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DANMAP 2016 - Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, food and humans in Denmark

TL;DR: Borck Høg, Birgitte; Korsgaard, Helle Bisgaard; Wolff Sönksen, Ute; Torpdahl, Mia; Vorobieva, Veronika as mentioned in this paper.
Abstract: Borck Høg, Birgitte; Korsgaard, Helle Bisgaard; Wolff Sönksen, Ute; Bager, Flemming; Bortolaia, Valeria; Ellis-Iversen, Johanne; Hendriksen, Rene S.; Borck Høg, Birgitte; Jensen, Lars Bogø; Korsgaard, Helle Bisgaard; Pedersen, Karl; Dalby, Tine; Træholt Franck, Kristina ; Hammerum, Anette M; Hasman, Henrik; Hoffmann, Steen; Gaardbo Kuhn, Katrin; Rhod Larsen, Anders; Larsen, Jesper; Møller Nielsen, Eva; Schytte Olsen, Stefan; Petersen, Andreas; Roer, Louise; Skovgaard, Sissel; Wolff Sönksen, Ute; Torpdahl, Mia; Vorobieva, Veronika

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Citations
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Journal ArticleDOI
TL;DR: WHO recently has launched new guidelines on the use of medically important antimicrobials in food-producing animals, recommending that farmers and the food industry stop using antimicroBials routinely to promote growth and prevent disease in healthy animals.
Abstract: One Health is the collaborative effort of multiple health science professions to attain optimal health for people, domestic animals, wildlife, plants, and our environment. The drivers of antimicrobial resistance include antimicrobial use and abuse in human, animal, and environmental sectors and the spread of resistant bacteria and resistance determinants within and between these sectors and around the globe. Most of the classes of antimicrobials used to treat bacterial infections in humans are also used in animals. Given the important and interdependent human, animal, and environmental dimensions of antimicrobial resistance, it is logical to take a One Health approach when addressing this problem. This includes taking steps to preserve the continued effectiveness of existing antimicrobials by eliminating their inappropriate use and by limiting the spread of infection. Major concerns in the animal health and agriculture sectors are mass medication of animals with antimicrobials that are critically important for humans, such as third-generation cephalosporins and fluoroquinolones, and the long-term, in-feed use of medically important antimicrobials, such as colistin, tetracyclines, and macrolides, for growth promotion. In the human sector it is essential to prevent infections, reduce over-prescribing of antimicrobials, improve sanitation, and improve hygiene and infection control. Pollution from inadequate treatment of industrial, residential, and farm waste is expanding the resistome in the environment. Numerous countries and several international agencies have included a One Health approach within their action plans to address antimicrobial resistance. Necessary actions include improvements in antimicrobial use regulation and policy, surveillance, stewardship, infection control, sanitation, animal husbandry, and alternatives to antimicrobials. WHO recently has launched new guidelines on the use of medically important antimicrobials in food-producing animals, recommending that farmers and the food industry stop using antimicrobials routinely to promote growth and prevent disease in healthy animals. These guidelines aim to help preserve the effectiveness of antimicrobials that are important for human medicine by reducing their use in animals.

489 citations

Journal ArticleDOI
TL;DR: The toxicological data of TCs indicate that several TCs are more toxic to algae than fish and daphnia, and risk assessments based on individual compound exposure indicate that the risks arising from the current concentrations ofTCs in the aquatic environment cannot be ignored.

384 citations

Journal ArticleDOI
TL;DR: In the face of the previously recognized microbiological hazards, a risk assessment tool could be applied in applications for marketing authorization for medicinal products for companion animals to allow the approval of new veterinary medicinal antimicrobials for which risk levels are estimated as acceptable for public health.
Abstract: Antimicrobials are important tools for the therapy of infectious bacterial diseases in companion animals. Loss of efficacy of antimicrobial substances can seriously compromise animal health and welfare. A need for the development of new antimicrobials for the therapy of multiresistant infections, particularly those caused by Gram-negative bacteria, has been acknowledged in human medicine and a future corresponding need in veterinary medicine is expected. A unique aspect related to antimicrobial resistance and risk of resistance transfer in companion animals is their close contact with humans. This creates opportunities for interspecies transmission of resistant bacteria. Yet, the current knowledge of this field is limited and no risk assessment is performed when approving new veterinary antimicrobials. The objective of this review is to summarize the current knowledge on the use and indications for antimicrobials in companion animals, drug-resistant bacteria of concern among companion animals, risk factors for colonization of companion animals with resistant bacteria and transmission of antimicrobial resistance (bacteria and/or resistance determinants) between animals and humans. The major antimicrobial resistance microbiological hazards originating from companion animals that directly or indirectly may cause adverse health effects in humans are MRSA, methicillin-resistant Staphylococcus pseudintermedius, VRE, ESBL- or carbapenemase-producing Enterobacteriaceae and Gram-negative bacteria. In the face of the previously recognized microbiological hazards, a risk assessment tool could be applied in applications for marketing authorization for medicinal products for companion animals. This would allow the approval of new veterinary medicinal antimicrobials for which risk levels are estimated as acceptable for public health.

235 citations

Journal Article
TL;DR: For most bacterial species there is currently insufficient evidence to support the use of WGS-inferred AST to guide clinical decision making, so W GS-AST should be a funding priority if it is to become a rival to phenotypic AST.

