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Your search keyword '"Tozzi, Margherita"' showing total 3 results
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3 results on '"Tozzi, Margherita"'

1. Continuous infusion versus intermittent administration of meropenem in critically ill patients (MERCY): A multicenter randomized double-blind trial. Rationale and design.

Author

Monti G, Galbiati C, Toffoletto F, Calabrò MG, Colombo S, Ferrara B, Giardina G, Lembo R, Marzaroli M, Moizo E, Mucci M, Pasculli N, Plumari VP, Scandroglio AM, Tozzi M, Momesso E, Boffa N, Lobreglio R, Montrucchio G, Guarracino F, Benedetto U, Biondi-Zoccai G, D'Ascenzo F, D'Andrea N, Paternoster G, Ananiadou S, Ballestra M, De Sio A, Pota V, Cotoia A, Della Selva A, Bruni A, Iapichino G, Bradić N, Corradi F, Gemma M, Nogtev P, Petrova M, Agrò FE, Cabrini L, Forfori F, Likhvantsev V, Bove T, Finco G, Landoni G, and Zangrillo A

Subjects
Anti-Bacterial Agents therapeutic use, Critical Care, Humans, Meropenem, Critical Illness, Sepsis drug therapy
Abstract

Objective: Meropenem is a β-lactam, carbapenem antibacterial agent with antimicrobial activity against gram-negative, gram-positive and anaerobic micro-organisms and is important in the empirical treatment of serious infections in Intensive Care Unit (ICU) patients. Multi-drug resistant gram-negative organisms, coupled with scarcity of new antibiotic classes, forced healthcare community to optimize the therapeutic potential of available antibiotics. Our aim is to investigate the effect of continuous infusion of meropenem against bolus administration, as indicated by a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens in a population of ICU patients., Design: Double blind, double dummy, multicenter randomized controlled trial (1:1 allocation ratio)., Setting: Tertiary and University hospitals., Interventions: 600 ICU patients with sepsis or septic shock, needing by clinical judgment antibiotic therapy with meropenem, will be randomized to receive a continuous infusion of meropenem 3 g/24 h or an equal dose divided into three daily boluses (i.e. 1g q8h)., Measurements: The primary endpoint will be a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens. Secondary endpoints will be death from any cause at day 90, antibiotic-free days at day 28, ICU-free days at day 28, cumulative SOFA-free (Sequential Organ Failure Assessment) score from randomization to day 28 and the two, separate, components of the primary endpoint. We expect a primary outcome reduction from 52 to 40% in the continuous infusion group., Conclusions: The trial will provide evidence for choosing intermittent or continuous infusion of meropenem for critically ill patients with multi-drug resistant gram-negative infections., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Published
2021
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2. A Bayesian reanalysis of the standard versus accelerated initiation of renal-replacement therapy in acute kidney injury (STARRT-AKI) trial

