Determining the clinical and environmental impact, burden and cost of extensively drug resistant Enterobacteriaceae in China (DETER-XDRE-CHINA)

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)

• 批准号: MR/P007295/1
• 负责人: Timothy Walsh
• 金额: $ 128.01万
• 依托单位: CARDIFF UNIVERSITY
• 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=MR%2FP007295%2F1
• 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 centre 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 humanity back to the "dark ages". Recent announcements from Prime Minister David Cameron, the UK Chief Medical Officer (Professor Sally Davies), and the US president, Barak Obama, is clear evidence that we are loosing one of medicines precious resources. 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. Very recently, 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. Following on from this discovery and using the same network of Chinese colleagues, hospitals and faming sectors, we intend to use MCR-1 (MCRPE) and carbapenem-resistant Enterobacteriaceae (E. coli and E. coli-like bacteria)(CRE) as markers to understand how it has spread throughout the Chinese animal population (colistin is used in animal feed in China). Firstly, we have a comprehensive sampling platform: work package (WP) 1, primary and secondary care infections; WP2, normal flora carriage; WP3, chicken farms and slaughter houses; WP4, retail meat; WP5 Environmental sampling. We will analyze at least 100 samples every 3 months to examine seasonal variation and sample from three distinct provinces in China: Shandong, Zhejiang and Guangdong. 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 all the bacteria in the human gut 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 is likely to withdraw colistin from animal feed 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 so as 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 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, has a proven track record of working together in China and expertise to undertake this exciting and challenging proposal.

抗菌素耐药性 (AMR) 现在被认为是 21 世纪人类面临的最大全球威胁。抗菌素耐药性已成为全球健康问题的焦点，但大多数非专业人士并不知道抗菌素耐药性将对全球人口产生的影响，以及它有可能将人类带回到“黑暗时代”。英国首相戴维·卡梅伦、英国首席医疗官（莎莉·戴维斯教授）和美国总统巴拉克·奥巴马最近的声明清楚地表明，我们正在失去一种宝贵的药物资源。因此，根据“同一个世界健康”的总体理念，各国之间显然需要更好地协调一致的思想和更密切的合作，协同活动、知识和技能，以更好地理解和预防抗菌素耐药性。迄今为止，世界各地大多数研究 AMR 影响的研究都是小规模、一维的，而且往往存在偏见——过于关注 AMR 细菌，而不是研究整个细菌群体。最近，我们与中国同事发表了一篇文章，预示着最后一种抗生素粘菌素的问世，这种抗生素用于治疗由大肠杆菌（俗称大肠杆菌）等已经产生耐药性的细菌引起的非常严重的感染。这一新发现的不同之处在于，粘菌素耐药性（称为 MCR-1）的机制是可移动的，即可以很容易地从一种细菌传播到另一种细菌，甚至在关系较远的细菌之间传播。根据这一发现，并利用中国同事、医院和农业部门的相同网络，我们打算使用 MCR-1 (MCRPE) 和耐碳青霉烯类肠杆菌科细菌（大肠杆菌和类大肠杆菌）(CRE) 作为标记以了解它如何在中国动物种群中传播（粘菌素在中国用于动物饲料）。首先，我们有一个全面的采样平台：工作包（WP）1，初级和二级护理感染； WP2，正常菌群运输； WP3、养鸡场和屠宰场； WP4，零售肉类； WP5 环境采样。我们将每 3 个月分析至少 100 个样本，以检查季节性变化，样本来自中国三个不同的省份：山东、浙江和广东。细菌将通过基本微生物学技术进行分析，并选择进行全基因组测序，我们可以询问细菌的整个 DNA 并将其与其他细菌进行比较，看看它们是否已经从一个部门（例如苍蝇）传播到另一个部门（例如人类）。这项研究还将对人类肠道中的所有细菌进行测序，以了解 AMR 细菌种群的动态。我们还将在养鸡场进行对照实验，监测 CRE 和 MRCPE 的传播情况，并利用数学模型了解 AMR 如何在动物中传播。重要的是，中国政府可能会从动物饲料中撤回粘菌素，因此这项研究非常及时地衡量了这种影响，即撤回粘菌素是否会对环境中的 MCRPE 发生率、人类肠道水平以及导致人类感染的 MCRPE 产生影响？与之前的研究不同，这项研究有意采用整体方法，以便了解抗菌素耐药性在广泛的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 对人群的影响以及中国卫生系统的负担和成本。它还将帮助我们通过数学模型了解抗菌素耐药性对鸡肉和生猪贸易的影响。这项研究将对中国的动物、人类和经济部门产生巨大影响。我们的网络非常完善，在中国拥有良好的合作记录，并且拥有承接这一激动人心且富有挑战性的提案所需的专业知识。

项目成果

An Emerging Clone, Klebsiellapneumoniae Carbapenemase 2-Producing K. pneumoniae Sequence Type 16, Associated With High Mortality Rates in a CC258-Endemic Setting.

• DOI: 10.1093/cid/ciz1095
• 发表时间: 2020-10-23
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
• 作者: Andrey DO;Pereira Dantas P;Martins WBS;Marques De Carvalho F;Almeida LGP;Sands K;Portal E;Sauser J;Cayô R;Nicolas MF;Vasconcelos ATR;Medeiros EA;Walsh TR;Gales AC
• 通讯作者: Gales AC

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

Antibiotic resistance, stewardship, and consumption - Authors' reply.

抗生素耐药性、管理和消费——作者的回复。

• DOI: 10.1016/s2542-5196(18)30263-8
• 发表时间: 2019
• 期刊: The Lancet. Planetary health
• 作者: Collignon P