Retrospective evidence for a biological cost of vancomycin resistance determinants in the absence of glycopeptide selective pressures

To estimate the relative fitness differences between glycopeptide-resistant Enterococcus faecium (GREF) and glycopeptide-susceptible E. faecium (GSEF) from yearly surveillance data on the occurrence of GREF in Danish poultry farm environments. A population genetic model was adapted to retrospectively estimate the biological fitness cost of acquired resistance. Maximization of a likelihood function was used to predict the longitudinal persistence of acquired resistance. Our analysis suggests strong selection against GREF following the 1995 ban on the glycopeptide growth promoter avoparcin. However, parameterizing the model with two selection coefficients suggesting a reduced negative effect of the acquired resistance on bacterial fitness over time significantly improved the fit of the model. Our analyses suggest that the acquired glycopeptide resistance will persist for >25 years. Conclusions Acquired resistance determinants in commensal E. faecium populations in Danish farm environments are likely to persist for decades, even in the absence of glycopeptide use

The path of least resistance: Paying for antibiotics in non-human uses

Antibiotic resistance is a critical threat to human and animal health. Despite the importance of antibiotics, regulators continue to allow antibiotics to be used in low-value applications - subtherapeutic dosing in animals, and spraying tobacco plants for blue mold, for example - where the benefits are unlikely to outweigh the costs in terms of increased resistance. We explore the application of a user fee in non-human uses of antibiotics. Such a fee would efficiently deter low value uses while also providing funding to support the development of the urgently needed new antibiotics

Excess Mortality Associated with Antimicrobial Drug-Resistant Salmonella Typhimurium

In a matched cohort study, we determined the death rates associated with drug resistance in Salmonella Typhimurium. We linked data from the Danish Surveillance Registry for Enteric Pathogens with the Civil Registration System and the Danish National Discharge Registry. By survival analysis, the 2-year death rates were compared with a matched sample of the general Danish population, after the data were adjusted for differences in comorbidity. In 2,047 patients with S. Typhimurium, 59 deaths were identified. Patients with pansusceptible strains of S. Typhimurium were 2.3 times more likely to die 2 years after infection than persons in the general Danish population. Patients infected with strains resistant to ampicillin, chloramphenicol, streptomycin, sulfonamide, and tetracycline were 4.8 times (95% CI 2.2 to 10.2) more likely to die, whereas quinolone resistance was associated with a mortality rate 10.3 times higher than the general population