Author

Zampieri, Fernando G., da Costa, Bruno R., Vaara, Suvi T., Lamontagne, François, Rochwerg, Bram, Nichol, Alistair D., McGuinness, Shay, McAuley, Danny F., Ostermann, Marlies, Wald, Ron, Bagshaw, Sean M., Adhikari, Neill K. J., Bellomo, Rinaldo, Dreyfuss, Didier, Du, Bin, Gallagher, Martin P., Gaudry, Stéphane, Joannidis, Michael, Liu, Kathleen D., McAuley, Daniel F., McGuinness, Shay P., Palevsky, Paul M., Qiu, Haibo, Pettilä, Ville, Schneider, Antoine G., Smith, Orla M., Vaara, Suvi, Weir, Matthew, Eastwood, Glenn M., Peck, Leah, Young, Helen, Kruger, Peter, Laurie, Gordon, Saylor, Emma, Meyer, Jason, Venz, Ellen, Wetzig, Krista, French, Craig, McGain, Forbes, Mulder, John, Fennessy, Gerard, Koottayi, Sathyajith, Bates, Samantha, Towns, Miriam, Morgan, Rebecca, Tippett, Anna, Udy, Andrew, Mason, Chris, Licari, Elisa, Gantner, Dashiell, McClure, Jason, Nichol, Alistair, McCracken, Phoebe, Board, Jasmin, Martin, Emma, Vallance, Shirley, Young, Meredith, Vladic, Chelsey, McGloughlin, Steve, Gattas, David, Buhr, Heidi, Coles, Jennifer, Hutch, Debra, Wun, James, Cole, Louise, Whitehead, Christina, Lowrey, Julie, Masters, Kristy, Gresham, Rebecca, Campbell, Victoria, Gutierrez, David, Brailsford, Jane, Forbes, Loretta, Murray, Lauren, Maguire, Teena, NiChonghaile, Martina, Orford, Neil, Bone, Allison, Elderkin, Tania, Salerno, Tania, Chimunda, Tim, Fletcher, Jason, Broadfield, Emma, Porwal, Sanjay, Knott, Cameron, Boschert, Catherine, Smith, Julie, Richardson, Angus, Hill, Dianne, Duke, Graeme, Oziemski, Peter, Cegarra, Santiago, Chan, Peter, Welsh, Deborah, Hunter, Stephanie, Roodenburg, Owen, Dyett, John, Kokotsis, Nicos, Moser, Max, Yang, Yang, Padayachee, Laven, Vetro, Joseph, Gangopadhyay, Himangsu, Kaufman, Melissa, Ghosh, Angaj, Said, Simone, Patel, Alpesh, Bihari, Shailesh, Matheson, Elisha, Jin, Xia, Shrestha, Tapaswi, Schwartz, Kate, Cross, Rosalba, Cheung, Winston, Wong, Helen, Kol, Mark, Shah, Asim, Wang, Amanda Y., Endre, Zoltan, Bradford, Celia, Janin, Pierre, Finfer, Simon, Diel, Naomi, Gatward, Jonathan, Hammond, Naomi, Delaney, Anthony, Bass, Frances, Yarad, Elizabeth, Buscher, Hergen, Reynolds, Claire, Baker, Nerilee, Bellmann, Romuald, Peer, Andreas, Hasslacher, Julia, Koglberger, Paul, Klein, Sebastian, Zotter, Klemens, Brandtner, Anna, Finkenstedt, Armin, Ditlbacher, Adelheid, Hartig, Frank, Fries, Dietmar, Bachler, Mirjam, Schenk, Bettina, Wagner, Martin, Eller, Philipp, Staudinger, Thomas, Tiller, Esther, Schellongowski, Peter, Bojic, Andja, Hoste, Eric, Bracke, Stephanie, De Crop, Luc, Vermeiren, Daisy, Thome, Fernando, Chiella, Bianca, Fendt, Lucia, Antunes, Veronica, Lafrance, Jean-Philippe, D’Aragon, Frédérick, St-Arnaud, Charles, Mayette, Michael, Carbonnaeu, Élaine, Marchand, Joannie, Masse, Marie-Hélène, Ladouceur, Marilène, Turgeon, Alexis F., Lauzier, François, Bellemare, David, Francoeur, Charles