To characterize the clinical and genomic features of vancomycin-resistant enterococci (VRE) in a tertiary hospital in Huizhou and identify risk factors to inform local infection control.
Methods:
A retrospective study included 58 VRE and 25 vancomycin-susceptible Enterococci (VSE) strains (August 2023–May 2025). Clinical data and antimicrobial susceptibility were analyzed; whole-genome sequencing (WGS) was performed on 54 VRE strains.
Results:
Midstream urine was the primary VRE-positive specimen. ICU admission, polyantibiotic use (≥3 agents), and urinary catheterization were key risk factors for VRE. All VRE isolates were Enterococcus faecium and showed a predominantly clonal population structure, dominated by CC17/ST80 (68.8%) and CC2/ST106 (64.6%) under the two multilocus sequence typing schemes; five novel STs were ultimately identified in the latter scheme. VRE was universally resistant to ampicillin, with high resistance to penicillin, levofloxacin, and teicoplanin, while linezolid and tigecycline remained effective. Genotypically, 94.8% carried vanA, 100% carried virulence gene esp, and aminoglycoside and macrolide resistance genes were prevalent. A unique VRE strain (VRE48) showed resistance without canonical van genes, harboring a Ddl Ser210Tyr mutation.
Guzman PrietoAM, van SchaikW, RogersMRC, et al.Global emergence and dissemination of enterococci as nosocomial pathogens: Attack of the clones? Front Microbiol2016;7:788; doi: 10.3389/fmicb.2016.00788
2.
FujiiA, Kawada-MatsuoM, Nguyen-Tra LeM, et al.Antibiotic susceptibility and genome analysis of Enterococcus species isolated from inpatients in one hospital with no apparent outbreak of vancomycin-resistant Enterococcus in Japan. Microbiol Immunol2024;68(8):254–266; doi: 10.1111/1348-0421.13155
3.
GuanL, BeigM, WangL, et al.Global status of antimicrobial resistance in clinical Enterococcus faecalis isolates: Systematic review and meta-analysis. Ann Clin Microbiol Antimicrob2024;23(1):80; doi: 10.1186/s12941-024-00728-w
4.
O’TooleRF, LeongKWC, CummingV, et al.Vancomycin-resistant Enterococcus faecium and the emergence of new sequence types associated with hospital infection. Res Microbiol2023;174(4):104046; doi: 10.1016/j.resmic.2023.104046
5.
LombardiA, RipabelliG, SammarcoML, et al.Enterococcus faecium as an Emerging Pathogen: Molecular epidemiology and antimicrobial resistance in clinical strains. Pathogens2025;14(5):483; doi: 10.3390/pathogens14050483
6.
FaronML, LedeboerNA, BuchanBW. Resistance mechanisms, epidemiology, and approaches to screening for vancomycin-resistant Enterococcus in the health care setting. J Clin Microbiol2016;54(10):2436–2447; doi: 10.1128/JCM.00211-16
7.
Billot-KleinD, BlanotD, GutmannL, et al.Association constants for the binding of vancomycin and teicoplanin to N-acetyl-D-alanyl-D-alanine and N-acetyl-D-alanyl-D-serine. Biochem J1994;304 (Pt 3)(Pt 3):1021–1022.
8.
ArthurM, QuintilianiR. Regulation of VanA- and VanB-type glycopeptide resistance in enterococci. Antimicrob Agents Chemother2001;45(2):375–381.
9.
ShenH, ZhangQ, LiS, et al.Surveillance and characteristics of vancomycin-resistant Enterococcus isolates in a Chinese tertiary hospital in Shenzhen, 2018 to 2024. J Glob Antimicrob Resist2025;40:29–33; doi: 10.1016/j.jgar.2024.11.002
10.
RohdeAM, WalkerS, BehnkeM, et al.; DZIF R-NET Study Group. Vancomycin-resistant Enterococcus faecium: Admission prevalence, sequence types and risk factors-a cross-sectional study in seven German university hospitals from 2014 to 2018. Clin Microbiol Infect2023;29(4):515–522; doi: 10.1016/j.cmi.2022.11.025
11.
LeeRS, Gonçalves da SilvaA, BainesSL, et al.The changing landscape of vancomycin-resistant Enterococcus faecium in Australia: A population-level genomic study. J Antimicrob Chemother2018;73(12):3268–3278; doi: 10.1093/jac/dky331
12.
CimenC, BerendsMS, BathoornE, et al.Vancomycin-resistant enterococci (VRE) in hospital settings across European borders: A scoping review comparing the epidemiology in the Netherlands and Germany. Antimicrob Resist Infect Control2023;12(1):78; doi: 10.1186/s13756-023-01278-0
13.