Estratégias para melhorar o desempenho de leitões desmamados

Orientador : Prof. Dr. Alex MaiorkaCoorientador : Prof. Dr. Everton Luís KrabbeTese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Agrárias, Programa de Pós-Graduação em Ciências Veterinárias. Defesa: Curitiba, 23/02/2017Inclui referências : f. 59-83;103-109;120-124;142-145;164-169;172-208Área de concentração: Ciências VeterináriasResumo: O desmame de suínos nas condições comerciais modernas causa estresse (ambiental, nutricional, psicológico/social) e está associado com alterações marcantes na fisiologia, microbiologia e imunologia do trato gastrointestinal, sendo um período geralmente caracterizado por crescimento abaixo do ideal, eficiência alimentar prejudicada, elevada incidência de perturbações intestinais e mortalidade elevada. Dessa forma, o objetivo desta tese foi avaliar o uso de estratégias para melhorar o desempenho de leitões desmamados, abordando o uso de antibióticos promotores do crescimento (APC), bem como o processamento e forma física da dieta como alternativa ao seu uso. Para isso, a tese foi dividida em cinco capítulos. O capítulo 1 abrange uma revisão de literatura sobre o uso de APC e sobre o processamento da dieta para leitões desmamados. No capítulo 2 foi demonstrado que a colistina e tilosina, utilizados como APC para leitões desmamados, aumentaram significativamente o consumo de ração, resultando em maior peso corporal, além de promoverem redução significativa na incidência de diarreia e modularem a resposta imune. No capítulo 3 foi avaliado o uso da lincomicina como APC para leitões desmamados, a qual promoveu redução na incidência de diarreia dos leitões, mas não apresentou efeito sobre os parâmetros de desempenho avaliados. No capítulo 4 foi avaliada a influência de diferentes tipos de processamento e forma física da ração sobre o desempenho de leitões desmamados e sobre a digestibilidade da dieta. Não foram observados efeitos do processamento e forma física da ração sobre o ganho de peso e consumo de ração em leitões desmamados, mas verificou-se que a peletização a 2,5 mm proporcionou melhor conversão alimentar em comparação às dietas farelada e farelada condicionada, o que pode ser atribuído ao maior coeficiente de digestibilidade do extrato etéreo das dietas peletizadas. Não foi observado efeito do tamanho do pelete sobre os parâmetros de desempenho avaliados. No capítulo 5 foi avaliado o efeito de diferentes formas de processamento e forma física da dieta sobre a preferência alimentar de leitões desmamados e verificou-se que os mesmos influenciam a preferência alimentar dos animais. Leitões desmamados preferem dietas submetidas a algum tipo de processamento em comparação à dieta farelada simples, bem como preferem dietas peletizadas à fareladas, peletes de 2,5 mm em comparação à peletes de 4,75 mm (intactos ou triturados), e peletes de 4,75 mm triturados em comparação à peletes de 4,75 mm intactos, demonstrando que dietas processadas termicamente são mais palatáveis. No entanto, a preferência pela dieta peletizada não se refletiu em maior consumo da mesma em relação à farelada, provavelmente por fatores pós ingestivos, como mecanismos de retroalimentação. Estes resultados demonstram que o processamento térmico pode tornar a dieta mais atrativa e aumentar a digestibilidade de alguns nutrientes, o que pode reduzir o período de jejum pós-desmame e auxiliar na manutenção da função intestinal, podendo ser uma alternativa ao uso dos APC. Palavras-chave: Aditivos. Desmame. Peletização. Resistência bacteriana. Suínos.Abstract: Weaning pigs under modern commercial conditions causes stress (environmental, nutritional, psychological/social) and is associated with marked changes in physiology, microbiology and immunology of the gastrointestinal tract, being a period generally characterized by growth below ideal, impaired food efficiency, high incidence of intestinal disturbances and high mortality. Thus, the objective of this thesis was to evaluate the use of strategies to improve the performance of weaned piglets, addressing the use of antibiotic growth promoters (AGP), as well as the processing and physical form of the diet as an alternative to its use. For this, the thesis was divided into five chapters. Chapter 1 covers a literature review on the use of AGP and on diet processing for weaned piglets. In Chapter 2, it was demonstrated that colistin and tylosin, used as AGP for weaned piglets, significantly increased feed intake, resulting in a higher body weight, besides promoting a significant reduction in diarrhea incidence and modulation in the immune system. In Chapter 3, the use of lincomycin as an AGP for weaned piglets was evaluated, and this antibiotic promoted a reduction in the diarrhea incidence, but did not show any effect on the performance parameters evaluated. In Chapter 4 the influence of different types of processing and physical form of the diet on weaned piglets performance and on the diet digestibility, were evaluated. No effects of processing and physical form of the diet on weight gain and feed intake were observed in weaned piglets, but it was found that 2.5 mm pelleting resulted in better feed conversion compared to the mash and conditioned mash diets, which can be attributed to the higher digestibility coefficient of the ethereal extract of the pelleted diets. No effect of the pellet size was observed on the evaluated performance parameters. In Chapter 5 the effect of different forms of processing and physical form of the diet on the feeding preference of weanling piglets were evaluated, and it was verified that they influence the animals feeding preference. Weaned piglets prefer diets subjected to some sort of processing compared to simple mash diets, as well as prefer pelleted diets to mash diets, 2.5 mm pellets compared to 4.75 mm pellets (intact or crumbled), and crumbled pellets of 4.75 mm compared to intact pellets of 4.75 mm, demonstrating that thermally processed diets are more palatable. However, the preference for the pelleted diet was not reflected in the higher intake of the same in relation to the meal diet, probably by post ingestive factors, as feedback mechanisms. These results demonstrate that thermal processing may make the diet more attractive and increase the digestibility of some nutrients, which may reduce the postweaning fasting period and help maintain intestinal function, and may be an alternative to AGP use. Key-words: Additives. Bacterial resistance. Pelletizing. Swine. Weaning

Antimicrobial Resistance: the use of antimicrobials in the Livestock Sector

The use of antimicrobials in livestock production provides a basis for improving animal health and productivity. This in turn contributes to food security, food safety, animal welfare, protection of livelihoods and animal resources. However, there is increasing concern about levels of antimicrobial resistance in bacteria isolated from human, animal, food and environmental samples and how this relates to use of antimicrobials in livestock production. The report examines antimicrobial usage in livestock and its impact on public health and the food economy. Policy issues and knowledge gaps to manage antimicrobial use and the risk of antimicrobial resistance are identified and discussed

