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Assignment of Canadian Defined Daily Doses and Canadian Defined Course Doses for Quantification of Antimicrobial Usage in Cattle.

ABSTRACT: Standardized units are essential to allow quantification and comparison of antimicrobial usage (AMU) between species and regions. In Canada, defined daily and course doses have not yet been harmonized for cattle. Our objective was to assign defined daily and course doses (named DDDbovCA and DCDbovCA, respectively) for cattle in Canada, by antimicrobial agent (AM) and by route of administration, based on the label of all products containing at least one AM, marketed and authorized in Canada for use in cattle. In April and December 2019, a systematic search was performed from the online Drug Product Database (DPD) of Health Canada to identify veterinary products containing at least one AM, marketed in Canada for use in cattle. Products were divided by route of administration (intramammary, intrauterine, injectable, oral, and topical). The monograph was retrieved for each product from the DPD, or from the Canadian Edition of the Compendium of Veterinary Products (CVP), and read completely to extract recommended dosages in cattle. Standard weights were applied to compute doses if required. DDDbovCA and DCDbovCA were assigned by calculating an average of daily and course doses, respectively, by AM and route of administration. Two products were excluded from calculations because of their claim as growth promotion or feed efficiency (no longer authorized in Canada for certain categories of AM). Overall, 39 injectable, 75 oral (including 23 medicated premixes), 8 intramammary (4 for lactating cows and 4 for dry cows), 5 intrauterine, and 4 topical products were used for calculations. DDDbovCA and DCDbovCA values were assigned successfully for each AM identified, by route of administration. These metrics will allow harmonized and transparent quantification of AMU in cattle in Canada.

SUBMITTER: Larde H

PROVIDER: S-EPMC7001643 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Assignment of Canadian Defined Daily Doses and Canadian Defined Course Doses for Quantification of Antimicrobial Usage in Cattle.

Lardé Hélène H Dufour Simon S Archambault Marie M Léger David D Loest Daleen D Roy Jean-Philippe JP Francoz David D

Frontiers in veterinary science 20200129

Standardized units are essential to allow quantification and comparison of antimicrobial usage (AMU) between species and regions. In Canada, defined daily and course doses have not yet been harmonized for cattle. Our objective was to assign defined daily and course doses (named DDDbovCA and DCDbovCA, respectively) for cattle in Canada, by antimicrobial agent (AM) and by route of administration, based on the label of all products containing at least one AM, marketed and authorized in Canada for u ...[more]

PMID: 32083099

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Project description:Introduction: While treatment frequency as an indicator of antimicrobial consumption is often assessed using defined doses, it can also be calculated directly as an Animal Treatment Index (ATI). In this study, the correlation of calculating antimicrobial usage on Swiss pig farms using either national Defined Daily Doses (DDDch) or an ATI (number of treatments per animal per year) and the agreement between the different methods for the identification of high usage farms were investigated. Material and Methods: The antimicrobial consumption of 893 Swiss pig herds was calculated separately for suckling piglets, weaned piglets, fattening pigs, lactating and gestating sows using the indicators nDDDch (number of DDDch) per animal per year and ATI. Correlations between the indicators were investigated by calculating Spearman's Rho coefficients. The 5, 10, and 25% highest usage farms were determined by applying both methods and the interrater reliability was described using Cohen's Kappa coefficients and visualized by Bland-Altman plots. Results: The Spearman's Rho coefficients showed strong correlations (r > 0.5) between nDDDch/animal/year and ATI. The lowest coefficient was shown for the correlation of both indicators in gestating sows (r = 0.657) and the highest in weaned piglets (r = 0.910). Kappa coefficients identifying high usage farms were the highest in weaned piglets (k = 0.71, 0.85, and 0.91, respectively for 5, 10, and 25% most frequent users) and the lowest in gestating sows (k = 0.54, 0.58, and 0.55 for 5, 10, and 25% most frequent users). Conclusions: In general, the investigated indicators showed strong correlations and a broad agreement in terms of the calculated levels of antimicrobial usage and the identification of high usage farms. Nevertheless, a certain proportion of the farms were defined differently depending on the indicator used. These differences varied by age category and were larger in all age categories except weaned piglets when a higher percentage benchmark was used to define high usage farms. These aspects should be considered when designing scientific studies or monitoring systems and considering which indicator to use.

