碳青霉烯类耐药肺炎克雷伯菌对喹诺酮类的高度耐药性及其耐药机制  

High level quinolone resistance and the mechanisms of resistance in carbapenem-resistant Klebsiella pneumo

作　　者：阿力米热·艾买提 孙哲伟 徐庆庆 徐晓刚 王明贵 ALIMIRE Aimaiti;SUN Zhewei;XU Qingqing;XU Xiaogang;WANG Minggui(Institute of Antibiotics,Huashan Hospital,Fudan University,Shanghai 200040,China)

机构地区：[1]复旦大学附属华山医院抗生素研究所,上海200040

出　　处：《中国感染与化疗杂志》2024年第3期326-331,共6页Chinese Journal of Infection and Chemotherapy

基　　金：国家重大疾病多学科合作诊疗能力建设(3030248002);第一三共(中国)投资有限公司(2019QD041)。

摘　　要：目的了解碳青霉烯类耐药肺炎克雷伯菌(CRKP)对喹诺酮类的耐药性及其耐药机制,包括可移动喹诺酮类耐药(TMQR)基因分布。方法对2019年我国7所医院临床分离的CRKP菌株采用肉汤微量稀释法进行抗菌药物敏感性试验。采用Illumina HiseqX测序平台进行基因组测序,并分析CRKP携带的毒力基因、MLST分型、染色体喹诺酮类耐药决定区(QRDR)的变异情况,以及TMQR基因分布。结果481株CRKP对左氧氟沙星和环丙沙星不敏感率分别为98.4%和99.2%,ST11型和ST15型为优势克隆。303株携带毒力基因的CRKP(CV-CRKP)中,ST11型和ST15型菌株分别为92.1%和5.0%。178株不携带毒力基因的CRKP(non-CV-CRKP)中,ST11型和ST15型菌株分别为53.4%和34.3%。全部ST11和ST15型菌株对喹诺酮类耐药并伴有gyrA和parC基因变异,对喹诺酮类敏感菌株均为非ST11和非ST15型菌株。可移动元件介导的喹诺酮耐药基因中,qnrS1(294株,61.1%)、qnrB4(48株,10.0%)及aac(6)-Ib-cr(90株,18.7%)的检出率高,其他基因的检出较低,包括有qnrB1(4株)、qnrB2(2株)、qnrD1(2株)、qnrB6(1株)。其中,qnrB4主要分布在左氧氟沙星高度耐药(MIC≥8 mg/L)菌株中。aac(6)-Ib-cr主要分布在环丙沙星耐药(MIC>8 mg/L)菌株中。结论临床分离的CRKP菌株对喹诺酮类耐药率高。喹诺酮类耐药的CRKP菌株中QRDR变异率高,TMQR基因携带率高。Objective To examine the quinolone resistance and mechanisms of resistance,including prevalence of transferable mechanisms of quinolone resistance(TMQR)genes in carbapenem-resistant Klebsiella pneumoniae(CRKP).Methods Antimicrobial susceptibility was tested for CRKP isolated from 7 hospitals in China during 2019 by broth microdilution method.Genome sequencing analysis was performed on Illumina HiseqX sequencing platform.The virulence genes,multilocus sequence typing(MLST),chromosome quinolone resistance-determining region(QRDR)variation,and prevalence of TMQR genes in CRKP were analyzed.Results Overall,98.4%and 99.2%of the 481 CRKP strains were non-susceptible to levofloxacin and ciprofloxacin,respectively.ST11(77.8%)and ST15(15.8%)were the dominant clones.Among the 303 CRKP strains carrying virulence gene(CV-CRKP),ST11 type and ST15 type strains accounted for 92.1%and 5.0%,respectively,while ST11 and ST15 type strains accounted for 53.4%and 34.3%in the 178 CRKP strains without the virulence gene(non-CV-CRKP).All of the ST11 and ST15 type strains were resistant to quinolones associated with gyrA and parC mutation.All of the quinolone-sensitive strains were not ST11 type or not ST15 type.TMQR analysis showed that qnrS1(61.1%,294 strains),qnrB4(10.0%,48 strains)and aac(6)-Ib-cr(18.7%,90 strains)were most prevalent in CRKPs,while qnrB1(4 strains),qnrB2(2 strains),qnrD1(2 strains)and qnrB6(1 strain)were infrequently identified in CRKPs.Specifically,qnrB4 was mainly identified in high-level levofloxacin-resistant strains(MIC≥8 mg/L),while aac(6)-Ib-cr was found mainly in ciprofloxacin-resistant strains(MIC>8 mg/L).Conclusions Clinical CRKPs were highly resistant to quinolone.The rate of QRDR variation were high in quinolone resistant CRKP strains,with high TMQR gene carriage.

关 键 词：碳青霉烯类耐药肺炎克雷伯菌 左氧氟沙星 环丙沙星 多位点序列分型 喹诺酮类耐药决定区 QNR aac(6)-Ib-cr 

分 类 号：R378.996[医药卫生—病原生物学]