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  • 1.
    Backhaus, Erik
    et al.
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Berg, Stefan
    Queen Silvia Children's Hospital, Göteborg, Sweden.
    Trollfors, Birger
    Queen Silvia Children's Hospital, Göteborg, Sweden.
    Andersson, Rune
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Persson, Elisabet
    Queen Silvia Children's Hospital, Göteborg, Sweden.
    Claesson, Bernt E. B.
    Department of Clinical Bacteriology, Skaraborg Hospital, Skövde, Sweden.
    Larsson, Peter
    Department of Clinical Bacteriology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Ek, Elisabeth
    Department of Clinical Bacteriology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Jonsson, Lars
    Department of Clinical Bacteriology, Borås Hospital, Borås, Sweden.
    Rådberg, Gunilla
    Uddevalla Hospital, Uddevalla, Sweden.
    Johansson, Siv
    Halmstad Hospital, Halmstad, Sweden.
    Ripa, Torvald
    Halmstad Hospital, Halmstad, Sweden.
    Karlsson, Diana
    University of Skövde, School of Life Sciences.
    Andersson, Kerstin
    Department of Clinical Bacteriology, Skaraborg Hospital, Skövde, Sweden.
    Antimicrobial susceptibility of invasive pneumococcal isolates from a region in south-west Sweden 1998-20012007In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 39, no 1, p. 19-27Article in journal (Refereed)
    Abstract [en]

    Invasive disease caused by antibiotic resistant pneumococci is a worldwide problem. All invasive pneumococcal strains in an area of south-west Sweden with 1.7 million inhabitants were collected prospectively during 1998-2001. Minimum inhibitory concentrations (MICs) were determined by E-test and correlated to serotypes and clinical characteristics. Of 827 strains, 744 (90%) were susceptible (S) to all agents tested and 83 (10%) were indeterminate (I) or resistant (R) to at least 1 agent. 22 isolates (2.7%) were I to penicillin (MIC gt0.06 to ≤1.0 mg/l), but none were R (MIC gt1.0 mg/l). Numbers and proportions of decreased susceptibility against other agents tested were as follows: erythromycin R: 30 (3.6%), clindamycin R: 6 (0.7%), tetracycline R: 16 (1.9%), moxifloxacin R: 1 (0.1%), cotrimoxazole I: 17 (2%) and R: 31(4%). Non-susceptibility to at least 1 agent was not correlated with age, clinical manifestation, underlying diseases and outcome. The serotype distribution differed between non-susceptible and susceptible strains. The serotypes in the 7-valent pneumococcal conjugate vaccine covered 42% of all infections and 73% of those caused by non-susceptible strains. In conclusion, the impact of antibiotic resistance in invasive pneumococcal disease remains limited in south-west Sweden.

  • 2.
    Browall, Sarah
    et al.
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Backhaus, Erik
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Naucler, Pontus
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden / Department of Infectious Diseases, Karolinska University Hospital, Solna, Sweden.
    Galanis, Ilias
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Sjöström, Karin
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
    Karlsson, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Berg, Stefan
    Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Luthander, Joachim
    Department of Paediatrics, Karolinska University Hospital, Solna, Sweden.
    Eriksson, Margareta
    Department of Paediatrics, Karolinska University Hospital, Solna, Sweden.
    Spindler, Carl
    Department of Infectious Diseases, Karolinska University Hospital, Solna, Sweden.
    Ejdebäck, Mikael
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Trollfors, Birger
    Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Darenberg, Jessica
    Public Health Agency of Sweden, Solna, Sweden.
    Kalin, Mats
    Department of Infectious Diseases, Karolinska University Hospital, Solna, Sweden.
    Örtqvist, Åke
    Department of Communicable Diseases Control and Prevention, Stockholm County Council, Stockholm, Sweden / Department of Medicine, Unit of Infectious Diseases, Karolinska Institutet, Solna, Sweden.
    Andersson, Rune
    Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
    Henriques-Normark, Birgitta
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden Dept of Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden.
    Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types2014In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 44, no 6, p. 1646-1657Article in journal (Refereed)
  • 3.
    Dave, Vivek Priy
    et al.
    Technical University of Denmark, Lyngby, Denmark.
    Ngo, Tien Anh
    Technical University of Denmark, Lyngby, Denmark.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Kanit, Krishna
    Technical University of Denmark, Lyngby, Denmark.
    Nguyen, Trieu
    Technical University of Denmark, Lyngby, Denmark.
    Wolff, Anders
    Technical University of Denmark, Lyngby, Denmark.
    Bang, Dang Duong
    Technical University of Denmark, Lyngby, Denmark.
    MicroRNA amplification and detection technologies: opportunities and challenges for point of care diagnostics2018In: Laboratory Investigation, ISSN 0023-6837, E-ISSN 1530-0307, Vol. 99, no 4, p. 452-469Article, review/survey (Refereed)
    Abstract [en]

