title: Endothelial Cell Toxicity of Vancomycin Infusion Combined with Other Antibiotics.
abstract: French guidelines recommend central intravenous (i.v.) infusion for high concentrations of vancomycin, but peripheral intravenous (p.i.v.) infusion is often preferred in intensive care units. Vancomycin infusion has been implicated in cases of phlebitis, with endothelial toxicity depending on the drug concentration and the duration of the infusion. Vancomycin is frequently infused in combination with other i.v. antibiotics through the same administrative Y site, but the local toxicity of such combinations has been poorly evaluated. Such an assessment could improve vancomycin infusion procedures in hospitals. Human umbilical vein endothelial cells (HUVEC) were challenged with clinical doses of vancomycin over 24 h with or without other i.v. antibiotics. Cell death was measured with the alamarBlue test. We observed an excess cellular death rate without any synergistic effect but dependent on the numbers of combined infusions when vancomycin and erythromycin or gentamicin were infused through the same Y site. Incompatibility between vancomycin and piperacillin-tazobactam was not observed in our study, and rinsing the cells between the two antibiotic infusions did not reduce endothelial toxicity. No endothelial toxicity of imipenem-cilastatin was observed when combined with vancomycin. p.i.v. vancomycin infusion in combination with other medications requires new recommendations to prevent phlebitis, including limiting coinfusion on the same line, reducing the infusion rate, and choosing an intermittent infusion method. Further studies need to be carried out to explore other drug combinations in long-term vancomycin p.i.v. therapy so as to gain insight into the mechanisms of drug incompatibility under multidrug infusion conditions.
authors.affiliation: University Lille Nord de France, Lille, France Université Lille, CHU Lille, EA 7365, Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA), Lille, France Department of Pharmacy, Lille University Hospital, Lille, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Drouet
authors.affiliation: University Lille Nord de France, Lille, France INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, Université Lille, Lille, France.
authors.forename: Feng
authors.initials: F
authors.lastname: Chai
authors.affiliation: University Lille Nord de France, Lille, France Université Lille, CHU Lille, EA 7365, Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA), Lille, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Barthélémy
authors.affiliation: Department of Anesthesia and Intensive Care, Lille University Hospital, Lille, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Lebuffe
authors.affiliation: Department of Anesthesia and Intensive Care, Poitiers University Hospital, Inserm U1070, Poitiers, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Debaene
authors.affiliation: University Lille Nord de France, Lille, France Université Lille, CHU Lille, EA 7365, Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA), Lille, France Department of Pharmacy, Lille University Hospital, Lille, France bertrand.decaudin@univ-lille2.fr.
authors.forename: Bertrand
authors.identifier: http://orcid.org/0000-0001-8267-5594
authors.initials: B
authors.lastname: Décaudin
authors.affiliation: University Lille Nord de France, Lille, France Université Lille, CHU Lille, EA 7365, Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA), Lille, France Department of Pharmacy, Lille University Hospital, Lille, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Odou
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D015377:Cilastatin / Q000008:administration & dosage / Q000009:adverse effects; D000077728:Cilastatin, Imipenem Drug Combination; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000009:adverse effects*; D004917:Erythromycin / Q000008:administration & dosage / Q000009:adverse effects; D005839:Gentamicins / Q000008:administration & dosage / Q000009:adverse effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D015378:Imipenem / Q000008:administration & dosage / Q000009:adverse effects; D007262:Infusions, Intravenous / Q000379:methods; D014640:Vancomycin / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D005839:Gentamicins; D015377:Cilastatin; D004917:Erythromycin; D014640:Vancomycin; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination