亚抑菌浓度的穿心莲内酯及与红霉素联用影响表皮葡萄球菌生物膜形成的初步研究

Influence of sub-MIC andrographolide alone or in combination with erythromycin on biofilm formation of Staphylococcus epidermidis: a preliminary study

目的观察亚抑菌浓度(亚-MIC)穿心莲内酯及其与红霉素联用对表皮葡萄球菌生物膜形成的影响。方法连续稀释法测定穿心莲内酯和红霉素对表皮葡萄球菌的MIC;棋盘格法测定穿心莲内酯和红霉素联用对表皮葡萄球菌悬浮菌的作用;体外构建表皮葡萄球菌生物膜,XTT减低法评价亚-MIC穿心莲内酯及与红霉素联用对表皮葡萄球菌生物膜内细菌代谢及初始黏附能力的影响,扫描电镜观察用药后表皮葡萄球菌形态和生物膜结构改变。结果穿心莲内酯对表皮葡萄球菌悬浮菌的MIC大于1000 mg/L,穿心莲内酯和红霉素联用对表皮葡萄球菌悬浮菌的FIC指数(联合抑菌分数)>2;亚抑菌浓度穿心莲内酯对表皮葡萄球菌生物膜黏附及膜内菌代谢均有抑制作用;穿心莲内酯和红霉素联用对表皮葡萄球菌的黏附能力的影响表现为协同作用,对悬浮菌和膜内菌代谢作用表现为拮抗。结论亚抑菌浓度穿心莲内酯对表皮葡萄球菌生物膜黏附及膜内菌代谢均有抑制作用;穿心莲内酯和红霉素联用对表皮葡萄球菌悬浮菌及膜内菌代谢存在拮抗,提示临床治疗表皮葡萄球菌感染时应避免同时使用这两种药物。

Objective To observe the effect of sub-MIC andrographolide alone or in combination with erythromycin on the biofilm formation of Staphylococcus epidermidis.Methods Minimum inhibitory concentrations（MICs） of andrographolide and erythromycin against S.epidermidis were determined by serial dilution method;the effect of andrographolide combined with erythromycin against planktonic S.epidermidis was evaluated by checkerboard method.S.epidermidis biofilms were constructed in vitro.XTT reduction assay was used to evaluate the influences of sub-MIC andrographolide alone or in combination with erythromycin on metabolism and adhension of S.epidermidis biofilm;scanning electronic microscope（SEM） was applied to observe the morphological and the structural changes of the biofilms after using the drugs.Results The MIC of andrographolide to planktonic S.epidermidis was greater than 1000 mg/L;while the FIC of andrographolide in combination with erythromycin to planktonic S.epidermidis was greater than 2.The sub-MIC andrographolide had an inhibitory effect on adhesion and bacterial metabolism of S.epidermidis,while andrographolide in combination with erythromycin had synergistic effect on the adhension,and an antagonistic effect on planktonic S.epidermidis and bacterial metabolism.Conclusion Sub-MIC andrographolide had inhibitory effect on both the adhesion and bacterial metabolism of S.epidermidis biofilm.Combination of the two agents showed antagonistic effects on planktonic S.epidermidis and bacterial metabolism,prompting that for S.epidermidis infection,doctors should avoid using the two agents simultaneously during the clinical treatment.