    The volume of point of care (POC) testing continues to grow steadily due to the increased availability of easy-to-use devices, thus making it possible to deliver less costly care closer to the patient site in a shorter time relative to the central laboratory services. A novel class of molecules called microRNAs have recently gained attention in healthcare management for their potential as biomarkers for human diseases. The increasing interest of miRNAs in clinical practice has led to an unmet need for assays that can rapidly and accurately measure miRNAs at the POC. However, the most widely used methods for analyzing miRNAs, including Northern blot-based platforms, in situ hybridization, reverse transcription qPCR, microarray, and next-generation sequencing, are still far from being used as ideal POC diagnostic tools, due to considerable time, expertize required for sample preparation, and in terms of miniaturizations making them suitable platforms for centralized labs. In this review, we highlight various existing and upcoming technologies for miRNA amplification and detection with a particular emphasis on the POC testing industries. The review summarizes different miRNA targets and signals amplification-based assays, from conventional methods to alternative technologies, such as isothermal amplification, paper-based, oligonucleotide-templated reaction, nanobead-based, electrochemical signaling-based, and microfluidic chip-based strategies. Based on critical analysis of these technologies, the possibilities and feasibilities for further development of POC testing for miRNA diagnostics are addressed and discussed.

  • 4.
    Enroth, Helena
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Retz, Karolina
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Andersson, Sofie
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Andersson, Carl
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Svensson, Kristina
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Ljungström, Lars
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Evaluation of QuickFISH and maldi Sepsityper for identification of bacteria in bloodstream infection2019In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 51, no 4, p. 249-258Article in journal (Refereed)
    Abstract [en]

    Background: Early detection of bacteria and their antibiotic susceptibility patterns are critical to guide therapeutic decision-making for optimal care of septic patients. The current gold standard, blood culturing followed by subculture on agar plates for subsequent identification, is too slow leading to excessive use of broad-spectrum antibiotic with harmful consequences for the patient and, in the long run, the public health. The aim of the present study was to assess the performance of two commercial assays, QuickFISH® (OpGen) and Maldi Sepsityper™ (Bruker Daltonics) for early and accurate identification of microorganisms directly from positive blood cultures.

    Materials and methods: During two substudies of positive blood cultures, the two commercial assays were assessed against the routine method used at the clinical microbiology laboratory, Unilabs AB, at Skaraborg Hospital, Sweden.

    Results: The Maldi Sepsityper™ assay enabled earlier microorganism identification. Using the cut-off for definite species identification according to the reference method (>2.0), sufficiently accurate species identification was achieved, but only among Gram-negative bacteria. The QuickFISH®assay was time-saving and showed high concordance with the reference method, 94.8% (95% CI 88.4–98.3), when the causative agent was covered by the QuickFISH® assay.

    Conclusions: The use of the commercial assays may shorten the time to identification of causative agents in bloodstream infections and can be a good complement to the current clinical routine diagnostics. Nevertheless, the performance of the commercial assays is considerably affected by the characteristics of the causative agents.

