title: In vitro analyses of the effects of heparin and parabens on Candida albicans biofilms and planktonic cells.
abstract: Infections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin on Candida albicans biofilms and planktonic cells have not been previously studied. Therefore, we sought to determine the in vitro effect of a heparin sodium preparation (HP) on biofilms and planktonic cells of C. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformed C. albicans biofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P < 0.0001). Pure-H, MP, and PP each inhibited C. albicans biofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H have in vitro antifungal activity against C. albicans mature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention of C. albicans biofilms is warranted.
authors: Department of Internal Medicine, Oakwood Hospital and Medical Center, Dearborn, Michigan, USA.
authors: Marisa H
authors: MH
authors: Miceli
authors: Stella M
authors: SM
authors: Bernardo
authors: T S Neil
authors: TS
authors: Ku
authors: Carla
authors: C
authors: Walraven
authors: Samuel A
authors: SA
authors: Lee
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D055499:Catheter-Related Infections / Q000517:prevention & control; D002405:Catheterization, Central Venous; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D010226:Parabens / Q000494:pharmacology*; D010933:Plankton / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D013778:Tetrazolium Salts
chemical_list: D000935:Antifungal Agents; D010226:Parabens; D013778:Tetrazolium Salts; C059087:2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5-((phenylamino)carbonyl)-2H-tetrazolium hydroxide; D006493:Heparin; C015358:methylparaben; C006068:propylparaben