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

doi:10.1186/s13567-021-00906-0

Cited by 6 publications

(6 citation statements)

References 33 publications

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“…Tylosin bioavailability following IM injection in chicken was ranged from 22.5 to 34.0%, while it was ranged from 70 to 95% in pigs, cows, and sheep after oral administration [ 12 – 14 ]. In contrast, the reported oral bioavailability in mink is poor (41%), while the IM-injected bioavailability in olive flounder is high (approximately 87%) [ 7 , 15 ].…”

Section: Resultsmentioning

confidence: 99%

Re-evaluation of a microbiological acceptable daily intake for tylosin based on its impact on human intestinal microflora

Kim

Choi

et al. 2023

Toxicol Res.

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As veterinary drugs available for fish is very restricted, there is growing trials for repurposing livestock drugs as aquatic animal drugs. Tylosin is one of the most effective antibiotics to treat bacterial infections approved for livestock, and would be used in fish. Hence, we investigated the toxicological and microbiological aspects of tylosin to establish health-based guidance value (HBGV) and maximum residue limit (MRL) in fishes, and reevaluated the microbiological acceptable daily intake (mADI) based on updated relevant data and international guildeline. Lastly, exposure assessment was performed to confirm the appropriateness of MRL. By investigating available microbiologcial studies on tylosin, the microbiological point of departure was determined as 0.308 μg/mL, which was mean 50% minimum inhibitory concentration (MIC50), obtained from the Food Safety Committee of Japan (FSCJ) evaluation report. Furthermore, as a factor for the derivation of mADI, the volume of colon content was recently changed to 500 mL in compliance with the International Cooperation on Harmonization of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) guidelines. This was previously defined as the mass of colon content (220 g). We applied correction factor 0.224 to the mean MIC50 for tylosin in the equation of mADI, since the drug is transformed to metabolites with reduced activity prior to entering the colon and bound to fecal materials within the colon of human. The mADI was evaluated as 0.01 mg/kg bw/day. Finally, the hazard index, calculated by dividing the estimated chronic dietary exposure by mADI, did not exceed 100%, suggesting that chronic dietary exposure to tylosin residues from veterinary use was unlikely to be a public health concern. Overall, this study contributes significantly in updating HBGV by application of the concept of mADI for the first time in Korea based on the revised microbiological risk assessment guidelines and in providing scientific rationale for the risk management of veterinary drug residues in food.

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Section: Resultsmentioning

confidence: 99%

Re-evaluation of a microbiological acceptable daily intake for tylosin based on its impact on human intestinal microflora

Kim

Choi

et al. 2023

Toxicol Res.

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“…This model has been adapted to evaluate the PK/PD indices of florfenicol against P. multocida [ 17 ]. It has also been applied to evaluate the dosage regimen of tylosin against Staphylococcus delphini [ 18 ]. In addition, semi-mechanistic PD model can characterize the emergency of resistance, which will provide an available way to identify dose regimens that can prevent bacterial drug resistance [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the model can capture the emergence and spread of resistance. Currently, some studies have applied them to evaluate the rationality of dose [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Optimization and Validation of Dosage Regimen for Ceftiofur against Pasteurella multocida in Swine by Physiological Based Pharmacokinetic–Pharmacodynamic Model

Hou

et al. 2022

IJMS

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Model informed drug development is a valuable tool for drug development and clinical application due to its ability to integrate variability and uncertainty of data. This study aimed to determine an optimal dosage of ceftiofur against P. multocida by ex vivo pharmacokinetic/pharmacodynamic (PK/PD) model and validate the dosage regimens by Physiological based Pharmacokinetic-Pharmacodynamic (PBPK/PD) model. The pharmacokinetic profiles of ceftiofur both in plasma and bronchoalveolar lavage fluid (BALF) are determined. PD performance of ceftiofur against P. multocida was investigated. By establishing PK/PD model, PK/PD parameters and doses were determined. PBPK model and PBPK/PD model were developed to validate the dosage efficacy. The PK/PD parameters, AUC0–24 h/MIC, for bacteriostatic action, bactericidal action and elimination were determined as 44.02, 89.40, and 119.90 h and the corresponding dosages were determined as 0.22, 0.46, and 0.64 mg/kg, respectively. AUC24 h/MIC and AUC 72 h/MIC are simulated by PBPK model, compared with the PK/PD parameters, the therapeutic effect can reach probability of target attainment (PTA) of 90%. The time-courses of bacterial growth were predicted by the PBPK/PD model, which indicated the dosage of 0.46 mg/kg body weight could inhibit the bacterial growth and perform good bactericidal effect.

