Doctors in Liverpool working with researchers at the Centre for Trials Research, at Cardiff University have identified promising evidence for the effectiveness of an early and rapid diagnostic test for sepsis.
Funded by the National Institute for Health and Care Research (NIHR), teams from the University of Liverpool and NHS University Hospitals of Liverpool Group conducted the study to address this common and serious condition. They were joined by colleagues at the Centre for Trials Research, at Cardiff University, as well as investigators at 20 NHS acute care hospitals in England and Wales.
Sepsis is a serious complication arising from infection, which can swiftly progress to life-threatening organ failure and is responsible for around 48,000 deaths annually in England. Recent findings, published today in The Lancet Respiratory Medicine, demonstrate that an accessible clinical decision-making tool significantly reduced mortality, with the greatest benefit seen among patients from the most deprived communities. However, the study also showed no difference in the speed of intravenous antibiotic initiation, despite initial expectations.
Diagnosing sepsis in emergency departments remains difficult, as many non-infectious illnesses can mimic its symptoms and there is currently no definitive diagnostic test. This uncertainty contributes to both over- and underdiagnosis. In both situations, delayed treatment can cost lives, while rapid antibiotics are required for those with confirmed sepsis some patients may be treated for sepsis unnecessarily, contributing to the urgent global issue of antimicrobial resistance (AMR). At the same time, misdiagnosis can lead to a failure to correctly identify and treat the actual underlying condition.
A procalcitonin‑guided algorithm is a clinical decision‑making tool that uses levels of the biomarker procalcitonin (PCT) to help guide antibiotic therapy in patients with suspected bacterial infections. However, it is not currently recommended for use in emergency settings because previous research has been inconsistent.
To address this gap, the research team conducted a large, controlled trial which randomised 7,667 patients who presented to emergency departments with suspected sepsis. The study tested whether adding the rapid procalcitonin-guided algorithm testing to current clinical practice could help clinicians recognise sepsis more accurately, reduce unnecessary antibiotic prescribing, and maintain at least the same level of patient safety, measured by overall mortality.
The study shows:
- There was a 17% relative reduction in mortality from 16.6% to 13.6% which means for every 1,000 patient treated as suspected sepsis, 31 lives are potentially saved.
- Patients from the most deprived areas experienced the greatest mortality benefit. Existing research explores inequality in sepsis outcomes, and this latest research may help to overcome identified systemic biases.
- Importantly, the trial found that regardless of whether patients were treated with the procalcitonin‑guided algorithm or received standard care, there was no difference in how quickly intravenous antibiotics were started. Although the research team had anticipated that the algorithm might improve early antibiotic initiation, the trial showed it did not - a key finding, given this was one of the co‑primary outcomes.
Co-chief investigator, Dr Stacy Todd, Consultant in Infectious Diseases and General Medicine, NHS University Hospitals of Liverpool Group, said: "The evidence supports the value of early and rapid diagnostics and indicates a need for further biomarker and algorithm development. Uptake of procalcitonin-guided care into health systems will now depend on greater understanding of the mechanism of effect, further health economic evaluations, and robust implementation frameworks."
Neil French, co-chief investigator on the study and Professor of Infectious Diseases and Global Health at the University of Liverpool, and Honorary Consultant in Infectious Diseases, NHS University Hospitals of Liverpool Group, said: "Sepsis leads to tens of thousands of deaths each year. However, there are ways to prevent this, and we already have tools available to help do so. What's critical is robust, peer‑reviewed research to understand their effectiveness. This study plays an important role in advancing that work, giving clinicians on the ground greater confidence to incorporate these approaches into their practice.
"While many questions remain, these findings encourage further investigation and mark a step in the right direction."
Professor Anthony Gordon, Director of NIHR's Health Technology Assessment (HTA) Programme, said: "Each year tens of thousands of people die from sepsis. Early detection and prompt management are crucial. These new findings demonstrate how better diagnostic tests can help clinicians care for patients with sepsis in the race to save lives, while also tackling the global threat of antimicrobial resistance.
"This major trial demonstrates how for the last two decades NIHR has transformed the health and care research landscape for the health and wealth of the nation, targeting the most urgent health and care challenges."
The paper, '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' was published in The Lancet Respiratory Medicine.
