目的 探讨丁香油体外抗耐甲氧西林金黄色葡萄球菌（MRSA）活性，以及与3种β-内酰胺类抗生素（阿莫西林、头孢氨苄和头孢吡肟）联合使用抗MRSA的体外活性。方法 采用96孔板微量稀释法分别测定丁香油、丁香油与3种β-内酰胺类抗生素联合使用对2株MRSA标准株和32株MRSA临床分离株的最低抑菌浓度（MIC）；微量棋盘法分别测定丁香油与3种β-内酰胺类抗生素的分级抑菌浓度（FIC）指数；生长曲线法分析丁香油以及丁香油和头孢氨苄联合使用对MRSA生长的影响。结果 丁香油具有明显的体外抗MRSA活性，MIC为0.25、0.51 mg/mL。丁香油分别与3种β-内酰胺类抗生素（阿莫西林、头孢氨苄和头孢吡肟）联合使用时，FIC指数集中分布在≤ 0.5和0.5~1，主要表现为协同和相加作用，其中与阿莫西林、头孢氨苄和头孢吡肟的协同率分别为58.8%、97.0%、64.7%；丁香油能明显增强β-内酰胺类抗生素抗MRSA活性，降低β-内酰胺类抗生素的用量，使其MIC₅₀和MIC₉₀降低为单独用药的1/4~1/2和1/2~1。生长曲线结果表明，丁香油能明显延长MRSA延滞期，抑制其生长速度，生长量明显降低，且抑制MRSA生长呈明显量效关系；当丁香油（1/4 MIC）与头孢氨苄（1/4 MIC）联合使用后，MRSA生长几乎被抑制。结论 丁香油不仅自身具有较强的抗MRSA活性，还具有协同增效β-内酰胺类抗生素抗MRSA作用，具备治疗MRSA感染新药的开发与应用前景。

Objective To investigate the antimicrobial activities of clove oil alone and in combination with three kinds of β-lactam antibiotics (amoxicillin, cephalexin, and cefepime) against methicillin-resistant Staphylococcus aureus (MRSA). Methods The minimum inhibitory concentrations (MICs) of clove oil alone and in combination with three kinds of β-lactam antibiotics against two standard MRSA and 32 MRSA isolated from clinic were determined by 96-well plate micro-dilution method. The fractional inhibitory concentrations (FICs) of clove oil and three kinds of β-lactam antibiotics were determined by using the micro-chessboard method. The growth curve of MRSA ATCC43300 effected by clove oil or clove oil combined with cephalexin was analyzed. Results Clove oil showed significant anti-MRSA activity in vitro, with MIC of 0.25 mg/mL and 0.51 mg/mL. The FICs were mainly distributed in the range of ≤ 0.5 and 0.5 to 1, and the synergy rates were 58.8%, 97.0%, and 64.7%, when the clove oil was combined with amoxicillin, cephalexin and cefepime, respectively. Clove oil enhanced the activity of β-lactam antibiotics against MRSA significantly, and reduced the dosage of it. The growth curve showed that the clove oil significantly inhibited the growth of MRSA, and prolonged its lag phase. And the effect showed a significant dose-effect relationship. The growth of MRSA was nearly inhibited when 1/4 MIC cefepime combined with 1/4 MIC clove oil. Conclusion Clove oil not only could exhibit strong anti-MRSA activity itself, but could enhance the activity of β-lactam antibiotics against MRSA. Hence, clove oil would be a potential new drug, which can be used as a new drug for preventing and treating MRSA infection.

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国家大学生创新创业训练项目（201613705041）；四川省科技厅应用基础（重点）项目（2016JY0014）；四川省省属高校科研创新团队建设计划（16TD0027）；教育部春晖计划（Z2016120）；成都市科技局科技惠民技术研发项目（2016-HM01-00362-SF）；成都医学院校基金（CYZ15-02）；四川省教育厅科研项目（16ZB0285）；食品生物技术重点实验室开放课题（szjj2015-011）；成都中医药大学中药资源系统研究与开发利用省部共建国家重点实验室培育基地开放基金