人体肠道菌群中抗生素耐药基因的水平转移研究

抗生素的广泛使用导致环境中出现了大量耐药菌，其携带的耐药基因会通过水平转移在微生物间传播，加重了耐药基因及耐药菌对环境的污染。由于肠道菌群多样性较高且包含多种抗生素耐药基因，人体肠道逐渐成为抗生素耐药基因发生水平转移的适宜场所。抗生素的过度使用容易改变肠道微生物的组成，影响宿主免疫功能，导致定植抗性的丧失，促使外源耐药菌在肠道定植，对人体健康造成潜在风险。影响人体肠道中耐药基因组成的因素多种多样，包括抗生素的使用，食物，饮水等。本文介绍了肠道菌群耐药基因的组成和传播，总结了肠道菌群中抗生素耐药基因的研究方法，并对未来研究重点进行了展望，以增强对人体肠道抗生素耐药基因的认识，并为减少或控制肠道中抗生素耐药性方法的开发提供新思路。     

大气环境中抗生素耐药菌的来源与传播扩散研究进展

摘要：抗生素耐药性日益成为威胁人类健康的重大挑战。目前,抗生素耐药菌在水和土壤中的传播扩散已被广泛研究,但 大气环境中耐药菌的污染现状还鲜有报道。大气作为一种强流动性的耐药菌存储库,可使细菌在空气介质中长时间跨区域传播 扩散,并可直接被人体吸入,从而对人体健康产生严重的危害。本文介绍了大气环境中抗生素耐药菌的国内外研究现状,分析 了大气中耐药菌的来源以及对人体的潜在健康风险,对今后有关大气环境耐药菌的研究重点进行了展望,对正确揭示耐药菌在 空气中的传播扩散具有重要理论意义     

食源性细菌耐药性:抗生素使用与风险分析

食源性细菌耐药性系指源于人类食物链的对抗生素耐药的细菌及其耐药基因,日渐成为全球关注的食品安全和公共健康问题.由食源性耐药沙门菌、大肠埃希菌、弯曲杆菌、肠球菌及金黄色葡萄球菌等所致的人类健康风险尤其备受关注.控制这些风险要求进行有效的风险分析及制定必要的风险策略,包括监控非人类医学领域抗生素使用及其安全评估,如对上市前后的食品动物抗菌药物耐药性进行系统监测和健康风险分析.本文结合目前相关领域的国际发展状况,探讨了与食源性细菌耐药性相关的抗生素使用安全问题与风险分析对策,期望能引起对控制及降低食源性细菌耐药性危害的更大关注与科学研究.     

世界卫生组织、欧盟和中国抗生素耐药性监测现状

随着抗生素在人类和动物中的使用,抗生素耐药性已经成为一个危害健康的全球性问题。人类、动物和食品之间的活动,加强了耐药细菌及耐药基因的传播。本文综述了世界卫生组织、欧盟国家和我国近年来对来源于人医和兽医上的耐药细菌的监测现状。     

致病菌的耐药趋势与抗生素的合理应用

回顾了人类社会环境中致病菌的变迁 ,详细分析了当前细菌耐药的发展状况、细菌耐药的机制和造成耐药性迅速发展的主要原因。明确指出 ,抗生素在人类与抗感染疾病斗争中起了举足轻重的作用 ,但是 ,由于目前滥用抗生素的现象极其严重 ,造成许多致病菌耐药。细菌耐药已成为全球性的灾难 ,人类必须高度警惕。为了持续与致病菌作斗争 ,就必须合理使用抗生素。文章对合理应用抗生素的基本原则、经验用药的方法、预防用药、耐药性菌的抗生素选择以及联合用药等问题进行了深入的讨论     

致病菌的耐药趋势与抗生素的合理应用

回顾了人类社会环境中致病菌的变迁,详细分析了当前细菌耐药的发展状况、细菌耐药的机制和造成耐药性迅速发展的主要原因.明确指出,抗生素在人类与抗感染疾病斗争中起了举足轻重的作用,但是,由于目前滥用抗生素的现象极其严重,造成许多致病菌耐药.细菌耐药已成为全球性的灾难,人类必须高度警惕.为了持续与致病菌作斗争,就必须合理使用抗生素.文章对合理应用抗生素的基本原则、经验用药的方法、预防用药、耐药性菌的抗生素选择以及联合用药等问题进行了深入的讨论.     

