A major UK patient trial of a new biomarker testing protocol for sepsis has shown it is possible to safely stop antibiotic treatment earlier than current care.
The duration reduction of around 10% could provide significant cost savings to health systems, limit unwanted drug side-effects, reduce overtreatment and reduce the development of antimicrobial resistance in individuals, across communities and internationally.
The study was commissioned and funded by the National Institute for Health and Care Research (NIHR), and its leading partners were Northern Care Alliance NHS Foundation Trust, The University of Manchester and Warwick Medical School’s Clinical Trials Unit, who specialise in research in emergency and critical care.
Chief investigator Paul Dark, an NHS Consultant in Critical Care Medicine at Salford Royal and Professor of Critical Care at The University of Manchester, presented the findings to a global online audience at the prestigious Critical Care Reviews Meeting this week.
The research team have also published their peer reviewed findings in JAMA – one of the world’s leading medical journals.
Around 37,000 people are estimated to die of sepsis in the UK each year, which develops when the body’s immune system overreacts to an infection and starts attacking its own tissues and organs.
Accounting for 100,000 hospital admissions a year in the UK, it is estimated that there are 49 million cases and 1 million deaths a year globally.
Simple test
Recognising sepsis and starting antibiotics early are crucial but until now the recommended duration of such treatment has been uncertain.
The only available option recommended for doctors currently is to use their judgement to decide when to discontinue the potent broad spectrum antibiotics, usually reserved to treat the condition.
The new decision support system is based on a simple blood test, carried out daily and available in most NHS hospital laboratories.
It tests for levels of a circulating protein called procalcitonin (PCT), which is produced as part of the body’s immune system responses to bacterial infections.
Higher levels indicate a greater likelihood of bacterial infection and sepsis, with subsequent falling levels indicating favourable responses to treatments
A computer automated response, based on the PCT levels from the blood test, advises doctors whether to discontinue antibiotic treatment or not. A further commonly measured circulating inflammation protein (C-reactive protein or CRP) was also tested.
Intensive care
The randomized controlled trial was based at 41 intensive care units across the UK, involving 2,760 adults from January 2018 to June 2024. These included patients at NCA’s Salford Royal and The Royal Oldham Hospital.
It compared 918 patients on a PCT protocol with 924 patients on a C-reactive protein (CRP) and 918 patients on current standard care.
Clinicians responsible for managing patients received daily standardized written advice on either standard care or on PCT or CRP biomarker-guided antibiotic discontinuation.
The protocols in the study were uniquely designed to conceal laboratory test results from clinical staff to reduce potential bias and patients were randomly assigned to one of the three groups.
The team found that a PCT protocol reduced total antibiotic duration by 10% and all-cause mortality, a key patient safety measure, was the same as standard care.
There was no difference in total antibiotic duration between standard care and CRP protocols.
Health challenge
Professor Dark said: “This simple protocol, if implemented, could significantly change the way sepsis is treated and safely help to combat antimicrobial overuse and resistance – one of the world’s leading health challenges.
“It is also a powerful illustration of how precision medicine can make a real difference to patient care when treatment is tailored to individual test results of each patient.
“It’s also important to acknowledge that this study would not have been possible without the generous contribution of patients with this life threatening condition who like all of us, are committed to finding better ways to deal with sepsis.”
He added: “Sepsis has been at the forefront of policy makers minds ever since the publication of 2013 Health Service Ombudsman report which focused on sepsis patients who were not treated urgently enough.
“Ever since then, developing better diagnostics and treatment guidance for GPs and hospital clinicians to help them recognise sepsis at an early stage has been a national priority.
“This trial has been planned to address NICEs recommendations so that its results will inform their future guidance on antibiotic duration in sepsis.”
- Critically ill patients recruited to the trial had already begun antibiotics for sepsis, so the study does not provide evidence for biomarker use in initiating antibiotic therapy.
The University of Manchester, University of Warwick and Northern Care Alliance NHS Foundation Trust researchers would like to thank the NIHR Clinical Research Network (CRN) for help delivering the study in the NHS and the NIHR Health Technology Assessment Programme for funding the trial. The collaborative co-investigator funded team in this national study are linked here https://fundingawards.nihr.ac.uk/award/15/99/02. They would also like to thank Abbott Diagnostics and Roche Diagnostics for their contracted support to assist NHS laboratories participate in the study.