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Lookup NU author(s): Dr Tom HellyerORCiD, Dr Ian McCullagh, Dr Anthony Rostron
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 American Medical Association. All rights reserved.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.
Author(s): Dark P, Hossain A, McAuley DF, Brealey D, Carlson G, Clayton JC, Felton TW, Ghuman BK, Gordon AC, Hellyer TP, Lone NI, Manazar U, Richards G, McCullagh IJ, McMullan R, McNamee JJ, McNeil HC, Mouncey PR, Naisbitt MJ, Parker RJ, Poole RL, Rostron AJ, Singer M, Stevenson MD, Walsh TS, Welters ID, Whitehouse T, Whiteley S, Wilson P, Young KK, Perkins GD, Lall R
Publication type: Article
Publication status: Published
Journal: JAMA
Year: 2025
Volume: 333
Issue: 8
Pages: 682-693
Print publication date: 25/02/2025
Online publication date: 09/12/2024
Acceptance date: 25/11/2024
Date deposited: 12/05/2025
ISSN (print): 0098-7484
ISSN (electronic): 1538-3598
Publisher: American Medical Association
URL: https://doi.org/10.1001/jama.2024.26458
DOI: 10.1001/jama.2024.26458
ePrints DOI: 10.57711/sggx-5884
Data Access Statement: Data Sharing Statement: see Supplement 5 (https://jamanetwork.com/journals/jama/fullarticle/2828036#note-JOI240153-1)
PubMed id: 39652885
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