Analysis of molecular epidemiological characteristics and antimicrobial susceptibility of vancomycin-resistant and linezolid-resistant Enterococcus in China.
Linezolid
/ pharmacology
Humans
China
/ epidemiology
Microbial Sensitivity Tests
Enterococcus faecium
/ genetics
Gram-Positive Bacterial Infections
/ microbiology
Male
Middle Aged
Enterococcus faecalis
/ genetics
Female
Vancomycin
/ pharmacology
Anti-Bacterial Agents
/ pharmacology
Molecular Epidemiology
Adult
Vancomycin Resistance
/ genetics
Aged
Retrospective Studies
Vancomycin-Resistant Enterococci
/ genetics
Young Adult
Enterococcus
/ genetics
Enterococcus faecalis
Enterococcus faecium
Antibiotic resistance
Linezolid
Vancomycin
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
01 Jul 2024
01 Jul 2024
Historique:
received:
07
03
2024
accepted:
21
06
2024
medline:
2
7
2024
pubmed:
2
7
2024
entrez:
2
7
2024
Statut:
epublish
Résumé
This study investigates the distribution and characteristics of linezolid and vancomycin susceptibilities among Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) and explores the underlying resistance mechanisms. A total of 2842 Enterococcus clinical isolates from patients were retrospectively collected, and their clinical data were further analyzed. The minimum inhibitory concentrations (MICs) of vancomycin and linezolid were validated by broth dilution method. The resistance genes optrA, cfr, vanA, vanB and vanM were investigated using polymerase chain reaction (PCR). Housekeeping genes and resistance genes were obtianed through whole-genome sequencing (WGS). Of the 2842 Enterococcus isolates, 88.5% (2516) originated from urine, with E. faecium accounted for 60.1% of these. The vanA gene was identified in 27/28 vancomycin resistant Enterococcus (VRE) isolates, 4 of which carried both vanA and vanM genes. The remaining strain was vanM positive. The optrA gene was identified in all E. faecalis isolates among linezolid resistant Enterococcus (LRE). E. faecium showed a higher multiple antibiotic resistance index (MAR index) compared to E. faecalis. The multi-locus sequence typing (MLST) showed the sequence type of E. faecium mainly belongs to clonal complex (CC) 17, nearly E. faecalis isolates analyzed were differentiated into 7 characteristics of sequence types (STs), among which ST16 of CC16 were the major lineage. Urine was the primary source of VRE and LRE isolates in this study. E. faecium showed higher levels of resistance compared to E. faecalis. OptrA gene was detected in 91.6% of LRE, which could explain linezolid resistance, and van genes were detected in all vancomycin resistant Enterococcus strains, while vanA was a key resistance mechanism in VRE identified in this study.
Sections du résumé
BACKGROUND
BACKGROUND
This study investigates the distribution and characteristics of linezolid and vancomycin susceptibilities among Enterococcus faecalis (E. faecalis) and Enterococcus faecium (E. faecium) and explores the underlying resistance mechanisms.
METHODS
METHODS
A total of 2842 Enterococcus clinical isolates from patients were retrospectively collected, and their clinical data were further analyzed. The minimum inhibitory concentrations (MICs) of vancomycin and linezolid were validated by broth dilution method. The resistance genes optrA, cfr, vanA, vanB and vanM were investigated using polymerase chain reaction (PCR). Housekeeping genes and resistance genes were obtianed through whole-genome sequencing (WGS).
RESULTS
RESULTS
Of the 2842 Enterococcus isolates, 88.5% (2516) originated from urine, with E. faecium accounted for 60.1% of these. The vanA gene was identified in 27/28 vancomycin resistant Enterococcus (VRE) isolates, 4 of which carried both vanA and vanM genes. The remaining strain was vanM positive. The optrA gene was identified in all E. faecalis isolates among linezolid resistant Enterococcus (LRE). E. faecium showed a higher multiple antibiotic resistance index (MAR index) compared to E. faecalis. The multi-locus sequence typing (MLST) showed the sequence type of E. faecium mainly belongs to clonal complex (CC) 17, nearly E. faecalis isolates analyzed were differentiated into 7 characteristics of sequence types (STs), among which ST16 of CC16 were the major lineage.
CONCLUSION
CONCLUSIONS
Urine was the primary source of VRE and LRE isolates in this study. E. faecium showed higher levels of resistance compared to E. faecalis. OptrA gene was detected in 91.6% of LRE, which could explain linezolid resistance, and van genes were detected in all vancomycin resistant Enterococcus strains, while vanA was a key resistance mechanism in VRE identified in this study.
