The use of aminopenicillins in animals within the EU, emergence of resistance in bacteria of animal and human origin and its possible impact on animal and human health. - Related Documents




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418401.0000The use of aminopenicillins in animals within the EU, emergence of resistance in bacteria of animal and human origin and its possible impact on animal and human health. Aminopenicillins have been widely used for decades for the treatment of various infections in animals and humans in European countries. Following this extensive use, acquired resistance has emerged among human and animal pathogens and commensal bacteria. Aminopenicillins are important first-line treatment options in both humans and animals, but are also among limited therapies for infections with enterococci and Listeria spp. in humans in some settings. Therefore, there is a need to assess the impact of the use of these antimicrobials in animals on public and animal health. The most important mechanisms of resistance to aminopenicillins are the β-lactamase enzymes. Similar resistance genes have been detected in bacteria of human and animal origin, and molecular studies suggest that transmission of resistant bacteria or resistance genes occurs between animals and humans. Due to the complexity of epidemiology and the near ubiquity of many aminopenicillin resistance determinants, the direction of transfer is difficult to ascertain, except for major zoonotic pathogens. It is therefore challenging to estimate to what extent the use of aminopenicillins in animals could create negative health consequences to humans at the population level. Based on the extent of use of aminopenicillins in humans, it seems probable that the major resistance selection pressure in human pathogens in European countries is due to human consumption. It is evident that veterinary use of these antimicrobials increases the selection pressure towards resistance in animals and loss of efficacy will at minimum jeopardize animal health and welfare.202337229552
420110.9999Antimicrobial Resistance on Farms: A Review Including Biosecurity and the Potential Role of Disinfectants in Resistance Selection. Resistance to therapeutic antimicrobial agents is recognized as a growing problem for both human and veterinary medicine, and the need to address the issue in both of these linked domains is a current priority in public policy. Efforts to limit antimicrobial resistance (AMR) on farms have so far focused on control of the supply and use of antimicrobial drugs, plus husbandry measures to reduce infectious disease. In the United Kingdom and some other countries, substantial progress has been made recently against targets on agricultural antimicrobial drug use. However, evidence suggests that resistant pathogenic and commensal bacteria can persist and spread within and between premises despite declining or zero antimicrobial drug use. Reasons for this are likely complex and varied but may include: bacterial adaptations to ameliorate fitness costs associated with maintenance and replication of resistance genes and associated proteins, horizontal transmission of genetic resistance determinants between bacteria, physical transfer of bacteria via movement (of animals, workers, and equipment), ineffective cleaning and disinfection, and co-selection of resistance to certain drugs by use of other antimicrobials, heavy metals, or biocides. Areas of particular concern for public health include extended-spectrum cephalosporinases and fluoroquinolone resistance among Enterobacteriaceae, livestock-associated methicillin-resistant Staphylococcus aureus, and the emergence of transmissible colistin resistance. Aspects of biosecurity have repeatedly been identified as risk factors for the presence of AMR on farm premises, but there are large gaps in our understanding of the most important risk factors and the most effective interventions. The present review aims to summarize the present state of knowledge in this area, from a European perspective.201933336931
408220.9999The food safety perspective of antibiotic resistance. Bacterial antimicrobial resistance in both the medical and agricultural fields has become a serious problem worldwide. Antibiotic resistant strains of bacteria are an increasing threat to animal and human health, with resistance mechanisms having been identified and described for all known antimicrobials currently available for clinical use. There is currently increased public and scientific interest regarding the administration of therapeutic and sub-therapeutic antimicrobials to animals, due primarily to the emergence and dissemination of multiple antibiotic resistant zoonotic bacterial pathogens. This issue has been the subject of heated debates for many years, however, there is still no complete consensus on the significance of antimicrobial use in animals, or resistance in bacterial isolates from animals, on the development and dissemination of antibiotic resistance among human bacterial pathogens. In fact, the