Completed Infection & Immunity Lungs & Breathing

Understanding and predicting the evolution of antibiotic resistance in human infection

Funder Wellcome Charity-funded
Associated organisations University of Dundee · University of Liverpool · University of Manchester · University of Sheffield Europe PMC affiliations are not treated as award recipients or mapped locations.
Funding £1.8M
Period Oct 2020 — Sept 2025

In plain English

AI plain-English summary

Ciprofloxacin resistance emerged in roughly 40% of patients treated for chronic lung infections in two major clinical trials—and no one knows why it happened in some people but not others. This matters because antibiotic resistance is a growing threat, especially for patients with chronic infections like those caused by *Pseudomonas aeruginosa*, a WHO Priority-1 pathogen. Most studies of resistance evolution happen in lab dishes, not inside actual human patients. The researchers identified a unique opportunity: two completed Phase-III randomised trials of inhaled ciprofloxacin, which provide a controlled, replicated natural experiment. They will analyse bacterial and host samples from those trials to discover the evolutionary mechanisms driving resistance, identify which bacterial and host properties predict its emergence, and test whether those biomarkers can forecast resistance in other patients. If successful, this work could give clinicians a practical tool: a way to predict which patients are most likely to develop resistance during treatment, allowing them to choose alternative therapies early. It would also transform how future antibiotic trials are designed, turning them into powerful experiments for studying evolution in real time.

View original technical description
The evolution of antibiotic resistance is a threat to modern medicine. Patients with chronic bacterial infections are at particular risk from antibiotic resistant genotypes, which typically arise from within the infection. However, a lack of controlled studies means that we don't understand how antibiotic resistance evolves within the human host environment, and why the emergence of resistance varies among patients. We identify randomised clinical trials (RCTs) of new antibiotic treatments as a powerful way to study resistance evolution in action during a controlled, replicated natural experiment. We will exploit a unique opportunity to perform an evolutionary analysis of two parallel Phase-III RCTs for inhaled ciprofloxacin treatment of chronic lung infections caused by Pseudomonas aeruginosa, which is a WHO Priority-1 pathogen in critical need of improved antibiotic therapies. Ciprofloxacin resistance emerged in ~40% of the treated patient infections but this patient-to-patient variation is unexplained. We aim to explain why resistance evolved in some patients but not in others. To do this, we will (1) discover the evolutionary mechanisms of resistance emergence in patient infections, (2) identify the bacterial and host properties that drove resistance evolution, and then (3) test how well biomarkers of these drivers predict resistance emergence in other patients.

View the original record at the funder ↗

Researchers

Craig Winstanley (EPMC Awardee)Dylan Childs (EPMC Awardee)James Chalmers (EPMC Awardee)Michael Brockhurst (EPMC Awardee)Steve Paterson (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Ecological and Evolutionary Drivers of Antibiotic Resistance in Patients
Determining the architecture of antibiotic resistance evolvability
How repeatable is the evolution of antibiotic resistance in different bacterial habitats?
Combating drug resistance with evolutionary biology
Understanding and preventing the evolution of antibiotic tolerance

Original classification

Collaborative Award in Science

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.