, C, Pocidalo, J J, and Carbon, C

Abstract

The influence of the pre-treatment duration of infection on the efficacies of three different antibiotic regimens was investigated in a rabbit model of subacute endocarditis caused by a novel, nutritionally-variant species, strain GaD. Treatment was initiated either 6 or 10 days after bacterial inoculation (days 7 and 11 respectively) and comprised procaine penicillin (150,000 IU/kg bd), alone or combined with tobramycin (12 mg/kg od), teicoplanin (10 mg/kg bd), all administered by the intramuscular route for 4 days. The MICs and MBCs of penicillin, tobramycin and teicoplanin were 0·015 and 1 mg/L, 8 and 16 mg/L and 0· and 256 mg/L respectively. In the control rabbits, the mean (±S.D.) weights of the vegetations were 25±16 mg on day 7 and 45±34 mg on day 11 (=0·06). The mean (±S.D.) reductions in the number of cfu in the vegetations of the treated groups of animals after completion of therapy which had been started on days 7 and 11, compared with the mean numbers of cfu in the vegetations of the untreated controls on days 7 and 11 (Δlog cfu/g) were 4·0±1·3 and 2·1±1·5 respectively for penicillin (<0·05), 3·2±1·8 and 2·4±1·8 respectively for teicoplanin and 5·4±1·2 and 5·2±1· respectively for the combination of penicillin and tobramycin. The increase in the size of the vegetations and changes in the metabolism of the bacteria within the vegetations between days 7 and 11, as demonstrated by electron microscopy, might explain why penicillin was more effective earlier in the course of the disease and why the influence of the duration of infection before treatment was initiated, varied according to the antibiotic regimen. These results suggest that the use of bactericidal regimens, such as the combination of penicillin and tobramycin, which are equally effective in reducing the bacterial counts in vegetations which have been infected for both long and short periods could minimize the risk of relapse in patients with endocarditis in whom there have been long delays before initiating treatment and/or who have large vegetations. [ABSTRACT FROM PUBLISHER]

Published
1993

35. [alpha]-Hemolysin, Not Panton-Valentine Leukocidin, Impacts Rabbit Mortality from Severe Sepsis With Methicillin-Resistant Staphylococcus aureus Osteomyelitis.

Author

Crémieux, Anne-Claude, Saleh-Mghir, Azzam, Danel, Claire, Couzon, Florence, Dumitrescu, Oana, Lilin, Thomas, Perronne, Christian, Etienne, Jérôme, Lina, Gerard, and Vandenesch, François

Abstract

Background. Severe sepsis, combining acute osteomyelitis and lung involvement, has been described increasingly in healthy children with the spread of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA). Methods. Outcomes (mortality, hematogenous spread, lung and bone involvements) of rabbit osteomyelitis caused by CA-MRSA LAC(WT) USA300 and its Panton-Valentine leukocidin (PVL)- and [alpha]-hemolysin (Hla)-negative isogenic derivatives (LAC[Delta]pvl and LAC[Delta]hla, respectively) were compared. Results. Three days after inoculation (D3), all LAC(WT)- and LAC[Delta]pvl-, and 72% of LAC[Delta]hla-infected rabbits had no hematogenous spread and similar lung and bone bacterial densities. LAC[Delta]pvl and LAC[Delta]hla caused less severe histological lung lesions than LAC(WT) (P <= .01). Between D3 and D9, 10 (53%) LAC(WT)-, 11 (55%) LAC[Delta]pvl-, but no LAC[Delta]hla-infected rabbits (P < .005) died of severe sepsis with disseminated infection. Unlike deceased animals, most LAC(WT), LAC[Delta]pvl, and LAC[Delta]hla D14 survivors had no hematogenous spread (P < .001). LAC(WT) (88%) caused more bone abscesses than LAC[Delta]pvl (0, P = .001) or LAC[Delta]hla (30%, P = .01). Conclusion. In this model, both PVL and Hla seemed to be required for early lung involvement via hematogenous spread. Hla, but not PVL, significantly impacted severe sepsis-related mortality. PVL was the predominant factor determining late-stage bone abscesses. [ABSTRACT FROM AUTHOR]

Published
2014
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36. Emergence of Daptomycin Resistance in Daptomycin-Naïve Rabbits with Methicillin-Resistant Staphylococcus aureus Prosthetic Joint Infection Is Associated with Resistance to Host Defense Cationic Peptides and mprF Polymorphisms.

