PMID- 27441664
OWN - NLM
STAT- MEDLINE
DCOM- 20170731
LR  - 20190212
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 7
DP  - 2016
TI  - 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.
PG  - e0159475
LID - 10.1371/journal.pone.0159475 [doi]
LID - e0159475
AB  - BACKGROUND AND OBJECTIVES: 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.
FAU - Balestrino, Damien
AU  - Balestrino D
AD  - UMR CNRS 6023, Laboratoire Microorganismes: Genome et Environnement, Clermont 
      Universite, Universite d'Auvergne, Clermont Ferrand, 63000, France.
AD  - Universite d'Auvergne, Faculte de Pharmacie, Laboratoire de Bacteriologie, F- 
      63001, Clermont-Ferrand, France.
FAU - Quintana, Mercedes
AU  - Quintana M
AD  - Universite d'Auvergne, Faculte de Pharmacie, Laboratoire de Chimie analytique et 
      spectrometrie de masse, F- 63001, Clermont-Ferrand, France.
AD  - Inserm, UMR 990, IMTV, F-63005, Clermont-Ferrand, France.
FAU - Charbonnel, Nicolas
AU  - Charbonnel N
AD  - Universite d'Auvergne, Faculte de Pharmacie, Laboratoire de Bacteriologie, F- 
      63001, Clermont-Ferrand, France.
FAU - Forestier, Christiane
AU  - Forestier C
AD  - UMR CNRS 6023, Laboratoire Microorganismes: Genome et Environnement, Clermont 
      Universite, Universite d'Auvergne, Clermont Ferrand, 63000, France.
AD  - Universite d'Auvergne, Faculte de Pharmacie, Laboratoire de Bacteriologie, F- 
      63001, Clermont-Ferrand, France.
FAU - Lartigue, Claire
AU  - Lartigue C
AD  - Inserm, UMR 990, IMTV, F-63005, Clermont-Ferrand, France.
FAU - Souweine, Bertrand
AU  - Souweine B
AD  - UMR CNRS 6023, Laboratoire Microorganismes: Genome et Environnement, Clermont 
      Universite, Universite d'Auvergne, Clermont Ferrand, 63000, France.
AD  - Reanimation Medicale, Hopital Gabriel Montpied, CHU-Clermont-Ferrand, 63000, 
      France.
LA  - eng
PT  - Journal Article
DEP - 20160721
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Albumins)
RN  - 0 (Anticoagulants)
RN  - 0 (Enoxaparin)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Polyurethanes)
RN  - 0 (Solutions)
RN  - 3K9958V90M (Ethanol)
SB  - IM
MH  - Albumins/metabolism
MH  - Anticoagulants/*pharmacology
MH  - Biofilms/*drug effects
MH  - *Catheters
MH  - Chemical Fractionation
MH  - Chemical Precipitation
MH  - Chromatography, High Pressure Liquid
MH  - Enoxaparin/*pharmacology
MH  - Ethanol/*chemistry
MH  - Gas Chromatography-Mass Spectrometry
MH  - Hemolysis/drug effects
MH  - Heparin, Low-Molecular-Weight
MH  - Humans
MH  - *Injections
MH  - Polyurethanes/*pharmacology
MH  - Solubility
MH  - Solutions
PMC - PMC4956118
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2016/07/22 06:00
MHDA- 2017/08/02 06:00
PMCR- 2016/07/21
CRDT- 2016/07/22 06:00
PHST- 2016/05/24 00:00 [received]
PHST- 2016/06/08 00:00 [accepted]
PHST- 2016/07/22 06:00 [entrez]
PHST- 2016/07/22 06:00 [pubmed]
PHST- 2017/08/02 06:00 [medline]
PHST- 2016/07/21 00:00 [pmc-release]
AID - PONE-D-16-20619 [pii]
AID - 10.1371/journal.pone.0159475 [doi]
PST - epublish
SO  - PLoS One. 2016 Jul 21;11(7):e0159475. doi: 10.1371/journal.pone.0159475. 
      eCollection 2016.