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Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis
Paul Dark, Md. Anower Hossain, Daniel F. McAuley, David Brealey, Jonathan C. Clayton, Timothy Felton, Belinder Ghuman, Anthony Gordon, Thomas P Hellyer, Nazir Lone, Uzma Manazar, Gillian Richards, Iain McCullagh, Ronan McMullan, James J. McNamee, Hannah C. McNeil, Paul Mouncey, Micheal J. Naisbitt, Robert Parker, Ruth Louise Poole, Anthony Rostron, Mervyn Singer, Matt Stevenson, Timothy Walsh, Ingeborg Welters, Tony Whitehouse, Simon Whiteley, Peter Wilson, Keith A. Young, Gavin D. Perkins, Ranjit Lall, Julian Bion, Alasdair MacGowan, Paul McCrone, Maurice O’Kane, Ben Attwood, Gordon Sturmey, Ly‐Mee Yu, Tom Clutton-Brock, Duncan Young, John Simpspm, Kay Marshall, Simon Gates, Judith White, Dipesh Mistry, Scott Regan, Dalbir Kaur, Chen Ji, Nessa Nevels, David Shaw, Victoria Waugh, Julie Patrick-Heselton, C. Paisley, Suzannah Phillips, Emily Johnson, Jaime Fernandez Roman, Maria Lopez Martinez, Arra Mahiya, Daniel Watkin, Zachary M. Thomas, Andrew Davison, Maria Norris, Silvia Manes, Josh Colfar, Caitlin Lythgoe, Ibrahim Almafreji, Lisa Bailey, Robert Parker, Ian Turner-Bone, Laura Wilding, Michaela Lloyd, Harriet Murrant, Leanne Smith, Ben Morton, Dylan Middleton, William D. McCaig, Lucy Fuller, Dominic Kay, Sharon Barber, Jane Parez, Stephanie J. Lee, Reece Doonan, Lisa Swindells, Jessica Pendlebury, Jessica Holden, Jacob Hadfeild, Jay Naisbitt, Andrew Caxton, Emma Parkin, Daniel Horner, Anila sukumaian, Benedict Gyamerah, Alice Dunombe, DR Wadhi Habeichi, Joanna Borzomato, Paul Ferris, Justin Roberts, James Nesbitt, Jonathan B. Clayton, John A. Macdonald, Alistair Roy, Lindsey Woods, Sarah Cornell, Kimberley Rogerson, J Boxall, Jonathan Vernazza, Maxwell J. Richardson, Matthew Bickerton, Andrew Camplejohn, Julie Sheriff, Helena Baker, Jessica Watson, Max Ridley, Richard Gould, Sarah Perrin, Elizabeth Wilby, Susan Trott, Sheila Salada, Sarah Watts, Zoe Friar, Bethan Ogg, Clare Howcroft, Kate Long, Alistair Morris, Julia Sampson, Alexandra Gibbins, C. Peters, Megan Meredith, Alice Baddeley, Anthony Baidoo, Daniel Harvey, Alexandra McCoy, Sophie Lubbock, David A. Ford, Amy Clark, Laura V. Lloyd, Mohammed Habib, Gemma Clark, Ian King, Angela Sellick, Jennifer Dengate, Matthew Grice, Chinyere Ajonu, Samuel Redgate, Wendy Smith, Manjinder Khakh, Hannah C. Howson‐Wells, Max Casbon, Bhavin Mistry, Victoria Mitchinson, Arti Gulati, Benjamin Brown, Stephanie Grieveson, Tara Lal Shrestha, Ian C. Storey, Fatima Simoes, Verity Calder, Carole Hays, Maite Babio-Galan, Deborah White, Jennifer Collins, Leigh Dunn, Susan Taylor, Luzgie Gavina, Pamela Garcia, Lauren Butler, James Savage, Jayne Harwood, Sarah Cook, Stephen S. Hamilton, Jonathan Shelton, I Clement', Samantha Burn, Nathan Carroll, Lauren Clark, Lauren Ferguson, Sam Foggett, A. Hague, C. Hewison, Laura Mceachan, Nicole Mcewen, Ryan Perry, Olivia Purdy, Stephanie Williams, Glykeria Pakou, Helder Filipe, Margaret McNeil, Sara Mingo, Catarina Veiga, Poh Choo Teoh, Amitaa Maharajh, Mark De Neef, CH Cole, Alex Ross, Mark Belsham, Shatha Abu-Hijleh, Saida Solkar, Oghenemega Okotete, Peter Alexander, Luke Ward, Joanne Rothwell, Sherly George, Hannah Currie, Katharine Sellers, Jo Gresty, Ellie Reeves, Teresa Melody, Helen R. Taylor, Celinamma Maliaykal, William J. McIver, Mohamed Mooradun, Tay-yibah Mohamed, Heather