Author

Mishra, Nagendra N., Yang, Soo-Jin, Chen, Liang, Muller, Claudette, Saleh-Mghir, Azzam, Kuhn, Sebastian, Peschel, Andreas, Yeaman, Michael R., Nast, Cynthia C., Kreiswirth, Barry N., Crémieux, Anne-Claude, and Bayer, Arnold S.

Subjects
STAPHYLOCOCCUS aureus, METHICILLIN-resistant staphylococcus aureus, LABORATORY rabbits, ARTIFICIAL joints, BASIC proteins, GENETIC polymorphisms, DISEASES
Abstract

Background: Previous studies of both clinically-derived and in vitro passage-derived daptomycin–resistant (DAP-R) Staphylococcus aureus strains demonstrated the coincident emergence of increased DAP MICs and resistance to host defense cationic peptides (HDP-R). Methods: In the present investigation, we studied a parental DAP-susceptible (DAP-S) methicillin-resistant Staphylococcus aureus (MRSA) strain and three isogenic variants with increased DAP MICs which were isolated from both DAP-treated and DAP-untreated rabbits with prosthetic joint infections. These strains were compared for: in vitro susceptibility to distinct HDPs differing in size, structure, and origin; i.e.; thrombin-induced platelet microbicidal proteins [tPMPs] and human neutrophil peptide-1 [hNP-1]; cell membrane (CM) phospholipid and fatty acid content; CM order; envelope surface charge; cell wall thickness; and mprF single nucleotide polymorphisms (SNPs) and expression profiles. Results: In comparison with the parental strain, both DAP-exposed and DAP-naive strains exhibited: (i) significantly reduced susceptibility to each HDP (P<0.05); (ii) thicker cell walls (P<0.05); (iii) increased synthesis of CM lysyl-phosphatidylglycerol (L-PG); (iv) reduced content of CM phosphatidylglycerol (PG); and (v) SNPs within the mprF locus No significant differences were observed between parental or variant strains in outer CM content of L-PG, CM fluidity, CM fatty acid contents, surface charge, mprF expression profiles or MprF protein content. An isolate which underwent identical in vivo passage, but without evolving increased DAP MICs, retained parental phenotypes and genotype. Conclusions: These results suggest: i) DAP MIC increases may occur in the absence of DAP exposures in vivo and may be triggered by organism exposure to endogenous HDPs: and ii) gain-in-function SNPs in mprF may contribute to such HDP-DAP cross-resistance phenotypes, although the mechanism of this relationship remains to be defined. [ABSTRACT FROM AUTHOR]

Published
2013
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37. Panton-Valentine Leukocidin Enhances the Severity of Community-Associated Methicillin-Resistant Staphylococcus aureus Rabbit Osteomyelitis.

Author

Crémieux, Anne-Claude, Dumitrescu, Oana, Lina, Gerard, Vallee, Christian, Côté, Jean-François, Muffat-Joly, Martine, Lilin, Thomas, Etienne, Jerome, Vandenesch, François, and Saleh-Mghir, Azzam

Subjects
MEDICAL research, METHICILLIN resistance, OSTEOMYELITIS treatment, LABORATORY rabbits, IMMUNOGLOBULINS, DRUG resistance in microorganisms, STAPHYLOCOCCUS aureus infections, OSTEOMYELITIS, BONE diseases, TIBIAL nerve
Abstract

