Abstract

BackgroundKnowledge of therapy-induced intestinal tract concentrations of antimicrobials allows for interpretation and prediction of antimicrobial resistance selection within the intestinal microbiota. This study describes the impact of three different doses of enrofloxacin (ENR) and two different administration routes on the intestinal concentration of ENR and on the fecal Escherichia coli populations in pigs. Enrofloxacin was administered on three consecutive days to four different treatment groups. The groups either received an oral bolus administration of ENR (conventional or half dose) or an intramuscular administration (conventional or double dose).ResultsQuantitative analysis of fecal samples showed high ENR concentrations in all groups, ranging from 5.114 ± 1.272 μg/g up to 39.54 ± 10.43 μg/g at the end of the treatment period. In addition, analysis of the luminal intestinal content revealed an increase of ENR concentration from the proximal to the distal intestinal tract segments, with no significant effect of administration route. Fecal samples were also screened for resistance in E. coli isolates against ENR. Wild-type (MIC≤0.125 μg/mL) and non-wild-type (0.125 < MIC≤2 μg/mL) E. coli isolates were found at time 0 h. At the end of treatment (3 days) only non-wild-type isolates (MIC≥32 μg/mL) were found.ConclusionsIn conclusion, the observed intestinal ENR concentrations in all groups showed to be both theoretically (based on pharmacokinetic and pharmacodynamic principles) and effectively (in vivo measurement) capable of significantly reducing the intestinal E. coli wild-type population.

Highlights

  • Knowledge of therapy-induced intestinal tract concentrations of antimicrobials allows for interpretation and prediction of antimicrobial resistance selection within the intestinal microbiota

  • The formation and selection of resistant strains in the gut commensal microbiota can facilitate the environmental spread of resistance genes and resistant bacteria [7]

  • Liquid Chromatography-Mass Spectrometry (LC-MS)/MS method validation The results of the different validation parameters are given in supplementary Table B1 and B2 and fulfilled all criteria as described by the Veterinary International Conference of Harmonization (VICH, guideline 49 [17]) and the European Commission directives concerning the performance of analytical methods and interpretation [18]

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Summary

Introduction

Knowledge of therapy-induced intestinal tract concentrations of antimicrobials allows for interpretation and prediction of antimicrobial resistance selection within the intestinal microbiota. A direct relation has been described between the use of antimicrobials and subsequent antimicrobial resistance [2,3,4]. The formation and selection of resistant strains in the gut commensal microbiota can facilitate the environmental spread of resistance genes and resistant bacteria [7]. This type of spread poses a significant risk for the animal to human resistance transfer and vice versa [8], pointing towards the need for a ‘One Health’ approach

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