Langis, LeBlanc, Guillaume, Guilbault, Gabrielle, Grenier, Stéphanie, Cloutier, Eve, Boivin, Annick, Delisle-Thibault, Charles, Giannakouros, Panagiota, Costerousse, Olivier, Cailhier, Jean-François, Carrier, François-Martin, Ghamraoui, Ali, Lebrasseur, Martine, Benettaib, Fatna, Salamé, Maya, Boumahni, Dounia, Sia, Ying Tung, Naud, Jean-François, Roy, Isabelle, Stelfox, Henry T., Ruddell, Stacey, Manns, Braden J., Duggan, Shelley, Carney, Dominic, Barchard, Jennifer, Whitlock, Richard P., Belley-Cote, Emilie, Savija, Nevena, Sabev, Alexandra, Campbell, Troy, Creary, Thais, Devereaux, Kelson, Brodutch, Shira, Rigatto, Claudio, Paunovic, Bojan, Mooney, Owen, Glybina, Anna, Harasemiw, Oksana, Di Nella, Michelle, Harmon, John, Mehta, Navdeep, Lakatos, Louis, Haslam, Nicole, Lellouche, Francois, Simon, Mathieu, Tung, Ying, Lizotte, Patricia, Bourchard, Pierre-Alexandre, Karachi, Tim, Millen, Tina, Muscedere, John, Maslove, David, Gordon Boyd, J., Sibley, Stephanie, Drover, John, Hunt, Miranda, Georgescu, Ilinca, Wax, Randy, Lenga, Ilan, Sridhar, Kavita, Steele, Andrew, Fusco, Kelly, Ghate, Taneera, Tolibas, Michael, Robinson, Holly, Weir, Matthew A., Taneja, Ravi, Ball, Ian M., Garg, Amit, Campbell, Eileen, Ovsenek, Athena, van Diepen, Sean, Baig, Nadia, Magder, Sheldon, Yao, Han, Alam, Ahsan, Campisi, Josie, MacIntyre, Erika, Rokosh, Ella, Scherr, Kimberly, Lapinsky, Stephen, Mehta, Sangeeta, Shah, Sumesh, Niven, Daniel J., Russell, Michael, Jim, Kym, Brown, Gillian, Oxtoby, Kerry, Hall, Adam, Benoit, Luc, Sokolowski, Colleen, Prasad, Bhanu, Rao, Jag, Giebel, Shelley, Kutsogiannis, Demetrios J., Thompson, Patricia, Thompson, Tayne, Cirone, Robert, Kavikondala, Kanthi, Soth, Mark, Clarke, France, Takaoka, Alyson, Mazer, David, Burns, Karen, Friedrich, Jan, Klein, David, Sandhu, Gyan, Santos, Marlene, Khalid, Imrana, Hodder, Jennifer, Dodek, Peter, Ayas, Najib, Alcuaz, Victoria, Suen, Gabriel, Rewa, Oleksa, Singh, Gurmeet, Norris, Sean, Gibson, Neil, Arias, Castro, Shami, Aysha, Pelletier, Celine, Zahirieh, Alireza, Amaral, Andre, Marinoff, Nicole, Kaur, Navjot, Perez, Adic, Wang, Jane, Haljan, Gregory, Condin, Christopher, McIntyre, Lauralyn, Gomes, Brigette, Porteous, Rebecca, Watpool, Irene, Hiremath, Swapnil, Clark, Edward, Herridge, Margaret S., Backhouse, Felicity, Elizabeth Wilcox, M., Walczak, Karolina, Ki, Vincent, Sharman, Asheer, Romano, Martin, Noel Gibney, R. T., Romanovsky, Adam S., McCoshen, Lorena, Wood, Gordon, Ovakim, Daniel, Auld, Fiona, Carney, Gayle, Duan, Meili, Ji, Xiaojun, Guo, Dongchen, Qi, Zhili, Lin, Jin, Zhang, Meng, Dong, Lei, Liu, Jingfeng, Liu, Pei, Zhi, Deyuan, Bai, Guoqiang, Qiu, Yu, Yang, Ziqi, Bai, Jing, Liu, Zhuang, Zhuang, Haizhou, Wang, Haiman, Li, Jian, Zhao, Mengya, Zhou, Xiao, Shi, Xianqing, Ye, Baning, Liu, Manli, Wu, Jing, Fu, Yongjian, Long, Dali, Pan, Yu, Wang, Jinlong, Mei, Huaxian, Zhang, Songsong, Wen, Mingxiang, Yang, Enyu, Mu, Sijie, Li, Jianquan, Hu, Tingting, Qin, Bingyu, Li, Min, Wang, Cunzhen, Dong, Xin, Wang, Kaiwu, Wang, Haibo, Yang, Jianxu, Wang, Chuanyao, Wang, Dongxin, Li, Nan, Yu, Zhui, Xu, Song, Yao, Lan, Hou, Guo, Liu, Zhou, Lu, Liping, Lian, Yingtao, Wang, Chunting, Zhang, Jichen, Ding, Ruiqi, Qi, Guoqing, Wang, Qizhi, Wang, Peng, Meng, Zhaoli, Chen, Man, Hu, Xiaobo, He, Xiandi, Zhao, Shibing, Hang, Lele, Li, Rui, Qin, Suhui, Lu, Kun, Dun, Shijuan, Liu, Cheng, Zhou, Qi, Chen, Zhenzhen, Mei, Jing, Zhang, Minwei, Xu, Hao, Lin, Jincan, Shi, Qindong, Fu, Lijuan, Zeng, Qinjing, Ma, Hongye, Yan, Jinqi, Gao, Lan, Liu, Hongjuan, Zhang, Lei, Li, Hao, He, Xiaona, Fan, Jingqun, Guo, Litao, Liu, Yu, Wang, Xue, Sun, Jingjing, Liu, Zhongmin, Yang, Juan, Ding, Lili, Sheng, Lulu, Liu, Xingang, Yan, Jie, Wang, Quihui, Wang, Yifeng, Zhao, Dan, Zhao, Shuangping, Hu, Chenghuan, Li, Jing, Deng, Fuxing, Qui, Haibo, Yang, Yi, Mo, Min, Pan, Chun, Wu, Changde, Huang, Yingzi, Huang, Lili, Liu, Airan, Korhonen, Anna-Maija, Törnblom, Sanna, Sutinen, Sari, Pettilä, Leena, Heinonen, Jonna, Lappi, Eliria, Suhonen, Taria, Karlsson, Sari, Hoppu, Sanna, Jalkanen, Ville, Kuitunen, Anne, Levoranta, Markus, Långsjö, Jaakko, Ristimäki, Sanna, Malila, Kaisa, Wootten, Anna, Varila, Simo, Järvisalo, Mikko J., Inkinen, Outi, Kentala, Satu, Leivo, Keijo, Haltia, Paivi, Ricard, Jean-Damien, Messika, Jonathan, Tiagarajah, Abirami, Emery, Malo, Dechanet, Aline, Gernez, Coralie, Roux, Damien, Martin-Lefevre, Laurent, Fiancette, Maud, Vinatier, Isabelle, Lacherade, Jean Claude, Colin, Gwenhaël, Lebert, Christine, Azais, Marie-Ange, Yehia, Aihem, Pouplet, Caroline, Lagarrigue, Matthieu Henry, Seguin, Amélie, Crosby, Laura, Maizel, Julien, Titeca-Beauport, Dimitri, Combes, Alain, Nieszkowska, Ania, Masi, Paul, Demoule, Alexandre, Mayaux, Julien, Dres, Martin, Morawiec, Elise, Decalvele, Maxens, Demiri, Suela, Faure, Morgane, Marios, Clémence, Mallet, Maxime, Ordon, Marie Amélie, Morizot, Laura, Cantien, Marie, Pousset, François, Poirson, Florent, Cohen, Yves, Argaud, Laurent, Cour, Martin, Bitker, Laurent, Simon, Marie, Hernu, Romain, Baudry, Thomas, De La Salle, Sylvie, Robine, Adrien, Sedillot, Nicholas, Tchenio, Xavier, Bouisse, Camille, Roux, Sylvie, Barbar, Saber Davide, Trusson, Rémi, Tamion, Fabienne, Grangé, Steven, Carpentier, Dorothée, Chevrel, Guillaume, Ensenyat-Martin, Luis, Marque, Sophie, Quenot, Jean-Pierre, Andreu, Pascal, Dargent, Auguste, Large, Audrey, Chudeau, Nicolas, Landais, Mickael, Derrien, Benoit, Callahan, Jean Christophe, Guitton, Christophe, Le Moal, Charlène, Robert, Alain, Asehnoune, Karim, Cinotti, Raphaël, Grillot, Nicolas, Demeure, Dominique, Vinsonneau, Christophe, Rahmani, Imen, Marzouk, Mehdi, Dekeyser, Thibault, Sejourne, Caroline, Verlay, Mélanie, Thevenin, Fabienne, Delecolle, Lucie, Thevenin, Didier, Souweine, Bertrand, Coupez, Elisabeth, Adda, Mireille, Eraldi, Jean-Pierre, Marchalot, Antoine, De Prost, Nicolas, Dessap, Armand Mekontso, Razazi, Keyvan, Meziani, Ferhat, Boisrame-Helms, Julie, Clere-Jehl, Raphael, Delabranche, Xavier, Kummerlen, Christine, Merdji, Hamid, Monnier, Alexandra, Rabouel, Yannick, Rahmani, Hassene, Allam, Hayat, Chenaf, Samir, Franja, Vincenta, Pons, Bertrand, Carles, Michel, Martino, Frédéric, Richard, Régine, Zuber, Benjamin, Lacave, Guillaume, Lakhal, Karim, Rozec, Bertrand, Van, Hoa