Occurrence, selection and spread of resistance to antimicrobial agents used for growth promotion for food animals in Denmark.

APMIS. Supplementum Pub Date : 2000-01-01
F M Aarestrup
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The thesis gives a brief overview of the use, consumption, function and benefit of antimicrobial growth promoters and a more thorough description of the potential resistance problems arising by the use of these agents. 14.2 THE USE OF ANTIMICROBIAL AGENTS IN A HISTORICAL PERSPECTIVE: Soon after the introduction of antimicrobial agents for therapy of bacterial infections in humans and animals, the growth promoting effect of antimicrobial agents was observed, and since the beginning of the 1950'ties antimicrobial agents have been included in feed for food animals as a way to improve growth and reduce production costs. 14.3 CONSUMPTION OF ANTIMICROBIAL GROWTH PROMOTERS: Exact figures on the consumption of antimicrobial agents for clinical and growth promoting purposes are very difficult to get, and estimates are only available for a few countries. In Denmark, the total annual consumption of antimicrobial agents for growth promotion increased from 67 tonnes to 116 tonnes from 1989 to 1995. After the ban on avoparcin in 1995 the total consumption of growth promoters decreased to 94 tonnes. An increase up to 107 tonnes took place during 1996 and 1997, but during 1998, the consumption decreased to approximately 49 tonnes. The data that are available for different countries show that the use of antimicrobial agents for growth promotion normally equals or exceeds the usage of antimicrobial agents for therapy for food animals. Based on the information available, it can be estimated that the financial sale of antimicrobial agents for animals amounts to approximately 25% to 35% of the world-wide sale, of which the use of antimicrobial agents as feed additives is at least 50%. 14.4 MODE OF ACTION OF ANTIMICROBIAL GROWTH PROMOTERS: The mode of action of antimicrobial growth promoters is not fully understood. However, the main effects are believed to be a reduction of the growth of bacteria in the intestinal tract and thereby less microbial degradation of useful nutritients, and the prevention of infections with pathogenic bacteria. 14.5 BENEFIT FROM THE USE OF ANTIMICROBIAL GROWTH PROMOTERS: Numerous studies on the economic benefit of the use of antimicrobial growth promoters have been performed. The growth response is normally larger in young animals than in older animals. Large variations in the estimates have been observed, but in general a improvement in growth rate and feed utilisation has been observed. 14.6 SUSCEPTIBILITY AND RESISTANCE TO ANTIMICROBIAL GROWTH PROMOTERS: The definition of a bacterium as susceptible or resistant to an antimicrobial agent ultimately depends on clinical outcome. Since the exact mode of action of antimicrobial growth promoters are not known, the only way to define break points is based on the population distributions of susceptibilities to different agents. For antimicrobial agents used both for therapy and growth promotion the break points for therapy have been used. For avilamycin, avoparcin, flavomycin, monensin and salinomycin, that are used for growth promotion only, tentative break points based on population distributions have to be defined. The tentative break points for avoparcin and avilamycin have been confirmed by cross-resistance to other antimicrobial agents belonging to the same class and the presence of resistance mechanisms. 14.7 OCCURRENCE OF AND SELECTION FOR RESISTANCE TO ANTIMICROBIAL AGENTS USED FOR GROWTH PROMOTION: Information on the occurrence of resistance is needed to guide policy and detect changes that require intervention strategies. In 1995, a continuous monitoring of antimicrobial resistance in bacteria isolated from food animals was established in Denmark. Among food animals 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 MIC-determinations. In all known cases antimicrobial resistance has emerged following the introduction of new antimicrobial compounds for therapy. The occurrence of resistance to antimicrobial agents used for growth promotion indicates that resistance will also emerge following the introduction of antimicrobials for growth promotion. Comparison of the occurrence of resistance among reservoirs with different usage of antimicrobial agents for growth promotion also shows that the occurrence of resistance will follow the usage. 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Abstract

