Addlestone, United Kingdom
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Van Duijkeren E.,National Institute for Public Health and the Environment | Greko C.,National Veterinary Institute | Pringle M.,National Veterinary Institute | Baptiste K.E.,Danish Health and Medicines Authority | And 12 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2014

Pleuromutilins (tiamulin and valnemulin) are antimicrobial agents that are used mainly in veterinary medicine, especially for swine and to a lesser extent for poultry and rabbits. In pigs, tiamulin and valnemulin are used to treat swine dysentery, spirochaete-associated diarrhoea, porcine proliferative enteropathy, enzootic pneumonia and other infections where Mycoplasma is involved. There are concerns about the reported increases in the MICs of tiamulin and valnemulin for porcine Brachyspira hyodysenteriae isolates from different European countries, as only a limited number of antimicrobials are available for the treatment of swine dysentery where resistance to these antimicrobials is already common and widespread. The loss of pleuromutilins as effective tools to treat swine dysentery because of further increases in resistance or as a consequence of restrictions would present a considerable threat to pig health, welfare and productivity. In humans, only one product containing pleuromutilins (retapamulin) is authorized currently for topical use; however, products for oral and intravenous administration to humans with serious multidrug-resistant skin infections and respiratory infections, including those caused by methicillin-resistant Staphylococcus aureus (MRSA), are being developed. The objective of this review is to summarize the current knowledge on the usage of pleuromutilins, resistance development and the potential impact of this resistance on animal and human health. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

De Briyne N.,Federation of Veterinarians of Europe | Atkinson J.,Veterinary Medicines Directorate | Borriello S.P.,Veterinary Medicines Directorate | Pokludova L.,Institute for State Control of Veterinary Biologicals and Medicines
Veterinary Record | Year: 2014

The Heads of Medicines Agencies and the Federation of Veterinarians of Europe undertook a survey to gain an insight into European prescribing of antibiotics for animals, in particular to highlight the diseases for which antibiotics are most commonly said to be prescribed and which different classes, including human critically important antibiotics (CIAs). The survey was completed by 3004 practitioners from 25 European countries. Many older antibiotics (eg, penicillins, tetracyclines) are cited most frequently as the prescribed classes to treat the main food producing species. The frequency of citation of non-CIAs predominates. CIAs are mostly frequently cited to be prescribed for: urinary diseases in cats (62 per cent), respiratory diseases in cattle (45 per cent), diarrhoea in cattle and pigs (respectively 29 per cent and 34 per cent), locomotion disorders in cattle (31 per cent), postpartum dysgalactia syndrome complex in pigs (31 per cent) and dental disease in dogs (36 per cent). Clear 'preferences' between countries can be observed between antibiotic classes. The use of national formularies and guidance helps to drive responsible use of antibiotics and can significantly reduce the extent of use of CIAs. A more widespread introduction of veterinary practice antibiotic prescribing policies and monitoring obedience to these should ensure more widespread compliance with responsible use guidelines.

PubMed | National Institute for Public Health and the Environment, Royal Veterinary College University of London, Agence Nationale de Securite Sanitaire ANSES, Public Health England and 11 more.
Type: | Journal: The Journal of antimicrobial chemotherapy | Year: 2016

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.

Heinrich K.,UK Environment Agency | Chan D.,UK Environment Agency | Fussell R.J.,UK Environment Agency | Kay J.F.,Veterinary Medicines Directorate | Sharman M.,UK Environment Agency
Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment | Year: 2013

Ceftiofur is a third-generation cephalosporin antibiotic used to treat cattle and swine for bacterial infection of the respiratory tract. It is not authorised for use in poultry within the European Union. Due to the complexity of the chemistry and metabolism of ceftiofur, maximum residue limits (MRLs) are based on desfuroylceftiofur (DFC) equivalents after chemical conversion of all compounds that have an intact ß-lactam ring. In practice the DFC is usually stabilised as the acetamide (desfuroylceftiofur acetamide - DFCA) for analysis. Because of recent evidence of off-label use in the European Union, a policy need emerged to develop a cost-effective method for the detection of ceftiofur residues in poultry tissues. One-day-old chicks were each dosed subcutaneously with ceftiofur and samples taken from day 1 to day 44 post-dosing. Residues of ceftiofur parent compound were detected in whole chicks, wing feathers and faeces. On the basis of this finding it was decided to evaluate ceftiofur parent, as the marker, instead of proceeding with the time-consuming conversion to DFCA. Expected metabolites, DFC and desfuroylceftiofur cysteine disulfide (DCCD), were not detected in whole chicks, muscle or liver, but DFC was found in wing feathers. These results indicate that determination of ceftiofur parent compound in either whole chicks or possibly wing feathers and faeces may allow the detection of the misuse of ceftiofur. © 2013 Copyright Crown copyright.