关于参加为WHO起草"对人类健康极为重要抗生素目录"专家小组会议的汇报

随着抗生素在人类、畜牧业、水产业和农业上的广泛使用,细菌在抗生素的选择性压力下产生的对抗生素的耐药性不断加剧和蔓延已引起了全球的关注,由于细菌耐药现象是一个多因素问题,需要多方位多部门互相配合才能予以控制,因此国际粮农组织(FAO)/世界卫生组织(WHO)/国际动物健康组织(OIE),共同于2003年12月在瑞士日内瓦、2004年3月在挪威奥斯陆召开了两次关于人类医学领域之外抗生素使用和细菌耐药性研讨会,鉴于抗生素是保证人类和动物健康及社会福利的必需药物,而抗生素的非人类使用导致耐药菌株的出现和传播对人类健康的影响已日趋明显.     

抗生素联合用药可选择性地作用于耐药菌?

抗生素自用于细菌性感染的治疗以来大大延长了人的寿命,然而伴随着抗生素的大量使用,抗生素耐药性问题也日益严重,而且耐药性的产生速度远远超出了新抗生素的开发速度。因此,对现有药物的联合使用在阻止病原菌耐药性的传播上起着越来越重要的作用。此外,进行这方面的研究也有助于人类对细菌生态学和进化的了解。尽管多药联用对细菌生长的影响已经得到了广泛的研究,但对于敏感菌和耐药菌间的选择性差异却知之甚少,鉴于此,哈佛医学院的研究人员对这方面进行了研究,以期为抗感染研究工作提出一个以提高对耐药菌的选择性为目标的多药联用抗菌治疗新策略。结果作者发现,临床上因考虑到药效而不主张使用的抑制型药物组合——多西环素-环丙沙星联合用药可以发挥对多西环素耐药菌的选择性杀灭作用。相反,临床上倡导使用的协同型药物组合——多西环素-红霉素在绝对增强对耐药菌和敏感菌作用的同时,也增强了多西环素耐药菌的选择性富集,致使细菌的耐药性不断增强。这些发现指向一个内在的折中,即传统上在临床回避使用的抑制型药物组合却可能有助于降低耐药性,甚至逆转对耐药菌的选择性。     

抗生素耐药基因古老起源与现代进化及其警示

细菌抗生素耐药性系全球关注的医学及社会问题.新近对古老细菌DNA与现代病原菌的研究揭示了抗生素耐药基因的古老起源、多样性及快速的现代进化,并促使了耐药基因组(resistome)的问世.耐药基因决定簇及其与进化有关的基因可移动元件如质粒、插入顺序、转座子和整合子等远存在于人类抗生素时代之前.在过去短短的70年抗生素时代期间,人类大量应用各类抗生素等行为明显地造成了对细菌的选择性压力,加之细菌基因本身的自突变性和水平基因转移能力等多种因素促使了耐药基因的进化及新型耐药特征的出现.人类重要病原菌如ESKAPE病原菌(肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠道杆菌属)所呈现的高度多重耐药性或泛耐药性便充分展示了耐药基因起源、进化和传播的复杂性,并严重地威胁着感染性疾病的治疗.所有这些均警示人类需要同时采取多种有效措施控制各类抗生素尤其是人类极为重要抗生素的使用.任何环境下的抗生素滥用当止!     

金黄色葡萄球菌食品分离株与临床分离株耐药谱的相关性分析

<正>抗生素是人类与致病菌斗争的产物,为人类健康做出了巨大贡献。但随着抗生素的大量使用,越来越多的泛耐药菌及多重耐药菌随之产生,使大多数抗菌药物治疗无效,尤其对婴幼儿和老年人、免疫力低下者构成极大威胁。治疗用抗生素是细菌产生耐药性的一个因素,但是,抗生素作为饲料添加剂长时间低剂量和不规范的使用,也是细菌产生耐药性的另一个重要因素。本文对山西地区2015—2016年收集的     

人类肠道菌群中抗生素耐药基因的研究进展

抗生素耐药性在细菌病原体中不断出现并蔓延,其遗传物质基础抗生素耐药基因(ARG)可通过基因突变或水平基因转移等方式获得,并赋予宿主对抗生素的耐药性,从而严重威胁人类的健康.人类肠道菌群作为ARG产生和传播的重要场所越来越受到重视.人类肠道菌群含众多种类的ARG,可通过水平基因转移等方式实现ARG的传播.影响肠道菌群中A...     

Antimicrobial resistance in foodborne pathogens--a cause for concern?