ShenC, LuoL, ZhouH, et al.Emergence and ongoing outbreak of ST80 vancomycin-resistant Enterococcus faecium in Guangdong province, China from 2021 to 2023: A multicenter, time-series and genomic epidemiological study. Emerg Microbes Infect2024;13(1):2361030; doi: 10.1080/22221751.2024.2361030
14.
LiL, WangX, XiaoY, et al.; Shenzhen Pathogen Infection Research Alliance (SPIRA). Rapid transmission and divergence of vancomycin-resistant Enterococcus faecium sequence type 80, China. Emerg Infect Dis2025;31(5):1000–1005; doi: 10.3201/eid3105.241649
15.
AbdelbaryMHH, SennL, GreubG, et al.Whole-genome sequencing revealed independent emergence of vancomycin-resistant Enterococcus faecium causing sequential outbreaks over 3 years in a tertiary care hospital. Eur J Clin Microbiol Infect Dis2019;38(6):1163–1170; doi: 10.1007/s10096-019-03524-z
16.
TangP, CroxenMA, HasanMR, et al.Infection control in the new age of genomic epidemiology. Am J Infect Control2017;45(2):170–179; doi: 10.1016/j.ajic.2016.05.015
17.
BolgerAM, LohseM, UsadelB. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics2014;30(15):2114–2120; doi: 10.1093/bioinformatics/btu170
18.
BankevichA, NurkS, AntipovD, et al.SPAdes: A new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol2012;19(5):455–477; doi: 10.1089/cmb.2012.0021
19.
GurevichA, SavelievV, VyahhiN, et al.QUAST: Quality assessment tool for genome assemblies. Bioinformatics2013;29(8):1072–1075; doi: 10.1093/bioinformatics/btt086
ShenW, LeS, LiY, et al.SeqKit: A cross-platform and ultrafast toolkit for FASTA/Q file manipulation. PLoS One2016;11(10):e0163962; doi: 10.1371/journal.pone.0163962
22.
MinhBQ, SchmidtHA, ChernomorO, et al.IQ-TREE 2: New models and efficient methods for phylogenetic inference in the genomic era. Mol Biol Evol2020;37(5):1530–1534; doi: 10.1093/molbev/msaa015
23.
LetunicI, BorkP. Interactive Tree Of Life (iTOL) v5: An online tool for phylogenetic tree display and annotation. Nucleic Acids Res2021;49(W1):W293–W296; doi: 10.1093/nar/gkab301
24.
HomanWL, TribeD, PoznanskiS, et al.Multilocus sequence typing scheme for Enterococcus faecium. J Clin Microbiol2002;40(6):1963–1971.
25.
BezdicekM, HanslikovaJ, NykrynovaM, et al.New multilocus sequence typing scheme for Enterococcus faecium based on whole genome sequencing data. Microbiol Spectr2023;11(4):e0510722; doi: 10.1128/spectrum.05107-22
26.
JolleyKA, BrayJE, MaidenMCJ. Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res2018;3:124; doi: 10.12688/wellcomeopenres.14826.1
27.
SilvaM, MachadoMP, SilvaDN, et al.chewBBACA: A complete suite for gene-by-gene schema creation and strain identification. Microb Genom2018;4(3):e000166; doi: 10.1099/mgen.0.000166
28.
HyattD, ChenG-L, LocascioPF, et al.Prodigal: Prokaryotic gene recognition and translation initiation site identification. BMC Bioinformatics2010;11:119; doi: 10.1186/1471-2105-11-119
29.
FranciscoAP, BugalhoM, RamirezM, et al.Global optimal eBURST analysis of multilocus typing data using a graphic matroid approach. BMC Bioinformatics2009;10:152; doi: 10.1186/1471-2105-10-152
30.
ZankariE, HasmanH, CosentinoS, et al.Identification of acquired antimicrobial resistance genes. J Antimicrob Chemother2012;67(11):2640–2644; doi: 10.1093/jac/dks261
31.
ChenL, YangJ, YuJ, et al.VFDB: A reference database for bacterial virulence factors. Nucleic Acids Res2005;33(Database issue):D325–D328.
32.
AlcockBP, RaphenyaAR, LauTTY, et al.CARD 2020: Antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Res2020;48(D1):D517–D525; doi: 10.1093/nar/gkz935
33.
KatohK, StandleyDM. MAFFT multiple sequence alignment software version 7: Improvements in performance and usability. Mol Biol Evol2013;30(4):772–780; doi: 10.1093/molbev/mst010
34.
