In vitro and in vivo enhancement of bactericidal activity of phagocytes against Klebsiella pneumoniae treated with subminimal inhibitory concentrations of cefodizime.

The effects of a subminimal inhibitory concentration (sub-MIC) of cefodizime on the bactericidal activity of phagocytes against encapsulated Klebsiella pneumoniae were studied in an in vitro system using an established mouse macrophage cell line, and in an in vivo system using mice in which many phagocytes were induced in the peritoneal cavity. In the in vitro system, the bactericidal activity of mouse macrophages against K. pneumoniae treated with a sub-MIC of cefodizime was significantly enhanced, and was greater than that of cefotaxime or cefoperazone. Significantly more bacteria treated with a sub-MIC of cefodizime were killed by serum complement than those treated with cefotaxime or cefoperazone. In the in vivo system, cefodizime-treated bacteria were phagocytosed and killed by phagocytes in the mouse peritoneal cavity, whereas, cefotaxime- and cefoperazone-treated and untreated bacteria were hardly phagocytosed at all or killed by phagocytes in the mouse peritoneal cavity, and bacterial regrowth was observed 24 h after bacterial challenge. Furthermore, the virulence of K. pneumoniae in mice was reduced more by treatment with cefodizime than with cefotaxime or cefoperazone. These findings indicate that K. pneumoniae treated with a sub-MIC of cefodizime become more susceptible to the bactericidal activity of phagocytes both in vitro and in vivo. This provides evidence that cefodizime at a sub-MIC may act together with the phagocytes against bacterial infections.