The widespread use of antibiotics in food animal production systems has resulted in the emergence of antibiotic resistant zoonotic bacteria that can be transmitted to humans through the food chain. Infection with antibiotic resistant bacteria negatively impacts on public health, due to an increased incidence of treatment failure and severity of disease. Development of resistant bacteria in food animals can result from chromosomal mutations but is more commonly associated with the horizontal transfer of resistance determinants borne on mobile genetic elements. Food may represent a dynamic environment for the continuing transfer of antibiotic resistance determinants between bacteria. Current food preservation systems that use a combination of environmental stresses to reduce growth of bacteria, may serve to escalate development and dissemination of antibiotic resistance among food related pathogens. The increasing reliance on biocides for pathogen control in food production and processing, heightens the risk of selection of biocide-resistant strains. Of particular concern is the potential for sublethal exposure to biocides to select for bacteria with enhanced multi-drug efflux pump activity capable of providing both resistance to biocides and cross-resistance to multiple antibiotics. Although present evidence suggests that biocide resistance is associated with a physiological cost, the possibility of the development of adaptive mutations conferring increased fitness cannot be ruled-out. Strategies aimed at inhibiting efflux pumps and eliminating plasmids could help to restore therapeutic efficacy to antibiotics and reduce the spread of antibiotic resistant foodborne pathogens through the food chain.     

Antibiotic usage in animals: impact on bacterial resistance and public health.

Antibiotic use whether for therapy or prevention of bacterial diseases, or as performance enhancers will result in antibiotic resistant micro-organisms, not only among pathogens but also among bacteria of the endogenous microflora of animals. The extent to which antibiotic use in animals will contribute to the antibiotic resistance in humans is still under much debate. In addition to the veterinary use of antibiotics, the use of these agents as antimicrobial growth promoters (AGP) greatly influences the prevalence of resistance in animal bacteria and a poses risk factor for the emergence of antibiotic resistance in human pathogens. Antibiotic resistant bacteria such as Escherichia coli, Salmonella spp., Campylobacter spp. and enterococci from animals can colonise or infect the human population via contact (occupational exposure) or via the food chain. Moreover, resistance genes can be transferred from bacteria of animals to human pathogens in the intestinal flora of humans. In humans, the control of resistance is based on hygienic measures: prevention of cross contamination and a decrease in the usage of antibiotics. In food animals housed closely together, hygienic measures, such as prevention of oral-faecal contact, are not feasible. Therefore, diminishing the need for antibiotics is the only possible way of controlling resistance in large groups of animals. This can be achieved by improvement of animal husbandry systems, feed composition and eradication of or vaccination against infectious diseases. Moreover, abolishing the use of antibiotics as feed additives for growth promotion in animals bred as a food source for humans would decrease the use of antibiotics in animals on a worldwide scale by nearly 50%. This would not only diminish the public health risk of dissemination of resistant bacteria or resistant genes from animals to humans, but would also be of major importance in maintaining the efficacy of antibiotics in veterinary medicine.     

Agricultural Applications for Antimicrobials. A Danger to Human Health: An Official Position Statement of the Society of Infectious Diseases Pharmacists

The use of antibiotics in agriculture, particularly in food‐producing animals, is pervasive and represents the overwhelming majority of antibiotic use worldwide. The link between antibiotic use in animals and antibiotic resistance in humans is unequivocal. Transmission can occur by ingesting undercooked meats harboring resistant bacteria, by direct contact of animals by animal handlers, and by various other means. Antibiotics used in aquaculture and antifungals used in horticulture are also an evolving threat to human health. Regulations aimed at decreasing the amount of antibiotics used in food production to limit the development of antibiotic resistance have recently been implemented. However, further action is needed to minimize antibiotic use in agriculture. This article describes the extent of this current problem and serves as the official position of the Society of Infectious Diseases Pharmacists on this urgent threat to human health.     

Epidemiology of resistance to antibiotics. Links between animals and humans

An inevitable side effect of the use of antibiotics is the emergence and dissemination of resistant bacteria. Most retrospective and prospective studies show that after the introduction of an antibiotic not only the level of resistance of pathogenic bacteria, but also of commensal bacteria increases. Commensal bacteria constitute a reservior of resistance genes for (potentially) pathogenic bacteria. Their level of resistance is considered to be a good indicator for selection pressure by antibiotic use and for resistance problems to be expected in pathogens. Resistant commensal bacteria of food animals might contaminate, like zoonotic bacteria, meat (products) and so reach the intestinal tract of humans. Monitoring the prevalence of resistance in indicator bacteria such as faecal Escherichia coli and enterococci in different populations, animals, patients and healthy humans, makes it feasible to compare the prevalence of resistance and to detect transfer of resistant bacteria or resistance genes from animals to humans and vice versa. Only in countries that use or used avoparcin (a glycopeptide antibiotic, like vancomycin) as antimicrobial growth promoter (AMGP), is vancomycin resistance common in intestinal enterococci, not only in exposed animals, but also in the human population outside hospitals. Resistance genes against antibiotics, that are or have only been used in animals, i.e. nourseothricin, apramycin etc. were found soon after their introduction, not only in animal bacteria but also in the commensal flora of humans, in zoonotic pathogens like salmonellae, but also in strictly human pathogens, like shigellae. This makes it clear that not only clonal spread of resistant strains occurs, but also transfer of resistance genes between human and animal bacteria. Moreover, since the EU ban of avoparcin, a significant decrease has been observed in several European countries in the prevalence of vancomycin resistant enterococci in meat (products), in faecal samples of food animals and healthy humans, which underlines the role of antimicrobial usage in food animals in the selection of bacterial resistance and the transport of these resistances via the food chain to humans. To safeguard public health, the selection and dissemination of resistant bacteria from animals should be controlled. This can only be achieved by reducing the amounts of antibiotics used in animals. Discontinuing the practice of routinely adding AMGP to animal feeds would reduce the amounts of antibiotics used for animals in the EU by a minimum of 30% and in some member states even by 50%.     

