Determining the clinical and environmental impact, burden and cost of Extensively Drug Resistant Enterobacteriaceae in China (DETER-XDRE-CHINA-HUB)

确定中国广泛耐药肠杆菌科细菌的临床和环境影响、负担和成本 (DETER-XDRE-CHINA-HUB)

• 批准号: MR/S013768/2
• 负责人: Timothy Walsh
• 金额: $ 175.04万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS013768%2F2
• 关键词: Determining; clinical; environmental; impact; burden

Antimicrobial resistance (AMR) is now deemed to be the biggest global threat facing humanity in the 21C. AMR has taken center stage as a global health issue yet most non-specialists are unaware the impact AMR will have on global populations and the potential it has of taking the treatment of infections back to the "dark ages". Therefore, in keeping with the general notion of "One World Health", there clearly needs to a better alignment of thinking and closer co-operation between countries synergizing activities, knowledge and skills to better understand and prevent AMR. Hitherto, most studies around the world studying the impact of AMR have been small, one dimensional and often biased - too focused on AMR bacteria as oppose to studying the whole bacterial population. Two years ago, we published an article with our Chinese colleagues heralding the breech of the last antibiotic, colisitin, that is used to treat the very serious infections caused by already resistant bacteria such as Escherichia coli (commonly known as E. coli). The difference with this new discovery is that the mechanism of colistin resistance (named MCR-1) is mobile i.e. can be readily passed around from one bacteria to another - even between distantly related bacteria. This article reached global acclaim and has been cited over 1000 times reflecting its broad impact. Following on from this discovery and using the same network of Chinese colleagues, hospitals, farming and environmental sectors, we intend to use MCR (MCRPE) and carbapenem-resistant Enterobacteriaceae (E. coli and E. coli-like bacteria)(CRE) as markers to understand how AMR has spread throughout the Chinese human and animal populations (colistin is used in animal feed in China). Firstly, we have a comprehensive sampling platform: work package (WP) 1, normal flora carriage; WP2, primary and secondary care infections; WP3, chicken, duck and pigs including slaughter houses; WP4, flies and wild birds; WP5, Water, soil and waste; WP6, Aquaculture; and WP7, Domestic animals. Pending the type of sample, we will analyze at least 100 samples every 3/6 months to examine seasonal variation and sample from three distinct provinces in China: Shandong, Guangdong and Jiangsu; additionally, we will also chose Qinghai as a control region. Bacteria will be analyzed by basic microbiology techniques and selected to be whole genome sequenced where we can interrogate the bacteria's whole DNA and compare it to other bacteria to see if they have spread from one sector (e.g. flies) to another (e.g. humans). This study will also sequence bacteria in the human gut (called the microbiome) to understand the dynamics of AMR bacterial populations. We will also undertake controlled experiments in chicken farms to monitor the spread on CRE and MRCPE and use mathematical models to understand how AMR spreads in animals. Importantly, the Chinese government has recently (2017) withdrawn the antibiotic colistin so this study is very timely in measuring that effect i.e. will withdrawing colistin impact on MCRPE rates in the environment, human gut levels and MCRPE causing human infections? Unlike previous studies, this study is deliberately holistic in its approach to understand the dynamics and transmission of AMR across a broad range of environmental and human sectors. This study will let us understand the impact of CRE and MCRPE on human populations and the burden and cost to the Chinese health system. It will also help us understand the impact AMR on the chicken, duck and pig trade by using mathematical models. The impact of this study will have immense consequences for the animal, human and economic sectors in China. Our network is well established, high successful and has a proven track record of working together in China and expertise to undertake this exciting and challenging proposal.

