Written by Denrick Cooper
Spoon Feed
Adding procalcitonin to a NEWS2-guided sepsis pathway was associated with lower mortality, although the mechanism by which this benefit occurred remains uncertain.
The biomarker worked… maybe just not how we expected.
NEWS2 is commonly used in the UK as a sensitive screening tool for identifying sepsis, though it lacks specificity. Procalcitonin has been proposed as an adjunct biomarker due to its relative specificity for bacterial infection and potential to reduce diagnostic uncertainty.
The PRONTO trial was a multicenter, randomized, open-label phase 3 trial evaluating whether point-of-care procalcitonin combined with NEWS2 improved sepsis management in emergency department patients with suspected sepsis. Among 7667 patients, procalcitonin-guided care did not reduce the initiation of intravenous antibiotics within 3 hours compared with usual care (48.4% vs. 48.2%; adjusted risk difference –0.08%, 95%CI –2.58 to 2.42). However, 28-day mortality was significantly lower in the procalcitonin group (13.6% vs. 16.6%; adjusted risk difference –3.12%, 90%CI –4.68 to –1.57). The upper 90%CI (–1.57) was below the pre-specified non-inferiority margin of 2.5%, indicating non-inferiority and superiority.
A limitation is that evolving sepsis management and antimicrobial stewardship practices during the COVID era may have influenced antibiotic prescribing independent of the intervention. In addition, adherence to the procalcitonin-guided algorithm was limited, with many clinicians either not reviewing it or not following its recommendations. In post-hoc analyses stratified by final discharge diagnosis, mortality appeared lower with procalcitonin-guided care in both infectious and noninfectious groups.
How does this change my practice?
This will not change my current sepsis screening practice, as procalcitonin is not routinely incorporated into most U.S. ED sepsis pathways and current evidence does not support its use alone to guide antibiotic initiation in high-risk sepsis. However, procalcitonin may have future utility as an adjunctive tool for diagnostic uncertainty, antimicrobial stewardship, and possibly mortality reduction, although further research is needed to better understand the mechanisms underlying these findings before widespread incorporation into sepsis screening algorithms.
Source
PRONTO Trial Group. Procalcitonin testing combined with NEWS2 evaluation compared with usual care based on NEWS2 for identification of sepsis and antibiotic initiation in the emergency department in England and Wales (PRONTO): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Respir Med. 2026 May;14(5):417-431. doi: 10.1016/S2213-2600(25)00433-3. Epub 2026 Mar 22. Erratum in: Lancet Respir Med. 2026 May;14(5):e31. doi: 10.1016/S2213-2600(26)00115-3. PMID: 41881047; PMCID: PMC13125698.
