E. coli evolves antibiotic resistance during treatment, study finds

Researchers have provided rare, real-time evidence of antibiotic resistance evolving within a patient, revealing how E. coli can adapt and evade treatment mid-course. The findings, published in the Journal of Medical Microbiology, have serious implications for diagnostics, treatment strategies, and the development of new antibiotics.

The study [1], led by the Liverpool School of Tropical Medicine (LSTM), describes the case of a critically ill patient with a bloodstream infection caused by E. coli. Initially responsive to piperacillin/tazobactam (TZP) - a commonly used combination of a beta-lactam antibiotic and enzyme inhibitor - the infection became increasingly resistant during therapy, ultimately leading to treatment failure.

Unlike many cases of resistance where bacteria acquire entirely new genes, the E. coli strain in this case rapidly amplified an existing gene known as blaTEM-1, which encodes a beta-lactamase enzyme that breaks down beta-lactam antibiotics like piperacillin. Gene copy numbers increased tenfold, raising the bacteria’s resistance to levels 32 times higher than at the start of treatment.

“This case is a striking demonstration of how quickly bacteria can evolve when exposed to antibiotic pressure,” said Dr Thomas Edwards, co-senior author and researcher at LSTM’s Centre for Drugs and Diagnostics. “Gene amplification is a subtle but powerful mechanism that can escape routine diagnostic detection.”

The team, including collaborators from Liverpool Clinical Laboratories, Liverpool University Hospital Foundation Trust, and the University of Strathclyde, used whole-genome sequencing to track genetic changes during the patient’s treatment. Further lab work confirmed that continued TZP exposure could drive E. coli to increase blaTEM-1 copies even further.

Lead author Alice Fraser, a PhD student funded by the MRC, added: “Not only did we observe resistance escalating rapidly, but we also found other gene duplications suggesting wider bacterial adaptation, possibly impacting virulence or persistence in the host.”

Crucially, the study raises concerns about the widespread reliance on TZP and similar beta-lactam/beta-lactamase inhibitor combinations. With over 40% of antibiotics in development belonging to this class, emerging resistance mechanisms like gene amplification could threaten their long-term effectiveness.

Dr Edwards emphasised the need for advanced diagnostics: “Standard resistance tests may miss these adaptive changes. We must invest in surveillance tools capable of detecting evolving resistance - not just static gene presence.”

The team is now embarking on a two-year project, funded by the Academy of Medical Sciences, to further explore gene amplification and its clinical impact.

More information online

1.    A high-resolution genomic and phenotypic analysis of resistance evolution of an Escherichia coli strain from a critically unwell patient treated with piperacillin/tazobactam published in the Journal of Medical Microbiology