Multispecies Outbreak of Verona Integron-Encoded Metallo-ß-Lactamase-Producing Multidrug-Resistant Bacteria Driven by a Promiscuous Incompatibility Group A/C2 Plasmid

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Dissemination Routes of Carbapenem and Pan-Aminoglycoside Resistance Mechanisms in Hospital and Urban Wastewater Canalizations of Ghana

“…The circulation of different plasmids among Enterobacteriaceae isolates caused the emergence of novel cointegrative plasmid structures and generated novel resistance gene associations. The main plasmid responsible for these multiplasmid rearrangements was the IncC plasmid pCW-NDM-1, which showed a high interspecies promiscuity, as observed in other IncC plasmids ( 31 ). pCW-NDM-1 showed a mosaic structure, exhibiting a high capacity to gain, lose, and rearrange from small genetic regions to large plasmid modules and even to be completely cointegrated with other plasmid structures.…”

Nosocomial outbreak of monoclonal VIM carbapenemase-producing Enterobacter cloacae complex in an intensive care unit during the COVID-19 pandemic: an integrated approach

“…and ECC in sinks and sink drains even after terminal cleaning and disinfection [ 33 ]. Another one also identified VIM-producing CPE in a case-patient sink drain during an outbreak [ 34 ]. Even if the data provided by the epidemiological investigation in this study do not definitely support a link between colonization/infection of the cases identified in this study and an environmental source, these observations confirm that sinks and sink drains warrant further investigations and management measures to limit MDR persistence and spread.…”

Global Threat of Carbapenem-Resistant Gram-Negative Bacteria

“…Notably, numerous outbreaks related to CRE involving a wide range of microbial species harboring diverse carbapenemase-encoding genes ( bla KPC , bla NDM , bla VIM , bla OXA , etc. ) have been reported in the literature ( Chitnis et al., 2012 ; Kanamori et al., 2017 ; Mehta and Muscarella, 2020 ; Tavoschi et al., 2020 ; De Man et al., 2021 ). From March 2017 to September 2018, an epidemic spread of CRE, which was rapidly transmitted between hospitalized patients and associated with high mortality rates at 12 Vietnamese hospitals was reported by Tran et al.…”