  • 5.
    Enroth, Helena
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Unilabs AB.
    Wefer, Hugo
    Clinical genomics, Science for Life Laboratories.
    Ljungström, Lars
    Dept. of Infectious Diseases, Skaraborg Hospital Skövde.
    Tilevik, Diana
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    NGS pilot study of E. coli ESBL from patients with suspected sepsis2015Conference paper (Refereed)
  • 6.
    Helldin, Tove
    et al.
    University of Skövde, School of Informatics. University of Skövde, The Informatics Research Centre.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Towards a Clinical Support System for the Early Diagnosis of Sepsis2017In: Digital Human Modeling - Applications in Health, Safety, Ergonomics, and Risk Management: Health and Safety: 8th International Conference, DHM 2017 Held as Part of HCI International 2017 Vancouver, BC, Canada, July 9–14, 2017, Proceedings, Part II / [ed] Vincent G. Duffy, Springer, 2017, p. 23-35Conference paper (Refereed)
    Abstract [en]

    Early and accurate diagnosis of sepsis is critical for patientsafety. However, this is a challenging task due to the very general symptomsassociated with sepsis, the immaturity of the tools used by theclinicians as well as the time-delays associated with the diagnostic methodsused today. This paper explores current literature regarding guidelinesfor clinical decision support, and support for sepsis diagnosis inparticular, together with guidelines extracted from interviews with fourclinicians and one biomedical analyst working at a hospital and clinicallaboratory in Sweden. The results indicate the need for the developmentof visual and interactive aids for enabling early and accurate diagnosisof sepsis.

  • 7.
    Jansson, Andreas
    et al.
    University of Skövde, School of Life Sciences.
    Fagerlind, Magnus
    University of Skövde, School of Life Sciences.
    Karlsson, Diana
    University of Skövde, School of Life Sciences.
    Nilsson, Patric
    University of Skövde, School of Life Sciences.
    Cooley, Margaret
    School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
    In silico simulations suggest that Th-cell development is regulated by both selective and instructive mechanisms2006In: Immunology and Cell Biology, ISSN 0818-9641, E-ISSN 1440-1711, Vol. 84, no 2, p. 218-226Article in journal (Refereed)
    Abstract [en]

    Th-cell differentiation is highly influenced by the local cytokine environment. Although cytokines such as IL-12 and IL-4 are known to polarize the Th-cell response towards Th1 or Th2, respectively, it is not known whether these cytokines instruct the developmental fate of uncommitted Th cells or select cells that have already been committed through a stochastic process. We present an individual based model that accommodates both stochastic and deterministic processes to simulate the dynamic behaviour of selective versus instructive Th-cell development. The predictions made by each model show distinct behaviours, which are compared with experimental observations. The simulations show that the instructive model generates an exclusive Th1 or Th2 response in the absence of an external cytokine source, whereas the selective model favours coexistence of the phenotypes. A hybrid model, including both instructive and selective development, shows behaviour similar to either the selective or the instructive model dependent on the strength of activation. The hybrid model shows the closest qualitative agreement with a number of well-established experimental observations. The predictions by each model suggest that neither pure selective nor instructive Th development is likely to be functional as exclusive mechanisms in Th1/Th2 development.

  • 8.
    Karlsson, Diana
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Probabilistic network modelling of the impact of penicillin consumption on spread of pneumococci2011In: Epidemiology and Infection, ISSN 0950-2688, E-ISSN 1469-4409, Vol. 139, no 9, p. 1351-1360Article in journal (Refereed)
    Abstract [en]

    The worldwide increase of resistant S. pneumoniae is a growing clinical problem. In several countries, a more restrictive use of penicillin has been promoted in hope of slowing the rates of resistant pneumococci. However, the consequences of such an action on pneumococcal population dynamics are not fully understood. Thus, a network model was constructed to assess the impacts of penicillin consumption and between-strain competition on the spread of penicillin non-susceptible pneumococci. Model simulations suggest that the age distribution for carriage of penicillin non-susceptible pneumococci, in contrast to susceptible pneumococci, is affected by penicillin consumption. Furthermore, it appears extremely difficult to reduce the incidence of penicillin non-susceptible pneumococci by simply controlling penicillin consumption, assuming that reduced penicillin susceptibility does not confer a fitness cost for the organism. A more judicious use of penicillin together with control measures are in that case required to manage penicillin resistance in pneumococci.

