亚胺培南联合多黏菌素B对不同表型铜绿假单胞菌体外抗菌活性的研究

Study on in vitro antibacterial activity of the combined therapy of imipenem with polymyxin B against Pseudomonas aeruginosa with different phenotypes

目的探讨多黏菌素B与亚胺培南联用对不同耐药表型铜绿假单胞菌的体外抗菌活性。方法自仁济医院西部及瑞金医院临床标本中分离铜绿假单胞菌133株,运用纸片扩散(K-B)法分析其耐药表型,采用琼脂稀释法检测亚胺培南和多黏菌素B单用及联用时对不同表型铜绿假单胞菌的最低抑菌浓度(MIC),计算部分抑菌浓度(FIC),判断联合效应。分别探讨2个不同的配比浓度,即亚胺培南∶多黏菌素B为1∶0.5和1∶1时的抗菌效果。结果对2种药物组合进行Kappa一致性检验,药物敏感性结果一致性微弱。亚胺培南与多黏菌素B以1∶1联用时协同率为51.13%,明显高于1∶0.5时的19.55%。运用Fisher's精确概率法分析不同表型间的联合抑菌效应,亚胺培南与多黏菌素B以1∶1浓度配比时,对各表型间均有较高的协同率,不存在明显的统计学差异;而1∶0.5时差异明显。结论体外联合应用亚胺培南与多黏菌素B对铜绿假单胞菌的抗菌效果明显优于单用亚胺培南。以1∶1联用时的协同率优于1∶0.5,且对不同耐药表型的铜绿假单胞菌作用稳定,值得向临床推广。

Objective To investigate the in vitro antibacterial activity of the combined therapy of imipenem with polymyxin B against Pseudomonas aeruginosa with different phenotypes. Methods A total of 133 clinically isolated Pseudomonas aeruginosa were collected from Renji Hospital （West Department ） and Ruijin Hospital, and the phenotypes were determined by disc diffusion （K-B） method. The minimum inhibitory concentrations （MIC） of imipenem, polymyxin B and imipenem with polymyxin B against Pseudomoaas aeruginosa were calculated by agar dilution method, and the fractional inhibitory concentrations （FIC） were calculated. The combined effect was analyzed. There were 2 ratios, 1 ： 0.5 and 1 ： 1 with imipenem to polymyxin B. Results The drug sensitivities of those 2 therapies turned out to be inconsistent when conducting Kappa test. The synergistic rate of 1 ： 1 with imipenem to polymyxin B was 51.13%, which was much higher than 1：0.5 with imipenem to polymyxin （ 19.55% ）. Fisher＇s exact test demonstrated that 1：1 with imipenem to polymyxin B maintained high synergistic rate between different phenotypes, and there was no statistically significant difference, However, the difference was significant regarding to 1 ： 0. 5 with imipenem to polymyxin B. Conclusions Comparing with monotherapy, the combined therapy of imipenem with polymyxin B significantly increases the sensitivity of Pseudomonas aeruginosa in vitro. The combined therapy applying 1：1 with imipenem to polymyxin B with a higher synergistic rate than that applying 1：0.5 with imipenem to polymyxin B and a good stability may be a good choice for the antibiotics resistant Pseudomonas aeruginosa with different phenotypes.