New biomarker testing protocol could shorten antibiotic treatment for sepsis

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.

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.

Chief investigator Paul Dark, Professor of Critical Care at the University of Manchester will present the findings to a global online audience at the prestigious Critical Care Reviews Meeting this week (10/12/24), where it will be scrutinized and debated by some of the world’s leading experts in the field.

The research team also publish their peer reviewed findings in JAMA – one of the world’s leading medical journals – today

According to the charity Sepsis Research FEAT, around 50,000 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.

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..

Professor Dark, who is also an NHS Consultant in Critical Care Medicine at Salford Royal, 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.”

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 recognize 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.”

Paul Dark, Chief investigator and Professor of Critical Care, University of Manchester

Sepsis Research FEAT trustee Beth Budgen developed sepsis as a result of a seemingly innocuous Strep A infection on Christmas Day 2022, resulting in quadruple amputations.

She said: “Within 24hrs I was fighting for my life and have been left with life changing injuries as a result. If this can happen to me, it really can happen to anyone. It really is that scary

“The University of Manchester study is one of several significant projects currently being undertaken in the UK in the field of antibiotic treatment for sepsis patients – an extremely important area of research which Sepsis Research FEAT fully endorses.

“The priority setting partnership exercise that the charity recently completed with the James Lind Alliance will also now be crucial in ensuring that the best research into sepsis takes place UK-wide.”

• 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.