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  • 1.
    Månsson, Emeli
    Örebro University, School of Medical Sciences.
    Molecular epidemiology of Staphylococcus epidermidis in prosthetic joint infections2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Staphylococcus epidermidis is ubiquitous in the human microbiota, but also an important pathogen in healthcare-associated infections, such as prosthetic joint infections (PJIs). In this thesis, aspects of the molecular epidemiology of S. epidermidis in PJIs were investigated with the aim of improving our understanding of the pre- and perioperative measures required to reduce the incidence of S. epidermidis PJIs.

    In Paper I, S. epidermidis retrieved from air sampling in the operating field during arthroplasty was characterized by multilocus sequence typing and antibiotic susceptibility testing. No isolates belonging to sequence types (STs) 2 and 215, previously associated with PJIs, were found in the air of the operating field. During air sampling, several Staphylococcus pettenkoferi isolates were identified, and as a spin-off of Paper I, the genomic relatedness of these isolates to S. pettenkoferi isolates from blood cultures was described in Paper II.

    In Paper III, genetic traits distinguishing S. epidermidis isolated from PJIs were determined using genome-wide association study accounting for population effects after whole-genome sequencing (WGS) of a population- based 10-year collection of S. epidermidis isolates from PJIs and of nasal isolates retrieved from patients scheduled for arthroplasty. Genes associated with antimicrobial agents used for prophylaxis in arthroplasty, i.e., beta-lactam antibiotics, aminoglycosides, and chlorhexidine, were associated with PJI origin. S. epidermidis from PJIs were dominated by the ST2a, ST2b, ST5, and ST215 lineages.

    In Paper IV, selective agar plates were used to investigate colonization with methicillin resistant S. epidermidis (MRSE) in patients scheduled for arthroplasty. MRSE were further characterized by WGS. A subset of patients was found to harbour PJI-associated S. epidermidis lineages in their microbiota before hospitalization, but no isolates belonging to the ST2a lineage nor any rifampicin-resistant isolates were retrieved.

    List of papers
    1. Sequence types of Staphylococcus epidermidis associated with prosthetic joint infections are not present in the laminar airflow during prosthetic joint surgery
    Open this publication in new window or tab >>Sequence types of Staphylococcus epidermidis associated with prosthetic joint infections are not present in the laminar airflow during prosthetic joint surgery
    2015 (English)In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 123, no 7, p. 589-595Article in journal (Refereed) Published
    Abstract [en]

    Molecular characterization of Staphylococcus epidermidis isolates from prosthetic joint infections (PJIs) has demonstrated a predominance of healthcare-associated multi-drug resistant sequence types (ST2 and ST215). How, and when, patients acquire these nosocomial STs is not known. The aim was to investigate if sequence types of S. epidermidis associated with PJIs are found in the air during prosthetic joint surgery. Air sampling was undertaken during 17 hip/knee arthroplasties performed in operating theaters equipped with mobile laminar airflow units in a 500-bed hospital in central Sweden. Species identification was performed using MALDI-TOF MS and 16S rRNA gene analysis. Isolates identified as S. epidermidis were further characterized by MLST and antibiotic susceptibility testing. Seven hundred and thirty-five isolates were available for species identification. Micrococcus spp. (n = 303) and coagulase-negative staphylococci (n = 217) constituted the majority of the isolates. Thirty-two isolates of S. epidermidis were found. S. epidermidis isolates demonstrated a high level of allelic diversity with 18 different sequence types, but neither ST2 nor ST215 was found. Commensals with low pathogenic potential dominated among the airborne microorganisms in the operating field during prosthetic joint surgery. Nosocomial sequence types of S. epidermidis associated with PJIs were not found, and other routes of inoculation are therefore of interest in future studies.

    Place, publisher, year, edition, pages
    Hoboken, USA: Wiley-Blackwell, 2015
    Keywords
    Staphylococcus epidermidis, ST2, ST215, prosthetic joint infections, airborne transmission
    National Category
    Infectious Medicine Immunology in the medical area
    Research subject
    Immunology; Microbiology; Pathology
    Identifiers
    urn:nbn:se:oru:diva-44704 (URN)10.1111/apm.12392 (DOI)000356972400007 ()25951935 (PubMedID)2-s2.0-84932196136 (Scopus ID)
    Note

    Funding Agencies:

