The human health implication of the use of antimicrobial agents in animal feeds

Antimicrobials given in subtherapeutic levels in feed are credited with having contributed to lower cost of meat, milk and eggs. The practice often is associated with the acquisition of resistant enteric flora by the involved animals, and this may in turn contribute to the human reservoir of antimicrobial resistant coliforms and salmonellae. Associated farm workers may transiently acquire resistant flora and on rare occasions develop salmonellosis. Although irrefutable evidence of growth promotant properties of antibiotics in animal feed was provided 30 to 40 years ago, additional studies on mechanisms of the effect are presently needed. It may be possible to identify factors effective in promoting growth without deleterious effects on flora. A national surveillance programme of antimicrobial utilisation (both subtherapeutic and therapeutic) among food producing animals should be established. Molecular epidemiologic research efforts will need to be undertaken to establish whether genetic information of animal origin importantly contributes to the human environmental pool of antimicrobial resistance. In the meantime, it does not appear that the use of drugs as feed additives, while allowing their unrestricted use for therapy in both animals and persons, would favorably influence the problems of antimicrobial resistance of salmonellosis in human populations.     

Human health aspects of antibiotic use in food animals: a review

Antibiotic use not only selects for resistance in pathogenic bacteria, but also in the commensal flora of exposed individuals. Veterinary surgeons regularly prescribe antibiotics for food animals to treat bacterial infections just as doctors do for human patients. In addition, however, animal feeds contain added antibiotics not for therapy but for economic reasons: to enhance the growth rate of these animals. Several of the antibiotics used as growth promoters are analogues of and fully cross resistant with important antibiotics used in human medicine. As a result of this high exposure to antibiotics, the prevalence of resistant bacteria in the faecal flora of these animals is high. These resistant bacteria can be directly and indirectly, via foods of animal origin, transferred to humans and either colonize the human intestinal tract or exchange their resistance genes with commensal bacteria of humans. As the intestinal flora functions as a reservoir of resistance genes for pathogenic bacteria and because many bacterial species of the intestinal flora are potential pathogens, the efficacy of antibiotic therapy in human medicine may be jeopardized.     

Public health and policy

Antimicrobial agent usage data are essential for focusing efforts to reduce misuse and overuse of antimicrobial agents in food producing animals because these practices may select for resistance in bacteria of animals. Transfer of resistant bacteria from animals to humans can lead to human infection caused by resistant pathogens. Resistant infections can lead to treatment failures, resulting in prolonged or more severe illness. Multiple World Health Organization (WHO) reports have concluded that both antimicrobial resistance and antimicrobial usage should be monitored on the national level. The system for collecting antimicrobial usage data should be clear and transparent to facilitate trend analysis and comparison within and among countries. Therapeutic, prophylactic and growth promotion use should be recorded, along with route of administration and animal species and/or production class treated. The usage data should be compared to resistance data, and the comparison should be made available in a timely manner. In the United States, surveillance of antimicrobial resistance in foodborne bacteria is performed by the National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria, however, the United States still lacks a mechanism for collecting antimicrobial usage data. Combined with antimicrobial resistance information from NARMS, antimicrobial usage data will help to direct education efforts and policy decisions, minimizing the risk that people will develop antimicrobial resistant infections as a result of eating food of animal origin. Ultimately mitigation strategies guided by usage data will be more effective in maintaining antimicrobial drugs for appropriate veterinary use and in protecting human health.     

Health council report: "Antimicrobial growth promoters"

The Health Council of the Netherlands has issued a report on the risk of development of resistance among bacteria as result of the use of antibiotics as growth promotors in livestock farming. The committee appointed by the Health Council conclude that the use of antimicrobial growth promotors contributes to the problem of resistance among human pathogens. The conclusions are based on evidence regarding the development of resistance in livestock as the result of the use of antimicrobial growth promotors, the possibility of colonisation/infection of humans with resistant bacteria from the intestinal flora of productive livestock, and the transfer of resistance genes from livestock bacteria to human pathogenic microorganisms. Effective measures for the limitation of the public health risk should focus on termination of the use of antimicrobial growth promotors that confer resistance to (related) antibiotics currently used (or which will be available) to treat patients suffering from bacterial infections. In addition, the committee advised ending the use of antimicrobial growth promotors in 3 years.     

