Li Z, He M, Dong X, Lin H, Ge H, Shen S, Li J, Ye R D, Chen D
School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China; China State Institute of Pharmaceutical Industry, Shanghai Institute of Pharmaceutical Industry, Shanghai, China; Shanghai Institute of Pharmaceutical Industry, 1320 West Beijing Road, Jing'an District, Shanghai, 200040, China.
Lett Appl Microbiol. 2015 Apr;60(4):352-8. doi: 10.1111/lam.12378. Epub 2015 Jan 14.
Newly synthesized erythromycin derivatives were screened for synergy with oxacillin and other β-lactam antibiotics against methicillin-resistant Staphylococcus aureus (MRSA). MRSA ATCC43300 and some clinically isolated MRSA were used. Several erythromycin derivatives were found to possess high synergism with oxacillin against MRSA. The newly synthesized erythromycin derivatives were also tested for their inhibitory effects against MRSA, either separately or in combination with oxacillin, using serial broth dilution, disc diffusion, Etest strips, growth curves and time-kill curves. A representative derivative, SIPI-8294, could potentiate almost all β-lactam antibiotics tested against the model strain MRSA ATCC43300 from 4 to 128 times and had synergism with oxacillin against 12 of 16 clinical isolates of MRSA under one-fourth of the minimum inhibitory concentration (MIC) of the compounds. This is the first report on the synergistic activity of these new erythromycin derivatives. These findings provide a new choice for the treatment of infection caused by MRSA and lead us to further study the synergistic mechanism.
This study is the first report on the synergy of anti-MRSA between new erythromycin derivatives and β-lactam antibiotics in vitro. The results show that although the erythromycin derivatives have poor anti-MRSA effects alone, they possess high synergism with oxacillin against MRSA ATCC43300 and clinically isolated MRSA. These novel compounds can significantly reduce the dosage of β-lactam antibiotics against MRSA, while this synergistic effect is different from the combination of β-lactams and β-lactamase inhibitors. The research may provide a new choice for the treatment of infection caused by MRSA and be useful to the research and development of new combination of medicines.
对新合成的红霉素衍生物与苯唑西林及其他β-内酰胺类抗生素联合抗耐甲氧西林金黄色葡萄球菌（MRSA）的协同作用进行了筛选。使用了MRSA ATCC43300和一些临床分离的MRSA菌株。发现几种红霉素衍生物与苯唑西林联合对MRSA具有高度协同作用。还采用肉汤稀释法、纸片扩散法、Etest试纸条法、生长曲线法和时间杀菌曲线法，分别或联合苯唑西林检测了新合成的红霉素衍生物对MRSA的抑制作用。一种代表性衍生物SIPI-8294可使针对模型菌株MRSA ATCC43300检测的几乎所有β-内酰胺类抗生素的活性增强4至128倍，并且在化合物最低抑菌浓度（MIC）的四分之一浓度下，与苯唑西林联合对16株临床分离的MRSA中的12株具有协同作用。这是关于这些新型红霉素衍生物协同活性的首次报道。这些发现为治疗由MRSA引起的感染提供了新的选择，并促使我们进一步研究其协同机制。
本研究是关于新型红霉素衍生物与β-内酰胺类抗生素体外联合抗MRSA协同作用的首次报道。结果表明，尽管红霉素衍生物单独抗MRSA效果不佳，但它们与苯唑西林联合对MRSA ATCC43300和临床分离的MRSA具有高度协同作用。这些新型化合物可显著降低β-内酰胺类抗生素针对MRSA的用药剂量，而这种协同作用不同于β-内酰胺类与β-内酰胺酶抑制剂的联合。该研究可能为治疗由MRSA引起的感染提供新的选择，并有助于新型联合药物的研发。
