EFFECT OF SINGLE ORAL DOSE OF AZITHROMYCIN, CLARITHROMYCIN, AND ROXITHROMYCIN ON POLYMORPHONUCLEAR LEUKOCYTE FUNCTION ASSESSED EX-VIVO BY FLOW-CYTOMETRY

Azithromycin was given as a single oral dose (20 mg/kg of body weight) to 12 volunteers in a crossover study with roxithromycin (8 to 12 mg/ kg) and clarithromycin (8 to 12 mg/kg), Flow cytometry was used to stu dy the phagocytic functions and the release of reactive oxygen product s following phagocytosis by neutrophil granulocytes prior to administr ation of the three drugs, 16 h after azithromycin administration, and 3 h after clarithromycin and roxithromycin administration, Phagocytic capacity was assessed by measuring the uptake of fluorescein isothiocy anate-labeled bacteria. Reactive oxygen generation after phagocytosis of unlabeled bacteria was estimated by the amount of dihydrorhodamine 123 converted to rhodamine 123 intracellularly. Azithromycin resulted in decreased capacities of the cells to phagocytize Escherichia coli ( median [range], 62% [27 to 91%] of the control values; P < 0.01) and g enerate reactive oxygen products (75% [34 to 26%] of the control value s; P < 0.01), Clarithromycin resulted in reduced phagocytosis (82% [75 to 98%] of control values; P < 0.01) but did not alter reactive oxyge n production (84% [63 to 113%] of the control values; P > 0.05), Roxit hromycin treatment did not affect granulocyte phagocytosis (92% [62 to 118%] of the control values; P > 0.05) or reactive oxygen production (94% [66 to 128%] of the control value; P > 0.05). No relation between intra- and/or extracellular concentrations of azithromycin and/or rox ithromycin and the polymorphonuclear phagocyte function and/or reactiv e oxygen production existed (P > 0.05 for all comparisons), These resu lts demonstrate that the accumulation of macrolides in neutrophils can suppress the response of phagocytic cells to bacterial pathogens afte r a therapeutic dose.