Monitoring of antimicrobial resistance among food animals: principles and limitations

Large amounts of antimicrobial agents are in the production of food animals used for therapy and prophylactics of bacterial infections and in feed to promote growth. The use of antimicrobial agents causes problems in the therapy of infections through the selection for resistance among bacteria pathogenic for animals or humans. 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 regimes to limit the development of resistance is incomplete. Programmes monitoring the occurrence and development of resistance are essential to determine the most important areas for intervention and to monitor the effects of interventions. When designing a monitoring programme it is important to decide on the purpose of the programme. Thus, there are major differences between programmes designed to detect changes in a national population, individual herds or groups of animals. In addition, programmes have to be designed differently according to whether the aim is to determine changes in resistance for all antimicrobial agents or only the antimicrobial agents considered most important in relation to treatment of humans. In 1995 a continuous surveillance for antimicrobial resistance among bacteria isolated from food animals was established in Denmark. Three categories of bacteria, indicator bacteria, zoonotic bacteria and animal pathogens are continuously isolated from broilers, cattle and pigs and tested for susceptibility to antimicrobial agents used for therapy and growth promotion by disc diffusion or minimal inhibitory concentration determinations. This programme will only detect changes on a national level. However, isolating the bacteria and testing for several antimicrobial agents will enable us to determine the effect of linkage of resistance. Since 1995 major differences in the consumption pattern of different antimicrobial agents have occurred in Denmark. The Danish monitoring programme has enabled us to determine the effect of these changes on the occurrence of resistance. The Danish monitoring is, however, not suited to determine changes on a herd level or to detect emergence of new types of resistance only occurring at a low level.     

欧盟兽用抗菌药耐药性管理概述

介绍负责管理欧盟兽用抗菌药耐药性的欧洲药品局下设的兽用药品委员会、健康与消费者保护司和食品安全局等相关管理机构以及成立耐药性管理工作组、进行耐药性风险分析、制定相关文件和实施耐药性监测等的管理措施,为我国兽药耐药性相关政策的制定和措施的实行提供参考.     

Antimicrobial drug use and resistance in dogs

Fifteen years (1984-1998) of records from a Veterinary Teaching Hospital were analyzed to determine whether antimicrobial drug resistance in coagulase-positive Staphylococcus spp. (S. aureus, S. intermedius) isolated from clinical infections in dogs has increased, and whether there has been a change in the species of bacteria isolated from urinary tract infections in dogs. In coagulase-positive Staphylococcus spp., a complex pattern showing both increases and decreases of resistance to different classes of antimicrobial drugs was observed, reflecting the changing use of different antimicrobial drug classes in the hospital over a similar period (1990-1999). In canine urinary tract infections identified from 1984 to 1998, an increase in the incidence of multiresistant Enterococcus spp. was apparent, with marginal increases also in incidence in Enterobacter spp. and in Pseudomonas aeruginosa, both of which, like Enterococcus spp., are innately antimicrobial-resistant bacteria. A survey of directors of veterinary teaching hospitals in Canada and the United States identified only 3 hospitals that had any policy on use of "last resort" antimicrobial drugs (amikacin, imipenem, vancomycin). Evidence is briefly reviewed that owners may be at risk when dogs are treated with antimicrobial drugs, as well as evidence that some resistant bacteria may be acquired by dogs as a result of antimicrobial drug use in agriculture. Based in part on gaps in our knowledge, recommendations are made on prudent use of antimicrobial drugs in companion animals, as well as on the need to develop science-based infection control programs in veterinary hospitals.     

