Developing personalised treatments to tackle antibiotic resistance – Antimicrobial Resistance Week

Antimicrobial Resistance (AMR) Awareness Week, running from 18 to 24 November, is a global campaign to raise awareness and understanding of AMR. New research at Wythenshawe Hospital, part of Manchester University NHS Foundation Trust (MFT), has the potential to limit the development of antibiotic (antimicrobial) resistance while improving patient outcomes, when treating very ill patients with pneumonia and sepsis.

As a result of drug resistance, antibiotics become ineffective and infections become difficult or impossible to treat, increasing the risk of disease spread, severe illness and death.

Pneumonia is inflammation (swelling) of the lungs, usually caused by a bacterial or viral infection. Sometimes people with pneumonia become very ill and need to be admitted to hospital, or even an intensive care unit (ICU). In the UK, approximately 30,000 patients die from pneumonia every year and average length of stay in ICU is 22 days.

Sepsis can sometimes develop from pneumonia. It is a life-threatening reaction to infection when the immune system overreacts and starts to damage the body’s own tissues and organs. These critically ill patients need timely antibiotic treatment to tackle the infection.

Dr Jan Hansel, a National Institute for Health and Care Research (NIHR) Doctoral Fellow in Intensive Care Medicine at Wythenshawe Hospital, is leading the three-year SIPRES study, which aims to help clinicians personalise antibiotic treatment for critically ill patients with pneumonia and sepsis, to ensure their effectiveness and prevent over-or under-dosing.

Dr Hansel said: “Antibiotics fail to achieve the same consistent result for every patient. With the SIPRES study we aim to find out why antibiotics work differently in certain patients with severe pneumonia and sepsis.

“With current standard of careall patients are given antibiotics at a standard prescribed dose. However, for up to 30 per cent of patients who are very unwell, when we measure their concentrations of antibiotic in the bloodstream, we find it is not at high enough levels to have the desired effect.

“This work aims to identify a group of patients at risk of low antibiotic levels in blood, who are less likely to improve with standard treatment and more likely to develop antibiotic resistance. If we can do so early in their course of illness, using advanced point-of-care blood tests, we could, in the future, individualise antibiotic doses to mitigate the risk of resistance and improve outcomes.”

The study, taking place at Wythenshawe Hospital will aim to recruit 119 participants over 18 months. The research will assess how adult patients with severe pneumonia respond when treated with the most commonly used antibiotic in the ICU called

piperacillin/tazobactam – which is used to treat bacterial infections in many different parts of the body, including pneumonia.

Alongside information on how quickly the patients get better, and how long they need to stay in hospital or in ICU, blood samples will be used to measure antibiotic levels and assess each patient’s immune system during their treatment.

The state-of-the-art facilities at the recently opened NIHR Centre for Precision Approaches to Combatting Antimicrobial Resistance at Wythenshawe Hospital will allow the research team to conduct the advanced analyses needed to deliver the SIPRES study.

Using advanced diagnostics, the research will assess patients’ immune responses and classify them into two groups, those who have very pronounced (strong) or gradual (lesser) inflammation of the lungs. The SIPRES study will look at whether these different responses require different targeted treatments, to find the optimal dose.

The research funded by NIHR is part of a doctoral fellowship and supported by the NIHR Manchester Biomedical Research Centre (BRC).

Dr Hansel said: “I believe the findings of this work will help patients survive and get better faster. Individualised dosing for patients with low antibiotic levels in blood, as opposed to ‘one size fits all’ prescribing also has the potential to limit the development of antibiotic resistance by ensuring patients receive the right dose, at the right time.”

The SIPRES study builds on the work of the TDM-TIME study (Therapeutic Drug Monitoring – Targeting IMproved Effectiveness) which Dr Hansel discussed in his blog for last year’s Antimicrobial Resistance Week. The full results of that study will be available in early 2025.