Multiple hospital outbreaks of<i>vanA Enterococcus faecium</i>in Denmark, 2012–13, investigated by WGS, MLST and PFGE

Pinholt, Mette; Larner-Svensson, Hanna; Littauer, Pia; Moser, Claus; Pedersen, Michael; Lemming, Lars; Ejlertsen, Tove; Søndergaard, Turid Snekloth; Holzknecht, Barbara Juliane; Justesen, Ulrik Stenz; Dzajic, Esad; Olsen, Stefan S.; Nielsen, Julius; Worning, Peder; Hammerum, Anette M.; Westh, Henrik; Jakobsen, Lotte

doi:10.1093/jac/dkv142

Cited by 90 publications

(79 citation statements)

References 27 publications

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“…The accuracy of MLST has been evaluated using whole-genome sequencing (WGS) in three previous studies. Howden et al (2013) reported that five of the seven MLST genes in E. faecium are under recombination and identified two of 61 isolates with a discrepancy between WGS data and MLST, a finding supported by van Hal et al (2016), while Pinholt et al (2015) compared MLST to WGS data for 132 E. faecium isolates from across Denmark and found good correlation.…”

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confidence: 89%

“…Four WGS-based studies of bacterial collections ranging in size from 61 to 132 E. faecium isolates have been published to date (Howden et al 2013;Lebreton et al 2013;Pinholt et al 2015;van Hal et al 2016). A study of a global collection of 73 E. faecium from a range of sources reported the presence of two clades (Clade A1 and B) associated with human clinical and commensal isolates, respectively, together with a third genetically distinct clade associated with animals (Clade A2) (Lebreton et al 2013).…”

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confidence: 99%

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A decade of genomic history for healthcare-associated Enterococcus faecium in the United Kingdom and Ireland

et al. 2016

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Vancomycin-resistant Enterococcus faecium (VREfm) is an important cause of healthcare-associated infections worldwide. We undertook whole-genome sequencing (WGS) of 495 E. faecium bloodstream isolates from 2001-2011 in the United Kingdom and Ireland (UK&I) and 11 E. faecium isolates from a reference collection. Comparison between WGS and multilocus sequence typing (MLST) identified major discrepancies for 17% of isolates, with multiple instances of the same sequence type (ST) being located in genetically distant positions in the WGS tree. This confirms that WGS is superior to MLST for evolutionary analyses and is more accurate than current typing methods used during outbreak investigations. E. faecium has been categorized as belonging to three clades (Clades A1, hospital-associated; A2, animal-associated; and B, community-associated). Phylogenetic analysis of our isolates replicated the distinction between Clade A (97% of isolates) and Clade B but did not support the subdivision of Clade A into Clade A1 and A2. Phylogeographic analyses revealed that Clade A had been introduced multiple times into each hospital referral network or country, indicating frequent movement of E. faecium between regions that rarely share hospital patients. Numerous genetic clusters contained highly related vanA-positive and -negative E. faecium, which implies that control of vancomycin-resistant enterococci (VRE) in hospitals also requires consideration of vancomycin-susceptible E. faecium. Our findings reveal the evolution and dissemination of hospital-associated E. faecium in the UK&I and provide evidence for WGS as an instrument for infection control.

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confidence: 89%

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confidence: 99%

A decade of genomic history for healthcare-associated Enterococcus faecium in the United Kingdom and Ireland

et al. 2016

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“…PFGE was for a long time considered the gold standard for typing E. faecium. However, the extent of genome plasticity in E. faecium, which results in a high degree of DNA banding pattern polymorphisms among strains, complicates the assignment of strains to outbreaks (12,13). The development of MLST for E. faecium has boosted our insight into the population structure of this organism.…”

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confidence: 99%

“…Furthermore, the fact that MLST results in an allelic profile assigned from sequences of a limited number of genes makes this technique well suited for library typing, i.e., the establishment of a Web-based central database that can be interrogated to study the epidemiology of E. faecium over time and to track the regional and global spread of particular E. faecium clones (11,18,19). One drawback of MLST is that its resolving power is insufficient for hospital outbreak investigations (13,20).…”

