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  • 1.
    Hällgren, Anita
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Lindqvist, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases.
    Enterococcal endocarditis among intravenous drug users: Report of a cluster of cases, possibly caused by contaminated amphetamine2011In: SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES, ISSN 0036-5548, Vol. 43, no 5, p. 395-398Article in journal (Refereed)
    Abstract [en]

    Intravenous drug use imposes a high risk of acquiring bacterial infections. In this report we present 3 cases of enterococcal endocarditis in intravenous drug users, diagnosed over a period of 3 months. Genotyping revealed that 2 of the cases were caused by closely related isolates, suggesting possible spread by contaminated drugs.

  • 2.
    Kågedal, Bertil
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Lindqvist, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine.
    Farnebäck, Malin
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry.
    Lenner, Liselotte
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Experimental Hematology .
    Peterson, Curt
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Clinical Pharmacology . Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Failure of the PAXgene™ Blood RNA System to maintain mRNA stability in whole blood2005In: Clinical Chemistry and Laboratory Medicine, ISSN 1434-6621, E-ISSN 1437-4331, Vol. 43, no 11, p. 1190-1192Article in journal (Refereed)
    Abstract [en]

    In multicentre studies of malignant and inflammatory diseases, whole blood, cell or tissue samples are often collected for analyses of gene expression to predict or monitor treatment effects. For correct analysis, sample stability during handling and transport is crucial. In developing the logistics for multicentre studies in malignant melanoma and inflammatory bowel disease, we found poor stability of a number of transcripts using the PAXgene™ Blood RNA System, which was advertised to maintain RNA stability for several days at room temperature. The results indicate that general statements on sample stability are not reliable and have to be verified for the specific transcripts of interest. © 2005 by Walter de Gruyter. Berlin.

  • 3.
    Lindqvist, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Health and Developmental Care, Department of Infection Control.
    Epidemiological and molecular biological studies of multi-resistant methicillin-susceptible Staphylococcus aureus2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Antibiotic resistance is increasingly recognised as a major problem and threat. During the last decades Gram-positive bacteria in general, and methicillin-resistant Staphylococcus aureus (MRSA) in particular, have been in focus both concerning matters of antibiotic resistance and as pathogens causing health care-associated (nosocomial) infections. In contrast to MRSA, studies on clonal distribution of methicillin-susceptible S. aureus (MSSA) are scarce. However, interest in MSSA has increased since it was shown that MRSA emerges from susceptible backgrounds by acquisition of a staphylococcal cassette chromosome element, carrying the mecA gene encoding methicillin-resistance (SCCmec).

    In an outbreak investigation of MRSA in Östergötland County, Sweden, in 2005, a high incidence of MSSA isolates with concomitant resistance to erythromycin, clindamycin and tobramycin (ECT-R) was detected. Analysis showed that 91 % of the investigated isolates were genetically related (clonal). The ECT-R clone was divided into four different but closely related patterns with pulsed-field gel electrophoresis (PFGE), and was designated spa type t002. Whole genome sequencing revealed that the ECT-R clone carried a pseudo-SCC element estimated to be 12 kb in size, showing a resemblance of more than 99 % with the SCCmec type II element of MRSA strain N315 (New York/Japan clone). This suggested a probable derivation from a highly successful MRSA strain, which had partially excised its SCCmec. The clonal outbreak was concentrated in eight hospital departments and two primary care centres, all located in the city of Linköping. Despite a high exchange of patients with the hospitals in the neighbouring counties in southeast Sweden (Jönköping- and Kalmar County), the ECT-R clone seemed to be limited to Östergötland County. However, a tobramycin-resistant clone predominated by isolates of spa type t084 was found in all three counties in southeast Sweden, and in particular among newborns, suggesting inter-hospital transmission.

    The ECT-R clone has survived as an abundant MSSA clone for a decade in Östergötland County, which indicates an insufficiency in the maintenance of basic hygiene guidelines, and that the clone probably possesses mechanisms of virulence and transmission that are yet to be discovered.

