title: Dicloxacillin and erythromycin at high concentrations increase ICAM-1 expression by endothelial cells: a possible factor in the pathogenesis of infusion phlebitis.
abstract: OBJECTIVE
  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.
authors.affiliation: Departments of Infectious Diseases and Medical Microbiology, Malmö University Hospital, Lund University, SE 205 02 Malmö, Sweden. Peter.Lanbeck@inf.mas.lu.se
authors.forename: Peter
authors.initials: P
authors.lastname: Lanbeck
authors.forename: Inga
authors.initials: I
authors.lastname: Odenholt
authors.forename: Kristian
authors.initials: K
authors.lastname: Riesbeck
mesh_terms: D000900:Anti-Bacterial Agents / Q000633:toxicity*; D002460:Cell Line; D004009:Dicloxacillin / Q000633:toxicity*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004917:Erythromycin / Q000633:toxicity*; D005434:Flow Cytometry; D006801:Humans; D007262:Infusions, Intravenous / Q000009:adverse effects*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D010406:Penicillins / Q000633:toxicity*; D010689:Phlebitis / Q000139:chemically induced* / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D010406:Penicillins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D004917:Erythromycin; D013925:Thromboplastin; D004009:Dicloxacillin