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  • 151.
    Palm, Eleonor
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Demirel, Isak
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bengtsson, Torbjörn
    Örebro University, School of Medicine, Örebro University, Sweden.
    Khalaf, Hazem
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    The role of toll-like and protease-activated receptors in the expression of cytokines by gingival fibroblasts stimulated with the periodontal pathogen Porphyromonas gingivalisManuscript (preprint) (Other academic)
  • 152.
    Palm, Eleonor
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Biomedicine, Örebro University Hospital, Örebro, Sweden.
    Demirel, Isak
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Biomedicine, Örebro University Hospital, Örebro, Sweden.
    Bengtsson, Torbjörn
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Biomedicine, Örebro University Hospital, Örebro, Sweden.
    Khalaf, Hazem
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Biomedicine, Örebro University Hospital, Örebro, Sweden.
    The role of toll-like and protease-activated receptors in the expression of cytokines by gingival fibroblasts stimulated with the periodontal pathogen Porphyromonas gingivalis2015In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 76, no 2, p. 424-432Article in journal (Refereed)
    Abstract [en]

    Porphyromonas gingivalis is a periodontitis-associated pathogen and interactions between the bacterium and gingival fibroblasts play an important role in development and progression of periodontitis, an inflammatory disease leading to degeneration of tooth-supporting structures. Gingival fibroblasts, which expresses protease activated receptors (PARs) as well as toll-like receptors (TLRs), produces inflammatory mediators upon bacterial challenges. In this study, we elucidated the importance of PAR1, PAR2, TLR2 and TLR4 for the expression and secretion of CXCL8, interleukin-6 (IL-6), transforming growth factor-beta 1 (TGF-beta 1) and secretory leukocyte inhibitor (SLPI). Human gingival fibroblasts were transfected with small-interfering RNA against the target genes, and then stimulated with P. gingivalis wild-type W50 and W50-derived double rgp mutant E8 and kgp mutant K1A. TLR2-silencing reduced P. gingivalis-induced CXCL8 and IL-6. IL-6 was also reduced after PAR1-silencing. No effects were observed for TGF-beta 1. SLPI was suppressed by P. gingivalis and silencing of PAR1 as well as TLR2, gave additional suppression at the mRNA level. TLR4 was not involved in the regulation of the investigated mediators. CXCL8 and IL-6 are important for progression and development of periodontitis, leading to a chronic inflammation that may contribute to the tissue destruction that follows an exacerbated host response. Therefore, regulating the expression of TLR2 and subsequent release of CXCL8 and IL-6 in periodontitis could attenuate the tissue destruction seen in periodontitis.

  • 153.
    Palm, Eleonor
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Khalaf, Hazem
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bengtsson, Torbjörn
    Örebro University, School of Medicine, Örebro University, Sweden.
    Porphyromonas gingivalis downregulates the immune response of fibroblasts2013In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 13, p. 155-Article in journal (Refereed)
    Abstract [en]

    Background: Porphyromonas gingivalis is a key pathogen in periodontitis, an inflammatory disease leading to destruction of bone and tooth-supporting tissue. P. gingivalis possesses a number of pathogenic properties to enhance growth and survival, including proteolytic gingipains. Accumulating data shows that gingipains are involved in the regulation of host inflammatory responses. The aim of this study was to determine if P. gingivalis infection modulates the inflammatory response of fibroblasts, including the release of chemokines and cytokines. Human gingival fibroblasts or primary dermal fibroblasts were pre-stimulated with tumor-necrosis factor-alpha (TNF-alpha) and cocultured with P. gingivalis. Gingipain inhibitors were used to explore the effect of gingipains. CXCL8 levels were determined with ELISA and the relative levels of various inflammatory mediators were determined by a cytokine assay.

    Results: TNF-alpha-triggered CXCL8 levels were completely abolished by viable P. gingivalis, whereas heat-killed P. gingivalis did not suppress CXCL8. Accumulation of CXCL8 was partially restored by an arginine-gingipain inhibitor. Furthermore, fibroblasts produced several inflammatory mediators, notably chemokines, all of which were suppressed by viable P. gingivalis.

    Conclusion: These findings provide evidence that fibroblast-derived inflammatory signals are modulated by heat-instable gingipains, whereby the bacteria can escape killing by the host immune system and promote its own growth and establishment. In addition, we show that fibroblasts are important mediators of inflammation in response to infection and thereby play a crucial role in determining the nature and magnitude of the invasion of immune cells.

  • 154.
    Palm, Eleonor
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Khalaf, Hazem
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Bengtsson, Torbjörn
    Örebro University, School of Medicine, Örebro University, Sweden.
    Suppression of inflammatory responses of human gingival fibroblasts by gingipains from Porphyromonas gingivalis2015In: Molecular Oral Microbiology, ISSN 2041-1006, E-ISSN 2041-1014, Vol. 30, no 1, p. 74-85Article in journal (Refereed)
    Abstract [en]

    The interaction between human gingival fibroblasts (HGFs) and Porphyromonas gingivalis plays an important role in the development and progression of periodontitis. Porphyromonas gingivalis possesses several virulence factors, including cysteine proteases, the arginine-specific (Rgp) and lysine-specific (Kgp) gingipains. Studying the mechanisms that P.gingivalis, and its derived virulence, use to propagate and interact with host cells will increase the understanding of the development and progression of periodontitis. In this study, we aimed to elucidate how P.gingivalis influences the inflammatory events in HGFs regarding transforming growth factor-(1) (TGF-(1)), CXCL8, secretory leucocyte protease inhibitor (SLPI), c-Jun and indoleamine 2,3-dioxygenase (IDO). HGFs were inoculated for 6 and 24h with the wild-type strains ATCC 33277 and W50, two gingipain-mutants of W50 and heat-killed ATCC 33277. The P.gingivalis regulated CXCL8 and TGF-(1) in HGFs, and the kgp mutant gave significantly higher immune response with increased CXCL8 (P<0.001) and low levels of TGF-(1). We show that HGFs express and secrete SLPI, which was significantly suppressed by P.gingivalis (P<0.05). This suggests that by antagonizing SLPI, P.gingivalis contributes to the tissue destruction associated with periodontitis. Furthermore, we found that P.gingivalis inhibits the expression of the antimicrobial IDO, as well as upregulating c-Jun (P<0.05). In conclusion, P.gingivalis both triggers and suppresses the immune response in HGFs. Consequently, we suggest that the pathogenic effects of P.gingivalis, and especially the activity of the gingipains on the inflammatory and immune response of HGFs, are crucial in periodontitis.

  • 155.
    Parihar, Vishal Singh
    et al.
    Örebro University, School of Health and Medical Sciences.
    Barbuddhe, Sukhadeo
    Danielsson-Tham, Marie-Louise
    Örebro University, School of Hospitality, Culinary Arts & Meal Science.
    Tham, Wilhelm
    Örebro University, School of Hospitality, Culinary Arts & Meal Science.
    Isolation and characterization of Listeria species from tropical seafoods2008In: Food Control, ISSN 0956-7135, E-ISSN 1873-7129, Vol. 19, no 6, p. 566-569Article in journal (Refereed)
    Abstract [en]

    The incidence of Listeria species in the seafood of markets in Goa, India was studied. One hundred and fifteen raw/fresh seafoods bought at the fish markets were sampled and tested for presence of Listeria spp. using a two step enrichment procedure, followed by plating on two selective agars. The confirmation of the isolates was based on biochemical identification. Twenty eight seafood samples were positive for Listeria spp. and in 10 samples Listeria monocytogenes was detected. L.innocua was the most common Listeria species recovered and was detected in 18 samples. L. monocytogenes in raw seafood may pose a health risk in kitchen if contaminating ready-to-eat food.

  • 156.
    Parihar, Vishal Singh
    et al.
    Örebro University, Department of Restaurant & Culinary Arts. Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden.
    Lopez-Valladares, Gloria
    Örebro University, School of Hospitality, Culinary Arts & Meal Science.
    Danielsson-Tham, Marie-Louise
    Örebro University, School of Hospitality, Culinary Arts & Meal Science.
    Peiris, Inoka
    Helmersson, Seved
    Department of Environmental Assessment, SLU, Uppsala, Sweden.
    Unemo, Magnus
    Örebro University, School of Health and Medical Sciences. Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Birgitta
    Department of Bacteriology, Malmö University Hospital, Malmö, Sweden.
    Arneborn, Malin
    The Swedish Institute for Infectious Disease Control and MTC, Karolinska Institutet, Solna, Sweden.
    Bannerman, Elizabeth
    Centre National des Listeria, Institut de Microbiologie, Lausanne, Switzerland.
    Barbuddhe, Sukhadeo
    ICAR Research Complex for Goa, Old Goa, India.
    Bille, Jacques
    Centre National des Listeria, Institut de Microbiologie, Lausanne, Switzerland.
    Hajdu, Lajos
    AstraZeneca AB, Södertälje, Sweden.
    Jacquet, Christine
    Laboratoire des Listeria, Institut Pasteur, Paris, France.
    Johansson, Christina
    The Swedish Institute for Infectious Disease Control and MTC, Karolinska Institutet, Solna, Sweden.
    Löfdahl, Margareta
    The Swedish Institute for Infectious Disease Control and MTC, Karolinska Institutet, Solna, Sweden.
    Möllerberg, Gunnel
    The Swedish Institute for Infectious Disease Control and MTC, Karolinska Institutet, Solna, Sweden.
    Ringberg, Håkan
    Regional Centre for Communicable Disease Control and Prevention, Malmö, Sweden.
    Rocourt, Jocelyne
    Centre Pasteur du Cameroun, Yaounde, Cameroon.
    Tjernberg, Ingela
    Department of Bacteriology, Malmö University Hospital, Malmö, Sweden.
    Ursing, Jan
    Department of Bacteriology, Malmö University Hospital, Malmö, Sweden.
    Henriques-Normark, Birgitta
    The Swedish Institute for Infectious Disease Control and MTC, Karolinska Institutet, Solna, Sweden.
    Tham, Wilhelm
    Örebro University, School of Hospitality, Culinary Arts & Meal Science. Department of Restaurant and Culinary Arts, Örebro University, Grythyttan, Sweden.
    Characterization of human invasive isolates of Listeria monocytogenes in Sweden 1986-20072008In: Foodborne pathogens and disease, ISSN 1535-3141, E-ISSN 1556-7125, Vol. 5, no 6, p. 755-761Article in journal (Refereed)
    Abstract [en]

    Since 1986, 68% of the Listeria monocytogenes isolates from human cases of invasive listeriosis in Sweden are available for retrospective studies. The aim of the present study was to characterize 601 human invasive isolates of L. monocytogenes in Sweden from 1986 to 2007 by using serotyping and pulsed-field gel electrophoresis. Since 1996, serovar 4b was permanently reduced to the second or third most common serovar in human cases in Sweden. During the latter period, 2000-2007, only 13% belonged to serovar 4b and 71% to 1/2a. The dendrogram, based on pulsovars, reveals two clusters with different serovars. Cluster 1 exhibits serovars 4b and 1/2b, whereas cluster 2 consists of serovar 1/2a. Serovar 1/2a seems to be more heterogeneous than serovar 4b.

  • 157.
    Persson, Alexander
    et al.
    Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Blomgran-Julinder, Robert
    Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Rahman, Sayma
    Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Zheng, Limin
    Department of Biochemistry, College of Life Sciences, Sun Yansen (Zhongshan) University, Guangzhou, People's Republic of China.
    Stendahl, Olle
    Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Mycobacterium tuberculosis-induced apoptotic neutrophils trigger a pro-inflammatory response in macrophages through release of heat shock protein 72, acting in synergy with the bacteria2008In: Microbes and infection, ISSN 1286-4579, E-ISSN 1769-714X, Vol. 10, no 3, p. 233-240Article in journal (Refereed)
    Abstract [en]

    Mycobacterium tuberculosis (Mtb) survive inside macrophages by manipulating microbicidal functions such as phago-lysosome fusion, production of reactive oxygen species and nitric oxide, and by rendering macrophages non-responsive to IFN-gamma. Mtb-infected lung tissue does however not only contain macrophages, but also significant numbers of infiltrating polymorphonuclear neutrophils (PMN). These are able to phagocytose and kill ingested Mtb, but are short-lived cells that constantly need to be removed from tissues to avoid tissue damage. Phagocytosis of aged or UV-induced apoptotic PMN by macrophages induce an anti-inflammatory response in macrophages. However, in the present study, we show that engulfment of Mtb-induced apoptotic PMN by macrophages initiates secretion of TNF-alpha from the macrophages, reflecting a pro-inflammatory response. Moreover, Mtb-induced apoptotic PMN up-regulate heat shock proteins 60 and 72 (Hsp60, Hsp72) intracellularly and also release Hsp72 extracellularly. We found that both recombinant Hsp72 and released Hsp72 enhanced the pro-inflammatory response to both Mtb-induced apoptotic PMN and Mtb. This stimulatory effect of the supernatant was abrogated by depleting the Hsp72 with immunoprecipitation. These findings indicate that released Hsp72 from Mtb-infected PMN can trigger macrophage activation during the early stage of Mtb infections, thereby creating a link between innate and adaptive immunity.

