SynopsisBackgroundOur primary aim was to test whether cattle-associated fluoroquinolone-resistant (FQ-R) Escherichia coli found on dairy farms were a significant cause of bacteriuria in humans living in the same 50 x 50 km geographical region located in South West England. Another aim was to identify risk factors for the presence of FQ-R E. coli on dairy farms.MethodsFQ-R E. coli were isolated during 2017-18 from 42 dairy farms and from community urine samples. Forty-two cattle and 489 human urinary isolates were subjected to WGS, allowing phylogenetic comparisons. Risk factors were identified using a Bayesian regularisation approach.ResultsOf 489 FQ-R human isolates, 255 were also 3rd generation cephalosporin-resistant (3GC-R), with strong genetic linkage between aac(6’)Ib-cr and blaCTX-M-15. We identified possible farm-to-human sharing for pairs of ST744 and ST162 isolates, but core genome SNP distances (71 and 63, respectively) were smaller in pairs of ST744 and ST162 isolates from different farms (7 and 3 SNPs, respectively). Total farm fluoroquinolone use showed a positive association with the odds of isolating FQ-R E. coli while total dry cow therapy use showed a negative association.ConclusionsThis work suggests that FQ-R E. coli found on dairy farms have a limited impact on community bacteriuria within the local human population, however, this appears greater than observed for 3GC-R E. coli when studied in parallel. Reducing fluoroquinolone use may reduce the on-farm prevalence of FQ-R E. coli, and this reduction may be greater when dry cow therapy is targeted to the ecology of resistant E. coli on the farm.