Identifiants
pubmed: 38951840
doi: 10.1186/s12920-024-01948-x
pii: 10.1186/s12920-024-01948-x
doi:
Substances chimiques
Linezolid
ISQ9I6J12J
Vancomycin
6Q205EH1VU
Anti-Bacterial Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
174Subventions
Organisme : Hangzhou agricultural and social development Scientific Research
ID : 20201203B151
Informations de copyright
© 2024. The Author(s).
Références
Fiore E, Van Tyne D, Gilmore MS. Pathogenicity Enterococci Microbiol Spectr. 2019;7(4).
Hollenbeck BL, Rice LB. Intrinsic and acquired resistance mechanisms in enterococcus. Virulence. 2012;3(5):421–33.
doi: 10.4161/viru.21282
pubmed: 23076243
pmcid: 3485979
Kristich CJ, Rice LB, Arias CA. Enterococcal infection—treatment and antibiotic resistance. In: Gilmore MS, Clewell DB, Ike Y, Shankar N, editors. Enterococci: from commensals to leading causes of drug resistant infection. Boston: Massachusetts Eye and Ear Infirmary; 2014.
Guzman Prieto AM, van Schaik W, Rogers MR, Coque TM, Baquero F, Corander J, et al. Global emergence and dissemination of Enterococci as nosocomial pathogens: attack of the clones? Front Microbiol. 2016;7:788.
doi: 10.3389/fmicb.2016.00788
pubmed: 27303380
pmcid: 4880559
Rao C, Dhawan B, Vishnubhatla S, Kapil A, Das B, Sood S. Emergence of high-risk multidrug-resistant Enterococcus faecalis CC2 (ST181) and CC87 (ST28) causing healthcare-associated infections in India. Infect Genet Evolution: J Mol Epidemiol Evolutionary Genet Infect Dis. 2020;85:104519.
doi: 10.1016/j.meegid.2020.104519
Aung MS, Urushibara N, Kawaguchiya M, Ohashi N, Hirose M, Kudo K et al. Antimicrobial Resistance, virulence factors, and genotypes of Enterococcus faecalis and Enterococcus faecium clinical isolates in Northern Japan: identification of optrA in ST480 E. faecalis. Antibiot (Basel Switzerland). 2023;12(1).
Smith TT, Tamma PD, Do TB, Dzintars KE, Zhao Y, Cosgrove SE, et al. Prolonged linezolid use is associated with the development of linezolid-resistant Enterococcus faecium. Diagn Microbiol Infect Dis. 2018;91(2):161–3.
doi: 10.1016/j.diagmicrobio.2018.01.027
pubmed: 29496381
Garcia-Solache M, Rice LB. The Enterococcus: a model of adaptability to its environment. Clin Microbiol Rev. 2019;32(2).
Weiner LM, Webb AK, Limbago B, Dudeck MA, Patel J, Kallen AJ, et al. Infect Control Hosp Epidemiol. 2016;37(11):1288–301. Antimicrobial-Resistant Pathogens Associated With Healthcare-Associated Infections: Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011–2014.
Egan SA, Shore AC, O’Connell B, Brennan GI, Coleman DC. Linezolid resistance in Enterococcus faecium and Enterococcus faecalis from hospitalized patients in Ireland: high prevalence of the MDR genes optrA and poxtA in isolates with diverse genetic backgrounds. J Antimicrob Chemother. 2020;75(7):1704–11.
doi: 10.1093/jac/dkaa075
pubmed: 32129849
pmcid: 7303821
Sun L, Qu T, Wang D, Chen Y, Fu Y, Yang Q, et al. Characterization of vanM carrying clinical Enterococcus isolates and diversity of the suppressed vanM gene cluster. Infect Genet Evolution: J Mol Epidemiol Evolutionary Genet Infect Dis. 2019;68:145–52.
doi: 10.1016/j.meegid.2018.12.015
Bender JK, Cattoir V, Hegstad K, Sadowy E, Coque TM, Westh H, et al. Update on prevalence and mechanisms of resistance to linezolid, tigecycline and daptomycin in enterococci in Europe: towards a common nomenclature. Drug Resist Updates. 2018;40:25–39.
doi: 10.1016/j.drup.2018.10.002
Gagetti P, Faccone D, Ceriana P, Lucero C, Menocal A, Argentina GL, et al. Emergence of optra-mediated linezolid resistance in clinical isolates of Enterococcus faecalis from Argentina. J Global Antimicrob Resist. 2023;35:335–41.
doi: 10.1016/j.jgar.2023.10.014
Sordo M, Grilo T, Freire S, Rodrigues B, Bouvier M, Poirel L, et al. Rapid culture-based LNZ test for detection of linezolid susceptibility/resistance in staphylococci and enterococci. Diagn Microbiol Infect Dis. 2023;107(3):116058.
doi: 10.1016/j.diagmicrobio.2023.116058
pubmed: 37657232
Yang JX, Liu CW, Wu FW, Zhu L, Liang GW. Molecular characterization and biofilm formation ability of Enterococcus faecium and Enterococcus faecalis bloodstream isolates from a Chinese tertiary hospital in Beijing. Int Microbiology: Official J Span Soc Microbiol. 2023.
