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Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison): a pharmacokinetic-pharmacodynamic approach

Authors
  • Ronaghinia, Amir Atabak1, 2
  • Birch, Julie Melsted3, 2
  • Frandsen, Henrik Lauritz4
  • Toutain, Pierre-Louis5, 6
  • Damborg, Peter1
  • Struve, Tina2
  • 1 University of Copenhagen, Stigbøjlen 4, Frederiksberg C, 1870, Denmark , Frederiksberg C (Denmark)
  • 2 Kopenhagen Fur a.m.b.a., Langagervej 60, Glostrup, 2600, Denmark , Glostrup (Denmark)
  • 3 University of Copenhagen, Ridebanevej 3, Frederiksberg C, 1870, Denmark , Frederiksberg C (Denmark)
  • 4 National Food Institute, Technical University of Denmark, Kemitorvet, Building 204, Kongens Lyngby, 2800, Denmark , Kongens Lyngby (Denmark)
  • 5 University of London, Hawkshead Campus, Hatfield, AL9 7TA, UK , Hatfield (United Kingdom)
  • 6 INTHERES, Université de Toulouse, INRA, ENVT, 23 Chemin des Capelles, Toulouse Cedex 3, France , Toulouse Cedex 3 (France)
Type
Published Article
Journal
Veterinary Research
Publisher
BioMed Central
Publication Date
Feb 27, 2021
Volume
52
Issue
1
Identifiers
DOI: 10.1186/s13567-021-00906-0
Source
Springer Nature
License
Green

Abstract

Staphylococcus delphini is one of the most common pathogens isolated from mink infections, especially dermatitis. Tylosin (TYL) is used frequently against these infections, although no evidence-based treatment regimen exists. This study aimed to explore the dosage of TYL for infections caused by S. delphini in mink. Two animal experiments with a total of 12 minks were conducted to study the serum pharmacokinetic (PK) characteristics of TYL in mink after 10 mg/kg IV and oral dosing, respectively. The concentration of TYL in serum samples collected before and eight times during 24 h after TYL administration was quantitated with liquid chromatography quadrupole time-of-flight mass spectrometry, and the TYL disposition was analyzed using non-linear mixed effect analysis. The pharmacodynamics (PD) of TYL against S. delphini were studied using semi-mechanistic modeling of in vitro time-kill experiments. PKPD modeling and simulation were done to establish the PKPD index and dosage regimen. The disposition of TYL was described by a two-compartmental model. The area under the free concentration–time curve of TYL over the minimum inhibitory concentration of S. delphini (fAUC/MIC) was determined as PKPD index with breakpoints of 48.9 and 98.7 h for bacteriostatic and bactericidal effect, respectively. The calculated daily oral dose of TYL was 2378 mg/kg, which is 238-fold higher than the currently used TYL oral dosage regimen in mink (10 mg/kg). Accordingly, sufficient TYL concentrations are impossible to achieve in mink plasma, and use of this drug for extra-intestinal infections in this animal species must be discouraged.

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