Dang, Boulet, Éric, Fadel, Fouad, Cleophax, Cedric, Dufour, Nicolas, Grant, Caroline, Thuong, Marie, Reignier, Jean, Canet, Emmanuel, Nicolet, Laurent, Boulain, Thierry, Nay, Mai-Anh, Benzekri, Dalila, Barbier, François, Bretagnol, Anne, Kamel, Toufik, Mathonnet, Armelle, Muller, Grégoire, Skarzynski, Marie, Rossi, Julie, Pradet, Amandine, Dos Santos, Sandra, Guery, Aurore, Muller, Lucie, Felix, Luis, Bohé, Julien, Thiéry, Guillaume, Aissaoui, Nadia, Vimpere, Damien, Commeureuc, Morgane, Diehl, Jean-Luc, Guerot, Emmanuel, Liangos, Orfeas, Wittig, Monika, Zarbock, Alexander, Küllmar, Mira, van Waegeningh, Thomas, Rosenow, Nadine, Brickell, Kathy, Doran, Peter, Murray, Patrick T., Landoni, Giovanni, Lembo, Rosalba, Zangrillo, Alberto, Monti, Giacomo, Tozzi, Margherita, Marzaroli, Matteo, Lombardi, Gaetano, Paternoster, Gianluca, Vitiello, Michelangelo, Parke, Rachael, Butler, Magdalena, Gilder, Eileen, Cowdrey, Keri-Anne, Wallace, Samantha, Hallion, Jane, Woolett, Melissa, Neal, Philippa, Duffy, Karina, Long, Stephanie, McArthur, Colin, Simmonds, Catherine, Chen, Yan, McConnochie, Rachael, Newby, Lynette, Knight, David, Henderson, Seton, Mehrtens, Jan, Morgan, Stacey, Morris, Anna, Vander Hayden, Kymbalee, Burke, Tara, Bailey, Matthew, Freebairn, Ross, Chadwick, Lesley, Park, Penelope, Rolls, Christine, Thomas, Liz, Buehner, Ulrike, Williams, Erin, Albrett, Jonathan, Kirkham, Simon, Jackson, Carolyn, Browne, Troy, Goodson, Jennifer, Jackson, David, Houghton, James, Callender, Owen, Higson, Vicki, Keet, Owen, Dominy, Clive, Young, Paul, Hunt, Anna, Judd, Harriet, Lawrence, Cassie, Olatunji, Shaanti, Robertson, Yvonne, Latimer-Bell, Charlotte, Hendry, Deborah, Mckay-Vucago, Agnes, Beehre, Nina, Lesona, Eden, Navarra, Leanlove, Robinson, Chelsea, Jang, Ryan, Junge, Andrea, Lambert, Bridget, Thibault, Michel, Eckert, Philippe, Kissling, Sébastien, Polychronopoulos, Erietta, Poli, Elettra, Altarelli, Marco, Schnorf, Madeleine, Mallaird, Samia Abed, Heidegger, Claudia, Perret, Aurelie, Montillier, Philippe, Sangla, Frederic, Neils, Seigenthaller, De Watteville, Aude, Phull, Mandeep-Kaur, George, Aparna, Hussain, Nauman, Pogreban, Tatiana, Lobaz, Steve, Daniels, Alison, Cunningham, Mishell, Kerr, Deborah, Nicholson, Alice, Shanmugasundaram, Pradeep, Abrams, Judith, Manso, Katarina, Hambrook, Geraldine, McKerrow, Elizabeth, Salva, Juvy, Foulkes, Stephen, Wise, Matthew, Morgan, Matt, Brooks, Jenny, Cole, Jade, Davies, Tracy Michelle, Hill, Helen, Thomas, Emma, Vizcaychipi, Marcela, Baharlo, Behrad, Carungcong, Jaime, Costa, Patricia, Martins, Laura, Kapoor, Ritoo, Hazelton, Tracy, Moon, Angela, Musselwhite, Janine, Shelley, Ben, McCall, Philip, Arbane, Gill, Bociek, Aneta, Marotti, Martina, Lim, Rosario, Campos, Sara, Novellas, Neus