亚胺培南联合阿奇霉素治疗铜绿假单胞菌生物被膜感染的实验研究

Synergism of Bactericidal Activities of Imipenem Combined with Azithromyicn in Treatment of Infection Associated with Pseudomonas aeruginosa Biofilm

目的研究亚胺培南(IMP)联合阿奇霉素(AZM)在治疗铜绿假单胞菌生物被膜(BF)感染中的作用。方法色氨酸法测定AZM对多糖蛋白复合物(GLX)的抑制作用;通过噻唑蓝(MTT)法测定BF上的活菌数,比较IMP与AZM联合应用时对BF细菌的体外抑制作用;采用组织笼大鼠皮下埋植法建立细菌BF体内局部感染动物模型,并考察AZM对IMP的体内协同作用。结果AZM可以使细菌BF的GLX的含量显著地下降;在IMP浓度相同的情况下,加入1/4、1/16 MIC的AZM可使BF上的活菌数显著地减少;IMP和AZM联合应用时,铜绿假单胞菌BF感染局部的活菌数较IMP单独作用时显著减少。结论AZM可以在治疗铜绿假单胞菌BF感染中对IMP起到协同作用。

OBJECTIVE To study the synergism of imipenem（IMP） combined with azithromyicn （AZM） in the treatment of infection associated with Pseudornonas aeruginosa biofilm. METHODS The inhibitory activity of AZM to glycocalyx （GLX） production was detected with the L-tryptophan method. Viable counts in biofilms treated with AZM combined with IMP were detected with the methyl thiazolyl diphenyltetrazolium（MTT） method in vitro. The tissue cage method was used to establish the animal model of local P. aeruginosa biofilm infection and the synergism of IMP combined with AZM was also studied in vivo. RESULTS AZM could inhibit the production of GLX. When IMP was combined with 1/4MIC or 1/16MIC of AZM viable counts in biofilms were less than they were when IMP was given alone in vitro. When AZM and IMP were administered at the same time viable counts in tissue cage fluids were also less than they were when IMP was administered alone in vivo. CONCLUSIONS AZM could enhance the antibacterial activity of IMP in the treatment of infection associated with biofilm.