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Biomarker-guided antibiotic duration for hospitalized patients with suspected sepsis

Title: Biomarker-guided antibiotic duration for hospitalized patients with suspected sepsis
Authors: Dark, Paul; Hossain, Anower; McAuley, Daniel F; Brealey, David; Carlson, Gordon; Clayton, Jonathan C; Felton, Timothy W; Ghuman, Belinder K; Gordon, Anthony C; Hellyer, Thomas P; Lone, Nazir I; Manazar, Uzma; Richards, Gillian; McCullagh, Iain J; McMullan, Ronan; McNamee, James J; McNeil, Hannah C; Mouncey, Paul R; Naisbitt, Micheal J; Parker, Robert J; Poole, Ruth L; Rostron, Anthony J; Singer, Mervyn; Stevenson, Matt D; Walsh, Tim S; Welters, Ingeborg D; Whitehouse, Tony; Whiteley, Simon; Wilson, Peter; Young, Keith K; Perkins, Gavin D; Lall, Ranjit; Bion, Julian; MacGowan, Alasdair; McCrone, Paul; O'Kane, Maurice; Attwood, Ben; Sturmey, Gordon; Prentice, Janet; Yu, Ly-mee; Clutton-Brock, Tom; Young, Duncan; Simpspm, John; Marshall, Kay; Gates, Simon; White, Judith; Mistry, Dipesh; Regan, Scott; McGowan, Noicola; Kaur, Dalbir; Ji, Chen; Nevels, Nessa; Williams, Karen; Shaw, David; Waugh, Victoria; Patrick-Heselton, Julie; Paisley, Carol; Phillips, Suzannah; Johnson, Emily; Fernandez Roman, Jaime; Lopez Martinez, Maria; Mahiya, Arra; Watkin, Daniel; Thomas, Zachary; Davison, Andrew; Farina, Sofia; Norris, Maria; Manes, Silvia; Yuan, Jin-Xi; Colfar, Josh; Lythgoe, Caitlin; Almafreji, Ibrahim; Bailey, Lisa; Parker, Robert; Turner-Bone, Ian; Wilding, Laura; Lloyd, Michaela; Murrant, Harriet; Smith, Leanne; Morton, Ben; Middleton, Dylan; Mccaig, William; Hughes, Amie; Fuller, Lucy; Kay, Dominic; Barber, Sharon; Parez, Jane; Lee, Stephanie; Doonan, Reece; Swindells, Lisa; Pendlebury, Jessica; Holden, Jessica; Hadfeild, Jacob; Naisbitt, Jay; Caxton, Andrew; Parkin, Emma; Horner, Daniel; sukumaian, Anila; Gyamerah, Benedict; Dunombe, Alice; Taylor, DR Chris; Habeichi, DR Wadhi; Borzomato, Joanna; Ferris, Paul; Roberts, Justin; Nesbitt, James; Clayton, Jonathan; Macdonald, John; Roy, Alistair; Rostron, Anthony; Woods, Lindsey; Cornell, Sarah; Rogerson, Kimberley; Boxall, Jo; Burns, Trina; Cooper, Susan; Knight, Kirstie; Constable, Sarah; Kenny, Laura; Vernazza, Jonathan; Richardson, Maxwell; Bickerton, Matthew; Camplejohn, Andrew; Cope, Roseanne; Sheriff, Julie; Baker, Helena; Watson, Jessica; Sedgwick, Jodie; Ridley, Max; Gould, Richard; Perrin, Sarah; Wilby, Elizabeth; Trott, Susan; Salada, Sheila; Watts, Sarah; Friar, Zoe; Ogg, Bethan; Howcroft, Clare; Long, Kate; Morris, Alistair; Sampson, Julia; Gibbins, Alexandra; Peters, Celia; Meredith, Megan; Baddeley, Alice; Baidoo, Anthony; Harvey, Dan; McCoy, Alexandra; Lubbock, Sophie; Ford, David; Clark, Amy; Lloyd, Laura; Habib, Mohammed; Clark, Gemma; King, Ian; Goode, Carla; Sellick, Angela; Sharma, Shova; Assi, Anita; Dengate, Jennifer; Grice, Matthew; Brammer, Laura; Ajonu, Chinyere; Redgate, Samuel; Smith, Wendy; Khakh, Manjinder; Howson-Wells, Hannah; Atkin, Simon; Casbon, Max; Olsen, Frances; Mistry, Bhavin; Mitchinson, Victoria; Talbot, Aysha; McCullagh, Iain; Gulati, Arti; Brown, Benjamin; Grieveson, Stephanie; Shrestha, Tara; Storey, Ian; Simoes, Fatima; Calder, Verity; Hays, Carole; Babio-Galan, Maite; White, Deborah; Collins, Jennifer; Dunn, Leigh; Taylor, Susan; Gavina, Luzgie; Wilkinson, Tessa; Garcia, Pamela; Butler, Lauren; Savage, James; Harwood, Jayne; Cook, Sarah; Hamilton, Stephen; Shelton, Jonathan; Clement, Ian; Burn, Samantha; Carroll, Nathan; Clark, Lauren; Ferguson, Lauren; Foggett, Sam; Hague, Alison; Handley, Tracy; Hewison, Chelsea; Kitchener, Samantha; Mceachan, Laura; Mcewen, Nicole; Perry, Ryan; Purdy, Olivia; Thomson, Amie; Williams, Stephanie; Pakou, Glykeria; Filipe, Helder; McNeil, Margaret; Mingo, Sara; Veiga, Catarina; Teoh, Poh