Journal Article

Dicloxacillin and erythromycin at high concentrations increase ICAM-1 expression by endothelial cells: a possible factor in the pathogenesis of infusion phlebitis

Peter Lanbeck, Inga Odenholt and Kristian Riesbeck

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 53, issue 2, pages 174-179
Published in print February 2004 | ISSN: 0305-7453
Published online February 2004 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dkh056
Dicloxacillin and erythromycin at high concentrations increase  ICAM-1 expression by endothelial cells: a possible factor in the pathogenesis of infusion phlebitis

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Objectives: Antimicrobial agents are important risk factors for infusion phlebitis, but the risk varies between different antibiotics. Erythromycin and dicloxacillin are known to induce phlebitis frequently, as well as to exert toxic effects on cultured endothelial cells. The pathogenesis of infusion phlebitis is unclear, but chemical toxicity is thought to lead to inflammation and subsequent thrombosis. In the present study, endothelial cells were exposed to antibiotics at the range of concentrations used for intravenous administration, followed by analysis of pro-inflammatory and pro-coagulant surface molecules.

Methods: Primary human umbilical vein endothelial cells (HUVEC) and the endothelial hybrid cell line EaHy926 were exposed to dicloxacillin, erythromycin, benzylpenicillin and cefuroxime (all at 6250 mg/L) for 60 min, followed by washing. After 5 or 24 h additional incubation, cells were analysed for E-selectin (CD62E), tissue factor (TF) or intercellular adhesion molecule 1 (ICAM-1, CD54) density by flow cytometry.

Results: Despite constitutive expression of ICAM-1 (34%) in HUVEC, 6250 mg/L of dicloxacillin or erythromycin significantly increased the number of cells with ICAM-1 expression by 37% and 30%, respectively. In contrast, cefuroxime and benzylpenicillin did not up-regulate ICAM-1 above background levels. A similar pattern was seen with the endothelial cell line EaHy926. The E-selectin and TF density were not affected by the antibiotics examined.

Conclusions: The results of this study support the theory that endothelial cells that are affected by high concentrations of antibiotics may initiate an inflammatory response through expression of ICAM-1. This is a novel finding in the pathogenesis of infusion phlebitis.

Keywords: Keywords: phlebitis/chemically induced, antibiotics, adhesion molecules, CD54

Journal Article.  3449 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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