Human health hazards associated with the administration of antimicrobials to slaughter animals. Part II. An assessment of the risks of resistant bacteria in pigs and pork

Risks for the consumer regarding the acquisition of resistant bacteria and/or resistance genes via the consumption of pork are discussed. In general, Salmonella spp. and Escherichia coli that originate from animals do not easily transfer their resistance genes to the resident intestinal flora of humans. The prevalence of resistant E. coli in humans seems more associated with being a vegetarian (odds ratio (OR) 1.89) than with the consumption of meat and meat products. Other risk factors are treatment with antimicrobials (OR 2-5), becoming hospitalized (OR 5.93), or working in a health setting (OR 4.38). In the Netherlands, annually an estimated 45,000 people (0-150,000) become a carrier of resistant E. coli and/or resistance genes that ori ginate from pigs, while an estimated 345,000 persons (175,000-600,000) become a carrier of resistant E. coli and/or resistance genes that originate from hospitals, e.g. other patients. Any problems with resistant Salmonella spp. that stem from pigs are, in fact, an integral part of the total problem of food-borne salmonellosis. Sometimes there are outbreaks of a specific multi-resistant clone of S. typhimurium that causes problems in both farm animals and humans. The probability that in the next 30 years there is no or maximally one outbreak of a specific clone that originates from pig herds is estimated at about 75%. Antimicrobials used as a growth promoter can have a measurable influence on the prevalence of resistant bacteria. The likely chain of events regarding avoparcin and the selection and dissemination of resistance against vancomycin in the enterococci gives the impression that the impact of the use of antimicrobials in animals on the prevalence of resistance in humans is largely determined by whether resistance genes are, or become, located on a self-transferable transposon. Furthermore, consumer health risks of antimicrobials used in slaughter pigs are mainly determined by the selection and dissemination of bacterial resistance and much less by the toxicological properties of any residues in pork. It is also concluded that most of the problems with resistant bacteria in humans are associated with the medical use of antimicrobials, and that the impact of particularly the veterinary use of antimicrobials is limited. However, the impact of antimicrobials used as a feed additive appears to be much greater than that of antimicrobials used for strictly veterinary purposes. The use of antimicrobials as a feed additive should therefore be seriously reconsidered.     

Salmonella and antimicrobial resistance in broilers: A review

Salmonella enterica is a zoonotic pathogen which can readily pass from animal to man through the consumption of contaminated food. The prevalence of Salmonella enterica associated with poultry and poultry meat products has been well-documented and this prevalence has both public health and economic implications. The estimated total cost for nontyphoidal Salmonella is in excess of 14 billion dollars/year in the United States alone. Almost 41,930 cases of nontyphoidal foodborne salmonellosis are confirmed annually with an estimated total number of 1 million cases of foodborne salmonellosis not reported. The emergence of antimicrobial resistant Salmonella recovered from meat products has heightened concerns regarding antimicrobial use in food animal production. This review will cover the history and taxonmy of Salmonella enterica, Salmonella in poultry and poultry products, colonization factors, transmission, detection and characterization, antibiotics, antimicrobial resistance, mechanisms of resistance in Salmonella by class, transmission of antimicrobial resistance, and the global implications of antimicrobial resistance.     

Antimicrobial use in food and companion animals

The vast literature on antimicrobial drug use in animals has expanded considerably recently as the antimicrobial resistance (AMR) crisis in human medicine leads to questions about all usage of antimicrobial drugs, including long-term usage in intensively managed food animals for growth promotion and disease prevention. Attention is also increasingly focusing on antimicrobial use and on bacterial resistance in companion animals, which are in intimate contact with the human population. They may share resistant bacteria with their owners, amplify resistant bacteria acquired from their owners, and act as a reservoir for human infection. Considerable effort is being made to describe the basis of AMR in bacterial pathogens of animals. Documentation of many aspects of use of antimicrobials in animals is, however, generally less developed and only a few countries can describe quantities of drugs used in animals to kg levels annually. In recent years, many national veterinary associations have produced 'prudent use guidelines' to try to improve antimicrobial drug use and decrease resistance, but the impact of guidelines is unknown. Within the evolving global movement for 'antimicrobial stewardship', there is considerable scope to improve many aspects of antimicrobial use in animals, including infection control and reduction of use, with a view to reducing resistance and its spread, and to preserving antimicrobial drugs for the future.     

