Uptake of azithromycin by human monocytes and enhanced intracellular antibacterial activity against Staphylococcus aureus.

The uptake of azithromycin by human monocytes and the intracellular antibacterial activity of azithromycin against Staphylococcus aureus were investigated. With an extracellular pH of 6.9, the maximum intracellular concentration of azithromycin in monocytes was about six times the extracellular concentration. The half-life for diffusion was 44 min. The results support the view that no active transport is involved in the intracellular accumulation of azithromycin. In cell-free medium, the maximum effect of azithromycin on S. aureus was bacteriostasis, which was achieved at a concentration of 5 mg/liter. In contrast, concentrations greater than 1.5 mg of azithromycin per liter were bactericidal for S. aureus ingested by monocytes. The difference in maximum growth inhibition on S. aureus for the two conditions was 0.1.68 h-1 (95% confidence interval, 0.128 to 0.208). The concentration of the drug that achieved 50% of the maximum effect was 0.434 mg/liter for both conditions. The enhancement of the effect on S. aureus ingested by monocytes suggests that the intracellular environment in human monocytes favors the antibacterial action of azithromycin. Enhancement of the antibacterial activity of azithromycin was not observed with granulocytes.