Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison): a pharmacokinetic-pharmacodynamic approach
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 caus...
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| Format: | Article |
| Language: | English |
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BMC
2021-02-01
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| Series: | Veterinary Research |
| Online Access: | https://doi.org/10.1186/s13567-021-00906-0 |
| _version_ | 1818615471572779008 |
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| author | Amir Atabak Ronaghinia Julie Melsted Birch Henrik Lauritz Frandsen Pierre-Louis Toutain Peter Damborg Tina Struve |
| author_facet | Amir Atabak Ronaghinia Julie Melsted Birch Henrik Lauritz Frandsen Pierre-Louis Toutain Peter Damborg Tina Struve |
| author_sort | Amir Atabak Ronaghinia |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T16:34:26Z |
| format | Article |
| id | doaj.art-5dca4651dbae4f4aa2087b1a38a2fb64 |
| institution | Directory Open Access Journal |
| issn | 1297-9716 |
| language | English |
| last_indexed | 2024-12-16T16:34:26Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Veterinary Research |
| spelling | doaj.art-5dca4651dbae4f4aa2087b1a38a2fb642022-12-21T22:24:31ZengBMCVeterinary Research1297-97162021-02-0152111610.1186/s13567-021-00906-0Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison): a pharmacokinetic-pharmacodynamic approachAmir Atabak Ronaghinia0Julie Melsted Birch1Henrik Lauritz Frandsen2Pierre-Louis Toutain3Peter Damborg4Tina Struve5Department of Veterinary and Animal Sciences, University of CopenhagenDepartment of Veterinary and Animal Sciences, University of CopenhagenNational Food Institute, Technical University of DenmarkRoyal Veterinary College, University of London, Hawkshead CampusDepartment of Veterinary and Animal Sciences, University of CopenhagenKopenhagen Diagnostics, Department of Health and Diagnostics, Kopenhagen Fur a.m.b.a.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.https://doi.org/10.1186/s13567-021-00906-0 |
| spellingShingle | Amir Atabak Ronaghinia Julie Melsted Birch Henrik Lauritz Frandsen Pierre-Louis Toutain Peter Damborg Tina Struve Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison): a pharmacokinetic-pharmacodynamic approach Veterinary Research |
| title | Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison): a pharmacokinetic-pharmacodynamic approach |
| title_full | Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison): a pharmacokinetic-pharmacodynamic approach |
| title_fullStr | Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison): a pharmacokinetic-pharmacodynamic approach |
| title_full_unstemmed | Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison): a pharmacokinetic-pharmacodynamic approach |
| title_short | Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison): a pharmacokinetic-pharmacodynamic approach |
| title_sort | evaluating a tylosin dosage regimen for treatment of staphylococcus delphini infection in mink neovison vison a pharmacokinetic pharmacodynamic approach |
| url | https://doi.org/10.1186/s13567-021-00906-0 |
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