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.

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Deposition of cadmium onto the olfactory epithelium results in transport of the metal along the primary olfactory neurons to the olfactory bulbs of the brain. The present investigation was undertaken to determine the intracellular ligand binding of cadmium during this process. (109)Cd(2+) was applied on the olfactory epithelium of rats and pikes, and the subcellular distribution of the metal in the olfactory pathways was then examined. Two groups of rats were used: one pretreated with intranasal instillations of nonlabeled cadmium and the other given physiological saline (controls). Cellular fractionations showed that the (109)Cd(2+) was predominantly present in the cytosol of all samples, both in the rats and the pikes. Gel filtrations of the olfactory epithelium of control rats killed 2 h after the (109)Cd(2+) instillation showed that the metal was recovered in two peaks with elution volumes corresponding to metallothionein (MT) and glutathione (GSH)-the latter peak being the predominant one. However, in the epithelium of the cadmium-pretreated rats killed at 2 h, (109)Cd(2+) was recovered in one peak corresponding to MT. In the olfactory epithelium and bulbs of both groups of rats killed at 48 h, as well as in the olfactory epithelium, nerves, and bulbs of pikes killed at this interval, (109)Cd(2+) was recovered in one peak corresponding to MT. Immunohistochemistry of the olfactory system of rats given cadmium in the right nasal cavity showed induction of MT in the neuronal, sustentacular, and basal cells of the right olfactory epithelium, in the nerve fascicles in the lamina propria of the right olfactory mucosa, and in the olfactory nerve layer of the right olfactory bulb. On the left side, the immunoreactivity was low in these structures. MT immunoreactivity was observed in the glomeruli of both the right and the left olfactory bulbs. However, the staining was homogeneously distributed within the entire glomeruli of the right bulb, whereas it showed a mesh-like pattern corresponding to the localization of astrocytes in the glomeruli of the left bulb. We conclude that exposure of the olfactory epithelium to cadmium results in induction of MT in the primary olfactory neurons and a transport of the metal in these neurons as a cadmium-metallothionein (CdMT) complex. Our results further indicate that GSH is a ligand that can interact with cadmium before the metal binds to MT.

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