百里香酚联合苯唑西林对耐甲氧西林金黄色葡萄球菌(MRSA)生物被膜的影响

【背景】耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus，MRSA)能以生物被膜的状态存在，从而产生多重耐药性和持续性感染。【目的】通过研究百里香酚和苯唑西林单用和联用对耐甲氧西林金黄色葡萄球菌生物被膜的形成抑制和清除作用，探究联合用药对MRSA生物被膜的影响，为临床联合应用抗MRSA药物提供理论依据。【方法】采用微量肉汤稀释法测定苯唑西林对MRSA标准菌株USA300的最低抑菌浓度；采用结晶紫染色法和菌落计数法评估百里香酚和苯唑西林单用和联用对USA300生物被膜形成抑制和清除作用。【结果】百里香酚和苯唑西林在亚抑菌浓度下对USA300生物被膜的形成具有一定的抑制作用。在较高浓度下，百里香酚对其24 h和72 h形成的生物被膜有良好的清除作用，而苯唑西林无清除作用。两药联用对生物被膜的抑制和清除作用进一步增强，在较低浓度下有较好的抑制和清除效果。【结论】百里香酚和苯唑西林联合用药与单独用药相比，对USA300的生物被膜的抑制和清除作用增强，两药联合有协同抗菌作用。

Effect of thymol combined with oxacillin on methicillin-resistant Staphylococcus aureus (MRSA) biofilm

Background] methicillin-resistant Staphylococcus aureus (MRSA) can exist in the state of biofilms, which results in multiple resistance and persistent infections. Objective] By investigating the inhibition and clearance of thymol and oxacillin separately and concurrently on the biofilm formation of MRSA, the effects of combined medications on MRSA biofilms were explored to provide the theoretical basis for clinical combined application of anti-MRSA drugs. Methods] Broth microdilution method was used to measure oxacillin minimal inhibitory concentration against USA300 strain. The effect of thymol and oxacillin separately and concurrently on the inhibition and clearance of biofilm formation in USA300 was evaluated by crystal violet staining method and colony counting method. Results] Thymol and oxacillin inhibited the formation of USA300 biofilm at subinhibitory concentrations. At high concentrations, thymol had good removal effects on the biofilm formed in 24 and 72 hours, while oxacillin had no removal effect. The inhibition and clearance effect of the combination of the two drugs on biofilms was further enhanced, and it had a better inhibition and clearance effect at low concentrations. Conclusion] Compared with thymol and oxacillin alone, the combination of thymol and oxacillin has an enhanced inhibitory and clearance effect on the biofilm of USA300. The combination of the two drugs has a synergistic antibacterial effect.