Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Epidemic Intelligence Service, Division of Scientific Education and Professional Development, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
Clin Infect Dis. 2021 Feb 1;72(3):414-420. doi: 10.1093/cid/ciaa049.
Antibiotic resistance is often spread through bacterial populations via conjugative plasmids. However, plasmid transfer is not well recognized in clinical settings because of technical limitations, and health care-associated infections are usually caused by clonal transmission of a single pathogen. In 2015, multiple species of carbapenem-resistant Enterobacteriaceae (CRE), all producing a rare carbapenemase, were identified among patients in an intensive care unit. This observation suggested a large, previously unrecognized plasmid transmission chain and prompted our investigation.
Electronic medical record reviews, infection control observations, and environmental sampling completed the epidemiologic outbreak investigation. A laboratory analysis, conducted on patient and environmental isolates, included long-read whole-genome sequencing to fully elucidate plasmid DNA structures. Bioinformatics analyses were applied to infer plasmid transmission chains and results were subsequently confirmed using plasmid conjugation experiments.
We identified 14 Verona integron-encoded metallo-ß-lactamase (VIM)-producing CRE in 12 patients, and 1 additional isolate was obtained from a patient room sink drain. Whole-genome sequencing identified the horizontal transfer of blaVIM-1, a rare carbapenem resistance mechanism in the United States, via a promiscuous incompatibility group A/C2 plasmid that spread among 5 bacterial species isolated from patients and the environment.
This investigation represents the largest known outbreak of VIM-producing CRE in the United States to date, which comprises numerous bacterial species and strains. We present evidence of in-hospital plasmid transmission, as well as environmental contamination. Our findings demonstrate the potential for 2 types of hospital-acquired infection outbreaks: those due to clonal expansion and those due to the spread of conjugative plasmids encoding antibiotic resistance across species.
抗生素耐药性通常通过接合质粒在细菌群体中传播。然而，由于技术限制，临床环境中并不太容易识别质粒转移，而医疗保健相关感染通常是由单一病原体的克隆传播引起的。2015 年，在重症监护病房的患者中发现了多种产碳青霉烯类抗生素的肠杆菌科细菌（CRE），这些细菌都产生一种罕见的碳青霉烯酶。这一观察结果表明存在一条以前未被认识到的大型质粒传播链，并促使我们进行了调查。
电子病历回顾、感染控制观察和环境采样完成了流行病学暴发调查。对患者和环境分离株进行的实验室分析包括长读长全基因组测序，以充分阐明质粒 DNA 结构。生物信息学分析用于推断质粒传播链，随后使用质粒接合实验进行验证。
我们在 12 名患者中发现了 14 株 Verona 整合子编码的金属β-内酰胺酶（VIM）产 CRE，从患者病房水槽排水管中获得了 1 个额外的分离株。全基因组测序确定了 blaVIM-1 的水平转移，这是一种在美国罕见的碳青霉烯类抗生素耐药机制，通过一种易位的不相容群 A/C2 质粒传播，该质粒在从患者和环境中分离的 5 种细菌物种中传播。
这项调查代表了迄今为止美国已知的最大的 VIM 产 CRE 暴发，涉及多种细菌物种和菌株。我们提供了医院内质粒传播以及环境污染的证据。我们的发现表明，存在 2 种类型的医院获得性感染暴发：一种是由于克隆扩展引起的，另一种是由于编码抗生素耐药性的可接合质粒在物种间传播引起的。