欧盟禁用饲料药物添加剂的历史和法规

欧盟考虑到抗生素耐药性的发展和抗生素耐药基因可能从动物到人微生物的转移,决定从2006年1月1日起禁止抗生素作为生长促进剂,甚至还建议禁止在动物饲料中全面使用所有的抗菌剂。收集和整理欧盟饲料药物添加剂的禁用清单和法规,介绍欧盟禁用饲料药物添加剂的历史及其对动物健康的影响,以期为中国饲料药物添加剂的使用和管理提供借鉴和参考。     

Antimicrobial resistance in bacteria from Swiss veal calves at slaughter

Bacteria with antimicrobial resistance can be transferred from animals to humans and may compromise antimicrobial treatment in case of infection. To determine the antimicrobial resistance situation in bacteria from Swiss veal calves, faecal samples from 500 randomly selected calves originating from 129 farms were collected at four big slaughterhouses. Samples were cultured for Escherichia coli, Enterococcus sp. and Campylobacter sp. and isolated strains were tested for antimicrobial susceptibility to selected antimicrobial agents by the minimal inhibitory concentration technique using the broth microdilution method. From 100 farms, data on farm management, animal husbandry and antimicrobial treatments of the calves were collected by questionnaire. Risk factors associated with antimicrobial resistance were identified by logistic regression. In total, 467 E. coli, 413 Enterococcus sp. and 202 Campylobacter sp. were isolated. Of those, 68.7%, 98.7% and 67.8%, respectively, were resistant to at least one of the tested antimicrobial agents. Resistance was mainly observed to antimicrobials frequently used in farm animals. Prevalence of resistance to antimicrobials important for human treatment was generally low. However, a rather high number of quinupristin/dalfopristin-resistant Enterococcus faecium and ciprofloxacin-resistant Campylobacter sp. were detected. External calf purchase, large finishing groups, feeding of milk by-products and administration of antimicrobials through feed upon arrival of the animals on the farm significantly increased the risk of antimicrobial resistance at farm level. Participation in a quality assurance programme and injection of a macrolide upon arrival of the animals on the farm had a protective effect. The present study showed that veal calves may serve as a reservoir for resistant bacteria. To ensure food safety, veal calves should be included in the national monitoring programme for antimicrobial resistance in farm animals. By improving farm management and calf husbandry the prevalence of resistance may be reduced.     

Complex bacterial flora of imported pet tortoises deceased during quarantine: Another zoonotic threat?

Turtoises are a great puzzle when it comes to their bacterial flora, the composition and structure of which are still unknown in details. Its component which has been best described so far is Salmonella spp., presumably due to the threat of reptile-associated salmonellosis in humans. This investigation tried to assess and characterize intestinal bacterial flora of imported tortoises found dead during quarantine. Most of the animals carried various serovars of Salmonella showing no antimicrobial resistance. Presence of multiresistant Escherichia coli was possibly a result of industrial breeding and high usage of antimicrobials. Thirteen bacterial species or genera like Citrobacter spp., Morganella spp., Pseudomonas spp. were identified. Their commensal character is assumed, although pathogenic potential might be verified. The results indicate global tortoise trade as a source of common and exotic bacteria or antimicrobial resistance mechanisms in new geographical areas. These dangers indicate the need for a systematic survey of exotic pets and establishment of legal requirements for reptile health conditions on breeding, trade premises and in households with such pets.     

Antimicrobial usage and resistance in beef production

Antimicrobials are critical to contemporary high-intensity beef production. Many different antimicrobials are approved for beef cattle, and are used judiciously for animal welfare, and controversially, to promote growth and feed efficiency. Antimicrobial administration provides a powerful selective pressure that acts on the microbial community, selecting for resistance gene determinants and antimicrobial-resistant bacteria resident in the bovine flora. The bovine microbiota includes many harmless bacteria, but also opportunistic pathogens that may acquire and propagate resistance genes within the microbial community via horizontal gene transfer. Antimicrobial-resistant bovine pathogens can also complicate the prevention and treatment of infectious diseases in beef feedlots,threatening the efficiency of the beef production system. Likewise, the transmission of antimicrobial resistance genes to bovine-associated human pathogens is a potential public health concern. This review outlines current antimicrobial use practices pertaining to beef production, and explores the frequency of antimicrobial resistance in major bovine pathogens. The effect of antimicrobials on the composition of the bovine microbiota is examined, as are the effects on the beef production resistome. Antimicrobial resistance is further explored within the context of the wider beef production continuum, with emphasis on antimicrobial resistance genes in the food chain, and risk to the human population.     

