UPTAKE OF AZITHROMYCIN BY HUMAN MONOCYTES AND ENHANCED INTRACELLULAR ANTIBACTERIAL ACTIVITY AGAINST STAPHYLOCOCCUS-AUREUS

The uptake of azithromycin by human monocytes and the intracellular an tibacterial activity of azithromycin against Staphylococcus aureus wer e investigated. With an extracellular pH of 6.9, the maximum intracell ular concentration of azithromycin in monocytes was about six times th e extracellular concentration. ne half-life for diffusion was 44 min. The results support the view that no active transport is involved in t he intracellular accumulation of azithromycin. In cell-free medium, th e maximum effect of azithromycin on S. aureus was bacteriostasis, whic h was achieved at a concentration of 5 mg/liter. In contrast, concentr ations 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 0.168 h-1 (95% con fidence 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 conditi ons. 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 antibacte rial activity of azithromycin was not observed with granulocytes.