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

Ronaghinia, Amir Atabak; Birch, Julie Melsted; Frandsen, Henrik Lauritz; Toutain, Pierre-Louis; Damborg, Peter; Struve, Tina

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.

Citation

Ronaghinia, A. A., Birch, J. M., Frandsen, H. L., Toutain, P., Damborg, P., & Struve, T. (2021). Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison): a pharmacokinetic-pharmacodynamic approach. Veterinary Research, 52(1), https://doi.org/10.1186/s13567-021-00906-0

• Journal Article Type: Article
• Acceptance Date: Jan 14, 2021
• Online Publication Date: Feb 27, 2021
• Publication Date: 2021-12
• Deposit Date: May 10, 2021
• Publicly Available Date: Jun 21, 2021
• Journal: Veterinary Research
• Print ISSN: 0928-4249
• Publisher: BioMed Central
• Peer Reviewed: Peer Reviewed
• Volume: 52
• Issue: 1
• DOI: https://doi.org/10.1186/s13567-021-00906-0
• Keywords: General Veterinary
• Public URL: https://rvc-repository.worktribe.com/output/1548656
• Additional Information: Received: 14 July 2020; Accepted: 14 January 2021; First Online: 27 February 2021; : All animal experiments in this study were approved by the Danish Animal Experiments Inspectorate (Permit No. 2017-15-0201-01291) and by the Danish Medicines Agency (Permit No. 2017083950).; : The authors declare that they have no competing interests.