Pharmacokinetic/pharmacodynamic integration and modelling of oxytetracycline for the porcine pneumonia pathogensActinobacillus pleuropneumoniaeandPasteurella multocida

Pharmacokinetic–pharmacodynamic ( PK / PD ) integration and modelling were used to predict dosage schedules of oxytetracycline for two pig pneumonia pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida . Minimum inhibitory concentration ( MIC ) and mutant prevention concentration ( MPC ) were determined in broth and porcine serum. PK / PD integration established ratios of average concentration over 48 h ( C av0–48 h )/ MIC of 5.87 and 0.27 μ g/mL ( P. multocida ) and 0.70 and 0.85 μ g/mL ( A. pleuropneumoniae ) for broth and serum MIC s, respectively. PK / PD modelling of in vitro time–kill curves established broth and serum breakpoint values for area under curve ( AUC 0–24 h )/ MIC for three levels of inhibition of growth, bacteriostasis and 3 and 4 log 10 reductions in bacterial count. Doses were then predicted for each pathogen, based on Monte Carlo simulations, for: (i) bacteriostatic and bactericidal levels of kill; (ii) 50% and 90% target attainment rates ( TAR ); and (iii) single dosing and daily dosing at steady‐state. For 90% TAR , predicted daily doses at steady‐state for bactericidal actions were 1123 mg/kg ( P. multocida ) and 43 mg/kg ( A. pleuropneumoniae ) based on serum MIC s. Lower TAR s were predicted from broth MIC data; corresponding dose estimates were 95 mg/kg ( P. multocida ) and 34 mg/kg ( A. pleuropneumoniae ).