debate regarding antimicrobial use in animals and subsequent human health implications has been going on for over 30 years, beginning with the release of the Swann report in the United Kingdom. The latest report released by the National Research Council (1998) confirmed that there were substantial information gaps that contribute to the difficulty of assessing potential detrimental effects of antimicrobials in food animals on human health. Regardless of the controversy, bacterial pathogens of animal and human origin are becoming increasingly resistant to most frontline antimicrobials, including expanded-spectrum cephalosporins, aminoglycosides, and even fluoroquinolones. The lion's share of these antimicrobial resistant phenotypes is gained from extra-chromosomal genes that may impart resistance to an entire antimicrobial class. In recent years, a number of these resistance genes have been associated with large, transferable, extra-chromosomal DNA elements, called plasmids, on which may be other DNA mobile elements, such as transposons and integrons. These DNA mobile elements have been shown to transmit genetic determinants for several different antimicrobial resistance mechanisms and may account for the rapid dissemination of resistance genes among different bacteria. The increasing incidence of antimicrobial resistant bacterial pathogens has severe implications for the future treatment and prevention of infectious diseases in both animals and humans. Although much scientific information is available on this subject, many aspects of the development of antimicrobial resistance still remain uncertain. The emergence and dissemination of bacterial antimicrobial resistance is the result of numerous complex interactions among antimicrobials, microorganisms, and the surrounding environments. Although research has linked the use of antibiotics in agriculture to the emergence of antibiotic-resistant foodborne pathogens, debate still continues whether this role is significant enough to merit further regulation or restriction.200212212946
419330.9999Use of antimicrobial agents in veterinary medicine and food animal production. Antimicrobial resistance is a growing area of concern in both human and veterinary medicine. This review presents an overview of the use of antimicrobial agents in animals for therapeutic, metaphylactic, prophylactic and growth promotion purposes. In addition, factors favouring resistance development and transfer of resistance genes between different bacteria, as well as transfer of resistant bacteria between different hosts, are described with particular reference to the role of animals as a reservoir of resistance genes or resistant bacterial pathogens which may cause diseases in humans.200111397611
418240.9999Spread of resistant bacteria and resistance genes from animals to humans--the public health consequences. The paper reviews the lines of evidence which link the use of antimicrobial drugs for food animals with the emergence of antimicrobial drug resistance in bacteria pathogenic to humans, with a particular focus on the public health aspects. Deductions from the epidemiology of food-borne infections, ecological studies, outbreak investigations, typing studies and direct epidemiological observations show that resistant bacteria are transferred from food animals to man. In addition to transfer in the food chain, exchange of mobile genetic elements among commensal and pathogenic bacteria contributes to the emergence of drug resistance. There is growing evidence that this has measurable consequences for human public health. One consequence is increased transmission supported by unrelated use of anti-microbials in humans. Other consequences are related to reduced efficacy of early empirical treatment, limitations in the choices for treatment after confirmed microbiological diagnosis, and finally a possible coselection of virulence traits. Recent epidemiological studies have measured these consequences in terms of excess mortality associated with resistance, increased duration of illness, and increased risk of invasive illness or hospitalization following infections with resistant Salmonella.200415525367
389850.9999Enterococci as a One Health indicator of antimicrobial resistance. The rapid increase of antimicrobial-resistant bacteria in humans and livestock is concerning. Antimicrobials are essential for the treatment of disease in modern day medicine, and their misuse in humans and food animals has contributed to an increase in the prevalence of antimicrobial-resistant bacteria. Globally, antimicrobial resistance is recognized as a One Health problem affecting humans, animals, and environment. Enterococcal species are Gram-positive bacteria that are widely distributed in nature. Their occurrence, prevalence, and persistence across the One Health continuum make them an ideal candidate to study antimicrobial resistance from a One Health perspective. The objective of this review was to summarize the role of enterococci as an indicator of antimicrobial resistance across One Health sectors. We also briefly address the prevalence of enterococci in human, animal, and environmental settings. In addition, a 16S RNA gene-based phylogenetic tree was constructed to visualize the evolutionary relationship among enterococcal species and whether they segregate based on host environment. We also review the genomic basis of antimicrobial resistance in enterococcal species across the One Health continuum.202438696839
