Endometrial tissue and blood plasma concentration of ceftiofur and metabolites following intramuscular administration of ceftiofur crystalline free acid to mares.
Abstract: Systemic administration of ceftiofur crystalline free acid (CCFA) may be a potential treatment for infectious endometritis caused by Streptococcus equi ssp. zooepidemicus (S. zooepidemicus) and other susceptible bacterial organisms in the mare. Objective: To determine if i.m. administration of CCFA at the label dose will exceed the minimum inhibitory concentration (MIC) of S. zooepidemicus in the endometrium following single administration and multiple administration protocols. Methods: Experimental pharmacokinetic study. Methods: Three mares (Group 1) were administered a single i.m. dose of CCFA (6.6 mg/kg bwt) and blood and endometrial biopsies were collected at selected intervals for 144 h. Six additional mares (Groups 2 and 3) received CCFA at times 0, 4, 11 and 18 days, and were sampled at predetermined times for 25 or 49 days, respectively. Plasma and tissue samples were analysed by high-pressure liquid chromatography with tandem mass spectrometry for desfuroylceftiofur acetamide concentration, which is a direct measure of all ceftofur and ceftiofur metabolites in the sample. Results: A mean plasma desfuroylceftiofur acetamide concentration of 0.367 ± 0.0162 μg/ml (mean ± s.e.) was detected at 96 h following administration. Mean endometrial tissue concentration was 0.510 ± 0.0418 μg/g at 96 h and exceeded the MIC for S. zooepidemicus (0.25 μg/ml) throughout the 144 h monitoring period for Group 1. Mares in Groups 2 and 3, given multiple doses of CCFA, maintained plasma concentrations above the MIC for S. zooepidemicus for 25 days. Endometrial tissue levels remained above the MIC at most data collection points for 25 days. Conclusions: Ceftiofur crystalline free acid reaches appropriate endometrial tissue values to exceed the MIC of S. zooepidemicus, a common cause of bacterial endometritis. Therefore, CCFA should be effective in the treatment of equine bacterial endometritis caused by S. zooepidemicus and other susceptible bacterial pathogens in the mare.
© 2013 EVJ Ltd.
Publication Date: 2013-12-06 PubMed ID: 24111546DOI: 10.1111/evj.12192Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study investigates the effectiveness of ceftiofur crystalline free acid (CCFA) in treating infectious endometritis in mares, a condition often caused by a bacterium called Streptococcus equi ssp. zooepidemicus. The researchers tested whether an intramuscular injection of CCFA could maintain therapeutic levels in the horse’s endometrial tissue and blood plasma, finding that it does so for up to 25 days and should thus be a suitable treatment.
Objective and Methods
- The primary objective of this study was to ascertain if intramuscular (i.m.) administration of CCFA could exceed the minimum inhibitory concentration (MIC) of Streptococcus equi ssp. zooepidemicus in a horse’s endometrium, both after a single dose and multiple doses.
- For the experiment, the researchers used nine mares divided into three groups. The first group, consisting of three mares, was given a single i.m. dose of CCFA and monitored for 144 hours. Tissue biopsies and blood samples were collected at pre-designated intervals.
- The remaining two groups, each consisting of three mares, were given CCFA on days 0, 4, 11, and 18, and samples were collected over 25 or 49 days respectively.
- The blood and tissue samples were analysed using high-pressure liquid chromatography with tandem mass spectrometry to evaluate the concentration of desfuroylceftiofur acetamide, a direct measure of all ceftofur and ceftiofur metabolites in the sample.
Results
- Analysis revealed that the average concentration of desfuroylceftiofur acetamide in the blood plasma was 0.367 ± 0.0162 μg/ml at 96 hours post-administration.
- The average concentration in endometrial tissue was slightly higher at 0.510 ± 0.0418 μg/g at 96 hours and exceeded the MIC for Streptococcus equi ssp. zooepidemicus (0.25 μg/ml) for the entire 144-hour monitoring period in Group 1.
- Mares in Groups 2 and 3, which were given multiple doses of CCFA, maintained effective plasma concentrations for 25 days.
- Similarly, concentrations in the endometrial tissue remained above the MIC at most collection points for 25 days in these two groups.
Conclusions
- The study concluded that CCFA can maintain an effective concentration in a mare’s endometrial tissue for treating infections caused by Streptococcus equi ssp. zooepidemicus.
- Therefore, CCFA appears to be a promising method for the treatment of equine bacterial endometritis caused by this bacterium and other similar pathogens.
Cite This Article
APA
Scofield D, Black J, Wittenburg L, Gustafson D, Ferris R, Hatzel J, Traub-Dargatz J, McCue P.
(2013).
Endometrial tissue and blood plasma concentration of ceftiofur and metabolites following intramuscular administration of ceftiofur crystalline free acid to mares.
Equine Vet J, 46(5), 606-610.
https://doi.org/10.1111/evj.12192 Publication
Researcher Affiliations
- Select Breeders Services-Veterinary Services, LLC, Chesapeake City, Maryland, USA.
MeSH Terms
- Animals
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / blood
- Anti-Bacterial Agents / metabolism
- Anti-Bacterial Agents / pharmacokinetics
- Cephalosporins / administration & dosage
- Cephalosporins / blood
- Cephalosporins / metabolism
- Cephalosporins / pharmacokinetics
- Drug Resistance, Bacterial
- Endometrium / chemistry
- Endometrium / metabolism
- Female
- Horses / blood
- Horses / metabolism
- Injections, Intramuscular
- Microbial Sensitivity Tests
- Streptococcus equi / drug effects
- Tissue Distribution
Citations
This article has been cited 4 times.- Köhne M, Hofbauer L, Böttcher D, Tönissen A, Hegger A, Görgens A, Ulrich R, Sieme H. Comparison of systemic trimethoprim-sulfadimethoxine treatment and intrauterine ozone application as possible therapies for bacterial endometritis in equine practice. Front Vet Sci 2023;10:1102149.
- Díaz-Bertrana ML, Deleuze S, Pitti Rios L, Yeste M, Morales Fariña I, Rivera Del Alamo MM. Microbial Prevalence and Antimicrobial Sensitivity in Equine Endometritis in Field Conditions. Animals (Basel) 2021 May 20;11(5).
- Caol S, Divers T, Crisman M, Chang YF. In vitro susceptibility of Borrelia burgdorferi isolates to three antibiotics commonly used for treating equine Lyme disease. BMC Vet Res 2017 Sep 29;13(1):293.
- Beckers KF, Liu CC, Gomes VCL, Schulz CJ, Childers GW, Fedorka CE, Sones JL. Effects of Intra-uterine Ceftiofur on the Equine Uterine Microbiome. Vet Sci 2025 Aug 30;12(9).
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