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      Country Income Is Only One of the Tiles: The Global Journey of Antimicrobial Resistance among Humans, Animals, and Environment

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          Abstract

          Antimicrobial resistance (AMR) is one of the most complex global health challenges today: decades of overuse and misuse in human medicine, animal health, agriculture, and dispersion into the environment have produced the dire consequence of infections to become progressively untreatable. Infection control and prevention (IPC) procedures, the reduction of overuse, and the misuse of antimicrobials in human and veterinary medicine are the cornerstones required to prevent the spreading of resistant bacteria. Purified drinking water and strongly improved sanitation even in remote areas would prevent the pollution from inadequate treatment of industrial, residential, and farm waste, as all these situations are expanding the resistome in the environment. The One Health concept addresses the interconnected relationships between human, animal, and environmental health as a whole: several countries and international agencies have now included a One Health Approach within their action plans to address AMR. Improved antimicrobial usage, coupled with regulation and policy, as well as integrated surveillance, infection control and prevention, along with antimicrobial stewardship, sanitation, and animal husbandry should all be integrated parts of any new action plan targeted to tackle AMR on the Earth. Since AMR is found in bacteria from humans, animals, and in the environment, we briefly summarize herein the current concepts of One Health as a global challenge to enable the continued use of antibiotics.

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          Mobile Genetic Elements Associated with Antimicrobial Resistance

          SUMMARY Strains of bacteria resistant to antibiotics, particularly those that are multiresistant, are an increasing major health care problem around the world. It is now abundantly clear that both Gram-negative and Gram-positive bacteria are able to meet the evolutionary challenge of combating antimicrobial chemotherapy, often by acquiring preexisting resistance determinants from the bacterial gene pool. This is achieved through the concerted activities of mobile genetic elements able to move within or between DNA molecules, which include insertion sequences, transposons, and gene cassettes/integrons, and those that are able to transfer between bacterial cells, such as plasmids and integrative conjugative elements. Together these elements play a central role in facilitating horizontal genetic exchange and therefore promote the acquisition and spread of resistance genes. This review aims to outline the characteristics of the major types of mobile genetic elements involved in acquisition and spread of antibiotic resistance in both Gram-negative and Gram-positive bacteria, focusing on the so-called ESKAPEE group of organisms ( Enterococcus faecium , Staphylococcus aureus , Klebsiella pneumoniae , Acinetobacter baumannii , Pseudomonas aeruginosa , Enterobacter spp., and Escherichia coli ), which have become the most problematic hospital pathogens.
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            Identification of Novel Mobilized Colistin Resistance Gene mcr-9 in a Multidrug-Resistant, Colistin-Susceptible Salmonella enterica Serotype Typhimurium Isolate

            Colistin is a last-resort antibiotic that is used to treat severe infections caused by MDR and extensively drug-resistant (XDR) bacteria. The World Health Organization (WHO) has designated colistin as a “highest priority critically important antimicrobial for human medicine” (WHO, Critically Important Antimicrobials for Human Medicine, 5th revision, 2017, https://www.who.int/foodsafety/publications/antimicrobials-fifth/en/), as it is often one of the only therapies available for treating serious bacterial infections in critically ill patients. Plasmid-borne mcr genes that confer resistance to colistin pose a threat to public health at an international scale, as they can be transmitted via horizontal gene transfer and have the potential to spread globally. Therefore, the establishment of a complete reference of mcr genes that can be used to screen for plasmid-mediated colistin resistance is essential for developing effective control strategies.
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              Review of Antimicrobial Resistance in the Environment and Its Relevance to Environmental Regulators

              The environment is increasingly being recognized for the role it might play in the global spread of clinically relevant antibiotic resistance. Environmental regulators monitor and control many of the pathways responsible for the release of resistance-driving chemicals into the environment (e.g., antimicrobials, metals, and biocides). Hence, environmental regulators should be contributing significantly to the development of global and national antimicrobial resistance (AMR) action plans. It is argued that the lack of environment-facing mitigation actions included in existing AMR action plans is likely a function of our poor fundamental understanding of many of the key issues. Here, we aim to present the problem with AMR in the environment through the lens of an environmental regulator, using the Environment Agency (England’s regulator) as an example from which parallels can be drawn globally. The issues that are pertinent to environmental regulators are drawn out to answer: What are the drivers and pathways of AMR? How do these relate to the normal work, powers and duties of environmental regulators? What are the knowledge gaps that hinder the delivery of environmental protection from AMR? We offer several thought experiments for how different mitigation strategies might proceed. We conclude that: (1) AMR Action Plans do not tackle all the potentially relevant pathways and drivers of AMR in the environment; and (2) AMR Action Plans are deficient partly because the science to inform policy is lacking and this needs to be addressed.
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                Author and article information

                Journal
                Antibiotics (Basel)
                Antibiotics (Basel)
                antibiotics
                Antibiotics
                MDPI
                2079-6382
                01 August 2020
                August 2020
                : 9
                : 8
                : 473
                Affiliations
                [1 ]Infectious Diseases Unit; Bolzano Central Hospital, 39100 Bolzano, Italy; angela.pieri@ 123456sabes.it
                [2 ]Antimicrobial Stewardship Program; Bolzano Central Hospital, 39100 Bolzano, Italy; richard.aschbacher@ 123456sabes.it (R.A.); giadafasani@ 123456hotmail.com (G.F.); elisabetta.pagani@ 123456sabes.it (E.P.)
                [3 ]Department of Veterinary Medical Sciences (DIMEVET), University of Bologna, 40126 Bologna; Italy; jole.mariella2@ 123456unibo.it
                [4 ]Faculty of Science and Technology; Free University of Bolzano, 39100 Bolzano, Italy; lorenzo.brusetti@ 123456unibz.it
                [5 ]Division of General Surgery, Macerata Hospital, 62100 Macerata; Italy; massimosartelli@ 123456gmail.com
                Author notes
                [* ]Correspondence: lpagani.id@ 123456gmail.com ; Tel.: +39-0471-908131; Fax: +39-0471-908552
                Author information
                https://orcid.org/0000-0002-1773-6618
                https://orcid.org/0000-0002-2553-9147
                Article
                antibiotics-09-00473
                10.3390/antibiotics9080473
                7460298
                32752276
                b9f34837-557b-4942-aa7c-3e5deccc05c5
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 July 2020
                : 29 July 2020
                Categories
                Review

                antimicrobial resistance,one health,environment,humans,animals,antibiotic resistance genes,water,antimicrobial stewardship

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