title: Effect of quinupristin/dalfopristin on 3T3 and Eahy926 cells in vitro in comparison to other antimicrobial agents with the potential to induce infusion phlebitis.
abstract: Infusion phlebitis is a common clinical problem that is observed with some antimicrobial agents, when being administered intravenously. In this study, cultured murine fibroblasts and immortalised human endothelial cells were exposed to three antibiotics at clinically relevant concentrations to assess their toxic potential in two established cytotoxicity assays. BALB/c 3T3 fibroblasts and Eahy926 endothelial cells were exposed to quinupristin/dalfopristin (QD), erythromycin and levofloxacin at increasing concentrations. For assessment of cytotoxicity the cells were incubated with neutral red (NR) or stained with crystal violet (CV). Measurements were done by photometry. At the concentration range tested QD and erythromycin showed a concentration-dependent cytotoxic effect in both cell cultures. In 3T3 cells the half-maximal effect concentration (EC50) was 20 mg/l for QD and 340 mg/l for erythromycin in the NR uptake test and 12 and 200 mg/l, respectively, in the CV assay. In Eahy926 cells the EC50 was 50 mg/l for QD and 880 mg/l for erythromycin in the NR uptake test and 40 and 750 mg/l, respectively, in the CV assay. No EC50 could be established in both cell types for levofloxacin. Eahy926 cells were less sensitive to cytotoxic stimuli than 3T3 fibroblasts. Cytotoxic effects in both cell cultures occurred in the following order: QD > erythromycin >> levofloxacin. This ranking correlates well with the frequency of local adverse effects observed with the infusion of these antibiotics in patients. Thus, these in vitro assays may serve as an estimate for the prediction of local tolerability of antibiotics when administered parenterally.
authors.affiliation: Department of Toxicology, Institute of Clinical Pharmacology and Toxicology, Charité Campus Benjamin Franklin, Garystr. 5, 14195 Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kruse
authors.forename: Bülent
authors.initials: B
authors.lastname: Kilic
authors.forename: Burkhard
authors.initials: B
authors.lastname: Flick
authors.forename: Ralf
authors.initials: R
authors.lastname: Stahlmann
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000633:toxicity*; D041702:BALB 3T3 Cells; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects*; D004917:Erythromycin / Q000008:administration & dosage / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D020128:Inhibitory Concentration 50; D064704:Levofloxacin; D051379:Mice; D019055:No-Observed-Adverse-Effect Level; D015242:Ofloxacin / Q000008:administration & dosage / Q000633:toxicity*; D010689:Phlebitis / Q000139:chemically induced*; D015203:Reproducibility of Results; D018675:Toxicity Tests / Q000379:methods*; D014769:Virginiamycin / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D000900:Anti-Bacterial Agents; D014769:Virginiamycin; C062940:quinupristin-dalfopristin; D004917:Erythromycin; D064704:Levofloxacin; D015242:Ofloxacin