  • 9.
    Karlsson, Diana
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Studies on emergence and spread of antibiotic resistant Streptococcus pneumoniae2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Streptococcus pneumoniae is one of the major contributors to mortality and morbidity around  the  world.  It  causes  a  wide  variety  of  diseases  ranging  from  uncomplicated respiratory  infections  to  life-threatening  invasive  infections  such  as  meningitis  and septicemia. In recent years, the effectiveness of antibiotic therapy has been hampered by  the  increasing  rates  of  resistant  pneumococci.  As  antibiotic  resistance  increases, there is a growing need for interventions that minimize opportunities for development and spread  of resistant  pneumococci.  The aim  of this  thesis  was  to learn  more  about emergence  and  spread  of  antibiotic  resistant  pneumococci  using  both  theoretical  and empirical methods.  Since the increasing prevalence of resistant pneumococci is mainly due to the spread of strains belonging to few clones, interventions for controlling pneumococcal transmission  in  the  community  were  studied.  Model  predictions  suggested  that interventions for efficiently control organism transmission should include reduction of group sizes in the day-care centers. Simulations also indicated that it appears extremely difficult  to  reduce  the  rates  of  penicillin  non-susceptible  pneumococci  by  simply decreasing  the  penicillin  consumption  assumed  that  reduced  penicillin  susceptibility does not imply a fitness cost for the organism. Managing the penicillin resistance rates in pneumococci then probably requires a more restrictive use of penicillin together with other  control  measures  such  as  vaccine  programs.  Although  clonal  spread  is  the primary  mechanism  for  the  rapid  emergence  of  resistance  in  pneumococci,  natural competence  for  genetic  transformation  also  seems  to  be  involved.  Further  molecular understanding  of competence regulation  is  important  to be  able  to prevent  horizontal spread  of  resistance  genes.  Studying  the  competence  regulation  by  theoretical  means led  to  the  conclusion  that  down-regulation  of  competence  is  probably  caused  by  a repressor acting on the comCDE operon at the level of transcription.  Despite the globally emerging frequency of resistant pneumococci, we conclude in a prospective study that antimicrobial resistance in invasive pneumococci in south-west Sweden remains limited. Any correlations between resistance pattern and clinical parameters could not be revealed. However, the serotype distribution was observed to differ  between  strains  with  reduced  susceptibility  and  fully  susceptible  strains  as isolates  with  decreased  susceptibility  more  frequently  belonged  to  the  serotypes included in the 7-valent vaccine.

  • 10.
    Karlsson, Diana
    et al.
    University of Skövde, School of Life Sciences.
    Jansson, Andreas
    University of Skövde, School of Life Sciences.
    Normark, Birgitta Henriques
    Karolinska Inst, Swedish Inst Infect Dis Control, Dept Bacteriol, SE-17182 Solna, Sweden / Karolinska Inst, Dept Microbiol Tumor Biol & Cell Biol, SE-17177 Stockholm, Sweden.
    Nilsson, Patric
    University of Skövde, School of Life Sciences.
    An individual-based network model to evaluate interventions for controlling pneumococcal transmission2008In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 8, p. 83-Article in journal (Refereed)
    Abstract [en]

    Background: Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide, but also a common colonizer of the upper respiratory tract. The emergence and spread of antibiotic resistant pneumococcal strains has threatened effective therapy. The long-term effects of measures aiming to limit pneumococcal spread are poorly understood. Computational modeling makes it possible to conduct virtual experiments that are impractical to perform in real life and thereby allows a more full understanding of pneumococcal epidemiology and control efforts. Methods: We have developed a contact network model to evaluate the efficacy of interventions aiming to control pneumococcal transmission. Demographic data from Sweden during the mid-2000s were employed. Analyses of the model's parameters were conducted to elucidate key determinants of pneumococcal spread. Also, scenario simulations were performed to assess candidate control measures. Results: The model made good predictions of previous findings where a correlation has been found between age and pneumococcal carriage. Of the parameters tested, group size in day-care centers was shown to be one of the most important factors for pneumococcal transmission. Consistent results were generated from the scenario simulations. Conclusion: We recommend, based on the model predictions, that strategies to control pneumococcal disease and organism transmission should include reducing the group size in day-care centers.

