Hostname: page-component-848d4c4894-5nwft Total loading time: 0 Render date: 2024-05-26T08:28:40.861Z Has data issue: false hasContentIssue false

Staphylococcus epidermidis joint isolates: Whole-genome sequencing demonstrates evidence of hospital transmission and common antimicrobial resistance

Published online by Cambridge University Press:  15 December 2023

Samantha J. Simon
Research Department, New England Baptist Hospital, Boston, Massachusetts
Mohamad Sater
Day Zero Diagnostics, Boston, Massachusetts
Ian Herriott
Day Zero Diagnostics, Boston, Massachusetts
Miriam Huntley
Day Zero Diagnostics, Boston, Massachusetts
Emma Briars
Day Zero Diagnostics, Boston, Massachusetts
Brian L. Hollenbeck*
Research Department, New England Baptist Hospital, Boston, Massachusetts Infectious Diseases, New England Baptist Hospital, Boston, Massachusetts
Corresponding author: Brian L. Hollenbeck; Email:



We investigated genetic, epidemiologic, and environmental factors contributing to positive Staphylococcus epidermidis joint cultures.


Retrospective cohort study with whole-genome sequencing (WGS).


We identified S. epidermidis isolates from hip or knee cultures in patients with 1 or more prior corresponding intra-articular procedure at our hospital.


WGS and single-nucleotide polymorphism–based clonality analyses were performed, including species identification, in silico multilocus sequence typing (MLST), phylogenomic analysis, and genotypic assessment of the prevalence of specific antibiotic resistance and virulence genes. Epidemiologic review was performed to compare cluster and noncluster cases.


In total, 60 phenotypically distinct S. epidermidis isolates were identified. After removal of duplicates and impure samples, 48 isolates were used for the phylogenomic analysis, and 45 (93.7%) isolates were included in the clonality analysis. Notably, 5 S. epidermidis strains (10.4%) showed phenotypic susceptibility to oxacillin yet harbored mecA, and 3 (6.2%) strains showed phenotypic resistance despite not having mecA. Smr was found in all isolates, and mupA positivity was not observed. We also identified 6 clonal clusters from the clonality analysis, which accounted for 14 (31.1%) of the 45 S. epidermidis isolates. Our epidemiologic investigation revealed ties to common aspirations or operative procedures, although no specific common source was identified.


Most S. epidermidis isolates from clinical joint samples are diverse in origin, but we identified an important subset of 31.1% that belonged to subclinical healthcare–associated clusters. Clusters appeared to resolve spontaneously over time, suggesting the benefit of routine hospital infection control and disinfection practices.

Original Article
© The Author(s), 2023. Published by Cambridge University Press on behalf of The Society for Healthcare Epidemiology of America

