• 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, and ADAPT-Sepsis Collaborators.
• Division of Immunology, Immunity to Infection and Respiratory Medicine, University of Manchester, Critical Care Unit, Northern Care Alliance NHS Foundation Trust, Salford Care Organization, Greater Manchester, United Kingdom.
• JAMA. 2024 Dec 9.

ImportanceFor 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.ObjectiveTo determine whether decisions based on assessment of CRP or PCT safely results in a reduction in the duration of antibiotic therapy.Design, Setting, And ParticipantsA 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.InterventionFrom 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 MeasuresThe 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.ResultsAmong 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 RelevanceCare 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 Registrationisrctn.org Identifier: ISRCTN47473244.

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