PHARMACOKINETICS , MINIMAL INHIBITORY CONCENTRATIONS AND EFFICACY MODEL RELATIONSHIPS FOR SOME GUT INFECTIONS IN PIGS

Guidelines have been recently introduced in the European Union for antimicrobial products, to assess their potential for resistance development and for the demonstration of their efficacy using therapeutic regimens to minimise the risk of selecting antimicrobial resistance. A key part of this is the use of pharmacokinetic and pharmacodynamic analysis. Much work has been reported on the use of concentration-dependent bactericidal products such as the fluoroquinolones and aminoglycosides administered by injection, in both man and animals, for systemic or respiratory infections. In contrast, little work has been reported on bacteriostatic compounds administered orally for enteric infections, which is the most common route for pigs. Two examples have been described lincomycin for controlling Lawsonia intracellularis infections in the pig (porcine intestinal adenomatosis) and valnemulin for the prevention and treatment of Brachyspira hyodysenteriae (swine dysentery). Predicted concentrations of lincomycin in the ileum in relation to the intracellular inhibitory concentrations (IIC) of lincomycin against L. intracellularis corresponded very closely with the clinical responses found in challenge studies. This may be due to the IIC study being a bio-model itself. With valnemulin, the concentrations in colonic contents had to be nine times higher than the minimum inhibitory concentration for B. hyodysenteriae to achieve preventative inhibition in a challenge study and 90 times higher to achieve bacterial elimination in a treatment study, as other factors come into play. It demonstrates that prevention is a legitimate claim and not just an excuse for growth promotion and the reliance on treatment regimes only, might actually encourage B. hyodysenteriae resistance development, as seen in Germany.