418960.9999Antimicrobial 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
411670.9999Does the use of antibiotics in food animals pose a risk to human health? A critical review of published data. The use of antibiotics in food animals selects for bacteria resistant to antibiotics used in humans, and these might spread via the food to humans and cause human infection, hence the banning of growth-promoters. The actual danger seems small, and there might be disadvantages to human and to animal health. The low dosages used for growth promotion are an unquantified hazard. Although some antibiotics are used both in animals and humans, most of the resistance problem in humans has arisen from human use. Resistance can be selected in food animals, and resistant bacteria can contaminate animal-derived food, but adequate cooking destroys them. How often they colonize the human gut, and transfer resistance genes is not known. In zoonotic salmonellosis, resistance may arise in animals or humans, but human cross-infection is common. The case of campylobacter infection is less clear. The normal human faecal flora can contain resistant enterococci, but indistinguishable strains in animals and man are uncommon, possibly because most animal enterococci do not establish themselves in the human intestine. There is no correlation between the carriage of resistant enterococci of possible animal origin and human infection with resistant strains. Commensal Escherichia coli also exhibits host-animal preferences. Anti-Gram-positive growth promoters would be expected to have little effect on most Gram-negative organisms. Even if resistant pathogens do reach man, the clinical consequences of resistance may be small. The application of the 'precautionary principle' is a non-scientific approach that assumes that risk assessments will be carried out.200414657094
418580.9999Containment of antimicrobial resistance due to use of antimicrobial agents in animals intended for food: WHO perspective. The use of antimicrobial agents in humans and food-producing animals has important consequences for human and animal health, as it can lead to the development of resistant bacteria (pathogens and/or commensals with resistance genes). Moreover, resistant bacteria in animals can be transferred to people--usually through the consumption of food, but also through direct contact with food-producing animals or through environmental spread. Ultimately, this can result in human infections with bacteria that are resistant to antimicrobial agents and that can therefore be difficult or impossible to cure. Of special concern is resistance to antimicrobial agents classified by the World Health Organization (WHO) as critically important for human medicine, such as fluoroquinolones, third- and fourth-generation cephalosporins, and macrolides. WHO encourages the agricultural, food, veterinary and health sectors to work together to eliminate the burden of antimicrobial resistance arising from the use of antimicrobial agents in food-producing animals. Joint efforts should be made to reduce the inappropriate use of antimicrobial agents (e.g. the use of antimicrobials as growth promoters) and limit the spread of bacteria resistant to antimicrobial agents. WHO will continueto address this issue in conjunction with the Food and Agriculture Organization of the United Nations, the World Organisation for Animal Health, the animal health/production industry and other important stakeholders. It will also continue to enhance the capacity of its Member States (through training courses and sentinel studies), particularly developing countries, to conduct integrated surveillance of antimicrobial use and resistance, to carry out risk assessments to support the selection of risk management options and to implement strategies for the containment of antimicrobial resistance.201222849282
418790.9999Human health consequences of use of antimicrobial agents in aquaculture. Intensive use of antimicrobial agents in aquaculture provides a selective pressure creating reservoirs of drug-resistant bacteria and transferable resistance genes in fish pathogens and other bacteria in the aquatic environment. From these reservoirs, resistance genes may disseminate by horizontal gene transfer and reach human pathogens, or drug-resistant pathogens from the aquatic environment may reach humans directly. Horizontal gene transfer may occur in the aquaculture environment, in the food chain, or in the human intestinal tract. Among the antimicrobial agents commonly used in aquaculture, several are classified by the World Health Organisation as critically important for use in humans. Occurrence of resistance to these antimicrobial agents in human pathogens severely limits the therapeutic options in human infections. Considering the rapid growth and importance of aquaculture industry in many regions of the world and the widespread, intensive, and often unregulated use of antimicrobial agents in this area of animal production, efforts are needed to prevent development and spread of antimicrobial resistance in aquaculture to reduce the risk to human health.200919772389
