临床分离产气克雷伯菌整合子和质粒介导的喹诺酮耐药基因分布特征分析

Distribution characteristics of integrons and plasmid-mediated quinolone resistance genes in Klebsiella aerogenes clinical isolates

目的确定临床分离菌株产气克雷伯菌整合子、质粒介导的喹诺酮耐药(PMQR)基因的分布, 并分析整合子与临床常用抗菌药物耐药性的关系。方法收集2015年11月至2021年3月上海市奉贤区中心医院分离自临床样本中的产气克雷伯菌91株, PCR筛查第1、2类整合酶基因(intI1、intI2), 分析启动子类型和可变区基因盒组成结构。同时对分离株PMQR基因进行检测, 并分析整合子与临床常用抗感染治疗药物间的关系。结果 91株产气克雷伯菌对氨曲南耐药率>40.00%, 对其余常用抗菌药物耐药率均<35.00%。91株产气克雷伯菌中30株检出intI1, 未检出intI2。第1类整合子检出7种可变区基因盒组合, 在产气克雷伯菌中检出基因盒组合aac(6′)-11C-ΔereA2-IS1247-aac3-arr-ΔereA2。第1类整合子可变区启动子以活性较弱的PcH1启动子为主。intI1阳性菌株与intI1阴性菌株在ICU、神经外科和临床其他科室的检出率差异有统计学意义(P<0.05)。intI1阳性菌株对部分临床常用抗菌药物耐药率明显高于intI1阴性菌株(P<0.05)。qnrS为PMQR基因的主要基因型。除2016年外, 其余年份分离的产气克雷伯菌中整合子和PMQR基因的检出率均较低。结论产气克雷伯菌耐药性的产生与整合子密切相关, 产气克雷伯菌中整合子在不同临床科室的分布具有一定的差异性, ICU和神经外科应持续加强细菌耐药的监测。qnrS是本地区产气克雷伯菌对喹诺酮类药物产生耐药的主要原因。

Objective To investigate the distribution of integrons and plasmid-mediated quinolone resistance(PMQR)genes in clinical isolates of Klebsiella aerogenes and to analyze the relationship between integrons and bacterial resistance to antimicrobial agents.Methods Ninety-one Klebsiella aerogenes strains isolated from clinical samples in the Fengxian District Central Hospital from November 2015 to March 2021 were used in this study.Class 1 and class 2 integron-integrase genes(intI1 and intI2)and PMQR genes were screened by PCR.The types of promoters and gene cassette arrays of variable regions were determined by sequencing.Besides,the relationship between integrons and antimicrobial resistance was analyzed.Results The resistance rate of the 91 Klebsiella aerogenes isolates to aztreonam was more than 40.00%and the resistance rates to other commonly used antimicrobial agents were less than 35.00%.Among the 91 isolates,30 carried the intI1 gene,while none of them carried the intI2 gene.Seven class 1 integron gene cassette arrays of variable regions were detected and the gene cassette array of aac(6′)-11C-ΔereA2-IS1247-aac3-arr-ΔereA2 was detected in Klebsiella aerogenes.PcH1 with weak activity was the predominant variable region promoter of class 1 integrons.The detection rates of intI1-positive and intI1-negative isolates in ICU,neurosurgery and other clinical departments were statistically different(P<0.05).The resistance rate of intI1-positive isolates to some commonly used antibiotics was significantly higher than that of intI1-negative isolates(P<0.05).qnrS gene was the prevalent PMQR gene.The detection rates of integrons and PMQR genes in Klebsiella aerogenes isolates was low except for the strains isolated in 2016.Conclusions Antimicrobial resistance in Klebsiella aerogenes was closely related to integrons.The distribution of integrons in Klebsiella aerogenes strains isolated from different clinical departments was different,and the monitoring of drug-resistant strains should be strengthened in ICU and neurosurgery.The resistance to quinolones in Klebsiella aerogenes strains in this region was mainly related to qnrS gene.