    List of papers
    1. A clonal outbreak of methicillin-susceptible Staphylococcus aureus with concomitant resistance to erythromycin, clindamycin and tobramycin in a Swedish county
    Open this publication in new window or tab >>A clonal outbreak of methicillin-susceptible Staphylococcus aureus with concomitant resistance to erythromycin, clindamycin and tobramycin in a Swedish county
    Show others...
    2009 (English)In: SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES, ISSN 0036-5548, Vol. 41, no 5, p. 324-333Article in journal (Refereed) Published
    Abstract [en]

    In contrast to methicillin-resistant Staphylococcus aureus (MRSA), studies on clonal distribution of methicillin-susceptible S. aureus (MSSA) are scarce. Since 2004, an increasing incidence of concomitant resistance to erythromycin, clindamycin and tobramycin (ECT) among MSSA has been detected in Ostergotland County, Sweden. The objectives of this study were to investigate the genetic relatedness among these isolates with 2 genotyping methods, pulsed-field gel electrophoresis (PFGE), and sequence-based typing of the polymorphic region X of the staphylococcal protein A gene (spa typing), and to determine the incidence of the Panton-Valentine leukocidin (PVL) gene. When genotyping 54 ECT-resistant MSSA isolates from 49 patients (1 isolate per patient per y), 91% were shown to be part of a clonal outbreak with both methods used (spa type t002). The clonal outbreak was concentrated in 8 hospital departments and 2 primary care centres, all located in the city of Linkoping. All isolates were negative for the PVL gene. In conclusion, this study demonstrates an ongoing clonal outbreak of PVL-negative ECT-resistant MSSA. This stresses the need to continuously maintain basic hygiene rules, since nosocomial transmission of pathogens is not limited to known resistant bacteria such as MRSA.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-18138 (URN)10.1080/00365540902801202 (DOI)
    Available from: 2009-05-09 Created: 2009-05-08 Last updated: 2014-01-22
    2. Detection and characterisation of SCCmec remnants in multiresistant methicillin-susceptible Staphylococcus aureus causing a clonal outbreak in a Swedish county
    Open this publication in new window or tab >>Detection and characterisation of SCCmec remnants in multiresistant methicillin-susceptible Staphylococcus aureus causing a clonal outbreak in a Swedish county
    Show others...
    2012 (English)In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 31, no 2, p. 141-147Article in journal (Refereed) Published
    Abstract [en]

    The purpose of this study was to investigate if multiresistant methicillin-susceptible Staphylococcus aureus (MR-MSSA) causing a clonal outbreak in A-stergotland County, Sweden, were derived from methicillin-resistant S. aureus (MRSA) by carrying remnants of SCCmec, and, if so, to characterise this element. A total of 54 MSSA isolates with concomitant resistance to erythromycin, clindamycin and tobramycin from 49 patients (91% clonally related, spa type t002) were investigated with the BD GeneOhm MRSA assay and real-time polymerase chain reaction (PCR) targeting the SCCmec integration site/SCCmec right extremity junction. DNA sequencing of one isolate representing the MR-MSSA outbreak clone was performed by massive parallel 454 pyrosequencing. All isolates that were part of the clonal outbreak carried SCCmec remnants. The DNA sequencing revealed the carriage of a pseudo-SCC element 12 kb in size, with a genomic organisation identical to an SCCmec type I (TM) I (TM) element, except for a 41-kb gap. This study demonstrates the presence of a pseudo-SCC element resembling SCCmec type II among MR-MSSA, suggesting possible derivation from MRSA. The presence of SCCmec remnants should always be considered when SCCmec typing is used for MRSA detection, and may not be suitable in locations with a high prevalence of MR-MSSA, since this might give a high number of false-positive results.

    Place, publisher, year, edition, pages
    Springer Verlag (Germany), 2012
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-74635 (URN)10.1007/s10096-011-1286-y (DOI)000298855900006 ()
    Note

    Funding Agencies|Ostergotland County Council||Scandinavian Society for Antimicrobial Chemotherapy (SSAC)|2009-22495|

    Available from: 2012-02-03 Created: 2012-02-03 Last updated: 2017-12-08
    3. Genetic relatedness of multi-resistant methicillin-susceptible Staphylococcus aureus in southeast Sweden
    Open this publication in new window or tab >>Genetic relatedness of multi-resistant methicillin-susceptible Staphylococcus aureus in southeast Sweden
    Show others...
    2014 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: A high exchange of patients occurs between the hospitals in southeast Sweden, resulting in a possible transmission of nosocomial pathogens. The objective of this study was to investigate the incidence and possible genetic relatedness of multi-resistant methicillinsusceptible Staphylococcus aureus (MSSA) in the region in general, and in particular the possible persistence and transmission of the ECT-R clone (t002) showing resistance to erythromycin, clindamycin and tobramycin previously found in Östergötland County.

    Methods: Three groups of S. aureus isolates with different antibiotic resistance profiles, including the ECT-R profile, were collected from the three County Councils in southeast Sweden and investigated with spa typing, real-time PCR targeting the staphylococcal cassette chromosome (SCC) mec right extremity junction (MREJ), and microarray.

