title: Use of pharmacokinetic modeling to assess antimicrobial pressure on enteric bacteria of beef cattle fed chlortetracycline for growth promotion, disease control, or treatment.
abstract: Antimicrobial use in food animals may increase antimicrobial resistance in their enteric bacteria that can be transferred to human microbiome. Over 70% of U.S. beef feedlots use non-ionophore in-feed antimicrobials for animal disease control, treatment, or growth promotion. The fraction of feedlots feeding chlortetracycline (CTC), mostly for disease control but also for treatment, has increased since the mid-1990s to present. Quantitative information on the antimicrobial selective pressure on the enteric bacteria of cattle fed CTC is lacking. Hence, the purpose of this study was to develop a deterministic mathematical model of the pharmacokinetics of ingested CTC in a beef steer and estimate the concentration of antimicrobially active (undegraded) CTC in the animal's large intestine. To evaluate the fit of the model to existing data, we also estimated the CTC concentrations in the central circulation, and fresh and aging manure from the steer. The model accounted for CTC abiotic degradation while in the gastrointestinal tract, absorption into the central circulation and tissues, biliary and renal excretion, and removal from the intestine by defecation. The model included an increase in the large intestine volume as the steer grew. We estimated that during CTC feeding to a 300-kg steer for growth promotion, the maximal drug concentration in the large intestine was 0.3 μg/mL; during disease control it was 1.7 μg/mL; and during treatment it was 31.5 μg/mL. The estimated CTC concentrations in the central circulation and the steer's manure agreed reasonably well with published data.
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University , Ithaca, New York.
authors.forename: Casey L
authors.initials: CL
authors.lastname: Cazer
authors.forename: Victoriya V
authors.initials: VV
authors.lastname: Volkova
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Gröhn
mesh_terms: D000821:Animal Feed / Q000032:analysis; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002417:Cattle / Q000254:growth & development; D002751:Chlortetracycline / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004032:Diet / Q000662:veterinary; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000302:isolation & purification; D005243:Feces / Q000737:chemistry; D005753:Gastric Mucosa / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008460:Meat / Q000382:microbiology*; D008962:Models, Theoretical
chemical_list: D000900:Anti-Bacterial Agents; D002751:Chlortetracycline