3897100.9999The use of aminoglycosides in animals within the EU: development of resistance in animals and possible impact on human and animal health: a review. Aminoglycosides (AGs) are important antibacterial agents for the treatment of various infections in humans and animals. Following extensive use of AGs in humans, food-producing animals and companion animals, acquired resistance among human and animal pathogens and commensal bacteria has emerged. Acquired resistance occurs through several mechanisms, but enzymatic inactivation of AGs is the most common one. Resistance genes are often located on mobile genetic elements, facilitating their spread between different bacterial species and between animals and humans. AG resistance has been found in many different bacterial species, including those with zoonotic potential such as Salmonella spp., Campylobacter spp. and livestock-associated MRSA. The highest risk is anticipated from transfer of resistant enterococci or coliforms (Escherichia coli) since infections with these pathogens in humans would potentially be treated with AGs. There is evidence that the use of AGs in human and veterinary medicine is associated with the increased prevalence of resistance. The same resistance genes have been found in isolates from humans and animals. Evaluation of risk factors indicates that the probability of transmission of AG resistance from animals to humans through transfer of zoonotic or commensal foodborne bacteria and/or their mobile genetic elements can be regarded as high, although there are no quantitative data on the actual contribution of animals to AG resistance in human pathogens. Responsible use of AGs is of great importance in order to safeguard their clinical efficacy for human and veterinary medicine.201931002332
3947110.9999Human health hazard from antimicrobial-resistant enterococci in animals and food. The use of antimicrobial agents in the modern farm industry has created a reservoir of resistant bacteria in food animals. Foods of animal origin are often contaminated with enterococci that are likely to contribute resistance genes, virulence factors, or other properties to enterococci IN humans. The potential hazard to human health from antimicrobial-resistant enterococci in animals is questioned by some scientists because of evidence of host specificity of enterococci. Similarly, the occurrences of specific nosocomial clones of enterococci in hospitals have lead to the misconception that antimicrobial-resistant animal enterococci should be disregarded as a human health hazard. On the basis of review of the literature, we find that neither the results provided by molecular typing that classify enterococci as host-specific organisms nor the occurrence of specific nosocomial clones of enterococci provide reasons to change the current view that antimicrobial-resistant enterococci from animals pose a threat to human health. On the contrary, antimicrobial resistance genes appear to spread freely between enterococci from different reservoirs, irrespective of their apparent host association.200616941376
4213120.9999Fluoroquinolone resistance of Escherichia coli and Salmonella from healthy livestock and poultry in the EU. The potential for transmission of antibiotic-resistant enteric zoonotic bacteria from animals to humans has been a public health concern for several decades. Bacteria carrying antibiotic resistance genes found in the intestinal tract of food animals can contaminate carcasses and may lead to food-borne disease in humans that may not respond to antibiotic treatment. It is consequently important to monitor changes in antimicrobial susceptibility of zoonotic and commensal organism; in this context, there are a number of veterinary monitoring programmes that collect bacteria in food-producing animals at slaughter and determine their susceptibility against antibiotics relevant for human medicine. The data generated are part of the risk analysis for potential food-borne transmission of resistance. There has been much debate about the use of fluoroquinolones in veterinary medicine, and so, this review will consider the fluoroquinolone data from two surveys and compare them to national surveillance programmes. At the outset, it must be pointed out that there is, however, a lack of agreement between several programmes on what is meant by the term 'fluoroquinolone resistance' through use of different definitions of resistance and different resistance breakpoints. An additional aim of this paper is to clarify some of those definitions. Despite the debate about the contribution of antibiotic use in veterinary medicine to the overall resistance development in human pathogens, the data suggest that clinical resistance to fluoroquinolones in Escherichia coli and nontyphoidal Salmonella is generally uncommon, except for a few countries. Ongoing surveillance will continue to monitor the situation and identify whether this situation changes within the respective animal populations. For the benefit of both the epidemiologist and the clinician, it would be strongly advantageous that national monitoring surveys report both percentages of clinical resistance and decreased susceptibility.201222066763