  • 158.
    Pluskal, Tomás
    et al.
    G0 Cell Unit, Okinawa Institute of Science and Technology (OIST), Onna Okinawa, Japan.
    Castillo, Sandra
    Quantitative Biology and Bioinformatics, VTT Technical Research Centre of Finland, Espoo, Finland.
    Villar-Briones, Alejandro
    G0 Cell Unit, Okinawa Institute of Science and Technology (OIST), Onna Okinawa, Japan.
    Oresic, Matej
    Quantitative Biology and Bioinformatics, VTT Technical Research Centre of Finland, Espoo, Finland.
    MZmine 2: modular framework for processing, visualizing, and analyzing mass spectrometry-based molecular profile data2010In: BMC Bioinformatics, ISSN 1471-2105, E-ISSN 1471-2105, Vol. 11, article id 395Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Mass spectrometry (MS) coupled with online separation methods is commonly applied for differential and quantitative profiling of biological samples in metabolomic as well as proteomic research. Such approaches are used for systems biology, functional genomics, and biomarker discovery, among others. An ongoing challenge of these molecular profiling approaches, however, is the development of better data processing methods. Here we introduce a new generation of a popular open-source data processing toolbox, MZmine 2.

    RESULTS: A key concept of the MZmine 2 software design is the strict separation of core functionality and data processing modules, with emphasis on easy usability and support for high-resolution spectra processing. Data processing modules take advantage of embedded visualization tools, allowing for immediate previews of parameter settings. Newly introduced functionality includes the identification of peaks using online databases, MSn data support, improved isotope pattern support, scatter plot visualization, and a new method for peak list alignment based on the random sample consensus (RANSAC) algorithm. The performance of the RANSAC alignment was evaluated using synthetic datasets as well as actual experimental data, and the results were compared to those obtained using other alignment algorithms.

    CONCLUSIONS: MZmine 2 is freely available under a GNU GPL license and can be obtained from the project website at: http://mzmine.sourceforge.net/. The current version of MZmine 2 is suitable for processing large batches of data and has been applied to both targeted and non-targeted metabolomic analyses.

  • 159.
    Prag, Gustaf
    et al.
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Falk-Brynhildsen, Karin
    Department of Cardiothoracic and Vascular Surgery, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden; Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Decreased susceptibility to chlorhexidine and prevalence of disinfectant resistance genes among clinical isolates of Staphylococcus epidermidis2014In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 10, p. 961-967Article in journal (Refereed)
    Abstract [en]

    Staphylococcus epidermidis, despite regarded as a commensal, is recognized as a nosocomial pathogen usually by acting as an opportunist, especially in infections associated with implanted foreign body materials. Pre-operative antiseptic preparation is an important strategy for reducing the risk of complications such as surgical site infection (SSI). The currently most widely used antiseptic compounds are alcohols and quaternary ammonium compounds (QACs), predominantly chlorhexidine.

    The aim of this study was to investigate if decreased susceptibility to chlorhexidine among S. epidermidis was present in our setting. S. epidermidis (n=143) were obtained from prosthetic joint infections (PJI) (n=61), commensals (n=24), post-operative infections after cardiothoracic surgery (n=31), and the skin of the chest after routine disinfection prior cardiothoracic surgery (n=27). Determination of MIC of chlorhexidine was performed on Müeller Hinton agar plates supplemented with serial dilutions of chlorhexidine. Five QAC resistance genes; qacA/B, smr, qacH, qacJ, and qacG, were detected using PCR.

    Decreased susceptibility to chlorhexidine was found in 54% of PJI isolates, 68% of cardiothoracic isolates, 21% of commensals, and 7% of isolates obtained from the skin of cardiothoracic patients, respectively.

    The qacA/B gene was present in 62/143 isolates (43%), smr in 8/143 (6%) and qacH in one isolate (0.7%). The qacA/B gene was found in 52% of PJI isolates, 61% of cardiothoracic isolates, 25% of commensals, and 19% of isolates obtained from the skin of cardiothoracic patients. In conclusion, decreased susceptibility to chlorhexidine as well as QAC resistance genes was highly prevalent among S. epidermidis causing deep SSIs.

  • 160.
    Rangel, Ignacio
    et al.
    Örebro University, School of Medical Sciences.
    Ganda Mall, John Peter
    Örebro University, School of Medical Sciences.
    Roger, Willén
    Department of Pathology and Cytology, Uppsala University Hospital, Uppsala, Sweden.
    Sjöberg, Fei
    Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro University, School of Medical Sciences.
    Degree of colitis correlates with microbial composition and cytokine responses in colon and caecum of Gαi2-deficient mice2016In: FEMS Microbiology Ecology, ISSN 0168-6496, E-ISSN 1574-6941, Vol. 92, no 7, article id fiw098Article in journal (Refereed)
    Abstract [en]

    An altered immune response and gut microbiota have been associated with the pathology of Inflammatory Bowel Diseases (IBD). However, there is limited knowledge of how inflammation is associated with changes in the microbiota. We studied the microbiota in the intestine and faeces as well as the cytokine gene expressions in caecum and colon of a mouse model (Gαi2(-/-)) of colitis, and analysed them in relation to the degrees of inflammation in the colon. The degree of colitis was associated with general changes in the complexity of the microbiota and was corroborated by quantitative analyses of the Bacteroides and Lactobacillus High gene expression levels of IL-17 and IFN-γ in colon and caecum were detected in Gαi2(-/-) mice with moderate and severe colitis. High IL-27 gene expression in the colon of mice with moderate and severe colitis and in the caecum of mice with moderate colitis was also detected. Negative correlations between IL-27 and Bacteroides and Lactobacillus and between IFN-γ and Lactobacillus were detected in caecum. This research indicates that the degree of colitis in IBD correlates with the gene expression of cytokines and with disturbances in the gut microbiota. Furthermore, the caecum could have an important role in the pathology of IBD.

  • 161.
    Rasmussen, Gunlög
    et al.
    Örebro University, School of Medical Sciences. Department of Infectious Diseases, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Cajander, Sara
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Bäckman, Anders
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Clinical Research Laboratory, Örebro University Hospital, Örebro, Sweden.
    Källman, Jan
    Department of Infectious Diseases, Örebro University Hospital, Örebro University, Örebro, Sweden; Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medical Sciences. Department of Infectious Diseases, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Strålin, Kristoffer
    Faculty of Medicine and Health, School of Medical Sciences, Örebro University, Örebro, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
    Expression of HLA-DRA and CD74 mRNA in whole blood during the course of complicated and uncomplicated Staphylococcus aureus bacteremia2017In: Microbiology and immunology, ISSN 0385-5600, E-ISSN 1348-0421, Vol. 61, no 10, p. 442-451Article in journal (Refereed)
    Abstract [en]

    To improve management of Staphylococcus aureus bacteremia (SAB), better understanding of host-pathogen interactions is needed. In vitro studies have shown that S. aureus bacteria induce dose-dependent immunosuppression that is evidenced by reduced expression of major histocompatibility complex (MHC) class II on antigen presenting cells. Thus, the aim of this study was to determine whether expression of the MHC class II-related genes HLA-DRA and CD74 is more greatly reduced in complicated SAB, with its probable higher loads of S. aureus, than in uncomplicated SAB. Adult patients with SAB were prospectively included and blood samples taken on the day of confirmation of SAB (Day 1) and on Days 2, 3, 5 and 7. HLA-DRA and CD74 mRNA expression was determined by quantitative reverse transcription PCR. Sepsis was defined according to the Sepsis-3 classification and SAB was categorized as complicated in patients with deep-seated infection and/or hematogenous seeding. Twenty patients with SAB were enrolled and samples obtained on all assessment days. HLA-DRA and CD74 expression did not differ significantly between patients with SAB and sepsis (n=13) and those without sepsis (n=7) on any assessment day. However, patients with complicated SAB (n=14) had significantly weaker HLA-DRA expression on all five assessment days than patients with uncomplicated SAB (n=6). Additionally, they tended to have weaker CD74 expressions. Neutrophil, monocyte and leukocyte counts did not differ significantly between complicated and uncomplicated SAB. In conclusion, patients with complicated SAB show weaker HLA-DRA expression than those with uncomplicated SAB during the first week of bacteremia.

  • 162.
    Rumyantseva, Tatiana
    et al.
    Central Research Institute for Epidemiology, Moscow, Russia.
    Shipitsyna, Elena
    Laboratory of Microbiology, D.O. Ott Research Institute of Obstetrics, Gynaecology and Reproductology, St. Petersburg, Russia; Department of Laboratory Medicine, Microbiology, WHO Collaborating Centre for Gonorrhoea and Other STIs, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Guschin, Alexander
    Central Research Institute for Epidemiology, Moscow, Russia.
    Unemo, Magnus
    Örebro University, School of Health Sciences. Department of Laboratory Medicine, Microbiology, WHO Collaborating Centre for Gonorrhoea and Other STIs, Örebro University Hospital, Örebro, Sweden.
    Evaluation and subsequent optimizations of the quantitative AmpliSens Florocenosis/Bacterial vaginosis-FRT multiplex real-time PCR assay for diagnosis of bacterial vaginosis2016In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 124, no 12, p. 1099-1108Article in journal (Refereed)
    Abstract [en]

    Traditional microscopy-based methods for diagnosis of bacterial vaginosis (BV) are underutilized in many settings, and molecular techniques may provide opportunities for rapid, objective, and accurate BV diagnosis. This study evaluated the quantitative AmpliSens Florocenosis/Bacterial vaginosis-FRT multiplex real-time PCR (Florocenosis-BV) assay. Vaginal samples from a previous study including unselected female subjects (n = 163) and using Amsel criteria and 454 pyrosequencing for BV diagnosis were examined with the Florocenosis-BV test and additionally tested for the presence and quantity of Gardnerella vaginalis clades 3 and 4. The Florocenosis-BV assay demonstrated 100% and 98% sensitivity compared with the Amsel criteria and 454 pyrosequencing, respectively, with 91% specificity. The modified Florocenosis-BV assay (detecting also G. vaginalis clades 3 and 4) resulted in 100% sensitivity vs the Amsel criteria and 454 pyrosequencing with specificity of 86% and 88%, respectively. Further optimizations of thresholds for the quantitative parameters used in the kit resulted in 99-100% accuracy vs Amsel criteria and 454 pyrosequencing for selected parameters. The Florocenosis-BV assay is an objective, accurate, sensitive, and specific method for BV diagnosis; however, the performance of the test can be further improved with some minor optimizations.

  • 163.
    Ryan, L.
    et al.
    Department of Clinical Microbiology, St James’s Hospital, Dublin, Ireland.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Fennelly, N.
    Department of Clinical Microbiology, St James’s Hospital, Dublin, Ireland.
    Rose, L.
    Department of Clinical Microbiology, St James’s Hospital, Dublin, Ireland.
    Walsh, P.
    Department of Computing, Cork Institute of Technology, Cork, Ireland.
    Lawlor, B.
    Department of Computing, Cork Institute of Technology, Cork, Ireland.
    Mac Aogáin, M.
    Department of Clinical Microbiology, Trinity Translational Medicine Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology.
    Crowley, B.
    Department of Clinical Microbiology, St James’s Hospital, Dublin, Ireland; Department of Virology, St James’s Hospital, Dublin, Ireland.
    Antimicrobial resistance and molecular epidemiology using whole-genome sequencing of Neisseria gonorrhoeae in Ireland, 2014-2016: focus on extended-spectrum cephalosporins and azithromycin2018In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 37, no 9, p. 1661-1672Article in journal (Refereed)
    Abstract [en]

    High-level resistance and treatment failures with ceftriaxone and azithromycin, the first-line agents for gonorrhoea treatment are reported and antimicrobial-resistant Neisseria gonorrhoeae is an urgent public health threat. Our aims were to determine antimicrobial resistance rates, resistance determinants and phylogeny of N. gonorrhoeae in Ireland, 2014-2016. Overall, 609 isolates from four University Hospitals were tested for susceptibility to extended-spectrum cephalosporins (ESCs) and azithromycin by the MIC Test Strips. Forty-three isolates were whole-genome sequenced based on elevated MICs. The resistance rate to ceftriaxone, cefixime, cefotaxime and azithromycin was 0, 1, 2.1 and 19%, respectively. Seven high-level azithromycin-resistant (HLAzi-R) isolates were identified, all susceptible to ceftriaxone. Mosaic penA alleles XXXIV, X and non-mosaic XIII, and G120K plus A121N/D/G (PorB1b), H105Y (MtrR) and A deletion (mtrR promoter) mutations, were associated with elevated ESC MICs. A2059G and C2611T mutations in 23S rRNA were associated with HLAzi-R and azithromycin MICs of 4-32 mg/L, respectively. The 43 whole-genome sequenced isolates belonged to 31 NG-MAST STs. All HLAzi-R isolates belonged to MLST ST1580 and some clonal clustering was observed; however, the isolates differed significantly from the published HLAzi-R isolates from the ongoing UK outbreak. There is good correlation between previously described genetic antimicrobial resistance determinants and phenotypic susceptibility categories for ESCs and azithromycin in N. gonorrhoeae. This work highlights the advantages and potential of whole-genome sequencing to be applied at scale in the surveillance of antibiotic resistant strains of N. gonorrhoeae, both locally and internationally.

  • 164. Saulo, Eleonor C.
    et al.
    Forsberg, Birger C.
    Premji, Zul
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Björkman, Anders
    Willingness and ability to pay for artemisinin-based combination therapy in rural Tanzania2008In: Malaria Journal, ISSN 1475-2875, E-ISSN 1475-2875, Vol. 7, p. 227-Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to analyse willingness to pay (WTP) and ability to pay (ATP) for ACT for children below five years of age in a rural setting in Tanzania before the introduction of artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria. Socio-economic factors associated with WTP and expectations on anti-malaria drugs, including ACT, were also explored.

    Methods

    Structured interviews and focus group discussions were held with mothers, household heads, health-care workers and village leaders in Ishozi, Gera and Ishunju wards in north-west Tanzania in 2004. Contingent valuation method (CVM) was used with "take-it-or-leave-it" as the eliciting method, expressed as WTP for a full course of ACT for a child and households' opportunity cost of ACT was used to assess ATP. The study included descriptive analyses with multivariate adjustment for potential confounding factors.

    Results

    Among 265 mothers and household heads, 244 (92%, CI = 88%–95%) were willing to pay Tanzanian Shillings (TSh) 500 (US$ 0.46) for a child's dose of ACT, but only 55% (49%–61%) were willing to pay more than TSh 500. Mothers were more often willing to pay than male household heads (adjusted odds ratio = 2.1, CI = 1.2–3.6). Socio-economic status had no significant effect on WTP. The median annual non-subsidized ACT cost for clinical malaria episodes in an average household was calculated as US$ 6.0, which would represent 0.9% of the average total consumption expenditures as estimated from official data in 2001. The cost of non-subsidized ACT represented 7.0% of reported total annual expenditure on food and 33.0% of total annual expenditure on health care.

    "Rapid effect," "no adverse effect" and "inexpensive" were the most desired features of an anti-malarial drug.

    Conclusion

    WTP for ACT in this study was less than its real cost and a subsidy is, therefore, needed to enable its equitable affordability. The decision taken in Tanzania to subsidize Coartem® fully at governmental health care facilities and at a consumer price of TSh 300–500 (US$ 0.28–0.46) at special designated shops through the programme of Accredited Drug Dispensing Outlets (ADDOs) appears to be well founded.

  • 165.
    Schnürer, Johan
    et al.
    Department of Antiviral Research, Research and Development Laboratories, Astra Läkemedel AB, Södertälje, Sweden.
    Öberg, B.
    Department of Antiviral Research, Research and Development Laboratories, Astra Läkemedel AB, Södertälje, Sweden.
    Inhibitory effects of foscarnet on herpesvirus multiplication in cell culture1981In: Archives of Virology, ISSN 0304-8608, E-ISSN 1432-8798, Vol. 68, no 3-4, p. 203-209Article in journal (Refereed)
    Abstract [en]

    The effect of phosphonoformate (INN; foscarnet sodium) on Herpes Simplex Virus type 1 replication in cell-culture has been studied. At 55 μm, foscarnet reduced the yield by 50 per cent which correlated well with a 50 per cent reduction of plaque formation at 60 μm. Foscarnet had to be added before 8 hours post infection to inhibit virus production. The inhibition of herpesvirus plaque formation by the presence of foscarnet for 24 hours was not reversed by the removal of the drug. The inhibition of virus replication by foscarnet could, in contrast to the inhibition by acycloguanosine, not be reversed by addition of deoxynucleosides.

  • 166.
    Selegård, Robert
    et al.
    Faculty of Medicine & Health, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Musa, Amani
    Örebro University, School of Medical Sciences.
    Nyström, Pontus
    Örebro University, School of Medical Sciences.
    Aili, Daniel
    Division of Molecular Physics, Department of Physics, Chemistry & Biology (IFM), Linköping University, Linköping, Sweden.
    Bengtsson, Torbjörn
    Örebro University, School of Medical Sciences.
    Khalaf, Hazem
    Örebro University, School of Medical Sciences.
    Plantaricins markedly enhance the effects of traditional antibiotics against Staphylococcus epidermidis2019In: Future microbiology, ISSN 1746-0913, Vol. 14, no 3, p. 195-206Article in journal (Refereed)
    Abstract [en]

    AIM: Bacteriocins are considered as promising alternatives to antibiotics against infections. In this study, the plantaricins (Pln) A, E, F, J and K were investigated for their antimicrobial activity against Staphylococcus epidermidis.

    MATERIALS & METHODS: The effects on membrane integrity were studied using liposomes and viable bacteria, respectively.

    RESULTS: We show that PlnEF and PlnJK caused rapid and significant lysis of S. epidermidis, and induced lysis of liposomes. The PlnEF and PlnJK displayed similar mechanisms by targeting and disrupting the bacterial cell membrane. Interestingly, Pln enhanced the effects of different antibiotics by 30- to 500-fold.

    CONCLUSION: This study shows that Pln in combination with low concentrations of antibiotics is efficient against S. epidermidis and may be developed as potential treatment of infections.

  • 167.
    Serwin, Agnieszka Beata
    et al.
    Department of Dermatology and Venereology, Medical University of Bialystok, Bialystok, Poland.
    Bulhak-Koziol, Violetta
    Diagnostic and Research Centre for Sexually Transmitted Diseases, Bialystok, Poland.
    Sokolowska, Marianna
    Diagnostic and Research Centre for Sexually Transmitted Diseases, Bialystok, Poland.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Unemo, Magnus
    WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Trichomonas vaginalis is very rare among women with vaginal discharge in Podlaskie province, Poland2017In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 125, no 9, p. 840-843Article in journal (Refereed)
    Abstract [en]

    Trichomonas vaginalis is the most common curable sexually transmitted pathogen globally. However, in the European Union (EU), trichomoniasis appears to be a rare condition. The aim of this study was to examine the prevalence of T. vaginalis among females attending an STI centre in Bialystok, Poland, using the highly sensitive and specific APTIMA T. vaginalis assay. Consecutive females, referred by gynaecologists mainly because of abnormal vaginal discharge, were diagnosed using wet mount microscopy, culture and APTIMA T. vaginalis assay. Among 272 women studied, 82% were pre- and 18% postmenopausal. The average age was 36.0 +/- 13.9 (range: 18-86) years. Abnormal discharge (alone or accompanied by itch or vulvovaginal burning) was the most frequent complain in both groups (66.2% and 48.0%). Erythema and discharge were the most frequent abnormal signs (58.6% and 56.0%). Not a single T. vaginalis-positive sample was detected using wet mount microscopy, culture or APTIMA T. vaginalis assay. Despite using the highly sensitive APTIMA T. vaginalis assay for detection, the pathogen could not be identified in females in the studied setting, similar to results from other EU settings. The need for general screening using NAAT for this pathogen while diagnosing vulvovaginal symptoms in females in Poland appears to be low.

  • 168. Shalepo, Kira
    et al.
    Savicheva, Alevtina
    Shipitsyna, Elena
    Unemo, Magnus
    Örebro University, Department of Clinical Medicine.
    Domeika, Marius
    Diagnosis of Chlamydia trachomatis in Russia--in-house PCR assays may be effective but overall optimization and quality assurance are urgently needed2006In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 114, no 7-8, p. 500-507Article in journal (Refereed)
    Abstract [en]

    In the present study, the performance of the cell culture method, two non-Russian direct immunofluorescence (DIF) assays, and three different in-house polymerase chain reaction (PCR) tests used in St. Petersburg, Russia, for detection of Chlamydia trachomatis in urogenital specimens was evaluated. A total of 650 patients were examined and it was most disquieting that previous C. trachomatis positivity with Russian DIF assays could - 7 days later - be confirmed only in 26% of the women and 30% of the men. Overall, the highest diagnostic sensitivity was obtained using PCR analysis. However, the sensitivity varied significantly: from 79% to 100% between the different PCR assays, sex of the patients, and type of samples. The highest sensitivity was obtained for female vaginal and male urine samples (100%). The specificity of the PCR assays varied from 97% to 100%. The sensitivity of cell culture and both the examined DIF assays was low, i.e. it varied from 46% to 56% and 55% to 75%, respectively. Meanwhile, cell culture was 100% specific and the DIFs showed a specificity varying from 99% to 100%. In conclusion, in a Russian perspective, adequate in-house PCR methods may be used quite effectively for detection of C. trachomatis in invasive as well as non-invasive clinical material. Simultaneous analysis of two different specimens from women resulted in a significantly increased detection rate of C. trachomatis. Nevertheless, in Russia the need for optimization and quality assurance of diagnostic methods for C. trachomatis, especially Russian DIF assays, has to be emphasized.

  • 169.
    Shimuta, Ken
    et al.
    Natl Inst Infect Dis, Tokyo, Japan.
    Unemo, Magnus
    Örebro University Hospital. Dept Lab Med, WHO Collaborating Ctr Gonorrhoea & Other STIs, Örebro University Hospital, Örebro, Sweden.
    Nakayama, Shu-ichi
    Natl Inst Infect Dis, Tokyo, Japan.
    Morita-Ishihara, Tomoko
    Natl Inst Infect Dis, Tokyo, Japan.
    Dorin, Misato
    Natl Inst Infect Dis, Tokyo, Japan.
    Kawahata, Takuya
    Osaka Prefectural Inst Publ Hlth, Osaka, Japan.
    Ohnishi, Makoto
    Natl Inst Infect Dis, Tokyo, Japan.
    Antimicrobial Resistance and Molecular Typing of Neisseria gonorrhoeae Isolates in Kyoto and Osaka, Japan, 2010 to 2012: Intensified Surveillance after Identification of the First Strain (H041) with High-Level Ceftriaxone Resistance2013In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 57, no 11, p. 5225-5232Article in journal (Refereed)
    Abstract [en]

    In 2009, the first high-level ceftriaxone-resistant Neisseria gonorrhoeae strain (H041) was isolated in Kyoto, Japan. The present study describes an intensified surveillance (antimicrobial resistance and molecular typing) of Neisseria gonorrhoeae isolates in Kyoto and its neighboring prefecture Osaka, Japan, in 2010 to 2012, which was initiated after the identification of H041. From April 2010 to March 2012, 193 N. gonorrhoeae isolates were collected and the MICs (mu g/ml) to six antimicrobials, including ceftriaxone, were determined. All isolates showed susceptibility to ceftriaxone and cefixime (MIC values,< 0.5 mu g/ml), and spectinomycin. The rates of resistance (intermediate susceptibility) to azithromycin, penicillin G, and ciprofloxacin were 3.6% (19.7%), 24.4% (71.0%), and 78.2% (0.5%), respectively. Multilocus sequence typing (MLST) showed that 40.9%, 19.2%, and 17.1% of isolates belonged to ST1901, ST7359, and ST7363, respectively. Furthermore, N. gonorrhoeae multiantigen sequence typing (NG-MAST) revealed that 12 (63%) of the 19 isolates with decreased susceptibility to ceftriaxone (MIC> 0.064 mu g/ml) were of ST1407. NG-MAST ST1407 was also the most prevalent ST (16.1%; 31 of 193 isolates). In those NG-MAST ST1407 strains, several mosaic type penA alleles were found, including SF-A type (penicillin binding protein 2 allele XXXIV) and its derivatives. These were confirmed using transformation of the penA mosaic alleles as critical determinants for enhanced cefixime and ceftriaxone MICs. The intensified surveillance in Kyoto and Osaka, Japan, did not identify any dissemination of the highlevel ceftriaxone-resistant N. gonorrhoeae strain H041, suggesting that H041 might have caused only a sporadic case and has not spread further.

