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，拯救了数百万人的生命。然而，细菌对抗生素产生了抗药性，一些抗生素已经停止起作用。我们将其称为抗菌素耐药性-AMR。我们不仅对人使用抗生素，对农场动物也使用类似剂量的抗生素。英国每年饲养的农场动物超过9亿只，抗生素治疗对它们的福利、农场作为企业以及我们享受负担得起的食物至关重要。然而，农场可能对AMR的发展做出了贡献。这个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AMR的理解。这一认识将帮助农民和兽医找到新的方法来减少AMR，而不会损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养殖场-它的200头奶牛生产大量牛奶和大量粪便。废物储存在300万升的泥浆池中，任何多余的废物都会进入700万升的泻湖。这种泥浆可作为有机肥施于田间。牛粪含有许多无害的细菌，但有些细菌，如O157大肠杆菌，可引起人的严重感染。当奶牛生病时，它们会被抗生素治疗。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，只能被丢弃在浆液中。足部感染用抗菌足浴进行治疗，足浴也被倒入泥浆罐中。因此，泥浆罐中含有细菌、抗生素和其他抗菌剂的混合物，可储存数月。在抗生素存在的情况下存活的细菌更有可能具有抗生素耐药性。这种抗性编码在它们的基因中，因此传递给下一代。更糟糕的是，这些基因可以传递给泥浆中的其他细菌。在我们写这份提案之前，我们调查了我们自己农场的泥浆罐，看看这种情况是否可能发生。我们从泥浆中检测了160株大肠杆菌；大多数携带抗生素耐药性。我们还在水箱中发现了抗生素--包括一些细菌具有抗药性的抗生素。我们的数学模型显示，在预防耐药性方面，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。与农场兽医的谈话显示，他们知道AMR，并更改了一些抗生素处方。但这些分析给我们带来的问题比答案更多。在这个项目中，我们想要找出目前的耕作方法是否会导致泥浆中有害的抗生素耐药性细菌的发展，这些细菌随后可能会被人类和动物遇到。要做到这一点，我们需要整合科学和文化方法：-泥浆中有什么细菌？有多少是有害的？它们携带哪些抗性基因？这些基因是如何传播的？-抗生素能在罐子里保留多久？它们会降解吗？-细菌和抗生素在田间传播后会发生什么？-农民、兽医和科学家如何解释有关AMR的证据？他们隐藏的假设是什么？我们能改进AMR风险管理的协作决策吗？-我们能通过避免在泥浆中混合细菌和抗菌剂来降低耐药性吗？-我们能预测出现耐药病原体和接触耐药病原体的风险吗？考虑到人为和科学因素，我们能预测哪些干预措施可能最有效地降低AMR吗？通过这项研究，我们将了解实际可以做些什么来降低这种风险；不仅在这个农场，而且在整个英国。我们将与农民、兽医和政策制定者合作，确保我们的结果将对降低农业中出现有害AMR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.