4192130.9999Food and human gut as reservoirs of transferable antibiotic resistance encoding genes. The increase and spread of antibiotic resistance (AR) over the past decade in human pathogens has become a worldwide health concern. Recent genomic and metagenomic studies in humans, animals, in food and in the environment have led to the discovery of a huge reservoir of AR genes called the resistome that could be mobilized and transferred from these sources to human pathogens. AR is a natural phenomenon developed by bacteria to protect antibiotic-producing bacteria from their own products and also to increase their survival in highly competitive microbial environments. Although antibiotics are used extensively in humans and animals, there is also considerable usage of antibiotics in agriculture, especially in animal feeds and aquaculture. The aim of this review is to give an overview of the sources of AR and the use of antibiotics in these reservoirs as selectors for emergence of AR bacteria in humans via the food chain.201323805136
4115140.9999Antibiotic Use for Growth Promotion in Animals: Ecologic and Public Health Consequences. Antibiotics have successfully treated infectious diseases in man, animals and agricultural plants. However, one consequence of usage at any level, subtherapeutic or therapeutic, has been selection of microorganisms resistant to these valuable agents. Today clinicians worldwide face singly resistant and multiply resistant bacteria which complicate treatment of even common infectious agents. This situation calls for a critical evaluation of the numerous ways in which antibiotics are being used so as to evaluate benefits and risks. About half of the antibiotics produced in the United States arc used in animals, chiefly in subtherapeutic amounts for growth promotion. This usage is for prolonged periods leading to selection of multiply-resistant bacteria which enter a common environmental pool. From there, resistance determinants from different sources spread from one bacterium to another, from one animal host to another, from one area to another. The same resistance determinants have been traced to many different genera associated with humans, animals and foods where they pose a continued threat to public health. Since alternative measures for growth promotion, such as antimicrobials which are not used for human therapy and which do not select for multiple-resistances are available, their use, instead of antibiotics, would remove a major factor contributing to the environmental pool of transferable resistance genes.198730965484
4119150.9999How to modify conditions limiting resistance in bacteria in animals and other reservoirs. Antimicrobial agents in veterinary medicine are used for three purposes: therapy, prophylaxis, and nutrition. The major public health risk is that selection pressure leads to an increase in the pool of resistance genes. Since 1987, the nutritional use of antimicrobials in Europe has been regulated by a council directive, which demands special investigations into the potential of antimicrobials to increase rates of drug resistance. However, the prophylactic and therapeutic use of antimicrobials has sometimes led to the emergence of resistant bacteria. For example, the selective effect of the prophylactic use of gentamicin and the therapeutic use of quinolones led to the emergence of resistant salmonellae. To prevent the spread of resistant microorganisms from animals to humans, it should be recognized that antibiotics are not suitable as a compensation for poor hygiene standards or for the eradication of a pathogen from a certain environment. They should be used only by doctors or veterinarians.19978994793
4334160.9999Association between the consumption of antimicrobial agents in animal husbandry and the occurrence of resistant bacteria among food animals. Antimicrobial agents are used in food animals for therapy and prophylaxis of bacterial infections and in feed to promote growth. The use of antimicrobial agents for food animals may cause problems in the therapy of infections by selecting for resistance among bacteria pathogenic for animals or humans. The emergence of resistant bacteria and resistance genes following the use of antimicrobial agents is relatively well documented and it seems evident that all antimicrobial agents will select for resistance. However, current knowledge regarding the occurrence of antimicrobial resistance in food animals, the quantitative impact of the use of different antimicrobial agents on selection for resistance and the most appropriate treatment regimens to limit the development of resistance is incomplete. Surveillance programmes monitoring the occurrence and development of resistance and consumption of antimicrobial agents are urgently needed, as is research into the most appropriate ways to use antimicrobial agents in veterinary medicine to limit the emergence and spread of antimicrobial resistance.199910493603