Background: Extensive spread of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in the United States, and the concomitant increase in severe invasive staphylococcal infections, including osteomyelitis, in healthy children, has led to renewed interest in Panton-Valentine leukocidin (PVL). However, the pathogenetic role of PVL in staphylococcal infections remains controversial, possibly because it depends on the site of infection. Methodology/Principal Findings: We compared the course of experimental rabbit osteomyelitis due to the PVL-positive CA-MRSA strain USA 300 (LAC) and its PVL-negative isogenic derivative (LACDpvl), using a low and a high inoculum (8×105 and 4×108 CFU). With the low inoculum, bone infection was less frequent on day 7 (D7) and day 28 (D28) with LACDpvl than with LAC (respectively 12/19 and 18/19 animals, p = 0.042). With the high inoculum of both strains, all the animals were infected on D7 and the infection persisted on D28 in almost every case. However, tibial bacterial counts and the serum CRP concentration fell significantly between D7 and D28 with LACΔpvl but not with LAC. Respectively 67% and 60% of LACinfected rabbits had bone deformation and muscle/joint involvement on D7, compared to 0% and 7% of LACΔpvl-infected rabbits (p = 0.001 and p = 0.005 respectively). Between D0 and D28, the anti-PVL antibody titer increased significantly only with the high inoculum of LAC. Conclusions/Significance: PVL appears to play a role in the persistence and rapid local extension of rabbit osteomyelitis, in keeping with the greater severity of human bone infections due to PVL-positive S. aureus. The possible therapeutic implications of these findings are discussed. [ABSTRACT FROM AUTHOR]

Published
2009
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38. Evaluation of 99mTc-UBI 29-41 scintigraphy for specific detection of experimental Staphylococcus aureus prosthetic joint infections.

Author

Sarda-Mantel, Laure, Saleh-Mghir, Azzam, Welling, Mick M., Meulemans, Alain, Vrigneaud, Jean-Marc, Raguin, Olivier, Hervatin, Florence, Martet, Geneviève, Chau, Françoise, Lebtahi, Rachida, and Le Guludec, Dominique

Subjects
POSITRON emission tomography, STAPHYLOCOCCUS aureus, PEPTIDE antibiotics, ARTIFICIAL joints, ARTIFICIAL knees
Abstract

99mTc-UBI 29-41 (UBI), an antimicrobial peptide, specifically targets bacteria. We tested the ability of UBI to discriminate between infected and uninfected prosthetic joints using a rabbit model previously validated. Left knee arthroplasty was performed on 20 New Zealand rabbits, then 107 cfu of S. aureus ( n = 12) or sterile saline ( n = 8) was injected into the joint. On days 9 and 20 after surgery, planar UBI scintigraphy was performed in six infected and four uninfected rabbits, 1 h and 4 h p.i. (150 MBq), on a gamma camera. Operated-to-normal knee activity ratio (ONKR) was calculated on each scintigram. Then, after sacrifice, tissue samples of both knees were counted in a gamma counter. One rabbit injected with sterile saline had cutaneous infection at sacrifice and was excluded from analysis. ONKR was higher in infected than in uninfected animals 4 h p.i. 20 days after surgery: 1.75 ± 0.48 vs 1.13 ± 0.11, p = 0.04. From 1 h to 4 h p.i., ONKR increased in 9/12 infected and 0/7 uninfected animals. According to UBI uptake intensity and kinetics, scintigraphy was truly positive in all infected cases on day 9 and in four of six infected cases on day 20. It was truly negative in two of three sterile inflamed prosthetic knees on day 9, and in all cases on day 20. Biodistribution studies revealed increased UBI uptake in periprosthetic tissues in all animals 9 days after surgery, and only in infected animals on day 20. In this experimental study, 99mTc-UBI 29-41 scintigraphy permitted the early detection of acute prosthetic joint infection, and exclusion of infection in chronic sterile prosthetic joint inflammation. [ABSTRACT FROM AUTHOR]

Published
2007
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40. Native bone and joint infections caused by extended-spectrum β-lactamase-producing Enterobacterales: experience of a reference centre in the Greater Paris area.