  • 11.
    Karlsson, Diana
    et al.
    University of Skövde, School of Life Sciences.
    Karlsson, Stefan
    University of Skövde, School of Life Sciences.
    Gustafsson, Erik
    University of Skövde, School of Life Sciences.
    Henriques Normark, Birgitta
    Swedish Institute for Infectious Disease Control, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
    Nilsson, Patric
    University of Skövde, School of Life Sciences.
    Modeling the regulation of the competence-evoking quorum sensing network in Streptococcus pneumoniae2007In: Biosystems (Amsterdam. Print), ISSN 0303-2647, E-ISSN 1872-8324, Vol. 90, no 1, p. 211-223Article in journal (Refereed)
    Abstract [en]

    Competence for genetic transformation seems to play a fundamental role in the biology of Streptococcus pneumoniae and is believed to account for serotype switching, evolution of virulence factors, and rapid emergence of antibiotic resistance. The initiation of competence is regulated by the quorum sensing system referred as the ComABCDE pathway. Experimental studies reveal that competence is down-regulated a short time after its induction and several hypotheses about the mechanism(s) responsible for this shut-down have been presented. Possibly, a ComX-dependent gene product, such as a repressor or a phosphatase, is involved. To better understand the down-regulation of the competence-evoking system in S. pneumoniae, a mathematical model was set up. By analyzing the model, we suggest that shut-down of competence possibly occurs at the transcriptional level on the comCDE operon. As a result of introducing a putative comX-dependent repressor, which inhibits expression of comCDE and comX, in the mathematical model, competence is demonstrated to appear in waves. This is supported by experimental studies showing the appearance of successive competence cycles in pneumococcal batch cultures.

  • 12.
    Karlsson, Diana
    et al.
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Ljungström, Lars
    Department of Infectious Diseases- Skaraborg Hospital, Skövde, Sweden.
    Multimarker approach for sepsis diagnostics2015In: 25th European Congress of Clinical Mircobiology and Infectious Diseases, Copenhagen, April 25-28, 2015, European Society of ClinicalMicrobiology and Infectious Diseases (ESCMID) , 2015Conference paper (Refereed)
    Abstract [en]

    OBJECTIVES

    The aim of this study was to assess the performance of a multimarker model in distinguishing patients with sepsis from those with non-infective systemic inflammatory response.

    METHODS

    This study is part of a prospective study of community-onset severe sepsis and septic shock in adults conducted from September 2011 to June 2012 at Skaraborg Hospital, in the western region of Sweden. The levels of 92 inflammation-related human protein biomarkers were measured simultaneously using Proseek® Multiplex Inflammation I96x96 (Olink Bioscience, Sweden) in 122 plasma samples collected from patients suspected with sepsis. After pre-processing normalization procedure, measurements of the markers were obtained as Normalized Protein eXpression (NPX) units on a log2 scale (GenEx, MultiD Analyses AB, Sweden). The study was approved by the Regional Ethical Review Board of Gothenburg (376-11). All patients enrolled provided written informed consent.

    To reduce the number of markers, factor analysis was performed. Thereafter, a multimarker model for classification was derived using discriminant analysis. The multimarker model consisted of a linear function of the selected markers. Cross-validation was performed by classifying each sample by the discriminant function derived from all samples other than that specific sample. The performance was assessed as area under receiving operating characteristic (ROC) curve. The cut-off for sensitivity and specificity was derived from the cut score of the discriminant function. Statistical analyses were performed in SPSS 22.0 (IBM Corporation Somers, NY USA).

