title: Compatibility of Injectable Anticoagulant Agents in Ethanol; In Vitro Antibiofilm Activity and Impact on Polyurethane Catheters of Enoxaparin 400 U/mL in 40% v/v Ethanol.
abstract: OBJECTIVE
  Interdialytic lock solutions should maintain catheter patency and prevent catheter infections. We aimed to determine in which conditions injectable anticoagulant agents (IAAs) combined with ethanol are compatible and to assess the antibiofilm activity of the selected combination and its effects on dialysis catheters (DC).
  
  
  METHODS
  The solubility and compatibility of unfractionated heparin (UFH), low molecular weight heparins (LMWHs), heparinoids and fondaparinux (50 to 2,500 U/mL) in 30 to 70% ethanol were determined by visual observation. The stability of enoxaparin in ethanol and the ethanol content were assessed by high performance liquid chromatography (HPLC) and titrimetric control, respectively. The bactericidal effect was determined on 24h-old biofilms embedded in silicone-DC. The integrity of polyurethane-DC immersed in anticoagulant-ethanol was assessed by gas chromatography-mass spectrometry (GC-MS) and compared with previously published results.
  
  
  RESULTS
  The compatibility of IAAs and ethanol varied according to IAA type and concentration, and ethanol content. UFH in 40% ethanol was not compatible, whatever the UFH concentration used. Established limits of compatibility of enoxaparin, nadroparin, dalteparin and tinzaparin in 40% ethanol were 1350, 575, 307 and 207 U/ml, respectively, and up to 300 U/ml for danaparoid and 1 mg/mL for fondaparinux. Enoxaparin 400 U/mL in 40% ethanol (Enox/Eth) eradicated biofilm after 4 hours of exposure for Staphylococcus epidermidis, Pseudomonas aeruginosa and Candida albicans and after 24 hours for Klebsiella pneumoniae and S. aureus. Aliphatic carbonate and alcohol compounds were released by polyurethane-DC after Enox/Eth exposure, as after 40% ethanol or saline exposure. There was no significant difference between the amounts released after 30 minutes of exposure to Enox/Eth and 15 days to saline.
  
  
  CONCLUSIONS
  A 40% ethanol solution can be combined with all IAAs but UFH. Enox/Eth was effective as an anti-biofilm agent with minor impacts on DC integrity and could be a useful interdialytic lock solution.
authors.affiliation: UMR CNRS 6023, Laboratoire Microorganismes: Génome et Environnement, Clermont Université, Université d'Auvergne, Clermont Ferrand, 63000, France.|Université d'Auvergne, Faculté de Pharmacie, Laboratoire de Bactériologie, F- 63001, Clermont-Ferrand, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Balestrino
authors.affiliation: Université d'Auvergne, Faculté de Pharmacie, Laboratoire de Chimie analytique et spectrométrie de masse, F- 63001, Clermont-Ferrand, France.|Inserm, UMR 990, IMTV, F-63005, Clermont-Ferrand, France.
authors.forename: Mercédès
authors.initials: M
authors.lastname: Quintana
authors.affiliation: Université d'Auvergne, Faculté de Pharmacie, Laboratoire de Bactériologie, F- 63001, Clermont-Ferrand, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Charbonnel
authors.affiliation: UMR CNRS 6023, Laboratoire Microorganismes: Génome et Environnement, Clermont Université, Université d'Auvergne, Clermont Ferrand, 63000, France.|Université d'Auvergne, Faculté de Pharmacie, Laboratoire de Bactériologie, F- 63001, Clermont-Ferrand, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Forestier
authors.affiliation: Inserm, UMR 990, IMTV, F-63005, Clermont-Ferrand, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Lartigue
authors.affiliation: UMR CNRS 6023, Laboratoire Microorganismes: Génome et Environnement, Clermont Université, Université d'Auvergne, Clermont Ferrand, 63000, France.|Réanimation Médicale, Hôpital Gabriel Montpied, CHU-Clermont-Ferrand, 63000, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Souweine
mesh_terms: D000418:Albumins / Q000378:metabolism; D000925:Anticoagulants / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D057785:Catheters; D005591:Chemical Fractionation; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid; D017984:Enoxaparin / Q000494:pharmacology*; D000431:Ethanol / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry; D006461:Hemolysis / Q000187:drug effects; D006495:Heparin, Low-Molecular-Weight; D006801:Humans; D007267:Injections; D011140:Polyurethanes / Q000494:pharmacology*; D012995:Solubility; D012996:Solutions
chemical_list: D000418:Albumins; D000925:Anticoagulants; D017984:Enoxaparin; D006495:Heparin, Low-Molecular-Weight; D011140:Polyurethanes; D012996:Solutions; D000431:Ethanol