AZITHROMYCIN INDUCES IN-VITRO A TIME-DEPENDENT INCREASE IN THE INTRACELLULAR KILLING OF STAPHYLOCOCCUS-AUREUS BY HUMAN POLYMORPHONUCLEAR LEUKOCYTES WITHOUT DAMAGING PHAGOCYTES

Despite its clinical efficacy on intracellular pathogens, the in-vitro intracellular antimicrobial activity of azithromycin, has been shown to be absent or lower than expected from the intracellular concentrati ons reached. To test the possibility that the high intracellular conce ntrations of the drug could damage phagocytes, the present study evalu ated the effects of azithromycin on (a) the intracellular killing of S taphylococcus aureus by human blood neutrophils (PMNs) and (b) the via bility and the respiratory burst of PMNs. Using a fluorochrome assay, we assessed the phagocytosis and intracellular killing of S. aureus by PMNs preloaded with azithromycin, or by PMNs unloaded but with the dr ug in the culture medium. In addition, possible drug-induced damage to PMNs was evaluated measuring: (a) hydrogen peroxide (H2O2) production and (b) the percentages of PMNs dead at the end of the phagocytosis p rocess. Compared to control PMNs without drug, a time-dependent enhanc ement in the intracellular killing was observed which was statisticall y significant after 60 min incubation. The increased intracellular kil ling was higher in suspensions of unloaded PMNs and azithromycin (P < 0.01) that in suspensions of preloaded PMNs (P < 0.05). This increased intracellular killing was not associated with increased proportions o f dead phagocytes, either in preloaded or unloaded PMNs (P < 0.05, eac h comparison). Similarly no changes in the production of H2O2 by PMNs were observed in the presence of azithromycin. Thus, azithromycin indu ces a time-dependent increase in the bactericidal activity of human PM Ns, without increasing the phagocyte self-killing or modifying H2O2 pr oduction.