Pharmacokinetic/pharmacodynamic relationship of danofloxacin agaisnt Mannheimia haemolytica in a tissue-cage model in calves

Abstract

Objective: To evaluate an experimental model of the pharmacokinetic/pharmacodynamic (PK/PD) relationship of danofloxacin against Mannheimia haemolytica infection, using subcutaneously implanted tissue cages in calves. Methods: Tissue cages implanted subcutaneously in calves were infected with M. haemolytica and different concentration-time profiles of danofloxacin were simulated. Drug concentrations and bacterial counts were monitored over time and various PK/PD parameters calculated. Results: By using different types of cage and various doses, a range of PK/PD indices were simulated. The PK/PD index that best predicted the antimicrobial effect was the AUC/MIC ratio. The magnitude of this index needed for near-maximum effect (80%), assessed using the area under the bacterial kill curve to 48 h, was 244 h. Conclusions: The model described enabled different concentration-time profiles to be simulated, and PK/PD interactions to be studied in the presence of the host's defences. The validity of this model needs to be confirmed by clinical studies, but the results suggest that it may be a useful intermediary step between in vitro and clinical studies.