    RESULTS

    Of the 122 samples, 80 (66%) were from patients diagnosed with sepsis and 42 from patients with non-infective systemic inflammatory response syndrome (SIRS). The five markers selected for the multimarker model were interleukin-6 (IL-6), cystatin D (CST5), delta and notch-like epidermal growth factor-related receptor (DNER), STAM-binding protein (STAMPB), macrophage colony-stimulating factor 1 (CSF 1). Every single marker was statistically different between the groups (p value < 0.001), except for DNER (p value 0.064) and STAMPB (p value 0.060). The area under ROC was higher for the multimarker model (81%) than for each biomarker separately (Figure 1). The accuracy for the multimarker model was 72% [64-80, 95% CI]; sensitivity 84% [77-91, 95% CI]; specificity 60% [51-69, 95% CI]; positive predictive value 79% [72-86, 95% CI]; and negative predictive value 66% [58-74, 95% CI].

    CONCLUSION

    A higher power of discrimination is obtained by combining more than one biomarker. However, the multimarker candidates identified in this study need further assessment.

  • 13.
    Ljungström, Lars
    et al.
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Enroth, Helena
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Claesson, Berndt E. B.
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Ovemyr, Ida
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Karlsson, Jesper
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Fröberg, Berit
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Brodin, Anna-Karin
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Jacobsson, Gunnar
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Andersson, Rune
    Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden..
    Karlsson, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis2015In: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 15, no 1, article id 199Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Sepsis is a serious medical condition requiring timely administered, appropriate antibiotic therapy. Blood culture is regarded as the gold standard for aetiological diagnosis of sepsis, but it suffers from low sensitivity and long turnaround time. Thus, nucleic acid amplification tests (NAATs) have emerged to shorten the time to identification of causative microbes. The aim of the present study was to evaluate the clinical utility in everyday practice in the emergency department of two commercial NAATs in patients suspected with sepsis.

    METHODS: During a six-week period, blood samples were collected consecutively from all adult patients admitted to the general emergency department for suspicion of a community-onset sepsis and treated with intravenous antibiotics. Along with conventional blood cultures, multiplex PCR (Magicplex™) was performed on whole blood specimens whereas portions from blood culture bottles were used for analysis by microarray-based assay (Prove-it™). The aetiological significance of identified organisms was determined by two infectious disease physicians based on clinical presentation and expected pathogenicity.

    RESULTS: Among 382 episodes of suspected sepsis, clinically relevant microbes were detected by blood culture in 42 episodes (11%), by multiplex PCR in 37 episodes (9.7%), and by microarray in 32 episodes (8.4%). Although moderate agreement with blood culture (kappa 0.50), the multiplex PCR added diagnostic value by timely detection of 15 clinically relevant findings in blood culture-negative specimens. Results of the microarray corresponded very well to those of blood culture (kappa 0.90), but were available just marginally prior to blood culture results.

    CONCLUSIONS: The use of NAATs on whole blood specimens in adjunct to current culture-based methods provides a clinical add-on value by allowing for detection of organisms missed by blood culture. However, the aetiological significance of findings detected by NAATs should be interpreted with caution as the high analytical sensitivity may add findings that do not necessarily corroborate with the clinical diagnosis.

