摘要
客观的
通过全基因组测序分析耐碳青霉烯阴沟肠杆菌复合体（CREC）的分子流行病学，并探讨其临床特征。
方法
对2013-2021年在一家三级医院收集的阴沟肠杆菌复合物分离株进行全基因组测序，以确定抗微生物耐药性基因（ARGs）、序列类型（ST）和质粒复制子的分布。基于全基因组序列构建了CREC菌株的系统发育树，分析了它们之间的关系。收集临床患者信息进行危险因素分析。
后果
在收集的51株CREC菌株中，blaNDM-1（n=42，82.4%）是主要的碳青霉烯类水解β-内酰胺酶（CHβL），其次是blaIMP-4（n=11，21.6%）。还鉴定了其他几个超广谱β-内窥酶编码基因，其中blaSHV-12（n=30，58.8%）和blaTEM-1B（n=24，47.1%）是主要基因。多基因座序列分型显示25个不同的ST，ST418（n=12，23.5%）是主要的克隆。质粒分析鉴定出15种质粒复制子，其中以IncHI2（n=33，64.7%）和IncHI2A（n=33、64.7%）为主。危险因素分析显示，重症监护室（ICU）入院、自身免疫性疾病、肺部感染和1个月内既往使用皮质类固醇是获得CREC的主要危险因素。Logistic回归分析显示，ICU入院是CREC获得的独立危险因素，与ST418 CREC感染密切相关。
结论
BlaNDM-1和blaIMP-4是主要的碳青霉烯类抗性基因。携带BlaNDM-1的ST418不仅是主要克隆，而且在2019-2021年期间在我院重症监护室流通，这突出了在重症监护室监测该菌株的必要性。此外，有CREC获得危险因素的患者，包括ICU入院、自身免疫性疾病、肺部感染和1个月内既往使用皮质类固醇，需要密切监测CREC感染。
Abstract
Objective
To analyze the molecular epidemiology of carbapenem-resistant Enterobacter cloacae complex (CREC) by whole-genome sequencing and to explore its clinical characteristics.

Methods
Enterobacter cloacae complex isolates collected in a tertiary hospital during 2013–2021 were subjected to whole-genome sequencing to determine the distribution of antimicrobial resistance genes (ARGs), sequence types (STs), and plasmid replicons. A phylogenetic tree of the CREC strains was constructed based on the whole-genome sequences to analyze their relationships. Clinical patient information was collected for risk factor analysis.

Results
Among the 51 CREC strains collected, blaNDM-1 (n = 42, 82.4%) was the main carbapenem-hydrolyzing β-lactamase (CHβL), followed by blaIMP-4 (n = 11, 21.6%). Several other extended-spectrum β-lactamase-encoding genes were also identified, with blaSHV-12 (n = 30, 58.8%) and blaTEM-1B (n = 24, 47.1%) being the predominant ones. Multi-locus sequence typing revealed 25 distinct STs, and ST418 (n = 12, 23.5%) was the predominant clone. Plasmid analysis identified 15 types of plasmid replicons, among which IncHI2 (n = 33, 64.7%) and IncHI2A (n = 33, 64.7%) were the main ones. Risk factor analysis showed that intensive care unit (ICU) admission, autoimmune disease, pulmonary infection, and previous corticosteroid use within 1 month were major risk factors for acquiring CREC. Logistic regression analysis showed that ICU admission was an independent risk factor for CREC acquisition and was closely related with acquiring infection by CREC with ST418.

Conclusion
BlaNDM-1 and blaIMP-4 were the predominant carbapenem resistance genes. ST418 carrying BlaNDM-1 not only was the main clone, but also circulated in the ICU of our hospital during 2019–2021, which highlights the necessity for surveillance of this strain in the ICU. Furthermore, patients with risk factors for CREC acquisition, including ICU admission, autoimmune disease, pulmonary infection, and previous corticosteroid use within 1 month, need to be closely monitored for CREC infection.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9989974/