Characterisation of AmpC Hyper-Producing Escherichia coli from Humans and Dairy Farms Collected in Parallel in the Same Geographical Region

Objectives To characterise putative AmpC hyper-producing 3 rd generation cephalosporin-resistant E. coli from dairy farms and their phylogenetic relationships as well as to identify risk factors for their presence; to assess evidence for their zoonotic transmission into the local human population Methods Proteomics was used to explain differences in antimicrobial susceptibility. Whole genome sequencing allowed phylogenetic analysis. Multilevel, multivariable logistic regression modelling was used to identify risk factors. Results Increased use of amoxicillin-clavulanate was associated with an increased risk of finding AmpC hyper-producers on farms. Expansion of cephalosporin resistance in AmpC hyper-producers was seen in farm isolates with marR mutations (conferring cefoperazone resistance) or when AmpC was mutated (conferring 4 th generation cephalosporin and cefoperazone resistance). Phylogenetic analysis confirmed the dominance of ST88 amongst farm AmpC hyper-producers but there was no evidence for acquisition of farm isolates by members of the local human population. Conclusions In this two-year surveillance study of 53 dairy farms, AmpC hyper-production was the cause of cefotaxime resistance in 46.2% of E. coli . There was evidence of recent farm-to-farm transmission and of adaptive mutations to expand resistance. Whilst there was no evidence of isolates entering the local human population, efforts to reduce 3 rd generation cephalosporin resistance on dairy farms must address the high prevalence of AmpC hyper-producers. The finding that amoxicillin-clavulanate use was associated with increased risk of finding AmpC hyper-producers is important because this is not currently categorised as a highest-priority critically important antimicrobial and so is not currently targeted for specific usage restrictions in the UK.