小鼠烫伤MRSA感染模型的建立及对新型截短侧耳素衍生物WS-007抗菌活性的研究

Establishment of MRSA Infection Model in Scald Mice and the Antibacterial Activity of a Novel Pleuromutilin Derivative WS-007

建立小鼠烫伤MRSA感染模型,对截短侧耳素衍生物WS-007抑制耐甲氧西林金黄色葡萄球菌(Methicillin-resisitant Staphylococcus aureus,MRSA)的活性进行研究。采用琼脂二倍稀释法,对临床分离的金黄色葡萄球菌进行MRSA菌株的筛选及最低抑菌浓度(MIC)的测定;使用内充沸水的西林瓶对小鼠进行接触性烫伤,选用MRSA对烫伤部位进行感染;以局部涂抹方式进行给药,连续给药5 d,0.1 g/只,2次/d,观察局部给药5 d后的皮肤感染菌量变化。从107株金黄色葡萄球中筛选出38株MRSA,筛选率为35.5%;WS-007和氧氟沙星对38株MRSA的MIC50分别为0.06,64 mg/L;烫伤10 s形成的损伤符合实验要求,在烫伤部位对称取2个位点进行皮内注射菌液效果最佳;WS-007对烫伤MRSA感染的小鼠治疗效果优于氧氟沙星(P<0.05)。建立的皮肤烫伤感染模型具有一定的敏感性和有效性,可用于外用抗菌药物筛选及抗菌活性评价;体内外活性研究证明新截短侧耳素类化合物WS-007对MRSA具有很好的抗菌活性。

To establish the scald MRSA infection model in mice and to study the antibacterial activity of a novel pleuromutilin derivative WS-007 against methicillin-resistant Staphylococcus aureus( MRSA),two-fold agar dilution method was used to screen Methicillin-resistant Staphylococcus aureus( MRSA) from clinical isolates of Staphylococcus aureus and to determine the minimal inhibitory concentration( MIC) of WS-007 against the screened MRSA. The mice were injured by the vial filled with boiling water and the wounds were infected by intradermal injection with MRSA bacterial solution. Therapy was administered topically( 0. 1 g / mouse) bid( beginning at 1 and 7 h postinfection) and continued for 4 days( 5 days of therapy). Colony forming unit( CFU) in wound skin after 5 days was measured to evaluate the curative effect of WS-007 and Ofloxacin. 38 strains of MRSA were screened from 107 clinical isolates of staphylococcus aureus and the screening rate was 35. 5%. The MIC50 of WS-007 and Ofloxacin against 38 strains of MRSA were 0. 06,64 mg / L. The damage of 10 s scald conformed to the requirement of the experiment and the effect of infection was optimal by taking two located points in scald part by intradermal injection with bacterial solution. WS-007 had the better effect on scald MRSA infection model than that of Ofloxacin( P < 0. 05). The established scald infection model is sensitive and effective. It can be applied to screen and evaluate novel topical antimicrobial treatments of scald infection caused by MRSA. WS-007 had good antibacterial activity in vitro and in vivo against MRSA.