Antimicrobial resistance in humans, livestock and the wider environment. - Related Documents




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401901.0000Antimicrobial resistance in humans, livestock and the wider environment. Antimicrobial resistance (AMR) in humans is inter-linked with AMR in other populations, especially farm animals, and in the wider environment. The relatively few bacterial species that cause disease in humans, and are the targets of antibiotic treatment, constitute a tiny subset of the overall diversity of bacteria that includes the gut microbiota and vast numbers in the soil. However, resistance can pass between these different populations; and homologous resistance genes have been found in pathogens, normal flora and soil bacteria. Farm animals are an important component of this complex system: they are exposed to enormous quantities of antibiotics (despite attempts at reduction) and act as another reservoir of resistance genes. Whole genome sequencing is revealing and beginning to quantify the two-way traffic of AMR bacteria between the farm and the clinic. Surveillance of bacterial disease, drug usage and resistance in livestock is still relatively poor, though improving, but achieving better antimicrobial stewardship on the farm is challenging: antibiotics are an integral part of industrial agriculture and there are very few alternatives. Human production and use of antibiotics either on the farm or in the clinic is but a recent addition to the natural and ancient process of antibiotic production and resistance evolution that occurs on a global scale in the soil. Viewed in this way, AMR is somewhat analogous to climate change, and that suggests that an intergovernmental panel, akin to the Intergovernmental Panel on Climate Change, could be an appropriate vehicle to actively address the problem.201525918441
401810.9999Mobile elements, zoonotic pathogens and commensal bacteria: conduits for the delivery of resistance genes into humans, production animals and soil microbiota. Multiple antibiotic resistant pathogens represent a major clinical challenge in both human and veterinary context. It is now well-understood that the genes that encode resistance are context independent. That is, the same gene is commonly present in otherwise very disparate pathogens in both humans and production and companion animals, and among bacteria that proliferate in an agricultural context. This can be true even for pathogenic species or clonal types that are otherwise confined to a single host or ecological niche. It therefore follows that mechanisms of gene flow must exist to move genes from one part of the microbial biosphere to another. It is widely accepted that lateral (or horizontal) gene transfer (L(H)GT) drives this gene flow. LGT is relatively well-understood mechanistically but much of this knowledge is derived from a reductionist perspective. We believe that this is impeding our ability to deal with the medical ramifications of LGT. Resistance genes and the genetic scaffolds that mobilize them in multiply drug resistant bacteria of clinical significance are likely to have their origins in completely unrelated parts of the microbial biosphere. Resistance genes are increasingly polluting the microbial biosphere by contaminating environmental niches where previously they were not detected. More attention needs to be paid to the way that humans have, through the widespread application of antibiotics, selected for combinations of mobile elements that enhance the flow of resistance genes between remotely linked parts of the microbial biosphere. Attention also needs to be paid to those bacteria that link human and animal ecosystems. We argue that multiply antibiotic resistant commensal bacteria are especially important in this regard. More generally, the post genomics era offers the opportunity for understanding how resistance genes are mobilized from a one health perspective. In the long term, this holistic approach offers the best opportunity to better manage what is an enormous problem to humans both in terms of health and food security.201323641238
405120.9999The human microbiome harbors a diverse reservoir of antibiotic resistance genes. The increasing levels of multi-drug resistance in human pathogenic bacteria are compromising our ability to treat infectious disease. Since antibiotic resistance determinants are readily exchanged between bacteria through lateral gene transfer, there is an increasing interest in investigating reservoirs of antibiotic resistance accessible to pathogens. Due to the high likelihood of contact and genetic exchange with pathogens during disease progression, the human microflora warrants special attention as perhaps the most accessible reservoir of resistance genes. Indeed, numerous previous studies have demonstrated substantial antibiotic resistance in cultured isolates from the human microflora. By applying metagenomic functional selections, we recently demonstrated that the functional repertoire of resistance genes in the