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Factors affecting the intracellular accumulation and activity of azithromycin
A Pascual1, M C Conejo, I García
1Department of Microbiology, School of Medicine, Sevilla, Spain.
Abstract:
Azithromycin is a new macrolide which accumulates in high concentrations in human phagocytes. The cellular to extracellular ratio (C/E) of azithromycin concentrations (fixed extracellular concentration 1 mg/L) in human polymorphonuclear leucocytes (PMN) were significantly affected by small increases in the environmental temperature (C/E 20.3 +/- 2 and 59.4 +/- 6 at 37 degrees C and 40 degrees C, respectively). PMN-associated azithromycin was not affected by the presence of different concentrations of human serum. The intracellular accumulation of azithromycin decreased slightly (C/E approximately 5) when cells were activated with PMA or opsonized with zymosan. The phagocytosis of opsonized Staphylococcus aureus or Haemophilus influenzae, however, slightly increased the intracellular concentrations of azithromycin. At different extracellular concentrations, azithromycin did not affect the production of hydrogen peroxide and superoxide radicals by PMN. The intracellular survival of H. influenzae in human PMN was abolished in the presence of concentrations higher than 0.125 mg/L of azithromycin. Under the same experimental conditions, however, azithromycin did not show any intracellular activity against S. aureus.
Insights
Azithromycin accumulates in human phagocytes, with temperature significantly impacting its concentration. This macrolide antibiotic effectively eliminates intracellular Haemophilus influenzae but not Staphylococcus aureus.
Area of Science:
- Pharmacology
- Microbiology
- Cell Biology
Background:
- Azithromycin is a macrolide antibiotic known for its accumulation in human phagocytic cells.
- Understanding azithromycin's intracellular behavior is crucial for optimizing its therapeutic efficacy.
Purpose of the Study:
- To investigate the factors influencing azithromycin accumulation in human polymorphonuclear leucocytes (PMN).
- To evaluate the effect of azithromycin on PMN function and intracellular bacterial survival.
Main Methods:
- Human PMN were incubated with azithromycin under varying temperature and serum conditions.
- Cellular azithromycin concentrations were measured, and PMN function (oxidative burst) was assessed.
- The intracellular survival of Staphylococcus aureus and Haemophilus influenzae within PMN was determined in the presence of azithromycin.
Main Results:
- Azithromycin accumulation in PMN was significantly temperature-dependent, increasing with higher temperatures.
- Cell activation or opsonization slightly decreased intracellular azithromycin, while phagocytosis of bacteria slightly increased it.
- Azithromycin effectively eradicated intracellular H. influenzae at concentrations above 0.125 mg/L but showed no activity against intracellular S. aureus.
Conclusions:
- Environmental temperature is a key factor modulating azithromycin's intracellular concentration in PMN.
- Azithromycin demonstrates selective intracellular bactericidal activity, being effective against H. influenzae but not S. aureus.