Oral Antimicrobials and their Correlation with the Therapy of Various Bacterial and Mycoplasmal Infections

Examination of the pharmacokinetic/pharmacodynamic (PK/PD) relationships of orally administered antimicrobials and their correlation with the therapy of various bacterial and mycoplasmal infections in pigs was the subject of the thesis submitted in accordance with the requirements of the Royal College of Veterinary Surgeons for the Diploma of Fellowship by David Burch earlier this year.

12 April 2012

4 minute read

The use of antimicrobial drugs in pigs to control bacterial and mycoplasmal infections is extremely common. In some countries, like the United Kingdom, it is estimated that over 50 per cent of veterinary antimicrobial use is in pigs. It was the purpose of this thesis to help veterinarians to understand better their use of antibiotics by examining basic pharmacokinetic and pharmacodynamic (PK/PD) relationships in comparison with clinical response, to enable them to improve their clinical success.

Respiratory Infections

Regarding common porcine respiratory infections, there was a clear PK/PD relationship between plasma concentration of the antibiotic using the area under the curve (AUC) and the minimal inhibitory concentration (MIC) of Mycoplasma hyopneumoniae. With the bactericidal drug, enrofloxacin, a fluoroquinolone, when a predictable AUC/MIC relationship of >100 could be achieved, the clinical response was good.

With the bacteriostatic drugs, the relationship was less clear until the minimum bactericidal concentration (MBC) was used. When it came to the respiratory bacteria, in particular Actinobacillus pleuropneumoniae, with those drugs that did not concentrate greatly in lung tissue, such as the fluoroquinolones and the tetracyclines, there was a predictable AUC/MIC relationship, regarding efficacy. However, with the antibiotics such as tilmicosin, tiamulin and tulathromycin, which concentrate in lung and leucocyte cells to a large extent, no plasma relationship could be established. This has led to the conclusion that leucocyte concentrations were more significant.

Gastrointestinal Infections

Regarding enteric infections, a model for estimating small intestinal concentrations of an antimicrobial compound was developed. Data on the colonic or faecal concentrations of antimicrobials were often reported and from the model, approximately 29 per cent of the colonic concentration was used to determine the ileal and 25 per cent the jejunal concentrations and also the AUC. The antimicrobial concentrations in the jejunum corresponded well to Escherichia coli susceptibility patterns comparing survey and clinical isolate MICs. New intracellular MIC data have been recently developed for Lawsonia intracellularis. There was a good correlation between ileal contents concentrations and AUCs derived from the model and the intracellular MICs and susceptibility patterns that had emerged.

Brachyspira hyodysenteriae and B. pilosicoli were also examined in relation to colonic contents concentration (CCC) and AUC. The method of MIC determination, whether in broth or agar had an impact, with agar MICs being considered close to MBCs. The CCC and AUC/MIC relationship correlated well with the clinical outcome, especially when potential protein-binding figures were used, derived from plasma.

In spite of deficiencies in the available published data and the variability in MIC determination, PK/PD principles could generally be applied to both respiratory and enteric infections in the pig.