肺炎链球菌氟喹诺酮耐药决定区突变位点研究  

Fluoroquinolone resistance determining region mutation in Streptococcus pneumonia isolates

作　　者：张菲菲[1] 赵春江[1] 王辉[1] 

机构地区：[1]北京大学人民医院检验科,100044

出　　处：《中华结核和呼吸杂志》2013年第12期940-944,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

摘　　要：目的 调查我国肺炎链球菌对不同氟喹诺酮类抗生素（FQ）的耐药性,研究耐药突变位点与FQ耐药性的关系.方法 收集2010年6-12月我国9个城市12家教学医院临床分离的232株肺炎链球菌,用琼脂稀释法测定环丙沙星、左氧氟沙星和莫西沙星等16种抗菌药物的抗菌活性.选取左氧氟沙星MIC≥1 mg/L的菌株进行parC、parE和gyrA基因喹诺酮耐药决定区（QRDR）PCR扩增和序列分析.结果 环丙沙星、左氧氟沙星和莫西沙星的敏感度分别53.9％ （125/232）、98.7％ （229/232）和98.7％ （229/232）.选取19株左氧氟沙星MIC≥2 mg/L的菌株并筛选出24株左氧氟沙星MIC值为1 mg/L的菌株,在选取的43株肺炎链球菌中,当parE靶点发生单一突变时,左氧氟沙星的MIC值为1～2 mg/L,环丙沙星的MIC值为2 mg/L,莫西沙星的MIC值为0.125～0.25 mg/L.当parE和parC靶点均有突变时,大部分菌株左氧氟沙星的MIC值为2 mg/L,环丙沙星的MIC值为4 mg/L,莫西沙星的MIC值为0.25 mg/L或0.50 mg/L.当parE和gyrA靶点同时突变时,左氧氟沙星的MIC值为16 mg/L,环丙沙星的MIC≥16 mg/L,莫西沙星的MIC值为4 mg/L.卡方检验结果发现,parE基因和parC基因双突变比parE基因单突变更能导致左氧氟沙星耐药性升高.结论 当parE/parC靶点产生突变时,左氧氟沙星和环丙沙星的MIC值已有升高,但莫西沙星MIC值还处于低水平;只有当parC/parE和gyrA双位点突变时,莫西沙星才达到耐药水平.Objective To investigate the relationship between different fluoroquinolone （FQ） resistance of Streptococcus pneumoniae and the mutations of target genes. Methods A total of 232 Streptococcus pneumoniae isolates were collected from 12 teaching hospitals at 9 cities between June and December 2010. The antibacterial activities of 16 antimicrobial agents were determined by agar dilution method. The ciprofloxacin,levofloxacin and moxifloxacin MIC I〉 1 mg/L isolates were selected to detect the mutations in QRDR （parC ,parE, and gyrA genes） through PCR combined sequencing, Results The susceptible rates of ciprofloxacin,levofloxacin and moxifloxacin were 53.9% （125/232）, 98. 7% （229/232）, 98. 7% （229/232）. Forty-three strains were randomly selected to be analyzed,including 19 levofloxacin MIC≥2 mg/L strains and 24 levofloxacin MIC = 1 mg/L strains. The MIC of levofloxacin were 1 -2 mg/L,ciprofloxacin were 2 mg/L and moxifloxacin were 0. 125 -0. 250 mg/L when a single mutation in parE occurred. The MIC of levofloxacin were 2 mg/L,ciprofloxacin were 4 mg/L and moxifloxacin were 0. 25 mg/L or 0. 50 mg/L when mutations in both parE and parC occurred. The MIC of levofloxacin were 16 mg/ L,ciprofloxacin were ≥ 16 mg/L and moxifloxacin were 4 mg/L when mutations in both parE and gyrA occurred. Conclusion The single mutation in parE/parC is associated with low level levofloxacin and ciprofloxacin resistance, while double mutations in both parC/parE and gyrA are associated with moxifloxacin resistance.

关 键 词：肺炎链球菌感染 喹诺酮类 基因 抗药性 细菌 

分 类 号：R378[医药卫生—病原生物学]