细菌耐药性产生机制及防控措施

细菌的耐药性,尤其是多重耐药性给临床治疗带来了巨大的难题。细菌耐药性可以分为天然耐药性和获得耐药性,各种细菌的耐药机制各有不同,但主要有产生灭活酶或钝化酶,药物作用靶位的变化,细胞壁通透性改变,主动外排机制等。只有了解这些机理才能更好地防止细菌产生耐药性。     

抗生素耐药性耐药机制的探讨

抗生素耐药性日益受到人们的重视。抗生素耐药机理包括酶对抗生素的修饰和破坏、减少抗生素向细菌内的摄入、增加抗生素的主动排出作用、新靶位的产生及药物作用靶位的过度表达。本文指出了目前临床存在耐药性机制以及获得耐药性的途径,以利于促进抗生素的研究。     

细菌耐药性研究进展

细菌抗生素类药物耐药性的产生是临床治疗感染性疾病的一大难题,已受到人们的广泛关注。细菌主要通过产生灭活酶或钝化酶获得耐药性,除此之外还有细胞壁的渗透障碍、外排泵的泵出作用、靶位改变等多种机制,这些机制相互作用共同决定细菌的耐药水平。随着新型抗生素的临床应用,新的耐药机制随之出现,耐药菌也越来越广泛。细菌耐药机制的研究对耐药菌的控制和新药开发具有指导性意义。文章从耐药性的起源、产生机理、耐药特性及耐药性的检测方法4个方面进行了阐述。     

细菌耐药性产生的分子生物学机理及控制措施

该文主要对细菌耐药性产生的分子生物学机理及耐药性的控制措施进行了阐述,旨在为临床上合理使用抗菌药物、开发新的抗菌药或防止细菌产生耐药机制提供科学依据。     

志贺菌耐药性的分子机制

随着抗菌药物的广泛应用,耐药及多重耐药细菌已经严重威胁着人类和动物的健康.志贺菌的耐药机制主要是产生灭活酶、细胞壁的改变、主动外排以及作用靶位结构的改变.本文对其耐药机制的研究进展作简要综述.     

氟喹诺酮类药物(FQs)耐药性产生的分子机制

随着氟喹诺酮类药物的广泛使用，细菌对该类药物产生耐药性日趋严重，这引起了国内外的高度重视。本文就FQs耐药性产生的分子机制，即药靶的改变，药物在菌体内蓄积浓度下降及由质粒介导的耐药等机制做了综述。     

质粒介导喹诺酮类耐药机制研究进展

质粒介导喹诺酮类耐药(PMQR)基因的出现,迅速提高了细菌对喹诺酮类药物的耐药性,给临床细菌性疾病的治疗带来了严重的威胁。目前虽然认为喹诺酮类耐药基因(qnr)只引起低水平耐药,但低水平耐药性可使细菌数量达到出现突变所需的浓度,从而出现高水平耐药。因此,对质粒介导该类药物耐药机制的研究,及耐药基因的分子传播机制的研究不仅能指导临床合理用药,而且有助于控制耐药菌株的产生和传播。     

细菌耐药性产生的分子机制及对细菌毒力的影响研究进展

抗菌药物选择压力导致细菌耐药性日趋严重,一些细菌菌株的分子耐药机制会引起细菌致病性的改变,说明两者之间存在一定的相关性。论文从细菌胞壁、胞膜、胞质和染色体4个部分概述了其相关主要大分子物质参与细菌耐药的机制,介绍了与耐药性密切相关的生物大分子参与细菌致病的过程,分析细菌耐药性的产生对细菌毒力变化的影响,以期为解决现今较严重的细菌耐药性及细菌性疾病的防治难题找到新方法和突破点。     