Resistência antimicrobiana em populações animais e seu impacto na saúde pública : uma revisão da literatura

Ao longo dos anos, os antimicrobianos (ATM) têm sido utilizados pela população humana e animal como uma ferramenta contra infecções. Entretanto, com o passar do tempo, percebeu-se que os microrganismos possuem mecanismos de adaptação aos fármacos e, a partir disso, conseguem adquirir resistência aos medicamentos usados. Ao adquirir resistência, a gama de ATM que são eficazes acaba diminuindo e causando uma série de prejuízos, como por exemplo, o aumento no número de morte em humanos, além do aumento dos recursos investidos nos sistemas de saúde para contornar essa situação. Estudos afirmam que ATM usados na produção animal, especialmente os promotores de crescimento, podem estar relacionados com o desenvolvimento de microrganismos resistentes que afetam os seres humanos. A transmissão de bactérias resistentes, patogênicas ou não patogênicas, mas que têm a capacidade de transferir genes de resistência para outras bactérias, pode ocorrer através da alimentação, contato direto com os animais ou pelo meio ambiente. Entretanto, esse problema é muito complexo, envolve vários fatores e a questão não foi, ainda, completamente esclarecida. Visando diminuir o avanço da resistência antimicrobiana (RAM), algumas medidas de prevenção e controle adotadas por vários países e estimuladas por organizações internacionais abrangem o desenvolvimento de sistemas de vigilância, a utilização consciente de ATM e o fim da utilização desses fármacos como promotores de crescimento. Assim, este trabalho tem como objetivo revisar, com base em dados publicados na literatura científica, os principais pontos referentes à resistência antimicrobiana na população humana e animal. Para isso, serão abordados os mecanismos biológicos envolvidos no processo de resistência antimicrobiana, seu impacto na saúde pública e as medidas propostas para a prevenção e controle adotadas por alguns países e organismos internacionais. O aumento da resistência antimicrobiana é um assunto muito preocupante e esforços estão sendo realizados com o objetivo de buscar alternativas para combater este problema.Over the years, antimicrobials (ATM) have been used by the human and animal population as a tool against infections. Over time, however, it has been observed that microorganisms have mechanisms of adaptation to the drugs and they are able to acquire resistance to the drugs used. By acquiring resistance, the range of ATM that are effective decreases and causes a number of losses, such as an increase in the number of deaths in humans, as well as increased resources invested in health systems to circumvent this situation. Studies indicate that ATM used in animal production, especially growth promoters, may be related to the development of resistant microorganisms that affect humans. Transmission of resistant bacteria, pathogenic or non-pathogenic, but which have the ability to transfer resistance genes to other bacteria, may occur through feeding, direct contact with animals or through the environment. However, this problem is very complex, involves several factors and the question has not yet been fully clarified. In order to reduce antimicrobial resistance, several prevention and control measures adopted by several countries and stimulated by international organizations cover the development of surveillance systems, the conscious use of ATM and the end of the use of these drugs as growth promoters . Thus, this work aims to review, based on data published in the scientific literature, the main points regarding antimicrobial resistance in the human and animal population. To this end, the biological mechanisms involved in the antimicrobial resistance process, its impact on public health and the proposed measures for prevention and control adopted by some countries and international organisms will be addressed. The increase in antimicrobial resistance is a very worrying subject and efforts are being made to find alternatives to combat this problem

A survey of antimicrobial usage in animals in South Africa with specific reference to food animals