  • 170. Shipitsyna, Elena
    et al.
    Roos, Annika
    Datcu, Raluca
    Hallén, Anders
    Fredlund, Hans
    Örebro University Hospital.
    Jensen, Jørgen S
    Engstrand, Lars
    Unemo, Magnus
    Örebro University Hospital, Örebro, Sweden.
    Composition of the vaginal microbiota in women of reproductive age--sensitive and specific molecular diagnosis of bacterial vaginosis is possible?2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 4, article id e60670Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVE: Bacterial vaginosis (BV) is the most common vaginal disorder, characterized by depletion of the normal lactobacillus-dominant microbiota and overgrowth of commensal anaerobic bacteria. This study aimed to investigate the composition of the vaginal microbiota in women of reproductive age (healthy women and women with BV), with the view of developing molecular criteria for BV diagnosis.

    MATERIALS AND METHODS: Vaginal samples from 163 women (79 control, 73 BV and 11 intermediate (Lactobacillary grade II flora) cases) were analyzed using 454 pyrosequencing of the hypervariable regions V3-V4 of the 16S rRNA gene and 16 quantitative bacterial species/genus-specific real-time PCR assays. Sensitivities and specificities of potential BV markers were computed using the Amsel criteria as reference standard for BV. The use of quantitative thresholds for prediction of BV, determined for both relative abundance measured with 454 pyrosequencing and bacterial load measured with qPCR, was evaluated.

    RESULTS: Relative to the healthy women, the BV patients had in their vaginal microbiota significantly higher prevalence, loads and relative abundances of the majority of BV associated bacteria. However, only Gardnerella vaginalis, Atopobium vaginae, Eggerthella, Prevotella, BVAB2 and Megasphaera type 1 detected at or above optimal thresholds were highly predictable for BV, with the best diagnostic accuracy shown for A. vaginae. The depletion of Lactobacillus species combined with the presence of either G. vaginalis or A. vaginae at diagnostic levels was a highly accurate BV predictor.

    CONCLUSIONS: Quantitative determination of the presence of G. vaginalis, A. vaginae, Eggerthella, Prevotella, BVAB2 and Megasphaera type 1 as well as the depletion of Lactobacillus was highly accurate for BV diagnosis. Measurements of abundance of normal and BV microbiota relative to total bacteria in vaginal fluid may provide more accurate BV diagnosis, and be used for test-of-cure, rather than qualitative detection or absolute counts of BV related microorganisms.

  • 171.
    Sjöberg, Maria
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Eriksson, Mats
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Centre for Health Care Sciences, Örebro University Hospital, Örebro, Sweden.
    Andersson, Josefin
    Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Norén, Torbjörn
    Örebro University Hospital. Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Transmission of Clostridium difficile spores in isolation room environments and through hospital beds2014In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 122, no 9, p. 800-803Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to determine the dissemination of Clostridium difficile (CD) spores in a hospital setting where the potassium monopersulfate-based disinfectant VirkonTM was used for cleaning. In the initial part of the study, we sampled 16 areas of frequent patient contact in 10 patient rooms where a patient with CD infection (CDI) had been accommodated. In the second part of the study, we obtained samples from 10 patient beds after discharge of CDI patients, both before and after the beds were cleaned. In the first part, CDspores were isolated in only 30% of the rooms. In the second part, which focused on transmission to hospital beds, C. difficile was found in four of 10 beds either before or after cleaning. In conclusion, in both parts of the study, we demonstrated a moderate spread of CD spores to the environment despite routine cleaning procedures involving VirkonTM. 

  • 172. Strauss, Reinhild
    et al.
    Törner, Anna
    Duberg, Ann-Sofi
    Örebro University, School of Health and Medical Sciences.
    Hultcrantz, Rolf
    Ekdahl, Karl
    Hepatocellular carcinoma and other primary liver cancers in hepatitis C patients in Sweden: a low endemic country2008In: Journal of Viral Hepatitis, ISSN 1352-0504, E-ISSN 1365-2893, Vol. 15, no 7, p. 531-537Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to assess the risk of hepatocellular carcinoma (HCC) and other primary liver cancers (PLC) in the nationwide cohort of hepatitis C virus (HCV) infected patients in Sweden. The basis was the total HCV-cohort notified in 1990-2004, after excluding 3238 people also reported with hepatitis B, the study cohort consisted of 36 126 people contributing an observation time of 246 105 person-years. The most common route of transmission was intravenous drug use (57%). The national Cancer Registry was used for follow-up, and 354 developed PLC (mainly HCC), of whom 234 were eligible for statistical analysis. The PLC incidence in the HCV cohort was compared with the incidence in the general population, and a standardized incidence ratio (SIR) was calculated for six different strata according to estimated duration of infection. The highest relative risk, SIR: 46 (95% CI: 36-56) was found in the stratum 25-30 years with HCV infection and SIR: 40 (95% CI: 31-51) in the stratum 30-35 years with infection. In the entire community-based HCV cohort in Sweden we found a highly increased risk of liver cancer compared to the general population. The highest relative risk was among people who had been infected for more than 25 years.

    PMID: 18397224 [PubMed - indexed for MEDLINE]

  • 173.
    Strålin, Kristoffer
    et al.
    Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Herrmann, Björn
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Abdeldaim, Guma
    Section of Clinical Bacteriology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Department of Microbiology, Faculty of Medicine, Benghazi University, Benghazi, Libyan Arab Jamahiriya; Department of Clinical Mycobacteriology, National Center for Diseases Control, Benghazi, Libyan Arab Jamahiriya.
    Olcén, Per
    Department of Laboratory Medicine/Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Holmberg, Hans
    Örebro University Hospital. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Örebro University Hospital. Department of Laboratory Medicine/Clinical Microbiology.
    Comparison of Sputum and Nasopharyngeal Aspirate Samples and of the PCR Gene Targets lytA and Spn9802 for Quantitative PCR for Rapid Detection of Pneumococcal Pneumonia2014In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 52, no 1, p. 83-89Article in journal (Refereed)
    Abstract [en]

    We aimed to compare sputum and nasopharyngeal aspirate (NpA) samples and the PCR gene targets lytA and Spn9802 in quantitative PCR (qPCR) assays for rapid detection of pneumococcal etiology in community-acquired pneumonia (CAP). Seventy-eight adult patients hospitalized for radiologically confirmed CAP had both good-quality sputum and NpA specimens collected at admission. These samples were subjected to lytA qPCR and Spn9802 qPCR assays with analytical times of < 3 h. Thirty-two patients had CAP with a pneumococcal etiology, according to conventional diagnostic criteria. The following qPCR positivity rates were noted in CAP cases with and without pneumococcal etiology: 96% and 15% (sputum lytA assay), 96% and 17% (sputum Spn9802 assay), 81% and 11% (NpA lytA assay), and 81% and 20% (NpA Spn9802 assay), respectively. The mean lytA and Spn9802 DNA levels were significantly higher in qPCR-positive sputum samples from cases with pneumococcal etiology than in qPCR-positive sputum samples from CAP cases without pneumococcal etiology or qPCR-positive NpA samples from cases with pneumococcal etiology (P < 0.02 for all comparisons). For detection of pneumococcal etiology, receiver operating characteristic curve analysis showed that sputum specimens were superior to NpA specimens as the sample type (P < 0.02 for both gene targets) and lytA tended to be superior to Spn9802 as the gene target. The best-performing test, the sputum lytA qPCR assay, showed high sensitivity (94%) and specificity (96%) with a cutoff value of 10(5) DNA copies/ml. In CAP patients with good sputum production,

  • 174.
    Sundqvist, Martin
    et al.
    Örebro University Hospital. Department of Clinical Microbiology, Central Hospital, Växjö, Sweden; Department of Medical Sciences, Division of Infectious Diseases, Uppsala University, Uppsala, Uppsala, Sweden; Department of Laboratory Medicine, Clinical Microbiology, University Hospital, Örebro, Sweden.
    Granholm, Susanne
    Dept Clin Microbiol, Lab Mol Infect Med Sweden, Umeå Univ, Umeå, Sweden.
    Naseer, Umaer
    Dept Microbiol & Infect Control, Reference Ctr Detect Antimicrobial Resistance, Univ Hosp North Norway, Tromsø, Norway; Dept Med Biol, Res Grp Host Microbe Interact, Univ Tromsø, Tromsø, Norway.
    Ryden, Patrik
    Dept Math & Math Stat, Umeå Univ, Umeå, Sweden.
    Brolund, Alma
    Publ Hlth Agcy Sweden, Solna, Sweden; Dept Microbiol Tumor & Cell Biol, Karolinska Inst, Stockholm, Sweden.
    Sundsfjord, Arnfinn
    Dept Microbiol & Infect Control, Reference Ctr Detect Antimicrobial Resistance, Univ Hosp North Norway, Tromsø, Norway; Dept Med Biol, Res Grp Host Microbe Interact, Univ Tromsø, Tromsø, Norway.
    Kahlmeter, Gunnar
    Dept Clin Microbiol, Cent Hosp Växjö, Växjö, Sweden; Div Clin Bacteriol, Dept Med Sci, Uppsala Univ, Uppsala, Sweden.
    Johansson, Anders
    Dept Clin Microbiol, Lab Mol Infect Med Sweden, Umeå Univ, Umeå, Sweden.
    Within-Population Distribution of Trimethoprim Resistance in Escherichia coli before and after a Community-Wide Intervention on Trimethoprim Use2014In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 58, no 12, p. 7492-7500Article in journal (Refereed)
    Abstract [en]

    A 2-year prospective intervention on the prescription of trimethoprim reduced the use by 85% in a health care region with 178,000 inhabitants. Here, we performed before-and-after analyses of the within-population distribution of trimethoprim resistance in Escherichia coli. Phylogenetic and population genetic methods were applied to multilocus sequence typing data of 548 consecutively collected E. coli isolates from clinical urinary specimens. Results were analyzed in relation to antibiotic susceptibility and the presence and genomic location of different trimethoprim resistance gene classes. A total of 163 E. coli sequence types (STs) were identified, of which 68 were previously undescribed. The isolates fell into one of three distinct genetic clusters designated BAPS 1 (E. coli phylogroup B2), BAPS 2 (phylogroup A and B1), and BAPS 3 (phylogroup D), each with a similar frequency before and after the intervention. BAPS 2 and BAPS 3 were positively and BAPS 1 was negatively associated with trimethoprim resistance (odds ratios of 1.97, 3.17, and 0.26, respectively). In before-and-after analyses, trimethoprim resistance frequency increased in BAPS 1 and decreased in BAPS 2. Resistance to antibiotics other than trimethoprim increased in BAPS 2. Analysis of the genomic location of different trimethoprim resistance genes in isolates of ST69, ST58, and ST73 identified multiple independent acquisition events in isolates of the same ST. The results show that despite a stable overall resistance frequency in E. coli before and after the intervention, marked within-population changes occurred. A decrease of resistance in one major genetic cluster was masked by a reciprocal increase in another major cluster.

  • 175.
    Svensson, Karolina
    et al.
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University, School of Medical Sciences.
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences. Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Characterization of SCCmec elements in methicillin-resistant Staphylococcus epidermidis isolated from blood cultures from neonates during three decades2011In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 119, no 12, p. 885-893Article in journal (Refereed)
    Abstract [en]

    Staphylococcus epidermidis is a major cause of nosocomial infections in immunocompromised patients and the predominant pathogen in catheter-related infections and bloodstream infections. Approximately 70-80% of S. epidermidis carry the mecA gene encoding methicillin resistance. The mecA gene is located on a mobile genetic element, the staphylococcal cassette chromosome mec (SCCmec). The aim of this study was to characterize the SCCmec elements as well as the adjacent arginine catabolic mobile element (ACME) in 30 clinical blood isolates of mecA positive S. epidermidis obtained from neonates and collected over a period of three decades. The ccr and mec gene complexes were identified using PCR. The SCCmec elements were found among 29/30 isolates and 13 different combinations of ccr gene complexes and mec gene complexes were identified. Staphylococcus epidermidis regularly carried multiple copies of ccr gene complexes, but only one class of mec gene complex. Three isolates could be assigned the SCCmec type III (3A). The combinations of ccr gene complexes and the mec gene complexes differed among the three decades. The most frequent combination was class B mec in combination with ccr1 and ccr2. Staphylococcus epidermidis may constitute a large reservoir for SCCmec elements, and frequent exchange of mobile genetic elements between staphylococcal species may explain the emergence of new MRSA strains.