human microbiome is much more diverse than suggested using previous culture-dependent methods. We showed that many resistance genes from cultured proteobacteria from human fecal samples are identical to resistance genes harbored by human pathogens, providing strong support for recent genetic exchange of this resistance machinery. In contrast, most of the resistance genes we identified with culture independent metagenomic sampling from the same samples were novel when compared to all known genes in public databases. While this clearly demonstrates that the antibiotic resistance reservoir of the large fraction of the human microbiome recalcitrant to culturing is severely under sampled, it may also suggest that barriers exist to lateral gene transfer between these bacteria and readily cultured human pathogens. If we hope to turn the tide against multidrug resistant infections, we must urgently commit to quantitatively characterizing the resistance reservoirs encoded by our diverse human microbiomes, with a particular focus on routes of exchange of these reservoirs with other microbial communities.201021178459
402130.9999What is a resistance gene? Ranking risk in resistomes. Metagenomic studies have shown that antibiotic resistance genes are ubiquitous in the environment, which has led to the suggestion that there is a high risk that these genes will spread to bacteria that cause human infections. If this is true, estimating the real risk of dissemination of resistance genes from environmental reservoirs to human pathogens is therefore very difficult. In this Opinion article, we analyse the current definitions of antibiotic resistance and antibiotic resistance genes, and we describe the bottlenecks that affect the transfer of antibiotic resistance genes to human pathogens. We propose rules for estimating the risks associated with genes that are present in environmental resistomes by evaluating the likelihood of their introduction into human pathogens, and the consequences of such events for the treatment of infections.201525534811
418940.9999Antimicrobial resistance at farm level. Bacteria that are resistant to antimicrobials are widespread. This article reviews the distribution of resistant bacteria in farm environments. Humans, animals, and environmental sites are all reservoirs of bacterial communities that contain some bacteria that are susceptible to antimicrobials and others that are resistant. Farm ecosystems provide an environment in which resistant bacteria and genes can emerge, amplify and spread. Dissemination occurs via the food chain and via several other pathways. Ecological, epidemiological, molecular and mathematical approaches are being used to study the origin and expansion of the resistance problem and its relationship to antibiotic usage. The prudent and responsible use of antibiotics is an essential part of an ethical approach to improving animal health and food safety. The responsible use of antibiotics during research is vital, but to fully contribute to the containment of antimicrobial resistance 'prudent use' must also be part of good management practices at all levels of farm life.200617094710
407050.9999Antibiotic Resistance Mechanisms in Bacteria: Relationships Between Resistance Determinants of Antibiotic Producers, Environmental Bacteria, and Clinical Pathogens. Emergence of antibiotic resistant pathogenic bacteria poses a serious public health challenge worldwide. However, antibiotic resistance genes are not confined to the clinic; instead they are widely prevalent in different bacterial populations in the environment. Therefore, to understand development of antibiotic resistance in pathogens, we need to consider important reservoirs of resistance genes, which may include determinants that confer self-resistance in antibiotic producing soil bacteria and genes encoding intrinsic resistance mechanisms present in all or most non-producer environmental bacteria. While the presence of resistance determinants in soil and environmental bacteria does not pose a threat to human health, their mobilization to new hosts and their expression under different contexts, for example their transfer to plasmids and integrons in pathogenic bacteria, can translate into a problem of huge proportions, as discussed in this review. Selective pressure brought about by human activities further results in enrichment of such determinants in bacterial populations. Thus, there is an urgent need to understand distribution of resistance determinants in bacterial populations, elucidate resistance mechanisms, and determine environmental factors that promote their dissemination. This comprehensive review describes the major known self-resistance mechanisms found in producer soil bacteria of the genus Streptomyces and explores the relationships between resistance determinants found in producer soil bacteria, non-producer environmental bacteria, and clinical isolates. Specific examples highlighting potential pathways by which pathogenic clinical isolates might acquire these resistance determinants from soil and environmental bacteria are also discussed. Overall, this article provides a conceptual framework for understanding the complexity of the problem of emergence of antibiotic resistance in the clinic. Availability of such knowledge will allow researchers to build models for dissemination of resistance genes and for developing interventions to prevent recruitment of additional or novel genes into pathogens.201830555448
