Projects

Projects in the NIHR Centre for Precision Approaches to Combatting Antimicrobial Resistance are funded by the NIHR, MRC and INNOVATE UK.

TDM-TIME

The TDM-TIME study (Therapeutic Drug Monitoring – Targeting Improved Effectiveness), led by Dr Jan Hansel, was a prospective observational study evaluating the feasibility of real-time therapeutic drug monitoring (TDM) in critically ill patients with respiratory sepsis. TDM uses liquid chromatography with tandem mass spectrometry to measure antibiotic blood levels, ensuring treatments are timely and within the therapeutic range. The study aimed to reduce turnaround times for TDM results, targeting actionable data within two dose intervals. Patients on piperacillin/tazobactam or meropenem had blood samples taken over 6–8 hours for analysis. Conducted at two intensive care units, the study also evaluated secondary outcomes such as process durations, therapeutic target attainment, ICU and hospital stay lengths, and 28-day mortality. Enrolment was completed in July 2024, and the study is now finished, with findings pending analysis.

RADicA

Rapid Access Diagnostics for Asthma (RADicA) is a study involving adults and children with symptoms consistent with asthma, not currently receiving regular treatment. Currently, there is no “gold standard” test to diagnose asthma. The condition is primarily identified through clinical evaluation based on typical symptoms and signs. As a result, asthma is often both overdiagnosed and underdiagnosed. Therefore, there is a pressing need for the development of highly sensitive and specific tests that could serve as a reliable standard for diagnosing asthma. The goal of RADicA study is to determine the optimum series of investigations to diagnose asthma. One of the promising novel investigation tests for detection of asthma is the analysis of volatile organic compounds (VOCs). In the AMR lab we identify the profile of biomarkers in VOCs, which could best predict asthma diagnosis by using thermal desorption – gas chromatography – mass spectrometry.

ELUCEDA

ELUCEDA is a collaborative study between MFT and Eluceda Limited which is funded by Innovate UK. Healthcare-associated infections (HAIs) are a significant public health issue and can lead to prolonged hospital stays, increased resistance to antimicrobials, and high mortality rates. The physical environment plays a significant role in the transmission of HAIs in the hospital, particularly high-touch surfaces (e.g. doors, bedside tables). Commercial ATP bioluminometers are widely used for monitoring cleaning processes in healthcare, however, non-pathogenic surface contaminants can significantly impact readings. Eluceda have developed a biosensor which detects five common bacterial pathogens in a real-time and accurate manner. This information has the potential to provide a better understanding of bacterial contamination in the hospital and support cleaning process monitoring to ensure that the highest standards are maintained. This study aims to assess the environmental microbiome of high-touch surfaces within the hospital and demonstrate if Eluceda’s novel technology could be beneficial for infection control.

SIPRES

The Subphenotyping Immune Profiles in Respiratory Sepsis (SIPRES) Study is an NIHR-funded doctoral fellowship study (NIHR 304654), sponsored by the University of Manchester. SIPRES aims to explore the interaction between transcriptomic signatures in sepsis and low levels of antibiotics in blood. This prospective observational study, with an embedded population pharmacokinetic substudy, will recruit 119 critically ill adults with pneumonia from two Manchester intensive care units. Participants will be classified into two signature categories (Davenport & Sinha), and the study will assess the risk of not achieving antimicrobial target levels in blood. The study is set to launch in November 2025, with Dr Jan Hansel as the principal investigator.

AcCReDiT

AcCReDiT is a study of novel approaches in the diagnosis and management of patients with acute respiratory infections and acute exacerbations of chronic respiratory diseases. This study is funded by the NIHR Manchester Biomedical Research Centre. Traditional diagnostic labels, such as pneumonia, acute exacerbation of chronic obstructive pulmonary disease (COPD), or asthma exacerbations, group together diverse presentations that may require disparate treatments. This study takes a disease label agnostic approach when assessing the clinical and immunological characteristics of acute respiratory conditions, to identify common treatable traits. The study developed a strategy to recruit patients upon presentation to the hospital and prior to receiving treatment. The study uses multi-omics, immune profiling and infection diagnostics to rigorously characterise acute infections and exacerbations and explores the clinical benefits this novel, label agnostic approach could yield.

DEMAND

Defining mechanisms underpinning antibiotic mediated disruption of pulmonary immune responses (DEMAND) is an RCT designed study to explore the impact of antibiotic administration on systemic and pulmonary immune responses through disruption of the commensal microbiota – in both asthmatics and healthy participants. Existing data indicates a link between altered commensal microbiota and regulation of immune responses including in the airways in asthma – including potential switching to a maladaptive Th2 immune endotype. DEMAND will characterise any causal link through deliberate disruption of the microbiome with amoxicillin (or placebo) in both healthy volunteers and asthmatics, with subsequent assessment of microbial metabolites and immune cell characterisation in both blood and broncho-alveolar fluid. DEMAND is a collaborative project with Dr Elizabeth Mann’s group based at the Lydia Becker Institute. Our group’s lead contributor and trial PI is Dr James Orr.