Project description:Defined Daily Doses (DDD) and Defined Course Doses (DCD) have been established in both human and veterinary medicine in order to standardize the measurement of treatments in a population. In 2016 the European Medicines Agency published average defined daily dose (DDDvet) and defined course dose (DCDvet) values for antimicrobial agents used in livestock production. Similarly, national defined doses (DDDch and DCDch) for the pig sector in Switzerland have recently been determined. The aim of this study was to compare the outcome of calculating antimicrobial consumption based on either DDDvet/DCDvet or DDDch/DCDch. Data from 227 Swiss pig farms describing antimicrobial use in 2015 was collected. The numbers of treatment days and treatments were calculated using DDDvet/DCDvet and DDDch/DCDch respectively, for each farm in total and for different antimicrobial classes. Associations between calculated numbers of DDDvet/DCDvet and DDDch/DCDch on farm level were investigated. In addition, differences concerning antimicrobial use were investigated between different production types of farms (piglet-producer, finishing farm or farrow-to-finishing farm). Using DDDch/DCDch values we calculated 1,805,494 treatment days and 433,678 treatments compared to 1,456,771 treatment days (19% ratio) and 303,913 treatments (30% ratio) based on DDDvet/DCDvet. Penicillins (21.4/26.6%), polypeptides (18.6/27.6%) and fluoroquinolones (9.5/8.8%) were the most frequently used classes of antimicrobials based on calculation using both DDDch and DDDvet. Similar findings were observed for complete treatments (DCDch/vet) (penicillins: 52.8/39.6%; polypeptides: 7.8/14.2%; fluoroquinolones: 13.2/12.9%). The number of treatment days or treatments per farm was higher for piglet-producers and farrow-to-finishing farms compared to finisher farms regardless of whether Swiss or European DDD or DCD values were used for the calculation (each P < 0.001). Similar results for antimicrobial use (AMU) obtained at farm level were observed when calculated either by Swiss or European definitions. Nevertheless, marked differences could be observed in the assessment of the use of specific antimicrobial classes in the field based on DDDvet/DCDvet compared to DDDch/DCDch.

Project description:Monitoring of antimicrobial use is essential in the management of the development and selection of antimicrobial resistance. A variety of indicators has become available to monitor antimicrobial use in human and animal medicine. One of them is an indicator based on defined daily dose (DDD). By using the number of DDDs administered and normalising it by the population at risk of being treated over a defined period, one can estimate the number of treatment days with antimicrobial agents in a population. For veterinary medicine, the European Medicines Agency (EMA) has published the European values of DDD (DDDvet) for food-producing animals. In this study, we defined Japanese defined daily doses for antimicrobial agents (DDDjp) using DDD values that we previously assigned for antimicrobial products approved for use in pigs, cattle and poultry in Japan and compared them with DDDvet values. For the comparison, the quotient of Japanese and European values (QDDD) was calculated and the effect of the administration route and the number of active substances contained in the preparation was investigated. A total of 59 DDDjp values were defined for 43 antimicrobial agents using the data of 276 products approved for use in pigs. Likewise, a total of 55 DDDjp values were defined for 32 antimicrobial agents using the data of 196 products for use in cattle, and a total of 27 DDDjps values were defined for 25 antimicrobial agents using the data of 131 products approved for use in poultry. A comparison was made for 42, 28 and 17 pairs of DDDjp and DDDvet values for antimicrobial agents used for pigs, cattle and poultry respectively. The comparison showed median QDDD value of 0.61 and 0.66 for antimicrobial agents used for pigs and cattle respectively (p<0.01), indicating that the Japanese daily doses are significantly lower than the corresponding EMA values in these species. For the antimicrobial agents used for poultry, no significant difference was observed between DDDjp and DDDvet values with a median QDDD value of 1.15. The difference between DDDvet and DDDjp values and absence of DDDvet values for some antimicrobial agents marketed in Japan indicate that DDDjp rather than DDDvet should be used as the basis for the calculation of antimicrobial use monitoring in farm animals in Japan.

Project description:IntroductionAntimicrobial resistance (AMR) is a global health concern, occurring when bacteria evolve to render antimicrobials no longer effective. Antimicrobials have important roles in beef production; however, the potential to introduce AMR to people through beef products is a concern. This scoping review identifies factors associated with changes in the prevalence of antimicrobial-resistant Enterococcus spp. applicable to the Canadian farm-to-fork beef continuum.MethodsFive databases (MEDLINE, BIOSIS, Web of Science, Embase, and CAB Abstracts) were searched for articles published from January 1984 to March 2022, using a priori inclusion criteria. Peer-reviewed articles were included if they met all the following criteria: written in English, applicable to the Canadian beef production context, primary research, in vivo research, describing an intervention or exposure, and specific to Enterococcus spp.ResultsOut of 804 screened articles, 26 were selected for inclusion. The included articles discussed 37 factors potentially associated with AMR in enterococci, with multiple articles discussing at least two of the same factors. Factors discussed included antimicrobial administration (n = 16), raised without antimicrobials (n = 6), metal supplementation (n = 4), probiotics supplementation (n = 3), pen environment (n = 2), essential oil supplementation (n = 1), grass feeding (n = 1), therapeutic versus subtherapeutic antimicrobial use (n = 1), feeding wet distiller grains with solubles (n = 1), nutritional supplementation (n = 1) and processing plant type (n = 1). Results were included irrespective of their quality of evidence.DiscussionComparability issues arising throughout the review process were related to data aggregation, hierarchical structures, study design, and inconsistent data reporting. Findings from articles were often temporally specific in that resistance was associated with AMR outcomes at sampling times closer to exposure compared to studies that sampled at longer intervals after exposure. Resistance was often nuanced to unique gene and phenotypic resistance patterns that varied with species of enterococci. Intrinsic resistance and interpretation of minimum inhibitory concentration varied greatly among enterococcal species, highlighting the importance of caution when comparing articles and generalizing findings.Systematic review registration[http://hdl.handle.net/1880/113592].