GouetP, CourcelleE, StuartDI, et al.ESPript: Analysis of multiple sequence alignments in PostScript. Bioinformatics1999;15(4):305–308.
35.
QinX, DingL, HaoM, et al.Antimicrobial resistance of clinical bacterial isolates in China: Current status and trends. JAC Antimicrob Resist2024;6(2):dlae052; doi: 10.1093/jacamr/dlae052
36.
ChopjittP, BoueroyP, JenjaroenpunP, et al.Genomic characterization of vancomycin-resistant Enterococcus faecium clonal complex 17 isolated from urine in tertiary hospitals in Northeastern Thailand. Front Microbiol2023;14:1278835; doi: 10.3389/fmicb.2023.1278835
37.
LeeAS, WhiteE, MonahanLG, et al.Defining the role of the environment in the emergence and persistence of vanA Vancomycin-resistant Enterococcus (VRE) in an intensive care unit: A molecular epidemiological study. Infect Control Hosp Epidemiol2018;39(6):668–675; doi: 10.1017/ice.2018.29
38.
FukushigeM, SyueL-S, MorikawaK, et al.Trend in healthcare-associated infections due to vancomycin-resistant Enterococcus at a hospital in the era of COVID-19: More than hand hygiene is needed. J Microbiol Immunol Infect2022;55(6 Pt 2):1211–1218; doi: 10.1016/j.jmii.2022.08.003
39.
Abu-LybdehO, MurikO, OsterY, et al.Vancomycin-resistant enterococcus bacteraemia in an endemic region: Clinical features and genomic analysis: A 12-year cohort. J Hosp Infect2022;121:105–113; doi: 10.1016/j.jhin.2021.11.021
40.
MokhtarJA, AttallahD, Al-RabiaMW, et al.Epidemiology and clinical impact of vancomycin-resistant Enterococcus at King Abdulaziz University Hospital (2015–2022): Prevalence, risk factors, and mortality. Int J Gen Med2025;18:2021–2031; doi: 10.2147/IJGM.S508262
41.
KayaA, KayaSY, BalkanII, et al.Risk factors for development of vancomycin-resistant enterococcal bacteremia among VRE colonizers: A retrospective case control study. Wien Klin Wochenschr2021;133(9–10):478–483; doi: 10.1007/s00508-020-01733-7
42.
AsginN, OtluB. Antibiotic resistance and molecular epidemiology of vancomycin-resistant Enterococci in a Tertiary Care Hospital in Turkey. Infect Drug Resist2020;13:191–198; doi: 10.2147/IDR.S191881
43.
HotaS, PatilSR, ManePM. Enterococcus: Understanding their resistance mechanisms, therapeutic challenges, and emerging threats. Cureus2025;17(2):e79628; doi: 10.7759/cureus.79628
44.
BiswasPP, DeyS, SenA, et al.Molecular characterization of virulence genes in vancomycin-resistant and vancomycin-sensitive Enterococci. J Glob Infect Dis2016;8(1):16–24; doi: 10.4103/0974-777X.176141
45.
FreitasAR, TedimAP, NovaisC, et al.Global spread of the hyl(Efm) colonization-virulence gene in megaplasmids of the Enterococcus faecium CC17 polyclonal subcluster. Antimicrob Agents Chemother2010;54(6):2660–2665; doi: 10.1128/AAC.00134-10
46.
XieZ, TangH. ISEScan: Automated identification of insertion sequence elements in prokaryotic genomes. Bioinformatics2017;33(21):3340–3347; doi: 10.1093/bioinformatics/btx433
47.
WanT-W, YeoH-H, LeeT-F, et al.Molecular epidemiology of bacteraemic vancomycin-resistant Enterococcus faecium isolates and in vitro activities of SC5005 and other comparators against these isolates collected from a medical centre in northern Taiwan, 2019-2020. J Antimicrob Chemother2023;78(2):457–465; doi: 10.1093/jac/dkac414
48.
AhmedMO, BaptisteKE. Vancomycin-resistant Enterococci: A review of antimicrobial resistance mechanisms and perspectives of human and animal health. Microb Drug Resist2018;24(5):590–606; doi: 10.1089/mdr.2017.0147
49.
Radford-SmithDE, AnthonyDC. Vancomycin-resistant E. faecium: Addressing global and clinical challenges. Antibiotics (Basel)2025;14(5):522; doi: 10.3390/antibiotics14050522
50.
Van BambekeF, ChauvelM, ReynoldsPE, et al.Vancomycin-dependent Enterococcus faecalis clinical isolates and revertant mutants. Antimicrob Agents Chemother1999;43(1):41–47.
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