Validating an empiric sulfadiazine–trimethoprim dosage regimen for treatment of Escherichia coli and Staphylococcus delphini infections in mink ( Neovison vison )

Ronaghinia, A A; Nikolaisen, N K; Hansen, S G; Poulsen, H H; Frandsen, H L; Struve, T; Toutain, P L; Damborg, P

Abstract

Antimicrobial agents are used extensively off?label in mink, as almost no agents are registered for this animal species. Pharmacokinetic (PK) and pharmacodynamic (PD) data are required to determine antimicrobial dosages specifically targeting mink bacterial pathogens. The aims of this study were to assess, in a PKPD framework, the empirical dosage regimen for a combination of trimethoprim (TMP) and sulfadiazine (SDZ) in mink, and secondarily to produce data for future setting of clinical breakpoints. TMP and SDZ PK parameters were obtained experimentally in 22 minks following IV or oral administration of TMP/SDZ (30 mg/kg, i.e. 5 mg/kg TMP and 25 mg/kg SDZ). fAUC/MIC with a target value of 24 hr was selected as the PKPD index predictive of TMP/SDZ efficacy. Using a modeling approach, PKPD cutoffs for TMP and SDZ were determined as 0.062 and 16 mg/L, respectively. By incorporating an anticipated potentiation effect of SDZ on TMP against Escherichia coli and Staphylococcus delphini, the PKPD cutoff of TMP was revised to 0.312 mg/L, which is above the tentative epidemiological cutoffs (TECOFF) for these species. The current empirical TMP/SDZ dosage regimen (30 mg/kg, PO, once daily) therefore appears adequate for treatment of wild?type E. coli and S. delphini infections in mink.

Citation

Ronaghinia, A. A., Nikolaisen, N. K., Hansen, S. G., Poulsen, H. H., Frandsen, H. L., Struve, T., …Damborg, P. (2020). Validating an empiric sulfadiazine–trimethoprim dosage regimen for treatment of Escherichia coli and Staphylococcus delphini infections in mink ( Neovison vison ). Journal of Veterinary Pharmacology and Therapeutics,

• Journal Article Type: Article
• Acceptance Date: Jul 2, 2020
• Publication Date: Sep 13, 2020
• Deposit Date: Oct 7, 2020
• Journal: Journal of Veterinary Pharmacology and Therapeutics
• Print ISSN: 0140-7783
• Publisher: American Academy of Veterinary Pharmacology and Therapeutics
• Peer Reviewed: Peer Reviewed
• Keywords: Pharmacology, General Veterinary
• Public URL: https://rvc-repository.worktribe.com/output/1375799