Influence of human monocytes on the antibacterial activity of kanamycin and gentamicin for Staphylococcus aureus

The present study was performed to compare the antibacterial activities of kanamycin and gentamicin on Staphylococcus aureus phagocytosed by human monocytes and on nonphagocytosed S. aureus. The method used permitted the measurement of the effect of antibiotics on intracellular bacteria independent of phagocytosis and intracellular killing by the monocytes. A morphological assay with lysostaphin established the intracellular localization of about 70% of the cell-associated S. aureus in the monocyte-bacterium suspension. After 1 h of incubation, the antibacterial activity of both aminoglycosides was greater against intracellular than against nonphagocytosed S. aureus, but after 3 h, the reverse was true. The maximal effect on phagocytosed S. aureus, i.e., killing of about 98% of the bacteria, was reached in the first hour of incubation at kanamycin and gentamicin concentrations of 5 and 1 microgram/ml, respectively. A cell-free medium in which monocytes had been incubated increased the antibacterial activity of kanamycin, indicating that monocytes secrete a factor that enhances the antibacterial activity of aminoglycosides.