Clinical question: Can using daily biomarker-guided protocols, procalcitonin (PCT), or C-reactive protein (CRP) to guide antibiotic duration in adults hospitalized with sepsis safely reduce antibiotic use compared with standard care?
Background: Appropriate antibiotic duration in sepsis is critical. Overtreatment increases side effects and antimicrobial resistance, while undertreatment risks worsening infection. Biomarkers like PCT and CRP have been studied to guide antibiotic cessation, with previous trials suggesting PCT may safely shorten antibiotic courses, but evidence quality was low, and routine adoption in sepsis remained uncertain.
Study design: Multicenter, intervention-concealed, randomized, clinical trial
Setting: 41 intensive care units in the U.K.
Synopsis: A total of 2,760 critically ill adults hospitalized with suspected sepsis requiring intravenous antibiotics were randomized between January 2018 and June 2024 to daily PCT-guided, daily CRP-guided, or standard-care antibiotic duration protocols. The primary effectiveness outcome was total antibiotic days up to 28 days after randomization, and the primary safety outcome was 28-day all-cause mortality. Patients in the PCT-guided group had a statistically significant reduction in total antibiotic duration versus standard care (approximately 9.8 versus 10.7 days) and met the noninferiority criteria for 28-day mortality. In contrast, the CRP-guided protocol did not reduce total antibiotic duration and showed inconclusive mortality results. Secondary outcomes (intensive care unit or hospital stay, superinfection rates) showed no major differences. Limitations include modest absolute reduction in antibiotic days, potential clinician behavior influences, and generalizability limited to well-resourced settings.
Bottom line: In hospitalized patients with suspected sepsis, a daily procalcitonin-guided protocol can safely reduce antibiotic duration compared with standard care; daily CRP guidance does not.
Citation: Dark P, et al. Biomarker-guided antibiotic duration for hospitalized patients with suspected sepsis: the ADAPT-sepsis randomized clinical trial. JAMA. 2025;333(8):682-693. doi:10.1001/jama.2024.26458.
Dr. Abdel Ahad is a hospitalist at the Cleveland Clinic and a clinical assistant professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, both in Cleveland.