OIE抗菌药耐药性国际标准

兽用抗菌药耐药性已经成为一个全球普遍关注的公共健康问题,各国际组织都积极采取相应的措施控制耐药性的产生和蔓延。介绍了国际组织世界动物卫生组织OIE制定的五个国际标准,包括协调抗菌药耐药性监督和检测程序指南、畜牧业抗菌药消耗量监测指南、兽用抗菌药慎用指南、抗菌药敏感性检测的实验室方法指南、动物源抗菌药耐药性对公共健康潜在影响的风险分析方法指南,以期为我国政策制定者和决策者参照国际标准制定出符合我国国情的耐药性相关指南。     

beta-Lactam resistance and beta-lactamases in bacteria of animal origin

beta-Lactams are among the most clinically important antimicrobials in both human and veterinary medicine. Bacterial resistance to beta-lactams has been increasingly observed in bacteria, including those of animal origin. The mechanisms of beta-lactam resistance include inaccessibility of the drugs to their target, target alterations and/or inactivation of the drugs by beta-lactamases. The latter contributes predominantly to beta-lactam resistance in Gram-negative bacteria. A variety of beta-lactamases have been identified in bacteria derived from food-producing and companion animals and may further serve as a reservoir for beta-lactamase-producing bacteria in humans. While this review mainly describes beta-lactamases from animal-derived Escherichia coli and Salmonella spp., beta-lactamases from animal-derived Campylobacter spp., Enterococcus spp., Staphylococcus spp. and other pathogens are also discussed. Of particular concern are the increasingly-isolated plasmid-encoded AmpC-type CMY and extended-spectrum CTX-M beta-lactamases, which mediate acquired resistance to extended-spectrum beta-lactams. The genes encoding these enzymes often coexist with other antimicrobial resistance determinants and can also be associated with transposons/integrons, increasing the potential enrichment of multidrug resistant bacteria by multiple antimicrobial agents as well as dissemination of the resistance determinants among bacterial species. Characterization of beta-lactam-resistant animal-derived bacteria warrants further investigation of the type and distribution of beta-lactamases in bacteria of animal origin and their potential impact on human medicine.     

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.     

国际组织兽用抗菌药耐药性管理

抗菌药在畜牧养殖业中的广泛应用导致耐药性的产生,引起动物和人类疾病治疗的失败。因此,兽用抗菌药耐药性问题已经成为一个国际上关注的问题。作者主要介绍了国际组织兽用抗菌药耐药性管理措施,指出中国耐药性管理现状及存在的问题,并提出建议,希望为中国兽用抗菌药的使用和耐药性的管理提供一定的参考和依据。     

Tracking Detection and Analysis of Drug Resistance of Chicken-derived Escherichia coli in a Broiler Farm

From 2012 to 2014,300 chicken cloacal swab samples were collected from a broiler farm in Liaoning province,152 strains of chicken-derived Escherichia coli were isolated and identified.The 152 strains of chicken-derived Escherichia coli were detected on 14 kinds of veterinary antimicrobial drugs and 16 kinds of antimicrobial drugs for human by using trace dilution method,and reference to CLSI enterobacter decision criteria to determine.The results showed that chicken-derived Escherichia coli had obvious resistance to veterinary antimicrobial drugs (amoxicillin,ampicillin,enrofloxacin,trimethoprim-sulfamethoxazole,sulfafurazole,tetracycline) and antimicrobial drugs for human (piperacillin,ticarcillin,ciprofloxacin),the resistance rates were high.The resistance test results of isolated chicken-derived Escherichia coli comparing with the MIC value distribution of EUCAST wild type strains were same,but through comparing MIC value distribution,the results showed the isolates of spectinomycin,ampicillin,enrofloxacin,trimethoprim-sulfamethoxazole,cefalotin,cefuroxime,ciprofloxacin and tobramycin drugs MIC value moved to the right obviously,indicated that the antibiotic resistant strength of Escherichia coli increased gradually.The process of breeding and strict biosecurity measures should be taken scientifically to control diseases,and the antibacterial agents should be applied reasonably to control broiler farm production and propagation of bacterial drug resistance.     

