The Complex Epidemiology of Carbapenem-Resistant<i>Enterobacter</i>Infections: A Multicenter Descriptive Analysis

Lazarovitch, Tsilia; Amity, Keren; Coyle, Joseph; Ackerman, Benjamin; Tal-Jasper, Ruthy; Ofer-Friedman, Hadas; Hayakawa, Kayoko; Bogan, Christopher; Lephart, Paul; Kaplansky, Tamir; Maskit, Moran; Azouri, Tal; Pérez, Federico; Kaye, Keith S.; Marchaim, Dror

doi:10.1017/ice.2015.186

Cited by 15 publications

(16 citation statements)

References 39 publications

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“…Patient-to-patient transmission is an important mode for acquisition of carbapenemresistant E. cloacae (23,25), but transmission from the hospital environment may occur since room surfaces in surroundings of CRE carriers have been frequently identified as contaminated (26). On the other hand, our previous study showed that CRE (Enterobacter and Klebsiella species) survived poorly in a hospital environment for 24 h and was infrequently isolated from environmental surfaces in rooms housing CRE-colonized/ infected patients (27); thus, the role of hospital environmental surfaces for CRE transmission is yet to be clarified.…”

Section: Discussionmentioning

confidence: 99%

A Prolonged Outbreak of KPC-3-Producing Enterobacter cloacae and Klebsiella pneumoniae Driven by Multiple Mechanisms of Resistance Transmission at a Large Academic Burn Center

Kanamori

Parobek

Juliano

et al. 2017

Antimicrob Agents Chemother

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Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacter cloacae has been recently recognized in the United States. Whole-genome sequencing (WGS) has become a useful tool for analysis of outbreaks and for determining transmission networks of multidrug-resistant organisms in health care settings, including carbapenem-resistant Enterobacteriaceae (CRE). We experienced a prolonged outbreak of CRE E. cloacae and K. pneumoniae over a 3-year period at a large academic burn center despite rigorous infection control measures. To understand the molecular mechanisms that sustained this outbreak, we investigated the CRE outbreak isolates by using WGS. Twenty-two clinical isolates of CRE, including E. cloacae (n ϭ 15) and K. pneumoniae (n ϭ 7), were sequenced and analyzed genetically. WGS revealed that this outbreak, which seemed epidemiologically unlinked, was in fact genetically linked over a prolonged period. Multiple mechanisms were found to account for the ongoing outbreak of KPC-3-producing E. cloacae and K. pneumoniae. This outbreak was primarily maintained by a clonal expansion of E. cloacae sequence type 114 (ST114) with distribution of multiple resistance determinants. Plasmid and transposon analyses suggested that the majority of bla was transmitted via an identical Tn4401b element on part of a common plasmid. WGS analysis demonstrated complex transmission dynamics within the burn center at levels of the strain and/or plasmid in association with a transposon, highlighting the versatility of KPCproducing Enterobacteriaceae in their ability to utilize multiple modes to resistance gene propagation.

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Section: Discussionmentioning

confidence: 99%

A Prolonged Outbreak of KPC-3-Producing Enterobacter cloacae and Klebsiella pneumoniae Driven by Multiple Mechanisms of Resistance Transmission at a Large Academic Burn Center

Kanamori

Parobek

Juliano

et al. 2017

Antimicrob Agents Chemother

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“…Overall, Enterobacter spp. are the sixth leading cause of health care-associated infections globally (8). …”

Section: Introductionmentioning

confidence: 99%

Comprehensive Genome Analysis of Carbapenemase-Producing Enterobacter spp.: New Insights into Phylogeny, Population Structure, and Resistance Mechanisms

