Following the ban of all food animal growth-promoting antibiotics by Sweden in 1986, the European Union banned avoparcin in 1997 and bacitracin, spiramycin, tylosin and virginiamycin in 1999. Three years later, the only attributable effect in humans has been a diminution in acquired resistance in enterococci isolated from human faecal carriers. There has been an increase in human infection from vancomycin-resistant enterococci in Europe, probably related to the increased in usage of vancomycin for the treatment of methicillin-resistant staphylococci. The ban of growth promoters has, however, revealed that these agents had important prophylactic activity and their withdrawal is now associated with a deterioration in animal health, including increased diarrhoea, weight loss and mortality due to Escherichia coli and Lawsonia intracellularis in early post-weaning pigs, and clostridial necrotic enteritis in broilers. A directly attributable effect of these infections is the increase in usage of therapeutic antibiotics in food animals, including that of tetracycline, aminoglycosides, trimethoprim/sulphonamide, macrolides and lincosamides, all of which are of direct importance in human medicine. The theoretical and political benefit of the widespread ban of growth promoters needs to be more carefully weighed against the increasingly apparent adverse consequences.

Ahsfrurt:Minipigs have become a popular alternative to the traditional non-rodent species although little information is available on their P450 system. The total P450, the enzyme activity and immunochemical levels of some of the most important drug metabolizing isoenzymes CYPIA2, CYP2A6, CYP2C19, CYP2D6, CYP2El and CYP3A4 were measured in liver microsomes from 8 minipigs and 12 conventional pigs of both sexes and castrate conventional pigs. The mRNA expression was analyzed for 3 isoenzymes: CYPlA2, CYP2A6 and CYP2El. The total P450 activity was slightly higher in minipigs compared to conventional pigs but no sex differences were detected. CYPlA2 activity was 4 times higher in female than in male minipigs. The activity of the male minipigs possessed the same activity as were identical to the conventional females, males and castrates. The activity of CYP2El was 4 times higher in female than in male minipigs and 2 times higher in female than in male pigs. No activity of CYP2D6 or CYP2C19 could be detected. The CYP3A4 activity detected in minipigs was higher than the activity in conventional pigs. A slight sex difference was seen in both strains. Correlations between enzyme activity and immunochemical levels were found for CYPIAZ, CYP2A6 and CYP3A4 but not for CYP2E1. The mRNA concentration of CYPIA2, CYP2A6 and CYP2El was determined because the activity of these enzymes showed marked sex differences. A Spearman ranking correlation analysis between mRNA expression and enzyme activity showed a weak correlation for CYP2A6, but not for CYPlA2 and CYP2EI.These results seem to indicate that CYP2A6 could be transcriptionally regulated, whereas CYPlA2 might be post-transcriptionally regulated.

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.

Amoxycillin was administered to pigs intravenously (i.v.), intramuscularly (i.m.) and orally (p.o.), in a cross-over design to examine the bioavailability (F) of various drug formulations. These included: a sodium salt for reconstitution in water and administration i.v.; trihydrate salt in an oil base for intramuscular administration producing 'conventional' duration of plasma concentrations; a trihydrate salt in oil base giving prolonged (LA) duration, and a trihydrate powder for oral administration in solution. The concentration of amoxycillin in plasma was measured by high-performance liquid chromatography, and its pharmacokinetic variables were assessed for the individual pigs by use of noncompartmental methods. Following i.v. administration (8.6 mg/kg), amoxycillin was eliminated rapidly with a mean residence time (MRT) of 1.4 h. After i.m. administration of the conventional formulation (14.7 mg/kg), the plasma amoxycillin concentration peaked at 2 h at 5.1 micrograms/mL. The bioavailability was 0.83. Intramuscular administration (14.1 mg/kg) of the long acting formulation (i.m. LA), lead to two peaks in plasma at 1.3 and 6.6 h. The bioavailability was calculated to be 1.11. After p.o. administration to fasted pigs, peak concentration was reached after 1.9 h, and the bioavailability was 0.33. In fed pigs, the corresponding values were 3.6 h and 0.28. Data showed that treatment of respiratory tract diseases in pigs by p.o. dosing alone, may not be optimal, because of the relatively low bioavailability and the fact that infections often result in reduced feed and water consumption. A rational treatment regime for susceptible respiratory pathogens includes an initial i.m. injection, followed by p.o. dosing every 12 h. Alternatively, the long acting formulation may be administered i.m. in a dose of 15 mg/kg, which would lead to active plasma concentrations for approximately 48 h.

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Macrocyclic lactones are characterized by their long persistence in animals because of their extensive distribution into fat. This study examined the influence of body condition on the disposition of ivermectin (IVM) and moxidectin (MXD) in blood and fat following subcutaneous (s.c.) drug administration. 'Fat' and 'thin' lines of pigs were established using two different diets. All animals were then injected with either MXD or IVM at 300 microg/kg and blood samples were taken at regular intervals until slaughter. Two IVM-treated animals from each diet group were slaughtered at either 3 days or 3 weeks posttreatment. Two MXD-treated animals from each diet group were slaughtered at 3 days, 3, 6 or 9 weeks after treatment. Samples of backfat were taken from all animals at slaughter. Fluorescence HPLC was used to determine the concentrations of MXD or IVM in the plasma and fat samples. The plasma IVM concentration peaked more rapidly in the thin IVM treated pigs compared with the fat pigs. The concentration of IVM in backfat was significantly lower in the thin animals slaughtered 3 weeks after treatment. The MXD plasma concentration peaked within the first hour in both the thin and fat groups, but from 12 h posttreatment there was a higher MXD concentration in the plasma of the fat pigs resulting in MXD being detectable in these pigs for 28 days compared with only 17 days in the thin pigs. Despite this difference in plasma persistence no differences were seen in the MXD concentration of backfat between fat and thin animals. Body condition influenced the kinetic disposition of IVM and MXD following s.c. drug administration with both drugs being less persistent in thin compared with fat animals.

Results indicate that fenbendazole was rapidly eliminated from plasma of pigs. The drug was rapidly absorbed after oral administration, but systemic bioavailability was low.

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