INFLUENCE OF AZITHROMYCIN AND OTHER MACROLIDES ON THE INTRACELLULAR KILLING OF STAPHYLOCOCCUS-AUREUS BY HUMAN POLYMORPHONUCLEAR LEUKOCYTES OF HEALTHY DONORS AND A PATIENT WITH CHEDIAK-HIGASHI-SYNDROME

A mixture of human blood phagocytes from healthy donors and opsonized staphylococci was incubated in vitro for 30 min. After that time all the bacteria were phagocytosed. The test tubes were further incubated for 2, 4 and 24 h with or without addition of a macrolide (erythromycin, azithromycin, clarithromycin, roxithromycin) and the effect of these drugs on the survival of intracellular staphylococci (Staphylococcus aureus ATCC 25923) was measured. The minimal effective concentration of the antibiotic which killed 80-90% of the bacteria after a 4-hour incubation was 0.1 mg/l for erythromycin, azithromycin and clarithromycin and 1.2 mg/l for roxithromycin. The percentage of surviving bacteria after 2 and 4 h incubation was not significantly different between these macrolides at the minimal effective concentration. Increasing the concentration of each antibiotic above the minimal effective concentration did not alter the killing rate of intracellular staphylococci. The bacterial activity of polymorphonuclear leucocytes (PMNL) from a patient with Chediak-Higashi syndrome was less in comparison to PMNL from healthy donors, but was improved in vitro by the addition of erythromycin or azithromycin.