Ceftiofur formulation differentially affects the intestinal drug concentration, resistance of fecal Escherichia coli, and the microbiome of steers

Autoři: Derek M. Foster aff001;  Megan E. Jacob aff001;  Kyle A. Farmer aff001;  Benjamin J. Callahan aff001;  Casey M. Theriot aff001;  Sophia Kathariou aff002;  Natalia Cernicchiaro aff003;  Timo Prange aff004;  Mark G. Papich aff005
Působiště autorů: Department of Population Health and Pathobiology, College of Veterinary Medicine, NC State University, Raleigh, NC, United States of America aff001;  Department of Food, Bioprocessing, and Nutrition Sciences, College of Agriculture and Life Sciences, NC State University, Raleigh, NC, United States of America aff002;  Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, United States of America aff003;  Department of Clinical Sciences, College of Veterinary Medicine, NC State University, Raleigh, NC, United States of America aff004;  Department of Molecular and Biomedical Sciences, College of Veterinary Medicine, NC State University, Raleigh, NC, United States of America aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223378


Antimicrobial drug concentrations in the gastrointestinal tract likely drive antimicrobial resistance in enteric bacteria. Our objective was to determine the concentration of ceftiofur and its metabolites in the gastrointestinal tract of steers treated with ceftiofur crystalline-free acid (CCFA) or ceftiofur hydrochloride (CHCL), determine the effect of these drugs on the minimum inhibitory concentration (MIC) of fecal Escherichia coli, and evaluate shifts in the microbiome. Steers were administered either a single dose (6.6 mg/kg) of CCFA or 2.2 mg/kg of CHCL every 24 hours for 3 days. Ceftiofur and its metabolites were measured in the plasma, interstitium, ileum and colon. The concentration and MIC of fecal E. coli and the fecal microbiota composition were assessed after treatment. The maximum concentration of ceftiofur was higher in all sampled locations of steers treated with CHCL. Measurable drug persisted longer in the intestine of CCFA-treated steers. There was a significant decrease in E. coli concentration (P = 0.002) within 24 hours that persisted for 2 weeks after CCFA treatment. In CHCL-treated steers, the mean MIC of ceftiofur in E. coli peaked at 48 hours (mean MIC = 20.45 ug/ml, 95% CI = 10.29–40.63 ug/ml), and in CCFA-treated steers, mean MIC peaked at 96 hours (mean MIC = 10.68 ug/ml, 95% CI = 5.47–20.85 ug/ml). Shifts in the microbiome of steers in both groups were due to reductions in Firmicutes and increases in Bacteroidetes. CCFA leads to prolonged, low intestinal drug concentrations, and is associated with decreased E. coli concentration, an increased MIC of ceftiofur in E. coli at specific time points, and shifts in the fecal microbiota. CHCL led to higher intestinal drug concentrations over a shorter duration. Effects on E. coli concentration and the microbiome were smaller in this group, but the increase in the MIC of ceftiofur in fecal E. coli was similar.

Klíčová slova:

Antimicrobial resistance – Cattle – Colon – Gastrointestinal tract – Ileum – Livestock care – Microbiome – Drug interactions


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