Discussion

Many studies and meeting reports have suggested that the use of some antibiotics in food animals can compromise the treatment of some infectious diseases in humans. Although the studies and reports are timely and important, it is difficult to assess the relative value of the conclusions in relationship to the overall situation concerning antibiotic resistant foodborne bacteria because the data used in the analyses are often of disparate origin. The studies have attempted to establish a cause and effect relationship between the use ('consumption') of antibiotics in food animals and treatment failures in human disease on the basis of [1] antibiotic usage data; [2] in vitro determinations of antibiotic susceptibility of animal and human isolates, [3] results obtained from controlled animal experiments or [4] epidemiological data. Each approach has sought to associate bacterial antibiotic resistance data with it's own immediate focus area of investigation. However, a true assessment of the degree of contribution to human antibiotic resistance problems from animal use can only be facilitated by comprehensively organizing these different approaches into a concerted, coordinated effort. Concurrently, the implementation of a multinational programme aimed at monitoring antibiotic usage in food animals and resistance in specific bacteria associated with those animals should be instituted. In parallel with this endeavour is the implementation of new prudent use guidelines for antibiotic use by veterinarians. Through the use of science-based approaches like these, the development and spread of antibiotic resistant bacteria associated with food animals could be minimized and contained.     

Standards of the in vitro mutation frequency study and the antimicrobial activity study in gut

In view of the recent rapid increase in incidence of infection with antimicrobial resistant bacteria in human medicine, there is international controversy as to the medical risk that is created by transfer of antimicrobial resistant bacteria and antimicrobial resistant genes, which may be produced through the processes of administration of antimicrobials to food-producing animals, via the food chain. Accordingly, International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) provides the comprehensive guidelines for characterizing selection of antimicrobial resistance by bacteria which may adversely affect human health in order to establish the system of registry of antimicrobial drugs to be administered to food- producing animals. Currently, Japanese Society of Antimicrobials for Animals recognizes the lack of technical test standards in compliance with VICH guidelines in the world and has established the test standards for "in vitro mutation frequency studies" to evaluate the appearance frequency and resistant level of resistant bacteria and those for studies on the "antimicrobial activity in gut" to estimate the effects on intestinal flora from professional aspects.     

Antibiotic resistance in Escherichia coli isolates obtained from animals, foods and humans in Spain.

Antibiotic resistance was investigated in 474 Escherichia coli isolates recovered from animal faeces (broilers, pigs, pets, bulls and horses), human faeces (patients and healthy volunteers) and food products of animal origin. E. coli isolates (3260) recovered from human significant infectious samples were also included. There was a high frequency of nalidixic acid, ciprofloxacin and gentamicin resistance in E. coli isolates from broilers (88, 38 and 40%, respectively), and from foods (53, 13 and 17%). High levels of resistance to trimethoprim-sulphamethoxazole and tetracycline have been found in E. coli isolates from broilers, pigs and foods. These data raise important questions about the potential impact of antibiotic use in animals and the possible entry of resistant pathogens into the food chain.     

A risk analysis framework for the long-term management of antibiotic resistance in food-producing animals

In recent years, there has been increasing concern that the use of antibiotics in food-producing animals, particularly their long-term use for growth promotion, contributes to the emergence of antibiotic-resistant bacteria in animals. These resistant bacteria may spread from animals to humans via the food chain. They may also transfer their antibiotic-resistance genes into human pathogenic bacteria, leading to failure of antibiotic treatment for some, possibly life-threatening, human conditions. To assist regulatory decision making, the actual risk to human health from antibiotic use in animals needs to be determined (risk assessment) and the requirements for risk minimisation (risk management and risk communication) determined. We propose a novel method of risk analysis involving risk assessment for three interrelated hazards: the antibiotic (chemical agent), the antibiotic-resistant bacterium (microbiological agent) and the antibiotic-resistance gene (genetic agent). Risk minimisation may then include control of antibiotic use and/or the reduction of the spread of bacterial infection and/or prevention of transfer of resistance determinants between bacterial populations.