Inside HealthTech Research: Working in partnership to tackle sepsis and antimicrobial resistance

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What was the problem

Sepsis is a common, life-threatening condition that affects approximately a quarter of a million people in the UK each year. Antibiotics play a key role in treating patients with sepsis but using antibiotics for too long does not improve outcomes for patients with sepsis and may, in fact, be harmful leading to an increase in antimicrobial resistance, side-effects and lengthen hospital stay. Antimicrobial resistance currently costs the NHS an estimated £180 million annually.  The government has set a target aiming to control antimicrobial resistance by 2040.

Current sepsis guidelines recommend a 7-10 day course of antibiotics. However, some patients require shorter or longer antibiotic courses depending on how they respond to treatment. Measuring a marker of inflammation in blood, like C-reactive protein and procalcitonin, can tell clinicians if the infection is controlled and the antibiotics can be safely stopped. This is a precision approach tailoring antibiotic course length to each individual patient depending on how they respond to treatment.

The ADAPT-Sepsis trial, led by Professor Paul Dark (NIHR Manchester Biomedical Research Centre and HRC in Emergency and Acute Care investigator) and funded by a £2 million NIHR Health Technology Assessment award, tested this precision approach. The 3,000-patient trial compared using either C-reactive protein or procalcitonin with standard NHS care to identify when to stop antibiotics in critically ill patients with sepsis. The ADAPT-Sepsis results were published in JAMA in December 2024 and showed we could safety reduce antibiotic use by 10% using procalcitonin to guide when to stop antibiotics.

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Working in partnership across Manchester’s hosted NIHR infrastructure

Building on the findings of the ADAPT-Sepsis trial, we brought together experts from 3 Manchester based NIHR infrastructure to put the trial results in context with the existing evidence and explore how the results could be used to guide clinical practice and improve patient outcomes. We systematically reviewed all available evidence on the clinical effectiveness of blood tests for guiding antibiotic therapy in patients with sepsis where the trials aimed to determine if antibiotic courses can be safely shortened without compromising patient safety.

Evidence synthesis specialists from the NIHR Applied Research Collaboration Greater Manchester (ARC-GM) led a rapid systematic review, working collaboratively with investigators from the NIHR HealthTech Research Centre in Emergency and Acute Care (HRC) providing expertise in clinical evaluation of infection biomarkers. Investigators from the NIHR Manchester Biomedical Research Centre (BRC) played a key role in framing the research question and providing the clinical context. Investigators from all three infrastructures worked together closely to collect and analyse the data to deliver a rigorous, clinically informed review and report on the findings in a clear and meaningful way that had practical applications for patient care.

This project is an example of collaboration across Manchester’s hosted NIHR infrastructure, made possible by the Manchester NIHR Oversight Board. The board brings together all NIHR centres in the region to identify shared priorities and enable joint working.

Together, the 3 NIHR centres combined their strengths to deliver high-quality research that will improve treatment decisions and support better use of antibiotics in the NHS reducing the impact of AMR. We are now continuing this collaborative working to explore the implementation of these research findings in clinical practice.

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The impact of this research

For Patients:

• Safer care with fewer side effects and reduced exposure to unnecessary antibiotics.
• Lower risk of complications and improved recovery times.

For the NHS:

• Shorter hospital stays and better use of resources.
• Significant cost savings and progress toward the government’s goal of controlling antimicrobial resistance (AMR) by 2040.
• Supports national AMR action plans and strengthens antimicrobial stewardship.

For Public Health:

• AMR is a major global health threat. This research provides practical, evidence-based solutions to reduce its impact.
• If adopted nationally, these findings could prevent thousands of unnecessary antibiotic days, reduce resistance, and improve patient outcomes across the UK.

The review found that using procalcitonin to guide antibiotic duration can safely shorten treatment by nearly two days while maintaining patient safety. There is also evidence that this approach may slightly reduce the risk of death. These findings demonstrate how precision medicine can transform sepsis care and help protect the effectiveness of antibiotics for the future. This work is already influencing clinical thinking and shaping future guidance, showing how NIHR-funded collaboration can deliver rapid, high-quality evidence that translates into real-world improvements for patients and the health system.

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The role of the NIHR hosted infrastructure

This project was only possible because of the unique strength and connectivity of Manchester’s NIHR infrastructure. NIHR funding didn’t just support the research, it created the conditions for rapid, coordinated action when it mattered most. By linking 3 specialist centres, (the HealthTech Research Centre in Emergency and Acute Care, the Manchester BRC, and the Applied Research Collaboration Greater Manchester) we combined expertise in clinical trials, evidence synthesis, and real-world implementation. This collaboration enabled us to move quickly, share knowledge, and produce high-quality evidence that could influence practice without delay.

Without this integrated infrastructure, the review would have taken far longer, and the opportunity to shape national guidance might have been missed. This case study demonstrates how NIHR funding builds a research ecosystem that turns ideas into real-world improvements, linking early scientific work, evidence gathering and practical implementation, to deliver better outcomes for patients and the health system.