联合用药对白色念珠菌-金黄色葡萄球菌混合生物膜的作用及其影响因素  

In vitrointeractions and infectors of drug combinations against mixed biofilm of Candida albicans and Staphylococcus aureus

作　　者：刘萍[1,2] 候应龙[3] 孙淑娟[3] 

机构地区：[1]山东大学药学院,山东济南250012 [2]淄博市中心医院,山东淄博255036 [3]山东省千佛山医院,山东济南250014

出　　处：《中国医院药学杂志》2014年第3期170-175,共6页Chinese Journal of Hospital Pharmacy

基　　金：山东省自然基金课题(编号:ZR2011HL049;2007GG20002026)

摘　　要：目的:混合生物膜(biofilm,BF)感染发生率较前增高,联合用药是解决BF相关耐药的途径之一。通过筛选不同药物组合抗混合BF的作用,寻找有效药物组合,并探讨钙调节剂对联合用药作用的影响。方法:利用棋盘法筛选抗菌药物万古霉素、米诺环素、利福平、左氧氟沙星、磷霉素和阿奇霉素与氟康唑合用抗白色念珠菌-金黄色葡萄球菌混合BF的作用,并观察钙离子通道阻滞剂及钙离子络合剂对联合用药效果的影响。结果:米诺环素与氟康唑合用具有良好抗混合BF的作用,优于药物单用;钙离子通道阻滞剂贝尼地平、钙离子络合剂乙二胺四乙酸(EDTA)可以增强米诺环素与氟康唑联用的抗BF作用效果。结论:成熟的混合BF耐药性增强,联合用药可产生协同抗混合BF作用;扰乱细胞内钙平衡可增强抗菌作用。OBJECTIVE Polymicrobial biofilms represent as an understudied and clinically relevant health problem, drug combination is one of the potential therapies. In order to find new therapies against mixed bioflims, the combined effects of antibacterial agents and f｜uconazole （FLC） against planktonic and sessile C. albicans mixed with Staphylococcus aureus was stud- ied. And also the effects of calcium regulation agents on the combinations were explored. METHODS According to the method described in CLSI M27-A3, the microdilution method was used to investigate the combined antimicrobial effects of fluconazole with antibacterial agents（rifampin, minocycline, ofloxacin, fosfomycin, vancomycin and azithromycin）against Candida albi- cans mixed with Staphylococcus aureus both in plantonic and in biofilm. And also the effects of Ca^2＋ regulations were carried by microdilution method. The results were evaluated both by visual observation and XTT （OD value） method, and two nonparametric methods （FICI and A E） were used to analyze the results. RESULTS Combined therapies of MINO and FLC had the strongest effects against mixed BF. Calcium channel blocker benidipine, EDTA could enhance the anti-BF effect of minocycline in combination with fluconazole. CONCLUSION Drug combinations had synergistic effect against mixed BF resistance. But the sentience of the bioflm was weaker when the BF was matured. Disrupting intracellular calcium balance could enhance the synergistic effect.

关 键 词：白色念珠菌 金黄色葡萄球菌 氟康唑 混合生物膜 钙调节剂 

分 类 号：R961[医药卫生—药理学]