某肉鸡场鸡源大肠杆菌耐药性跟踪检测与分析

2012~2014年从辽宁某肉鸡养殖场采集300份鸡泄殖腔拭子,分离获得152株鸡源大肠杆菌。采用微量稀释法对152株鸡源大肠杆菌进行了14种兽用和16种人用抗菌药的药物敏感性测定,并参照CLSI肠杆菌判定标准进行判定。结果显示,鸡源大肠杆菌对兽用阿莫西林、氨苄西林、恩诺沙星、复方新诺明、磺胺异噁唑、四环素和人用哌拉西林、替卡西林、环丙沙星均产生明显耐药性,耐药率较高。对所分离的鸡源大肠杆菌耐药性检测结果与EUCAST发布的野生型菌株MIC值分布进行比较分析,耐药结果基本一致,但通过MIC值分布比较,结果显示出分离菌株的大观霉素、氨苄西林、恩诺沙星、复方新诺明、头孢噻吩、头孢呋辛、环丙沙星和妥布霉素药物的MIC值发生了明显右移,表明该肉鸡场大肠杆菌对上述抗菌药的耐药强度呈现逐渐增强的趋势。在养殖过程中应采取科学饲养和严格的生物安全措施防控疾病,科学合理使用抗菌药物,控制肉鸡场细菌耐药性的产生和传播。     

美国兽用抗菌药耐药性管理

全面介绍了美国兽用抗菌药耐药性的管理机构和管理措施,希望为我国兽药耐药性相关政策的制定和措施的实行提供一定的依据和参考。     

Antimicrobial resistance.

Development of antimicrobial resistance is an inevitable consequence of exposure of microorganisms to antimicrobial agents. Although emergence of resistance cannot be prevented, it can be retarded by minimizing use of antimicrobial agents and avoiding selection of relatively resistant pathogenic and nonpathogenic strains caused by exposure to tissue concentrations that confer a competitive advantage. Most attention in veterinary medicine has focused on the emergence of resistance in food-borne pathogens, with relatively little attention being devoted to small companion animals, despite the frequent use of antimicrobial agents in these animals, evidence that resistance is emerging, and potential for transfer of resistance between companion animals and people. To retard further emergence of resistance in small companion animals, it is imperative that surveillance programs be instituted to monitor development of resistance.     

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.     

2017-2021年上海市动物源粪肠球菌、屎肠球菌耐药性情况变迁分析

为了解上海地区动物源粪肠球菌、屎肠球菌对常见抗菌药物的耐药及其最小抑菌浓度(minimal inhibitory concentration,MIC)变迁情况,采用微量肉汤稀释法对近五年采集的粪肠球菌、屎肠球菌进行10种常见抗菌药物敏感性测试。结果表明,458株粪肠球菌及283株屎肠球菌对头孢西丁、头孢噻呋及氧氟沙星耐药率较高(均高于60%),对青霉素、阿莫西林/克拉维酸及万古霉素的耐药率较低(均低于11%),粪肠球菌耐药率整体高于屎肠球菌,两者对氧氟沙星、头孢噻呋、氟苯尼考、庆大霉素、利奈唑胺、恩诺沙星的耐药率存在较大差异（耐药率差异为15%~44%）。五年间,粪肠球菌对阿莫西林/克拉维酸、氧氟沙星的MIC50及MIC90均呈下降趋势;屎肠球菌对阿莫西林/克拉维酸、头孢西丁及氟苯尼考的MIC50及MIC90均呈下降趋势。研究表明,近年来上海地区动物源粪肠球菌、屎肠球菌的耐药情况有好转趋势,仍需继续加强肠球菌耐药性监测。     

In vitro susceptibility of avian Escherichia coli and Pasteurella multocida to danofloxacin and five other antimicrobials.

The in vitro susceptibility of Escherichia coli and Pasteurella multocida isolated from poultry was determined to danofloxacin, a novel fluoroquinolone, and five other commonly used antimicrobials. A total of 1737 E. coli field isolates and 107 P. multocida isolates were tested by veterinary diagnostic laboratories in Europe, Japan, South Africa, and North America during the period 1989-91. The antimicrobial susceptibility of these isolates was determined using the Sensititre broth microdilution technique. The minimum inhibitory concentrations (MIC) of danofloxacin, furaltadone, lincomycin, oxytetracycline, spectinomycin, and trimethoprim:sulfamethoxazole that prevented growth of 90% of the bacteria were 0.25 > 64, > 64, > 64, > 128, and > 16 micrograms/ml, respectively, against E. coli isolates and 0.25, 64, 64, 16, 128, and 8 micrograms/ml, respectively, against P. multocida isolates. Danofloxacin demonstrated considerable in vitro potency against these important poultry pathogens, many of which showed extensive resistance to the other antimicrobials tested.     