    Örebro County Council Research Committee, Örebro Sweden

    Centre for Clinical Research, Västerås

    County Council of Västmanland Research Fund

    Available from: 2015-05-27 Created: 2015-05-27 Last updated: 2019-11-12Bibliographically approved
    2. Genomic relatedness of Staphylococcus pettenkoferi isolates of different origins
    Open this publication in new window or tab >>Genomic relatedness of Staphylococcus pettenkoferi isolates of different origins
    Show others...
    2017 (English)In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 66, no 5, p. 601-608Article in journal (Refereed) Published
    Abstract [en]

    Purpose: The aim of the study was to characterize clinical and environmental Staphylococcus pettenkoferi isolates with regard to genomic diversity and antibiotic susceptibility pattern. Repetitive-sequence-based PCR and core genome phylogenetic analysis of whole-genome sequencing (WGS) data verified the presence of distinct clades comprising closely related S. pettenkoferi isolates from different geographical locations and origins.

    Methodology: Phylogenetic relationships between 25 S. pettenkoferi isolates collected from blood cultures and intra-operative air sampling were determined by repetitive-sequence-based PCR typing and analysis of similar to 157 000 SNPs identified in the core genome after WGS. Antibiotic susceptibility testing and tests for biofilm production (microtitre plate assay) were performed.

    Results: Repetitive-sequence-based PCR as well as WGS data demonstrated the close relatedness of clinically significant blood culture isolates to probable contaminants, as well as to environmental isolates. Antibiotic-susceptibility testing demonstrated a low level of antimicrobial resistance. The mecA gene was present in two cefoxitin-resistant isolates. No isolates were found to produce biofilm.

    Conclusion: Close genomic relatedness of S. pettenkoferi isolates from different geographical locations and origins were found within clades, but with substantial genomic difference between the two major clades. The ecological niche of S. pettenkoferi remains unconfirmed, but the presence of S. pettenkoferi in the air of the operating field favours the suggestion of a role in skin flora. Identification of S. pettenkoferi in clinical samples should, in a majority of cases, most likely be regarded as a probable contamination, and its role as a possible pathogen in immunocompromised hosts remains to be clarified.

    Place, publisher, year, edition, pages
    Microbiology Society, 2017
    Keywords
    Staphylococcus pettenkoferi, genotypic relatedness, repetitive-sequence based PCR typing, whole-genome sequencing
    National Category
    Microbiology in the medical area
    Identifiers
    urn:nbn:se:oru:diva-58000 (URN)10.1099/jmm.0.000472 (DOI)000401984900007 ()28530888 (PubMedID)2-s2.0-85019900525 (Scopus ID)
    Note

    Funding Agencies:

    Örebro County Council Research Committee, Örebro, Sweden

    Centre for Clinical Research, Västerås  

    County Council of Västmanland Research Fund 

    Available from: 2017-06-13 Created: 2017-06-13 Last updated: 2019-11-12Bibliographically approved
    3. Genomic traits in Staphylococcus epidermidis associated with prosthetic joint infections
    Open this publication in new window or tab >>Genomic traits in Staphylococcus epidermidis associated with prosthetic joint infections
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-77834 (URN)
    Available from: 2019-11-12 Created: 2019-11-12 Last updated: 2019-11-12Bibliographically approved
    4. Methicillin resistant Staphylococcus epidermidis lineages in the nasal and skin microbiota of patients scheduled for arthroplasty surgery
    Open this publication in new window or tab >>Methicillin resistant Staphylococcus epidermidis lineages in the nasal and skin microbiota of patients scheduled for arthroplasty surgery
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-77835 (URN)
    Available from: 2019-11-12 Created: 2019-11-12 Last updated: 2019-11-12Bibliographically approved
  • 2.
    Månsson, Emeli
    et al.
    Örebro University, School of Medical Sciences. Region Västmanland – Uppsala University, Centre for Clinical Research, Hospital of Västmanland, Västerås, Sweden.
    Bech Johannesen, Thor
    Statens Serum Institut, Copenhagen, Denmark.
    Nilsdotter, Åsa
    Department of Infectious Diseases, and Department of Clinical and Experimental Medicine, Linköping University, Norrköping, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Microbiology.
    Stegger, Marc
    Statens Serum Institut, Copenhagen, Denmark.
    Genomic traits in Staphylococcus epidermidis associated with prosthetic joint infectionsManuscript (preprint) (Other academic)
  • 3.
    Månsson, Emeli
    et al.
    Örebro University, School of Medical Sciences. Centre for Clinical Research, Hospital of Västmanland Västerås, Västerås, Sweden.
    Hellmark, Bengt
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine.
    Stegger, Marc
    Statens Serum Institut, Copenhagen, Denmark.
    Andersen, Paal Skytt
    Statens Serum Institut, Copenhagen, Denmark.
    Sundqvist, Martin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Genomic relatedness of Staphylococcus pettenkoferi isolates of different origins2017In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 66, no 5, p. 601-608Article in journal (Refereed)
    Abstract [en]

    Purpose: The aim of the study was to characterize clinical and environmental Staphylococcus pettenkoferi isolates with regard to genomic diversity and antibiotic susceptibility pattern. Repetitive-sequence-based PCR and core genome phylogenetic analysis of whole-genome sequencing (WGS) data verified the presence of distinct clades comprising closely related S. pettenkoferi isolates from different geographical locations and origins.

