Development and validation of the first environmental risk assessment tool to protect against selection for antimicrobial resistance in situ

抗生素通过选择性耐药性（AMR）对自然环境构成当代污染挑战，这对人类和动物健康、食品安全和环境保护具有深远的社会和经济影响。如果不改善我们的抗菌素管理和抗生素开发管道，预计到2050年，抗菌素耐药性（AMR）将成为全球死亡的主要原因，每年导致1000万人死亡[1]。AMR也是全球经济的重大负担。世界银行集团估计，到2050年，AMR将使全球英镑和全球出口每年分别减少3.8%。对医疗保健和粮食安全的影响也将是巨大的，每年需要额外的7000亿美元用于医疗保健费用，牲畜产量每年下降7.5%[2]。出于这些原因，首席医疗官Dame Sally Davies将AMR威胁比作气候变化，并呼吁将其添加到国家风险登记册中。这项研究将使用一种健康方法来解决AMR威胁。目前，关于环境中抗生素造成的选择性危害的数据非常少，并且没有标准化的测试来生成这些数据。检测整个细菌群落中的AMR基因（下一代测序）并准确量化这些基因数量（平行实时定量PCR（qPCR））的尖端技术将用于生成“大数据”，以提高对AMR选择的基本科学理解。这将用于开发和验证一种有可能成为经合组织认可的生态毒理学测试的测定方法，该方法评估抗菌剂在选择AMR时可能造成的危害-这是同类测试中的第一个。重要的合作者包括Defra、阿斯利康（最近为生命科学产业战略提供了建议）和废水处理公司塞文特伦特。Defra将为政策制定过程提供建议，以确保研究在全国范围内产生影响。阿斯利康将提供生态毒理学测试、现行立法和监管实践方面的专业知识;并为研究提供信息，以最大限度地发挥影响。塞文特伦特将利用这些数据为他们自己的创新AMR研究计划提供信息，为实验提供废水样本，并促进与废水行业的直接接触。这种测定的好处是显着的和众多的，并包括通过降低资源和能源消耗相比，许多目前的生态毒理学测试改善资源管理。该测试的快速性可以减少新药上市所需的时间，并通过确定哪些药物可能已经具有自然发生的耐药性机制来选择作用，从而延长新型抗生素的使用寿命。在药物开发过程中包括这种检测方法将减少与抗生素和污染相关的任何声誉风险，同时确保新投资对环境负责。该试验将有助于经济恢复，为药物开发带来积极的经济影响（可能会减少解决当前抗生素市场失灵所需的财政干预，如生命科学产业战略[4]所详述），长期药物疗效（以及对医疗保健和粮食安全的相关好处）;通过确认返回环境的水是安全的和/或可重复使用的，并将AMR进一步发展的风险降至最低，从而保护生态系统服务。参考文献：1.奥尼尔（2014）。2.世界银行集团（2017年）。3. HRMG（2015年）。4. Bell（2017）.

Antibiotics pose a contemporary pollution challenge to the natural environment by selecting for antimicrobial resistance (AMR), which has far-reaching societal and economic implications for human and animal health, food security and environmental protection. Without improving our antimicrobial stewardship and the antibiotic development pipeline, it has been predicted that by 2050 antimicrobial resistance (AMR) will be the leading cause of death worldwide, resulting in 10 million deaths annually[1]. AMR is also a significant burden on the global economy. The World Bank Group has estimated that by 2050, AMR will annually reduce global GBP and global exports by up to 3.8%, each. Effects on healthcare and food security will also be massive, with an additional $700 billion required for healthcare costs annually and a decline in livestock production of up to 7.5% per year[2]. For these reasons, Chief Medical Officer Dame Sally Davies has likened the AMR threat to climate change, and campaigned for it to be added to the National Risk Register[3]. This research will tackle the AMR threat using the One Health approach. Currently, there are extremely few data pertaining to the selective hazard posed by antibiotics in the environment, and no standardised test to generate this data is available. Cutting edge technologies which detect AMR genes in whole bacterial communities (next-generation sequencing) and accurately quantify numbers of these genes (parallel real-time quantitative PCR (qPCR)) will be used to generate 'big data' to improve fundamental, scientific understanding of selection for AMR. This will be used to develop and validate an assay with the potential to become an OECD recognised ecotoxicological test, which assesses the hazard posed by antimicrobials in their potential to select for AMR - the first test of its kind. Significant collaborators include Defra, AstraZeneca (who recently provided recommendations to the Life Sciences Industrial Strategy) and the waste water company Severn Trent. Defra will advise on policy making processes to ensure the research is impactful on a national scale. AstraZeneca will offer expertise in ecotoxicological testing, current legislation and regulation practices; and inform the research to maximise impact. Severn Trent will use this data to inform their own innovative AMR research programme, provide waste water samples for experiments and facilitate direct engagement with the waste water industry. The benefits of this assay are significant and numerous, and include improved resource management via lowered resource and energy consumption compared to many current ecotoxicological tests. The rapidity of the test could reduce the time required for novel drugs to reach market and prolong novel antibiotic lifetime by establishing which drugs may already have naturally-occurring resistance mechanisms for selection to act upon. Including this assay during drug development would reduce any reputational risks associated with antibiotics and pollution, whilst ensuring new investments are environmentally responsible. The assay would contribute to a resilient economy, bringing positive economic impacts to drug development (potentially reducing the fiscal interventions which may be required to address the current antibiotic market failure, as detailed in the Life Sciences Industrial Strategy[4]), long-term drug efficacy (and associated benefits to healthcare and food security); and by safeguarding ecosystem services through confirming water which is returned to the environment is safe and/or reusable, and poses minimal risk of further development of AMR. References: 1. O'Neill (2014). 2. World Bank Group (2017). 3. HRMG (2015). 4. Bell (2017).