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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 intracellular microbial pathogens. After coincubation (45 min at 37 degrees 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 neutrophil 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-activated 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. [ABSTRACT FROM AUTHOR]

The effects of erythromycin on neutrophil random migration and motility to the leucoattractant endotoxin-activated serum (EAS), post-phagocytic hexosemonophosphate shunt activity (HMS), myeloperoxidase (MPO)-mediated iodination of ingested and lymphocyte transformation to the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A) have been investigated and . For studies erythromycin was investigated as the base compound and as the stearate and succinate forms. Erythromycin stearate was used for studies in normal adult volunteers. Erythromycin but not caused significant stimulation of neutrophil motility and random migration at concentrations of 10 M -5 × 10 M. These concentrations caused inhibition of MPO-mediated iodination. Slight but insignificant stimulation of lymphocyte-transformation to both mitogens following ingestion of erythromycin was observed. The migration-stimulatory effects of erythromycin were potentiated by ascorbate and thiamine and by thiamine . Using the horse-radish peroxidase (HRP)/HO/sodium iodide system it was demonstrated that the enhancing effect of erythromycin on neutrophil motility and lymphocyte transformation was due to the anti-oxidant activity of the anti biotic. Exposure to the HRP/HO/iodide system had no adverse effects on the antimicrobial activity of erythromycin. [ABSTRACT FROM PUBLISHER]

The effects of erythromycin stearate over a concentration range of 10–10 on neutrophil functions were investigated. It was found that erythromycin at concentrations of 10–10 caused detectable stimulation of chemotaxis to autologous endotoxin-activated serum and inhibition of neutrophil post-phagocytic myelperoxidase mediated protein iodination at concentrations of >5×10. No effects on phagocytosis or post-phagocytic hexose monophosphate shunt activity were observed. studies before and after the ingestion of therapeutic doses of erythromycin by six individuals showed no change in neutrophil functions and levels of serum immunoglobulins IgG, IgA and IgM, total haemolytic complement and serum levels of the complement components C3 and C4. However ingestion of erythromycin was associated with increased lymphocyte transformation in five individuals. [ABSTRACT FROM PUBLISHER]

Erythromycin base and its 6-0-methyl derivative clarithromycin were actively accumulated 7.3 +/- 1.2-fold and 9.2 +/- 2-fold respectively by human neutrophils in vitro. The intraphagocytic bioactivities of the antimicrobial agents were investigated using the combination of a radioassay, colony counting method and a fluorescence microassay which facilitates the distinction between intracellular bacteriostatic and bactericidal mechanisms. Staphylococcus aureus, Listeria monocytogenes and Legionella micdadei were used as the test intraphagocytic microbial pathogens. Both agents were found to possess intracellular bioactivity for all three species of bacteria with clarithromycin being consistently more active than erythromycin. Under the assay conditions used both agents were bacteriostatic (intracellularly) for S. aureus and Leg. micdadei and bactericidal for List. monocytogenes. Clarithromycin is clearly a potent intraphagocytic antibiotic and potentially superior in this respect to erythromycin. [ABSTRACT FROM AUTHOR]