| Autor: |
I. García, A. Pascual, S. Ballesta, C. del Castillo, E.J. Perea |
| Předmět: |
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| Zdroj: |
Journal of Antimicrobial Chemotherapy (JAC); Jul2003, Vol. 52 Issue 1, p24-28, 5p |
| Abstrakt: |
Objectives: To evaluate the penetration of ketolide cethromycin (ABT-773) into human polymorphonuclear leucocytes (PMNs) and its intracellular activity. Methods: The uptake of radiolabelled cethromycin by PMNs was determined by a velocity gradient centrifugation technique. The activity of cethromycin against intracellular Staphylococcus aureus ATCC 25923 in PMNs was also evaluated. Results: The cellular to extracellular concentration (C/E) ratio for cethromycin was >200 at an extracellular concentration of 2 mg/L. The uptake of cethromycin into PMNs was rapid and saturable. Cethromycin was slowly released from the loaded PMNs (cell associated drug>50% after 2 h of incubation). Intracellular penetration was significantly affected by the environmental temperature (C/E ratio at 4°C and 37°C: 13 ± 6 and 226 ± 31, respectively; P < 0.05), by cell viability (C/E ratio for dead and viable cells: 100 ± 38 and 226 ± 31, respectively; P < 0.05), by pH (C/E ratio was significantly increased at basic pH) and by the metabolic inhibitors 2,4-dinitrophenol and carbonyl cyanide m-chlorophenylhydrazone. The intracellular accumulation of cethromycin also decreased significantly when cells were activated with phorbol myristate acetate or opsonized zymosan. These data indicate that a potentially active mechanism could be involved in the uptake of cethromycin by PMNs. At high extracellular concentrations of 5 and 10 mg/L, cethromycin showed significant intracellular activity against S. aureus. Conclusions: Cethromycin achieves high intracellular concentrations within human PMNs, remaining active intracellularly. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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