    Methodology: Phylogenetic relationships between 25 S. pettenkoferi isolates collected from blood cultures and intra-operative air sampling were determined by repetitive-sequence-based PCR typing and analysis of similar to 157 000 SNPs identified in the core genome after WGS. Antibiotic susceptibility testing and tests for biofilm production (microtitre plate assay) were performed.

    Results: Repetitive-sequence-based PCR as well as WGS data demonstrated the close relatedness of clinically significant blood culture isolates to probable contaminants, as well as to environmental isolates. Antibiotic-susceptibility testing demonstrated a low level of antimicrobial resistance. The mecA gene was present in two cefoxitin-resistant isolates. No isolates were found to produce biofilm.

    Conclusion: Close genomic relatedness of S. pettenkoferi isolates from different geographical locations and origins were found within clades, but with substantial genomic difference between the two major clades. The ecological niche of S. pettenkoferi remains unconfirmed, but the presence of S. pettenkoferi in the air of the operating field favours the suggestion of a role in skin flora. Identification of S. pettenkoferi in clinical samples should, in a majority of cases, most likely be regarded as a probable contamination, and its role as a possible pathogen in immunocompromised hosts remains to be clarified.

  • 4.
    Månsson, Emeli
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Centre for Clinical Research, Uppsala University, Uppsala, Sweden; County Hospital, Västerås, Sweden.
    Hellmark, Bengt
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Sundqvist, Martin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden.
    Sequence types of Staphylococcus epidermidis associated with prosthetic joint infections are not present in the laminar airflow during prosthetic joint surgery2015In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 123, no 7, p. 589-595Article in journal (Refereed)
    Abstract [en]

    Molecular characterization of Staphylococcus epidermidis isolates from prosthetic joint infections (PJIs) has demonstrated a predominance of healthcare-associated multi-drug resistant sequence types (ST2 and ST215). How, and when, patients acquire these nosocomial STs is not known. The aim was to investigate if sequence types of S. epidermidis associated with PJIs are found in the air during prosthetic joint surgery. Air sampling was undertaken during 17 hip/knee arthroplasties performed in operating theaters equipped with mobile laminar airflow units in a 500-bed hospital in central Sweden. Species identification was performed using MALDI-TOF MS and 16S rRNA gene analysis. Isolates identified as S. epidermidis were further characterized by MLST and antibiotic susceptibility testing. Seven hundred and thirty-five isolates were available for species identification. Micrococcus spp. (n = 303) and coagulase-negative staphylococci (n = 217) constituted the majority of the isolates. Thirty-two isolates of S. epidermidis were found. S. epidermidis isolates demonstrated a high level of allelic diversity with 18 different sequence types, but neither ST2 nor ST215 was found. Commensals with low pathogenic potential dominated among the airborne microorganisms in the operating field during prosthetic joint surgery. Nosocomial sequence types of S. epidermidis associated with PJIs were not found, and other routes of inoculation are therefore of interest in future studies.

  • 5.
    Månsson, Emeli
    et al.
    Örebro University, School of Medical Sciences. Centre for Clinical Research, Hospital of Västmanland Västerås, Region Västmanland, Västerås, Sweden; Centre for Clinical Research, Hospital of Västmanland Västerås, Uppsala University, Västerås, Sweden.
    Sahdo, Berolla
    Örebro University, Örebro, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Department of Infectious Diseases, and Department of Clinical and Experimental Medicine, Linköping University, Norrköping, Sweden.
    Särndahl, Eva
    Örebro University, School of Medical Sciences.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Microbiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Lower activation of caspase-1 by Staphylococcus epidermidis isolated from prosthetic joint infections compared to commensals2018In: Journal of bone and joint infection, ISSN 2206-3552, Vol. 3, no 1, p. 10-14Article in journal (Refereed)
    Abstract [en]

    Nosocomial sequence types of Staphylococcus epidermidis dominate in prosthetic joint infections. We examined caspase-1 activation in human neutrophils after incubation with Staphylococcus epidermidis isolated from prosthetic joint infections and normal skin flora. Active caspase-1 was lower after incubation with isolates from prosthetic joint infections than after incubation with commensal isolates. Both host and isolate dependent differences in active caspase-1 were noted. Our results indicate that there might be a host-dependent incapacity to elicit a strong caspase-1 response towards certain strains of S. epidermidis. Further experiments with a larger number of individuals are warranted.

