title: Pharmacokinetics of enrofloxacin and ceftiofur in plasma, interstitial fluid, and gastrointestinal tract of calves after subcutaneous injection, and bactericidal impacts on representative enteric bacteria.
abstract: This study's objectives were to determine intestinal antimicrobial concentrations in calves administered enrofloxacin or ceftiofur sodium subcutaneously, and their impact on representative enteric bacteria. Ultrafiltration devices were implanted in the ileum and colon of 12 steers, which received either enrofloxacin or ceftiofur sodium. Samples were collected over 48 h after drug administration for pharmacokinetic/pharmacodynamic analysis. Enterococcus faecalis or Salmonella enterica (5 × 10(5) CFU/mL of each) were exposed in vitro to peak and tail (48 h postadministration) concentrations of both drugs at each location for 24 h to determine inhibition of growth and change in MIC. Enrofloxacin had tissue penetration factors of 1.6 and 2.5 in the ileum and colon, while ciprofloxacin, an active metabolite of enrofloxacin, was less able to cross into the intestine (tissue penetration factors of 0.7 and 1.7). Ceftiofur was rapidly eliminated leading to tissue penetration factors of 0.39 and 0.25. All concentrations of enrofloxacin were bactericidal for S. enterica and significantly reduced E. faecalis. Peak ceftiofur concentration was bactericidal for S. enterica, and tail concentrations significantly reduced growth. E. faecalis experienced growth at all ceftiofur concentrations. The MICs for both organisms exposed to peak and tail concentrations of antimicrobials were unchanged at the end of the study. Enrofloxacin and ceftiofur achieved intestinal concentrations capable of reducing intestinal bacteria, yet the short exposure of ceftiofur in the intestine may select for resistant organisms.
authors.affiliation: Department of Population Health and Pathobiology, College of Veterinary Medicine, NC State University, Raleigh, NC, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Foster
authors.affiliation: Department of Population Health and Pathobiology, College of Veterinary Medicine, NC State University, Raleigh, NC, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Jacob
authors.affiliation: Department of Population Health and Pathobiology, College of Veterinary Medicine, NC State University, Raleigh, NC, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Warren
authors.affiliation: Department of Molecular and Biomedical Sciences, College of Veterinary Medicine, NC State University, Raleigh, NC, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Papich
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002417:Cattle / Q000097:blood*; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D024881:Drug Resistance, Bacterial; D000077422:Enrofloxacin; D013293:Enterococcus faecalis / Q000187:drug effects; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D006207:Half-Life; D007422:Intestines / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D019779:Salmonella enterica / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D024841:Fluoroquinolones; D000077422:Enrofloxacin; C053503:ceftiofur