细菌耐药机理与抗菌药物的合理应用

一、细菌的耐药机理抗生素广泛用于临床后,细菌可在数月或数年间对其产生耐药性。细菌基因的突变是导致细菌产生耐药的根本原因,在一个感染周期中,处于对数生长期的细菌突变率约为1/107,如该突变可对抗生素耐药,将使细菌在敏感菌被杀灭后迅速繁殖成为优势菌。在抗生素的选择性压力下,突变率可成百倍增加,并极易发展为多重耐药。耐药性的迅速扩散通常由携带抗生素耐药性的质粒在不同种属的细菌间穿梭和复制所导致,高度耐药的细菌常同时涉及以下几种耐药机理。1.主动泵出机理药物在达到靶位发挥作用之前,必须通过G-菌的外膜和内膜、G 菌胞壁…     

多粘菌素耐药基因mcr-1的研究进展

多粘菌素耐药基因mcr-1由1626个核苷酸序列组成,其主要作用是介导肠杆菌科细菌对多粘菌素产生抗药性。mcr-1基因可携带完整的ISApl1或ISApl1片段,翻译一段由541个氨基酸组成具有介导磷酸乙醇胺转移作用的酶。mcr-1能整合于质粒,可以随质粒在不同细菌中水平传播,甚至可以与其他的耐药基因共同存在于同一质粒,表达后产生多种耐药机制。mcr-1基因介导多粘菌素类药物耐药,但并不耐受目前所有的抗生素。本文对mcr-1基因的发现、分布、流行及耐药性等研究进展进行综述,以期为人类共同遏制多粘菌素类药物耐药基因的流行,及抗生素的安全用药提供可参考依据。     

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.     

Antimicrobial resistance in bacteria from horses: Epidemiology of antimicrobial resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections. While the epidemiology of antimicrobial resistance in bacteria from man has been studied extensively, less work has been undertaken in companion animals, particularly horses. Methicillin‐resistant Staphylococcus aureus has been identified as a cause of infections, with a low prevalence of nasal carriage by horses in the community but higher for hospitalised horses. Molecular characterisation has shown methicillin‐resistant Staphylococcus aureus strains either to be predominantly of types associated with horses or of sequence type ST398. Antimicrobial‐resistant Escherichia coli (including multidrug‐resistant and extended spectrum β‐lactamase‐producing isolates) have caused infections and been documented in faecal carriage by horses, with many significant resistance mechanisms identified. More sporadic reports and molecular characterisation exist for resistance in other bacteria such as enterococci, Salmonella, Acinetobacter and Pseudomonas species. Limited work has been undertaken evaluating risk factors and much of the epidemiology of antimicrobial resistance in bacteria from horses remains to be determined.     

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.     

The management of risk arising from the use of antimicrobial agents in veterinary medicine in EU/EEA countries – a review

Antimicrobials are essential medicines for the treatment of many microbial infections in humans and animals. Only a small number of antimicrobial agents with new mechanisms of action have been authorized in recent years for use in either humans or animals. Antimicrobial resistance (AMR) arising from the use of antimicrobial agents in veterinary medicine is a concern for public health due to the detection of increasing levels of resistance in foodborne zoonotic bacteria, particularly gram‐negative bacteria, and due to the detection of determinants of resistance such as Extended‐spectrum beta‐lactamases (ESBL) in bacteria from animals and in foodstuffs of animal origin. The importance and the extent of the emergence and spread of AMR from animals to humans has yet to be quantified. Likewise, the relative contribution that the use of antimicrobial agents in animals makes to the overall risk to human from AMR is currently a subject of debate that can only be resolved through further research. Nevertheless, risk managers have agreed that the impact on public health of the use of antimicrobials in animals should be minimized as far as possible and a variety of measures have been introduced by different authorities in the EU to achieve this objective. This article reviews a range of measures that have been implemented within European countries to reduce the occurrence and the risk of transmission of AMR to humans following the use of antimicrobial agents in animals and briefly describes some of the alternatives to the use of antimicrobial agents that are being developed.     

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.     

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.     

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.     

