6种临床常用药物对耐碳青霉烯类肺炎克雷伯菌的体外抗菌作用

In vitro test of the antibacterial activity of six commonly used antibiotics against carbapenem resistant Klebsiella pneumoniae

目的评价多黏菌素B、亚胺培南、米诺环素、替加环素、磷霉素、多西环素等6种临床常用抗生素单独或联合使用对耐碳青霉烯类肺炎克雷伯菌(Carbapenem Resistant Klebsiella Pneumoniae,CRKP)的体外抗菌活性,筛选最优给药方案,为临床治疗CRKP感染提供参考。方法(1)收集自广州地区某三甲医院2018年10月-2019年9月住院患者分离的非重复菌株,用VITEK MS IVD3.0质谱仪、Vitek2 Compect鉴定药敏分析系统及改良hodge试验初筛产碳青霉烯酶的肺炎克雷伯菌,用PCR技术鉴定耐药基因。(2)①用微量肉汤稀释法检测6种药物的最低抑菌浓度(minimal inhibitory concentration,MIC);②应用微量棋盘法,分别检测6种不同药物组合,计算联合抑菌指数(fraction Inhibitory concentration index,FICI)。结果(1)共检出肺炎克雷伯菌616株,PCR结果显示CRKP 37(7.47%)株,其中KPC型30(81%)株,IMP型2(5.4%)株,VIM型2(5.4%)株,NDM-1型2(5.4%)株,OXA-型1(2.8%)株;(2)①多黏菌素B、替加环素均为高度敏感(92.8%、87.8%);②最佳药物组合为亚胺培南联合磷霉素,共有28株菌表现为协同作用;其次为多黏菌素B联合磷霉素,共有15株菌表现为协同作用;亚胺培南与替加环素联合有26株菌表现为拮抗作用,与多西环素联合有20株菌表现出拮抗作用,与多黏菌素B联合,有15株表现为拮抗作用;其他药物组合表现为相加或无关作用为主。结论多黏菌素B、亚胺培南联合磷霉素对CRKP有很好的抗菌活性,但亚胺培南联合替加环素、多西环素、多黏菌素B抗菌活性显著降低,其他组合无明显优势,提示临床应谨慎选用联合用药方案。

Objective To evaluate the efficacy of polymyxin B,imipenem,minocycline,tigecycline,fosfomycin and doxycycline on carbapenem resistant Klebsiella pneumoniae(CRKP)in vitro and screen the optimal administration regimen for clinical treatment of CRKP infection.Methods Non-repetitive strains of Klebsiella pneumoniae were collected from patients in a hospital in Guangzhou from October 2018 to September 2019.CRKP were identified by VITEK MS IVD3.0 mass spectrometer,Vitek2 Compect drug sensitivity analysis system and improved Hodge test,and the resistance genes were analyzed by PCR.The minimal inhibitory concentration(MIC)and the fraction inhibitory concentration index(FICI)of different kinds of two drugs in combination were determined and calculated by broth microdilution method.Results(1)616 strains of Klebsiella pneumoniae were collected,in which 37 cases were identified as CRKP strains(7.47%)by PCR,including types of KPC(30,81%),IMP(2,5.4%),VIM(2,5.4%),NDM-1(2,5.4%)and OXA(1,2.8%).(2)All strains were highly sensitive to polymyxin B and tigecycline(92.8%and 87.8%).Imipenem and fosfomycin united was the best combination on antibacterial activity,which showed noticeable synergism effect in 28 strains,followed by polymyxin B and fosfomycin in combination,which showed synergism effect in 15 strains.Imipenem and tigecycline/doxycycline/polymyxin B in combination showed antagonistic effect in 26 strains,20 strains or 15 strains.Other drugs in combination showed the same antibacterial activity as alone use.Conclusion Polymyxin B,imipenem combined with fosfomycin have excellent antibacterial activity against CRKP.However,the antibacterial activity of imipenem combined with tigecycline,doxycycline and polymyxin B is significantly reduced,while others have no obvious advantages.Therefore,the combination therapy should be chosen carefully.