Effect of penicillin G on the reproduction of Salmonella cholerasuis in the presence and absence of porcine alveolar macrophages in a pharmacodynamic model

Current antimicrobial susceptibility testing methods do not assess the influence of host defenses, the dynamics of drug disposition, or the interaction between changing drug concentrations and a bacterium in a host environment. The purpose of this research project was to modify an in vitro model for examining the effects of changing penicillin G concentrations on the reproduction of logarithmic growing Salmonella cholerasuis in the presence and absence of porcine alveolar macrophage (PAM). The results of an intra-arterial penicillin G dosing trial completed in swine indicated that the disappearance of penicillin from plasma could be accurately described by an open two-compartment model. A dynamic in vitro capillary model was modified to accurately simulate the disappearance of penicillin from swine after its intra-arterial administration. The in vitro model study was designed to determine if the number of Salmonella cholerasuis (MIC of 8 $\mu$g penicillin/ml) in four experimental chambers containing no penicillin, penicillin, PAM, and penicillin and PAM differed with respect to time. Three different doses of penicillin were used to determine if the inhibition of bacterial growth was dose related. Bacterial samples were removed from each of the four experimental chambers at six times points after drug administration in order to make the above comparisons. The peak drug concentrations obtained in the experimental chambers were 8.3 $\pm$ 0.5, 14.6 $\pm$ 1.9, and 30.7 $\pm$ 2.2 times the MIC of Salmonella cholerasuis. Maximum inhibition of bacterial growth occurred 2 hours following its addition to the central compartment. The increase in bacterial numbers after 2 hours coincided with the elimination of penicillin from the model. The dose effect proved to be statistically significant which indicated that increasing doses of penicillin produced decreases in the number of viable bacteria in the chambers containing the drug. The addition of PAMs did not produce a significant decrease in the number of viable bacteria in the chamber when compared to a chamber with no PAMs. The comparison to determine if penicillin and PAMs acted synergistically in reducing the numbers of Salmonella cholerasuis in experimental chambers was not statistically significant. However, slight nonsignificant depressions in the bacterial growth curves were observed in chambers containing penicillin and PAMs when compared to those observed in chambers containing only penicillin.U of I OnlyETDs are only available to UIUC Users without author permissio