目的研究替加环素与临床常用抗生素对碳青霉烯耐药高毒力肺炎克雷伯菌(hypervirulent and carbapenemresistant Klebsiella pneumonia,CR-HvKP)的体外联合抗菌活性。方法收集2017~2019年河北医科大学第二医院临床分离非重复性CR-HvKP共2...目的研究替加环素与临床常用抗生素对碳青霉烯耐药高毒力肺炎克雷伯菌(hypervirulent and carbapenemresistant Klebsiella pneumonia,CR-HvKP)的体外联合抗菌活性。方法收集2017~2019年河北医科大学第二医院临床分离非重复性CR-HvKP共20株。应用微量肉汤稀释法测定替加环素与5种抗生素的最低抑菌浓度(MIC),采用棋盘稀释法检测替加环素与5种抗生素(多黏菌素、头孢哌酮钠/舒巴坦钠、美罗培南、阿米卡星、磷霉素钠)的联合药敏试验。结果20株CR-HvKP主要来源于呼吸ICU 13例(65%),均为ST11型,碳青霉烯酶基因均为KPC-2型。血清型12株(60%)为K2型,为主要的血清型,1株(5%)为K1型。拉丝试验及毒力基因rmpA2均为阳性。替加环素与多黏菌素出现协同作用,百分比为60%。替加环素与美罗培南、磷霉素钠、头孢哌酮钠/舒巴坦钠均未出现协同作用。结论替加环素与多黏菌素体外联合有协同作用,可供临床作为参考治疗CR-HvKP感染。展开更多
目的研究碳青霉烯耐药高毒力肺炎克雷伯菌(hypervirulent and carbapenem-resistant Klebsiella pneumonia,CR-HvKP)实验室检测及临床转归相关危险因素。方法回顾性研究2016年12月~2017年12月河北医科大学第二医院CR-HvKP感染患者20例,...目的研究碳青霉烯耐药高毒力肺炎克雷伯菌(hypervirulent and carbapenem-resistant Klebsiella pneumonia,CR-HvKP)实验室检测及临床转归相关危险因素。方法回顾性研究2016年12月~2017年12月河北医科大学第二医院CR-HvKP感染患者20例,对患者临床资料进行分析,采用PCR检测毒力基因(rmpA和rmpA2)、血清型(K1和K2)以及碳青霉烯酶基因(KPC-2,NDM-1,OXA,VIM和IMP)。结果20例CR-HvKP感染患者中,毒力基因rmpA2均为阳性,拉丝试验阳性17例(85%),K2血清型16例(80%)和碳青霉烯酶基因KPC-2型18例(90%)。标本来源主要为痰/肺泡灌洗液16例(80%),治疗好转9例(45%)和治疗无效11例(55%)。患者使用气管插管辅助呼吸以及感染并发症危及生命的感染性休克治疗无效和好转比较,差异均具有统计学意义(χ^2=5.690~7.593,均P<0.05)。结论CR-HvKP感染临床治愈率低,传播性强,应引起高度重视。展开更多
The global spread of hypervirulent Klebsiella pneumoniae(hvKp)poses a serious public health threat.In this study,we conducted genomic epidemiology analysis on 2097 global hvKp isolates,including our 900 isolates seque...The global spread of hypervirulent Klebsiella pneumoniae(hvKp)poses a serious public health threat.In this study,we conducted genomic epidemiology analysis on 2097 global hvKp isolates,including our 900 isolates sequenced through the Illumina platform(177 of them fully sequenced through PacBio platform),representing the most comprehensive genomic analysis of hvKp to date.Our results identified six dominant clonal groups(CGs),particularly including CG23 and CG258,and 17 major virulence determinant combinations(VDCs)comprising 10 virulence gene profiles(VGPs),four types of virulence plasmids,four ICEKp variants,Tn7399,and all_island.Each CG harbored distinct advantageous VDCs,indicating strong genomic correlation and co-evolution.Additionally,the phylogeny and evolutionary history of CG23 and CG258 were characterized in depth.Notably,41.58%of the 2097 isolates were multidrug-resistant and 33.29%were carbapenem-resistant,indicating serious antimicrobial resistance.Overall,our study provides a global genomic landscape of hvKp,emphasizing the genetic basis for their global dissemination and the need for precise prevention and control.展开更多
