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Equine veterinary journal2020; 53(5); 1047-1055; doi: 10.1111/evj.13385

Determination of the pharmacokinetic-pharmacodynamic cut-off values of marbofloxacin in horses to support the establishment of a clinical breakpoint for antimicrobial susceptibility testing.

Abstract: Marbofloxacin (MBX), a fluoroquinolone (FQ), is considered as a critical antibiotic requiring antimicrobial susceptibility testing (AST) for prudent use. No clinical breakpoint (CBP) currently exists to interpret the results of such tests in horses. Objective: To compute PK/PD cut-offs (PK/PDCO ) that is one of the three minimum inhibitory concentrations (MICs) considered establishing a CBP for antimicrobial susceptibility test interpretation. Methods: A meta-analysis conducted by combining five sets of previously published pharmacokinetic data, obtained in clinical and nonclinical settings. Methods: Horses (n = 131) received MBX intravenously at doses of either 2 or 10 mg/kg BW. They were richly sampled (five or six samples per horse). A population model was built to generate a virtual population of 5000 MBX disposition curves by Monte Carlo simulations (MCS) over 24 hours. The selected PK/PD index was the ratio of Area Under the free plasma concentration-time Curve divided by the MIC (fAUC/MIC). The PK/PDCO , which is the highest MIC for which 90% of horses can achieve an a priori selected critical value for the numerical value of the PK/PD index, was established for Gram-positive and Gram-negative bacteria for a dose of 2 mg/kg. Results: The PK/PDCO of MBX in horses was 0.125 mg/L for Gram-positive pathogens and 0.0625 mg/L for Gram-negative pathogens. MBX MICs determined by broth microdilution for 54 Escherichia coli and 189 Streptococcus equi isolates are reported. Conclusions: No clinical data are taken into account in the determination of a PK/PDco . Conclusions: The computed PK/PDco predicts that MBX may be efficacious in horses to treat infections associated with Enterobacteriaceae but unlikely to those involving Staphylococcus aureus or Streptococcus equi.
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Publication Date: 2020-12-04 PubMed ID: 33169427DOI: 10.1111/evj.13385Google Scholar: Lookup
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  • Journal Article
  • Meta-Analysis

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research examined the use of marbofloxacin (MBX), an antibiotic, in horses. Using a detailed process, scientists were able to determine dosage guidelines (pharmacokinetic-pharmacodynamic cut-offs). These guidelines are key in helping make decisions about how to use this antibiotic responsibly to treat bacterial infections.

Methodology

  • The research involved an intricate process that combined data from five previous studies. This meta-analysis used pharmacokinetic data, which relates to how the body affects a drug, including processes of absorption, distribution, metabolism, and excretion.
  • In the studies, a total of 131 horses were given MBX either at a dose of 2g/kg or 10g/kg of body weight, and were sampled multiple times for accurate results.
  • They used a population model to create 5000 projected MBX disposition curves over 24 hours. This was done using a method called Monte Carlo simulations.
  • The pharmacokinetic-pharmacodynamic (PK/PD) cut-off, which is a form of MIC, was computed for Gram-positive and Gram-negative bacteria at a dose of 2mg/kg. MIC, or minimum inhibitory concentration, is the lowest concentration of an antibiotic that will inhibit the visible growth of a microorganism.

Results

  • The found PK/PD cut-off for MBX in horses was 0.125mg/L for Gram-positive bacteria and 0.0625mg/L for Gram-negative bacteria.
  • The researchers have also provided MBX MICs for specific bacterias, Escherichia coli and Streptococcus equi, determined through a test known as broth microdilution.

Conclusions

  • In this experiment, no clinical data was considered while deciding the PK/PD cut-off. This is significant as it means that the decisions were based solely on the scientific data gathered from the test results.
  • The conclusions from the test results predict that MBX might be effective in horses to treat infections related to certain bacteria (Enterobacteriaceae), but it is unlikely to be effective in treating infections caused by Staphylococcus aureus or Streptococcus equi.

Cite This Article

APA
Bousquet-Mélou A, Schneider M, El Garch F, Broussou DC, Ferran AA, Lallemand EA, Triboulloy C, Damborg P, Toutain PL. (2020). Determination of the pharmacokinetic-pharmacodynamic cut-off values of marbofloxacin in horses to support the establishment of a clinical breakpoint for antimicrobial susceptibility testing. Equine Vet J, 53(5), 1047-1055. https://doi.org/10.1111/evj.13385

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 53
Issue: 5
Pages: 1047-1055

Researcher Affiliations

Bousquet-Mélou, Alain
  • INTHERES, Université de Toulouse, INRA, ENVT, Toulouse, France.
Schneider, Marc
  • Vétoquinol, Global Drug Development Division, Lure Cedex, France.
El Garch, Farid
  • Vétoquinol, Global Drug Development Division, Lure Cedex, France.
Broussou, Diane C
  • INTHERES, Université de Toulouse, INRA, ENVT, Toulouse, France.
  • Vétoquinol, Global Drug Development Division, Lure Cedex, France.
Ferran, Aude A
  • INTHERES, Université de Toulouse, INRA, ENVT, Toulouse, France.
Lallemand, Elodie A
  • INTHERES, Université de Toulouse, INRA, ENVT, Toulouse, France.
Triboulloy, Cyrielle
  • Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg C, Denmark.
Damborg, Peter
  • Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg C, Denmark.
Toutain, Pierre-Louis
  • INTHERES, Université de Toulouse, INRA, ENVT, Toulouse, France.
  • The Royal Veterinary College, Hawkshead Campus, Hatfield, Hertfordshire, UK.

MeSH Terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents
  • Fluoroquinolones / pharmacology
  • Gram-Negative Bacteria
  • Gram-Positive Bacteria
  • Horses
  • Microbial Sensitivity Tests / veterinary

Grant Funding

  • Vetoquinol

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Citations

This article has been cited 4 times.
  1. Ambros LA, Kreil V, de Lucas Burneo JJ, Tinti MG, San Andrés Larrea MI, Lorenzutti AM. Pharmacokinetic and Pharmacodynamic Modeling of Enrofloxacin and Its Metabolite Ciprofloxacin in Pregnant Goats. Vet Sci 2025 Jun 15;12(6).
    doi: 10.3390/vetsci12060588pubmed: 40559826google scholar: lookup
  2. Ferran AA, Roques BB, Chapuis L, Kuroda T, Lacroix MZ, Toutain PL, Bousquet-Melou A, Lallemand EA. Predicted efficacy and tolerance of different dosage regimens of benzylpenicillin in horses based on a pharmacokinetic study with three IM formulations and one IV formulation. Front Vet Sci 2024;11:1409266.
    doi: 10.3389/fvets.2024.1409266pubmed: 38881781google scholar: lookup
  3. Toutain PL. Why the racing industry and equestrian disciplines need to implement population pharmacokinetics: To learn, explain, summarize, harmonize, and individualize. Drug Test Anal 2025 Feb;17(2):250-258.
    doi: 10.1002/dta.3706pubmed: 38685692google scholar: lookup
  4. Kuroda T, Minamijima Y, Niwa H, Mita H, Tamura N, Fukuda K, Toutain PL, Ohta M. Pharmacokinetics/pharmacodynamics cut-off determination for fosfomycin using Monte Carlo simulation in healthy horses. J Vet Med Sci 2024 Apr 10;86(4):413-420.
    doi: 10.1292/jvms.23-0476pubmed: 38346727google scholar: lookup
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