磷霉素联合多黏菌素B对碳青霉烯类耐药肠杆菌目细菌的体外抗菌活性分析

In Vitro Antibacterial Activity Analysis of Fosfomycin Combined with Polymyxin B Against Carbapenem Resistant Enterobacterales

目的分析磷霉素联合多黏菌素B对碳青霉烯类耐药肠杆菌目细菌(carbapenem-resistant Enterobacterales,CRE)的体外抗菌活性。方法收集2020~2022年西安交通大学第二附属医院分离的CRE 78株,其中碳青霉烯类耐药大肠埃希菌(carbapenem-resistant Escherichia coli,CREC)32株、碳青霉烯类耐药肺炎克雷伯菌(carbapenem-resistant Klebsiella pneumonia,CRKP)46株;碳青霉烯类敏感肠杆菌目细菌(carbapenem-sensitive Enterobacterales,CSE)132株,其中碳青霉烯类敏感大肠埃希菌(carbapenem-sensitive Escherichia coli,CSEC)72株、碳青霉烯类敏感肺炎克雷伯菌(carbapenem-sensitive Klebsiella pneumonia,CSKP)60株。采用琼脂稀释法和肉汤微量稀释法(broth microdilution,BMD)分别测定磷霉素和多黏菌素B的最低抑菌浓度(minimum inhibitory concentration,MIC),采用肉汤微量稀释棋盘法测定CRE对磷霉素联合多黏菌素B的最低抑菌浓度,并计算部分抑菌浓度指数(fractional inhibitory concentration index,FIC),判定其联合效应。结果78株CRE中28株对磷霉素耐药,总耐药率为35.90%(28/78),其中6株同时还对多黏菌素B耐药,总耐药率为7.69%(6/78)。132株CSE中18株仅对磷霉素耐药,总耐药率为13.64%(18/132);未检测到对多黏菌素B耐药。多黏菌素B联合磷霉素对CREC为相加作用,对CRKP为协同作用。结论磷霉素和多黏菌素B单药耐药率均明显升高,二者联合用药可有效降低耐药率,提供一种新的治疗思路。

Objective To analyze the in vitro antibacterial activity of fosfomycin combined with polymyxin B against carbapenem resistant Enterobacterales(CRE).Methods 78 strains of CRE isolated from the Second Affiliated Hospital of Xi’an Jiaotong University from 2020 to 2022 were collected,including 32 strains of carbapenem-resistant Escherichia coli(CREC),and 46 strains of carbapenem-resistant Klebsiella pneumonia(CRKP),132 strains of carbapenem-sensitive Enterobacterales(CSE),including 72 strains of carbapenem-sensitive Escherichia coli(CSEC),and 60 strains carbapenem-sensitive Klebsiella pneumonia(CSKP).The minimum inhibitory concentration(MIC)of fosfomycin and polymyxin B was determined by AGAR dilution method,and minimum inhibitory concentration(BMD),and the MIC of fosfomycin combined with polymyxin B was determined by broth microdilution chessboard method.Fractional inhibitory concentration index(FIC)was calculated to determine the joint effect.Results In this study,28 of 78 CRE strains were resistant to fosfomycin,with a total resistance rate of 35.90%(28/78),of which 6 were also resistant to polymyxin B,and the total resistance rate was 7.69%(6/78).18 of 132 CSE strains were only resistant to fosfomycin,with the total resistance rate of 13.64%(18/132).No resistance to polymyxin B was detected.Polymyxin B combined with fosfomycin has additive effect on CREC and synergistic effect on CRKP.Conclusion The single drug resistance rate of fosfomycin and polymyxin B increased significantly,the combination of fosfomycin and polymyxin B can effectively reduce the drug resistance rate and provide a new treatment idea.