Scarth J.,A Quotient Bioresearch Ltd. Company | Clarke A.,A Quotient Bioresearch Ltd. Company | Hands J.,A Quotient Bioresearch Ltd. Company | Teale P.,A Quotient Bioresearch Ltd. Company | And 2 more authors.
Chromatographia | Year: 2010

A quantitative multi-residue LC- and GC-MS-MS based assay was validated for the analysis of endogenous androgens, progestagens and oestrogens in bovine urine. The method is targeted at analytes indicative of the abuse of nandrolone, boldenone, testosterone, progesterone and oestradiol in cattle. Using a single aliquot of urine, androgens and progestagens are extracted for analysis by GC-MS-MS on a Varian 320 instrument using an enol-TBDMS derivative, while oestrogens are removed into a separate fraction using an extraction derivatisation with dansyl chloride and analysed using LC-MS-MS on a Sciex 5000 instrument. Using a standard addition calibration line approach in pooled bovine urine, the method was found to be sensitive, with limits of detection ranging from 10.9 to 160.7 pg mL-1, and was linear between the endogenous concentrations and those augmented with 3,000 pg mL-1. The method is now being applied to large numbers of animals from controlled populations in order to establish thresholds for detecting the abuse of these steroids in food production. © 2009 Vieweg+Teubner | GWV Fachverlage GmbH.

Scarth J.P.,HFL Sport Science | Clarke A.,HFL Sport Science | Teale P.,HFL Sport Science | Mill A.,UK Environment Agency | And 2 more authors.
Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment | Year: 2011

The use of steroids as growth-promoting agents in food production is banned under European Union legislation. Detecting the abuse of testosterone, nandrolone, boldenone, oestradiol and progesterone is complicated by the fact that these steroids are known to be endogenous in certain situations. In this study, the concentrations of characteristic metabolites of each of these steroids were quantified in populations of untreated steers and heifers. Steroid concentration population data were then used by a statistical model (the Chebyshev inequality) to produce threshold concentrations for screening and confirming the abuse of these steroids in steer and nonpregnant heifer urine. In addition to thresholds based on testing one animal (a '1 out of 1' approach), new methods based on testing multiple animals from a herd (a 'y out of n' approach) allowed threshold concentrations to be significantly reduced and hence false compliances to be minimised. In the majority of cases, the suggested thresholds were found to be capable of confirming the abuse of endogenous steroids in steers and heifers. In the case of oestradiol abuse in the female, however, confirmation based on a threshold is not possible and alternative methods such as gas chromatography-combustion-isotope ratio mass spectrometry are required. In addition to the steer and heifer populations, a small number of pregnant animals were also tested, yielding insights into the biosynthetic pathways of some of the steroids. © 2011 Taylor & Francis.

Stead S.L.,UK Environment Agency | Ashwin H.,UK Environment Agency | Johnston B.,Somagenics, Inc. | Tarbin J.A.,UK Environment Agency | And 3 more authors.
Analytical Chemistry | Year: 2010

A robust screening assay employing solid phase extraction (SPE) followed by a novel aptamer-based procedure is presented for the rapid detection and semiquantitation of the triphenylmethane dye, Malachite Green (MG) and its primary metabolite Leucomalachite Green (LMG) in fish tissue. To the authors' knowledge, this is the first reported use of an RNA aptamer for the development of a diagnostic assay for the detection of chemical residues in food. The aptamer based screening assay is found to be highly specific for MG; but has negligible affinity for the LMG metabolite. However, because the LMG metabolite is lipophilic and known to be highly persistent in tissues, an oxidation step has been incorporated within the sample cleanup procedure to ensure that all LMG residues are converted to MG prior to measurement. This article provides evidence that an oligonucleotide aptamer can be used as an alternative recognition element to conventional antibodies with application to the detection of residues in food. Furthermore, this finding has the future potential to reduce the number of animals currently being used in the production of antibodies for immunodiagnostic kits. © 2010 American Chemical Society.

