16Little is known about the drivers of critically important antibacterial resistance in 17 species with zoonotic potential present on farms (e.g. CTX-M ꞵ-lactamase-positive 18 Escherichia coli). There is also debate about the influence of farms on the circulation 19 of resistance in local human populations. This was a two-year surveillance study on 20 53 dairy farms. E. coli positive for blaCTX-M were detected in 224/4145 (5.4%) of all 21 samples from faecally-contaminated sites. E. coli positive for blaCTX-M were more 22 prevalent (98/631; 15.5%) in calf samples and less prevalent (12/630; 1.9%) in 23 samples collected from pastureland, including publicly accessible sites. Multilevel, 24 multivariable logistic regression showed antibiotic dry cow therapeutic choice to be 25 associated with risk of blaCTX-M positivity, including use of cefquinome or framycetin; 26 74% of blaCTX-M-positive E. coli were framycetin-resistant. Low temperature was 27 associated with low risk of blaCTX-M positivity. This was additional to the effect of 28 temperature on total E. coli density, a finding with profound implications for 29 surveillance. There was no evidence that study farms had a significant impact on 30 circulating blaCTX-M plasmids in the local human population: across 296 fully 31 sequenced E. coli isolates, two cattle isolates shared blaCTX-M plasmids with eight 32 urinary isolates collected in parallel.33 34 Antimicrobial resistance (AMR) -and particularly antibacterial resistance (ABR) -is a 35 significant global challenge. Many countries are implementing plans to reduce the 36 use of antibacterial drugs (ABs) in food-producing animals. For example, the most 37 recent UK five-year National Action Plan includes a target to reduce AB use (ABU) in 38the treatment of food-producing animals by 25% (1). In Europe, AB sales for food-39 producing animals fell by 20% from 2011 to 2016 (2). In the UK dairy industry, 40 overall ABU dropped from 24 mg/kg in 2015 to 17 mg/kg in 2017 (3, 4). In 2018, 41 additional industry-led policies were enforced in the UK that aim to almost eliminate 42 the use of highest priority critically important antimicrobials (HP-CIAs) such as third-43 and fourth-generation cephalosporins (3GCs and 4GCs) and fluoroquinolones on 44 dairy farms. One reason for reducing ABU in farming is the belief that such 45 measures will reduce the prevalence of ABR bacteria carried by farm animals. 46 However, there is a need for better data on drivers of ABR in farming. More 47 granularity of understanding is required concerning the risks of using individual ABs 48 and other management practices. This is especially important in terms of drivers of 49 HP-CIA resistance. One key focus is on 3GC resistance in Escherichia coli, a 50 species commonly found in animal faeces and considered one of the most significant 51 potential zoonotic threats to humans (5).
523GC-resistance is increasingly common in E. coli causing infections in humans (6) 53 and is also found in farmed and domestic animals around the world (7). The...