Patient trial finds biomarker test could significantly reduce antibiotic use in sepsis
The study was commissioned and funded by the National Institute for Health and Care Research (NIHR), and its leading partners were The University of Manchester, Northern Care Alliance NHS Foundation Trust and Warwick Medical School’s Clinical Trials Unit, who specialize in research in emergency and critical care
11 Dec 2024
A major UK patient trial of a new biomarker testing protocol for sepsis, led by University of Manchester researchers, 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.
Chief investigator Paul Dark, Professor of Critical Care at the University of Manchester, presented the findings to a global online audience at the Critical Care Reviews Meeting, where it was scrutinized and debated by some of the world’s leading experts in the field. The research team also published their peer reviewed findings in the Journal of the American Medical Association.
According to the charity Sepsis Research FEAT, around 50,000 people are estimated to die of sepsis in the UK each year. Recognizing 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 favorable 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.
The randomized controlled trial was based at 41 intensive care units across the UK, involving 2,760 adults from January 2018 to June 2024. 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.
Critically ill patients recruited to the trial had already commenced antibiotics for sepsis, so the study does not provide evidence for biomarker use in initiating antibiotic therapy.
Want the latest science news straight to your inbox? Become a SelectScience member for free today>>