Grau, Cennamo, Armando, Slack, Andrew, Wyncoll, Duncan, Camporota, Luigi, Sparkes, Simon, Tilley, Rosalinde, Rattray, Austin, Moreland, Gayle, Duffy, Jane, McGonigal, Elizabeth, Hopkins, Philip, Finney, Clare, Smith, John, Noble, Harriet, Watson, Hayley, Harris, Claire-Louise, Clarey, Emma, Corcoran, Eleanor, Beck, James, Howcroft, Clare, Youngs, Nora, Wilby, Elizabeth, Ogg, Bethan, Wolverson, Adam, Lee, Sandra, Butler, Susie, Okubanjo, Maryanne, Hindle, Julia, Welters, Ingeborg, Williams, Karen, Johnson, Emily, Patrick-Heselton, Julie, Shaw, David, Waugh, Victoria, Stewart, Richard, Mwaura, Esther, Wren, Lynn, Mew, Louise, Sutherland, Sara-Beth, Adderley, Jane, Ruddy, Jim, Harkins, Margaret, Kaye, Callum, Scott, Teresa, Mitchell, Wendy, Anderson, Felicity, Willox, Fiona, Jagannathan, Vijay, Clark, Michele, Purv, Sarah, Sharman, Andrew, Meredith, Megan, Ryan, Lucy, Conner, Louise, Peters, Cecilia, Harvey, Dan, Roshdy, Ashraf, Collins, Amy, Sim, Malcolm, Henderson, Steven, Chee, Nigel, Pitts, Sally, Bowman, Katie, Dilawershah, Maria, Vamplew, Luke, Howe, Elizabeth, Rogers, Paula, Hernandez, Clara, Prendergast, Clara, Benton, Jane, Rosenberg, Alex, Forni, Lui G., Grant, Alice, Carvelli, Paula, Raithatha, Ajay, Bird, Sarah, Richardson, Max, Needham, Matthew, Hirst, Claire, Ball, Jonathan, Leaver, Susannah, Howlett, Luisa, Delgado, Carlos Castro, Farnell-Ward, Sarah, Farrah, Helen, Gray, Geraldine, Joseph, Gipsy, Robinson, Francesca, Tridente, Ascanio, Harrop, Clare, Shuker, Karen, McLaughlan, Derek, Ramsey, Judith, Meehan, Sharon, Rose, Bernd Oliver, Reece-Anthony, Rosie, Gurung, Babita, Whitehouse, Tony, Snelson, Catherine, Veenith, Tonny, Johnston, Andy, Cooper, Lauren, Carrera, Ron, Ellis, Karen, Fellows, Emma, Harkett, Samanth, Bergin, Colin, Spruce, Elaine, Despy, Liesl, Goundry, Stephanie, Dooley, Natalie, Mason, Tracy, Clark, Amy, Dignam, Gemma, Ward, Geraldine, Attwood, Ben, Parsons, Penny, Mason, Sophie, Margarson, Michael, Lord, Jenny, McGlone, Philip, Hodgson, Luke E., Chadbourn, Indra, Gomez, Raquel, Margalef, Jordi, Pretorius, Rinus, Hamshere, Alexandra, Carter, Joseph, Cahill, Hazel, Grainger, Lia, Howard, Kate, Forshaw, Greg, Guy, Zoe, Kashani, Kianoush B., Albright, Robert C., Amsbaugh, Amy, Stoltenberg, Anita, Niven, Alexander S., Lynch, Matthew, O’Mara, AnnMarie, Naeem, Syed, Sharif, Sairah, Goulart, Joyce McKenney, Tolwani, Ashita, Lyas, Claretha, Latta, Laura, Bihorac, Azra, Hashemighouchani, Haleh, Efron, Philip, Ruppert, Matthew, Cupka, Julie, Kiley, Sean, Carson, Joshua, White, Peggy, Omalay, George, Brown, Sherry, Velez, Laura, Marceron, Alina, Neyra, Javier A., Aycinena, Juan Carlos, Elias, Madona, Ortiz-Soriano, Victor M., Hauschild, Caroline, Dorfman, Robert, Investigators, STARRT-AKI, Investigators, STARRT-AKI, Zampieri Fernando, G, da Costa Bruno, R, Vaara Suvi, T, Lamontagne, Françoi, Rochwerg, Bram, Nichol Alistair, D, Mcguinness, Shay, McAuley Danny, F, Ostermann, Marlie, Wald, Ron, Bagshaw Sean, M, STARRT-AKI, Investigator, Landoni, G, and Zangrillo, A

