PHARMACOKINETICS OF ANTIMICROBIALS AT DIFFERENT LEVELS OF THE INTESTINAL TRACT AND THEIR RELATIONSHIP TO ESCHERICHIA COLI RESISTANCE PATTERNS IN THE PIG
D.G.S. Burch

Abstract
The first part of the paper looked at the pharmacokinetics of a liquid non-absorbable compound as it passed along the small intestines of adult pigs. Only 38.8% of the dose was recovered in the upper small intestine, 71.5% in the middle third, but 100% in the lower third or ileum over a 12 hour period. The first time point was at two hours after dosing, when the stomach had passed 51% of the dose and 71.5% by 4 hours. It was thought that inadequate sampling points prior to two hours meant that a substantial portion of the dose had been missed in the upper small intestine and had already passed down to the lower small intestine. A calculation was made, based on the area under the curve (AUC) from the stomach and added to the upper small intestine and this increased the recovered dose to 81.6%. Using the routine in-feed usage pharmacokinetic data of AUC projected over 24 hours and available gut or faecal concentration data or estimations, the mid-small intestine concentrations were compared with the epidemiological cut-off values (ECOV) for various antimicrobials against porcine E. coli from Danish slaughterhouse monitoring and diagnostic isolates. Similarly, the clinical breakpoints (CBP) (one dilution lower than the NCCLS resistance breakpoints) were also examined in this AUC/MIC analysis. Most of the bacteriostatic antimicrobials were around or exceeded the AUC/MIC ECOV ratio of 24, which denotes inhibition, and all the bactericidal compounds exceeded 100. When the AUC/MIC CBP ratios were examined, the majority of bactericidal antimicrobials exceeded 100, except enrofloxacin, and for the bacteriostatic compounds, spectinomycin was well below. Trimethoprim and sulphonamides alone were also consistently low, but when used in a combination, their synergistic bactericidal activity exceeded the 100 threshold. Fundamental pharmacokinetic /pharmacodynamic analysis of antimicrobials in gut contents appears to be applicable to E. coli infections in the small intestine.

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