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Acquisition and Selection of Antibiotic Resistance in Companion and Farmed Animals and Implications for Transmission to Humans

伴侣动物和养殖动物抗生素耐药性的获得和选择及其对人类传播的影响

基本信息

批准号：
NE/N01961X/1
负责人：
Matthew Avison
金额：
$ 181.79万
依托单位：
University of Bristol
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=NE%2FN01961X%2F1
关键词：
Acquisition Selection Antibiotic Resistance Companion

项目摘要

Without antimicrobial drugs, the risk of bacterial infection would render many common medical procedures too dangerous to contemplate because of the risk of infections caused by "opportunistic bacteria". They can live on the patient's skin, or in their intestines, and infection occurs when bacteria get into parts of the body that are normally sterile. A perfect example is urinary tract infection (UTI) caused by faecal bacteria. E. coli is particularly abundant in human faeces so is perfectly placed to cause opportunistic infections. It is one of the most common causes of healthcare pneumonia, surgical site infection, bloodstream infection and UTI in the UK. In order to prevent against and treat opportunistic infections, patients are given antimicrobials.Almost all antimicrobials are "antibiotics", which means they are derived from natural chemicals produced by microbes found in the environment. Natural antibiotics have been present in the environment for millions of years, and so bacteria living in their presence have had time to evolve mechanisms that can resist their actions, encoded by "resistance genes". Opportunistic bacteria like E. coli can randomly acquire these pre-evolved resistance genes and in a single step, they become insusceptible to a particular antimicrobial. If that insusceptible E. coli colonises a person and then causes an opportunistic infection, the infection will not be treatable with that particular antimicrobial. We refer to this as "antimicrobial resistance" (AMR); however AMR bacteria don't just resist clinical antimicrobial therapy, they beat it.Animals also carry an abundance of E. coli in their intestines and are frequently treated with antimicrobials. This can select for the acquisition of AMR E. coli which can then be passed on to another animals, directly, or via contamination of the environment with faeces. Theoretically, the AMR E. coli could also be passed on to people, and there is much debate about whether such "zoonotic transmission" happens to any significant degree. This is an important debate because it has led to calls from some to dramatically reduce the amount of antimicrobials that are given to animals with the view that it will reduce the level of AMR in animals, and so the possibility of zoonotic transmission to people. But the potential impact on welfare and food production means this should only be done if there is evidence that it will work.In this project we will identify what drives acquisition of AMR in animals using E. coli as the exemplar bacterium and dairy cows and dogs as exemplar farmed and companion animals. We will test whether AMR bacteria encountered by an animal as it interacts with the environment influence the AMR profile in its faeces, and/or whether early life antimicrobial use plays a part in selection of AMR bacteria in animals. We will also test whether reducing antimicrobial use in dairy cows actually does reduce AMR in the near-farm environment that is contaminated with their faeces. We will test whether exercising in these contaminated near-farm environments influences the abundance of AMR bacteria in dogs, and whether there is any evidence of direct acquisition of AMR E. coli by dogs from near-farm environments, which might be brought into the home.Finally, we will investigate whether AMR abundance in human UTI E. coli reduces as antimicrobial drug prescribing reduces in primary care; whether living close to a farm affects AMR abundance in UTI E. coli; whether there is direct evidence for E. coli carried by dogs or found in near-farm environments contaminated by cattle faeces also causing UTIs in humans.These interlaced studies will provide much needed data about the management changes that might reduce AMR in animals and in humans, and are designed to address the fundamental question of whether zoonotic transmission is particularly significant as a driver of AMR in people relative to antimicrobial drug use by doctors.

