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 ,   ADAPT-Sepsis Collaborators, 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 , Welters Ingeborg D , 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 , Whiteley Simon , 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 D G , 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, P, K , 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 , Brealey David , 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 , Whitehouse Tony , 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 
Published: December 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