  • 14.
    Ljungström, Lars
    et al.
    Department of Infectious Diseases, Skaraborg Hospital.
    Jacobsson, Gunnar
    Department of Infectious Diseases, Skaraborg Hospital / The swedish strategic program against antibiotic resistance.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    The diagnostic value of PCT as biomarker in patients suspected with community-onset bacterial sepsis2017Conference paper (Refereed)
  • 15.
    Ljungström, Lars
    et al.
    Skaraborg Hospital Skövde, Sweden.
    Karlsson, Diana
    Skaraborg Hospital Skövde, Sweden.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Andersson, R.
    Institute of Biosciences, Sahlgrenska Academy at the University of Gothenburg, Sweden.
    Jacobsson, Gunnar
    Skaraborg Hospital Skövde, Sweden.
    Neutrophil to lymphocyte count ratio performs better than procalcitonin as a biomarker for bacteremia and severe sepsis in the emergency department2015In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 19, no Suppl 1, article id P66Article in journal (Refereed)
  • 16.
    Ljungström, Lars
    et al.
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Jacobsson, Gunnar
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden / CARe–Center for Antibiotic Resistance Research, Gothenburg University, Gothenburg, Sweden.
    Andersson, Rune
    CARe–Center for Antibiotic Resistance Research, Gothenburg University, Gothenburg, Sweden / Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University and Sahlgrenska University Hospital, Gothenburg, Sweden.
    Usener, Barbara
    Department of Clinical Chemistry, Unilabs AB, Skövde, Sweden.
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Diagnostic accuracy of procalcitonin, neutrophil-lymphocyte count ratio, C-reactive protein, and lactate in patients with suspected bacterial sepsis2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 7, article id e018704Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Early recognition is a key factor to achieve improved outcomes for septic patients. Combinations of biomarkers, as opposed to single ones, may improve timely diagnosis and survival. We investigated the performance characteristics of sepsis biomarkers, alone and in combination, for diagnosis of verified bacterial sepsis using Sepsis-2 and Sepsis-3 criteria, respectively.

    METHODS:

    Procalcitonin (PCT), neutrophil-lymphocyte count ratio (NLCR), C-reactive protein (CRP), and lactate were determined in a total of 1,572 episodes of adult patients admitted to the emergency department on suspicion of sepsis. All sampling were performed prior to antibiotic administration. Discriminant analysis was used to construct two composite biomarkers consisting of linear combinations of the investigated biomarkers, one including three selected biomarkers (i.e., NLCR, CRP, and lactate), and another including all four (i.e., PCT, NLCR, CRP, and lactate). The diagnostic performances of the composite biomarkers as well as the individual biomarkers were compared using the area under the receiver operating characteristic curve (AUC).

    RESULTS:

    For diagnosis of bacterial sepsis based on Sepsis-3 criteria, the AUC for PCT (0.68; 95% CI 0.65-0.71) was comparable to the AUCs for the both composite biomarkers. Using the Sepsis-2 criteria for bacterial sepsis diagnosis, the AUC for the NLCR (0.68; 95% CI 0.65-0.71) but not for the other single biomarkers, was equal to the AUCs for the both composite biomarkers. For diagnosis of severe bacterial sepsis or septic shock based on the Sepsis-2 criteria, the AUCs for both composite biomarkers were significantly greater than those of the single biomarkers (0.85; 95% CI 0.82-0.88 for the composite three-biomarker, and 0.86; 95% CI 0.83-0.89 for the composite four-biomarker).

    CONCLUSIONS:

    Combinations of biomarkers can improve the diagnosis of verified bacterial sepsis in the most critically ill patients, but in less severe septic conditions either the NLCR or PCT alone exhibit equivalent performance.

  • 17.
    Owemyr, Ida
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Enroth, Helena
    Unilabs AB, Skövde, Sweden.
    Ljungström, Lars
    Skaraborg Hospital, Skövde, Sweden.
    Jacobsson, Gunnar
    Skaraborgs Sjukhus, Skövde, Sweden.
    Pernestig, Anna-Karin
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Karlsson, Diana
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Evaluation of microarray-based assay for identification of bloodstream bacteria in patients with suspected sepsis2013Conference paper (Refereed)
  • 18.
    Owemyr, Ida
    et al.
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Life Sciences.
    Enroth, Helena
    Unilabs AB, Skövde.
    Ljungström, Lars
    Kärnsjukhuset, Skövde.
    Pernestig, Anna-Karin
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Karlsson, Diana
    University of Skövde, School of Life Sciences. University of Skövde, The Systems Biology Research Centre.
    Utvärdering av microarray-baserad plattform för snabb identifiering av patogener hos patienter med misstänkt sepsis2012Conference paper (Refereed)
  • 19.
    Retz, Carolina
    et al.
    University of Skövde, The Systems Biology Research Centre.
    Andersson, Sofie
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Enroth, Helena
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Ljungström, Lars
    Department of Infectious Diseases, Skaraborg Hospital.
    Karlsson, Diana
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    Pernestig, Anna-Karin
    University of Skövde, The Systems Biology Research Centre. University of Skövde, School of Bioscience.
    Quicker identification of Gram-positive cocci in clusters in patients with suspected sepsis2014Conference paper (Refereed)
    Abstract [en]

