Journal of Antimicrobial Chemotherapy (1992) 30, 509-523
© 1992 The British Society for Antimicrobial Chemotherapy
research-article |
Investigation of the in-vitro uptake, intraphagocytic biological activity and effects on nentrophil superoxide generation of dirithromycin compared with erythromycin
Medical Research Council Unit For The Study of Phagocyte Function, Department of Immunology, Institute For Pathology, University of Pretoria Pretoria 0001, Republic of South Africa
Received 25 October 1991; returned 20 March 1992; accepted 20 March 1992
The cellular uptake by human neutrophils and the intraphagocytic biological activity of the new macrolide antimicrobial agent dirithromycin (0-01-2 mg/L) compared with erythromycin was investigated in vitro. Staphylococcus aureus, Listeria monocytogenes and Legionella pneumophila were used as the test intra-ccllular microbial pathogens. After coincubation (45 min at 37°C) of neutrophils with a fixed concentration of 2 mg/L of each antibiotic the respective intracellular/extracellular ratios for erythromycin and dirithromycin were 6·1±2·5 and 10·6±2 respectively (P < 0·005). Using a combination of techniques (colony counting, radiometry and fluorescence microscopy) both erythromycin and dirithromycin at concentrations of 0·01 and 0·5 mg/L and higher, respectively, were found to possess dose-related intraphagocytic bacteristatic activity for each of the test microbial pathogens. The effects of dirithromycin and erythromycin (1–20 mg/L) on neutro-phil chemotaxis and generation of reactive oxidants by these cells were also investigated in vitro. Both antimicrobial agents caused a dose-related stimulation of neutrophil migration which was associated with inhibition of leucoattractant-acti-vated generation of superoxide and activity of the myeloperoxidase/H2O2/halide system. However, superoxide generation by neutrophils activited with opsonized zymosan or phorbol myristate acetate was unaffected by the macrolides. These findings demonstrate that dirithromycin accumulates in human neutrophils, is biologically active intracellularly and modulates leucoattractant-activated superoxide generation and chemotaxis.
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