407160.9999Antibiotic resistance in the environment: a link to the clinic? The emergence of resistance to all classes of antibiotics in previously susceptible bacterial pathogens is a major challenge to infectious disease medicine. The origin of the genes associated with resistance has long been a mystery. There is a growing body of evidence that is demonstrating that environmental microbes are highly drug resistant. The genes that make up this environmental resistome have the potential to be transferred to pathogens and indeed there is some evidence that at least some clinically relevant resistance genes have originated in environmental microbes. Understanding the extent of the environmental resistome and its mobilization into pathogenic bacteria is essential for the management and discovery of antibiotics.201020850375
410170.9999What Is the Role of the Environment in the Emergence of Novel Antibiotic Resistance Genes? A Modeling Approach. It is generally accepted that intervention strategies to curb antibiotic resistance cannot solely focus on human and veterinary medicine but must also consider environmental settings. While the environment clearly has a role in transmission of resistant bacteria, its role in the emergence of novel antibiotic resistance genes (ARGs) is less clear. It has been suggested that the environment constitutes an enormous recruitment ground for ARGs to pathogens, but its extent is practically unknown. We have constructed a model framework for resistance emergence and used available quantitative data on relevant processes to identify limiting steps in the appearance of ARGs in human pathogens. We found that in a majority of possible scenarios, the environment would only play a minor role in the emergence of novel ARGs. However, the uncertainty is enormous, highlighting an urgent need for more quantitative data. Specifically, more data is most needed on the fitness costs of ARG carriage, the degree of dispersal of resistant bacteria from the environment to humans, and the rates of mobilization and horizontal transfer of ARGs. This type of data is instrumental to determine which processes should be targeted for interventions to curb development and transmission of ARGs in the environment.202134792330
419080.9999Insects represent a link between food animal farms and the urban environment for antibiotic resistance traits. Antibiotic-resistant bacterial infections result in higher patient mortality rates, prolonged hospitalizations, and increased health care costs. Extensive use of antibiotics as growth promoters in the animal industry represents great pressure for evolution and selection of antibiotic-resistant bacteria on farms. Despite growing evidence showing that antibiotic use and bacterial resistance in food animals correlate with resistance in human pathogens, the proof for direct transmission of antibiotic resistance is difficult to provide. In this review, we make a case that insects commonly associated with food animals likely represent a direct and important link between animal farms and urban communities for antibiotic resistance traits. Houseflies and cockroaches have been shown to carry multidrug-resistant clonal lineages of bacteria identical to those found in animal manure. Furthermore, several studies have demonstrated proliferation of bacteria and horizontal transfer of resistance genes in the insect digestive tract as well as transmission of resistant bacteria by insects to new substrates. We propose that insect management should be an integral part of pre- and postharvest food safety strategies to minimize spread of zoonotic pathogens and antibiotic resistance traits from animal farms. Furthermore, the insect link between the agricultural and urban environment presents an additional argument for adopting prudent use of antibiotics in the food animal industry.201424705326