Author

Davido, B., Saleh-Mghir, A., Rottman, M., Jaffal, K., Salomon, E., Bouchand, F., Lawrence, C., Bauer, T., Herrmann, J.L., De Truchis, P., Noussair, L., and Cremieux, A.C.

Subjects
*KLEBSIELLA pneumoniae, *KLEBSIELLA infections, *OSTEOMYELITIS, *JOINT infections, *JOINTS (Anatomy), *REOPERATION, *PRESSURE ulcers, *INFECTION
Abstract

• Native osteomyelitis caused by ESBL-producing Enterobacteriaceae remains a rare condition. • Osteomyelites caused by Klebsiella pneumoniae appeared to be associated with an unfavourable outcome. • Treatment is complex and mainly based on combination therapy with carbapenems. Antibiotic treatment of native osteomyelitis caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) is a challenge. Limited epidemiological and outcome data are available. This retrospective cohort study included osteomyelitis patients with ESBL-PE infections treated in a reference centre for bone and joint infections (BJIs) between 2011–2019. Twenty-nine patients with native BJI (mean age, 44.4 ± 15.7 years) were analysed. Fifteen cases were paraplegic patients with ischial pressure sores breaching the hip capsule. Other cases included eight other hip infections, four tibial infections and two foot infections. Infections were mostly polymicrobial (n = 23; 79.3%), including Staphylococcus aureus (n = 13; 8 methicillin-resistant). Klebsiella pneumoniae (n = 13) was the most frequent ESBL-producing species identified, followed by Escherichia coli (n = 10), including 3 E. coli / K. pneumoniae co-infections, and Enterobacter spp. (n = 9). ESBL-PE were rarely susceptible to fluoroquinolones (n = 4; 13.8%). Most therapies were based on carbapenems (n = 22) and combination therapies (n = 19). The median duration of treatment was 41 (5–60) days. Primary control of the infection was achieved in 62.1% (18/29) of cases and up to 86.2% after second look surgeries, after a median follow-up of 6 (1–36) months. Infection with ESBL-producing K. pneumoniae was associated with failure (P = 0.001), whereas age, infection location, prior colonisation and antimicrobial therapy were not found to be predictors of outcome. ESBL-PE native BJIs are often polymicrobial and fluoroquinolone-resistant infections caused by K. pneumoniae , highlighting the need for expert centres with pluridisciplinary meetings with experienced surgeons. [ABSTRACT FROM AUTHOR]

Published
2022
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41. Germs of thrones - spontaneous decolonization of Carbapenem-Resistant Enterobacteriaceae (CRE) and Vancomycin-Resistant Enterococci (VRE) in Western Europe: is this myth or reality?

Author

Davido, Benjamin, Moussiegt, Aurore, Dinh, Aurélien, Bouchand, Frédérique, Matt, Morgan, Senard, Olivia, Deconinck, Laurene, Espinasse, Florence, Lawrence, Christine, Fortineau, Nicolas, Saleh-Mghir, Azzam, Caballero, Silvia, Escaut, Lelia, and Salomon, Jérome