Subjects
Kidney-replacement therapy, Critical Illness, Acute Kidney Injury/therapy, Randomized, Bayes Theorem, Acute Kidney Injury, Critical Care and Intensive Care Medicine, Bayesian, Trial, Acute kidney injury, Renal Replacement Therapy, Renal Replacement Therapy/methods, Critical Illness/therapy, Medicine and Health Sciences, Humans, Mortality, Dialysis, Probability
Abstract

Background Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. Methods We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. Results The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. Conclusions In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation.

Published
2022
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3. Continuous infusion versus intermittent administration of meropenem in critically ill patients (MERCY): A multicenter randomized double-blind trial. Rationale and design

Author

Ingrid Marcela Pabon, Barbara Azzali, Mattia Bozzetti, Vincenzo Pota, Antonio De Sio, Andrey Yavorovskiy, Natascia D'Andrea, Rosetta Lobreglio, Andrea Della Selva, Evgeny Fominskiy, Federico Canavosio, Barbara Ferrara, Vittorio Pazzanese, Francesca Gallicchio, Nicola Pasculli, Valery Likhvantsev, Eugenio Garofalo, Sergio Colombo, Anna Mara Scandroglio, Felice Eugenio Agrò, Margherita Tozzi, Gianluca Paternoster, Francesco Corradi, Tiziana Bove, Filippo Palmesino, Elena Momesso, Luigi Vetrugno, Francesco Giuseppe Nisi, Giorgia Montrucchio, Daniela Missio, Mara Bernasconi, Giacomo Monti, Mariano Ballestra, Marco Gemma, Giovanni Marino, Silvia Ajello, Alberto Zangrillo, Rosalba Lembo, Maria Grazia Calabrò, Romina Perone, Andrea Bruni, Pavel Nogtev, Alberto Cappelletti, Gabriele Finco, Daniele Cristadoro, Leonarda Pia Cantatore, Marina Pieri, Sofia Ananiadou, Italo Calamai, Chiara Millin, A. Mattei, Luca Cabrini, Marina Petrova, Valentina Paola Plumari, Nicoletta Boffa, Davide Maraggia, Elena Moizo, Gianna Curci, Giovanni Landoni, Giuseppe Biondi-Zoccai, Giuseppe Giardina, Giacomo Iapichino, Carola Galbiati, Fabio Guarracino, Antonella Cotoia, Matteo Marzaroli, Nikola Bradic, Umberto Benedetto, Giorgio Gallioli, Fabrizio D'Ascenzo, Francesco Forfori, Fabio Toffoletto, Milena Mucci, Manuela Mainetti, Monti, G., Galbiati, C., Toffoletto, F., Calabro, M. G., Colombo, S., Ferrara, B., Giardina, G., Lembo, R., Marzaroli, M., Moizo, E., Mucci, M., Pasculli, N., Plumari, V. P., Scandroglio, A. M., Tozzi, M., Momesso, E., Boffa, N., Lobreglio, R., Montrucchio, G., Guarracino, F., Benedetto, U., Biondi-Zoccai, G., D'Ascenzo, F., D'Andrea, N., Paternoster, G., Ananiadou, S., Ballestra, M., De Sio, A., Pota, V., Cotoia, A., Della Selva, A., Bruni, A., Iapichino, G., Bradic, N., Corradi, F., Gemma, M., Nogtev, P., Petrova, M., Agro, F. E., Cabrini, L., Forfori, F., Likhvantsev, V., Bove, T., Finco, G., Landoni, G., Zangrillo, A., Ajello, S., Cappelletti, A. M., Fominskiy, E., Nisi, F. G., Pazzanese, V., Pieri, M., Canavosio, F., Palmesino, F., Bernasconi, M., Gallioli, G., Marino, G., Vetrugno, L., Millin, C., Missio, D., Gallicchio, F., Azzali, B., Bozzetti, M., Cristadoro, D., Perone, R., Cantatore, L. P., Curci, G., Pabon, I. M., Garofalo, E., Mainetti, M., Calamai, I., Maraggia, D., Mattei, A., Yavorovskiy, A., Monti, Giacomo, Galbiati, Carola, Toffoletto, Fabio, Calabrò, Maria Grazia, Colombo, Sergio, Ferrara, Barbara, Giardina, Giuseppe, Lembo, Rosalba, Marzaroli, Matteo, Moizo, Elena, Mucci, Milena, Pasculli, Nicola, Plumari, Valentina, Scandroglio, Anna Mara, Tozzi, Margherita, Momesso, Elena, Boffa, Nicoletta, Lobreglio, Rosetta, Montrucchio, Giorgia, Guarracino, Fabio, Benedetto, Umberto, Biondi-Zoccai, Giuseppe, D'Ascenzo, Fabrizio, D'Andrea, Natascia, Paternoster, Gianluca, Ananiadou, Sofia, Ballestra, Mariano, De Sio, Antonio, Pota, Vincenzo, Cotoia, Antonella, Selva, Andrea Della, Bruni, Andrea, Iapichino, Giacomo, Bradić, Nikola, Corradi, Francesco, Gemma, Marco, Nogtev, Pavel, Petrova, Marina, Agrò, Felice Eugenio, Cabrini, Luca, Forfori, Francesco, Likhvantsev, Valery, Bove, Tiziana, Finco, Gabriele, Landoni, Giovanni, and Zangrillo, Alberto