Antibiotic resistance in Escherichia coli isolates from poultry environment and UTI patients in Kerala,India: A comparison study

BackgroundThere are only narrow insights regarding the antimicrobial resistance of pathogens in poultry environment in India and its transmission to humans. The use of antimicrobials in food animal production is not properly regulated in India. So, many clinically important antimicrobials are used indiscriminately.ObjectiveOur aim was to do a comparative analysis of antibiotic resistance in Escherichia coli isolates from poultry environment and UTI patients.MethodologyTwo poultry farms each from six areas in Muvattupuzha region of the state of Kerala in India were selected for the study. From each farm, samples of fresh fecal matter, litter from inside the shed, litter from outside the shed, nearby agricultural soil and control soilwere collected. E. coli was isolated from each sample, and antimicrobial susceptibility testing of E. coli was done with fifteen antibiotics. Antibiograms of UTI patients were collected from the tertiary care hospital included in the study and those were compared with the antibiograms of poultrysamples.ResultAll samples were resistant to ampicillin, amoxicillin, meropenem and tetracycline. Similar resistance pattern in poultry environment and UTI patients was seen for antibiotics such as ampicillin, amoxicillin, amikacin, and ofloxacin. A statistically significant difference (p < .00601) was established in the total number of isolates resistant to various antibiotics from areas near to farms compared to those away from farms.ConclusionE. coli were resistant not only to extended spectrum beta lactams but also to carbapenems which might have disseminated to environment where litter was used as manure. This might be due to irrational use of antibiotics in chicken and poultry feed as growth promoter.     

Antimicrobial resistance in bacteria from food-producing animals. risk management tools and strategies

The application of antimicrobial agents has proved to be the main risk factor for development, selection and spread of antimicrobial resistance. This link applies to the use of antimicrobial agents in human and in veterinary medicine. Furthermore, antimicrobial-resistant bacteria and resistant genes can be transmitted from animals to humans either by direct contact or via the food chain. In this context, risk management has to be discussed regarding prevention and control of the already existing antimicrobial resistance. One of the primary risk management measures in order to control the development and spread of antimicrobial resistances is by regulating the use of antimicrobial agents and subjecting their use to guidelines. Thereby, the occurrence of antimicrobial resistant bacteria in the human and veterinary habitat can be controlled to a certain degree. There is little information about past attempts to prevent the development of resistances or to control them, and even less is known about the effectiveness or the cost intensiveness of such efforts. Most of the strategies focus on preventing and controlling antimicrobial resistance by means of the reduction or limitation of the use of antimicrobial agents in food-producing animals.     

Resistance to antibiotics in the normal flora of animals.

The normal bacterial flora contains antibiotic resistance genes to various degrees, even in individuals with no history of exposure to commercially prepared antibiotics. Several factors seem to increase the number of antibiotic-resistant bacteria in feces. One important factor is the exposure of the intestinal flora to antibacterial drugs. Antibiotics used as feed additives seem to play an important role in the development of antibiotic resistance in normal flora bacteria. The use of avoparcin as a feed additive has demonstrated that an antibiotic considered "safe" is responsible for increased levels of antibiotic resistance in the normal flora enterococci of animals fed with avoparcin and possibly in humans consuming products from these animals. However, other factors like stress from temperature, crowding, and management also seem to contribute to the occurrence of antibiotic resistance in normal flora bacteria. The normal flora of animals has been studied with respect to the development of antibiotic resistance over four decades, but there are few studies with the intestinal flora as the main focus. The results of earlier studies are valuable when focused against the recent understanding of mobile genetics responsible for bacterial antibiotic resistance. New studies should be undertaken to assess whether the development of antibiotic resistance in the normal flora is directly linked to the dramatic increase in antibiotic resistance of bacterial pathogens. Bacteria of the normal flora, often disregarded scientifically, should be studied with the intention of using them as active protection against infectious diseases and thereby contributing to the overall reduction of use of antibioties in both animals and humans.     