Choo; Maharajh, Amitaa; De Neef, Mark; Cole, Coral; Ross, Alex; Belsham, Mark; Abu-Hijleh, Shatha; Solkar, Saida; Okotete, Oghenemega; Alexander, Peter DG; Ward, Luke; Rothwell, Joanne; George, Sherly; Currie, Hannah; Sellers, Katharine; Perkins, Gavin; Gresty, Jo; Reeves, Ellie; Melody, Teresa; Taylor, Helen; Bawa, Sara; Maliaykal, Celinamma; McIver, William; Mooradun, Mohamed; Mohamed, Tay-yibah; Willis, Heather; Butler, Aidan; Hooper, Amy; Boulton, Adam; Linhartova, Lucie; Smith, Rachel; Park, Daniel; Dennis, Anna; Yeung, Joyce; Ebrahim, Hozefa; Crooks, Neil; Milton-White, Sarah; Ballinger, Sarah; Carling, Natalie; Norman, Chloe; Thomas, Marie; Nance, Alexandra; Evans, Emma; Horton, Lesley; Balasubramaniam, Madhu; Flanagan, Rebecca; McKenna, Emma; Latham, Scott; Hollick, Danielle; Subudhi, Chinari PK; Chu, Celia; Edwards, Katy; Gupta, Rashmi; Williams, Carolyn; Mashangombe, Lindwe; Javed, Misbah; Walsh, Timothy; Amamio, Maria; Andrew, Gillian; Barclay, Lucy; Birch, Sophie; Briton, Kate; Butt, Lisa-Marie; Clark, Sarah; Crossan, Jessica; Doverman, Katherine; Gillies, Michael; Griffith, David; Hope, David; Kefala, Kallirroi; Laurenson, Ian; Lone, Nazir; Macdonald, Lucy; Marshall, Craig; McCulloch, Corrienne; McNeill, Gregor; Rea, Nicola; Simpson, Scott; Singleton, Jo; Czarniak, Elzbieta; Moncayo Nieto, Olga Lucia; Thompson, Joanne; Lynch, Ceri; Gibson, Bethan; Toth-tarsoly, Piroska; Auer, Zolton; Law, Daniel; Singh, Jayparaska; Oram, Shaun; Zaki, Arsalan; Dodd, Alan; Deacon, Bethan; Roche, Lisa; Jones, Leannne; Smeaton, Justyna; Agravante, Kevin; Akinyoola, Oladele; Turner, Keri; Pugh, Joanne; Evans, Sam; Mellish, Lisa; Rees, Angharad; Lewis, Geraint; Burke, John; Bromage, Nia; Llewellyn, Nicola; Evans, Justine; Constantino, Marlo; Tully, Redmond P; Drummond, Andrew; Dearden, Joy; Mulcahy, Michelle; Blessen, Carrole; Vian-Michael, Angiy; O'Connor, Grainne; Scargill, Jonathan; Winnard, Sarah; McNamee, James; Mcauley, Danny; McGuigan, Peter; Ward, Kathyrn; Ward, Justine; O'Neill, Aisling; Finn, Stephanie; Collins, Erin; Green, Jackie; Turley, Christine; Quinn, Gerard; Adams, Matthew; Wright, Chris; McKeeman, Gareth; Loughlin, Rory; Reilly, Lynsey; Gallagher, Heather; Coward, Steve; Morrison, Rachel; Laha, Shondipon; Madanapalli Raghunath, Sushruth; Fonseca, Alex Jude; Williams, Alexandra; Connor, Sacha; Allock, Rebecca; Halsall, Lisa; McMullen, Sean; Rajasekar, Jayanthi; Purvis, Sarah; Garg, Isha; Jagannathan, Vijay; Corr, Hillie; Stefaniak, Magda; Sinclair, Simon; Wilson, Chris; MacCallum, Niall; Hass, Ingrid; Bercades, Georgia; Smyth, Deborah; Martir, Gladys; Reyes, Anna; Zapata Martinez, Maria Alexandra; Gallagher, Laura; Omer, Hodan; Bannard -Smith, Jonathan; Paripoorani, Deborah; Taylor, Charlotte; Yates, Gregory; Wylie, Katharine; Salah, Sadiya; Quilty, Fionn; Bonner, Stephen; Henning, Jeremy; Thompson, Amy; Jones, Jessica; Liggett, Steven; Mower, Craig; Bircham, Sarah; Kamangu, Bobette; Shoremekun, Abiola; Ratnakumar, Anitha; Hugill, Keith; Lawton, Tom; Robinson, Amy; Azad, Rafaq; Kitching, Megan; Cockcroft, Chris; Akeroyd, Louise; Todd, Jackie; Kimachia, Susan; Burgess, Lisa; Bano, Shereen; Jutsum, Fiona; Price, Laura; Pajak, Susie; Gibson, Hannah; Bates, Mark; Reid, Karen; Bland, Alison; Stephens, Alison; Donaldson, Denise; Beekes, Mandy; Stickley, Jo; Adams, Colene; Bowes, Amy; Jose, Sanal; Manetas-Stavrakakis, Nikolaos; Wilcox, Rebecca; Rikunenko, Rachel; Houghton, Maria; Donnelly, Andrew; Summers, Julie; Mowatt, Christopher; Richmond, Katherine; Jones, Rebecca; Davie, Tammy; Barnsley, Michael; Pursglove, Mick; Pearce, James; Lane, Philippa; Cole, Natasha; Phillips, Megan; Jasiewicz, Joanna; Hamad, Sarah; Sharma, Jyoti; Adeeb, Muhammad; Qasim, Mohammad; Barnsley, Lisa; Walton, Louise; Wright, Claire; Kaura, Helen; McCormack, Cathy; Latham, Dave; Wynne, Emily; McCormack, Catherine; Richmond, Kathy; Thompson, Christopher; Gellamucho, Minnie; Delaney, Jane; Davies, Michelle; Sernicola, Elisa; Bailey, Lucy; Cope, Angelene; Hudson, Claire; Mohyddin, Umar; Lee, Jack; Storey-Waters, Ben; Halliday, Faye; Mathew, George; Birch, Sarah; Karangoda, Dumindu; Treus, Estefania; Howard, Leanne; Luck, Georgina; Gabriel, Claire; Lowsby, Richard; Matovu, Elijah; Pagett, Katherine; Maren, Deborah; Adeyemo, Tenifayo; David, Hannah; Quiambao, Mark; Harold, Joanne; Clarke, Sheron; Gurov, Valery; Mkandhla, Anthony; Duff, Chris; Duce, Helen; Ratcliffe, Liz; Casey, Anna; Dooley, Natalie; Ellis, Karen; Sheridan, Christopher; Moody, Lisa; Mulholland, Puja; Webster, Rachel; Harkett, Samantha; Beddows, Sophia; Dooley, Caroline; Reda, Eamonn; Goundry, Stephanie; Spruce, Elaine; Veenith, Tonny; Parekh, Dhruv; Walmsley, Natalie; Saba, Malikah; Gill, Rebecca; Thomas, Esther; Patel, Jaimin; Bangash, Mansoor; Denmade, Craig; White, Sarah; Clare, Rosie; Huang, Ya-Wen J; Herbert, Dawn; Rowbottom, Lynn; McGRADY, Madeleine; Thomas, Matt; Thomas, Paul; Worner, Ruth; Borislavova, Borislava; Hayes, Kati; Faulkner, Beverley; Gendall, Emma; Goff, Elizabeth; Blackmore, Hayley; Spivey, Mike; Bean, Sarah; Burt, Karen; Pattterson, Anthea; Vipond, Lisa; Martin, Matthew; Vallotton, Nick; Waterman, Samuel; Kelsey, Michael; Zuriaga -Alvaro, Ana; Mostoles, Loreta; Pratley, Anezka; Amiruddin, Nabeel; Ashby, Helen; Wood, Gemma; Priestley, George; Antil, Phil; Carter, Joseph; Yates, David; Ferguson, Rob; Carter, Harriet; Cinquina, Zoe
Source: 693 ; 682
Publisher Information: American Medical Association
Publication Year: 2024
Collection: Imperial College London: Spiral
Description: 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 ...
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: JAMA: Journal of the American Medical Association; https://doi.org/10.1001/jama.2024.26458; http://hdl.handle.net/10044/1/116650; https://www.dx.doi.org/10.1001/jama.2024.26458
DOI: 10.1001/jama.2024.26458
Availability: http://hdl.handle.net/10044/1/116650; https://doi.org/10.1001/jama.2024.26458
Rights: Copyright © 2024 American Medical Association. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy) ; https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.E709B650
Database: BASE