Lyte Mark, Freestone Primrose P E, Neal Christopher P, Olson Barton A, Haigh Richard D, Bayston Roger, Williams Peter H
Department of Surgery, Minneapolis Medical Research Foundation, Hennepin County Medical Center, Minneapolis 55404, USA.
Lancet. 2003 Jan 11;361(9352):130-5. doi: 10.1016/S0140-6736(03)12231-3.
Bacterial colonisation of indwelling medical devices by coagulase-negative staphylococci is a prevalent risk in intensive-care units. Factors determining biofilm formation and progression to catheter- related infection are incompletely understood. We postulated that administration of inotropic agents via indwelling intravenous catheters may stimulate growth and formation of biofilms by Staphylococcus epidermidis.
Inocula representing physiologically relevant infecting doses of S epidermidis were incubated in a minimum medium supplemented with fresh human plasma in the presence or absence of pharmacological concentrations of norepinephrine or dobutamine. Biofilm formation on polystyrene and medical-grade silicone was examined. After incubation, cultures were assessed for growth and formation of biofilms by colony counting and scanning electronmicroscopy. The production of exopolysaccharide, a major constituent of S epidermidis biofilms, was also assessed by use of immunofluorescence microscopy.
Incubation of S epidermidis with catecholamine inotropes in the presence of human plasma resulted in a significant increase in growth compared with control on both polystyrene and silicone surfaces, with pronounced increases in biofilm formation as visualised by scanning electronmicroscopy. Experiments with transferrin labelled with radioactive iron showed the ability of catecholamine inotropes to facilitate acquisition of iron by S epidermidis. Immunofluorescence microscopy revealed extensive exopolysaccharide production associated with S epidermidis biofilms.
The ability of catecholamine inotropic drugs to stimulate bacterial proliferation and biofilm formation may be an aetiological factor in the development of intravascular catheter colonisation and catheter-related infection. The removal of iron from transferrin for subsequent use by S epidermidis is a possible mechanism by which catecholamine inotropes stimulate bacterial growth as biofilms.
凝固酶阴性葡萄球菌在留置医疗设备上的细菌定植是重症监护病房中普遍存在的风险。决定生物膜形成以及发展为导管相关感染的因素尚未完全明确。我们推测通过留置静脉导管给予血管活性药物可能会刺激表皮葡萄球菌生长并形成生物膜。
将代表生理相关感染剂量的表皮葡萄球菌接种物在补充有新鲜人血浆的基础培养基中培养,同时存在或不存在药理浓度的去甲肾上腺素或多巴酚丁胺。检测在聚苯乙烯和医用级硅胶上生物膜的形成情况。培养后,通过菌落计数和扫描电子显微镜评估培养物的生长及生物膜形成情况。还通过免疫荧光显微镜评估了表皮葡萄球菌生物膜的主要成分胞外多糖的产生情况。
在人血浆存在的情况下,将表皮葡萄球菌与儿茶酚胺类血管活性药物一起培养,与对照组相比,在聚苯乙烯和硅胶表面上的生长均显著增加,通过扫描电子显微镜观察到生物膜形成明显增加。用放射性铁标记转铁蛋白的实验表明,儿茶酚胺类血管活性药物能够促进表皮葡萄球菌获取铁。免疫荧光显微镜显示与表皮葡萄球菌生物膜相关的大量胞外多糖产生。
儿茶酚胺类血管活性药物刺激细菌增殖和生物膜形成的能力可能是血管内导管定植和导管相关感染发生的一个病因学因素。儿茶酚胺类血管活性药物刺激细菌作为生物膜生长的一种可能机制是从转铁蛋白中去除铁以供表皮葡萄球菌随后使用。