title: Catheter lock solutions influence staphylococcal biofilm formation on abiotic surfaces.
abstract: BACKGROUND
  Microbial biofilms form on central venous catheters and may be associated with systemic infections as well as decreased dialysis efficiency due to catheter thrombosis. The most widely used anticoagulant catheter lock solution in the US is sodium heparin. We have previously shown that sodium heparin in clinically relevant concentrations enhances Staphylococcus aureus biofilm formation. In the present study, we examine the effect of several alternative catheter lock solutions on in vitro biofilm formation by laboratory and clinical isolates of S. aureus and coagulase-negative staphylococci (CNS).
  
  
  METHODS
  Lepirudin, low molecular weight heparin, tissue plasminogen activator, sodium citrate, sodium citrate with gentamicin and sodium ethylene diamine tetra-acetic acid (EDTA) were assessed for their effect on biofilm formation on polystyrene, polyurethane and silicon elastomer.
  
  
  RESULTS
  Sodium citrate at concentrations above 0.5% efficiently inhibits biofilm formation and cell growth of S. aureus and Staphylococcus epidermidis. Subinhibitory concentrations of sodium citrate significantly stimulate biofilm formation in most tested S. aureus strains, but not in CNS strains. Sodium EDTA was effective in prevention of biofilm formation as was a combination of sodium citrate and gentamicin. Low molecular weight heparin stimulated biofilm formation of S. aureus, while lepirudin and tissue plasminogen activator had little effect on S. aureus biofilm formation.
  
  
  CONCLUSIONS
  This in vitro study demonstrates that heparin alternatives, sodium citrate and sodium EDTA, can prevent the formation of S. aureus biofilms, suggesting that they may reduce the risk of biofilm-associated complications in indwelling catheters. This finding suggests a biological mechanism for the observed improvement in catheter-related outcomes in recent clinical comparisons of heparin and trisodium citrate as catheter locking solutions. A novel and potential clinically relevant finding of the present study is the observation that citrate at low levels strongly stimulates biofilm formation by S. aureus.
authors.affiliation: Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA.
authors.forename: Robert M Q
authors.initials: RM
authors.lastname: Shanks
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Sargent
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Martinez
authors.forename: Martha L
authors.initials: ML
authors.lastname: Graber
authors.forename: George A
authors.initials: GA
authors.lastname: O'Toole
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016470:Bacteremia / Q000209:etiology / Q000517:prevention & control; D001422:Bacterial Adhesion / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects*; D002404:Catheterization; D002408:Catheters, Indwelling / Q000009:adverse effects / Q000382:microbiology; D002951:Citrates / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D004866:Equipment Contamination / Q000517:prevention & control; D005839:Gentamicins / Q000008:administration & dosage; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology; D006629:Hirudins / Q000494:pharmacology; D011137:Polystyrenes; D011140:Polyurethanes; D011994:Recombinant Proteins / Q000494:pharmacology; D012826:Silicone Elastomers; D000077559:Sodium Citrate; D012996:Solutions / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000254:growth & development; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D002951:Citrates; D005839:Gentamicins; D006495:Heparin, Low-Molecular-Weight; D006629:Hirudins; D011137:Polystyrenes; D011140:Polyurethanes; D011994:Recombinant Proteins; D012826:Silicone Elastomers; D012996:Solutions; D000077559:Sodium Citrate; D004492:Edetic Acid; D010959:Tissue Plasminogen Activator; C083544:lepirudin