PDF(Pubmed)
Abstract：
Over a 3-month period, we monitored the population of extended-spectrum β-lactam-resistant Escherichia coli (ESBL-EC) associated with the patients, staff, and environment of an intensive care unit (ICU) in Guangzhou, China. Thirty-four clinical isolates were obtained from the same hospital 12 months later. A total of 165 isolates were characterized and whole-genome sequenced, with 24 isolates subjected to long-read sequencing. The diverse population included representatives of 59 different sequence types (STs). ICU patient and environmental isolates were largely distinct from staff isolates and clinical isolates. We observed five instances of highly similar isolates (0 to 13 single nucleotide polymorphisms [SNPs]) being obtained from different patients or bed unit environments. ESBL resistance in this collection was largely conferred by blaCTX-M genes, which were found in 96.4% of all isolates. The contexts of blaCTX-M genes were diverse, situated in multiple chromosomal positions and in various plasmids. We identified blaCTX-M-bearing plasmid lineages that were present in multiple STs across the surveillance, staff, and clinical collections. Closer examination of ISEcp1-blaCTX-M transposition units shed light on the dynamics of their transmission, with evidence for the acquisition of chromosomal copies of blaCTX-M genes from specific plasmid lineages and for the movement of blaCTX-M-55 from a ST1193 chromosome to a small mobilizable plasmid. A carbapenem-resistant ST167 strain isolated from a patient that had been treated with meropenem and piperacillin-tazobactam contained seven copies of blaCMY-146, which appears to have been amplified by IS1. Our data revealed limited persistence and movement of ESBL-EC strains in the ICU environment, but we observed circulating plasmid lineages playing an essential and ongoing role in shaping the cephalosporin-resistance landscape in the population examined. IMPORTANCE ESBL resistance significantly impacts clinical management of E. coli infections in hospitals globally. It is important to understand the structures of ESBL-EC populations carried by hospital patients and staff, their capacity to persist in hospital environments, and the dynamics of mobile genes that drive the spread of ESBL resistance. In our 3-month study, ESBL-EC strains found in the ICU environment were strongly associated with patient carriage but distinct from strains found in staff. However, plasmid lineages carrying blaCTX-M genes were found across the ICU populations and in a collection of clinical isolates obtained 1 year later. By examining their content and contexts, we have traced the recent histories of chromosomal and plasmid-borne ISEcp1-blaCTX-M transposition units in the ICU population. This information allowed us to implicate specific plasmid lineages in the acquisition of chromosomal blaCTX-M genes, even when the plasmids were no longer present, and to detect recent transposition of blaCTX-M-55 from a chromosome to a mobilizable plasmid. Similar high-resolution approaches to the study of mobile genetic elements will be essential if the transmission routes associated with the spread of ESBL resistance are to be understood and subjected to interventions.
摘要：
在三个月的时间里，我们监测了与患者相关的超广谱β-内酰胺耐药大肠杆菌（ESBL-EC）的人群，工作人员,和广州重症监护室(ICU)的环境，中国。12个月后，从同一家医院获得了34个临床分离株。共对165株分离株进行了鉴定和全基因组测序，与24个分离物进行长读数测序。不同的群体包括59种不同序列类型(STs)的代表。ICU患者和环境分离株与工作人员分离株和临床分离株在很大程度上不同。我们观察到5例高度相似的分离株（0至13个单核苷酸多态性[SNP]）是从不同的患者或床单位环境中获得的。该集合中的ESBL抗性主要由blaCTX-M基因赋予，在所有分离株的96.4％中发现。blaCTX-M基因的背景是多种多样的，位于多个染色体位置和各种质粒中。我们鉴定了携带blaCTX-M的质粒谱系，这些谱系存在于整个监测中的多个ST中，工作人员,和临床收藏。对ISEcp1-blaCTX-M换位单元的仔细检查揭示了它们传输的动力学，有证据表明可以从特定质粒谱系中获得blaCTX-M基因的染色体拷贝，以及blaCTX-M-55从ST1193染色体移动到小的可移动质粒。从接受美罗培南和哌拉西林-他唑巴坦治疗的患者中分离出的耐碳青霉烯的ST167菌株含有7个拷贝的blaCMY-146，似乎已被IS1扩增。我们的数据显示ESBL-EC菌株在ICU环境中的持久性和移动有限，但是我们观察到循环质粒谱系在塑造所检查人群的头孢菌素耐药格局中起着重要和持续的作用。重要性ESBL耐药性显著影响全球医院大肠杆菌感染的临床管理。重要的是要了解医院患者和工作人员携带的ESBL-EC人群的结构，他们在医院环境中坚持的能力，以及驱动ESBL抗性传播的移动基因的动力学。在我们为期3个月的研究中,在ICU环境中发现的ESBL-EC菌株与患者运输密切相关，但与工作人员中发现的菌株不同。然而,在ICU人群和1年后获得的临床分离株集合中发现了携带blaCTX-M基因的质粒谱系。通过检查他们的内容和背景，我们追踪了ICU人群中染色体和质粒携带的ISEcp1-blaCTX-M转座单位的最新历史。这些信息使我们能够在染色体blaCTX-M基因的获取中暗示特定的质粒谱系，即使质粒不再存在，并检测blaCTX-M-55从染色体到可移动质粒的近期转座。如果要了解与ESBL抗性传播相关的传播途径并进行干预，则研究移动遗传元件的类似高分辨率方法将是必不可少的。