  • 176.
    Svensson, Lovisa
    et al.
    Örebro University, School of Medical Sciences.
    Poljakovic, Mirjana
    Integrated Cardio Metabolic Centre, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden.
    Demirel, Isak
    Örebro University, School of Medical Sciences.
    Sahlberg, Charlotte
    Örebro University, School of Health Sciences.
    Persson, Katarina
    Örebro University, School of Medical Sciences.
    Host-Derived Nitric Oxide and Its Antibacterial Effects in the Urinary Tract2018In: Advances in Microbial Physiology, ISSN 0065-2911, E-ISSN 2162-5468, Vol. 73, p. 1-62Article, review/survey (Refereed)
    Abstract [en]

    Urinary tract infection (UTI) is one of the most common bacterial infections in humans, and the majority are caused by uropathogenic Escherichia coli (UPEC). The rising antibiotic resistance among UPEC and the frequent failure of antibiotics to effectively treat recurrent UTI and catheter-associated UTI motivate research on alternative ways of managing UTI. Abundant evidence indicates that the toxic radical nitric oxide (NO), formed by activation of the inducible nitric oxide synthase, plays an important role in host defence to bacterial infections, including UTI. The major source of NO production during UTI is from inflammatory cells, especially neutrophils, and from the uroepithelial cells that are known to orchestrate the innate immune response during UTI. NO and reactive nitrogen species have a wide range of antibacterial targets, including DNA, heme proteins, iron-sulfur clusters, and protein thiol groups. However, UPEC have acquired a variety of defence mechanisms for protection against NO, such as the NO-detoxifying enzyme flavohemoglobin and the NO-tolerant cytochrome bd-I respiratory oxidase. The cytotoxicity of NO-derived intermediates is nonspecific and may be detrimental to host cells, and a balanced NO production is crucial to maintain the tissue integrity of the urinary tract. In this review, we will give an overview of how NO production from host cells in the urinary tract is activated and regulated, the effect of NO on UPEC growth and colonization, and the ability of UPEC to protect themselves against NO. We also discuss the attempts that have been made to develop NO-based therapeutics for UTI treatment.

  • 177.
    Sánchez-Busó, Leonor
    et al.
    Pathogen Genomics, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology.
    Corander, Jukka
    Pathogen Genomics, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK: Helsinki Institute for Information Technology, Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland; Department of Biostatistics, University of Oslo, Oslo, Norway.
    Grad, Yonatan H.
    Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, MA, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
    Ohnishi, Makoto
    Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan; Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
    Flemming, Rebecca
    Faculty of Classics, University of Cambridge, Cambridge, UK.
    Parkhill, Julian
    Pathogen Genomics, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
    Bentley, Stephen D.
    Pathogen Genomics, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, National Reference Laboratory for Sexually Transmitted Infections, Department of Laboratory Medicine, Clinical Microbiology.
    Harris, Simon R.
    Pathogen Genomics, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.
    The impact of antimicrobials on gonococcal evolution2019In: Nature Microbiology, E-ISSN 2058-5276, Vol. 4, no 11, p. 1941-1950Article in journal (Refereed)
    Abstract [en]

    The sexually transmitted pathogen Neisseria gonorrhoeae is regarded as being on the way to becoming an untreatable superbug. Despite its clinical importance, little is known about its emergence and evolution, and how this corresponds with the introduction of antimicrobials. We present a genome-based phylogeographical analysis of 419 gonococcal isolates from across the globe. Results indicate that modern gonococci originated in Europe or Africa, possibly as late as the sixteenth century and subsequently disseminated globally. We provide evidence that the modern gonococcal population has been shaped by antimicrobial treatment of sexually transmitted infections as well as other infections, leading to the emergence of two major lineages with different evolutionary strategies. The well-described multidrug-resistant lineage is associated with high rates of homologous recombination and infection in high-risk sexual networks. A second, multisusceptible lineage is more associated with heterosexual networks, with potential implications for infection control.

  • 178.
    Säll, Olof
    et al.
    Örebro University, School of Medical Sciences. Dept. of Infectious Diseases, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Thulin-Hedberg, Sara
    Dept. of Laboratory Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Bom, Rabin
    United Mission Hospital Tansen, Tansen, Nepal.
    Dornon, Les
    United Mission Hospital Tansen, Tansen, Nepal.
    Tiwari, Sabina
    United Mission Hospital Tansen, Tansen, Nepal.
    Neander, Marita
    Dept. of Laboratory Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Sundqvist, Martin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Dept. of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Mölling, Paula
    Dept. of Laboratory Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Etiology of CNS infections in Nepal using the FilmArray meningitis/encephalitis panel2017In: International Journal of Antimicrobial Agents, ISSN 0924-8579, E-ISSN 1872-7913, Vol. 50, no Suppl. 2, p. S66-S66Article in journal (Other academic)
  • 179.
    Söderquist, Bo
    et al.
    Örebro University, School of Health and Medical Sciences.
    Berglund, C
    Methicillin-resistant Staphylococcus saprophyticus in Sweden carries various types of staphylococcal cassette chromosome mec (SCCmec)2009In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 15, no 12, p. 1176-1178Article in journal (Refereed)
    Abstract [en]

    Staphylococcus saprophyticus is a common cause of uncomplicated urinary tract infections and is usually susceptible to the antimicrobial agents used for their treatment. However, S. saprophyticus resistant to beta-lactam antibiotics and carrying mecA has been reported. Eight Swedish isolates of mecA-positive S. saprophyticus with diverse origin carrying at least three different types of staphylococcal cassette chromosome mec (SCCmec) are described here.

  • 180.
    Söderquist, Bo
    et al.
    Örebro University, School of Health and Medical Sciences.
    Holmberg, A.
    Unemo, Magnus
    Propionibacterium acnes as an etiological agent of arthroplastic and osteosynthetic infections: two cases with specific clinical presentation including formation of draining fistulae2010In: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 16, no 3, p. 304-306Article in journal (Refereed)
    Abstract [en]

    This report describes two patients with orthopaedic implant infections, with specific clinical presentations including formation of draining fistulae. Propionibacterium acnes was isolated in multiple cultures in both cases. Phenotypic and genetic characterisation of the isolates clearly emphasizes the significance of P. acnes as an etiological agent of implant infections. These infections are insidious with delayed presentation of symptoms and may have been overlooked because of the consideration of P. acnes as a contaminating commensal as well as the frequent use of suboptimal culture procedures.

  • 181.
    Sörqvist, S.
    et al.
    Faculty of Veterinary Medicine, University of Agricultural Sciences, Uppsala, Sweden.
    Danielsson Tham, Marie-Louise
    Faculty of Veterinary Medicine, University of Agricultural Sciences, Uppsala, Sweden.
    Survival of Campylobacter, Salmonella and Yersinia spp. in scalding water used at pig slaughter1990In: Fleischwirtschaft international, ISSN 0179-2415, Vol. 70, no 12, p. 1451-1454Article in journal (Refereed)
    Abstract [en]

    Heat resistance was determined for various strains of C. coli and C. jejuni at 53, 54 and 56°C and S. derby, S. montevideo, S. typhimurium and Y. enterocolitica at 58, 60 and 62°C in autoclaved scalding water (SW; pHca8) and in some experiments in sterile physiological saline (PS; pH7). D values for Campylobacter and Salmonella (but not Yersinia) were significantly lower in SW than in PS, which was attributed to the difference in pH. It is concluded that only small numbers of Campylobacter, Salmonella and Yersinia would be expected to survive in SW at the commonly used temperatures (58-62°C), but temperatures above 62°C are recommended to minimise the risk of contamination.

  • 182.
    Sörqvist, Sven
    et al.
    Abteilung Lebensmittelhygiene, Veterinärmedizinische Fakultät der Schwedischen Universität für Agrarwissenschaften, Uppsala, Sweden.
    Danielsson Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Überleben von Campylobacter-, Salmonella- und Yersinia-Arten im Brühwasser bei der Schweineschlachtung1990In: Fleischwirtschaft international, ISSN 0179-2415, Vol. 70, no 12, p. 1460-1466Article in journal (Refereed)
  • 183.
    Tabrizi, Sepehr N.
    et al.
    Dept Microbiol & Infect Dis, Royal Womens Hosp, Parkville Vic, Australia; Dept Obstet & Gynaecol, Royal Womens Hosp, Univ Melbourne, Parkville Vic, Australia; Murdoch Childrens Res Inst, Parkville Vic, Australia.
    Unemo, Magnus
    Örebro University Hospital. Dept Lab Med, WHO Collaborating Ctr Gonorrhoea & Other STIs, Örebro University Hospital, Örebro, Sweden.
    Golparian, Daniel
    Dept Lab Med, WHO Collaborating Ctr Gonorrhoea & Other STIs, Örebro University Hospital, Örebro, Sweden.
    Twin, Jimmy
    Dept Obstet & Gynaecol, Royal Womens Hosp, Univ Melbourne, Parkville Vic, Australia; Murdoch Childrens Res Inst, Parkville Vic, Australia.
    Limnios, Athena E.
    Dept Microbiol, WHO Collaborating Ctr STD, Prince Wales Hosp, Randwick NSW, Australia.
    Lahra, Monica
    Dept Microbiol, WHO Collaborating Ctr STD, Prince Wales Hosp, Randwick NSW, Australia.
    Guy, Rebecca
    Dept Microbiol, Univ NSW, Sydney NSW, Australia; Kirby Inst, Univ NSW, Sydney NSW, Australia.
    Analytical Evaluation of GeneXpert CT/NG, the First Genetic Point-of-Care Assay for Simultaneous Detection of Neisseria gonorrhoeae and Chlamydia trachomatis2013In: Journal of Clinical Microbiology, ISSN 0095-1137, E-ISSN 1098-660X, Vol. 51, no 6, p. 1945-1947Article in journal (Refereed)
    Abstract [en]

    GeneXpert CT/NG was evaluated with 372 characterized bacterial strains. Sensitivity of 10 genome copies/reaction was obtained for both agents. Four Neisseria mucosa and two Neisseria subflava isolates were positive for one of two gonococcal targets; however, the assay flagged all as negative. The assay was analytically highly sensitive and specific.

  • 184.
    Tevell, Staffan
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Infectious Diseases, Karlstad Hospital, Karlstad, Sweden.
    Claesson, C.
    Division of Clinical Microbiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Department of Clinical Microbiology, County Council of Östergötland, Linköping, Sweden.
    Hellmark, Bengt
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden; Department of Infectious Diseases, Örebro University Hospital, Örebro, Sweden.
    Nilsdotter-Augustinsson, Å.
    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.
    Heterogeneous glycopeptide intermediate Staphylococcus epidermidis isolated from prosthetic joint infections2014In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 33, no 6, p. 911-917Article in journal (Refereed)
    Abstract [en]

    Methicillin-resistant Staphylococcus epidermidis (MRSE) poses a major problem in prosthetic joint infections (PJIs). Vancomycin is often considered the drug of choice in the empirical treatment of staphylococcal PJIs. As recent decades have seen reports of heterogeneous glycopeptide intermediate S. aureus (hGISA), our aim was to examine the prevalence of heterogeneous glycopeptide intermediate S. epidermidis (hGISE) in PJIs. S. epidermidis isolates (n = 122) from 119 patients in three Swedish counties between 1993 and 2012 were included. All were isolated from perioperative tissue samples from revision surgery in clinically verified PJIs. Antimicrobial susceptibility testing against staphylococcal antibiotics was performed. The macromethod Etest (MME) and glycopeptide resistance detection (GRD) Etest were used to detect hGISE. Standard minimal inhibitory concentration (MIC) determination revealed no vancomycin-resistant isolates, while teicoplanin resistance was detected in 14 out of 122 isolates (11.5 %). hGISE was found in 95 out of 122 isolates (77.9 %), 64 out of 67 of isolates with teicoplanin MIC > 2 mg/L (95.5 %) and 31 out of 55 of isolates with teicoplanin MIC a parts per thousand currency sign2 mg/L (56.4 %). Thus, the presence of hGISE cannot be ruled out by teicoplanin MIC a parts per thousand currency sign2 mg/L alone. Multidrug resistance was detected in 86 out of 95 hGISE isolates (90.5 %) and in 16 out of 27 isolates (59.3 %), where hGISE could not be detected. In conclusion, hGISE detected by MME or GRD was common in this material. However, hGISE is difficult to detect with standard laboratory diagnostic routines. Glycopeptide treatment may not be sufficient in many of these PJIs, even if standard MIC classifies the isolated S. epidermidis as susceptible.

