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Home » Archive » 2008

TDK conference 2008

Pharmacokinetic investigation of the amoxicillin-clavulanic acid combination in turkeys and resistance of turkey-derived salmonella, E. coli, and pasteurella spp. to the combination
Papp Melinda Judit - year 5
Department of Pharmacology and Toxicology
Supervisors: Akos Jerzsele DVM, Gabor Nagy

Abstract:

The amoxicillin-clavulanic acid combination is one of the most frequently used antibiotics in the veterinary practice. Amoxicillin is a broad-spectrum aminopenicillin, which is sensitive to the bacterial β-lactamase enzimes. Clavulanic acid is a potent irreversible inhibitor of a large number of β-lactamases, thus combining the two agents achieves activity against many of the penicillinase-producing bacteria.

Pharmacokinetic investigations of the combination carried out before in turkeys are not complete, as no information is available on the bioavailability after oral administration and the pharmacokinetic profile of the two compounds. The aim of this experiment is to fill up the gaps in the above-mentioned data and investigate the resistance of turkey-derived E. coli, P. multocida, S. Enteritidis and S. Typhimurium strains to the amoxicillin-clavulanic acid combination.

After intravenous administration no significant difference (p>0,05) was found in the distribution half-life and MRT values of the two substances, while difference between their elimination half-lives, clearences and distribution volumes were significant (p<0,05). After oral administration no significant difference (p>0,05) was experienced between the bioavailability, absorption half-life, elimination half-life and time to achieve maximal plasma concentration values of amoxicillin and clavulanic acid. It can be stated that the most important parameters of the two compounds – referring to practical aspects - are quite similar and although some parameters showed slight, but statistically significant differences, these alterations are biologically not remarkable. On the whole, amoxicillin and clavulanic acid are effective as a combination in this species regarding to their mechanisms of effect and pharmacokinetic behaviour.

Within the frame of our experiment minimal inhibitory concentrations (MIC values) of the combination in all the strains isolated from turkeys were identified as well as the MIC90 values for the bacteria species/serotypes. MIC90 values (in respect of amoxicillin) were the following: 32 μg/ml in E.coli, 2 μg/ml in P. multocida and 1 μg/ml in S. Enteritidis and S. Typhimurium.

At the end a recommendation has been given for the correct dose and dosing interval against infections caused by the above mentioned organisms based on the sensitivity data and pharmacokinetical parameters of the combination.



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