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

耐药性细菌感染对人类健康的威胁日益增加，这引起了相当大的关注。这些耐药性感染发展的主要驱动力是人类和动物使用抗生素。每次使用抗生素时，各种各样的细菌，包括致病菌（“坏”），益生菌（“好”）和环境细菌都会被药物杀死，但是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。细菌可以通过其基因的随机变化（突变）或通过从另一种细菌获得新基因（水平基因转移）来产生耐药性。细菌共享抗生素抗性基因的能力是相当令人关注的，因为微生物和环境细菌可能充当病原菌可以获得的抗性基因的储存库。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。在英国，每年约有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，但家禽和养猪业占该用途的很大比例。虽然欧盟禁止使用抗生素作为生长促进剂，但它们仍用于农场动物的群体水平治疗。我们对抗生素在农场动物中的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中细菌和环境细菌的多样性，以及这与该系统中抗生素耐药基因的“数量”有何关系。我们也不知道在面对不同的抗生素治疗方案时，这些耐药基因会发生什么，是否有些方案在选择耐药性方面比其他方案“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，我们没有一个明确的证据基础，以最有效的方法来减少和改进抗生素的使用，以尽量减少抗生素耐药基因的选择。因此，这项工作的目的是证明，细菌的多样性和猪粪便及其环境中的抗生素耐药基因的“数量”的变化可以测量和相互关联，抗生素的使用和农场管理的变化。这项工作的应用将是制定一个框架，通过该框架可以提出农场管理实践和抗生素使用的变化，以最大限度地减少抗生素耐药性的选择。这将通过减少选择感染农场动物的耐药细菌的可能性而使农民受益，更普遍地通过减少人类中抗生素耐药性感染因农场动物中抗生素使用而发展的可能性而使社会受益。

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.