403290.9999Could bacteriophages transfer antibiotic resistance genes from environmental bacteria to human-body associated bacterial populations? Environments without any contact with anthropogenic antibiotics show a great abundance of antibiotic resistance genes that use to be chromosomal and are part of the core genes of the species that harbor them. Some of these genes are shared with human pathogens where they appear in mobile genetic elements. Diversity of antibiotic resistance genes in non-contaminated environments is much greater than in human and animal pathogens, and in environments contaminated with antibiotic from anthropogenic activities. This suggests the existence of some bottleneck effect for the mobilization of antibiotic resistance genes among different biomes. Bacteriophages have characteristics that make them suitable vectors between different biomes, and as well for transferring genes from biome to biome. Recent metagenomic studies and detection of bacterial genes by genomic techniques in the bacteriophage fraction of different microbiota provide indirect evidences that the mobilization of genes mediated by phages, including antibiotic resistance genes, is far more relevant than previously thought. Our hypothesis is that bacteriophages might be of critical importance for evading one of the bottlenecks, the lack of ecological connectivity that modulates the pass of antibiotic resistance genes from natural environments such as waters and soils, to animal and human microbiomes. This commentary concentrates on the potential importance of bacteriophages in transferring resistance genes from the environment to human and animal body microbiomes, but there is no doubt that transduction occurs also in body microbiomes.201324195016
4053100.9999Evidence for the circulation of antimicrobial-resistant strains and genes in nature and especially between humans and animals. The concern over antibiotic-resistant bacteria producing human infections that are difficult to treat has led to a proliferation of studies in recent years investigating resistance in livestock, food products, the environment and people, as well as in the mechanisms of transfer of the genetic elements of resistance between bacteria, and the routes, or risk pathways, by which the spread of resistance might occur. The possibility of transfer of resistant genetic elements between bacteria in mixed populations adds many additional and complex potential routes of spread. There is now considerable evidence that transfer of antimicrobial resistance from food-producing animals to humans directly via the food chain is a likely route of spread. The application of animal wastes to farmland and subsequent leaching into watercourses has also been shown to lead to many potential, but less well-documented, pathways for spread. Often, however, where contamination of water sources, processed foods, and other environmental sites is concerned, specific routes of circulation are unclear and may well involve human sources of contamination. Examination of water sources in particular may be difficult due to dilution and their natural flow. Also, as meat is comparatively easy to examine, and is frequently suspected of being a source of spread, there is some bias in favour of studying this vehicle. Such complexities mean that, with the evidence currently available, it is not possible to prioritise the importance of potential risk pathways and circulation routes.201222849279
4118110.9999Antimicrobial resistance in livestock. Antimicrobial resistance may become a major problem in veterinary medicine as a consequence of the intensive use and misuse of antimicrobial drugs. Related problems are now arising in human medicine, such as the appearance of multi-resistant food-borne pathogens. Product characteristics, dose, treatment interval and duration of treatment influence the selection pressure for antimicrobial drug resistance. There are theoretical, experimental and clinical indications that the emergence of de novo resistance in a pathogenic population can be prevented by minimizing the time that suboptimal drug levels are present in the infected tissue compartment. Until recently, attention has been focused on target pathogens. However, it should be kept in mind that when antimicrobial drugs are used in an individual, resistance selection mainly affects the normal body flora. In the long term, this is at least equally important as resistance selection in the target pathogens, as the horizontal transfer of resistance genes converts almost all pathogenic bacteria into potential recipients for antimicrobial resistance. Other factors contributing to the epidemiology of antimicrobial resistance are the localization and size of the microbial population, and the age, immunity and contact intensity of the host. In livestock, dynamic herd-related resistance patterns have been observed in different animal species.200312667177
4020120.9999Is there a role for intestinal sporobiota in the antimicrobial resistance crisis? Antimicrobial resistance (AMR) is a complex issue requiring specific, multi-sectoral measures to slow its spread. When people are exposed to antimicrobial agents, it can cause resistant bacteria to increase. This means that the use, misuse, and excessive use of antimicrobial agents exert selective pressure on bacteria, which can lead to the development of "silent" reservoirs of antimicrobial resistance genes. These genes can later be mobilized into pathogenic bacteria and contribute to the spread of AMR. Many socioeconomic and environmental factors influence the transmission and dissemination of resistance genes, such as the quality of healthcare systems, water sanitation, hygiene infrastructure, and pollution. The sporobiota is an essential part of the gut microbiota that plays a role in maintaining gut homeostasis. However, because spores are highly transmissible and can spread easily, they can be a vector for AMR. The sporobiota resistome, particularly the mobile resistome, is important for tracking, managing, and limiting the spread of antimicrobial resistance genes among pathogenic and commensal bacterial species.202439173554
