Uptake of azithromycin by various cells and its intracellular activity under in vivo conditions

Abstract

The concentrations of azithromycin in polymorphonuclear leukocytes (PMNLs), monocytes, erythrocytes, and plasma were measured in six healthy volunteers after the last treatment of a 3-day regimen of 500 mg once daily. Marked enrichment of azithromycin was found in PMNLs and monocytes. The drug concentrations after the last dose amounted to 114 +/- 43 (mean +/- standard deviation) mg/liter at 12 h in PMNLs and 34 +/- 17 mg/liter at 6 h in monocytes. Fourteen days thereafter, azithromycin was still detectable in the PMNLs at 53 +/- 34 mg/liter and in the monocytes at 1 +/- 2 mg/liter, although the drug was no longer detectable in plasma (< 0.02 mg/liter). Maximum drug concentrations for azithromycin in plasma (0.40 +/- 0.30 mg/liter) and erythrocytes (0.15 +/- 0.05 mg/liter) at 3 h after the last administration were much lower and occurred earlier than those observed in the phagocytic cells. The mean enrichment factors (cellular/extracellular ratios) of azithromycin in phagocytes relative to plasma came to 231 +/- 150 and 3,924 +/- 584 at 3 and 120 h, respectively, for PMNLs and 83 +/- 55 and 523 +/- 285 at 3 and 120 h for monocytes, respectively, after the last dose. The phagocytosis tests with PMNLs separated from the blood of volunteers at various times after the last treatment confirmed the enhanced intracellular activity of these cells against staphylococci.

Short‐Course Azithromycin for the Treatment of Uncomplicated Typhoid Fever in Children and Adolescents

“…This is possibly because susceptibility testing is based on serum drug levels, whereas for typhoid fever, a major mechanism of action is thought to be intracellular killing, in which the azithromycin levels may be 100-fold greater than serum levels [9][10][11].…”

“…Azithromycin, a member of the macrolide class of antibiotics, possesses many characteristics for effective and convenient treatment of typhoid fever, including in vitro activity against many enteric pathogens, excellent penetration into most tissues, and achievement of concentrations in macrophages and neutrophils that are 1100-fold higher than concentrations in serum [9][10][11]. Previous studies have demonstrated that a 7-day treatment course of azithromycin was highly effective against uncomplicated typhoid fever in adults and children [12][13][14].…”

Topical Azithromycin and Clarithromycin Inhibit Acute and Chronic Skin Inflammation in Sensitized Mice, with Apparent Selectivity for Th2-Mediated Processes in Delayed-Type Hypersensitivity

“…Azithromycin and clarithromycin accumulate in inflammatory cells, especially neutrophils and macrophages [5][6][7], inhibiting the synthesis of reactive oxygen species and/or secretion of cytokines and chemokines [3,[8][9][10][11]. Inhibition of adhesion molecule expression on epithelial cells, with suppression of leukocyte adhesion and infiltration into tissues has also been reported [3,8,12].…”

Triangular test applied to the clinical trial of azithromycin against relapses in Plasmodium vivax infections

“…Although early relapses cannot be ruled out, they are very unlikely because these patients were followed up for only 28 days. Recrudescence might be due to the insufficient free plasma and intra-erythrocytic [17] concentrations of azithromycin resulting from an insufficient dosing and/or too short a duration of the treatment. To allow for this, we administered a higher dose of azithromycin for a longer (7-day) course.…”