Pharmacokinetic/pharmacodynamic integration of tilmicosin against Pasteurella multocida in a piglet tissue cage model

Area of Science:

• Veterinary Pharmacology
• Antimicrobial Pharmacokinetics
• Bacterial Pathogenesis

Background:

• Tilmicosin is a semi-synthetic macrolide antibiotic used in veterinary medicine.
• Respiratory bacterial infections, particularly those caused by Pasteurella multocida, pose significant challenges in pig farming.
• Understanding the pharmacokinetic/pharmacodynamic (PK/PD) profile of tilmicosin is crucial for optimizing its efficacy.

Purpose of the Study:

• To integrate the pharmacokinetic/pharmacodynamic (PK/PD) properties of tilmicosin against Pasteurella multocida.
• To establish a piglet tissue cage infection model for evaluating tilmicosin's antibacterial effect.
• To identify the optimal PK/PD index and therapeutic targets for tilmicosin treatment.

Main Methods:

• A piglet tissue cage model was used to simulate Pasteurella multocida infection.
• Tilmicosin was administered orally at doses of 30, 40, 50, and 60 mg/kg once daily for 3 days.
• Concentrations of tilmicosin and bacterial counts were monitored; a sigmoidal Emax model was applied to PK/PD data.

Main Results:

• The area under the concentration-time curve over 24 hours divided by the minimum inhibitory concentration (AUC24h/MIC) was the best PK/PD index correlating with tilmicosin's efficacy.
• Required AUC24h/MIC values for 1/3-log, 1/2-log, and 3/4-log bacterial reductions were 19.65 h, 23.86 h, and 35.77 h, respectively.
• Dosages exceeding 50 mg/kg resulted in AUC24h/MIC > 35.77 h, indicating potent antibacterial activity due to slow elimination.

Conclusions:

• Tilmicosin demonstrates potent and sustained antibacterial effects against Pasteurella multocida, especially after multiple administrations.
• The AUC24h/MIC index is a reliable predictor of tilmicosin's therapeutic success against P. multocida.
• The findings provide valuable guidance for optimizing tilmicosin dosing regimens to effectively treat respiratory tract infections in pigs.