The purpose of this work was to set a benchmark for a monitoring and surveillance programme on the volumes of the eighteen classes of antimicrobials available and consumed by animals for the benefit of animal health in South Africa. In setting up such a programme, risk assessment and possible management and communication strategies of the potential health risks emanating from antimicrobial resistance in bacteria from animals and man were considered and the survey was compared with other overseas surveillance programmes established in Sweden, Denmark, the United Kingdom and Australia. The aim of the study was to contribute to the establishment of future surveillance programmes that will provide direction for the prudent and rational use of antimicrobials, involving all the relevant stake-holders, in order to preserve the future efficacy of those antimicrobials that are currently available. Such programmes will harmonize with international initiatives and contribute to the provision of databases for policy recommendations in South Africa. There are several benefits to the implementation of such surveys and addressing topical and relevant issues of antimicrobial use in the domain of animal health and its possible impact on human health. Furthermore, policy decisions to address concerns regarding antimicrobial resistance may be reached in a more informed and judicious manner, with the aim that the efficacy of available antimicrobials may be preserved for use in future generations of humans and animals. The authorized antimicrobials available in South Africa were firstly reviewed and compared with the volumes of antimicrobials supplied by the veterinary pharmaceutical companies. The majority of antimicrobials were registered under the Stock Remedies Act 36 of 1947. It was found that the class of antimicrobial representing the most registered products was the tetracyclines, followed by the penicillins, the sulphonamides, macrolides, lincosamides and pleuromutilins. This correlated well with the volumes of antimicrobials supplied, as these classes of antimicrobials also represented the top four groups of antimicrobials consumed. Eight of the pool of twenty-five veterinary pharmaceutical companies approached provided more detailed information on the volumes of antimicrobials consumed for the years under review, namely 2002 to 2004. The potency of antimicrobials was also requested, in order to establish trends of increasing or decreasing potency of the active ingredients, versus the volumes of antimicrobials supplied. It was established within the scope of this study, that the majority of consumed antimicrobials was from the classes of macrolides, lincosamides, and pleuromutilins, followed by the tetracycline class, the sulphonamide group and fourthly the penicillins. The potency of the active ingredients supplied by the companies did not change and therefore had no impact on the interpretation of antimicrobials consumed. These results give cause for concern in terms of the possibility of cross-resistance between antimicrobials used in the domain of animal health, and those used in the human medical field. There is also another concern, namely the exposure of humans to veterinary drug residues in food, causing modifications in the bacterial ecology of the human gut, thereby leading to a possible perturbation in the protective human gut barrier with overgrowth and invasion of pathogenic bacteria. Although much has been written about the possibility of anaphylactic reactions occurring in sensitized human individuals from â-lactams and macrolides administered in food animals, this issue has been reviewed extensively and it has been concluded that allergies from antimicrobial residues in the diet are extremely rare. The macrolide tylosin was the most extensively sold antimicrobial of all. Tylosin is one of four antimicrobials that was banned by the EU in 1999 because of its structural relatedness to therapeutic antimicrobials used for the treatment of disease in human medicine. The other three classes mentioned above, the penicillins, tetracyclines and sulphonamides are also relevant because of well-documented evidence of the ability to select for resistance or because of their structural relatedness to human therapeutic antimicrobials and their use in humans. The value of sales of antimicrobials were provided by SAAHA (South Africa Animal Health Association) and also scrutinized within the context of this study in order to obtain meaningful data on the national consumption of antimicrobials. However, as discussed in Chapter 5, the data were not of any value within the context of this study because the sales data were provided in monitory terms only. Volumes of sales of feed were also obtained and companies that mix feed approached to ascertain the percentages of antimicrobial medicated feeds consumed. It was ascertained in this survey that 68,5% of the grand total of antimicrobials surveyed during 2002 to 2004, were administered as in-feed medications. Tylosin was the most extensively used in-feed antimicrobial, followed by oxytetracycline, zinc bacitracin and olaquindox. This result emphasizes the importance of establishing a monitoring programme for the volumes of antimicrobials used, as many growth promoters used in-feed are administered at sub-therapeutic levels over long periods of time that tend to select for antimicrobial resistance. Whereas 17,5% of the total volume of antimicrobials utilized were parenteral antimicrobials, antimicrobials for water medication constituted 12% of the total. “Other” dosage forms such as the topical, aural, ophthalmic, and aerosol antimicrobials and intra-uterine pessaries and tablets constituted 1,5% of the total. Intramammary antimicrobials represented 0,04% of the total. In Chapters 1, 5&6 the surveillance systems for veterinary antimicrobials used by other countries are discussed and compared. It was concluded that a combination of the surveillance systems applied by Australia and the United Kingdom is the best model (with modifications) to apply to the animal health situation in South Africa. Such a surveillance system of the volumes of veterinary antimicrobials consumed should ideally be implemented in conjunction with a veterinary antimicrobial resistance surveillance and monitoring programme to generate meaningful data that will contribute to the rational use of antimicrobials in order to preserve the efficacy of the existing antimicrobials in South Africa. Possible trends of antimicrobial usage in animals may be uncovered over time from implementing a programme for the volumes of antimicrobials used and thereby lead to proactive application of rational policies for the veterinary use of antimicrobials. This information can also be compared with international data, in order to harmonize as much as possible with global monitoring programmes of veterinary antimicrobial usage. CopyrightDissertation (MMedVet)--University of Pretoria, 2008.Paraclinical Sciencesunrestricte