    Results: All isolates with the ECT-R resistance profile (n = 12) from Östergötland County and two additional isolates with another antibiotic resistance profile were designated spa type t002, MREJ type ii, and were clustered in the same clonal cluster (CC) (i.e. CC5) by the microarray result, indicating the persistence of the ECT-R clone. In addition, 60 % of the isolates belonged to CC15 from newborns, with 94 % sharing spa type t084, indicating interhospital transmission.

    Conclusions: The persistence of the ECT-R clone and the possible transmission of the t084 strain indicate that there is still an insufficiency in the maintenance of basic hygiene guidelines. The ECT-R clone probably possesses mechanisms of virulence and transmission that make it so successful.

    Keywords
    MSSA, multi-resistance, genetic relatedness, t002, t084
    National Category
    Clinical Medicine Medical Genetics
    Identifiers
    urn:nbn:se:liu:diva-103678 (URN)
    Available from: 2014-01-22 Created: 2014-01-22 Last updated: 2018-01-11Bibliographically approved
  • 4.
    Lindqvist, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Health and Developmental Care, Vårdhygien.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Microbiology. Östergötlands Läns Landsting, Centre for Health and Developmental Care, Vårdhygien.
    Grub, C.
    Oslo University Hospital.
    Jonassen, T. Ö.
    Oslo University Hospital.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Detection and characterisation of SCCmec remnants in multiresistant methicillin-susceptible Staphylococcus aureus causing a clonal outbreak in a Swedish county2012In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 31, no 2, p. 141-147Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to investigate if multiresistant methicillin-susceptible Staphylococcus aureus (MR-MSSA) causing a clonal outbreak in A-stergotland County, Sweden, were derived from methicillin-resistant S. aureus (MRSA) by carrying remnants of SCCmec, and, if so, to characterise this element. A total of 54 MSSA isolates with concomitant resistance to erythromycin, clindamycin and tobramycin from 49 patients (91% clonally related, spa type t002) were investigated with the BD GeneOhm MRSA assay and real-time polymerase chain reaction (PCR) targeting the SCCmec integration site/SCCmec right extremity junction. DNA sequencing of one isolate representing the MR-MSSA outbreak clone was performed by massive parallel 454 pyrosequencing. All isolates that were part of the clonal outbreak carried SCCmec remnants. The DNA sequencing revealed the carriage of a pseudo-SCC element 12 kb in size, with a genomic organisation identical to an SCCmec type I (TM) I (TM) element, except for a 41-kb gap. This study demonstrates the presence of a pseudo-SCC element resembling SCCmec type II among MR-MSSA, suggesting possible derivation from MRSA. The presence of SCCmec remnants should always be considered when SCCmec typing is used for MRSA detection, and may not be suitable in locations with a high prevalence of MR-MSSA, since this might give a high number of false-positive results.

  • 5.
    Lindqvist, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Health and Developmental Care, Department of Infection Control.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Health and Developmental Care, Department of Infection Control. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Microbiology.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Wistedt, Annika
    Department of Clinical Microbiology and Infection Control, Kalmar County Hospital, Kalmar, Sweden.
    Swanberg, Jonas
    Clinical Microbiology Laboratory, Ryhov Hospital, Jönköping, Sweden.
    Skov, Robert
    Staphylococcus Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
    Rhod Larsen, Anders
    Staphylococcus Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
    Larsen, Jesper
    Staphylococcus Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
    Petersen, Andreas
    Staphylococcus Laboratory, Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Genetic relatedness of multi-resistant methicillin-susceptible Staphylococcus aureus in southeast Sweden2014Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: A high exchange of patients occurs between the hospitals in southeast Sweden, resulting in a possible transmission of nosocomial pathogens. The objective of this study was to investigate the incidence and possible genetic relatedness of multi-resistant methicillinsusceptible Staphylococcus aureus (MSSA) in the region in general, and in particular the possible persistence and transmission of the ECT-R clone (t002) showing resistance to erythromycin, clindamycin and tobramycin previously found in Östergötland County.

    Methods: Three groups of S. aureus isolates with different antibiotic resistance profiles, including the ECT-R profile, were collected from the three County Councils in southeast Sweden and investigated with spa typing, real-time PCR targeting the staphylococcal cassette chromosome (SCC) mec right extremity junction (MREJ), and microarray.