Turner AM, Lee JYH, Gorrie CL, Howden BP, Carter GP. Genomic insights into last-line Antimicrobial Resistance in Multidrug-Resistant Staphylococcus and Vancomycin-resistant Enterococcus. Front Microbiol. 2021;12:637656.
doi: 10.3389/fmicb.2021.637656
pubmed: 33796088
pmcid: 8007764
Munita JM, Bayer AS, Arias CA. Evolving resistance among Gram-positive pathogens. Clin Infect Diseases: Official Publication Infect Dis Soc Am. 2015;61(Suppl 2):S48–57.
doi: 10.1093/cid/civ523
Gorrie C, Higgs C, Carter G, Stinear TP, Howden B. Genomics of Vancomycin-resistant Enterococcus faecium. Microb Genomics. 2019;5(7).
Humphries R, Bobenchik AM, Hindler JA, Schuetz AN. Overview of changes to the Clinical and Laboratory Standards Institute Performance Standards for Antimicrobial Susceptibility Testing, M100, 31st Edition. J Clin Microbiol. 2021;59(12):e0021321.
doi: 10.1128/JCM.00213-21
pubmed: 34550809
Ma X, Zhang F, Bai B, Lin Z, Xu G, Chen Z, et al. Linezolid Resistance in Enterococcus faecalis Associated with urinary tract infections of patients in a Tertiary hospitals in China: resistance mechanisms, virulence, and risk factors. Front Public Health. 2021;9:570650.
doi: 10.3389/fpubh.2021.570650
pubmed: 33614576
pmcid: 7893085
Shakir ZM, Alhatami AO, Ismail Khudhair Y, Muhsen Abdulwahab H. Antibiotic Resistance Profile and multiple antibiotic resistance index of Campylobacter species isolated from Poultry. Arch Razi Inst. 2021;76(6):1677–86.
pubmed: 35546994
pmcid: 9083853
Huang L, Huang C, Yan Y, Sun L, Li H. Urinary tract infection etiological profiles and antibiotic resistance patterns varied among different age categories: a retrospective study from a Tertiary General Hospital during a 12-Year period. Front Microbiol. 2021;12:813145.
doi: 10.3389/fmicb.2021.813145
pubmed: 35154037
Zhou X, Willems RJL, Friedrich AW, Rossen JWA, Bathoorn E. Enterococcus faecium: from microbiological insights to practical recommendations for infection control and diagnostics. Antimicrob Resist Infect Control. 2020;9(1):130.
doi: 10.1186/s13756-020-00770-1
pubmed: 32778149
pmcid: 7418317
Park B, Min YH. In vitro synergistic effect of retapamulin with erythromycin and quinupristin against Enterococcus faecalis. J Atibiotics. 2020;73(9):630–5.
doi: 10.1038/s41429-020-0312-7
Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018;18(3):318–27.
doi: 10.1016/S1473-3099(17)30753-3
pubmed: 29276051
Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infection: Official Publication Eur Soc Clin Microbiol Infect Dis. 2012;18(3):268–81.
doi: 10.1111/j.1469-0691.2011.03570.x
Osman K, Zolnikov TR, Badr J, Naim H, Hanafy M, Saad A, et al. Vancomycin and florfenicol resistant Enterococcus faecalis and Enterococcus faecium isolated from human urine in an Egyptian urban-rural community. Acta Trop. 2020;201:105209.
doi: 10.1016/j.actatropica.2019.105209
pubmed: 31600524
Pfaller MA, Cormican M, Flamm RK, Mendes RE, Jones RN. Temporal and Geographic Variation in Antimicrobial susceptibility and resistance patterns of Enterococci: results from the SENTRY Antimicrobial Surveillance Program, 1997–2016. Open forum infectious diseases. 2019;6(Suppl 1):S54–62.