  • 6.
    Månsson, Emeli
    et al.
    Örebro University, School of Medical Sciences. Centre for Clinical Research, Hospital of Västmanland, Region Västmanland, Västerås,Sweden; Centre for Clinical Research, Hospital of Västmanland, Uppsala University, Västerås, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Microbiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Department of Infectious Diseases, Department of Clinical and Experimental Medicine, Linköping University, Norrköping, Sweden.
    Särndahl, Eva
    Örebro University, School of Medical Sciences.
    Demirel, Isak
    Örebro University, School of Medical Sciences.
    Staphylococcus epidermidis from prosthetic joint infections induces lower IL-1 release from human neutrophils than isolates from normal flora2018In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 126, no 8, p. 678-684Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to test the hypothesis that Staphylococcus epidermidis isolated from prosthetic joint infections (PJIs) differs from S.epidermidis isolated from normal flora in terms of its capacity to induce activation of caspase-1 and release of IL-1 in human neutrophils. The amount of active caspase-1 was determined over 6h by detecting Ac-YVAD-AMC fluorescence in human neutrophils incubated with S.epidermidis isolates from PJIs (ST2) or normal flora. The amount of IL-1 was detected by ELISA in neutrophil supernatants after 6h of incubation. Mean IL-1 release was lower after incubation with S.epidermidis from PJIs compared to isolates from normal flora, but no statistically significant difference was found in active caspase-1. Substantial inter-individual differences in both active caspase-1 and IL-1 were noted. These results suggest that evasion of innate immune response, measured as reduced capacity to induce release of IL-1 from human neutrophils, might be involved in the predominance of ST2 in S.epidermidis PJIs, but that other microbe-related factors are probably also important.

  • 7.
    Månsson, Emeli
    et al.
    Örebro University, School of Medical Sciences. Region Västmanland – Uppsala University, Centre for Clinical Research, Hospital of Västmanland, Västerås, Västerås, Sweden..
    Tevell, Staffan
    Örebro University, School of Medical Sciences. Department of Infectious Diseases, Karlstad Hospital and Centre for Clinical Research, County Countil of Värmland, Karlstad, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Department of Infectious Diseases, and Department of Clinical and Experimental Medicine, Linköping University, Norrköping, Sweden.
    Stegger, Marc
    Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Clinical Microbiology.
    Methicillin resistant Staphylococcus epidermidis lineages in the nasal and skin microbiota of patients scheduled for arthroplasty surgeryManuscript (preprint) (Other academic)
  • 8.
    Salih, Lavin
    et al.
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Tevell, Staffan
    Örebro University, School of Medical Sciences. Department of Infectious Diseases, Karlstad Hospital, Karlstad, Sweden.
    Månsson, Emeli
    Örebro University, School of Medical Sciences. Centre for Clinical Research, Hospital of Västmanland, Region Västmanland, Västerås, Sweden; Centre for Clinical Research, Hospital of Västmanland, Uppsala University, Västerås, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Infectious Diseases, County Council of Östergötland, Linköping, Sweden.
    Hellmark, Bengt
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Staphylococcus epidermidis isolates from nares and prosthetic joint infections are mupirocin susceptible2018In: Journal of bone and joint infection, ISSN 2206-3552, Vol. 3, no 1, p. 1-4Article in journal (Refereed)
    Abstract [en]

    The objective of the present study was to investigate the antibiotic susceptibility including mupirocin among Staphylococcus. epidermidis isolated from prosthetic joint infections (PJIs) (n=183) and nasal isolates (n=75) from patients intended to undergo prosthetic joint replacements. Susceptibility to mupirocin (used for eradication of nasal carriership of Staphylococcus aureus) was investigated by gradient test, and susceptibility to various other antimicrobial agents was investigated by disc diffusion test. All isolates, except three from PJIs and one from the nares, were fully susceptible to mupirocin. Multi-drug resistance (≥3 antibiotic classes) was found in 154/183 (84.2%) of the PJI isolates but only in 2/75 (2.7%) of the nares isolates, indicating that S. epidermidis causing PJIs do not originate from the nares.

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