4060130.9999Current status of antibiotic resistance in animal production. It is generally accepted that the more antibiotics we use, the faster bacteria will develop resistance. Further it has been more or less accepted that once an antibiotic is withdrawn from the clinic, the resistance genes will eventually disappear, [table: see text] since they will no more be of any survival value for the bacterial cell. However, recent research has shown that after a long time period of exposure to antibiotics, certain bacterial species may adapt to this environment in such a way that they keep their resistance genes stably also after the removal of antibiotics. Thus, there is reason to believe that once resistance has developed it will not even in the long term be eradicated. What then can we do not to increase further the already high level of antibiotic-resistant bacteria in animals? We should of course encourage a prudent use of these valuable drugs. In Sweden antibiotics are not used for growth promoting purposes and are available only after veterinary prescription on strict indications. Generally, antimicrobial treatment of animals on individual or on herd basis should not be considered unless in connection with relevant diagnostics. The amounts of antibiotics used and the development of resistance in important pathogens should be closely monitored. Furthermore, resistance monitoring in certain non-pathogenic intestinal bacteria, which may serve as a reservoir for resistance genes is probably more important than hitherto anticipated. Once the usage of or resistance to a certain antibiotic seems to increase in an alarming way, steps should be taken to limit the usage of the drug in order to prevent further spread of resistance genes in animals, humans and the environment. Better methods for detecting and quantifying antibiotic resistance have to be developed. Screening methods must be standardized and evaluated in order to obtain comparable and reliable results from different countries. The genetic mechanisms for development of resistance and spread of resistance genes should be studied in detail. Research in these areas will lead to new ideas on how to inhibit the resistance mechanisms. So far, it has been well established that a heavy antimicrobial drug selective pressure in overcrowded populations of production animals creates favourable environments both for the emergence and the spread of antibiotic resistance genes.199910783714
4033140.9999Evolution and ecology of antibiotic resistance genes. A new perspective on the topic of antibiotic resistance is beginning to emerge based on a broader evolutionary and ecological understanding rather than from the traditional boundaries of clinical research of antibiotic-resistant bacterial pathogens. Phylogenetic insights into the evolution and diversity of several antibiotic resistance genes suggest that at least some of these genes have a long evolutionary history of diversification that began well before the 'antibiotic era'. Besides, there is no indication that lateral gene transfer from antibiotic-producing bacteria has played any significant role in shaping the pool of antibiotic resistance genes in clinically relevant and commensal bacteria. Most likely, the primary antibiotic resistance gene pool originated and diversified within the environmental bacterial communities, from which the genes were mobilized and penetrated into taxonomically and ecologically distant bacterial populations, including pathogens. Dissemination and penetration of antibiotic resistance genes from antibiotic producers were less significant and essentially limited to other high G+C bacteria. Besides direct selection by antibiotics, there is a number of other factors that may contribute to dissemination and maintenance of antibiotic resistance genes in bacterial populations.200717490428
4102150.9999Forces shaping the antibiotic resistome. Antibiotic resistance has become a problem of global scale. Resistance arises through mutation or through the acquisition of resistance gene(s) from other bacteria in a process called horizontal gene transfer (HGT). While HGT is recognized as an important factor in the dissemination of resistance genes in clinical pathogens, its role in the environment has been called into question by a recent study published in Nature. The authors found little evidence of HGT in soil using a culture-independent functional metagenomics approach, which is in contrast to previous work from the same lab showing HGT between the environment and human microbiome. While surprising at face value, these results may be explained by the lack of selective pressure in the environment studied. Importantly, this work suggests the need for careful monitoring of environmental antibiotic pollution and stringent antibiotic stewardship in the fight against resistance.201425213620