Stephens M.J.,Veterinary Medicines Directorate | Church D.B.,Royal Veterinary College University of London | Thomson P.C.,University of Sydney
Veterinary Record | Year: 2014

Feline hyperthyroidism is a commonly diagnosed endocrinopathy that can have a substantial deleterious impact on the welfare of affected cats. This study aimed to estimate the prevalence, associated factors and geographical distribution for feline hyperthyroidism in England, using primary-care veterinary practice clinical data from the VetCompass Animal Surveillance Project. Prevalence was estimated from the overall cat cohort. Associated factor analysis used an age-matched, nested, case-control design with multivariable logistic regression. There were 2,276 cases of feline hyperthyroidism identified from 95,629 cats attending 84 practices from September 2009 to December 2011. Cases were aged 6-25 years. 3.7 per cent of cases and 9.9 per cent of controls were purebred, 56.4 per cent of cases and 56.5 per cent of controls were female, and 88.1 per cent of cases and 86.0 per cent of controls were neutered. The apparent prevalence was 2.4 per cent (95% CI 2.3 to 2.5 per cent) overall, and 8.7 per cent (95% CI 8.3 to 9.0 per cent) in cats aged 10 years or above. Burmese (OR 0.15, 95% CI 0.07 to 0.32, P<0.0001), Persian (OR 0.17, 95% CI 0.08 to 0.33, P<0.0001), Siamese (OR 0.4, 95% CI 0.21 to 0.75, P=0.004) and purebred cats overall (OR 0.33, 95% CI 0.25 to 0.42, P<0.0001) had lower odds of feline hyperthyroidism than non-purebred cats. Insured cats had increased odds (OR 1.78, 95% CI 1.56 to 2.03, P<0.001). There was little evidence of spatial variation. This study highlights feline hyperthyroidism as a high-prevalence disease in England, and reports reduced odds of diagnosis in certain breeds and purebred cats overall.

European technical requirements for veterinary vaccines are laid down in Annex 1, Title II, to Directive 2001/82/EC, as amended by Directive 2009/9/EC, and the European Pharmacopoeia (Ph. Eur.). Safety tests carried out on each batch are generally overdosage studies carried out in at least one of the most sensitive target species and by at least the recommended route of administration that poses the greatest risk. The dose administered should preferably be twice the standard dose for inactivated vaccines and ten times the standard dose for live vaccines. Each batch must also be tested to show that it will contain the appropriate potency or titer to ensure its safety and efficacy. Live vaccines are usually tested by in vitro titration, while serological or challenge tests in vaccinated animals are commonly used for inactivated vaccines, although alternative methods are encouraged if satisfactorily validated. Several amendments have been introduced into the Ph. Eur. to facilitate reduction in the severity of tests and the numbers of animals used, including: the ability to waive the batch safety test when consistency of production has been established; in vitro methods to test for extraneous viruses in live poultry vaccines; and humane endpoints for rabies vaccine potency tests. This report discusses some preliminary conclusions concerning how these changes have affected the numbers of animals used during batch control testing of vaccines released via the UK batch release scheme. © 2011.

Woodland R.,Veterinary Medicines Directorate
Developments in biologicals | Year: 2012

The biological nature of IVMPs leads to some unavoidable batch to batch variation in production. The potency test is part of the quality control of the finished product intended to confirm consistency of production and that each batch is formulated equivalent to batches that have been demonstrated to be efficacious. Adequate validation of potency tests is essential to ensure that the results of the assays accurately reflect the amount, titre, or potency of the active substance measured and to indicate the limitations on the accuracy of the measurements to be expected from the test used. The CVMP/IWP published their conclusions concerning validation of potency tests in a Reflection Paper in March 2010. The test validation must demonstrate a dose response and the precision of the result should enable reliable detection of a sub-standard batch. However, the inherent variability in experimental animals often leads to unacceptably wide confidence intervals for in vivo tests which limits their ability to detect slight changes of the antigen amount. The development of in vitro methods as alternatives to in vivo potency tests is encouraged.

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