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confidence: 99%

“…It allows mapping of genome-wide variation, thereby providing the optimal resolution to infer phylogenetic relatedness, thus identifying possible, probable, or unlikely cases of epidemiological linkage of isolates. WGS has already been used to study the epidemiology of VRE (13,(21)(22)(23). In these four studies, an SNP-based approach was used in which VRE outbreak strains were sequenced, and reads were mapped against a reference genome.…”

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confidence: 99%

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Core Genome Multilocus Sequence Typing Scheme for High-Resolution Typing of Enterococcus faecium

et al. 2015

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Enterococcus faecium, a common inhabitant of the human gut, has emerged in the last 2 decades as an important multidrugresistant nosocomial pathogen. Since the start of the 21st century, multilocus sequence typing (MLST) has been used to study the molecular epidemiology of E. faecium. However, due to the use of a small number of genes, the resolution of MLST is limited. Whole-genome sequencing (WGS) now allows for high-resolution tracing of outbreaks, but current WGS-based approaches lack standardization, rendering them less suitable for interlaboratory prospective surveillance. To overcome this limitation, we developed a core genome MLST (cgMLST) scheme for E. faecium. cgMLST transfers genome-wide single nucleotide polymorphism (SNP) diversity into a standardized and portable allele numbering system that is far less computationally intensive than SNPbased analysis of WGS data. The E. faecium cgMLST scheme was built using 40 genome sequences that represented the diversity of the species. The scheme consists of 1,423 cgMLST target genes. To test the performance of the scheme, we performed WGS analysis of 103 outbreak isolates from five different hospitals in the Netherlands, Denmark, and Germany. The cgMLST scheme performed well in distinguishing between epidemiologically related and unrelated isolates, even between those that had the same sequence type (ST), which denotes the higher discriminatory power of this cgMLST scheme over that of conventional MLST. We also show that in terms of resolution, the performance of the E. faecium cgMLST scheme is equivalent to that of an SNP-based approach. In conclusion, the cgMLST scheme developed in this study facilitates rapid, standardized, and high-resolution tracing of E. faecium outbreaks. In the last 2 decades, Enterococcus faecium has emerged as an important multidrug-resistant nosocomial pathogen causing an increasing number of bloodstream infections, mainly in debilitated patients (1-3). Currently, Ͼ90% of the E. faecium strains causing infections have acquired ampicillin resistance, and an increasing number of health care-associated infections and outbreaks are caused by E. faecium strains that are resistant to both ampicillin and vancomycin (4). The global emergence of ampicillin-and vancomycin-resistant E. faecium (VRE) as nosocomial pathogens started in the United States in the late 1980s/early 1990s and occurred in other parts in the world 1 or 2 decades later. In Europe, more particularly in France, Germany, Denmark, and the Netherlands, VRE first spread among livestock due to the use of the vancomycin analog avoparcin as a growth promoter, and it only relatively recently became an important nosocomial pathogen (5, 6). Different molecular typing methods have been used to study the epidemiology of E. faecium, ranging from fingerprint-based methods, like pulsed-field gel electrophoresis (PFGE) (7), ribotyping (8), and amplified fragment length polymorphism (9), to PCR-based methods, like multilocus variable-number tandemrepeat analysis (10) and the sequenced-bas...

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Epidemiological Typing Using WGS

Alphen

Wintersdorff

Savelkoul

2021

Application and Integration of Omics-Powered Diagnostics in Clinical and Public Health Microbiology

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Multiple hospital outbreaks ofvanA Enterococcus faeciumin Denmark, 2012–13, investigated by WGS, MLST and PFGE

Cited by 90 publications

References 27 publications

A decade of genomic history for healthcare-associated Enterococcus faecium in the United Kingdom and Ireland

A decade of genomic history for healthcare-associated Enterococcus faecium in the United Kingdom and Ireland

Core Genome Multilocus Sequence Typing Scheme for High-Resolution Typing of Enterococcus faecium

Epidemiological Typing Using WGS

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