Project description:BackgroundAntimicrobials are extensively used in cattle and poultry production in Tanzania. However, there is dearth of information on its quantitative use. A questionnaire-based cross-sectional study was conducted from August to September 2019 in randomly selected poultry and small-scale dairy farms, in three districts of Dar es Salaam City eastern, Tanzania, to assess the practice and quantify antimicrobial use. Descriptive and statistical analyses were performed at a confidence interval of 95%. The ratio of Used Daily Dose (UDD) and Defined Daily Dose (DDD) were used to determine whether the antimicrobial was overdosed or under dosed.ResultsA total of 51 poultry and 65 small-scale dairy farms were involved in the study. The route of antimicrobial administration was 98% orally via drinking water and 2% in feeds for poultry and for small-scale dairy farms, all through parenteral route. Seventeen types of antimicrobials comprising seven classes were recorded in poultry farms while nine belonging to six classes in the small dairy farms. Majority of the farms (poultry, 87.7% and small scale dairy, 84.3%) used antimicrobials for therapeutic purposes. About 41% of the poultry and one third (34%) of the dairy farmers' were not compliant to the drug withdrawal periods. Beta-lactams, fluoroquinolones, sulphonamides, tetracyclines and macrolides were the commonly used antimicrobials on these farms. In the poultry farms both those with records and those which relied on recall, antimicrobials were overdosed whereas in the small dairy farms, sulfadimidine, oxytetracycline and neomycin were within the appropriate dosing range (0.8-1.2). The majority (58.6%) of farmers had adequate level of practices (favorable) regarding antimicrobial use in cattle and poultry production. This was associated with the age and level of education of the cattle and poultry farmers.ConclusionThe study revealed a widespread misuse of antimicrobials of different types and classes in both poultry and small-scale dairy farming in Dar es Salaam, Tanzania. This result gives insight into the antimicrobial use practices and its quantification. The information obtained can guide and promote prudent use of antimicrobials among the farmers by developing mitigate strategies that reduce antimicrobial resistance risk potentials.

Project description:One bottleneck in NMR structure determination lies in the laborious and time-consuming process of side-chain resonance and NOE assignments. Compared to the well-studied backbone resonance assignment problem, automated side-chain resonance and NOE assignments are relatively less explored. Most NOE assignment algorithms require nearly complete side-chain resonance assignments from a series of through-bond experiments such as HCCH-TOCSY or HCCCONH. Unfortunately, these TOCSY experiments perform poorly on large proteins. To overcome this deficiency, we present a novel algorithm, called NASCA: (NOE Assignment and Side-Chain Assignment), to automate both side-chain resonance and NOE assignments and to perform high-resolution protein structure determination in the absence of any explicit through-bond experiment to facilitate side-chain resonance assignment, such as HCCH-TOCSY. After casting the assignment problem into a Markov Random Field (MRF), NASCA: extends and applies combinatorial protein design algorithms to compute optimal assignments that best interpret the NMR data. The MRF captures the contact map information of the protein derived from NOESY spectra, exploits the backbone structural information determined by RDCs, and considers all possible side-chain rotamers. The complexity of the combinatorial search is reduced by using a dead-end elimination (DEE) algorithm, which prunes side-chain resonance assignments that are provably not part of the optimal solution. Then an A* search algorithm is employed to find a set of optimal side-chain resonance assignments that best fit the NMR data. These side-chain resonance assignments are then used to resolve the NOE assignment ambiguity and compute high-resolution protein structures. Tests on five proteins show that NASCA: assigns resonances for more than 90% of side-chain protons, and achieves about 80% correct assignments. The final structures computed using the NOE distance restraints assigned by NASCA: have backbone RMSD 0.8-1.5 Å from the reference structures determined by traditional NMR approaches.

Dataset Information

Assignment of Canadian Defined Daily Doses and Canadian Defined Course Doses for Quantification of Antimicrobial Usage in Cattle.

Publications

Assignment of Canadian Defined Daily Doses and Canadian Defined Course Doses for Quantification of Antimicrobial Usage in Cattle.

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