    Sepsis is the primary cause of death from infection. Globally, an estimated 18 million people die from sepsis annually, exceeding deaths caused by HIV/AIDS, breast cancer, and prostate cancer combined1. Early sepsis diagnosis and targeted antimicrobial (AM) therapy reduce the length of intensive care for patients and cost by 30%2. The current gold standard, using blood cultures (BC), takes 12-72 h to detect pathogens in the blood and even longer to identify the exact pathogen and its AM susceptibility for optimal therapy. The aim of this study was to determine whether the QuickFISHTMBC test (AdvanDx, Woburn, MA) could be robust, timesaving and specific in the clinical microbiology laboratory setting, for identification of the pathogens causing life-threatening bloodstream infections.

  • 20.
    Retz, Karolina
    et al.
    Department of Clinical Microbiology, Unilabs AB, Skövde.
    Andersson, Sofie
    Department of Clinical Microbiology, Unilabs AB, Skövde .
    Andersson, Carl
    University of Skövde.
    Svensson, Kristina
    Department of Clinical Microbiology, Unilabs AB, Skövde .
    Ljungström, Lars
    The Skaraborg Hospital, Skövde, Sweden .
    Enroth, Helena
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre. Department of Clinical Microbiology, Unilabs AB, Skövde .
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Pernestig, Anna-Karin
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Evaluation of the QuickFISH and the Sepsityper assays for early identification of etiological agents in bloodstream infection in a clinical routine setting2017Conference paper (Refereed)
  • 21.
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Long-term effects of penicillin resistance and fitness cost on pneumococcal transmission dynamics in a developed setting2016In: Infection Ecology & Epidemiology, ISSN 2000-8686, E-ISSN 2000-8686, Vol. 6, article id 31234Article in journal (Refereed)
    Abstract [en]

    Background: The increasing prevalence of penicillin non-susceptible pneumococci (PNSP) throughout the world threatens successful treatment of infections caused by this important bacterial pathogen. The rate at which PNSP clones spread in the community is thought to mainly be determined by two key determinants; the volume of penicillin use and the magnitude of the fitness cost in the absence of treatment. The aim of the study was to determine the impacts of penicillin consumption and fitness cost on pneumococcal transmission dynamics in a developed country setting.

    Methods: An individual-based network model based on real-life demographic data was constructed and applied in a developed country setting (Sweden). A population structure with transmission of carriage taking place within relevant mixing groups, i.e. families, day care groups, school classes, and other close contacts, was considered to properly assess the transmission dynamics for susceptible and PNSP clones. Several scenarios were simulated and model outcomes were statistically analysed.

    Results: Model simulations predicted that with an outpatient penicillin use corresponding to the sales in Sweden 2010 (118 recipes per 1,000 inhabitants per year), the magnitude of a fitness cost for resistance must be at least 5% to offset the advantage of penicillin resistance. Moreover, even if there is a fitness cost associated with penicillin resistance, a considerable reduction of penicillin usage appears to be required to significantly decrease the incidence of PNSP in a community.

    Conclusion: The frequency of PNSP clones is hard to reverse by simply reducing the penicillin consumption even if there is a biological cost associated with resistance. However, because penicillin usage does promote further spread of PNSP clones, it is important to keep down penicillin consumption considering future resistance problems.

  • 22.
    Wallenhammar, Ann-Charlotte
    et al.
    HS Konsult AB, Örebro, Sweden.
    Algerin, Maria
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Tilevik, Diana
    University of Skövde, School of Bioscience. University of Skövde, The Systems Biology Research Centre.
    Ny metod bedömer risk för bomullsmögel2017In: Arvensis, ISSN 2000-0871, no 3Article in journal (Other academic)
1 - 22 of 22
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