Day MJ, Hopkins KL, Wareham DW, et al. - In view of the observation that, in the UK, more than 5,000 cases of bacteraemias are caused by extended-spectrum β-lactamase-producing Escherichia coli isolates (ESBL-E coli) annually, researchers sought to recognize the most important reservoirs of ESBL-E coli that colonize and infect humans to identify strategic intervention points. From Aug 1, 2013, to Dec 15, 2014, they performed sampling for ESBL-E coli was done. Routinely submitted samples from human feces, and prospectively collected samples from sewage, farm slurry, and retail foodstuffs in London, East Anglia, northwest England, Scotland, and Wales were investigated for ESBL-E coli using selective media. Recovered isolates were sequenced and were compared with 293 bloodstream and 83 veterinary surveillance ESBL-E coli isolates from the same regions. ESBL-E coli were isolated from 2,157 (11%) of 20,243 human feces samples, including 678 (17%) of 3,995 in London. Sewage and retail chicken (104 [65%] of 159 meat samples) frequently contained ESBL-E coli. Findings revealed that in the UK, most human bacteraemias with ESBL-E coli involve internationally prevalent human-associated Sequence types (STs), particularly ST131; there seemed little contribution of non-human reservoirs to invasive human disease. Interventions that target food or livestock may affect the numbers of human infections caused by ESBL-E coli; prevention of the spread of resistant lineages among humans is more vital.