Use of a bacterial antimicrobial resistance gene microarray for the identification of resistant Staphylococcus aureus

As diagnostic and surveillance activities are vital to determine measures needed to control antimicrobial resistance (AMR), new and rapid laboratory methods are necessary to facilitate this important effort. DNA microarray technology allows the detection of a large number of genes in a single reaction. This technology is simple, specific and high-throughput. We have developed a bacterial antimicrobial resistance gene DNA microarray that will allow rapid antimicrobial resistance gene screening for all Gram-positive and Gram-negative bacteria. A prototype microarray was designed using a 70-mer based oligonucleotide set targeting AMR genes of Gram-negative and Gram-positive bacteria. In the present version, the microarray consists of 182 oligonucleotides corresponding to 166 different acquired AMR gene targets, covering most of the resistance genes found in both Gram-negative and -positive bacteria. A test study was performed on a collection of Staphylococcus aureus isolates from milk samples from dairy farms in Québec, Canada. The reproducibility of the hybridizations was determined, and the microarray results were compared with those obtained by phenotypic resistance tests (either MIC or Kirby-Bauer). The microarray genotyping demonstrated a correlation between penicillin, tetracycline and erythromycin resistance phenotypes with the corresponding acquired resistance genes. The hybridizations showed that the 38 antimicrobial resistant S. aureus isolates possessed at least one AMR gene.     

Stakeholder position paper: epidemiological perspectives on antibiotic use in animals

Epidemiologists studying antimicrobial resistance are often interested in analyzing the association between antimicrobial resistance and antimicrobial use in animals, and on the impact of antimicrobial use in animals on the occurrence of resistance in bacteria affecting human populations. Given the various potential antimicrobial use data sources, it seems likely there will be some variability in the utility of the data for interpreting trends in antimicrobial resistance and investigating the relationship between antimicrobial use in animals and antimicrobial resistance in bacteria affecting human health. From an epidemiologic perspective, the major issues related to incorporation of antimicrobial use data into antimicrobial resistance monitoring programs are the further development of epidemiologic methods for collecting, quantifying, analyzing and interpreting use data; an open and realistic consideration of the limitations of the data; developing an understanding of scaling, temporal and spatial heterogeneity issues; and the interpretative problems of ecologic and atomistic fallacy. Given the many potential biases in antimicrobial use data, attempts to relate levels of antimicrobial use to levels of antimicrobial resistance should be done with caution until the data are better understood and the aforementioned issues have been addressed.     

Stakeholder position paper: companion animal veterinarian

The total quantity of use in companion animals is generally believed to be relatively small in comparison with antimicrobial use in food animals. Use in companion animals is principally for treatment, whereas the greater proportion of use in food animals is for prophylaxis, metaphylaxis and growth promotion. Therefore, it is important to collect data on end use in companion animals so that overall estimates of use in companion animals can be generated and separated from estimates for food animals. However, data from antimicrobial use in companion animals are extremely limited and no serious attempts to collect such data have ever been made in the United States. The lack of usage data in is concomitant with the dearth of information on antimicrobial resistance in companion animals. Companion animals have been involved in the transmission to humans of, or become infected with, foodborne zoonotic bacteria such as Salmonella and Campylobacter. Companion animals are an integral part of the ecology of antimicrobial resistance through their contact with food animals and exposure to antimicrobials for disease treatment and through contact with humans and the environment. In the practice of companion animal medicine, antimicrobial use data are important for understanding the potential impact on companion animal heath posed by antimicrobial resistance transferred from food animals, humans and the environment, and the threat to humans and other companion animals posed by antimicrobial use in companion animals. Basic information on the patterns and quantities of antimicrobial use in combination with resistance surveillance data, could help companion animal veterinarians understand the potential for development, or evidence of, an antimicrobial resistance problem in their practices, the role of companion animals in the overall epidemiology of antimicrobial resistance, and for comparison with local, regional, or national data. The combination of data from either a sentinel site system of clinics or a use survey with national data from the pharmaceutical industry should provide sufficient data to credibly estimate the total volume and patterns of antimicrobial use in companion animal medicine. The time and effort for use monitoring or to complete a survey would likely become burdensome. Practice management software now utilized at most companion animal clinics could be used to generate antimicrobial use data as well as patient population data as surrogate for the true population at risk for patient encounters in a companion animal practice.