Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis
Authors: Paul Dark, Anower Hossain, Daniel F. McAuley, David Brealey, Gordon Carlson, Jonathan C. Clayton, Timothy W. Felton, Belinder K. Ghuman, Anthony C. Gordon, Thomas P. Hellyer, Nazir I. Lone, Uzma Manazar, Gillian Richards, Iain J. McCullagh, Ronan McMullan, James J. McNamee, Hannah C. McNeil, Paul R. Mouncey, Micheal J. Naisbitt, Robert J. Parker, Ruth L. Poole, Anthony J. Rostron, Mervyn Singer, Matt D. Stevenson, Tim S. Walsh, Ingeborg D. Welters, Tony Whitehouse, Simon Whiteley, Peter Wilson, Keith K. Young, Gavin D. Perkins, Ranjit Lall, Julian Bion, Alasdair MacGowan, Paul McCrone, Maurice O'Kane, Ben Attwood, Gordon Sturmey, Janet Prentice, Ly-mee Yu, Tom Clutton-Brock, Duncan Young, John Simpspm, Kay Marshall, Simon Gates, Judith White, Dipesh Mistry, Scott Regan, Noicola McGowan, Dalbir Kaur, Chen Ji, Nessa Nevels, Ingeborg D Welters, Karen Williams, David Shaw, Victoria Waugh, Julie Patrick-Heselton, Carol Paisley, Suzannah Phillips, Emily Johnson, Jaime Fernandez Roman, Maria Lopez Martinez, Arra Mahiya, Daniel Watkin, Zachary Thomas, Andrew Davison, Sofia Farina, Maria Norris, Silvia Manes, Jin-Xi Yuan, 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 Mccaig, Amie Hughes, Lucy Fuller, Dominic Kay, Sharon Barber, Jane Parez, Stephanie 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 Chris Taylor, DR Wadhi Habeichi, Joanna Borzomato, Paul Ferris, Justin Roberts, James Nesbitt, Jonathan Clayton, John Macdonald, Alistair Roy, Anthony Rostron, Lindsey Woods, Sarah Cornell, Kimberley Rogerson, Jo Boxall, Trina Burns, Susan Cooper, Kirstie Knight, Sarah Constable, Laura Kenny, Jonathan Vernazza, Maxwell Richardson, Matthew Bickerton, Andrew Camplejohn, Roseanne Cope, Julie Sheriff, Helena Baker, Jessica Watson, Jodie Sedgwick, Simon Whiteley, 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, Celia Peters, Megan Meredith, Alice Baddeley, Anthony Baidoo, Dan Harvey, Alexandra McCoy, Sophie Lubbock, David Ford, Amy Clark, Laura Lloyd, Mohammed Habib, Gemma Clark, Ian King, Carla Goode, Angela Sellick, Shova Sharma, Anita Assi, Jennifer Dengate, Matthew Grice, Laura Brammer, Chinyere Ajonu, Samuel Redgate, Wendy Smith, Manjinder Khakh, Hannah Howson-Wells, Simon Atkin, Max Casbon, Frances Olsen, Bhavin Mistry, Victoria Mitchinson, Aysha Talbot, Iain McCullagh, Arti Gulati, Benjamin Brown, Stephanie Grieveson, Tara Shrestha, Ian Storey, Fatima Simoes, Verity Calder, Carole Hays, Maite Babio-Galan, Deborah White, Jennifer Collins, Leigh Dunn, Susan Taylor, Luzgie Gavina, Tessa Wilkinson, Pamela Garcia, Lauren Butler, James Savage, Jayne Harwood, Sarah Cook, Stephen Hamilton, Jonathan Shelton, Ian Clement, Samantha Burn, Nathan Carroll, Lauren Clark, Lauren Ferguson, Sam Foggett, Alison Hague, Tracy Handley, Chelsea Hewison, Samantha Kitchener, Laura Mceachan, Nicole Mcewen, Ryan Perry, Olivia Purdy, Amie Thomson, Stephanie Williams, Glykeria Pakou, Helder Filipe, Margaret McNeil, Sara Mingo, Catarina Veiga, Poh Choo Teoh, Amitaa Maharajh, Mark De Neef, Coral Cole, Alex Ross, Mark Belsham, Shatha Abu-Hijleh, Saida Solkar, Oghenemega Okotete, Peter D G Alexander, Luke Ward, Joanne Rothwell, Sherly George, Hannah Currie, Katharine Sellers, Gavin Perkins, Jo Gresty, Ellie Reeves, Teresa Melody, Helen Taylor, Sara Bawa, Celinamma Maliaykal, William McIver, Mohamed Mooradun, Tay-yibah Mohamed, Heather Willis, Aidan Butler, Amy Hooper, Adam Boulton, Lucie Linhartova, Rachel Smith, Daniel Park, Anna Dennis, Joyce Yeung, Hozefa Ebrahim, Neil Crooks, Sarah Milton-White, Sarah Ballinger, Natalie Carling, Chloe Norman, Marie Thomas, Alexandra Nance, Emma Evans, Lesley Horton, Madhu Balasubramaniam, Rebecca Flanagan, Emma McKenna, Scott Latham, Danielle Hollick, Chinari, P, K Subudhi, Celia Chu, Katy Edwards, Rashmi Gupta, Carolyn Williams, Lindwe Mashangombe, Misbah Javed, Timothy Walsh, Maria Amamio, Gillian Andrew, Lucy