Rise and Fall of a Superbug: Analyzing the epidemic success of a distinct clone of vancomycin-resistant Enterococcus faecium ST117/CT71 in Germany, 2017 - 2024.
- 1Robert Koch Institut
Abstract
Vancomycin-resistant Enterococcus faecium (VREfm) is a major cause of healthcare-associated infections, yet outbreak analysis remains challenging, particularly for prevalent lineages. One of the most striking examples is the Sequence Type (ST) 117/Complex Type (CT) 71/vanB lineage, whose rapid expansion across Germany coincided with a sharp rise in VRE prevalence observed around 2019. Defining reliable genomic thresholds remains particularly difficult, as current core-genome Multi-Locus Sequence Typing (cgMLST) cutoffs are based largely on expert consensus or limited case series. Here, we evaluate the discriminatory performance of cgMLST and split k-mer analysis (SKA) for resolving relatedness within ST117/CT71 and investigate whether low core-genome diversity represents a lineage-specific trait or a population-wide property of E. faecium. While cgMLST captures the overall population structure of ST117/CT71, SKA provided higher resolution, distinguishing isolates identical by cgMLST. Analysis of 2,505 genomes showed that ST117/CT71 does not exhibit reduced allelic variability compared with other hospital-adapted lineages, suggesting that limited core-genome diversity is a broader population characteristic. Complementary transposon analyses further identified two temporally distinct ST117/CT71 sublineages carrying different Tn1549-like structures. To assess allelic variation within confirmed transmission events, we analyzed 138 outbreak clusters from 96 hospitals. Outbreak-associated isolates showed sharply compressed allelic differences (median = 1), with 90% of pairwise comparisons falling within [≤]9 alleles. Thus, the commonly applied [≤]20-allele threshold risks overestimating genomic relatedness and grouping unrelated isolates. Based on these data, we propose lowering the cgMLST alert threshold to [≤]9 alleles for initial cluster detection of local outbreaks, followed by confirmatory high-resolution analyses such as SKA.
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BibTeX
@misc{weber2026rise,
title = {{Rise and Fall of a Superbug: Analyzing the epidemic success of a distinct clone of vancomycin-resistant Enterococcus faecium ST117/CT71 in Germany, 2017 - 2024.}},
author = {R. E. Weber and G. Werner and J. K. Bender and B. Haldemann and O. Drechsel and M. A. Fischer},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.10.765572},
url = {https://www.biorxiv.org/content/10.64898/2026.11.10.765572v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Rise and Fall of a Superbug: Analyzing the epidemic success of a distinct clone of vancomycin-resistant Enterococcus faecium ST117/CT71 in Germany, 2017 - 2024.
AU - R. E. Weber
AU - G. Werner
AU - J. K. Bender
AU - B. Haldemann
AU - O. Drechsel
AU - M. A. Fischer
PY - 2026
DA - 2026/11/10
PB - bioRxiv
DO - 10.64898/2026.11.10.765572
UR - https://www.biorxiv.org/content/10.64898/2026.11.10.765572v1
AB - Vancomycin-resistant Enterococcus faecium (VREfm) is a major cause of healthcare-associated infections, yet outbreak analysis remains challenging, particularly for prevalent lineages. One of the most striking examples is the Sequence Type (ST) 117/Complex Type (CT) 71/vanB lineage, whose rapid expansion across Germany coincided with a sharp rise in VRE prevalence observed around 2019. Defining reliable genomic thresholds remains particularly difficult, as current core-genome Multi-Locus Sequence Typing (cgMLST) cutoffs are based largely on expert consensus or limited case series. Here, we evaluate the discriminatory performance of cgMLST and split k-mer analysis (SKA) for resolving relatedness within ST117/CT71 and investigate whether low core-genome diversity represents a lineage-specific trait or a population-wide property of E. faecium. While cgMLST captures the overall population structure of ST117/CT71, SKA provided higher resolution, distinguishing isolates identical by cgMLST. Analysis of 2,505 genomes showed that ST117/CT71 does not exhibit reduced allelic variability compared with other hospital-adapted lineages, suggesting that limited core-genome diversity is a broader population characteristic. Complementary transposon analyses further identified two temporally distinct ST117/CT71 sublineages carrying different Tn1549-like structures. To assess allelic variation within confirmed transmission events, we analyzed 138 outbreak clusters from 96 hospitals. Outbreak-associated isolates showed sharply compressed allelic differences (median = 1), with 90% of pairwise comparisons falling within [≤]9 alleles. Thus, the commonly applied [≤]20-allele threshold risks overestimating genomic relatedness and grouping unrelated isolates. Based on these data, we propose lowering the cgMLST alert threshold to [≤]9 alleles for initial cluster detection of local outbreaks, followed by confirmatory high-resolution analyses such as SKA.
ER -