EFSA and EMA have jointly reviewed measures taken in the EU to reduce the need for and use of antimicrobials in food-producing animals, and the resultant impacts on antimicrobial resistance (AMR). Reduction strategies have been implemented successfully in some Member States. Such strategies include national reduction targets, benchmarking of antimicrobial use, controls on prescribing and restrictions on use of specific critically important antimicrobials, together with improvements to animal husbandry and disease prevention and control measures. Due to the multiplicity of factors contributing to AMR, the impact of any single measure is difficult to quantify, although there is evidence of an association between reduction in antimicrobial use and reduced AMR. To minimise antimicrobial use, a multifaceted integrated approach should be implemented, adapted to local circumstances. Recommended options (non-prioritised) include: development of national strategies; harmonised systems for monitoring antimicrobial use and AMR development; establishing national targets for antimicrobial use reduction; use of on-farm health plans; increasing the responsibility of veterinarians for antimicrobial prescribing; training, education and raising public awareness; increasing the availability of rapid and reliable diagnostics; improving husbandry and management procedures for disease prevention and control; rethinking livestock production systems to reduce inherent disease risk. A limited number of studies provide robust evidence of alternatives to antimicrobials that positively influence health parameters. Possible alternatives include probiotics and prebiotics, competitive exclusion, bacteriophages, immunomodulators, organic acids and teat sealants. Development of a legislative framework that permits the use of specific products as alternatives should be considered. Further research to evaluate the potential of alternative farming systems on reducing AMR is also recommended. Animals suffering from bacterial infections should only be treated with antimicrobials based on veterinary diagnosis and prescription. Options should be reviewed to phase EFSA Journal 2017;15(1):4666 www.efsa.europa.eu/efsajournal out most preventive use of antimicrobials and to reduce and refine metaphylaxis by applying recognised alternative measures.

1. A sensitive method for the determination of 3-(4-cyano-2-oxobutylidene amino)-2-oxazolidone, the open-chain cyano-derivative of the veterinary drug furazolidone, in swine plasma and tissues is described. 2. After dosing adult swine orally with furazolidone (690 mg/animal per day) for 10 days no furazolidone was detected in liver, kidney and muscle (less than 2 ng/g). The half life of furazolidone as measured from the terminal phase of the plasma curves was 45 minutes. In urine, small amounts (less than 0.3% of total dose) of furazolidone were detected. 3. In contrast to other animals, 3-(4-cyano-2-oxobutylidene amino)-2-oxazolidone is a minor metabolite in swine with a plasma half life of 4 h. No cyano-derivative was detected in liver and kidney (less than 5 ng/g) 2 h after the last administration of furazolidone; 24 h after the last administration, the concentration in plasma was less than 2 ng/ml and in muscle less than 5/g. 4. The cyano-derivative was not mutagenic in the Salmonella/microsome test, with or without metabolic activation.

SUMMARYPlasma ampicillin concentrations were determined in an eight-ways crossover trial involving six ruminant calves, which were treated intravenously (i.v.) with sodium ampicillin at 15.5 mg/ kg and intramuscularly (i.m.) with five different ampicillin trihydrate or ampicillin anhydrate formulations at 7.7 mg I kg. The mean plasma concentration-time curve (Cp)after intravenous ampicillin sodium administration was described biexponentially, as: Cp = 38.8 e -0.0268t 0.45 e -0.

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Based on a physiologically based pharmacokinetic model, describing the relationship between the plasma concentration of a drug and its deposition into eggs, general transport constants into yolk and albumen were derived, for a number of compounds, using experimental data from literature. Using only generally accepted concepts in passive diffusion theory, these transport constants were used to derive and calibrate general equations, describing the transport into yolk and albumen, in terms of the physicochemical properties of a drug. It is shown that, in theory, it is possible to calculate/predict the transport constants, using the physicochemical parameters: pKa and plasma protein binding. For a number of sulfonamides, the model was used to predict their distribution between egg yolk and albumen; the outcome was compared to data found in literature. Within this dataset, the lipophilic nature of a drug does not seem to play a major role in explaining the distribution ratio of a drug between albumen and yolk.