Willis, Aidan Butler, Amy Hooper, Adam Boulton, Lucie Linhartová, Rachel Smith, Daniel E. Park, Anna Dennis, Joyce Yeung, Hozefa Ebrahim, Neil Crooks, Sarah Milton-White, Sarah Ballinger, Natalie Carling, Chloe Norman, Marie Thomas, Alexandra H. Nance, Emma Evans, Lesley Horton, Madhu Balasubramaniam, Emma McKenna, Scott Latham, Danielle Hollick, P Chinari, Celia Chu, Katy Edwards, Rashmi Gupta, Carolyn A. Williams, Lindwe Mashangombe, M JAVED, Maria Amamio, Gillian Andrew, Lucy Barclay, Sophie Birch, Kate Briton, Sarah L. Clark, J. Crossan, Katherine Doverman, Michael Gillies, David Griffith, David Hope, Kallirroi Kefala, Ian F. Laurenson, Lucy MacDonald, Craig Marshall, Corrienne McCulloch, Gregor McNeill, Nicola Rea, Scott A. Simpson, Jo Singleton, Elzbieta Czarniak, O. Nieto, Joanne Thompson, Ceri Lynch, Bethan Gibson, Piroska Toth-Tarsoly, Z Auer, D. C. Law, Shaun Oram, Alan Dodd, Bethan Deacon, L Roche, Justyna Smeaton, Kevin Agravante, Oladele Akinyoola, Keri Turner, Joanne Pugh, Sam Evans, Lisa Mellish, Geraint Lewis, John M. Burke, Nia Bromage, Nicola Llewellyn, Justine Evans, Redmond Tully, Andrew Drummond, Joy Dearden, Michelle Mulcahy, Carrole Blessen, Angiy Vian-Michael, Grainne O'Connor, Jonathan Scargill, Sarah Winnard, Peter McGuigan, Karen Ward, Aisling O’Neill, Stephanie Finn, Erin Collins, Jackie Green, Christine B. Turley, Gérard Quinn, Matthew D. Adams, Chris Wright, Gareth McKeeman, Heather Gallagher, Rachel Morrison, Shondipon Laha, Alex Jude Fonseca, Alexandra Williams, Rebecca Allock, Sean McMullen, Jayanthi Rajasekar, Sarah Purvis, Isha Garg, Vijay Jagannathan, Hillie Corr, M. Stefaniak, Simon Sinclair, Chris Wilson, Niall MacCallum, Ingrid Hass, Georgia Bercades, Deborah Smyth, Gladys Martir, Anna Reyes, Maria Alexandra Zapata Martinez, Laura Gallagher, John A. Smith, Deborah Paripoorani, Charlotte Taylor, Gregory P. Yates, Katharine Wylie, Fionn Quilty, Stephen Bonner, Jeremy Henning, Amy D. Thompson, Jessica Jones, Steven Liggett, Craig Mower, Sarah Bircham, Bobette Kamangu, Abiola Shoremekun, Anitha Ratnakumar, Keith Hugill, Tom Lawton, Amy Robinson, Rafaq Azad, M Kitching, Chris Cockcroft, Louise Akeroyd, Jackie Todd, Susan Kimachia, Lisa A. Burgess, Shereen Bano, Fiona Jutsum, Laura Price, Susie Pajak, Hannah Gibson, Mark C. Bates, Karen Reid, Alison Bland, Alison Stephens, Denise Donaldson, Mandy Beekes, Jo Stickley, Colene Adams, Amy Bowes, Sanal Jose, Nikolaos Manetas-Stavrakakis, Rebecca Wilcox, Rachel Rikunenko, Andrew J. Donnelly, Julie Summers, Christopher J Mowatt, Katherine Richmond, Rebecca Jones, Michael F. Barnsley, Mick Pursglove, James Pearce, Natasha Cole, Megan Phillips, J Jasiewicz, Samar Hamad, Jyoti Sharma, Muhammad Adeeb, Mohammad Qasim, Louise Walton, Claire Wright, Cathy McCormack, E. Staten Wynne, C.V. McCormack, K. M. V. Richmond, Christopher Thompson, Minnie Gellamucho, Jane Delaney, Michelle Davies, Elisa Sernicola, Lucy Bailey, Claire Hudson, Umar Mohyddin, Ben Storey-Waters, Faye Halliday, G. Mathew, Sarah Birch, Dumindu Karangoda, Estefania Treus, Leanne Howard, Claire Gabriel, Richard Lowsby, Elijah Matovu, Katherine Pagett, D Maren, Tenifayo Adeyemo, Hannah David, Mark Quiambao, Sheron Clarke, Valery Gurov, Anthony Mkandhla, Chris Duff, Helen Duce, Liz Ratcliffe, Anna Casey, Natalie Dooley, Karen Ellis, Christopher Sheridan, Lisa Moody, Rachel M. Webster, Samantha Harkett, Caroline