文摘目的研究碳青霉烯耐药高毒力肺炎克雷伯菌(hypervirulent and carbapenem-resistant Klebsiella pneumonia,CR-HvKP)实验室检测及临床转归相关危险因素。方法回顾性研究2016年12月~2017年12月河北医科大学第二医院CR-HvKP感染患者20例,对患者临床资料进行分析,采用PCR检测毒力基因(rmpA和rmpA2)、血清型(K1和K2)以及碳青霉烯酶基因(KPC-2,NDM-1,OXA,VIM和IMP)。结果20例CR-HvKP感染患者中,毒力基因rmpA2均为阳性,拉丝试验阳性17例(85%),K2血清型16例(80%)和碳青霉烯酶基因KPC-2型18例(90%)。标本来源主要为痰/肺泡灌洗液16例(80%),治疗好转9例(45%)和治疗无效11例(55%)。患者使用气管插管辅助呼吸以及感染并发症危及生命的感染性休克治疗无效和好转比较,差异均具有统计学意义(χ^2=5.690~7.593,均P<0.05)。结论CR-HvKP感染临床治愈率低,传播性强,应引起高度重视。
基金supported by the Fundamental Research Funds for the Central Universities (YD9100002013)the National Key Research and Development Program of China (2021YFC2300300)+1 种基金the National Natural Science Foundation of China (32070132)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29020000)
基金supported by the National Key R&D Program of China(2023YFC2605600 and 2023YFC2604400).
文摘The global spread of hypervirulent Klebsiella pneumoniae(hvKp)poses a serious public health threat.In this study,we conducted genomic epidemiology analysis on 2097 global hvKp isolates,including our 900 isolates sequenced through the Illumina platform(177 of them fully sequenced through PacBio platform),representing the most comprehensive genomic analysis of hvKp to date.Our results identified six dominant clonal groups(CGs),particularly including CG23 and CG258,and 17 major virulence determinant combinations(VDCs)comprising 10 virulence gene profiles(VGPs),four types of virulence plasmids,four ICEKp variants,Tn7399,and all_island.Each CG harbored distinct advantageous VDCs,indicating strong genomic correlation and co-evolution.Additionally,the phylogeny and evolutionary history of CG23 and CG258 were characterized in depth.Notably,41.58%of the 2097 isolates were multidrug-resistant and 33.29%were carbapenem-resistant,indicating serious antimicrobial resistance.Overall,our study provides a global genomic landscape of hvKp,emphasizing the genetic basis for their global dissemination and the need for precise prevention and control.
文摘目的建立转座子突变文库,筛选高毒力肺炎克雷伯菌(hypervirulent Klebsiella pneumoniae,hvKp)的新毒力基因。方法构建转座子突变文库,血清处理,通过转座子测序(transposon sequencing,Tn-seq)比较分析血清处理前后各基因突变株在文库中丰度变化,并对筛选出的基因进行KEGG(kyoto encyclopedia of genes and genomes)注释和富集分析。结果以处理后丰度低于初始丰度20%为界,共筛选出405个基因,其中351个基因在HS11286、NJST258_1、NTUH-K2044和RJF293等4株参考菌株中保守存在,占86.7%,10个基因为NTUH-K2044和RJF293两株高毒力株共有而低毒力株HS11286和NJST258_1缺失;荚膜多糖基因簇中基因如糖基转移酶基因wzy、聚集蛋白基因wzi、荚膜转运蛋白基因wza等突变株在血清处理后不能检出,气杆菌素、沙门氏菌素等铁载体基因簇在各文库中的丰度变化不超过1倍;KEGG注释结果显示,注释最多的基因为参与氨基酸代谢、辅助因子和维生素代谢、碳水化合物代谢等。结论Tn-seq是功能基因筛选的可靠方法,本研究成功筛选出405个hvKp的候选新毒力基因,为后续深入研究hvKp的新毒力基因功能和调控机制提供实验依据。