肺炎克雷伯杆菌对氟喹诺酮类抗生素耐药机制的研究
The mechanism of resistance of Klebsiella pneumoniae to Fluoroquinolones
作者：高山;普珍;孙晓明;刘小康;
Author：
收稿日期： 年卷（期）页码：2006,(01):-21-24
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：肺炎克雷伯杆菌;氟喹诺酮;耐药机制;聚合酶链反应;最低抑菌浓度
Key words：
基金项目：
中文摘要
目的研究临床分离的耐氟喹诺酮类药物肺炎克雷伯杆菌的耐药机制。方法临床分离、鉴定的肺炎克雷伯杆菌采用琼脂二倍稀释法测定氟喹诺酮的MIC,从中选取10株耐氟喹诺酮的菌株。通过聚合酶链反应(PCR)扩增gyrA基因和parC基因,扩增产物片段长度分别为6253、19 bp,经纯化后测序。用琼脂二倍稀释的方法测定5种氟喹诺酮类单独使用及与泵抑制剂CCCP合用后的MIC。结果5株耐氟喹诺酮肺炎克雷伯杆菌的gyrA和parC基因经测序分析,显示gyrA的第83位(TCC→ATC/TTG)均出现了突变,引起了相应氨基酸的改变(Ser-83→Ile/Leu)。其中有一株同时也出现了第87位点(GAC→AAC)的改变,氨基酸也由Asp→Asn。parC有4株出现了第80位点突变(AGC→ATC),引起氨基酸由Ser→Ile的改变。MIC测定结果显示,有一株肺炎克雷伯杆菌在单用5种氟喹诺酮类药物及与CCCP合用后,MIC降低了8~32倍;两株肺炎克雷伯杆菌分别对环丙沙星及左氧氟沙星所测的MIC降低了32倍和4倍;还有一株对左氧氟沙星和司帕沙星在使用CCCP前后的MIC降低了4倍。结论gyrA和parC基因突变是肺炎克雷杆菌对氟喹诺酮类产生耐药机制的主要原因,主动外排机制也是肺炎克雷伯杆菌耐氟喹诺酮类抗生素的因素之一。
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