动物源细菌耐药性评估在兽用抗菌药使用减量化行动中的应用

动物源细菌耐药性已引起广泛关注,全国正在逐步推进兽用抗菌药物使用减量化行动。为更好地推动减量化行动的实施,浙江省在耐药性的评估及应用方面进行探索。研究分析了耐药性评估在减量化行动中的作用,建立了耐药系数评估模型与应用方法,研判了目前耐药性监测可能存在的问题,以期更好地推进兽用抗菌药物使用减量化行动。     

Development of an antibiotic resistance monitoring system in Hungary

Because of the rapid development and spread of antimicrobial resistance it is important that a system be established to monitor antimicrobial resistance in pathogenic zoonotic and commensal bacteria of animal origin. Susceptibility testing of bacteria from carcasses and different samples of animal origin has been carried out in veterinary institutes for a long time but by an inconsistent methodology. The disc diffusion method proposed by the National Committee for Clinical Laboratory Standards (NCCLS) was introduced in all institutes in 1997. In order to obtain a coherent view of the antimicrobial resistance of bacteria a computer system was consulted, consisting of a central computer to store all data and some local computers attached to it through the network. At these local measuring stations computers are connected to a video camera, which displays the picture of Petri dishes on the monitor, and inhibition zone diameters of bacteria can be drawn with the mouse by the inspector. The software measures the diameters, evaluates whether or not the bacteria are sensitive, and stores the data. The evaluation is based upon the data of the NCCLS. The central computer can be connected to as many local computers with measuring stations as we wish, so it is suitable for an integrated system for monitoring trends in antimicrobial resistance of bacteria from animals, food and humans, facilitating comparison of the occurrence of resistance for each circumstance in the chain. It depends on the examiners which antibiotics they want to examine. Thirty-two different antibiotic panels were compiled, taking into consideration the active ingredients of medicinal products permitted for veterinary use in Hungary, natural resistance and cross-resistance, the mechanism of resistance and the animal species, i.e. which drugs were recommended for treatment in the given animal species, and the recommendations of the OIE Expert Group on Antimicrobial Resistance. The members of the panels can be changed any time, even during the measuring process. In addition to the inhibition zone diameters of bacteria the database also includes information about bacterial and animal species, the age of animals and the sample or organ where the bacteria are from. Since January 2001 the antibiotic susceptibility of E. coli, Salmonella, Campylobacter and Enterococcus strains isolated from the colons of slaughter cows, pigs and broiler chickens has also been examined. Each of the 19 counties of Hungary submits to the laboratory three tied colon samples from a herd of the above-mentioned animals every month.     

Monitoring of antimicrobial resistance in healthy dogs: first report of canine ampicillin-resistant Enterococcus faecium clonal complex 17

National surveillance programs on antimicrobial usage and antimicrobial resistance in animals have been established in various countries but few of them include bacteria from pets. The objectives of this study were to assess the prevalence of antimicrobial resistance in healthy dogs and to search for resistance phenotypes of clinical relevance. Escherichia coli and Enterococcus spp. were isolated from faecal swabs obtained from 127 dogs. Disk diffusion was used to measure antimicrobial susceptibility in 117 Escherichia coli, 10 Enterococcus faecium and 51 Enterococcus faecalis of canine origin. Resistance was relatively low compared with food animal species in Denmark. All Escherichia coli isolates were susceptible to broad-spectrum aminopenicillins, third generation cephalosporins and fluoroquinolones. Despite the low prevalence of resistance, statistical analysis of questionnaire data revealed a significant association (p=0.02) between recent antimicrobial treatment and resistance in Escherichia coli. Interestingly, two dogs were found to shed Enterococcus faecium resistant to ampicillin. Multilocus sequence typing of these isolates indicated that the two isolates belonged to sequence types associated with human nosocomial infections, and one (ST-192) was genetically related to human epidemic clonal complex 17. The detection of ampicillin-resistant Enterococcus faecium warrants further studies on the prevalence of these bacteria in dogs and on the possible implications to both animal and human health. The results suggest that distinct methods for detection and assessment of antimicrobial resistance in animals should be considered depending on the target animal species and the purposes of the study.     

