Activity of aminoglycosides against phagacytosed bacteria

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Abstract
The intracellular activity of streptomycin, getamicin, and netilmicin on Escherichia coli phagocytosed by murinc peritoneal macrophages was studied using a sensitive and standardized method. Intracellular activity of streptomycin and gentamicin at therapeutic concentrations was seen after 1 h of incubation of antibiotics with macrophages containing phagocytised bacteria, whilst for netilmicin a significant intracellular activity was observed only after 3 h exposure. The activity of these antibiotics against intraphagocytic bacteria was significantly lower than that observed against extracellular bacteria Sub-inhibitory concentrations of streptomycin were active against intracellular E. coli. Streptomycin was also active for a phagocytosed streptomycin-resistant strain of E. coli, but this activity was eliminated when the O2dependent killing mechanisms of macrophages werc inhibited by sodium fluoride. The data demonstrate that aminoglycosides may exert a dose-dependent intraphagocytic activity against E. coli that correlates with the time of incubation of the antibiotics with infected macrophagcs. Streptomycin appears to be the most effective agent followed by gentamicin and the least active was netilmicin.In the case of streptomycin, the intraphagocytic activity seems to be due, at least in part., to the stimulation of O2-dependent cellular microbactericidal mechanisms.

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