Unlabelled: 14.1

Introduction: This thesis is based on a number of monitoring and research programmes initiated at the Danish Veterinary Laboratory with the aim to determine the occurrence, selection and spread of resistance to antimicrobial agents used for growth promotion. The thesis gives a brief overview of the use, consumption, function and benefit of antimicrobial growth promoters and a more thorough description of the potential resistance problems arising by the use of these agents. 14.2 THE USE OF ANTIMICROBIAL AGENTS IN A HISTORICAL PERSPECTIVE: Soon after the introduction of antimicrobial agents for therapy of bacterial infections in humans and animals, the growth promoting effect of antimicrobial agents was observed, and since the beginning of the 1950'ties antimicrobial agents have been included in feed for food animals as a way to improve growth and reduce production costs. 14.3 CONSUMPTION OF ANTIMICROBIAL GROWTH PROMOTERS: Exact figures on the consumption of antimicrobial agents for clinical and growth promoting purposes are very difficult to get, and estimates are only available for a few countries. In Denmark, the total annual consumption of antimicrobial agents for growth promotion increased from 67 tonnes to 116 tonnes from 1989 to 1995. After the ban on avoparcin in 1995 the total consumption of growth promoters decreased to 94 tonnes. An increase up to 107 tonnes took place during 1996 and 1997, but during 1998, the consumption decreased to approximately 49 tonnes. The data that are available for different countries show that the use of antimicrobial agents for growth promotion normally equals or exceeds the usage of antimicrobial agents for therapy for food animals. Based on the information available, it can be estimated that the financial sale of antimicrobial agents for animals amounts to approximately 25% to 35% of the world-wide sale, of which the use of antimicrobial agents as feed additives is at least 50%. 14.4 MODE OF ACTION OF ANTIMICROBIAL GROWTH PROMOTERS: The mode of action of antimicrobial growth promoters is not fully understood. However, the main effects are believed to be a reduction of the growth of bacteria in the intestinal tract and thereby less microbial degradation of useful nutritients, and the prevention of infections with pathogenic bacteria. 14.5 BENEFIT FROM THE USE OF ANTIMICROBIAL GROWTH PROMOTERS: Numerous studies on the economic benefit of the use of antimicrobial growth promoters have been performed. The growth response is normally larger in young animals than in older animals. Large variations in the estimates have been observed, but in general a improvement in growth rate and feed utilisation has been observed. 14.6 SUSCEPTIBILITY AND RESISTANCE TO ANTIMICROBIAL GROWTH PROMOTERS: The definition of a bacterium as susceptible or resistant to an antimicrobial agent ultimately depends on clinical outcome. Since the exact mode of action of antimicrobial growth promoters are not known, the only way to define break points is based on the population distributions of susceptibilities to different agents. For antimicrobial agents used both for therapy and growth promotion the break points for therapy have been used. For avilamycin, avoparcin, flavomycin, monensin and salinomycin, that are used for growth promotion only, tentative break points based on population distributions have to be defined. The tentative break points for avoparcin and avilamycin have been confirmed by cross-resistance to other antimicrobial agents belonging to the same class and the presence of resistance mechanisms. 14.7 OCCURRENCE OF AND SELECTION FOR RESISTANCE TO ANTIMICROBIAL AGENTS USED FOR GROWTH PROMOTION: Information on the occurrence of resistance is needed to guide policy and detect changes that require intervention strategies. In 1995, a continuous monitoring of antimicrobial resistance in bacteria isolated from food animals was established in Denmark. Among food animals 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 MIC-determinations. In all known cases antimicrobial resistance has emerged following the introduction of new antimicrobial compounds for therapy. The occurrence of resistance to antimicrobial agents used for growth promotion indicates that resistance will also emerge following the introduction of antimicrobials for growth promotion. Comparison of the occurrence of resistance among reservoirs with different usage of antimicrobial agents for growth promotion also shows that the occurrence of resistance will follow the usage. (ABSTRACT TRUNCATED)

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丹麦用于促进食用动物生长的抗菌剂耐药性的发生、选择和传播。
引言:本论文基于丹麦兽医实验室发起的一系列监测和研究项目,目的是确定用于促进生长的抗菌剂耐药性的发生、选择和传播。本文简要概述了抗菌生长促进剂的使用、消费、功能和益处,并对使用这些药物引起的潜在耐药性问题进行了更全面的描述。14.2从历史的角度看抗菌剂的使用:在引入抗菌剂治疗人类和动物的细菌感染后不久,就观察到抗菌剂的生长促进作用,自20世纪50年代初以来,抗菌剂已被纳入食用动物的饲料中,作为提高生长和降低生产成本的一种方法。14.3抗菌生长促进剂的消费:用于临床和促进生长目的的抗菌药物消费的确切数字很难获得,只有少数国家的估计数字。在丹麦,用于促进生长的抗菌剂的年总消费量从1989年的67吨增加到1995年的116吨。在1995年禁止阿维帕素之后,生长促进剂的总消费量减少到94吨。1996年和1997年期间增加到107吨,但在1998年期间,消费量减少到大约49吨。不同国家的现有数据表明,用于促进生长的抗菌剂的使用量通常等于或超过用于治疗食用动物的抗菌剂的使用量。根据现有信息,可以估计,动物用抗菌剂的金融销售约占全球销售额的25%至35%,其中使用抗菌剂作为饲料添加剂至少占50%。14.4抗菌生长促进剂的作用方式:抗菌生长促进剂的作用方式尚不完全清楚。然而,据信其主要作用是减少肠道内细菌的生长,从而减少有益营养物质的微生物降解,并预防致病菌感染。14.5使用抗菌生长促进剂的好处:已经进行了许多关于使用抗菌生长促进剂的经济效益的研究。幼龄动物的生长反应通常比老年动物大。已观察到估计值有很大差异,但总的来说,已观察到生长率和饲料利用率有所改善。14.6对抗菌生长促进剂的敏感性和耐药性:细菌对抗菌药物敏感或耐药的定义最终取决于临床结果。由于抗菌生长促进剂的确切作用方式尚不清楚,定义断点的唯一方法是基于对不同药物的敏感性的群体分布。对于既用于治疗又用于促进生长的抗菌药物,已使用治疗的断点。对于仅用于促进生长的阿维霉素、阿维霉素、黄霉素、莫能菌素和盐霉素,必须根据种群分布确定暂定断点。阿沃帕素和阿维霉素的暂定断点已通过对属于同类的其他抗微生物药物的交叉耐药和耐药机制的存在得到证实。14.7用于促进生长的抗菌素耐药的发生和选择:需要关于耐药发生的信息来指导政策和发现需要干预策略的变化。1995年,丹麦对从食用动物中分离出来的细菌的抗微生物药物耐药性进行了连续监测。在食用动物中,从肉鸡、牛和猪中不断分离出三类细菌(指示细菌、人畜共患细菌和动物病原体),并通过盘扩散或mic测定法检测对用于治疗和促进生长的抗菌药物的敏感性。在所有已知病例中,在引入新的抗微生物化合物治疗后出现了抗微生物药物耐药性。对用于促进生长的抗微生物药物产生耐药性表明,在引入用于促进生长的抗微生物药物后也将出现耐药性。对不同促生长抗菌剂用量的水库耐药发生情况的比较也表明,耐药的发生随用量的增加而变化。(抽象截断)
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