A tissue cage model in calves for studies on pharmacokinetic/pharmacodynamic interactions of antimicrobials

Area of Science:

• Veterinary Medicine
• Pharmacology
• Infectious Diseases

Background:

• Understanding antimicrobial pharmacokinetic/pharmacodynamic (PK/PD) interactions is crucial for effective treatment strategies.
• Existing in vivo models may not fully replicate complex in-body drug dynamics and infection responses.

Purpose of the Study:

• To develop and validate a novel in vivo model for investigating PK/PD interactions of antimicrobials.
• To evaluate the predictive value of different PK/PD indices for antimicrobial efficacy in an established infection model.

Main Methods:

• An in vivo model was established in calves using implanted tissue cages of varying volumes.
• Infection was induced with Mannheimia haemolytica, and penicillin was administered directly into the cages.
• Different antimicrobial concentration-time profiles were simulated to monitor infection response.

Main Results:

• The model successfully simulated diverse PK/PD profiles and allowed for monitoring of infection effects.
• Area under the curve to minimum inhibitory concentration (AUC/MIC) and time above MIC were found to be equally predictive of antimicrobial effect.
• Cmax to MIC ratio was not a reliable predictor of treatment success in this model.

Conclusions:

• The developed tissue cage model provides a valuable platform for studying antimicrobial PK/PD interactions in vivo.
• AUC/MIC and time above MIC are key PK/PD indices for optimizing penicillin dosage against Mannheimia haemolytica infections.
• This model offers an alternative approach for exploring drug dosage optimization strategies in veterinary medicine.