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


Boddapati, V, Fu, MC, Mayman, DJ, Su, EP, Sculco, PK, McLawhorn, AS. Revision total knee arthroplasty for periprosthetic joint infection is associated with increased postoperative morbidity and mortality relative to noninfectious revisions. J Arthroplasty 2018;33:521526.CrossRefGoogle ScholarPubMed
Lentino, JR. Prosthetic joint infections: bane of orthopedists, challenge for infectious disease specialists. Clin Infect Dis 2003;36:11571161.CrossRefGoogle ScholarPubMed
Fischbacher, A, Borens, O. Prosthetic-joint infections: mortality over the last 10 years. J Bone Jt Infect 2019;4:198202.CrossRefGoogle ScholarPubMed
Maradit Kremers, H, Larson, DR, Crowson, CS, et al. Prevalence of total hip and knee replacement in the United States: J Bone Jt Surg Am 2015;97:13861397.10.2106/JBJS.N.01141CrossRefGoogle ScholarPubMed
Premkumar, A, Kolin, DA, Farley, KX, et al. Projected economic burden of periprosthetic joint infection of the hip and knee in the United States. J Arthroplasty 2021;36:14841489.CrossRefGoogle ScholarPubMed
Mussa, M, Manciulli, T, Corbella, M, et al. Epidemiology and microbiology of prosthetic joint infections: a nine-year, single-center experience in Pavia, Northern Italy. Musculoskelet Surg 2021;105:195200.CrossRefGoogle ScholarPubMed
Flurin, L, Greenwood-Quaintance, KE, Patel, R. Microbiology of polymicrobial prosthetic joint infection. Diagn Microbiol Infect Dis 2019;94:255259.CrossRefGoogle ScholarPubMed
Tsai, JC, Sheng, WH, Lo, WY, Jiang, CC, Chang, SC. Clinical characteristics, microbiology, and outcomes of prosthetic joint infection in Taiwan. J Microbiol Immunol Infect 2015;48:198204.CrossRefGoogle ScholarPubMed
Lowy, FD. Staphylococcus epidermidis infections. Ann Intern Med 1983;99:834.CrossRefGoogle ScholarPubMed
Post, V, Harris, LG, Morgenstern, M, et al. Comparative genomics study of Staphylococcus epidermidis isolates from orthopedic-device–related infections correlated with patient outcome. J Clin Microbiol 2017;55:30893103.CrossRefGoogle ScholarPubMed
Sánchez, A, Benito, N, Rivera, A, et al. Pathogenesis of Staphylococcus epidermidis in prosthetic joint infections: can identification of virulence genes differentiate between infecting and commensal strains? J Hosp Infect 2020;105:561568.CrossRefGoogle Scholar
Conlan, S, Mijares, LA, NISC Comparative Sequencing Program, et al. Staphylococcus epidermidis pan-genome sequence analysis reveals diversity of skin commensal and hospital infection-associated isolates. Genome Biol 2012;13:R64.CrossRefGoogle ScholarPubMed
Li, M, Wang, X, Gao, Q, Lu, Y. Molecular characterization of Staphylococcus epidermidis strains isolated from a teaching hospital in Shanghai, China. J Med Microbiol 2009;58:456461.CrossRefGoogle ScholarPubMed
Zhang, YQ, Ren, SX, Li, HL, et al. Genome-based analysis of virulence genes in a non–biofilm-forming Staphylococcus epidermidis strain (ATCC 12228): genome-based analysis of S. epidermidis strain ATCC 12228. Mol Microbiol 2003;49:15771593.CrossRefGoogle Scholar
Sundermann, AJ, Chen, J, Miller, JK, et al. Outbreak of Pseudomonas aeruginosa infections from a contaminated gastroscope detected by whole-genome sequencing surveillance. Clin Infect Dis 2021;73:e638e642.CrossRefGoogle ScholarPubMed
Sundermann, AJ, Chen, J, Kumar, P, et al. Whole-genome sequencing surveillance and machine learning of the electronic health record for enhanced healthcare outbreak detection. Clin Infect Dis 2022;75:476482.CrossRefGoogle ScholarPubMed
Sharma, H, Ong, MR, Ready, D, et al. Real-time whole-genome sequencing to control a Streptococcus pyogenes outbreak at a national orthopaedic hospital. J Hosp Infect 2019;103:2126.CrossRefGoogle Scholar
Sundermann, AJ, Chen, J, Miller, JK, et al. Whole-genome sequencing surveillance and machine learning for healthcare outbreak detection and investigation: a systematic review and summary. Antimicrob Steward Healthc Epidemiol 2022;2:e91.CrossRefGoogle ScholarPubMed
Wood, DE, Salzberg, SL. Kraken: ultrafast metagenomic sequence classification using exact alignments. Genome Biol 2014;15:R46.CrossRefGoogle ScholarPubMed
Croucher, NJ, Page, AJ, Connor, TR, et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole-genome sequences using GUBBINS. Nucleic Acids Res 2015;43:e15.CrossRefGoogle ScholarPubMed
