The pharmacodynamic effect of amoxycillin and danofloxacin against Actinobacillus pleuropneumoniae in an in-vitro pharmacodynamic model

The pharmacodynamic effect of amoxycillin and danofloxacin against two stra ins of Actinobacillus pleuropneumoniae was evaluated in an in-vitro pharmac odynamic model. For amoxycillin peak concentrations of 0.5, 1, and 4 mu g m l(-1) and half-lives of 3 and 15 hours were examined. For danofloxacin peak concentrations of 0.125, 0.5, and 1.5 mu g ml(-1) and half-lives of 1.5 an d 7 hours were evaluated. The initial bactericidal effect was measured as the reduction in colony cou nt (log CFU ml(-1)) during the first three hours, and the overall pharmacod ynamic effect as the area under the bacterial growth versus time curve (AUB C). The initial bactericidal effect of amoxycillin was maximal at peak conc entrations of two to four times the hnc. Peak concentration and half-life o nly influenced the pharmacodynamic effect of amoxycillin if the antibiotic concentration fell below the MIC during the experiments, which is consisten t with time > Mle as the most important parameter of pharmacodynamic effect of beta-lactam drugs. For danofloxacin maximal bactericidal effect initially was observed at peak concentrations of at least eight times the we. The pharmacodynamic effect was dependent on the peak concentration. The half-life only influenced the pharmacodynamic effect of danofloxacin in experiments with a peak concentra tion MIC ratio of less than eight. This indicated that for danofloxacin the peak concentration was the major determinant of pharmacodynamic effect.