Dooley, E. F. Mohamed Reda, Stephanie Goundry, Elaine Spruce, Tonny Veenith, Dhruv Parekh, Natalie Walmsley, Malikah Saba, Rebecca Gill, Esther Thomas, Jaimin Patel, Mansoor N. Bangash, Craig Denmade, Sarah E. White, Lynn Rowbottom, Matt Thomas, Paul Thomas, Ruth Worner, Borislava Borislavova, Kati Hayes, Beverley Faulkner, Emma Gendall, Elizabeth Goff, Hayley Blackmore, Mike Spivey, Sarah Bean, Karen Burt, Anthea Pattterson, Lisa Vipond, Matthew D. Martin, Nick Vallotton, Michael Kelsey, Ana Alvaro, Loreta Mostoles, Anezka Pratley, H. T. Ashby, Gemma Wood, Gail Priestley, Phil Antil, J. W. S. Carter, David Yates, Rob Ferguson, H. Ballentine Carter, Zoe Cinquina
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Résumé fourni par la source
Importance: For hospitalized critically ill adults with suspected sepsis, procalcitonin (PCT) and C-reactive protein (CRP) monitoring protocols can guide the duration of antibiotic therapy, but the evidence of the effect and safety of these protocols remains uncertain. Objective: To determine whether decisions based on assessment of CRP or PCT safely results in a reduction in the duration of antibiotic therapy. Design, Setting, and Participants: A multicenter, intervention-concealed randomized clinical trial, involving 2760 adults (≥18 years), in 41 UK National Health Service (NHS) intensive care units, requiring critical care within 24 hours of initiating intravenous antibiotics for suspected sepsis and likely to continue antibiotics for at least 72 hours. Intervention: From January 1, 2018, to June 5, 2024, 918 patients were assigned to the daily PCT-guided protocol, 924 to the daily CRP-guided protocol, and 918 assigned to standard care. Main Outcomes and Measures: The primary outcomes were total duration of antibiotics (effectiveness) and all-cause mortality (safety) to 28 days. Secondary outcomes included critical care unit data and hospital stay data. Ninety-day all-cause mortality was also collected. Results: Among the randomized patients (mean age 60.2 [SD, 15.4] years; 60.3% males), there was a significant reduction in antibiotic duration from randomization to 28 days for those in the daily PCT-guided protocol compared with standard care (mean duration, 10.7 [SD, 7.6] days for standard care and 9.8 [SD, 7.2] days for PCT; mean difference, 0.88 days; 95% CI, 0.19 to 1.58, P = .01). For all-cause mortality up to 28 days, the daily PCT-guided protocol was noninferior to standard care, where the noninferiority margin was set at 5.4% (19.4% [170 of 878] of patients receiving standard care; 20.9% [184 of 879], PCT; absolute difference, 1.57; 95% CI, -2.18 to 5.32; P = .02). No difference was found in antibiotic duration for standard care vs daily CRP-guided protocol (mean duration, 10.6 [7.7] days for CRP; mean difference, 0.09; 95% CI, -0.60 to 0.79; P = .79). For all-cause mortality, the daily CRP-guided protocol was inconclusive compared with standard care (21.1% [184 of 874] for CRP; absolute difference, 1.69; 95% CI, -2.07 to 5.45; P = .03). Conclusions and Relevance: Care guided by measurement of PCT reduces antibiotic duration safely compared with standard care, but CRP does not. All-cause mortality for CRP was inconclusive. Trial Registration: isrctn.org Identifier: ISRCTN47473244.
Sujets associés
Sepsis Diagnosis and TreatmentNeonatal and Maternal InfectionsBacterial Identification and Susceptibility Testing