Subjects
DRUG resistance in bacteria, ENTEROBACTERIACEAE
Abstract

Background: In France, Carbapenem-Resistant Enterobacteriaceae (CRE) and Vancomycin-Resistant Enterococci (VRE) are considered as Extensively Drug-Resistant (XDR) bacteria. Their management requires reinforcement of hospital’s hygiene policies, and currently there is few consistent data concerning the spontaneous decolonization in XDR colonized patients. Our aim is to study the natural history of decolonization of XDR carriers over time in a hospital setting in a low prevalence country. Material and methods: Retrospective multicenter study over 2 years (2015–2016) in 2 different tertiary care hospital sites and units having an agreement for permanent cohorting of such XDR carriers. We gathered the type of microorganisms, risk factors for colonization and rectal swabs from patient’s follow-up. We also evaluated patient care considering isolation precautions. Results: We included 125 patients, aged 63+/−19y, including 72.8% of CRE (n = 91), 24.8% of VRE (n = 31) and 2.4% (n = 3) co-colonized with CRE and VRE. CRE were mainly E. coli (n = 54), K. pneumoniae (n = 51) and E. cloacae (n = 6). Mechanisms of resistance were mainly OXA-48 (n = 69), NDM-1 (n = 11), OXA-232 (n = 8) and KPC (n = 3). Prior antibiotic therapy was reported in 38.4% (n = 48) of cases. Conversely, 17.6% (n = 22) received antibiotics during follow-up. Spontaneous decolonization occurred within the first 30 days in 16.4% (n = 19/116) of cases and up to 48.2% after day-90 with a median follow-up of 96 days (0–974). We estimated that XDR carriage was associated with a larger care burden in 13.6% (n = 17) of cases, especially due to a prolongation of hospitalization of 32.5 days (15–300). Conclusions: Our study shows that spontaneous decolonization is increasing over time (up to 48.2%). We can regret that only few patients underwent screening after 1 year, emphasizing the need for more monitoring and prospective studies. [ABSTRACT FROM AUTHOR]

Published
2018
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43. Effect of achieving bone sterilisation on bone architecture and bone marrow, in an experimental rabbit model of osteomyelitis caused by carbapenemase-producing Enterobacterales.

Author

Davido, B., Crémieux, A.C., Nich, C., De Truchis, P., Vaugier, I., Gatin, L., Tattevin, P., and Saleh-Mghir, A.

Subjects
*KLEBSIELLA infections, *OSTEOMYELITIS, *BONE marrow, *TREATMENT effectiveness, *RABBITS, *KLEBSIELLA pneumoniae, *ODDS ratio
Abstract

• Deformation of normal bone architecture usually appears after 2 weeks of infection. • Osteomyelitis caused by CPE is aggressive according to bone modification scales. • Achieving bone sterilisation promotes a lower degree of bone deformation. • Bone modifications under antibiotics is as a valuable proxy to predict outcome. Natural history and treatment of bone infections caused by carbapenemase-producing Enterobacterales (CPE) are poorly defined. We evaluated the effect of treatment on the progression of subacute osteomyelitis in a rabbit model. Two isolates were used: a KPC-producing Klebsiella pneumoniae and an Escherichia coli harbouring bla OXA-48 and bla CTX-M15 inserts, both susceptible to gentamicin, colistin, fosfomycin, and ceftazidime-avibactam. Osteomyelitis was induced in rabbits by tibial injection of 2 × 108 colony-forming units/mL. Antibiotics were started 14 d later, for 7 d, in 6 groups of 12 rabbits. Three days after treatment completion (D24), rabbits were euthanised and bones were cultured. Bone marrow and bone architecture macroscopic changes were evaluated through analysis of pictures by investigators unaware of the rabbit treatment group and microbiological outcome, using scales ranging from 0 (normal) to 3 (severe lesions) depending on modifications. Bone marrow modifications induced by local infection were similar between prematurely deceased animals and non-sterilised animals (P = 0.14) but differed significantly from animals that achieved bone sterilisation after treatment (P = 0.04). Conversely, when comparing bone deformity, rabbits who died early (n = 13) had similar bone architecture as those achieving bone sterilisation (P = 0.12), as opposed to those not sterilised after treatment (P = 0.04). After a multivariate logistic regression, bone marrow scale ≤2 was associated with bone sterilisation (P < 0.001), and bone architecture scale ≤2 was associated with bone sterilisation (adjusted odds ratio = 2.7; 95% confidence interval 1.14–6.37) and KPC infection (adjusted odds ratio = 5.1; 95% confidence interval 2.17–12.13). Effective antibacterial treatment reduces bone architecture distortion and bone marrow changes. These variables may be used as proxy for bone sterilisation. [ABSTRACT FROM AUTHOR]

Published
2023
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