Original Investigation 

Caring for the Critically Ill Patient

December 9, 2024

Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis: The ADAPT-Sepsis Randomized Clinical Trial

Paul Dark, Anower Hossain, Daniel F. McAuley, et al

JAMA. Published online December 9, 2024. doi:10.1001/jama.2024.26458

Key Points

Question  Do critically ill adult patients hospitalized for suspected sepsis and treated with intravenous antibiotics based on procalcitonin (PCT) or C-reactive protein (CRP) protocols, have a safe reduction in treatment duration compared with standard care?

Findings  In this multicenter, randomized trial of 2760 patients, the daily PCT-guided protocol reduced total antibiotic duration and had noninferior all-cause mortality compared with standard care. No difference was found in total antibiotic duration between standard care and daily CRP-guided protocol, and CRP showed inconclusive results for all-cause mortality.

Meaning  In hospitalized adults, daily PCT-guided protocol reduced antibiotic duration safely compared with standard care, but daily CRP-guided protocol does not.

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