摘要

      抗菌素耐药性（AMR）是人类面临的最大威胁之一。自从最初发现青霉素和随后引入磺胺类药物作为临床抗生素以来，临床和医院环境中耐药性的发展已经有了很好的记录。相反，最近才界定了传播阻力的环境（即社区获得的）方面。抗药性细菌（ARB）和抗药性基因（ARGs）在空气、水、土壤和食物之间的全球传播现在已经有了很好的记录，而影响ARB和ARG传播的因素（例如，水和空气质量、抗生素通量、城市化，卫生措施）在这些和其他环境矩阵中刚刚开始得到更充分的重视。在这篇文章中，我们讨论了全球阻力的持续性是如何由高度相互关联的社会经济风险因素决定的，并说明在制定应对AMR的全球战略时，应更充分地考虑发展状况。我们首先对中低收入国家（LMICs）和高收入国家（HICs）进行了区分，然后总结了商业化抗生素的作用模式，然后讨论了细菌对这些抗生素产生耐药性的四种主要机制。抗性通过垂直基因转移（VGT；亲子）和水平基因转移（HGT；遗传物质的细胞间转移）传播。阻碍控制抗药性传播的一个关键挑战是存在能够携带arg的本地环境细菌。这种环境“抵抗物”有可能通过HGT转移对病原体的抵抗力。特别值得关注的是对抗生素的最后抵抗力的发展，如头孢菌素、碳青霉烯类和多粘菌素。然后，我们就抗生素使用量及其在当地环境中的命运来说明LMICs与HICs的抗生素使用差异。在过去15年中，HICs中抗生素的使用一直保持平稳，而在LMICs中，由于经济的改善和饮食的改变，抗生素的使用在同一时期大幅增加。这些使用和命运的差异影响了当地公民，从而影响了AMR在当地的传播。LMIC内的各种物理、社会和经济环境可能有利于AMR的传播。我们关注三个物理因素：不断变化的人口密度、卫生基础设施和固体废物处理。我们的研究表明，生活在低污染城市中的人口密度高、卫生条件差和固体废物处理能力差的城市可能会影响抗药性的传播。在最后一节中，我们讨论了量化lmic和HICs内电阻扩散的潜在监测方法。我们认为，用于监测ARB和ARGs的基于培养的方法、分子方法和基于尖端纳米技术的方法应在HICs中考虑，并酌情在lmic中考虑。

       Antimicrobial resistance (AMR) is one of the greatest threats faced by humankind. The development of resistance in clinical and hospital settings has been well documented ever since the initial discovery of penicillin and the subsequent introduction of sulfonamides as clinical antibiotics. In contrast, the environmental (i.e., community-acquired) dimensions of resistance dissemination have been only more recently delineated. The global spread of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) between air, water, soil, and food is now well documented, while the factors that affect ARB and ARG dissemination (e.g., water and air quality, antibiotic fluxes, urbanization, sanitation practices) in these and other environmental matrices are just now beginning to be more fully appreciated. In this Account, we discuss how the global perpetuation of resistance is dictated by highly interconnected socioeconomic risk factors and illustrate that development status should be more fully considered when developing global strategies to address AMR. We first differentiate low to middle income countries (LMICs) and high-income countries (HICs), then we summarize the modes of action of commercially available antibiotics, and then discuss the four primary mechanisms by which bacteria develop resistance to those antibiotics. Resistance is disseminated via both vertical gene transfer (VGT; parent to offspring) as well as by horizontal gene transfer (HGT; cell to cell transference of genetic material). A key challenge hindering attempts to control resistance dissemination is the presence of native, environmental bacteria that can harbor ARGs. Such environmental "resistomes" have potential to transfer resistance to pathogens via HGT. Of particular concern is the development of resistance to antibiotics of last-resort such as the cephalosporins, carbapenems, and polymyxins. We then illustrate how antibiotic use differs in LMICs relative to HICs in terms of the volumes of antibiotics used and their fate within local environments. Antibiotic use in HICs has remained flat over the past 15 years, while in LMICs use over the same period has increased substantially as a result of economic improvements and changes in diet. These use and fate differences impact local citizens and thus the local dissemination of AMR. Various physical, social, and economic circumstances within LMICs potentially favor AMR dissemination. We focus on three physical factors: changing population density, sanitation infrastructure, and solid-waste disposal. We show that high population densities in cities within LMICs that suffer from poor sanitation and solid-waste disposal can potentially impact the dissemination of resistance. In the final section, we discuss potential monitoring approaches to quantify the spread of resistance both within LMICs as well as in HICs. We posit that culture-based approaches, molecular approaches, and cutting-edge nanotechnology-based methods for monitoring ARB and ARGs should be considered both within HICs and, as appropriate, within LMICs.

        https://pubs.acs.org/doi/10.1021/acs.accounts.8b00643