  • 185.
    Thorberg, Britt-Marie
    et al.
    Division of Food Hygiene and Bacteriology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Kühn, Inger
    Microbiology and Tumour Biology Centre, Karolinska Institute, Stockholm, Sweden.
    Møller Aarestrup, Frank
    Danish Institute for Food and Veterinary Research, Copenhagen, Denmark.
    Brändström, Boel
    The National Veterinary Institute, Uppsala, Sweden.
    Jonsson, Per
    County Administrative Board of Södermanland, Nyköping, Sweden.
    Danielsson Tham, Marie-Louise
    Division of Food Hygiene and Bacteriology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Pheno- and genotyping of Staphylococcus epidermidis isolated from bovine milk and human skin2006In: Veterinary Microbiology, ISSN 0378-1135, E-ISSN 1873-2542, Vol. 115, no 1-3, p. 163-172Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to improve our knowledge concerning the epidemiology and strain diversity of Staphylococcus epidermidis isolated from bovine milk in commercial dairy herds. A total of 341 S. epidermidis isolates obtained from cows' milk (317), farmers (17) and patients (7) were characterized. Of these 105 isolates were from cows' milk in two farms, where also 17 isolates were sampled from farmers. The remaining 212 isolates from cows' milk were from 170 farms. All isolates were examined by antimicrobial susceptibility, whereas 202 were examined by pulsed-field gel electrophoresis (PFGE) and 122 by ribotyping. PFGE showed single patterns in the human strains with one exception; one strain was categorised as the same clone as four of the milk strains. PFGE divided 73 of the milk strains into 62 different patterns. The PFGE method had high discriminatory power and shows that many different S. epidermidis types exist in milk samples. Antibiotic resistance patterns matched the SmaI profiles closely in the two herds, but poorly in the routinely collected milk samples. Isolates from herd I showed one to five patterns, depending on the typing method used. Isolates from the milker's skin showed one pattern, which was identical to the most common pattern found in the milk isolates. Isolates from herd 2 showed three to four patterns, two of these being identical to skin isolates from the milker. As dairy cows are not a natural host for S. epidermidis the results suggest a human source of these udder infections.

  • 186.
    Thorstenson, Andreas
    et al.
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden; Department of Molecular Medicine and Surgery, Section of Urology, Karolinska Institute, Stockholm, Sweden; Surgical Intervention Trials Unit, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
    Harmenberg, Ulrika
    Department of Oncology, Karolinska University Hospital, Solna, Stockholm, Sweden.
    Lindblad, Per
    Örebro University, School of Medicine, Örebro University, Sweden. Dept Urol, Örebro University Hospital, Örebro, Sweden.
    Holmström, Benny
    Department of Urology, Akademiska University Hospital, Uppsala, Sweden.
    Lundstam, Sven
    Department of Urology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Ljungberg, Börje
    Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
    Cancer Characteristics and Current Treatments of Patients with Renal Cell Carcinoma in Sweden2015In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, article id 456040Article in journal (Refereed)
    Abstract [en]

    Methodology: Since the start in 2005 virtually all patients with newly diagnosed renal cell carcinoma (RCC) in Sweden are reported to the National Swedish Kidney Cancer Register (NSKCR). The register contains information on histopathology, nuclear grade, clinical stage, preoperative work-up, treatment, recurrence, and survival.

    Results: A total of 8556 patients with newly diagnosed RCC were registered in the NSKCR from 2005 to 2013 resulting in a coverage of 99% as compared to the Swedish Cancer Registry. The mean tumor size at detection decreased from 70 mm in 2005 to 64 mm in 2010. The proportion of patients who were incidentally detected increased. The proportion of patients with tumor stage T1a who underwent partial nephrectomy increased from 22% in 2005 to 56% in 2012. Similarly, the proportion of laparoscopically performed radical nephrectomies increased from 6% in 2005 to 17% in 2010. During the five years of follow-up 20% of the patients had a recurrence.

    Conclusion: Over the last decade there has been a trend of earlier detection and less advanced tumors at detection in patients with RCC. An increasing proportion of the patients undergo laparoscopic and nephron-sparing procedures.

  • 187.
    Thulin Hedberg, Sara
    Örebro University, School of Health and Medical Sciences.
    Antibiotic susceptibility and resistance in Neisseria meningitidis: phenotypic and genotypic characteristics2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Neisseria meningitidis, also known as the meningococcus, is a globally spread obligate human bacterium causing meningitis and/or septicaemia. It is responsible for epidemics in both developed and developing countries. Untreated invasive meningococcal disease is often fatal, and despite modern intensive care units, the mortality is still remarkably high (approximately 10%). The continuously increasing antibiotic resistance in many bacterial pathogens is a serious public health threat worldwide and there have been numerous reports of emerging resistance in meningococci during the past decades.

    In paper I, the gene linked to reduced susceptibility to penicillins, the penA gene, was examined. The totally reported variation in all published penA genes was described. The penA gene was highly variable (in total 130 variants were identified). By examination of clinical meningococcal isolates, the association between penA gene sequences and penicillin susceptibility could be determined. Isolates with reduced susceptibility displayed mosaic structures in the penA gene. Two closely positioned nucleotide polymorphisms were identified in all isolates with reduced penicillin susceptibility and mosaic structured penA genes. These alterations were absent in all susceptible isolates and were successfully used to detect reduced penicillin susceptibility by real-time PCR and pyrosequencing in paper II. In papers III and IV, antibiotic susceptibility and characteristics of Swedish and African meningitis belt meningococcal isolates were comprehensively described. Although both populations were mainly susceptible to the antibiotics used for treatment and prophylaxis, the proportion of meningococci with reduced penicillin susceptibility was slightly higher in Sweden. A large proportion of the African isolates was resistant to tetracycline and erythromycin. In paper V, the gene linked to rifampicin resistance, the rpoB gene, was examined in meningococci from 12 mainly European countries. Alterations of three amino acids in the RpoB protein were found to always and directly lead to rifampicin resistance. A new breakpoint for rifampicin resistance in meningococci was suggested. The biological cost of the RpoB alterations was investigated in mice. The pathogenicity/virulence was significantly lower in rifampicin resistant mutants as compared with susceptible wild-type bacteria.

    List of papers
    1. Total variation in the penA gene of Neisseria meningitidis: correlation between susceptibility to beta-lactam antibiotics and penA gene heterogeneity
    Open this publication in new window or tab >>Total variation in the penA gene of Neisseria meningitidis: correlation between susceptibility to beta-lactam antibiotics and penA gene heterogeneity
    2006 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 50, no 10, p. 3317-3324Article in journal (Refereed) Published
    Abstract [en]

    In recent decades, the prevalence of Neisseria meningitidis isolates with reduced susceptibility to penicillins has increased. The intermediate resistance to penicillin (Pen(i)) for most strains is due mainly to mosaic structures in the penA gene, encoding penicillin-binding protein 2. In this study, susceptibility to beta-lactam antibiotics was determined for 60 Swedish clinical N. meningitidis isolates and 19 reference strains. The penA gene was sequenced and compared to 237 penA sequences from GenBank in order to explore the total identified variation of penA. The divergent mosaic alleles differed by 3% to 24% compared to those of the designated wild-type penA gene. By studying the final 1,143 to 1,149 bp of penA in a sequence alignment, 130 sequence variants were identified. In a 402-bp alignment of the most variable regions, 84 variants were recognized. Good correlation between elevated MICs and the presence of penA mosaic structures was found especially for penicillin G and ampicillin. The Pen(i) isolates comprised an MIC of >0.094 microg/ml for penicillin G and an MIC of >0.064 microg/ml for ampicillin. Ampicillin was the best antibiotic for precise categorization as Pen(s) or Pen(i). In comparison with the wild-type penA sequence, two specific Pen(i) sites were altered in all except two mosaic penA sequences, which were published in GenBank and no MICs of the corresponding isolates were described. In conclusion, monitoring the relationship between penA sequences and MICs to penicillins is crucial for developing fast and objective methods for susceptibility determination. By studying the penA gene, genotypical determination of susceptibility in culture-negative cases can also be accomplished.

    National Category
    Medical and Health Sciences
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:oru:diva-8529 (URN)10.1128/AAC.00353-06 (DOI)17005811 (PubMedID)
    Available from: 2009-11-25 Created: 2009-11-12 Last updated: 2017-12-12Bibliographically approved
    2. Combined real-time PCR and pyrosequencing strategy for objective, sensitive, specific, and high throughput identification of reduced susceptibility to penicillins in Neisseria meningitidis
    Open this publication in new window or tab >>Combined real-time PCR and pyrosequencing strategy for objective, sensitive, specific, and high throughput identification of reduced susceptibility to penicillins in Neisseria meningitidis
    2008 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 52, no 2, p. 753-756Article in journal (Refereed) Published
    Abstract [en]

    A segment of penA in Neisseria meningitidis strains (n = 127), including two nucleotide sites closely associated to reduced susceptibility to penicillins, was amplified and pyrosequenced. All results were in concordance with Sanger sequencing, and a high correlation between alterations in the two Pen(i)-specific sites and reduced susceptibility to penicillins was identified.

    Place, publisher, year, edition, pages
    Washington, DC: American Society for Microbiology, 2008
    Keywords
    Anti-Bacterial Agents/pharmacology, Bacterial Proteins/chemistry/genetics, Base Sequence, Humans, Microbial Sensitivity Tests/methods, Molecular Sequence Data, Neisseria meningitidis/*drug effects, Penicillin Resistance, Penicillin-Binding Proteins/chemistry/genetics, Penicillins/*pharmacology, Polymerase Chain Reaction/methods, Sensitivity and Specificity, Sequence Analysis; DNA
    National Category
    Medical and Health Sciences Infectious Medicine
    Research subject
    Infectious Diseases; Medicine
    Identifiers
    urn:nbn:se:oru:diva-3451 (URN)10.1128/AAC.00914-07 (DOI)18070955 (PubMedID)
    Available from: 2008-12-08 Created: 2008-12-08 Last updated: 2017-12-14Bibliographically approved
    3. Antibiotic susceptibility and characteristics of Neisseria meningitidis isolates from the African meningitis belt, 2000 to 2006: phenotypic and genotypic perspectives
    Open this publication in new window or tab >>Antibiotic susceptibility and characteristics of Neisseria meningitidis isolates from the African meningitis belt, 2000 to 2006: phenotypic and genotypic perspectives
    Show others...
    2009 (English)In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 53, no 4, p. 1561-1566Article in journal (Refereed) Published
    Abstract [en]

    Up-to-date information regarding the antibiotic susceptibility of Neisseria meningitidis strains from African countries is highly limited. Our aim was to comprehensively describe the antibiotic susceptibilities of a selection of N. meningitidis isolates recovered between 2000 and 2006 from 18 African countries, mainly those within the meningitis belt. Susceptibilities to 11 antibiotics were determined using Etest for 137 N. meningitidis isolates (stringently selected from 693 available isolates). The isolates were also characterized by serogrouping, multilocus sequence typing, genosubtyping, and penA allele identification. All N. meningitidis isolates were susceptible to ceftriaxone, chloramphenicol, and ciprofloxacin. No isolate produced beta-lactamase. Only three isolates (2%) displayed reduced susceptibility to penicillin G. The two isolates with the highest penicillin G MICs were the only isolates showing reduced susceptibility to ampicillin and cefuroxime. One of these isolates was also resistant to penicillin V. One percent of isolates displayed reduced susceptibility to rifampin, while 52% of the isolates were resistant to tetracycline, 74% were resistant to erythromycin, and 94% were resistant to sulfadiazine. The MICs of rifampin and tetracycline seemed to be associated with the serogroup of the isolates. In total, 18 sequence types (STs), 10 genosubtypes, and 8 different penA alleles were identified; the most common were ST-7, P1.20,9,35-1, and penA4, respectively. A high level of correlation was found between ST, genosubtype, and penA allele. In conclusion, N. meningitidis isolates from the African meningitis belt remain highly susceptible to the antibiotics used. Regarding beta-lactam antibiotics, rare isolates showed a reduced susceptibility to penicillins, but the expanded-spectrum cephalosporins are not affected at present.

    National Category
    Medical and Health Sciences Microbiology in the medical area
    Research subject
    Microbiology; Physiology; Biomedicine
    Identifiers
    urn:nbn:se:oru:diva-8630 (URN)10.1128/AAC.00994-08 (DOI)19188396 (PubMedID)
    Available from: 2009-11-25 Created: 2009-11-23 Last updated: 2018-01-12Bibliographically approved
    4. Antibiotic susceptibility of invasive Neisseria meningitidis isolates from 1995 to 2008 in Sweden: the meningococcal population remains susceptible
    Open this publication in new window or tab >>Antibiotic susceptibility of invasive Neisseria meningitidis isolates from 1995 to 2008 in Sweden: the meningococcal population remains susceptible
    2010 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 42, no 1, p. 61-64Article in journal (Refereed) Published
    Abstract [en]

    The susceptibility to 7 antibiotics was determined for all Swedish invasive Neisseria meningitidis isolates from 1995 to 2008 (N=717). In general, these remain highly susceptible to the antibiotics recommended for use. Accordingly, penicillin G remains effective for the treatment of invasive meningococcal disease and ciprofloxacin appropriate for prophylaxis.

