Interference by Subinhibitory Concentrations of Azithromycin with the Mechanism of Bacterial Adhesion to Human Epithelial Cells

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Abstract
Azithromycin is the first member of a novel 15-membered-ring ‘azalide’ group of macrolides that has entered into clinical practice, and its activity is not restricted to gram-positive bacteria, but extends also to gram-negative bacteria. The aim of this study was to investigate the ability of subinhibitory concentrations (sub-MICs) of azithromycin to interfere with the mechanism of bacterial adhesion to human epithelial cells. Azithromycin induced a significant inhibition of adhesion from 1/2 to 1/32 MIC for Staphylococcus aureus and from 1/2 to 1/16 MIC for Escherichia coli. 1/32 of the MIC for S. aureus means 0.048 μg/ml, while 1/16 of the MIC for E. coli means 0.25 μg/ml. At these concentrations no morphological changes in E. coli shape were seen, while sometimes S. aureus cells larger than the normal size appeared. Tissue concentrations of azithromycin decline with an estimated half-life of 2.5-3 days. Since sub-MICs of 0.25 and 0.048 μg/ml are still able to interfere with bacterial physiology, the effective activity of azithromycin, from a pharmacokinetic point of view, could be extended for 3 days beyond the expected period of antimicrobial activity.

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