现在，抗菌抗性（AMR）现在被视为21c人类面临的最大全球威胁。作为全球健康问题，AMR已成为中心阶段，但大多数非专家们并没有意识到AMR对全球人口的影响及其将感染治疗的潜力带回“黑暗时代”。因此，与“一个世界卫生”的一般概念保持一致，显然需要更好地保持思维和更紧密的合作，以协同活动，知识和技能，以更好地理解和预防AMR。迄今为止，世界各地研究AMR影响的大多数研究都很小，一维且经常有偏见 - 过于专注于AMR细菌，而不是研究整个细菌种群。两年前，我们与中国同事一起发表了一篇文章，预示了最后一位抗生素菌丝素的臀位，该文章用于治疗由已经抗药性细菌（例如Escherichia coli）（通常称为大肠杆菌）引起的非常严重的感染。与这一新发现的不同之处在于，结肠蛋白抗性的机理（称为MCR -1）是移动的，即可以很容易地从一种细菌传递到另一种细菌，甚至可以在远距离相关的细菌之间传递。这篇文章获得了全球的好评，并被引用了1000多次，以反映其广泛的影响。 Following on from this discovery and using the same network of Chinese colleagues, hospitals, farming and environmental sectors, we intend to use MCR (MCRPE) and carbapenem-resistant Enterobacteriaceae (E. coli and E. coli-like bacteria)(CRE) as markers to understand how AMR has spread throughout the Chinese human and animal populations (colistin is used in animal feed in China).首先，我们有一个全面的抽样平台：工作包（WP）1，普通植物车辆； WP2，初级和二级护理感染； WP3，鸡肉，鸭和猪，包括屠宰场； WP4，苍蝇和野鸟； WP5，水，土壤和废物； WP6，水产养殖；和WP7，家畜。在样本类型之前，我们将每3/6个月至少分析100个样本，以检查中国三个不同省份的季节性变化和样本：山东，广东和江苏；此外，我们还将选择青海作为对照区域。细菌将通过基本的微生物学技术进行分析，并被选为整个基因组测序，我们可以在其中询问细菌的整个DNA，并将其与其他细菌进行比较，以查看它们是否已经从一个部门（例如果蝇）与另一个部门（例如人类）进行了比较。这项研究还将对人肠道（称为微生物组）中的细菌进行测序，以了解AMR细菌种群的动力学。我们还将在鸡场中进行受控的实验，以监视CRE和MRCPE上的扩散，并使用数学模型来了解AMR如何在动物中传播。重要的是，中国政府最近有（2017年）撤回了抗生素结肠蛋白，因此这项研究非常及时地衡量这种影响，即会撤回对环境，人类肠道水平和MCRPE的MCRPE率的影响，从而导致人类感染？与以前的研究不同，这项研究是故意整体的方法，可以理解AMR在各种环境和人类领域的动态和传播。这项研究将使我们了解CRE和MCRPE对人口的影响以及中国卫生系统的负担和成本。它还将通过使用数学模型来帮助我们了解AMR对鸡肉，鸭子和猪贸易的影响。这项研究的影响将对中国的动物，人类和经济部门产生巨大后果。我们的网络已经建立了良好，成功，并具有在中国共同合作和专业知识来实现​​这一令人兴奋且充满挑战的建议的良好记录。

项目成果

Comparing Long-Read Assemblers to Explore the Potential of a Sustainable Low-Cost, Low-Infrastructure Approach to Sequence Antimicrobial Resistant Bacteria With Oxford Nanopore Sequencing.

• DOI: 10.3389/fmicb.2022.796465
• 发表时间: 2022
• 期刊: Frontiers in microbiology
• 影响因子: 5.2
• 作者: Boostrom I;Portal EAR;Spiller OB;Walsh TR;Sands K
• 通讯作者: Sands K

Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis.

• DOI: 10.1016/s0140-6736(21)02724-0
• 发表时间: 2022-02-12
• 期刊: Lancet (London, England)
• 作者: Antimicrobial Resistance Collaborators

Pre-existing chromosomal polymorphisms in pathogenic E. coli potentiate the evolution of antibiotic resistance by MCR-1 plasmid acquisition

致病性大肠杆菌中预先存在的染色体多态性通过 MCR-1 质粒的获得增强了抗生素耐药性的进化

• DOI: 10.1101/2022.02.20.481192
• 发表时间: 2022
• 作者: Jangir P