Enhanced phagocytosis, killing, and serum sensitivity of Escherichia coli and Staphylococcus aureus treated with sub-MICs of imipenem

The influence of pretreatment of Escherichia coli and Staphylococcus aureus with sub-MICs of the new beta-lactam antibiotic imipenem on phagocytosis and killing by murine peritoneal macrophages and the susceptibility of these organisms to serum bactericidal activity were studied. The effects of imipenem, a round form inducer in gram-negative rods, and piperacillin, a filamentous form inducer, were compared. Bacteria grown in the presence of sub-MICs of imipenem or piperacillin were incubated for 30 min with macrophage monolayers in the absence of antibiotic. Phagocytosis, killing, and survival within macrophages were evaluated by microbiological and fluorescence microscope assays. Bacteria grown in the presence of a sub-MIC of imipenem were phagocytized and killed in numbers significantly higher than untreated or piperacillin-treated bacteria were. Intracellular bacteria pretreated with a sub-MIC of imipenem were also readily killed by lymphokine-activated macrophages. Prior treatment with a sub-MIC of imipenem resulted in an increased susceptibility of E. coli but not S. aureus to the bactericidal activity of immune serum. Imipenem treatment and immune serum acted synergistically to enhance phagocytosis and killing. The data indicate that exposure of E. coli and S. aureus to a sub-MIC of imipenem enhances the susceptibility of these potential pathogens to cellular and humoral host defense mechanisms.