Chavda

Chen

Fouts

et al. 2016

mBio

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167

159

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Knowledge regarding the genomic structure of Enterobacter spp., the second most prevalent carbapenemase-producing Enterobacteriaceae, remains limited. Here we sequenced 97 clinical Enterobacter species isolates that were both carbapenem susceptible and resistant from various geographic regions to decipher the molecular origins of carbapenem resistance and to understand the changing phylogeny of these emerging and drug-resistant pathogens. Of the carbapenem-resistant isolates, 30 possessed blaKPC-2, 40 had blaKPC-3, 2 had blaKPC-4, and 2 had blaNDM-1. Twenty-three isolates were carbapenem susceptible. Six genomes were sequenced to completion, and their sizes ranged from 4.6 to 5.1 Mbp. Phylogenomic analysis placed 96 of these genomes, 351 additional Enterobacter genomes downloaded from NCBI GenBank, and six newly sequenced type strains into 19 phylogenomic groups—18 groups (A to R) in the Enterobacter cloacae complex and Enterobacter aerogenes. Diverse mechanisms underlying the molecular evolutionary trajectory of these drug-resistant Enterobacter spp. were revealed, including the acquisition of an antibiotic resistance plasmid, followed by clonal spread, horizontal transfer of blaKPC-harboring plasmids between different phylogenomic groups, and repeated transposition of the blaKPC gene among different plasmid backbones. Group A, which comprises multilocus sequence type 171 (ST171), was the most commonly identified (23% of isolates). Genomic analysis showed that ST171 isolates evolved from a common ancestor and formed two different major clusters; each acquiring unique blaKPC-harboring plasmids, followed by clonal expansion. The data presented here represent the first comprehensive study of phylogenomic interrogation and the relationship between antibiotic resistance and plasmid discrimination among carbapenem-resistant Enterobacter spp., demonstrating the genetic diversity and complexity of the molecular mechanisms driving antibiotic resistance in this genus.

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“…Recent surveillance studies have shown that Enterobacter spp. are often the second or third most common Enterobacteriaceae species associated with carbapenemases ( 3 , 4 ). Typically, KPCs are common among Enterobacter spp.…”

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confidence: 99%

Genomic Epidemiology of Global Carbapenemase-ProducingEnterobacterspp., 2008–2014

Peirano

Matsumura

Adams

et al. 2018

Emerg. Infect. Dis.

124

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We performed whole-genome sequencing on 170 clinical carbapenemase-producing Enterobacter spp. isolates collected globally during 2008–2014. The most common carbapenemase was VIM, followed by New Delhi metallo-β-lactamase (NDM), Klebsiella pneumoniae carbapenemase, oxacillin 48, and IMP. The isolates were of predominantly 2 species (E. xiangfangensis and E. hormaechei subsp. steigerwaltii) and 4 global clones (sequence type [ST] 114, ST93, ST90, and ST78) with different clades within ST114 and ST90. Particular genetic structures surrounding carbapenemase genes were circulating locally in various institutions within the same or between different STs in Greece, Guatemala, Italy, Spain, Serbia, and Vietnam. We found a common NDM genetic structure (NDM-GE-U.S.), previously described on pNDM-U.S. from Klebsiella pneumoniae ATCC BAA-214, in 14 different clones obtained from 6 countries spanning 4 continents. Our study highlights the importance of surveillance programs using whole-genome sequencing in providing insight into the molecular epidemiology of carbapenemase-producing Enterobacter spp.

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The Complex Epidemiology of Carbapenem-ResistantEnterobacterInfections: A Multicenter Descriptive Analysis

Cited by 15 publications

References 39 publications

A Prolonged Outbreak of KPC-3-Producing Enterobacter cloacae and Klebsiella pneumoniae Driven by Multiple Mechanisms of Resistance Transmission at a Large Academic Burn Center

A Prolonged Outbreak of KPC-3-Producing Enterobacter cloacae and Klebsiella pneumoniae Driven by Multiple Mechanisms of Resistance Transmission at a Large Academic Burn Center

Comprehensive Genome Analysis of Carbapenemase-Producing Enterobacter spp.: New Insights into Phylogeny, Population Structure, and Resistance Mechanisms

Genomic Epidemiology of Global Carbapenemase-ProducingEnterobacterspp., 2008–2014

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