The dynamics of antimicrobial resistance gene prevalence on a commercial pig farm: implications for policy

耐药细菌感染对人类健康的威胁日益严重，这令人相当关切。这些耐药感染发展的主要驱动因素是在人类和动物中使用抗生素。每次使用抗生素时，包括致病细菌（“坏”）、共生细菌（“好”）和环境细菌在内的各种细菌都会被药物杀死，但其中一些细菌会存活下来，因为它们会对所使用的抗生素产生耐药性。细菌可以通过基因的随机变化（突变）或从另一种细菌获得新基因（水平基因转移）而产生耐药性。细菌共享抗生素耐药基因的能力引起了相当大的关注，因为共生细菌和环境细菌可能会成为病原细菌获得耐药基因的储存库。使用的抗生素越多，这些耐药基因就越有可能在广泛的细菌和环境中建立起来。在英国，每年大约有590吨抗生素用于人类，420吨用于动物。没有关于动物使用的准确数据，但家禽和养猪业占这种使用的很大比例。虽然欧盟禁止使用抗生素作为生长促进剂，但它们仍被用于农场动物的群体治疗。我们对农场动物抗生素使用与不同农业系统中抗生素抗性基因水平的关系的理解非常简单。我们不知道农场的管理决策如何影响农场的共生细菌和环境细菌的多样性，以及这与该系统中抗生素抗性基因的“数量”有何关系。我们也不了解这些耐药基因在面对不同的抗生素治疗方案时会发生什么，是否有些方案在选择耐药方面比其他方案“更差”，以及当抗生素治疗停止时耐药基因的水平是否会下降。因此，对于减少和改进农场抗生素使用以尽量减少抗生素抗性基因选择的最有效方法，我们没有明确的证据基础。因此，这项工作的目的是证明，可以测量猪粪便及其环境中细菌多样性和抗微生物药物耐药性基因“数量”的变化，并将其与农场抗生素使用和管理变化相互关联。这项工作的应用将是制定一个框架，根据该框架，可以提出对农场管理实践和抗生素使用的改变，从而最大限度地减少抗生素耐药性的选择。这将使农民受益，因为它减少了选择感染农场动物和更广泛地感染社会的耐药细菌的可能性，减少了由于在农场动物中使用抗生素而导致人类产生抗生素耐药性感染的可能性。

There is considerable concern regarding the increasing threat to human health from drug resistant bacterial infections. The major driver for the development of these drug resistant infections is the use of antibiotics in humans and animals. Each time an antibiotic is used, a wide variety of bacteria including pathogenic ('bad'), commensal ('good') and environmental bacteria will be killed by the drug, however some of these bacteria will survive because they will have become resistant to the antibiotic used. Bacteria can become resistant either through a random change in their genes (mutation) or by acquiring a new gene(s) from another bacteria (horizontal gene transfer). The ability of bacteria to share antibiotic resistance genes is of considerable concern as it is possible that commensal and environmental bacteria could act as a reservoir of resistance genes that could be acquired by pathogenic bacteria. The more antibiotics that are used, the more likely it is that these resistance genes will become established within a broad range of bacteria and environments. Approximately 590 tonnes of antibiotics are used in humans and 420 tonnes in animals in the UK each year. Accurate data regarding use in animals is not available, however poultry and pig farming represent a significant proportion of this use. Whilst the use of antibiotics as growth promoters is banned in the EU, they are still used for group level treatments of farm animals. Our understanding as to how antibiotic use in farm animals relates to the levels of antibiotic resistance genes within different farming systems is very simplistic. We do not know how management decisions on farm impact on the diversity of the commensal and environmental bacteria on the farm and how this relates to the 'quantity' of antibiotic resistance genes in this system. We also do not understand what happens to these resistance genes in the face of different antibiotic treatment protocols, whether some protocols are 'worse' than others at selecting for resistance and whether the levels of resistance genes decay when antibiotic treatment is stopped. We therefore do not have a clear evidence base as to the most effective way to reduce and refine antibiotic use on farms to minimise selecting for antibiotic resistance genes.The aim of this work is therefore to demonstrate that changes in the diversity of bacteria and 'quantity' of antimicrobial resistance genes within pig faeces and their environment can be measured and related to one another, antibiotic use and management changes on the farm. The application of this work will be to develop a framework with which changes to both management practices and antibiotic use on farms can be proposed that minimise the selection for antibiotic resistance. This will benefit farmers by reducing the likelihood of selecting for resistant bacteria that infect farm animals and society more generally by reducing the likelihood that antibiotic resistant infections in humans will develop as a consequence of antibiotic use in farm animals.