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“…Macrolides are active against Gram-positive bacteria, e.g., S. delphini. However, a recent study found that tylosin is not an appropriate drug of choice for treating extraintestinal infections in mink caused by S. delphini because a therapeutic concentration of the active compound was not achievable in mink plasma [ 43 ]. Consequently, the currently used off-label dose in Danish mink might cause more harm than good, considering that these sub-bactericidal doses may still select for antibiotic resistance—for the pre-existing resistant strains, but it may also promote de novo resistance [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Association between Antibiotic Consumption and Resistance in Mink Production

et al. 2022

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Antibiotic consumption is considered to be a main driver of antibiotic resistant bacteria. Mink breeding follows a distinctive seasonal reproduction cycle, and all of the mink produced in the northern hemisphere are bred, born, and pelted around the same time of year. Some of the diseases are age-related, which is reflected in the seasonal variation of antibiotic consumption. The seasonality makes mink a good model for the investigation of the association between antibiotic consumption and resistance. The objectives of this study were (1) to monitor the farm level of antibiotic resistance during one production cycle and (2) to assess the potential associations between antibiotic consumption and resistance. Twenty-four farms were included in this study (Denmark n = 20, Iceland n = 2, and The Netherlands n = 2), following a cohort of animals born in 2018. Staphylococcus delphini and Escherichia coli were isolated from samples of the carcasses and faeces and were collected randomly. The isolates were susceptibility tested and subsequently divided into the sensitive wildtype (WT) and the resistant non-wildtype (NWT) populations. The antibiotic consumption relative to the sampling periods was assessed as having a short-term or a long-term impact, i.e., in two explanatory factors. For both S. delphini and E. coli, a large between-farm variation of NWT profiles was detected. In the final multivariable, generalized linear mixed models, significant associations between NWT isolates and the consumption of specific antibiotics were found: the short-term use of tetracyclines in the growth period was associated with the occurrence of tetracycline NWT E. coli in the growth period (OR: 11.94 [1.78; 89.28]), and the long-term use of macrolide and tetracyclines was associated with the occurrence of erythromycin NWT S. delphini in the weaning period (OR: 18.2 [2.26; 321.36]) and tetracycline NWT S. delphini in the growth period (OR: 8.2 [1.27; 63.31]), respectively. Farms with zero consumption in the study years prior to sampling also had a substantial proportion of NWT isolates, indicating that NWT isolates are persistent and/or widely spread in the environment. Generally, a high occurrence of tetracycline NWTs was observed. NWT isolates with resistance against the most commonly used antibiotics were found on all the farms, stressing the need for routine surveillance and the prudent use of antibiotics. The results offer a preview of the complex relationship between consumption and resistance, demonstrating some significant associations between use and resistance. Moreover, antibiotic-resistant bacteria are present even on farms with no antibiotic consumption over extended periods, and theoretical explanations supported by the data are offered.

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

Cited by 6 publications

References 33 publications

Re-evaluation of a microbiological acceptable daily intake for tylosin based on its impact on human intestinal microflora

Re-evaluation of a microbiological acceptable daily intake for tylosin based on its impact on human intestinal microflora

Optimization and Validation of Dosage Regimen for Ceftiofur against Pasteurella multocida in Swine by Physiological Based Pharmacokinetic–Pharmacodynamic Model

Association between Antibiotic Consumption and Resistance in Mink Production

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