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

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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).