    National Category
    Medical and Health Sciences
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:oru:diva-8532 (URN)10.3109/00365540903292682 (DOI)000274210500009 ()19883157 (PubMedID)
    Available from: 2009-11-25 Created: 2009-11-12 Last updated: 2018-02-23Bibliographically approved
    5. Defining the breakpoint for resistance to rifampicin in Neisseria meningitidis by rpoB sequencing
    Open this publication in new window or tab >>Defining the breakpoint for resistance to rifampicin in Neisseria meningitidis by rpoB sequencing
    Show others...
    2009 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Clinical isolates of Neisseria meningitidis resistant to rifampicin are important to identify asthey lead to failure of chemoprophylaxis of meningococcal disease. However, theidentification of these isolates is hindered by the absence of a harmonized breakpoint despiteefforts of standardization. In the present study, a large number (n=352) of clinical N.meningitidis isolates from 12 mainly European countries and spanning over 25 years (1984 to2009) were examined. The collection comprised all clinical isolates with MIC 0.25 mg/lreceived by the national reference laboratories for meningococci in the participating countries(n=161). In addition, representative isolates displaying MIC of rifampicin <0.25 mg/l wereexamined (n=191). Phenotyping and genotyping of isolates were performed and a 660 bpDNA fragment of the rpoB gene was sequenced in all the included isolates. Sequencesdiffering by at least one nucleotide were defined as a unique rpoB allele (n=55). Geometricmeans of MIC were calculated for isolates displaying the same allele. All the clinical isolatesdisplaying MIC >1 mg/l of rifampicin possessed rpoB alleles with critical mutations (in total21 alleles), resulting in substitutions at the codon H552 and less frequently at nearby codons(S548 and S557). These alterations were absent in the alleles (n=34) found in all isolates withMIC 1 mg/l. Based on these findings, rifampicin susceptible isolates could be defined asthose with MIC 1 mg/l. A new web site was created based on the data from this work (http://neisseria.org/nm/typing/rpoB). The rifampicin resistant isolates belonged to diversegenetic lineages and provoked lower bacteremia levels in mice. This biological cost mayexplain the non-expansion of the rifampicin resistant isolates.

    National Category
    Medical and Health Sciences
    Research subject
    Medicine
    Identifiers
    urn:nbn:se:oru:diva-8655 (URN)
    Available from: 2009-11-25 Created: 2009-11-25 Last updated: 2017-10-18Bibliographically approved
  • 188.
    Thulin Hedberg, Sara
    et al.
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Eriksson, Lorraine
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Demontis, Maria A.
    Imperial College, St Mary’s Hospital, London, UK.
    Mölling, Paula
    Department of Laboratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Sundqvist, Martin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Taylor, Graham
    Imperial College, St Mary’s Hospital, London, UK.
    Malm, Kerstin
    Örebro University, School of Health Sciences. Örebro University Hospital. Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Andersson, Sören
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine.
    Droplet digital PCR for absolute quantification of proviral load of human T-cell lymphotropic virus (HTLV) types 1 and 22018In: Journal of Virological Methods, ISSN 0166-0934, E-ISSN 1879-0984, Vol. 260, p. 70-74Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Human T-lymphotrophic virus (HTLV) types 1 and 2 cause lifelong infection whereby most infected individuals are asymptomatic whilst a minority develop infection-related disease. These latter patients invariably have been found to have high proviral load (PVL). Therefore, infected patients are monitored by determining the proportion of lymphocytes that are infected with HTLV-1/2. An increase in PVL has been shown to represent an increasing risk of developing HTLV-associated diseases. Monitoring of PVL requires a reliable and sensitive method. In this study assays based on droplet digital PCR (ddPCR) were established and evaluated for detection and quantification of HTLV-1/2.

    OBJECTIVES: To develop two parallel assays to detect the tax genes and determine the PVL of HTLV-1 and -2.

    STUDY DESIGN: Sixty-seven clinical samples from patients infected with HTLV-1 or HTLV-2 were analysed. The samples had previously been analysed with a qPCR and a comparison between ddPCR and qPCR was performed. The specificity of the assays were determined by analyzing samples from 20 healthy blood donors.

    RESULTS: The ddPCR was a stable and sensitive method for detection and quantification of HTLV-1 and -2. When comparing the qPCR and ddPCR the correlation was high (Pearsons correlation coefficient 0.96). The variability of the ddPCR was very low with intra-assay coefficient of variation (CV) of 0.97-3.3% (HTLV-1) and 1.7-8.2% (HTLV-2) and inter-assay CV of 1.8-6.1% (HTLV-1) and 1.2-12.9% (HTLV-2).

    CONCLUSIONS: The ddPCR reliably quantified HTLV DNA in clinical samples and could be a useful tool for monitoring of PVLs in HTLV-infected individuals.

  • 189.
    Titov, Leonid P.
    et al.
    Republ Res & Pract Ctr Epidemiol & Microbiol, Minsk, Byelarus.
    Siniuk, Kanstantsin V.
    Republ Res & Pract Ctr Epidemiol & Microbiol, Minsk, Byelarus.
    Wollenberg, Kurt K.
    National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda MD, USA.
    Unemo, Magnus
    Örebro University Hospital. Dept Lab Med, Natl Reference Lab Pathogen Neisseria, Örebro University Hospital, Örebro, Sweden.
    Thulin Hedberg, Sara
    Örebro University Hospital. Dept Lab Med, Natl Reference Lab Pathogen Neisseria, Örebro University Hospital, Örebro, Sweden.
    Glazkova, Slavyana E.
    Republ Res & Pract Ctr Epidemiol & Microbiol, Minsk, Byelarus.
    Lebedzeu, Fiodar A.
    Republ Res & Pract Ctr Epidemiol & Microbiol, Minsk, Byelarus.
    Nosava, Alena S.
    Republ Res & Pract Ctr Epidemiol & Microbiol, Minsk, Byelarus.
    Yanovich, Volcha O.
    Republ Res & Pract Ctr Epidemiol & Microbiol, Minsk, Byelarus.
    Xirasagar, Sadhia
    National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda MD, USA.
    Hurt, Darrell
    National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda MD, USA.
    Huyen, Yentram
    National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda MD, USA.
    Evolutionary epidemiology of Neisseria meningitidis strains in Belarus compared to other European countries2013In: Acta Microbiologica et Immunologica Hungarica, ISSN 1217-8950, Vol. 60, no 4, p. 397-410Article in journal (Refereed)
    Abstract [en]

    Introduction. Meningococcal infections are major causes of death in children globally. In Belarus, the incidence of cases and fatality rate of meningococcal infections are low and comparable to the levels in other European countries. Aim. In the present study, the molecular and epidemiological traits of Neisseria meningitidis strains circulating in Belarus were characterized and compared to isolates from other European countries. Materials and Methods. Twenty N. meningitidis strains isolated from patients (n = 13) and healthy contacts (n = 7) during 2006-2012 in Belarus were selected for multilocus sequence typing (MLST), genosubtyping and FetA typing. The STs of the Belarusian strains were phylogenetically compared to the STs of 110 selected strains from 22 other European countries. Results. Overall, eleven different genosubtypes were observed, there were seven variants of variable region of the fetA gene detected. The majority of the STs (95%) found in Belarus were novel and all those were submitted to the Neisseria MLST database for assignment. Several newly discovered alleles of fumC (allele 451) and gdh (allele 560 and 621) appeared to be descendants of alleles which are widespread in Europe, and single aroE alleles (602 and 603) occurred as a result of separate evolution. Conclusions. N. meningitidis strains circulating in Belarus are heterogeneous and include sequence types, possibly, locally evolved in Belarus as well as representatives of widespread European hyperinvasive clonal complexes.

  • 190. Toepfer, M.
    et al.
    Magnusson, C.
    Norén, Torbjörn
    Örebro University Hospital.
    Hansen, I.
    Iveroth, P.
    Offenbartl, K.
    Lömskt och omfattande utbrott av Clostridium difficile. Ändrade städrutiner och täta utvärderingar halverade infektionerna2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 1-2, p. 24-Article in journal (Refereed)
    Abstract [en]

    Höglandssjukhuset, a hospital in Jönköping County, serves 110,000 people. By 2011, local laboratory data and health care associated infection data indicated that the hospital had a significant CDI problem compared to the county's other two hospitals. Standards for monitoring CDI levels at the hospital level have not previously been established in Sweden. This local outbreak affected most hospital wards. Initiatives focused on room cleaning, diagnosis, and casereporting started in June 2011 but failed to improve levels after 6 months. Further countermeasures were implemented starting in May 2012, with use of hypochlorite in a one-time hospital »deep clean« and its subsequent use as standard CD cleaning agent. Thereafter, a more than 50% sustained reduction of CDI levels (~10 cases/ month) was noted as compared to corresponding monthly levels in 2011. Careful surveillance, cleaning with hypochlorite, and antibiotic stewardship initiatives comprise the continuing anti-CDI program.

  • 191.
    Tomberg, Joshua
    et al.
    Dept Pharmacol, University of North Carolina,Chapel Hill NC, USA.
    Unemo, Magnus
    Örebro University Hospital. Dept Lab Med, WHO Collaborating Ctr Gonorrhoea & Other STls, Örebro University Hospital, Örebro, Sweden.
    Ohnishi, Makoto
    Natl Inst Infect Dis, Tokyo, Japan.
    Davies, Christopher
    Dept Biochem & Mol Biol, Medical Univ South Carolina, Charleston SC, USA.
    Nicholas, Robert A.
    Dept Pharmacol, University of North Carolina, Chapel Hill NC, USA; Dept Microbiol & Immunol, University of North Carolina,Chapel Hill NC, USA.
    Identification of Amino Acids Conferring High-Level Resistance to Expanded-Spectrum Cephalosporins in the penA Gene from Neisseria gonorrhoeae Strain H0412013In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 57, no 7, p. 3029-3036Article in journal (Refereed)
    Abstract [en]

    The recent identification of a high-level-ceftriaxone-resistant (MIC = 2 to 4 mu g/ml) isolate of Neisseria gonorrhoeae from Japan (H041) portends the loss of ceftriaxone as an effective treatment for gonococcal infections. This is of grave concern because ceftriaxone is the last remaining option for first-line empirical antimicrobial monotherapy. The penA gene from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance (Ceph(i)) worldwide but has 13 additional mutations compared to the mosaic penA gene from the previously studied Ceph(i) strain 35/02 (penA35). When transformed into the wild-type strain FA19, the penA41 allele confers 300- and 570-fold increases in the MICs for ceftriaxone and cefixime, respectively. In order to understand the mechanisms involved in high-level ceftriaxone resistance and to improve surveillance and epidemiology during the potential emergence of ceftriaxone resistance, we sought to identify the minimum number of amino acid alterations above those in penA35 that confer high-level resistance to ceftriaxone. Using restriction fragment exchange and site-directed mutagenesis, we identified three mutations, A311V, T316P, and T483S, that, when incorporated into the mosaic penA35 allele, confer essentially all of the increased resistance of penA41. A311V and T316P are close to the active-site nucleophile Ser310 that forms the acyl-enzyme complex, while Thr483 is predicted to interact with the carboxylate of the beta-lactam antibiotic. These three mutations have thus far been described only for penA41, but dissemination of these mutations in other mosaic alleles would spell the end of ceftriaxone as an effective treatment for gonococcal infections.

  • 192.
    Unemo, Magnus
    et al.
    Örebro University, Department of Health Sciences.
    Friberg, Örjan
    Enquist, Emma
    Källman, Jan
    Söderquist, Bo
    Örebro University, School of Health and Medical Sciences.
    Genetic homogeneity/heterogeneity of Propionibacterium acnes isolated from patients during cardiothoracic reoperation2007In: Anaerobe, ISSN 1075-9964, E-ISSN 1095-8274, Vol. 13, no 3-4, p. 121-126Article in journal (Refereed)
    Abstract [en]

    Following cardiothoracic surgery, deep sternal wound infection (SWI) remains one of the most severe complications. Recently, Propionibacterium acnes has been suspected as an etiological agent of deep SWI. However, this bacterium constitutes part of the resident micro-flora of the human skin. Consequently, findings of P. acnes in invasive samples are difficult to value. The aims of this study were to develop and optimize a pulsed-field gel electrophoresis (PFGE) protocol for P. acnes, in order to investigate the genetic homogeneity/heterogeneity of P. acnes isolates from multiple tissue samples (predominantly biopsies), collected at different locations, from 12 patients during cardiothoracic reoperation. There were 24 distinguishable PFGE fingerprints identified among the P. acnes isolates (n=54). Five (42%) of the patients carried only isolates that were interpreted as presumably clonally related. From the remaining seven patients, two or three different P. acnes clones were cultured, however, from six of them, the clones were identified in multiple samples. P. acnes may be a relatively frequent etiological agent of postoperative cardiothoracic infections. Existence of several clonally related P. acnes isolates derived from multiple samples from patients suffering from deep SWI after cardiothoracic surgery has not previously been shown.

