In vitro evaluation of the activities of azithromycin ( Zithromax ) alone and combined with pyrimethamine against Toxoplasma gondii.

By using an in vitro microassay to assess drug interaction, azithromycin ( Zithromax ) combined to pyrimethamine was found more active than pyrimethamine alone against Toxoplasma gondii, and additivity between those drugs was demonstrated. Our results show that the combination of azithromycin ( Zithromax ) and pyrimethamine may lead to a more rapid control of T. gondii.

The dicationic macrolide antibiotic azithromycin ( Zithromax ) inhibits the uptake of horseradish peroxidase (HRP) by fluid-phase pinocytosis in fibroblasts in a time- and concentration-dependent fashion without affecting its decay (regurgitation and/or degradation). The azithromycin ( Zithromax ) effect is additive to that of nocodazole, known to impair endocytic uptake and transport of solutes along the endocytic pathway. Cytochemistry (light and electron microscopy) shows a major reduction by azithromycin ( Zithromax ) in the number of HRP-labeled endocytic vesicles at 5 min (endosomes) and 2 h (lysosomes). Within 3 h of exposure, azithromycin ( Zithromax ) also causes the appearance of large and light-lucentlelectron-lucent vacuoles, most of which can be labeled by lucifer yellow when this tracer is added to culture prior to azithromycin ( Zithromax ) exposure. Three days of treatment with azithromycin ( Zithromax ) result in the accumulation of very large vesicles filled with pleiomorphic content, consistent with phospholipidosis. These vesicles are accessible to fluorescein-labeled bovine serum albumin (FITC-BSA) and intensively stained with filipin, indicating a mixed storage with cholesterol. The impairment of HRP pinocytosis directly correlates with the amount of azithromycin ( Zithromax ) accumulated by the cells, but not with the phospholipidosis induced by the drug. The proton ionophore monensin, which completely suppresses azithromycin ( Zithromax ) accumulation, also prevents inhibition of HRP uptake. Erythromycylamine, another dicationic macrolide, also inhibits HRP pinocytosis in direct correlation with its cellular accumulation and is as potent as azithromycin ( Zithromax ) at equimolar cellular concentrations. We suggest that dicationic macrolides inhibit fluid-phase pinocytosis by impairing the formation of pinocytic vacuoles and endosomes.

Azithromycin ( Zithromax ) is an important antibiotic for the treatment of several different Gram-positive and Gram-negative bacterial infections. Erythromycin and clarithromycin are less useful antibiotics against Gram-negative infections. This difference in inhibitory activity was explored by comparing the effects of azithromycin ( Zithromax ) and erythromycin on cellular functions in Haemophilus influenzae cells. Effects of both antibiotics on translation, cell viability, and growth rates have been measured. An IC(50) of 0.4 microg/ml was found for the effects of azithromycin ( Zithromax ) on each of these processes. For erythromycin, an IC(50) of 1.5 microg/ml was observed, indicating a fourfold lower sensitivity of the organisms to this compound. The features of a second target for macrolide antibiotic inhibition in H. influenzae cells have also been examined. Inhibition of the synthesis of the large 50S ribosomal subunit was measured. Subunit formation was prevented in a concentration dependent fashion, with azithromycin ( Zithromax ) showing a ninefold greater effect on this process compared with erythromycin. Synthesis of the 30S ribosomal subunit was not effected. Pulse and chase labeling kinetics confirmed the slower synthesis rate of the 50S particle in the presence of each antibiotic. The results are discussed in terms of the stronger effect of azithromycin ( Zithromax ) on ribosome biosynthesis in this organism.

Summary of the clinical studies with azithromycin ( Zithromax ) in the pediatric fields

The clinical studies with azithromycin ( Zithromax ) fine granules and capsules were conducted during the period from March 1993 to October 1994. Cmax's in 16 patients who received 10 mg/kg fine granules, were 0.29 +/- 0.24 microgram/ml, T1/2's were 42.0 +/- 11.8 hours, and AUC 0 approximately infinity's were 10.72 +/- 5.00 micrograms.hr/ml. The clinical results for azithromycin ( Zithromax ) fine granule and capsules 10 mg/kg once daily for 3 days are as follows. The efficacy rate of fine granules, combining both "Excellent" and "Good", for pneumoniae where causative pathogenes were identified, was 95.3%, and for those which had failed to respond to previous chemotherapies, was 94.6%, respectively. The efficacy rate of capsules for 3 to 5 days was 100% in 40 cases where causative pathogenes were identified. Adverse reactions were found in 2.5%(fine granules) and in 5.4%(capsules) in cases eligible for evaluation. Abnormal changes in laboratory test were as follows: decrease of WBC by 5.6%(fine granules) and 9.3%(capsules) and increase in eosinophils by 7.1%(fine granules) and 11.4% (capsules). 59.8% of the patients claimed that the azithromycin ( Zithromax ) 10% fine granules product was "easy to take". The result of a questionnaire on parents' demand on the improvement of antibiotics, showed that most concern was on the drug frequency(preferably once or twice daily) and the drug administering period(preferably short: 3 days). With regard to the efficacy, safety and compliance, it can be concluded that Azithromycin ( Zithromax ) is one of the useful therapeutic regimens in the treatment of pediatric infections.