Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis
Paul Dark, Md. Anower Hossain, Daniel F. McAuley, David Brealey, Gordon Carlson, 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, ADAPT-Sepsis Collaborators, 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 Welters, Karen Williams, 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, 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 D. McCaig, Amie Hughes, 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
Abstract
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.