Defining the AMR Burden of Antimicrobial Manufacturing Waste in Puducherry and Chennai

定义本地治里和钦奈抗菌药物制造废物的 AMR 负担

• 批准号: NE/T013184/1
• 负责人: Nick Voulvoulis
• 金额: $ 108.52万
• 依托单位: Imperial College London
• 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: 未结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FT013184%2F1
• 关键词: Defining; AMR; Burden; Antimicrobial; Manufacturing

Pharmaceutical manufacturing waste is an important and neglected source of antimicrobial contamination in the environment that can result in expansion of antimicrobially-resistant microbes. Countries such as India, one of the world's main producers of Active Pharmaceutical Ingredients (APIs) including antibiotics are at particular risk. Studies indicate that pharmaceutical effluent waste in specific areas of India are associated with excessively high concentrations of antimicrobials in the surrounding environment and to increased frequency of antimicrobial resistance (AMR) in environmental water. The impact of such waste in other areas is unknown. There are currently no international standards to limit antimicrobials in antimicrobial manufacturing waste (AMW). Such pollution from manufacturing therefore creates environments that are spawning grounds for antimicrobial resistance in environmental bacteria; new genetic resistance factors can evolve through mutation, and, together with already-existing resistance traits will be enriched by selection. Due to the ability of bacterial to transfer genetic material on mobile genetic elements, AMR genetic traits may be transferred from environmental bacteria to harmful bacteria (pathogens), either within the environment, or within animals and humans, with potential harmful health consequences for everyone, regardless of where the pollution occurred.Focusing on Chennai and Puducherry, we will investigate the link between antibiotics manufactured by different methods, contamination levels in manufacturing wastes and downstream locations, where we will sample for antibiotics and antimicrobial resistance in waters, sediments, animals, and humans, contrasting our findings with control upstream environments. These two regions in India have a significant number of pharmaceutical companies (both active pharmaceutical ingredient manufacturers and formulation companies) producing a range of products including amoxicillin, cephalosporins, macrolides, tetracyclines, and fluroquinolones. We will validate techniques to detect and measure different antibiotics in environmental samples, and undertake state of the art bacterial, genomic and metagenomic studies on the same samples to identify AMR bacteria and the genetic elements conferring resistance, providing a library of AMR risk in this region of India. AMR data will be integrated with locations of sampling and levels of antibiotic contamination to determine the degree of association between these factors. Armed with this information, our work will provide a platform to advise on the risk posed by antimicrobial manufacturing waste and ultimately identify the need for risk-reducing investments by industry to deal with the proliferation of AMR. The project will develop novel analytical methods for the quantification of active pharmaceutical ingredients related to antibiotic manufacturing and novel approaches to quantify and characterise the penetration of AMR into the environment and animal and human microbiota. We will deliver mass balance methods and risk assessment tools that predict concentrations and risk based on production loads of antimicrobials, and policy recommendations for international environmental standards for antimicrobials in manufacturing effluents and receiving environments. Global implications of this work relate to larger pharma who purchase antibiotic ingredients, as well as medical professionals and patients; there may be a need to consider that the low cost of antibiotics should be balanced by a need to maintain environmental performance and sustainability of their manufacturing methods. Given the significant industrial emissions of antibiotics repeatedly documented in India, our work will encourage and support the Indian government in its determination to monitor and regulate antibiotic discharges from manufacturing, whilst supporting global efforts for tackling AMR.

制药废物是环境中重要且被忽视的抗菌剂污染源，可导致抗菌剂耐药性微生物的扩增。像印度这样的国家，包括抗生素在内的活性药物成分（API）的世界主要生产国之一，尤其面临风险。研究表明，印度特定地区的制药废水与周围环境中过高的抗菌剂浓度以及环境水中抗菌剂耐药性（AMR）频率增加有关。这些废物在其他地区的影响尚不清楚。目前还没有国际标准来限制抗菌剂制造废物（AMW）中的抗菌剂。因此，这种来自制造业的污染创造了环境，成为环境细菌抗菌素耐药性的滋生地;新的遗传耐药性因子可以通过突变进化，并且与已经存在的耐药性性状一起通过选择而丰富。由于细菌具有转移移动的遗传元件上的遗传物质的能力，AMR遗传性状可能从环境细菌转移到有害细菌（病原体），无论是在环境中，还是在动物和人类中，对每个人都有潜在的有害健康后果，无论污染发生在哪里。关注钦奈和普杜谢里，我们将调查不同方法制造的抗生素之间的联系，制造废物和下游地点的污染水平，我们将在沃茨，沉积物，动物和人类中采样抗生素和抗菌素耐药性，将我们的发现与控制上游环境进行对比。印度的这两个地区拥有大量制药公司（包括活性药物成分制造商和制剂公司），生产一系列产品，包括阿莫西林、头孢菌素、大环内酯类、四环素类和氟喹诺酮类。我们将验证检测和测量环境样品中不同抗生素的技术，并对相同样品进行最先进的细菌，基因组和宏基因组研究，以确定AMR细菌和赋予耐药性的遗传因素，提供印度该地区AMR风险的库。AMR数据将与采样位置和抗生素污染水平相结合，以确定这些因素之间的关联程度。有了这些信息，我们的工作将提供一个平台，就抗菌制造废物带来的风险提供建议，并最终确定行业降低风险投资的必要性，以应对AMR的扩散。该项目将开发新的分析方法，用于量化与抗生素生产相关的活性药物成分，并开发新的方法来量化和分析AMR对环境以及动物和人类微生物群的渗透。我们将提供质量平衡方法和风险评估工具，根据抗菌剂的生产负荷预测浓度和风险，并为生产废水和接收环境中的抗菌剂的国际环境标准提供政策建议。这项工作的全球影响涉及购买抗生素成分的大型制药公司，以及医疗专业人员和患者;可能需要考虑抗生素的低成本应与保持环境绩效和制造方法可持续性的需要相平衡。鉴于印度反复记录的抗生素工业排放量巨大，我们的工作将鼓励和支持印度政府监测和监管制造业抗生素排放的决心，同时支持全球应对AMR的努力。

项目成果

Fast and highly efficient liquid chromatographic methods for qualification and quantification of antibiotic residues from environmental waste

• DOI: 10.1016/j.microc.2022.107573
• 发表时间: 2022-05
• 期刊: Microchemical Journal
• 影响因子: 4.8
• 作者: Abhishesh Kumar Mehata;M. N. Lakshmi Suseela;P. Gokul;Ankit Kumar Malik;Matte Kasi Viswanadh;C. Singh;J. Selvin;M. S. Muthu

Delineating the impact of COVID-19 on antimicrobial resistance: An Indian perspective.

• DOI: 10.1016/j.scitotenv.2021.151702
• 发表时间: 2022-04-20
• 期刊: The Science of the total environment
• 作者: Seethalakshmi PS;Charity OJ;Giakoumis T;Kiran GS;Sriskandan S;Voulvoulis N;Selvin J
• 通讯作者: Selvin J

Advances in solid-phase extraction techniques: Role of nanosorbents for the enrichment of antibiotics for analytical quantification.

• DOI: 10.1016/j.chroma.2023.463937
• 发表时间: 2023-03
• 期刊: Journal of chromatography. A
• 作者: M. N. L. Suseela;Kasi Viswanadh Matte;A. K. Mehata;V. Priya;V. Setia;Ankit Malik;P. Gokul;J. Selvi