4095160.9999Antimicrobial resistance: more than 70 years of war between humans and bacteria. Development of antibiotic resistance in bacteria is one of the major issues in the present world and one of the greatest threats faced by mankind. Resistance is spread through both vertical gene transfer (parent to offspring) as well as by horizontal gene transfer like transformation, transduction and conjugation. The main mechanisms of resistance are limiting uptake of a drug, modification of a drug target, inactivation of a drug, and active efflux of a drug. The highest quantities of antibiotic concentrations are usually found in areas with strong anthropogenic pressures, for example medical source (e.g., hospitals) effluents, pharmaceutical industries, wastewater influents, soils treated with manure, animal husbandry and aquaculture (where antibiotics are generally used as in-feed preparations). Hence, the strong selective pressure applied by antimicrobial use has forced microorganisms to evolve for survival. The guts of animals and humans, wastewater treatment plants, hospital and community effluents, animal husbandry and aquaculture runoffs have been designated as "hotspots for AMR genes" because the high density of bacteria, phages, and plasmids in these settings allows significant genetic exchange and recombination. Evidence from the literature suggests that the knowledge of antibiotic resistance in the population is still scarce. Tackling antimicrobial resistance requires a wide range of strategies, for example, more research in antibiotic production, the need of educating patients and the general public, as well as developing alternatives to antibiotics (briefly discussed in the conclusions of this article).202032954887
4052170.9999Functional metagenomics for the investigation of antibiotic resistance. Antibiotic resistance is a major threat to human health and well-being. To effectively combat this problem we need to understand the range of different resistance genes that allow bacteria to resist antibiotics. To do this the whole microbiota needs to be investigated. As most bacteria cannot be cultivated in the laboratory, the reservoir of antibiotic resistance genes in the non-cultivatable majority remains relatively unexplored. Currently the only way to study antibiotic resistance in these organisms is to use metagenomic approaches. Furthermore, the only method that does not require any prior knowledge about the resistance genes is functional metagenomics, which involves expressing genes from metagenomic clones in surrogate hosts. In this review the methods and limitations of functional metagenomics to isolate new antibiotic resistance genes and the mobile genetic elements that mediate their spread are explored.201424556726
4022180.9999Antibiotic resistance in the environment. Antibiotic resistance is a global health challenge, involving the transfer of bacteria and genes between humans, animals and the environment. Although multiple barriers restrict the flow of both bacteria and genes, pathogens recurrently acquire new resistance factors from other species, thereby reducing our ability to prevent and treat bacterial infections. Evolutionary events that lead to the emergence of new resistance factors in pathogens are rare and challenging to predict, but may be associated with vast ramifications. Transmission events of already widespread resistant strains are, on the other hand, common, quantifiable and more predictable, but the consequences of each event are limited. Quantifying the pathways and identifying the drivers of and bottlenecks for environmental evolution and transmission of antibiotic resistance are key components to understand and manage the resistance crisis as a whole. In this Review, we present our current understanding of the roles of the environment, including antibiotic pollution, in resistance evolution, in transmission and as a mere reflection of the regional antibiotic resistance situation in the clinic. We provide a perspective on current evidence, describe risk scenarios, discuss methods for surveillance and the assessment of potential drivers, and finally identify some actions to mitigate risks.202234737424
4029190.9999Reservoirs of antibiotic resistance genes. A potential concern about the use of antibiotics in animal husbundary is that, as antibiotic resistant bacteria move from the farm into the human diet, they may pass antibiotic resistance genes to bacteria that normally reside in a the human intestinal tract and from there to bacteria that cause human disease (reservoir hypothesis). In this article various approaches to evaluating the risk of agricultural use of antibiotics are assessed critically. In addition, the potential benefits of applying new technology and using new insights from the field of microbial ecology are explained.200617127525