Antibiotic resistance presents a significant global threat to human health. Clinical laboratories
routinely test patient samples for resistance to guide treatment decisions. However, heteroresistance—
where a small subset of resistant cells exists within a predominantly susceptible bacterial population—
often goes undetected by standard testing protocols. This oversight can lead to treatment failures and
the development of full resistance. Although heteroresistance has been observed in many clinical
pathogens, its prevalence and underlying causes in clinical settings remain largely unknown.
To address this gap, we propose analyzing a comprehensive dataset of 2,000 Escherichia coli urinary
tract infection (UTI) samples, we collected in collaboration with Clalit Health Services’ Haifa and
Western Galilee district laboratory and the microbiology laboratories at Rambam Hospital. Our
objective is to systematically quantify the frequency and causes of heteroresistance to the most
clinically relevant antibiotics, and to compare heteroresistance levels and causes across different
clinical environments and antibiotic types.
The findings from this project will allow us identify clinical scenarios where heteroresistance poses the
greatest threat to effective antibiotic use, significantly enhancing our understanding of its clinical
relevance. Additionally, these insights will enable us to design further studies and obtain the necessary
ethical approvals for longitudinal sampling of patients, allowing us to even more directly investigate
the impact of heteroresistance on treatment outcomes.