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肝病患者中产碳青霉烯类耐药肠杆菌科细菌粪便携带的危险因素和分子流行病学。

Risk factors and molecular epidemiology of fecal carriage of carbapenem resistant Enterobacteriaceae in patients with liver disease.

机构信息

Department of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Ann Clin Microbiol Antimicrob. 2023 Jan 29;22(1):10. doi: 10.1186/s12941-023-00560-8.

Abstract

BACKGROUND

Carbapenem resistant Enterobacteriaceae (CRE) colonization is a risk factor for CRE infection. CRE infection results in an increase in mortality in patients with cirrhosis. However, minimal data regarding the prevalence and the risk factors of CRE colonization in patients with liver disease yet without liver transplantation are available. The present study aimed to investigate the prevalence, risk factors and molecular epidemiology characteristics of CRE fecal carriage among patients with liver disease.

METHODS

Stool specimens from 574 adult inpatients with liver disease were collected from December 2020 to April 2021. CRE were screened using selective chromogenic agar medium and identified by the Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). Antimicrobial susceptibility was determined using the broth microdilution method. Carbapenemase genes were characterized by polymerase chain reaction (PCR) and DNA sequencing. Multilocus sequence typing (MLST) was performed for Carbapenem Resistant Klebsiella pneumoniae (CR-KPN) isolates and Carbapenem Resistant Escherichia Coli (CR-ECO) isolates.

RESULTS

The total number of stool specimens (732) were collected from 574 patients with liver disease. 43 non-duplicated CRE strains were isolated from 39 patients with a carriage rate of 6.79% (39/574). The carriage rate was 15.60% (17/109) in patients with acute-on-chronic liver failure (ACLF). Multivariate analysis indicated that ACLF (P = 0.018), the history of pulmonary infection within past 3 months (P = 0.001) and the use of third generation cephalosporin/β-lactamases inhibitor within past 3 months (P = 0.000) were independent risk factors of CRE colonization in patients with liver disease. Klebsiella Pnuemoniae (KPN) (51.28%) and Escherichia coli (ECO) (30.77%) were main strains in these patients. All CRE strains showed high resistance to most antimicrobials except for polymyxin B and tigecycline. Most (83.72%, 36/43) of the CRE carried carbapenemase genes. bla was the major carbapenemase gene. The molecular epidemiology of KPN were dominated by ST11, while the STs of ECO were scattered.

CONCLUSIONS

The present study revealed that CRE fecal carriage rates were higher in patients with ACLF than in patients without liver failure. ACLF, the history of pulmonary infection within past 3 months and the use of third generation cephalosporin/β-lactamases inhibitor within past 3 months were independent risk factors of CRE colonization in patients with liver disease. Regular CRE screening for hospitalized patients with liver disease should be conducted to limit the spread of CRE strain.

摘要

背景

耐碳青霉烯肠杆菌科(CRE)定植是 CRE 感染的危险因素。CRE 感染会导致肝硬化患者的死亡率增加。然而,关于肝病患者(未进行肝移植)的 CRE 定植的患病率和危险因素的数据很少。本研究旨在调查肝病患者中 CRE 粪便携带的患病率、危险因素和分子流行病学特征。

方法

2020 年 12 月至 2021 年 4 月期间,采集了 574 名成年肝病住院患者的粪便标本。使用选择性显色琼脂培养基筛选 CRE,并使用基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF MS)进行鉴定。采用肉汤微量稀释法测定抗菌药物敏感性。采用聚合酶链反应(PCR)和 DNA 测序对碳青霉烯酶基因进行鉴定。对耐碳青霉烯肺炎克雷伯菌(CR-KPN)和耐碳青霉烯大肠埃希菌(CR-ECO)分离株进行多位点序列分型(MLST)。

结果

共采集了 574 名肝病患者的 732 份粪便标本。从 39 名患者中分离出 43 株非重复的 CRE 菌株,携带率为 6.79%(39/574)。急性肝衰竭合并慢性肝病(ACLF)患者的携带率为 15.60%(17/109)。多因素分析表明,ACLF(P=0.018)、过去 3 个月内肺部感染史(P=0.001)和过去 3 个月内使用第三代头孢菌素/β-内酰胺酶抑制剂(P=0.000)是肝病患者 CRE 定植的独立危险因素。这些患者的主要菌株为肺炎克雷伯菌(KPN)(51.28%)和大肠埃希菌(ECO)(30.77%)。除多黏菌素 B 和替加环素外,所有 CRE 菌株对大多数抗菌药物均显示出高度耐药性。大多数(83.72%,36/43)的 CRE 携带碳青霉烯酶基因。bla 是主要的碳青霉烯酶基因。KPN 的分子流行病学以 ST11 为主,而 ECO 的 ST 则较为分散。

结论

本研究表明,ACLF 患者的 CRE 粪便携带率高于无肝衰竭患者。ACLF、过去 3 个月内肺部感染史和过去 3 个月内使用第三代头孢菌素/β-内酰胺酶抑制剂是肝病患者 CRE 定植的独立危险因素。应定期对住院肝病患者进行 CRE 筛查,以限制 CRE 菌株的传播。

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