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Equine veterinary journal2019; 51(4); 544-551; doi: 10.1111/evj.13044

Diffusion of enrofloxacin to pregnancy fluids and effects on fetal cartilage after intravenous administration to late pregnant mares.

Abstract: In selective cases, enrofloxacin may be an alternative antibacterial agent to treat unresponsive infections in pregnant mares. Supratherapeutic doses of enrofloxacin are toxic to adult horses and also to newborn foals, however, it is unknown if enrofloxacin crosses the equine placenta or if it is toxic to the fetus. Objective: To assess the diffusion of enrofloxacin and its metabolite to fetal fluids and its effects on fetal cartilage when administered to pregnant mares. Methods: In vivo and terminal controlled experiment. Methods: Healthy mares at 260 days of gestation were allocated into three groups: untreated (n = 3), therapeutic treatment (5 mg/kg enrofloxacin, i.v., n = 7) or supratherapeutic treatment (10 mg/kg, i.v., n = 6) for 11 days. Fetal fluids were collected on days 1, 5 and 11 of treatment. Premature delivery was induced on day 11 with oxytocin and fetal fluids and plasma were collected during delivery. Plasma and fetal fluid enrofloxacin and ciprofloxacin concentrations were measured by liquid chromatography-mass spectrometry. Fetal articular cartilage was examined macroscopically and histologically for lesions. Results: Enrofloxacin and ciprofloxacin reached the minimum inhibitory concentrations for common pathogens in all fluids. Ciprofloxacin did not increase with the double enrofloxacin dose in maternal plasma, but allantoic fluid showed a 10-fold increase relative to fetal trough plasma concentrations. Administration of enrofloxacin at recommended doses did not result in cartilaginous lesions in fetuses. Conclusions: Only one time point in gestation was evaluated and mares treated in the study were healthy at the time of treatment. It remains to be determined if enrofloxacin shows toxicity at other stages of pregnancy, after a longer duration of treatment, or once the foals are delivered and articular surfaces are weightbearing. Conclusions: Short-term administration of enrofloxacin to late gestation mares resulted in detectable enrofloxacin and ciprofloxacin concentrations in fetal fluids and did not result in macroscopic or microscopic lesions in the fetus. While further research is needed to address long-term foal outcomes, enrofloxacin may be useful for select bacterial infections in pregnant mares.
Publication Date: 2019-01-02 PubMed ID: 30449030DOI: 10.1111/evj.13044Google Scholar: Lookup
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  • Clinical Trial
  • Veterinary
  • Journal Article

Summary

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The research is about testing the effects of an antibacterial drug, enrofloxacin, on pregnant horses at late stages of gestation and its diffusion into the fetus via the placenta. It aims to explore if this drug is a viable treatment option for infections and checking the impacts on fetal cartilage, to ensure the well-being of the unborn foal.

Objective and Methodology

  • The research aims to determine if enrofloxacin gets to the fetus when given to pregnant mares and the impact it has on the fetal cartilage.
  • Three sets of healthy mares were selected, each at 260 days of gestation. One group was given no treatment, another group received therapeutic doses of the drug, and the last group was given double the therapy dose.
  • The fetal fluids were collected at different stages, and after the 11th day, premature delivery was induced. Fluids and plasma samples were then collected and analyzed.
  • The concentrations of enrofloxacin and its metabolite, ciprofloxacin, in plasma and fetal fluid were measured using liquid chromatography-mass spectrometry.
  • The fetal articular cartilage was examined for possible lesions both macroscopically and histologically.

Results

  • The research results indicated that enrofloxacin and ciprofloxacin reached the minimum inhibitory concentrations for common pathogens in all fluids.
  • Even though ciprofloxacin level did not increase in maternal plasma with the increased dose of enrofloxacin, allantoic fluid showed a 10-fold increase relative to fetal trough plasma concentrations.
  • The use of enrofloxacin at recommended doses did not result in cartilaginous lesions in fetuses.