Cross-sectional study of antimicrobial-resistant bacteria in horses. Part 2: Risk factors for faecal carriage of antimicrobial-resistant Escherichia coli in horses

Reasons for performing study: The increasing prevalence of antimicrobial resistant bacteria such as antimicrobial‐resistant and extended spectrum β‐lactamase (ESBL)‐producing Escherichia coli represents a significant problem for human and veterinary medicine. Despite this, the risk factors for faecal carriage of such bacteria by horses in the UK, particularly those in the wider community, have not been well described. Objectives: To characterise the risk factors for faecal carriage of antimicrobial‐resistant E. coli amongst horses in the mainland UK. Methods: A cross‐sectional study of horses recruited by 65 randomly selected equine veterinary practices was conducted, with a faecal sample collected and self‐administered questionnaire completed by the horse owner. Faecal samples were cultured for antimicrobial‐resistant E. coli, with isolates confirmed as E. coli having their antimicrobial resistance profile determined. Multilevel, multivariable logistic regression models were used to investigate risk factors for the carriage of antimicrobial‐resistant E. coli in the sample population. Results: Faecal samples and completed questionnaires were obtained for 627 horses located on 475 premises. Recent hospitalisation, contact with specific types of nonequid animals, the type of premises, the surrounding land use, the reason for veterinary treatment received in the last 6 months and antimicrobial treatment in the previous 10 days were identified as risk factors for many of the antimicrobial‐resistance outcomes considered. Being stabled on the same yard as a recently hospitalised horse was identified as a risk factor for increased risk of carriage of ESBL‐producing E. coli. Conclusions and potential relevance: Increasing antimicrobial resistance may have significant health implications for the horse population of Great Britain. This form of epidemiological investigation highlights potential risk factors that may be controlled to limit the extent of the problem.     

四环素类抗生素的环境行为研究进展

四环素类抗生素被广泛用于动物疾病的治疗,并长期以亚治疗剂量添加于动物饲料中用于动物疾病的预防和促进动物生长.由于四环素类抗生素大量使用使其在环境中普遍存在,并导致了细菌耐药性.研究表明某些四环素类抗生素在环境中具有一定的持久性,因此其在环境中行为引起了众多学者的关注.论文回顾了四环素类抗生素在环境中残留、迁移转化等方面...     

ACVIM Consensus Statement on Therapeutic Antimicrobial Use in Animals and Antimicrobial Resistance

The epidemic of antimicrobial resistant infections continues to challenge, compromising animal care, complicating food animal production and posing zoonotic disease risks. While the overall role of therapeutic antimicrobial use in animals in the development AMR in animal and human pathogens is poorly defined, veterinarians must consider the impacts of antimicrobial use in animal and take steps to optimize antimicrobial use, so as to maximize the health benefits to animals while minimizing the likelihood of antimicrobial resistance and other adverse effects. This consensus statement aims to provide guidance on the therapeutic use of antimicrobials in animals, balancing the need for effective therapy with minimizing development of antimicrobial resistance in bacteria from animals and humans.     

"肺肠同制"思路对饲料替抗的启示

目前养猪业的饲料替抗方向大多专注于猪只肠道,主要针对肠道抗菌、抑菌、免疫调节、菌群调理和消化率提升等方面进行研究与尝试,往往忽略了肠道与肺部之间的关联性。替抗的本质是通过调节健康、调理代谢来改善猪只的生产性能。文章主要从三个方面阐述了肠道与肺部的关系,即肺部供氧状态与肠道结构功能之间的关系,肠道菌群平衡、肠道代谢产物变化与肺部功能之间的关系以及两者之间神经联系等,并提出"肺肠同制"理念,以期为替抗工作提供新思路。     

国内外食品源及动物源弯曲菌流行性及耐药性调查研究进展

弯曲菌是重要的食品源性致病微生物,在很多动物中属于正常携带细菌,能通过食物链传递给人类,可引起人类肠炎的暴发流行和食物中毒。在畜牧养殖业大量抗菌药物的使用,造成动物源弯曲菌耐药性日益增加,给人类带来健康风险。发达国家很早就开展了动物源性弯曲菌流行性和耐药性监测工作,很多发展中国家也对弯曲菌流行性和耐药性监测越来越重视,文章将就近年来国内外动物源性弯曲菌的流行及耐药情况调查工作做简单的总结,为中国动物源性弯曲菌流行性和耐药性工作的开展提供比较及理论分析数据。