肺炎克雷伯菌对复方新诺明的耐药性及其整合子分布差异的研究

Drug-resistance in Klebsiella pneumoniae to trimethoprim/sulfamethoxazole and its relation to integrons of bacteria

目的探讨肺炎克雷伯菌对复方新诺明的耐药性、整合子分布及其对耐药性的影响。方法收集温州医科大学附属第一医院2013年1月至2015年5月临床分离的肺炎克雷伯菌共812株,采用VITEK 2 Compact全自动微生物分析仪测定肺炎克雷伯菌临床分离株对临床常用的以复方新诺明为代表的抗菌药物耐药性,PCR方法筛查其Ⅰ、Ⅱ、Ⅲ型整合子,分析不同耐药表型菌株内整合子分布的差异。结果肺炎克雷伯菌对多种抗菌药物耐药率呈上升趋势,仅对复方新诺明耐药率呈逐年递减趋势,亚胺培南和厄他培南耐药肺炎克雷伯菌对复方新诺明保持相对较低的耐药率;肺炎克雷伯菌中Ⅰ型整合子总阳性率为37.2%,未检测到Ⅱ、Ⅲ型整合子,复方新诺明耐药菌株组Ⅰ型整合子阳性率明显高于敏感组(P<0.01);整合子阳性菌株组对临床常用抗菌药物的非敏感率(中介率与耐药率之和)几乎均明显高于整合子阴性菌株组(均P<0.05);复方新诺明耐药组和敏感组中,多重耐药菌株的Ⅰ型整合子阳性率均显著高于非多重耐药菌株,广泛耐药菌株的Ⅰ型整合子阳性率也均显著高于非广泛耐药菌株(均P<0.01)。结论 2013至2015年,肺炎克雷伯菌仅对复方新诺明的耐药率呈现逐年降低趋势,且耐碳青霉烯肺炎克雷伯菌对复方新诺明敏感性良好;肺炎克雷伯菌主要携带Ⅰ型整合子,由整合子介导的耐药基因的传播与复方新诺明耐药性、多重耐药表型、广泛耐药表型均密切相关。

Objective To investigate the drug resistance of Klebsiella pneumoniae to trimethoprim/sulfamethoxazole and its relation to integrons of the bacteria.Methods A total of 812 clinical isolates of K.pneumoniae were collected from the First Affiliated Hospital of Wenzhou Medical University during January 2013 to March 2015.The drug susceptibility of K.pneumoniae was tested by VITEK 2 Compact.Class 1,2 and 3 integrons were amplified by polymerase chain reaction(PCR).The impact of the distribution of integrons in K.pneumoniae strains of different resistance phenotypes were analyzed.Results The resistance rates of K.pneumoniae to most commonly used antibacterial agents were all increasing;while the declining trend of the resistant rate of K.pneumoniae was only observed in trimethoprim/sulfamethoxazole.The rates of imipenem-resistant strains and ertapenem-resistant strains to trimethoprim/sulfamethoxazole were relatively low.Positive rate of class 1 integron was 37.2%,class 2,3 integrons were not detected.Positive rate of class 1 integron was higher in trimethoprim/sulfamethoxazole-resistant strains than that in trimethoprim/sulfamethoxazole-susceptible strains(P<0.01).Unsusceptible rate of integron-positive strains to commonly used antimicrobial agents was higher than that of integron-negative strains(all P<0.05).Furthermore,higher positive rate of class 1 integron was observed in multi-drug resistant and extensively drug-resistant strains both in trimethoprim/sulfamethoxazole-resistant and trimethoprim/sulfamethoxazole-susceptible groups(all P<0.01).Conclusion The resistant rates of K.pneumoniae to trimethoprim/sulfamethoxazole have been declined year by year,and high susceptibility of carbapenem-resistant strains to trimethoprim/sulfamethoxazole are observed.The spread of resistance genes mediated by integrons is closely related to phenotypes of trimethoprim/sulfamethoxazole resistance,multi-drug resistance and extensively-drug resistance in Klebsiella pneumonia.