Conclusion

  • The research team concluded that the short-term administration of enrofloxacin to pregnant mares resulted in detectable levels of the drug and its metabolite in fetal fluids.
  • It was also noted that this did not result in macroscopic or microscopic lesions in the fetus.
  • The study cautions, however, that its findings are limited to just one point of gestation and that the mares were healthy at the time of treatment. Further research is therefore needed to fully understand the impact of enrofloxacin at different stages of pregnancy, after longer treatment durations, and once the foals are weight-bearing.
  • Notwithstanding, the study hints that enrofloxacin could be viable for treating select bacterial infections in pregnant mares, provided additional research validates the initial findings.

Cite This Article

APA
Ellerbrock RE, Canisso IF, Roady PJ, Rothrock LT, Zhong L, Wilkins P, Dirikolu L, Lima FS, Honoroto J. (2019). Diffusion of enrofloxacin to pregnancy fluids and effects on fetal cartilage after intravenous administration to late pregnant mares. Equine Vet J, 51(4), 544-551. https://doi.org/10.1111/evj.13044

Publication

ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 51
Issue: 4
Pages: 544-551

Researcher Affiliations

Ellerbrock, R E
  • Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois Urbana Champaign, Urbana, Illinois, USA.
  • Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana Champaign, Urbana, Illinois, USA.
Canisso, I F
  • Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois Urbana Champaign, Urbana, Illinois, USA.
Roady, P J
  • Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois Urbana Champaign, Urbana, Illinois, USA.
Rothrock, L T
  • Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois Urbana Champaign, Urbana, Illinois, USA.
Zhong, L
  • Roy J. Carver Biotechnology Center, University of Illinois Urbana-Champaign, Urbana, Illinois, USA.
Wilkins, P
  • Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois Urbana Champaign, Urbana, Illinois, USA.
Dirikolu, L
  • Department of Comparative Biosciences, College of Veterinary Medicine, University of Illinois Urbana Champaign, Urbana, Illinois, USA.
Lima, F S
  • Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois Urbana Champaign, Urbana, Illinois, USA.
Honoroto, J
  • Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois Urbana Champaign, Urbana, Illinois, USA.

MeSH Terms

  • Abortion, Veterinary / etiology
  • Animals
  • Anti-Bacterial Agents
  • Body Fluids / chemistry
  • Cartilage / drug effects
  • Cartilage / embryology
  • Ciprofloxacin / blood
  • Ciprofloxacin / metabolism
  • Enrofloxacin / blood
  • Enrofloxacin / chemistry
  • Enrofloxacin / metabolism
  • Enrofloxacin / pharmacokinetics
  • Female
  • Horses
  • Pregnancy

Grant Funding

  • USDA Hatch funds
  • Department of Veterinary Clinical Medicine
  • Koteska Fellowship
  • Thompson Fellowship of the College of Veterinary Medicine
  • University of Illinois Urbana-Champaign

Citations

This article has been cited 3 times.
  1. Tyrnenopoulou P, Fthenakis GC. Clinical Aspects of Bacterial Distribution and Antibiotic Resistance in the Reproductive System of Equids.. Antibiotics (Basel) 2023 Mar 28;12(4).
    doi: 10.3390/antibiotics12040664pubmed: 37107026google scholar: lookup
  2. Grabowski Ł, Gaffke L, Pierzynowska K, Cyske Z, Choszcz M, Węgrzyn G, Węgrzyn A. Enrofloxacin-The Ruthless Killer of Eukaryotic Cells or the Last Hope in the Fight against Bacterial Infections?. Int J Mol Sci 2022 Mar 26;23(7).
    doi: 10.3390/ijms23073648pubmed: 35409007google scholar: lookup
  3. Fan R, Zhang W, Jia L, Luo S, Liu Y, Jin Y, Li Y, Yuan X, Chen Y. Antagonistic Effects of Enrofloxacin on Carbendazim-Induced Developmental Toxicity in Zebrafish Embryos.. Toxics 2021 Dec 10;9(12).
    doi: 10.3390/toxics9120349pubmed: 34941783google scholar: lookup