Exposure time-dependent bactericidal activities of amoxicillin against Actinobacillus pleuropneumoniae; an in vitro and In vivo pharmacodynamic model

The pharmacodynamic effects of amoxicillin against Actinobacillus pleuropneumoniae at exposure concentration above and below minimum inhibitory concentration (MIC) were evaluated in both in vitro and in vivo. In vitro, the growth and morphological change of A. pleuropneumoniae in culture medium was observed. In vivo, the efficacy of amoxicillin on experimentally induced A. pleuropneumoniae infection in disease-free pigs was evaluated. Fifteen pigs were divided into three groups (n = 5 per group). After the onset of clinical respiratory disease symptoms, 6 h post-infection, amoxicillin sustained-release injectable formulation was injected intramuscularly at 7.5 mg/kg/day (group I) and 15 mg/kg/day (group II). Then the serum concentration of amoxicillin was measured. An untreated infected group served as controls. In each amoxicillin administration group, if symptoms were not absent after 48 h, the pig was injected with the amoxicillin sustained-release injectable formulation again using the same dosage. In vitro, the growth of A. pleuropneumoniae inhibited by amoxicillin exposure at the concentration above the MIC (1.28 x MIC), and the inhibition time was in directly proportion to the time of amoxicillin exposure. Moreover, all the cells were lysed. Whereas the bacterial growth inhibition at the amoxicillin exposure concentration below the MIC (0.25 x MIC) was not done, and the shape of cells were normal or long filamentous. In vivo, the group I clinical and pathological score was higher than the group II, and the group I weight gain was significantly less than the group II. Performance with respect to weight gain corresponded with clinical signs. The infected control group was severely affected with an 80% (4/5) mortality rate 24-96 h post-challenge. The duration of time above MIC (T > MIC) of serum amoxicillin concentration in the group I was less than group II. The present studies suggest that amoxicillin has exposure time-dependent bactericidal activity against A. pleuropneumoniae.