9种抗菌药物对大肠埃希菌最小抑菌浓度的测定

畜禽养殖中会用到一些抗菌药物,而药物选用需要进行药物敏感性试验,目前市售的药敏纸片多为人用抗菌药物,为了制备兽用抗菌药物的药敏纸片,需要对药物的最小抑菌浓度(MIC)进行测定。该研究筛选了国家兽用药物名录中规定的、兽医临床上常用6类共9种抗菌药物(头孢噻呋钠、硫酸链霉素、强力霉素、土霉素、氨苄西林、氟苯尼考、替米考星、硫酸新霉素、青霉素),以大肠埃希菌为指标菌,通过微量肉汤稀释法分别测定了9种常用抗菌药物的最小抑菌浓度(MIC)。结果表明,头孢噻呋钠、硫酸链霉素、强力霉素、土霉素、氨苄西林、氟苯尼考、替米考星、硫酸新霉素、青霉素对指标菌的MIC值分别为为2、4、4、16、8、16、64、32、250μg/mL。研究结果为这些药物的临床应用和药敏纸片的研制提供了基础资料。     

Nosocomial infections and antimicrobial resistance in critical care medicine

Objective: To review the human and companion animal veterinary literature on nosocomial infections and antimicrobial drug resistance as they pertain to the critically ill patient. Data sources: Data from human and veterinary sources were reviewed using PubMed and CAB. Human data synthesis: There is a large amount of published data on nosocomially‐acquired bloodstream infections, pneumonia, urinary tract infections and surgical site infections, and strategies to minimize the frequency of these infections, in human medicine. Nosocomial infections caused by multi‐drug‐resistant (MDR) pathogens are a leading cause of increased patient morbidity and mortality, medical treatment costs, and prolonged hospital stay. Epidemiology and risk factor analyses have shown that the major risk factor for the development of antimicrobial resistance in critically ill human patients is heavy antibiotic usage. Veterinary data synthesis: There is a paucity of information on the development of antimicrobial drug resistance and nosocomially‐acquired infections in critically ill small animal veterinary patients. Mechanisms of antimicrobial drug resistance are universal, although the selection effects created by antibiotic usage may be less significant in veterinary patients. Future studies on the development of antimicrobial drug resistance in critically ill animals may benefit from research that has been conducted in humans. Conclusions: Antimicrobial use in critically ill patients selects for antimicrobial drug resistance and MDR nosocomial pathogens. The choice of antimicrobials should be prudent and based on regular surveillance studies and accurate microbiological diagnostics. Antimicrobial drug resistance is becoming an increasing problem in veterinary medicine, particularly in the critical care setting, and institution‐specific strategies should be developed to prevent the emergence of MDR infections. The collation of data from tertiary‐care veterinary hospitals may identify trends in antimicrobial drug resistance patterns in nosocomial pathogens and aid in formulating guidelines for antimicrobial use.     

我国动物源细菌耐药性监测及预警的研究进展

利用调查和数据统计报道我国近年来的兽用抗生素使用、养殖业用药背景、抗菌药物耐药、动物源细菌耐药性监测、动物源细菌耐药监测数据库研究及国家制定的相关政策等现状,并针对我国动物源细菌的耐药和监测现状,提出了我国政府与各地区相关部门应科学评估分析动物源细菌耐药性监测数据及变化趋势;借鉴发达国家的经验和方法,完善我国动物源细菌耐药性监测网络和监测体系;加强教育和宣传等应对措施,为解决全球动物源细菌耐药性问题作出贡献。