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 study the phagocytic functions and the release of reactive oxygen products following phagocytosis by neutrophil granulocytes prior to administration 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 isothiocyanate-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 generate reactive oxygen products (75% [34 to 26%] of the control values; P < 0.01). Clarithromycin resulted in reduced phagocytosis (82% [75 to 98%] of control values; P < 0.01) but did not alter reactive oxygen production (84% [63 to 113%] of the control values; P > 0.05). Roxithromycin 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 roxithromycin and the polymorphonuclear phagocyte function and/or reactive oxygen production existed (P > 0.05 for all comparisons). These results demonstrate that the accumulation of macrolides in neutrophils can suppress the response of phagocytic cells to bacterial pathogens after a therapeutic dose.
Wenisch
C
C
Department of Infectious Diseases, Internal Medicine I, University Hospital of Vienna, Austria.
Parschalk
B
B
Zedtwitz-Liebenstein
K
K
Weihs
A
A
el Menyawi
I
I
Graninger
W
W
D000328:Adult; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D017963:Azithromycin / Q000378:metabolism / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D017291:Clarithromycin / Q000378:metabolism / Q000494:pharmacology*; D018592:Cross-Over Studies; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015575:Roxithromycin / Q000378:metabolism / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D017382:Reactive Oxygen Species; D015575:Roxithromycin; D017963:Azithromycin; D017291:Clarithromycin