Department of Internal Medicine, Oakwood Hospital and Medical Center, Dearborn, Michigan, USA.
Antimicrob Agents Chemother. 2012 Jan;56(1):148-53. doi: 10.1128/AAC.05061-11. Epub 2011 Oct 10.
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.
感染和血栓是与中心静脉导管相关的最常见并发症。预防和处理这些并发症的建议策略包括使用肝素涂层导管、肝素锁和抗菌锁治疗。然而,肝素对白色念珠菌生物膜和浮游细胞的影响尚未被研究过。因此,我们试图确定肝素钠制剂 (HP) 对白色念珠菌生物膜和浮游细胞的体外影响。由于 HP 含有两种防腐剂,即对羟基苯甲酸甲酯 (MP) 和对羟基苯甲酸丙酯 (PP),因此还单独测试了这些化合物和不含防腐剂的肝素钠 (Pure-H)。用 XTT [2,3-双-(2-甲氧基-4-硝基-5-磺苯基)-2H-四唑-5-羧酰胺] 还原和显微镜评估处理后成熟生物膜的代谢活性。Pure-H、MP 和 PP 分别导致成熟白色念珠菌生物膜的代谢活性减少了 75%、85%和 60%。与单独的化合物相比,HP 对成熟生物膜的最大功效达到 90% (P < 0.0001)。Pure-H、MP 和 PP 各自抑制白色念珠菌生物膜的形成高达 90%。HP 在 5000 U/ml 及更高浓度时完全抑制生物膜形成。当测试对浮游细胞的作用时,每种化合物都以剂量依赖性方式抑制生长。这些数据表明,HP、MP、PP 和 Pure-H 对白色念珠菌成熟生物膜、生物膜形成和浮游细胞具有体外抗真菌活性。有必要研究高剂量肝素基策略(例如肝素锁)与传统抗真菌药物联合用于治疗和/或预防白色念珠菌生物膜。