Clinical Breakpoint of Apramycin to Swine and Its Effect on Ileum Flora

The purpose of this study was to establish the clinical breakpoint (CBP) of apramycin (APR) against in swine and evaluate its effect on intestinal microbiota. The CBP was established based on three cutoff values of wild-type cutoff value (CO), pharmacokinetic-pharmadynamic (PK/PD) cutoff value (CO) and clinical cutoff value (CO). The effect of the optimized dose regimen based on ex vivo PK/PD study. The evolution of the ileum flora was determined by the gene sequencing and bioinformatics. This study firstly established the CO, CO in ileum, and CO of APR against swine , the value of these cutoffs were 32 µg/mL, 32 µg/mL and 8 µg/mL, respectively. According to the guiding principle of the Clinical Laboratory Standards Institute (CLSI), the final CBP in ileum was 32 µg/mL. Our results revealed the main evolution route in the composition of ileum microbiota of diarrheic piglets treated by APR. The change of the abundances of and was the most obvious during the evolution process. , , and were obtained as the highest abundance genus. The abundance of increased significantly when APR treatment carried and decreased in cure and withdrawal period groups. The abundance of in the tested groups was significantly lower than that in the healthy group. A decreased of abundance in was observed after infection and increased slightly after cure. increased significantly after infection and decreased significantly after APR treatment. In addition, the genera of and were defined as the key node. Valine, leucine and isoleucine biosynthesis, D-Glutamine and D-glutamate metabolism, D-Alanine metabolism, Peptidoglycan and amino acids biosynthesis were the top five Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the ileum microbiota of piglets during the infection and APR treatment process. Our study extended the understanding of dynamic shift of gut microbes during diarrheic piglets treated by APR.