    Results: All isolates with the ECT-R resistance profile (n = 12) from Östergötland County and two additional isolates with another antibiotic resistance profile were designated spa type t002, MREJ type ii, and were clustered in the same clonal cluster (CC) (i.e. CC5) by the microarray result, indicating the persistence of the ECT-R clone. In addition, 60 % of the isolates belonged to CC15 from newborns, with 94 % sharing spa type t084, indicating interhospital transmission.

    Conclusions: The persistence of the ECT-R clone and the possible transmission of the t084 strain indicate that there is still an insufficiency in the maintenance of basic hygiene guidelines. The ECT-R clone probably possesses mechanisms of virulence and transmission that make it so successful.

  • 6.
    Lindqvist, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Samuelsson, Annika
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Microbiology . Linköping University, Faculty of Health Sciences.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    A clonal outbreak of methicillin-susceptible Staphylococcus aureus with concomitant resistance to erythromycin, clindamycin and tobramycin in a Swedish county2009In: SCANDINAVIAN JOURNAL OF INFECTIOUS DISEASES, ISSN 0036-5548, Vol. 41, no 5, p. 324-333Article in journal (Refereed)
    Abstract [en]

    In contrast to methicillin-resistant Staphylococcus aureus (MRSA), studies on clonal distribution of methicillin-susceptible S. aureus (MSSA) are scarce. Since 2004, an increasing incidence of concomitant resistance to erythromycin, clindamycin and tobramycin (ECT) among MSSA has been detected in Ostergotland County, Sweden. The objectives of this study were to investigate the genetic relatedness among these isolates with 2 genotyping methods, pulsed-field gel electrophoresis (PFGE), and sequence-based typing of the polymorphic region X of the staphylococcal protein A gene (spa typing), and to determine the incidence of the Panton-Valentine leukocidin (PVL) gene. When genotyping 54 ECT-resistant MSSA isolates from 49 patients (1 isolate per patient per y), 91% were shown to be part of a clonal outbreak with both methods used (spa type t002). The clonal outbreak was concentrated in 8 hospital departments and 2 primary care centres, all located in the city of Linkoping. All isolates were negative for the PVL gene. In conclusion, this study demonstrates an ongoing clonal outbreak of PVL-negative ECT-resistant MSSA. This stresses the need to continuously maintain basic hygiene rules, since nosocomial transmission of pathogens is not limited to known resistant bacteria such as MRSA.

  • 7.
    Lindqvist, Maria
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Health and Developmental Care, Department of Infection Control.
    Isaksson, Barbro
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Health and Developmental Care, Department of Infection Control.
    Swanberg, J.
    Ryhov Hospital, Sweden.
    Skov, R.
    Statens Serum Institute, Denmark.
    Larsen, A. R.
    Statens Serum Institute, Denmark.
    Larsen, J.
    Statens Serum Institute, Denmark.
    Petersen, A.
    Statens Serum Institute, Denmark.
    Hällgren, Anita
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Faculty of Medicine and Health Sciences.
    Long-term persistence of a multi-resistant methicillin-susceptible Staphylococcus aureus (MR-MSSA) clone at a university hospital in southeast Sweden, without further transmission within the region2015In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 34, no 7, p. 1415-1422Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to characterise isolates of methicillin-susceptible Staphylococcus aureus (MSSA) with resistance to clindamycin and/or tobramycin in southeast Sweden, including the previously described ECT-R clone (t002) found in Östergotland County, focusing on clonal relatedness, virulence determinants and existence of staphylococcal cassette chromosome (SCC) mec remnants. MSSA isolates with resistance to clindamycin and/or tobramycin were collected from the three county councils in southeast Sweden and investigated with spa typing, polymerase chain reaction (PCR) targeting the SCCmec right extremity junction (MREJ) and DNA microarray technology. The 98 isolates were divided into 40 spa types, and by microarray clustered in 17 multi-locus sequence typing (MLST) clonal complexes (MLST-CCs). All isolates with combined resistance to clindamycin and tobramycin (n = 12) from Östergotland County and two additional isolates (clindamycin-R) were designated as spa type t002, MREJ type ii and were clustered in CC5, together with a representative isolate of the ECT-R clone, indicating the clones persistence. These isolates also carried several genes encoding exotoxins, Q9XB68-dcs and qacC. Of the isolates in CC15, 83 % (25/30) were tobramycin-resistant and were designated spa type t084. Of these, 68 % (17/25) were isolated from new-borns in all three counties. The persistence of the ECT-R clone in Östergotland County, although not found in any other county in the region, carrying certain virulence factors that possibly enhance its survival in the hospital environment, highlights the fact that basic hygiene guidelines must be maintained even when MRSA prevalence is low.

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