Inhibition of Intracellular Growth ofStaphylococcus aureusby 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, phagocytosed by human monocytes, were studied. The presence of both antibiotics, in the range of concentrations from 0.25 to 20 micrograms/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 24 h 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.

Azithromycin, a Lysosomotropic Antibiotic, Has Distinct Effects on Fluid-Phase and Receptor-Mediated Endocytosis, but Does Not Impair Phagocytosis in J774 Macrophages

“…This is consistent with other reports indicating that azithromycin does not impair the uptake of opsonized Staphylococcus aureus or zymosan [58,59] and underlines that endocytosis and phagocytosis are distinct processes, governed, at least partly, by distinct machineries.…”

Azithromycin, a Lysosomotropic Antibiotic, Has Distinct Effects on Fluid-Phase and Receptor-Mediated Endocytosis, but Does Not Impair Phagocytosis in J774 Macrophages

“…Third, azithromycin clearly leaves the phagocytosis pathway completely unaffected, which is an interesting feature for an antibiotic in a clinical perspective, since phagocytosis of bacteria is an important component of a successful host defense against infection. This is consistent with other reports indicating that azithromycin does not impair the uptake of opsonized Staphylococcus aureus or zymosan [58,59] and underlines that endocytosis and phagocytosis are distinct processes, governed, at least partly, by distinct machineries.…”

Disposition of oral telithromycin in foals and in vitro activity of the drug against macrolide‐susceptible and macrolide‐resistant Rhodococcus equi isolates

“…, 2009). A beneficial consequence of accumulation within cells is increased activity against intracellular pathogens (Labro, 1996; Fietta et al. , 1997).…”