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目的研究阿扎霉素F5a、F4a和F3a抗耐甲氧西林金黄色葡萄球菌(MRSA)活性及与其他化合物可能的协同抗MRSA作用。方法以标准菌株耐甲氧西林金黄色葡萄球菌ATCC 33592和临床分离株耐甲氧西林金黄色葡萄球菌01~08为指示菌,达托霉素为阳性对照药,采用微量肉汤稀释法测定阿扎霉素F 3个主要成分对耐甲氧西林金黄色葡萄球菌的最低抑菌浓度和最低杀菌浓度;然后运用棋盘格法设计试验,分别测定其与鼠尾草酸或三甲基氢醌的联合抗耐甲氧西林金黄色葡萄球菌作用。结果阿扎霉素F5a、F4a和F3a对指示菌耐甲氧西林金黄色葡萄球菌ATCC33592和耐甲氧西林金黄色葡萄球菌01~08的最低抑菌浓度分别为4~8、4和4~8μg·mL-1,最低杀菌浓度均为8~16μg·mL-1;与鼠尾草酸联合抗耐甲氧西林金黄色葡萄球菌的部分抑菌浓度指数(FICIs)均为0.75~1.25,呈无关的抗耐甲氧西林金黄色葡萄球菌作用;与三甲基氢醌联合抗耐甲氧西林金黄色葡萄球菌的FICIs均为0.25~0.50,呈协同抗耐甲氧西林金黄色葡萄球菌作用。结论阿扎霉素F 3个主要成分具有明显的抗耐甲氧西林金黄色葡萄球菌活性,且与三甲基氢醌具有协同抗耐甲氧西林金黄色葡萄球菌作用,作为新型抗耐甲氧西林金黄色葡萄球菌大环内酯,值得进一步研究与开发。
Objective To investigate the anti-methicillin-resistant Staphylococcus aureus (MRSA) activity of azacimin F5a, F4a and F3a and the possible synergistic anti-MRSA effect with other compounds. Methods The standard strains of methicillin-resistant Staphylococcus aureus ATCC 33592 and clinical isolates of methicillin-resistant Staphylococcus aureus 01 ~ 08 as indicator bacteria, daptomycin-positive control drug, the determination of trace broth dilution method The three main components of streptomycin F against methicillin-resistant Staphylococcus aureus minimum inhibitory concentration and minimum bactericidal concentration; and then use the checkerboard design test, were measured with the combination of carnosic acid or trimethylhydroquinone Resistant to methicillin-resistant Staphylococcus aureus. Results The minimum inhibitory concentrations (MICs) of azacimin F5a, F4a and F3a against methicillin-resistant Staphylococcus aureus ATCC33592 and methicillin-resistant Staphylococcus aureus 01 ~ 08 were 4 ~ 8, 4 and 4 ~ 8μg · ML-1, the minimum bactericidal concentration was 8 ~ 16μg · mL-1. The partial antibacterial concentration index (FICIs) of methicillin-resistant Staphylococcus aureus in combination with carnosic acid were all 0.75 ~ 1.25, Resistant to methicillin-resistant Staphylococcus aureus; FICIs resistant to methicillin-resistant Staphylococcus aureus in combination with trimethylhydroquinone were 0.25-0.50, showing a synergistic effect against methicillin-resistant Staphylococcus aureus. Conclusion The three main constituents of azacitidine F have obvious anti-methicillin-resistant Staphylococcus aureus activity and synergistic with methicillin-resistant methicillin-resistant Staphylococcus aureus as novel anti-methoxy Staphylococcus aureus macrolide, worth further research and development.