ICU血流感染患者碳青霉烯类抗菌药物耐药肺炎克雷伯菌的毒力和耐药基因分布及其与感染严重程度的相关性

Virulence and Resistance Gene Distribution of Carbapenem-resistant Klebsiella Pneumoniae in ICU Patients with Bloodstream Infections and Its Correlation with Severity of Infection

目的探讨重症监护病房(ICU)碳青霉烯类抗菌药物耐药肺炎克雷伯菌血流感染患者的临床特征,并分析菌株耐药和毒力基因的检出情况及其与感染严重程度的关系。方法选取2018年1月至2020年12月新疆医科大学第五附属医院检验科首次分离的180株非重复耐碳青霉烯类肺炎克雷伯菌(CR-KP),以上菌株来自180例ICU血流感染患者的血液样本。根据拉丝试验将所有菌株分为耐碳青霉烯类高毒力肺炎克雷伯菌(CR-hvKP)组和耐碳青霉烯类非高毒力肺炎克雷伯菌(CR-non-hvKP)组,比较两组CR-KP菌株宿主临床特征、碳青霉烯酶、血清荚膜分型和毒力基因的检出情况,并采用Spearman法分析毒力基因与患者脓毒症相关序贯器官衰竭(SOFA)评分的相关性。结果180株CR-KP宿主中CR-hvKP感染患者62例(34.4%)。CR-hvKP组年龄、合并糖尿病及30 d内死亡比例明显高于CR-non-hvKP组(P<0.05)。CR-hvKP组与CR-non-hvKP组携带肺炎克雷伯菌碳青霉烯酶基因和携带新德里金属-β-内酰胺酶基因的菌株比例比较差异无统计学意义(P>0.05)。ICU血流感染患者CR-KP菌株携带的毒力基因以ybtS(95.6%)和entB(81.7%)为主,其中CR-hvKP组菌株中携带rmpA、iutA和rmpA2毒力基因的比例高于CR-non-hvKP组[98.4%(61/62)比12.7%(15/118),87.1%(54/62)比27.1%(32/118),85.5%(53/62)比18.6%(22/118)](P<0.05),CR-hvKP与CR-non-hvKP组其余毒力基因分布比较差异无统计学意义(P>0.05)。Spearman相关性分析结果显示,毒力基因rmpA、iutA和rmpA2与SOFA评分呈正相关(r=0.498,P<0.001;r=0.652,P<0.001;r=0.630,P<0.001)。结论ICU碳青霉烯类抗菌药物耐药肺炎克雷伯菌血流感染患者毒力基因rmpA、iutA和rmpA2与感染严重程度存在密切关系,及时检测菌株毒力基因对临床治疗具有一定意义。

Objective To investigate the clinical characteristics of patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection in intensive care unit(ICU)and to analyze the detection of strain resistance and virulence genes and their relationship with the severity of infection.Methods One hundred and eighty non-repeated carbapenem-resistant Klebsiella pneumoniae(CR-KP)strains first isolated from the clinical laboratory of the Fifth Affiliated Hospital of Xinjiang Medical University from Jan.2018 to Dec.2020 were selected,which were obtained from the blood samples of 180 patients with ICU bloodstream infections.All strains were divided into a carbapenem-resistant,highly virulent Klebsiella pneumoniae(CR-hvKP)group and a carbapenem-resistant,non-highly virulent Klebsiella pneumoniae(CR-non-hvKP)group according to the pull-down test,and the clinical characteristics of hosts,carbapenemases,serum podotyping and virulence genes were compared between the two groups of CR-KP strains,and the Spearman method was used to analyze the relationship between virulence genes and sepsis-related sequential organ failure assessment(SOFA)scores in the patients.Results Among the 180 strains of CR-KP,62 patients(34.4%)were infected with CR-hvKP.The proportions of age,diabetes mellitus and death within 30 days in the CR-hvKP group were significantly higher than those in the CR-non-hvKP group(P<0.05).There was no significant difference in the proportion of strains carrying Klebsiella pneumoniae carbapenemase gene and New Delhi metallo-βlactamase gene between the CR-hvKP group and the CR-non-hvKP group(P>0.05).The virulence genes of CR-KP strain in ICU patients with bloodstream infection were mainly ybtS(95.6%)and entB(81.7%).The proportions of rmpA,iutA and rmpA2 virulence genes in the CR-hvKP group were higher than those in the CR-non-hvKP group[98.4%(61/62)vs 12.7%(15/118),87.1%(54/62)vs 27.1%(32/118),85.5%(53/62)vs 18.6%(22/118)](P<0.05),and there was no statistically significant difference in the distribution of other virulence genes between the CR-hvKP group and the CR-non-hvKP group(P>0.05).Spearman correlation analysis showed that virulence genes rmpA,iutA and rmpA2 were positively correlated with SOFA score(r=0.498,P<0.001;r=0.652,P<0.001;r=0.630,P<0.001).Conclusion The virulence genes rmpA,iutA and rmpA2 of patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection in ICU are closely related to the severity of infection,and timely detection of strain virulence genes has some significance for the clinical treatment.