210 citations

Journal ArticleDOI
TL;DR: A combination of compulsory and voluntary actions with clear reduction goals resulted in a 56% reduction in antimicrobial use in farm animals in the Netherlands between 2007 and 2012 and aims at accomplishing a 70% reduction target in 2015.
Abstract: Use of antimicrobials in animals poses a potential risk for public health as it contributes to the selection and spread of antimicrobial resistance. Although knowledge of the negative consequences of extensive antimicrobial use in humans and animals accumulated over the decades, total therapeutic antimicrobial use in farm animals in the Netherlands doubled between 1990 and 2007. A series of facts and events formed a window of opportunity to reduce antimicrobial use in farm animals. The recent discovery of significant reservoirs of antimicrobial-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and extended spectrum beta-lactamase-producing bacteria (ESBL) in farm animals, with potential public health implications, combined with an increasing lack of confidence of the public in intensive livestock industries, and discrepancy between the very low antimicrobial use in humans and high use in animals, resulted in intensive collaboration between the government, veterinary professional organizations and important stakeholders within the livestock sector. A combination of compulsory and voluntary actions with clear reduction goals resulted in a 56% reduction in antimicrobial use in farm animals in the Netherlands between 2007 and 2012 and aims at accomplishing a 70% reduction target in 2015. This article describes and analyses the processes and actions behind this transition from an abundant antimicrobial use in farm animals towards a more prudent application of antimicrobials in farm animals in the Netherlands.

204 citations

References
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TL;DR: An increase in the frequency of azole-resistant Aspergillus fumigatus has emerged and it is feared that this phenomenon may be linked to the spread of E.coli.
Abstract: Azoles are the mainstay of oral therapy for aspergillosis. Azole resistance in Aspergillus has been reported infrequently. The first resistant isolate was detected in 1999 in Manchester, UK. In a clinical collection of 519 A. fumigatus isolates, the frequency of itraconazole resistance was 5%, a significant increase since 2004 (p<0.001). Of the 34 itraconazole-resistant isolates we studied, 65% (22) were cross-resistant to voriconazole and 74% (25) were cross-resistant to posaconazole. Thirteen of 14 evaluable patients in our study had prior azole exposure; 8 infections failed therapy (progressed), and 5 failed to improve (remained stable). Eighteen amino acid alterations were found in the target enzyme, Cyp51A, 4 of which were novel. A population genetic analysis of microsatellites showed the existence of resistant mutants that evolved from originally susceptible strains, different cyp51A mutations in the same strain, and microalterations in microsatellite repeat number. Azole resistance in A. fumigatus is an emerging problem and may develop during azole therapy.

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24 Aug 2011
Abstract: Invasive aspergillosis due to multi-azole-resistant Aspergillus fumigatus has emerged in the Netherlands since 1999, with 6.0-12.8% of patients harbouring resistant isolates. The presence of a single resistance mechanism (denoted by TR/L98H), which consists of a substitution at codon 98 of cyp51A and a 34-bp tandem repeat in the gene-promoter region, was found in over 90% of clinical A fumigatus isolates. This is consistent with a route of resistance development through exposure to azole compounds in the environment. Indeed, TR/L98H A fumigatus isolates were cultured from soil and compost, were shown to be cross-resistant to azole fungicides, and genetically related to clinical resistant isolates. Azoles are abundantly used in the environment and the presence of A fumigatus resistant to medical triazoles is a major challenge because of the possibility of worldwide spread of resistant isolates. Reports of TR/L98H in other European countries indicate that resistance might already be spreading.

438 citations

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TL;DR: Azole resistance in Aspergillus fumigatus has now been reported from 6 continents and is emerging as a global health problem.
Abstract: Azole resistance in Aspergillus fumigatus has emerged as a global health problem. Although the number of cases of azole-resistant aspergillosis is still limited, resistance mechanisms continue to emerge, thereby threatening the role of the azole class in the management of diseases caused by Aspergillus. The majority of cases of azole-resistant disease are due to resistant A. fumigatus originating from the environment. Patient management is difficult due to the absence of patient risk factors, delayed diagnosis, and limited treatment options, resulting in poor treatment outcome. International and collaborative efforts are required to understand how resistance develops in the environment to allow effective measures to be implemented aimed at retaining the use of azoles both for food production and human medicine.

436 citations

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TL;DR: A new formula is presented that calculates the exact probability of detecting diseased animals, and considers both imperfect tests and finite population size, and enables the accurate calculation of survey sample-size requirements, and the precise analysis of survey results.

309 citations

Journal ArticleDOI
TL;DR: The study confirmed an incidence rate of fungemia in Denmark three times higher than those in other Nordic countries and identified marked differences related to age and gender.
Abstract: A 6-year nationwide study of fungemia in Denmark was performed using data from an active fungemia surveillance program and from laboratory information systems in nonparticipating regions. A total of 2,820 episodes of fungemia were recorded. The incidence increased from 2004 to 2007 (7.7 to 9.6/100,000) and decreased slightly from 2008 to 2009 (8.7 to 8.6/100,000). The highest incidences were seen at the extremes of age (i.e., 11.3 and 37.1/100,000 for those 50 years of age. The species distribution varied significantly by both age and gender. Candida species accounted for 98% of the pathogens, and C. albicans was predominant, although the proportion decreased (64.4% to 53.2%, P 4 μg/ml) occurred in C. albicans (7/1,183 [0.6%]), C. dubliniensis (2/65 [3.1%]), C. parapsilosis (5/83 [6.0%]), and C. tropicalis (7/104 [6.7%]). Overall, 70.8% of fungemia isolates were fully fluconazole susceptible, but the proportion decreased (79.7% to 68.9%, P = 0.02). The study confirmed an incidence rate of fungemia in Denmark three times higher than those in other Nordic countries and identified marked differences related to age and gender. Decreased susceptibility to fluconazole was frequent and increasing.

226 citations

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