Shanks Robert M Q, Sargent Jennifer L, Martinez Raquel M, Graber Martha L, O'Toole George A
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA.
Nephrol Dial Transplant. 2006 Aug;21(8):2247-55. doi: 10.1093/ndt/gfl170. Epub 2006 Apr 20.
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).
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.
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.
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.
微生物生物膜在中心静脉导管上形成，可能与全身感染以及因导管血栓形成导致的透析效率降低有关。美国使用最广泛的抗凝导管封管溶液是肝素钠。我们之前已经表明，临床相关浓度的肝素钠会增强金黄色葡萄球菌生物膜的形成。在本研究中，我们研究了几种替代导管封管溶液对金黄色葡萄球菌和凝固酶阴性葡萄球菌（CNS）的实验室及临床分离株体外生物膜形成的影响。
评估了重组水蛭素、低分子量肝素、组织型纤溶酶原激活剂、柠檬酸钠、含庆大霉素的柠檬酸钠以及乙二胺四乙酸钠（EDTA）对聚苯乙烯、聚氨酯和硅橡胶上生物膜形成的影响。
浓度高于0.5%的柠檬酸钠能有效抑制金黄色葡萄球菌和表皮葡萄球菌的生物膜形成及细胞生长。亚抑制浓度的柠檬酸钠在大多数测试的金黄色葡萄球菌菌株中显著刺激生物膜形成，但在CNS菌株中则不然。乙二胺四乙酸钠对生物膜形成有预防作用，柠檬酸钠和庆大霉素的组合也有此作用。低分子量肝素刺激金黄色葡萄球菌生物膜形成，而重组水蛭素和组织型纤溶酶原激活剂对金黄色葡萄球菌生物膜形成影响不大。
这项体外研究表明，肝素替代品柠檬酸钠和乙二胺四乙酸钠可以预防金黄色葡萄球菌生物膜的形成，这表明它们可能降低留置导管中生物膜相关并发症的风险。这一发现提示了在最近肝素和枸橼酸钠作为导管封管溶液的临床比较中观察到的导管相关结果改善的生物学机制。本研究一个新的且可能与临床相关的发现是，低水平的枸橼酸盐强烈刺激金黄色葡萄球菌形成生物膜。