Coll, F, Raven, KE, Knight, GM, et al. Definition of a genetic relatedness cutoff to exclude recent transmission of meticillin-resistant Staphylococcus aureus: a genomic epidemiology analysis. Lancet Microbe 2020;1:e328e335.CrossRefGoogle ScholarPubMed
Letunic, I, Bork, P. Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res 2021;49:W293W296.CrossRefGoogle ScholarPubMed
Parvizi, J, Zmistowski, B, Berbari, EF, et al. New definition for periprosthetic joint infection: from the workgroup of the Musculoskeletal Infection Society. Clin Orthop 2011;469:29922994.CrossRefGoogle ScholarPubMed
Parvizi, J, Gehrke, T, Chen, AF. Proceedings of the International Consensus on Periprosthetic Joint Infection. Bone Jt J 2013;95-B:14501452.CrossRefGoogle ScholarPubMed
Månsson, E, Bech Johannesen, T, Nilsdotter-Augustinsson, Å, Söderquist, B, Stegger, M. Comparative genomics of Staphylococcus epidermidis from prosthetic-joint infections and nares highlights genetic traits associated with antimicrobial resistance, not virulence. Microb Genomics 2021;7:504.CrossRefGoogle Scholar
Månsson, E, Tevell, S, Nilsdotter-Augustinsson, Å, et al. Methicillin-resistant Staphylococcus epidermidis lineages in the nasal and skin microbiota of patients planned for arthroplasty surgery. Microorganisms 2021;9:265.CrossRefGoogle ScholarPubMed
Datta, MS, Yelin, I, Hochwald, O, et al. Rapid methicillin resistance diversification in Staphylococcus epidermidis colonizing human neonates. Nat Commun 2021;12:6062.CrossRefGoogle ScholarPubMed
Cabrera-Contreras, R, Santamaría, RI, Bustos, P, et al. Genomic diversity of prevalent Staphylococcus epidermidis multidrug-resistant strains isolated from a Children’s Hospital in México City in an eight-year survey. Peer J 2019;7:e8068.CrossRefGoogle Scholar
Talbot, BM, Jacko, NF, Petit, RA, et al. Unsuspected clonal spread of methicillin-resistant Staphylococcus aureus causing bloodstream infections in hospitalized adults detected using whole-genome sequencing. Clin Infect Dis 2022;75:21042112.CrossRefGoogle ScholarPubMed
Wassenaar, T, Ussery, D, Nielsen, L, Ingmer, H. Review and phylogenetic analysis of qac genes that reduce susceptibility to quaternary ammonium compounds in Staphylococcus species. Eur J Microbiol Immunol 2015;5:4461.CrossRefGoogle ScholarPubMed
do Vale BCM, Nogueira, AG, Cidral, TA, Lopes, MCS, de Melo MCN. Decreased susceptibility to chlorhexidine and distribution of qacA/B genes among coagulase-negative Staphylococcus clinical samples. BMC Infect Dis 2019;19:199.Google Scholar
Horner, C, Mawer, D, Wilcox, M. Reduced susceptibility to chlorhexidine in staphylococci: is it increasing and does it matter? J Antimicrob Chemother 2012;67:25472559.CrossRefGoogle ScholarPubMed
Kampf, G. Acquired resistance to chlorhexidine—Is it time to establish an ‘antiseptic stewardship’ initiative? J Hosp Infect 2016;94:213227.CrossRefGoogle Scholar
Van den Poel, B, Saegeman, V, Schuermans, A. Increasing usage of chlorhexidine in health care settings: blessing or curse? A narrative review of the risk of chlorhexidine resistance and the implications for infection prevention and control. Eur J Clin Microbiol Infect Dis 2022;41:349362.CrossRefGoogle ScholarPubMed
Kim, DH, Spencer, M, Davidson, SM, et al. Institutional prescreening for detection and eradication of methicillin-resistant Staphylococcus aureus in patients undergoing elective orthopaedic surgery. J Bone Jt Surg 2010;92:18201826.CrossRefGoogle ScholarPubMed
Ortega-Peña, S, Vargas-Mendoza, CF, Franco-Cendejas, R, et al. sesA, sesB, sesC, sesD, sesE, sesG, sesH, and embp genes are genetic markers that differentiate commensal isolates of Staphylococcus epidermidis from isolates that cause prosthetic joint infection. Infect Dis 2019;51:435445.CrossRefGoogle ScholarPubMed
Qi, X, Jin, Y, Duan, J, et al. SesI may be associated with the invasiveness of Staphylococcus epidermidis . Front Microbiol 2018;8:2574.10.3389/fmicb.2017.02574CrossRefGoogle ScholarPubMed
Stimson, J, Gardy, J, Mathema, B, Crudu, V, Cohen, T, Colijn, C. Beyond the SNP threshold: identifying outbreak clusters using inferred transmissions. Mol Biol Evol 2019;36:587603.CrossRefGoogle ScholarPubMed
Supplementary material: File

Simon et al. supplementary material

Simon et al. supplementary material

Download Simon et al. supplementary material(File)
File 22 KB