Subjects
medicine.medical_specialty, Randomization, Critical Care, Antibiotic resistance, Critical patients, Critical Illness, Population, meropenem, intermitent or continuous infusion, critically ill, Intensive care unit, Meropenem, Mortality, Multi-drug resistant pathogens, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Sepsis, medicine, Clinical endpoint, polycyclic compounds, Humans, Pharmacology (medical), 030212 general & internal medicine, education, Antibacterial agent, education.field_of_study, 030505 public health, Septic shock, business.industry, Critical patient, General Medicine, medicine.disease, Anti-Bacterial Agents, Emergency medicine, 0305 other medical science, business, medicine.drug
Abstract

Objective Meropenem is a β-lactam, carbapenem antibacterial agent with antimicrobial activity against gram-negative, gram-positive and anaerobic micro-organisms and is important in the empirical treatment of serious infections in Intensive Care Unit (ICU) patients. Multi-drug resistant gram-negative organisms, coupled with scarcity of new antibiotic classes, forced healthcare community to optimize the therapeutic potential of available antibiotics. Our aim is to investigate the effect of continuous infusion of meropenem against bolus administration, as indicated by a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens in a population of ICU patients. Design Double blind, double dummy, multicenter randomized controlled trial (1:1 allocation ratio). Setting Tertiary and University hospitals. Interventions 600 ICU patients with sepsis or septic shock, needing by clinical judgment antibiotic therapy with meropenem, will be randomized to receive a continuous infusion of meropenem 3 g/24 h or an equal dose divided into three daily boluses (i.e. 1g q8h). Measurements The primary endpoint will be a composite outcome of reducing death and emergence of extensive or pan drug-resistant pathogens. Secondary endpoints will be death from any cause at day 90, antibiotic-free days at day 28, ICU-free days at day 28, cumulative SOFA-free (Sequential Organ Failure Assessment) score from randomization to day 28 and the two, separate, components of the primary endpoint. We expect a primary outcome reduction from 52 to 40% in the continuous infusion group. Conclusions The trial will provide evidence for choosing intermittent or continuous infusion of meropenem for critically ill patients with multi-drug resistant gram-negative infections.

Published
2021

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