Inhibition of Intracellular Growth of Staphylococcus aureus by Exposure of Infected Human Monocytes to Clarithromycin and Azithromycin

Abstract

The direct effect of clarithromycin and azithromycin on human polymorphonuclear leukocyte (PMN) functions and their intracellular activity against Staphylococcus aureus, phagocy-tosed by human monocytes, were studied. The presence of both antibiotics, in the range of concentrations from 0.25 to 20 μ/ml, did not affect chemotaxis, opsonized-zymosan phagocytosis, respiratory burst measured by nitroblue tetrazolium reduction and phorbol myristate acetate-induced superoxide production, or the microbicidal activity of human PMNs against Candida albicans. Both macrolides were bactericidal against staphylococci in the monocyte system, while bacteriostatic activity was found in cell free system. At concentrations equal to the minimum inhibitory concentrations (MICs) (0.75 and 0.1 respectively for azithromycin and clarithromycin) more than 99% of intraphagocytic S. aureus were killed after 24h incubation. Increasing the concentrations of each drug above the MICs (5 and 10 MICs) did not alter the killing rate of intracellular bacteria. Moreover, no differences between the intracellular bioactivity of these antibiotics were demonstrated, despite their different uptake kinetics.