alexa Antibiotic penetration of and bactericidal activity within endothelial cells.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Darouiche RO, Hamill RJ

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Abstract It has been observed that the number of cases of infective endocarditis arising in patients who have no previous identifiable cardiac abnormalities is increasing, suggesting that direct bacterial interactions with endothelium may occur. Furthermore, the prolonged natural history of endocarditis, need for lengthy therapy, and frequency of relapse suggest that intracellular bacteria that may be protected from antimicrobial action and host responses exist. Using high-performance liquid chromatography, we investigated the penetration of seven antibiotics used to treat Staphylococcus aureus infections into cultured human umbilical vein endothelial cells and the effect of these antibiotics on the intracellular killing of two strains of the organism. In general, endothelial cell penetration of lipophilic drugs, such as minocycline, ciprofloxacin, and rifampin, exceeded that of hydrophilic drugs, represented by nafcillin, cefazolin, cefuroxime, and vancomycin. Bacterial killing paralleled the intracellular penetration of all the antibiotics except rifampin, which concentrated well inside cells but had poor killing activity. However, when combined with the other antibiotics, rifampin potentiated their killing activity against intracellular S. aureus.
This article was published in Antimicrob Agents Chemother and referenced in Journal of Bioequivalence & Bioavailability

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