Barclay, Sophie Birch, Kate Briton, Lisa-Marie Butt, Sarah Clark, Jessica Crossan, Katherine Doverman, Michael Gillies, David Griffith, David Hope, Kallirroi Kefala, Ian Laurenson, Nazir Lone, Lucy Macdonald, Craig Marshall, Corrienne McCulloch, Gregor McNeill, Nicola Rea, Scott Simpson, Jo Singleton, Elzbieta Czarniak, Olga Lucia Moncayo Nieto, Joanne Thompson, Ceri Lynch, Bethan Gibson, Piroska Toth-tarsoly, Zolton Auer, Daniel Law, Jayparaska Singh, Shaun Oram, Arsalan Zaki, Alan Dodd, Bethan Deacon, Lisa Roche, Leannne Jones, Justyna Smeaton, Kevin Agravante, Oladele Akinyoola, Keri Turner, Joanne Pugh, Sam Evans, Lisa Mellish, Angharad Rees, Geraint Lewis, John Burke, Nia Bromage, Nicola Llewellyn, Justine Evans, Marlo Constantino, Redmond P Tully, Andrew Drummond, Joy Dearden, Michelle Mulcahy, Carrole Blessen, Angiy Vian-Michael, Grainne O'Connor, Jonathan Scargill, Sarah Winnard, James McNamee, Danny Mcauley, Peter McGuigan, Kathyrn Ward, Justine Ward, Aisling O'Neill, Stephanie Finn, Erin Collins, Jackie Green, Christine Turley, Gerard Quinn, Matthew Adams, Chris Wright, Gareth McKeeman, Rory Loughlin, Lynsey Reilly, Heather Gallagher, Steve Coward, Rachel Morrison, Shondipon Laha, Sushruth Madanapalli Raghunath, Alex Jude Fonseca, Alexandra Williams, Sacha Connor, Rebecca Allock, Lisa Halsall, Sean McMullen, Jayanthi Rajasekar, Sarah Purvis, Isha Garg, Vijay Jagannathan, Hillie Corr, Magda Stefaniak, Simon Sinclair, Chris Wilson, David Brealey, Niall MacCallum, Ingrid Hass, Georgia Bercades, Deborah Smyth, Gladys Martir, Anna Reyes, Maria Alexandra Zapata Martinez, Laura Gallagher, Hodan Omer, Jonathan Bannard -Smith, Deborah Paripoorani, Charlotte Taylor, Gregory Yates, Katharine Wylie, Sadiya Salah, Fionn Quilty, Stephen Bonner, Jeremy Henning, Amy Thompson, Jessica Jones, Steven Liggett, Craig Mower, Sarah Bircham, Bobette Kamangu, Abiola Shoremekun, Anitha Ratnakumar, Keith Hugill, Tom Lawton, Amy Robinson, Rafaq Azad, Megan Kitching, Chris Cockcroft, Louise Akeroyd, Jackie Todd, Susan Kimachia, Lisa Burgess, Shereen Bano, Fiona Jutsum, Laura Price, Susie Pajak, Hannah Gibson, Mark 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, Maria Houghton, Andrew Donnelly, Julie Summers, Christopher Mowatt, Katherine Richmond, Rebecca Jones, Tammy Davie, Michael Barnsley, Mick Pursglove, James Pearce, Philippa Lane, Natasha Cole, Megan Phillips, Joanna Jasiewicz, Sarah Hamad, Jyoti Sharma, Muhammad Adeeb, Mohammad Qasim, Lisa Barnsley, Louise Walton, Claire Wright, Helen Kaura, Cathy McCormack, Dave Latham, Emily Wynne, Catherine McCormack, Kathy Richmond, Christopher Thompson, Minnie Gellamucho, Jane Delaney, Michelle Davies, Elisa Sernicola, Lucy Bailey, Angelene Cope, Claire Hudson, Umar Mohyddin, Jack Lee, Ben Storey-Waters, Faye Halliday, George Mathew, Sarah Birch, Dumindu Karangoda, Estefania Treus, Leanne Howard, Georgina Luck, Claire Gabriel, Richard Lowsby, Elijah Matovu, Katherine Pagett, Deborah Maren, Tenifayo Adeyemo, Hannah David, Mark Quiambao, Joanne Harold, Sheron Clarke, Valery Gurov, Anthony Mkandhla, Chris Duff, Helen Duce, Tony Whitehouse, Liz Ratcliffe, Anna Casey, Natalie Dooley, Karen Ellis, Christopher Sheridan, Lisa Moody, Puja Mulholland, Rachel Webster, Samantha Harkett, Sophia Beddows, Caroline Dooley, Eamonn Reda, Stephanie Goundry, Elaine Spruce, Tonny Veenith, Dhruv Parekh, Natalie Walmsley, Malikah Saba, Rebecca Gill, Esther Thomas, Jaimin Patel, Mansoor Bangash, Craig Denmade, Sarah White, Rosie Clare, Ya-Wen J Huang, Dawn Herbert, Lynn Rowbottom, Madeleine McGRADY, 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 Martin, Nick Vallotton, Samuel Waterman, Michael Kelsey, Ana Zuriaga -Alvaro, Loreta Mostoles, Anezka Pratley, Nabeel Amiruddin, Helen Ashby, Gemma Wood, George Priestley, Phil Antil, Joseph Carter, David Yates, Rob Ferguson, Harriet Carter, Zoe Cinquina
Journal: JAMA (2024)

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