Disposition of desfuroylceftiofur acetamide in serum, placental tissue, fetal fluids, and fetal tissues after administration of ceftiofur crystalline free acid (CCFA) to pony mares with placentitis.
Abstract: The objective of this study was to determine the pharmacokinetics of CCFA in mares with placentitis and evaluate the disposition of the drug in fetal fluids, fetal membranes, colostrum, and serum of foals. A secondary objective was to obtain pilot data regarding the efficacy of CCFA for improving foal survival in mares with placentitis. Twelve pregnant pony mares were enrolled in the study, inoculated with Streptococcus zooepidemicus, intracervically and assigned to one of three groups: CEFT (n = 3; administered CCFA only; 6.6 mg/kg, i.m., q96h); COMBO (n = 6; administered combination therapy of CCFA, altrenogest, and pentoxifylline); UNTREAT (n = 3, no treatment). Treatment was initiated at the onset of clinical signs. Concentrations of desfuroylceftiofur acetamide (DCA), the acetamide derivative of ceftiofur and desfuroylceftiofur metabolites, were measured using high-performance liquid chromatography. Maximum and minimum serum concentrations of DCA at steady state in treated mares were 2.40±0.40 μg/mL and 1.06±0.29 μg/mL, respectively. Concentration of DCA in colostrum was 1.51±0.60 μg/mL. DCA concentrations in placenta and fetal tissues were very low (median = 0.03 μg/mL) and below the minimum inhibitory concentration of relevant pathogens. DCA was not detected in amniotic fluid or foal serum. Treatment did not appear to improve foal survival (CEFT: 0/3; COMBO: 2/6; UNTREAT: 2/3). Bacteria were recovered from the uterus of most mares postpartum and from blood cultures of most foals regardless of treatment.
© 2012 Blackwell Publishing Ltd.
Publication Date: 2012-03-26 PubMed ID: 22449008DOI: 10.1111/j.1365-2885.2012.01392.xGoogle Scholar: Lookup
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- Journal Article
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- Non-U.S. Gov't
Summary
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This research aimed to understand the behavior of ceftiofur crystalline free acid (CCFA), a type of antibiotic, in mares suffering from placentitis and its disposition in the fetus and its associated fluids and tissues. However, the results showed that the antibiotic does not significantly accumulate in the placenta or fetal tissues, nor does it improve foal survival.
Study Design and Execution
- The study involved twelve pregnant pony mares which were purposely infected with Streptococcus zooepidemicus.
- The mares were categorized into three groups: those given only the antibiotic CCFA (CEFT group), those provided with a combination therapy of CCFA, altrenogest, and pentoxifylline (COMBO group), and the third group remained untreated (UNTREAT group).
- Treatment for the two treated groups was initiated as soon as clinical signs were observed.
- The researchers examined the ceftiofur antibiotic in its metabolized state as desfuroylceftiofur acetamide (DCA).
Observations and Results
- High-performance liquid chromatography was used to measure the concentrations of the metabolized antibiotic.
- The serum concentration of DCA in the treated mares had a maximum of 2.40±0.40 μg/mL and a minimum of 1.06±0.29 μg/mL.
- The concentration of the antibiotic in colostrum was 1.51±0.60 μg/mL.
- The concentrations of the antibiotic in placental and fetal tissues were quite low (median of 0.03 μg/mL) and did not meet the necessary threshold (minimum inhibitory concentration) required to effectively halt the growth of pathogens.
- The treatment failed to significantly improve the survival rate of foals. This was based on the survival ratios in the CEFT, COMBO, and UNTREAT groups.
- Regardless of treatment, bacteria could be detected in the uterus of most mares after they had given birth and the in the blood culture of foals.
Conclusions
- The research concludes that the antibiotic CCFA may not be effective in treating placentitis in mares since it occurs in insufficient concentrations in the placenta and fetal tissues.
- The use of this antibiotic also did not benefit the survival rate of foals; therefore, its relevance in such a context remains uncertain.
- Detection of bacteria post treatment indicates that the therapy offered did not effectively manage the bacterial infection within the mares or prevent its transmission to the foals.
Cite This Article
APA
Macpherson ML, Giguère S, Hatzel JN, Pozor M, Benson S, Diaw M, Sanchez LC, Vickroy TW, Tell L, Wetzlich S, Sims J.
(2012).
Disposition of desfuroylceftiofur acetamide in serum, placental tissue, fetal fluids, and fetal tissues after administration of ceftiofur crystalline free acid (CCFA) to pony mares with placentitis.
J Vet Pharmacol Ther, 36(1), 59-67.
https://doi.org/10.1111/j.1365-2885.2012.01392.x Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA. macphersonm@ufl.edu
MeSH Terms
- Animals
- Anti-Bacterial Agents / analysis
- Anti-Bacterial Agents / blood
- Anti-Bacterial Agents / pharmacokinetics
- Anti-Bacterial Agents / therapeutic use
- Cephalosporins / analysis
- Cephalosporins / blood
- Cephalosporins / pharmacokinetics
- Cephalosporins / therapeutic use
- Colostrum / chemistry
- Extraembryonic Membranes / chemistry
- Female
- Fetus / chemistry
- Horses / metabolism
- Placenta / chemistry
- Placenta Diseases / drug therapy
- Placenta Diseases / veterinary
- Pregnancy
Citations
This article has been cited 2 times.- Tibary A. Grand Challenge Animal Reproduction-Theriogenology: From the Bench to Application to Animal Production and Reproductive Medicine.. Front Vet Sci 2017;4:114.
- Salyards GW, Knych HK, Hill AE, Kelly KR, Christe KL. Pharmacokinetics of Ceftiofur Crystalline Free Acid in Male Rhesus Macaques (Macaca mulatta) after Subcutaneous Administration.. J Am Assoc Lab Anim Sci 2015 Sep;54(5):557-63.
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