4216170.9999Antimicrobial Resistance in the Food Chain in the European Union. Consumers require safety foods but without losing enough supply and low prices. Food concerns about antimicrobial residues and antimicrobial-resistant (AMR) bacteria are not usually appropriately separated and could be perceived as the same problem. The monitoring of residues of antimicrobials in animal food is well established at different levels (farm, slaughterhouse, and industry), and it is preceded by the legislation of veterinary medicines where maximum residues limits are required for medicines to be used in food animal. Following the strategy of the World Health Organization, one of the proposed measures consists in controlling the use of critical antibiotics. The European Union surveillance program currently includes the animal species with the highest meat production (pigs, chickens, turkeys, and cattle) and the food derived from them, investigating antimicrobial resistance of zoonotic (Salmonella and Campylobacter) and indicator (Escherichia coli and enterococci) bacteria. AMR mechanisms encoded by genes have a greater impact on transfer than mutations. Sometimes these genes are found in mobile genetic elements such as plasmids, transposons, or integrons, capable of passing from one bacterium to another by horizontal transfer. It is important to know that depending on how the resistance mechanism is transferred, the power of dissemination is different. By vertical transfer of the resistance gene, whatever its origin, will be transmitted to the following generations. In the case of horizontal transfer, the resistance gene moves to neighboring bacteria and therefore the range of resistance can be much greater.201830077219
4205180.9999Public health risk of antimicrobial resistance transfer from companion animals. Antimicrobials are important tools for the therapy of infectious bacterial diseases in companion animals. Loss of efficacy of antimicrobial substances can seriously compromise animal health and welfare. A need for the development of new antimicrobials for the therapy of multiresistant infections, particularly those caused by Gram-negative bacteria, has been acknowledged in human medicine and a future corresponding need in veterinary medicine is expected. A unique aspect related to antimicrobial resistance and risk of resistance transfer in companion animals is their close contact with humans. This creates opportunities for interspecies transmission of resistant bacteria. Yet, the current knowledge of this field is limited and no risk assessment is performed when approving new veterinary antimicrobials. The objective of this review is to summarize the current knowledge on the use and indications for antimicrobials in companion animals, drug-resistant bacteria of concern among companion animals, risk factors for colonization of companion animals with resistant bacteria and transmission of antimicrobial resistance (bacteria and/or resistance determinants) between animals and humans. The major antimicrobial resistance microbiological hazards originating from companion animals that directly or indirectly may cause adverse health effects in humans are MRSA, methicillin-resistant Staphylococcus pseudintermedius, VRE, ESBL- or carbapenemase-producing Enterobacteriaceae and Gram-negative bacteria. In the face of the previously recognized microbiological hazards, a risk assessment tool could be applied in applications for marketing authorization for medicinal products for companion animals. This would allow the approval of new veterinary medicinal antimicrobials for which risk levels are estimated as acceptable for public health.201727999066
4083190.9999Antibiotic resistance gene discovery in food-producing animals. Numerous environmental reservoirs contribute to the widespread antibiotic resistance problem in human pathogens. One environmental reservoir of particular importance is the intestinal bacteria of food-producing animals. In this review I examine recent discoveries of antibiotic resistance genes in agricultural animals. Two types of antibiotic resistance gene discoveries will be discussed: the use of classic microbiological and molecular techniques, such as culturing and PCR, to identify known genes not previously reported in animals; and the application of high-throughput technologies, such as metagenomics, to identify novel genes and gene transfer mechanisms. These discoveries confirm that antibiotics should be limited to prudent uses.201424994584