携带耐药基因的肠杆菌科细菌对左氧氟沙星防耐药突变浓度的影响研究  

Study on the effect of mutation preventive concentration of levofloxacin against Enterobacteriaceae with resistance genes

作　　者：马攀 陈勇川 冯伟 袁慊 贾运涛 Ma Pan;Chen Yong-chuan;Feng Wei;Yuan Qian;Jia Yun-tao(School of Pharmacy,Chongqing Medical University,Chongqing 400016;Department of Pharmacy,the First Affiliated Hospital of Army Medical University,Chongqing 400038;Department of Pharmacy,Children’s Hospital of Chongqing Medical University/Ministry of Education Key Laboratory of Child Development and Disorders/China International Science and Technology Cooperation Base of Child Development and Critical Disorders/Chongqing Key Laboratory of Pediatrics/National Clinical Research Center for Child Health and Disorders,Chongqing 400014)

机构地区：[1]重庆医科大学药学院,重庆400016 [2]陆军军医大学第一附属医院药学部,重庆400038 [3]重庆医科大学附属儿童医院药学部/儿童发育疾病研究教育部重点实验室/儿童发育重大疾病国家国际科技合作基地/儿科学重庆市重点实验室/国家儿童健康与疾病临床医学研究中心,重庆400014

出　　处：《中国抗生素杂志》2021年第10期945-951,共7页Chinese Journal of Antibiotics

基　　金：重庆市科委基金(No.cstc2017shmsA130043)。

摘　　要：目的通过测定左氧氟沙星对大肠埃希菌和肺炎克雷伯菌的最低抑菌浓度(MIC)和防耐药突变浓度(MPC),研究携带耐药基因的肠杆菌科细菌对左氧氟沙星MPC的影响。方法采用琼脂二倍稀释法测定左氧氟沙星对76株大肠埃希菌和60株肺炎克雷伯菌的MIC、MPC并计算各自的MIC_(90)、MPC_(90)、SI(MPC/MIC)等值。采用PCR扩增超广谱β-内酰胺酶(ESBLs)和qnr耐药基因,并统计分析产与非产ESBLs和带与不带qnr各组间MIC、MPC的差异。结果左氧氟沙星对大肠埃希菌产ESBLs组和非产ESBLs组的MIC_(90)分别为4和1μg/mL,MPC_(90)分别为10.24和3.2μg/mL。对肺炎克雷伯菌产ESBLs组和非产ESBLs组的MIC_(90)分别是1和0.0625μg/mL,MPC_(90)分别为5.12和1.6μg/mL。左氧氟沙星对大肠埃希菌带qnr基因组和不带qnr基因组的MIC_(90)分别为0.5和1μg/mL,MPC_(90)分别为12.8和4.096μg/mL。对肺炎克雷伯菌带qnr基因组和不带qnr基因组的MIC_(90)均是0.5μg/mL,MPC_(90)分别为6.4和2.56μg/mL。产与非产ESBLs组和带与不带qnr基因组的MIC无统计学差异,但产ESBLs组的MPC明显高于非产组(P<0.001),耐药基因qnr的存在亦显著提高了临床菌株的MPC值(P<0.05)。结论本研究证明临床上产ESBLs和带qnr基因的肠杆菌会增加MPC从而导致细菌耐药。测定致病菌的MPC,尽量延长治疗期间血药浓度高于MPC的时间,则最大程度上抑制了耐药突变株的富集扩增。针对MIC在左氧氟沙星敏感折点以下的产ESBLs和/或带qnr基因的肠杆菌,应结合PK/PD特点和MSW理论优化给药方案从而达到兼顾临床疗效和耐药预防的目的。Objective To determine the minimum inhibitory concentration(MIC)and mutation prevention concentration(MPC)of levofloxacin against Escherichia coli and Klebsiella pneumoniae,and to study on the effect of mutation preventive concentration of levofloxacin against Enterobacteriaceae with resistance genes.Methods The agar double dilution method was used to determine the MIC and MPC of levofloxacin against 76 strains of Escherichia coli and 60 strains of Klebsiella pneumoniae,Then calculate the respective values of MIC_(90),MPC_(90),SI(MPC/MIC).PCR was used to amplify extended spectrumβ-lactamases(ESBLs)and qnr resistance genes,and statistical analysis of the differences in MIC and MPC between the ESBL-producing and non-ESBLs-producing bacterial groups and between the bacterial groups with and without qnr.Results The MIC_(90) of levofloxacin against ESBLs-producing Escherichia coli was 4μg/mL,and the MPC_(90) was 10.24μg/mL;for non-ESBLs-producing Escherichia coli,the MIC_(90) was 1μg/mL and MPC_(90) was 3.2μg/mL.The MIC_(90) for ESBLs-producing Klebsiella pneumoniae is 1μg/mL,and the MPC_(90) is 5.12μg/mL;the MIC_(90) for non-ESBLs-producing Klebsiella pneumoniae is 0.0625μg/mL,and the MPC_(90) is 1.6μg/mL.The MIC_(90) of levofloxacin against Escherichia coli with qnr was 0.5μg/mL,and the MPC_(90) was 12.8μg/mL;for Escherichia coli without qnr,the MIC_(90) was 1μg/mL and MPC_(90) was 4.096μg/mL.The MIC_(90) for Klebsiella pneumonia with qnr is 0.5μg/mL,and the MPC_(90) is 6.4μg/mL;the MIC_(90) for Klebsiella pneumoniae without qnr is 0.5μg/mL,and the MPC_(90) is 2.56μg/mL.There was no significant difference in MIC between ESBLs-producing and non-ESBLs-producing,with and without qnr.The MPC of ESBLs-producing strains was significantly higher than that of non-producing strains(P<0.001),and the presence of resistance gene qnr significantly increased the MPC value of clinical strains(P<0.05).Conclusion This study proved that clinically producing ESBLs and enterobacteria with qnr gene can increase MPC and

关 键 词：左氧氟沙星 大肠埃希菌 肺炎克雷伯菌 防耐药突变浓度 超广谱Β-内酰胺酶 

分 类 号：R978[医药卫生—药品]