Antibiotics and infusion phlebitis. Clinical and experimental studies

Abstract: Intravenous administration of antibiotics is often followed by infusion phlebitis. In this condition are vessel irritation, inflammation and sometimes superficial thrombosis included. In this thesis, the risk for infusion phlebitis for various antibiotics has been evaluated in a clinical study in 550 patients. Various effects of four antibiotics on cultured endothelial cells have also been examined. The aim was to find a simple cytotoxic assay for assessment of the phlebitogenic properties of i.v. antibiotics. In the clinical studies, it was found that patients on treatment with i.v. antibiotics had a doubled risk for infusion phlebitis (odds ratio 2.34). Dicloxacillin, erythromycin, cloxacillin, benzylpenicillin and cefuroxime, in that order, were the antibiotics associated with a higher risk for infusion phlebitis. In pair-wise comparison, dicloxacillin was found to confer a higher risk than cloxacillin. Other significant risk factors were the insertion site of the peripheral venous catheter and patients being 51-60 years. In the experimental studies, dicloxacillin and erythromycin, but not benzylpenicillin or cefuroxime, were found to inhibit DNA-synthesis in endothelial cells. The inhibition was dose dependent and time-related. Antibiotic concentrations and incubation times in the experiments were close to those used in the clinic. Dicloxacillin and erythromycin increased the expression of ICAM-1 in human umbilical vein endothelial cells, a finding with possible implications of the pathogenesis of infusion phlebitis. In conclusion, the concordance of the clinical and experimental studies in this thesis indicates that testing of i.v. antibiotics on endothelial cells is a valid test model for phlebitis prediction