Mercuro NJ, Davis SL, Zervos MJ, Herc ES. Combatting resistant enterococcal infections: a pharmacotherapy review. Expert Opin Pharmacother. 2018;19(9):979–92.
doi: 10.1080/14656566.2018.1479397
pubmed: 29877755
Miller WR, Murray BE, Rice LB, Arias CA. Resistance in vancomycin-resistant Enterococci. Infect Dis Clin N Am. 2020;34(4):751–71.
doi: 10.1016/j.idc.2020.08.004
Bender JK, Cattoir V, Hegstad K, Sadowy E, Coque TM, Westh H et al. Update on prevalence and mechanisms of resistance to linezolid, tigecycline and daptomycin in enterococci in Europe: towards a common nomenclature. Drug resistance updates: reviews and commentaries in antimicrobial and anticancer chemotherapy. 2018;40:25–39.
Sharkey LK, Edwards TA, O’Neill AJ. ABC-F Proteins Mediate Antibiotic Resistance through Ribosomal Protection. mBio. 2016;7(2):e01975.
doi: 10.1128/mBio.01975-15
pubmed: 27006457
pmcid: 4807367
Dejoies L, Boukthir S, Péan de Ponfilly G, Le Guen R, Zouari A, Potrel S, et al. Performance of commercial methods for linezolid susceptibility testing of Enterococcus faecium and Enterococcus faecalis. J Antimicrob Chemother. 2020;75(9):2587–93.
doi: 10.1093/jac/dkaa180
pubmed: 32449911
Sun HL, Liu C, Zhang JJ, Zhou YM, Xu YC. Molecular characterization of Vancomycin-resistant enterococci isolated from a hospital in Beijing, China. J Microbiol Immunol Infect. 2019;52(3):433–42.
doi: 10.1016/j.jmii.2018.12.008
pubmed: 30827858
Chen C, Sun J, Guo Y, Lin D, Guo Q, Hu F, et al. High prevalence of vanM in Vancomycin-resistant Enterococcus faecium isolates from Shanghai, China. Antimicrobial agents and chemotherapy. Antimicrob Agents Chemother. 2015;59(12):7795–8.
doi: 10.1128/AAC.01732-15
pubmed: 26369966
pmcid: 4649207
Hua R, Xia Y. Molecular Epidemiology and mechanisms of 43 low-level linezolid-resistant Enterococcus faecalis strains in Chongqing. China Annals Lab Med. 2019;39(1):36–42.
doi: 10.3343/alm.2019.39.1.36
Zhou W, Zhou H, Sun Y, Gao S, Zhang Y, Cao X, et al. Characterization of clinical enterococci isolates, focusing on the Vancomycin-resistant enterococci in a tertiary hospital in China: based on the data from 2013 to 2018. BMC Infect Dis. 2020;20(1):356.
doi: 10.1186/s12879-020-05078-4
pubmed: 32517758
pmcid: 7285731
Permana B, Harris PNA, Runnegar N, Lindsay M, Henderson BC, Playford EG, et al. Using Genomics to investigate an outbreak of vancomycin-resistant Enterococcus faecium ST78 at a large Tertiary Hospital in Queensland. Microbiol Spectr. 2023;11(3):e0420422.
doi: 10.1128/spectrum.04204-22
pubmed: 37191518
Yang J, Yuan Y, Tang M, Liu L, Yang K, Liu J. Phenotypic and genetic characteristics of Vancomycin-resistant Enterococcus faecium. Microb Pathog. 2019;128:131–5.
doi: 10.1016/j.micpath.2018.12.046
pubmed: 30597255
Rao C, Dhawan B, Vishnubhatla S, Kapil A, Das B, Sood S. Clinical and molecular epidemiology of Vancomycin-resistant Enterococcus faecium bacteremia from an Indian tertiary hospital. Eur J Clin Microbiol Infect Dis. 2021;40(2):303–14.
doi: 10.1007/s10096-020-04030-3
pubmed: 32909085
Xavier BB, Coppens J, De Koster S, Rajakani SG, Van Goethem S, Mzougui S et al. Novel Vancomycin resistance gene cluster in Enterococcus faecium ST1486, Belgium, June 2021. Euro Surveill. 2021;26(36).
Sabzi N, Moniri R, Sehat M, Fathizadeh H, Nazari-Alam A. Antimicrobial effect of silver and gold nanoparticles in combination with linezolid on Enterococcus biofilm. Iran J Microbiol. 2022;14(6):863–73.
pubmed: 36721451
pmcid: 9867620
Khan A, Miller WR. Antimicrobial susceptibility testing for Enterococci. J Clin Microbiol. 2022;60(9):e0084321.
doi: 10.1128/jcm.00843-21
pubmed: 35695560
Tacconelli E, Cataldo MA. Vancomycin-resistant enterococci (VRE): transmission and control. Int J Antimicrob Agents. 2008;31:99–106.
doi: 10.1016/j.ijantimicag.2007.08.026
pubmed: 18164908