如果没有抗微生物药物，细菌感染的风险将使许多常见的医疗程序过于危险而无法考虑，因为“机会性细菌”有引起感染的风险。它们可以生活在病人的皮肤上或肠道里，当细菌进入通常是无菌的身体部位时，就会发生感染。由粪便细菌引起的尿路感染（UTI）就是一个很好的例子。大肠杆菌在人类粪便中尤其丰富，因此很容易引起机会性感染。它是英国医疗保健肺炎、手术部位感染、血液感染和尿路感染的最常见原因之一。为了预防和治疗机会性感染，向患者提供抗菌素。几乎所有的抗菌剂都是“抗生素”，这意味着它们是从环境中发现的微生物产生的天然化学物质中提取的。天然抗生素已经在环境中存在了数百万年，因此生活在它们存在下的细菌有时间进化出能够抵抗它们的机制，这些机制由“抗性基因”编码。像大肠杆菌这样的机会性细菌可以随机获得这些预先进化的抗性基因，并且在一个简单的步骤中，它们变得对特定的抗菌素不敏感。如果这种不敏感的大肠杆菌在人体内定居，然后引起机会性感染，那么这种感染将无法用这种特定的抗菌素治疗。我们称之为“抗菌素耐药性”（AMR）；然而，AMR细菌不仅会抵抗临床抗菌药物治疗，还会击败它。动物的肠道中也携带着大量的大肠杆菌，经常使用抗菌剂治疗。这可以选择获得AMR大肠杆菌，然后直接或通过粪便污染环境将其传递给其他动物。从理论上讲，AMR大肠杆菌也可以传染给人类，关于这种“人畜共患传播”是否会发生重大程度的争论很多。这是一场重要的辩论，因为它导致一些人呼吁大幅减少给动物的抗菌素用量，认为这将降低动物的抗菌素耐药性水平，从而降低人畜共患疾病传播给人类的可能性。但是，对福利和粮食生产的潜在影响意味着，只有在有证据表明它会起作用的情况下，才应该这样做。在这个项目中，我们将以大肠杆菌为样本细菌，以奶牛和狗为样本养殖动物和伴侣动物，确定是什么导致了动物产生抗生素耐药性。我们将测试动物在与环境相互作用时遇到的抗菌素耐药性细菌是否会影响其粪便中的抗菌素耐药性谱，以及/或生命早期使用抗菌素是否在动物的抗菌素耐药性细菌选择中起作用。我们还将测试减少奶牛的抗菌药物使用是否真的能减少被奶牛粪便污染的农场附近环境中的抗生素耐药性。我们将测试在这些污染的农场附近环境中锻炼是否会影响狗体内AMR细菌的丰度，以及是否有证据表明狗从农场附近环境中直接获得AMR大肠杆菌，这些细菌可能会被带到家中。最后，我们将调查人类尿路感染大肠杆菌的AMR丰度是否会随着初级保健中抗菌药物处方的减少而减少；住在农场附近是否会影响尿路感染大肠杆菌的AMR丰度；是否有直接证据表明狗携带的大肠杆菌或在被牛粪便污染的农场附近环境中发现的大肠杆菌也会引起人类的尿路感染。这些相互交错的研究将提供有关可能减少动物和人类抗微生物药物耐药性的管理变化的急需数据，并旨在解决与医生使用抗微生物药物相比，人畜共患传播作为人类抗微生物药物耐药性的驱动因素是否特别重要的基本问题。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

One Health drivers of antibacterial resistance: Quantifying the relative impacts of human, animal and environmental use and transmission.

DOI：
10.1016/j.onehlt.2021.100220
发表时间：
2021-06
期刊：
One health (Amsterdam, Netherlands)
影响因子：
0
作者：
Booton RD;Meeyai A;Alhusein N;Buller H;Feil E;Lambert H;Mongkolsuk S;Pitchforth E;Reyher KK;Sakcamduang W;Satayavivad J;Singer AC;Sringernyuang L;Thamlikitkul V;Vass L;OH-DART Study Group;Avison MB;Turner KME
通讯作者：
Turner KME

Comparison of risk factors for, and prevalence of, antibiotic resistance in contaminating and pathogenic urinary Escherichia coli in children in primary care: prospective cohort study.