Abstract：
Methicillin-resistant Staphylococcus aureus (MRSA), a notorious bacterium with high drug resistance and easy recurrence after surgery, has posed significant clinical treatment challenges. In the current scarcity of new antibiotics, the identification of adjuvants to existing antibiotics is a promising approach to combat infections caused by multidrug-resistant Gram-positive bacteria. The in vitro synergy test, which included a MIC assay, time-kill curve, antimicrobial susceptibility testing, and live/dead bacteria staining assay, revealed that laurocapram, a widely used chemical transdermal enhancer, could potentiate the antibacterial activity of cephalosporins against MRSA. In vitro, laurocapram combined with cefixime showed an excellent synergistic activity against MRSA (FICI = 0.28 ± 0.00). In addition, the combination of laurocapram and cefixime may inhibited the formation of MRSA biofilm and caused cell membrane damage. Following that, we discovered that combining laurocapram with cefixime could alleviate the symptoms of mice in the MRSA skin infection model and the MRSA pneumonia model. In conclusion, laurocapram is a promising and low-cost antibacterial adjuvant, providing a new strategy for further exploring the use of lower doses of cephalosporins to combat MRSA infection.
摘要：
耐甲氧西林金黄色葡萄球菌(MRSA),一种臭名昭著的细菌，耐药性高，术后容易复发，提出了重大的临床治疗挑战。在目前新抗生素稀缺的情况下，鉴定现有抗生素的佐剂是对抗由多重耐药革兰氏阳性细菌引起的感染的有希望的方法。体外协同作用试验,其中包括MIC测定，时间-杀伤曲线,抗菌药物敏感性试验,和活/死细菌染色测定，透露了劳罗卡普兰，一种广泛使用的化学透皮促进剂，可以增强头孢菌素对MRSA的抗菌活性。体外，laurocapram联合头孢克肟对MRSA显示出优异的协同活性(FICI=0.28±0.00)。此外,美罗卡普兰与头孢克肟合用可能抑制MRSA生物膜的形成,引起细胞膜损伤。在此之后,我们发现,在MRSA皮肤感染模型和MRSA肺炎模型中,美罗卡普兰联合头孢克肟可以缓解小鼠的症状.总之,laurocapram是一种有前途的低成本抗菌佐剂，为进一步探索使用较低剂量的头孢菌素来对抗MRSA感染提供了新的策略。
