EVAL-FARMS: Evaluating the Threat of Antimicrobial Resistance in Agricultural Manures and Slurries

抗生素被广泛用于对抗细菌感染，并挽救了数百万人的生命。然而，这种细菌正在对抗生素产生耐药性，一些抗生素已经不起作用了。我们称之为抗菌素耐药性（AMR）。我们不只是对人使用抗生素；用于农场动物的药量也差不多。在英国，每年有超过9亿只农场动物被饲养，抗生素治疗对它们的福利、对农场的商业、对我们享受负担得起的食物都至关重要。然而，农场可能助长了抗菌素耐药性的发展。该项目的目的是提高我们对农场实践，特别是粪便处理方式，如何导致动物和人类病原体的抗生素耐药性的理解。这种理解将有助于农民和兽医找到减少抗生素耐药性的新方法，同时不伤害他们的动物或他们的企业。出于研究目的，诺丁汉大学维持着一个典型的高性能奶牛场——它的200头奶牛产出大量的牛奶和大量的粪便。废物被储存在一个300万升的泥浆池中，多余的废物被放入一个700万升的泻湖中。这种浆液作为有机肥施用于田地。牛粪含有许多无害的细菌，但有些细菌，如大肠杆菌O157，可引起人类严重感染。当奶牛生病时，用抗生素治疗。乳房感染的治疗方法是在乳房内注射抗生素。由于这种牛奶含有抗生素，所以不能出售，而是被丢弃在牛奶浆中。脚部感染用抗菌泡脚液治疗，泡脚液也被倒进浆液罐中。因此，浆液罐中含有细菌，抗生素和其他抗菌剂的混合物，可以储存数月。在抗生素存在下存活的细菌更有可能产生抗生素耐药性。这种抗性被编码在它们的基因中，从而传递给下一代。更糟糕的是，这些基因可以传递给浆液中的其他细菌。在我们写这个建议之前，我们调查了我们自己农场的泥浆罐，看看这种情况是否会发生。我们从浆液中检测了160株大肠杆菌；大多数都有抗生素耐药性。我们还在水箱里发现了抗生素，包括一些细菌耐药的抗生素。我们的数学模型显示，减少耐药基因在水箱中的传播可能比减少抗生素的使用更有效地预防耐药。与农场兽医的谈话显示，他们知道AMR，并改变了一些抗生素处方。但这些分析留给我们的问题多于答案。在这个项目中，我们想要找出当前的养殖方法是否导致了泥浆中有害的耐抗生素细菌的发展，这些细菌可能会被人类和动物遇到。要做到这一点，我们需要结合科学和文化方法：-浆液中有什么细菌？有多少是有害的？它们携带什么抗性基因？这些基因是如何传播的？-抗生素能在药箱中保存多久？它们会退化吗？——细菌和抗生素扩散到田地后会发生什么？农民、兽医和科学家如何解释有关抗生素耐药性的证据？他们隐藏的假设是什么？我们能否改进AMR风险管理方面的协作决策？-我们能否通过避免在浆料中混合细菌和抗菌剂来降低耐药性？-我们能否预测出现和接触耐药病原体的风险？考虑到人为因素和科学因素，我们能否预测哪些干预措施可能最有效地减少抗生素耐药性？通过这项研究，我们将了解如何切实地降低这种风险；不仅是这个农场，整个英国都是如此我们将与农民、兽医和政策制定者合作，确保我们的成果将对减少农业中产生有害的抗菌素耐药性细菌的风险产生影响。

Antibiotics are used extensively to fight bacterial infections and have saved millions of lives. However, the bacteria are becoming resistant to antibiotics and some antibiotics have stopped working. We refer to this as antimicrobial resistance - AMR. We don't just use antibiotics for people; similar amounts are given to farm animals. More than 900 million farm animals are reared every year in the UK and antibiotic treatments are vital for their welfare, for farms as businesses, and for us to enjoy affordable food. However, farms may be contributing to the development of AMR. The aim of this project is to improve our understanding of how farm practice, especially the way in which manure is handled, could lead to AMR in animal and human pathogens. This understanding will help farmers and vets find new ways to reduce AMR, without harming their animals or their businesses.For research purposes, Nottingham University maintains a typical high performance dairy farm - its 200 cows produce a lot of milk and a lot of manure. The waste is stored in a 3 million litre slurry tank, any excess goes into a 7 million litre lagoon. This slurry is applied to fields as organic fertilizer. Cow manure contains many harmless bacteria but some, e.g. E. coli O157, can cause severe infection in people. When cows get sick they are treated with antibiotics. Udder infections are treated by injection of antibiotics into the udder. Since this milk contains antibiotics, it cannot be sold but is discarded into the slurry. Foot infections are treated with an antibacterial footbath, which is also emptied into the slurry tank.As a result, slurry tanks contain a mixture of bacteria, antibiotics and other antimicrobials that are stored for many months. The bacteria that survive in the presence of antibiotics are more likely to have antibiotic resistance. This resistance is encoded in their genes so passed to the next generation. Worse still, the genes can be passed on to other bacteria in the slurry. Before we wrote this proposal, we investigated our own farm's slurry tank to see if this might be happening. We tested 160 E. coli strains from the slurry; most carried antibiotic resistance. We also found antibiotics in the tank - including some that bacteria were resistant to. Our mathematical modellers showed that reducing spread of resistance genes in the tank might be more effective in preventing resistance than cutting the use of antibiotics. Conversations with the farm vets revealed that they knew about AMR and had changed some of their antibiotic prescriptions. But these analyses leave us with more questions than answers.In this project, we want to find out if current farming methods are contributing to the development of harmful antibiotic-resistant bacteria in slurry, bacteria that may then be encountered by humans and animals. To do this, we need to integrate scientific and cultural approaches:- What bacteria are in the slurry? How many are harmful? What resistance genes do they carry? How do these genes spread?- How long do antibiotics remain in the tank? Do they degrade?- What happens to the bacteria and antibiotics after they are spread on fields?- How do farmers, vets and scientists interpret evidence about AMR? What are their hidden assumptions? Can we improve collaborative decision making on AMR risk management? - Can we reduce resistance by avoiding mixing together bacteria and antimicrobials in slurry?- Can we predict the risk of emergence of and exposure to resistant pathogens? Can we predict which interventions are likely to be most effective to reduce AMR, taking into account both human and scientific factors?Through this research, we will learn what can realistically be done to reduce this risk; not just on this farm, but UK wide. We will work with farmers, vets and policy makers to ensure that our results will make a difference to reducing the risk of harmful AMR bacteria arising in agriculture.