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

  • 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)
Published Article
Veterinary Research
BioMed Central
Publication Date
Feb 27, 2021
DOI: 10.1186/s13567-021-00906-0
Springer Nature


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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