  • 193.
    Unemo, Magnus
    et al.
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Golparian, Daniel
    WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and other STIs, Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden.
    First Three Neisseria gonorrhoeae Isolates with High-Level Resistance to Azithromycin in Sweden: a Threat to Currently Available Dual-Antimicrobial Regimens for Treatment of Gonorrhea?2014In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 58, no 1, p. 624-625Article in journal (Refereed)
  • 194.
    Unemo, Magnus
    et al.
    Örebro University Hospital. WHO Collaborating Ctr Gonorrhoea & Other STIs, Dept Lab Med, Swedish Reference Lab Pathogen Neisseria, Örebro University Hospital, Örebro, Sweden.
    Golparian, Daniel
    WHO Collaborating Ctr Gonorrhoea & Other STIs, Dept Lab Med, Swedish Reference Lab Pathogen Neisseria, Örebro University Hospital, Örebro, Sweden.
    Skogen, Vegard
    Dept Infect Dis, Univ Hosp N Norway, Tromsö, Norway; Inst Clin Med, Univ Tromsö, Tromsö, Norway.
    Olsen, Anne Olaug
    Olafiaklin, Oslo Univ Hosp, Oslo, Norway; Inst Clin Med, Univ Oslo, Oslo, Norway.
    Moi, Harald
    Olafiaklin, Oslo Univ Hosp, Oslo, Norway; Inst Clin Med, Univ Oslo, Oslo, Norway.
    Syversen, Gaute
    Dept Microbiol, Oslo Univ Hosp, Oslo, Norway.
    Hjelmevoll, Stig Ove
    Dept Microbiol & Infect Control, Univ Hosp N Norway, Tromsö, Norway.
    Neisseria gonorrhoeae Strain with High-Level Resistance to Spectinomycin Due to a Novel Resistance Mechanism (Mutated Ribosomal Protein S5) Verified in Norway2013In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 57, no 2, p. 1057-1061Article in journal (Refereed)
    Abstract [en]

    Gonorrhea may become untreatable, and new treatment options are essential. Verified resistance to spectinomycin is exceedingly rare. However, we describe a high-level spectinomycin-resistant (MIC, >1,024 mu g/ml) Neisseria gonorrhoeae strain from Norway with a novel resistance mechanism. The resistance determinant was a deletion of codon 27 (valine) and a K28E alteration in the ribosomal protein 5S. The traditional spectinomycin resistance gene (16S rRNA) was wild type. Despite this exceedingly rare finding, spectinomycin available for treatment of ceftriaxone-resistant urogenital gonorrhea would be very valuable.

  • 195.
    Unemo, Magnus
    et al.
    Örebro University, School of Health and Medical Sciences.
    Olcén, Per
    Örebro University, School of Health and Medical Sciences.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences.
    Hedberg, Sara Thulin
    Örebro University, School of Health and Medical Sciences.
    Real-time PCR and subsequent pyrosequencing for screening of penA mosaic alleles and prediction of reduced susceptibility to expanded-spectrum cephalosporins in Neisseria gonorrhoeae2008In: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, no 11, p. 1004-1008Article in journal (Refereed)
  • 196.
    Unemo, Magnus
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Örebro University Hospital, Örebro, Sweden; Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Ringlander, Johan
    WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Örebro University, Örebro Sweden; Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Wiggins, Catherine
    Sexually Transmitted Bacteria Reference Unit, Public Health England, London, United Kingdom.
    Fredlund, Hans
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Örebro University, Örebro Sweden; Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Jacobsson, Susanne
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Örebro University, Örebro Sweden; Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Cole, Michelle
    Sexually Transmitted Bacteria Reference Unit, Public Health England, London, United Kingdom.
    High In Vitro Susceptibility to the Novel Spiropyrimidinetrione ETX0914 (AZD0914) among 873 Contemporary Clinical Neisseria gonorrhoeae Isolates from 21 European Countries from 2012 to 20142015In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 59, no 9, p. 5220-5225Article in journal (Refereed)
    Abstract [en]

    Resistance in Neisseria gonorrhoeae against all antimicrobials available for the treatment of gonorrhea has emerged. The first gonococcal strains with high-level resistance to ceftriaxone, the last option for first-line empirical antimicrobial monotherapy, were recently described. Consequently, new treatment options are essential. In this study, the in vitro activity of the novel spiropyrimidinetrione ETX0914 (AZD0914), a DNA topoisomerase II inhibitor, was investigated among contemporary consecutive clinical N. gonorrhoeae isolates obtained in 21 European countries and compared to the activities of antimicrobials currently or previously recommended for treatment. Consecutive clinical N. gonorrhoeae isolates (n = 873) cultured in 21 European countries from 2012 to 2014 were examined for their susceptibility to ETX0914. The MICs of ETX0914 were determined using the agar dilution method. For comparison, the MICs of ceftriaxone, cefixime, azithromycin, and ciprofloxacin were determined using Etest or the agar dilution method. For ETX0914, the MIC range, modal MIC, MIC50, and MIC90 were <= 0.002 to 0.25 mg/liter, 0.125 mg/liter, 0.064 mg/liter, and 0.125 mg/liter, respectively. The MIC values were substantially lower than those of the fluoroquinolone ciprofloxacin and most other antimicrobials examined. No cross-resistance with any other examined antimicrobial was observed. In conclusion, the in vitro susceptibility to the novel spiropyrimidinetrione ETX0914 (AZD0914) among 873 contemporary clinical isolates from 21 European countries was high, and no cross-resistance to antimicrobials currently or previously used for gonorrhea treatment was indicated. Additional studies investigating the in vitro and in vivo induction and mechanisms of ETX0914 resistance in gonococci, pharmacokinetics/pharmacodynamics in modeling/simulations and in humans, and performance in randomized controlled gonorrhea treatment trials are essential.

  • 197.
    Unemo, Magnus
    et al.
    Örebro University, Department of Clinical Medicine.
    Savicheva, A.
    Budilovskaya, O.
    Sokolovsky, E.
    Larsson, M.
    Domeika, M.
    Laboratory diagnosis of Neisseria gonorrhoeae in St Petersburg, Russia: inventory, performance characteristics and recommended optimisations2006In: Sexually Transmitted Infections, ISSN 1368-4973, E-ISSN 1472-3263, Vol. 82, no 1, p. 41-44Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To perform a comprehensive inventory of the number of samples, performance characteristics, and quality assurance of the laboratory diagnosis of Neisseria gonorrhoeae at five laboratories in St Petersburg and Leningradskaya Oblast, Russia, in 2004, and to recommend optimisations for an increased adherence to international evidence based recommendations of diagnostics. METHODS: Surveillance data were obtained with questionnaire and site visits. For evaluation of the culture media utilised at the laboratories, N gonorrhoeae reference strains (n = 29) were used. RESULTS: During 2004 the total numbers of N gonorrhoeae samples analysed at the five laboratories using microscopy of stained smears and culturing were 330 879 (407 positive) and 38 020 (420 positive), respectively. Four laboratories used a Russian non-selective culture medium-that is, Complegon, and one laboratory utilised Biocult-GC. Both media seemed suboptimal. Only two of the laboratories used any species confirmative assay. Antibiotic susceptibility testing of N gonorrhoeae was performed at only two of the laboratories and each year only occasional isolates were analysed. None of the laboratories comprised a complete laboratory quality assurance system. CONCLUSIONS: According to international recommendations, the diagnosis of N gonorrhoeae in St Petersburg and Leningradskaya Oblast, Russia, is suboptimal. More samples need to be analysed by culturing on a highly nutritious and selective medium and, furthermore, species confirmation and antibiotic susceptibility testing should be more frequently performed. In addition, the utilised methods for culturing and antibiotic susceptibility testing, including medium and interpretative criteria used, ought to be optimised, standardised, and quality assured using systematic internal and external quality controls.

  • 198.
    Unemo, Magnus
    et al.
    Örebro University Hospital. WHO Collaborating Centre for Gonorrhoea and Other Sexually Transmitted Infections, National Reference Laboratory for Pathogenic Neisseria, Dept. of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Shafer, William M.
    Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta GA, United States; Laboratories of Bacterial Pathogenesis, Veterans Affairs Medical Center, Decatur GA, United States.
    Antimicrobial Resistance in Neisseria gonorrhoeae in the 21st Century: Past, Evolution, and Future2014In: Clinical Microbiology Reviews, ISSN 0893-8512, E-ISSN 1098-6618, Vol. 27, no 3, p. 587-613Article, review/survey (Refereed)
    Abstract [en]

    Neisseria gonorrhoeae is evolving into a superbug with resistance to previously and currently recommended antimicrobials for treatment of gonorrhea, which is a major public health concern globally. Given the global nature of gonorrhea, the high rate of usage of antimicrobials, suboptimal control and monitoring of antimicrobial resistance (AMR) and treatment failures, slow update of treatment guidelines in most geographical settings, and the extraordinary capacity of the gonococci to develop and retain AMR, it is likely that the global problem of gonococcal AMR will worsen in the foreseeable future and that the severe complications of gonorrhea will emerge as a silent epidemic. By understanding the evolution, emergence, and spread of AMR in N. gonorrhoeae, including its molecular and phenotypic mechanisms, resistance to antimicrobials used clinically can be anticipated, future methods for genetic testing for AMR might permit region-specific and tailor-made antimicrobial therapy, and the design of novel antimicrobials to circumvent the resistance problems can be undertaken more rationally. This review focuses on the history and evolution of gonorrhea treatment regimens and emerging resistance to them, on genetic and phenotypic determinants of gonococcal resistance to previously and currently recommended antimicrobials, including biological costs or benefits; and on crucial actions and future advances necessary to detect and treat resistant gonococcal strains and, ultimately, retain gonorrhea as a treatable infection.

  • 199.
    Unemo, Mats
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. World Health Organization Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Salado-Rasmussen, K.
    Department of Dermatovenereology, Bispebjerg University Hospital, Copenhagen, Denmark.
    Hansen, M.
    World Health Organization Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Olsen, A. O.
    Olafia Clinic and National Advisory Unit for Sexually Transmitted Infections, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Falk, M.
    Department of Dermatovenereology, Örebro University Hospital, Örebro, Sweden.
    Golparian, Daniel
    Örebro University, School of Medical Sciences. World Health Organization Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Aasterød, M.
    Olafia Clinic and National Advisory Unit for Sexually Transmitted Infections, Oslo University Hospital, Oslo, Norway.
    Ringlander, J.
    World Health Organization Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Nilsson, C. Stezckó
    Department of Dermatovenereology, Örebro University Hospital, Örebro, Sweden.
    Sundqvist, Martin
    Örebro University, School of Medical Sciences. Örebro University Hospital. World Health Organization Collaborating Centre for Gonorrhoea and Other STIs, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Schønning, K.
    Department of Clinical Medicine, Faculty of Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Microbiology, Hvidovre University Hospital, Hvidovre, Denmark.
    Moi, H.
    Olafia Clinic and National Advisory Unit for Sexually Transmitted Infections, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
    Westh, H.
    Department of Clinical Medicine, Faculty of Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Microbiology, Hvidovre University Hospital, Hvidovre, Denmark.
    Jensen, J. S.
    Infection Preparedness, Research Unit for Reproductive Tract Microbiology, Statens Serum Institut, Copenhagen, Denmark.
    Clinical and analytical evaluation of the new Aptima Mycoplasma genitalium assay, with data on M. genitalium prevalence and antimicrobial resistance in M. genitalium in Denmark, Norway and Sweden in 20162018In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 24, no 5, p. 533-539Article in journal (Refereed)
    Abstract [en]

    Objectives: Mycoplasma genitalium (MG) causes urethritis and cervicitis, potentially causing reproductive complications. Resistance in MG to first-line (azithromycin) and second-line (moxifloxacin) treatment has increased. We examined the clinical and analytical performance of the new Conformite Europeene (CE)/in vitro diagnostics (IVD) Aptima Mycoplasma genitalium assay (CE/IVD AMG; Hologic); the prevalence of MG, Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); and MG resistance to azithromycin and moxifloxacin in Denmark, Norway and Sweden in 2016.

    Methods: From February 2016 to February 2017, urogenital and extragenital (only in Denmark) specimens from consecutive attendees at three sexually transmitted disease clinics were tested with the CE/ IVD AMG, the research-use-only MG Alt TMA-1 assay (Hologic), Aptima Combo 2 (CT/NG) assay and a laboratory-developed TaqMan real-time mgpB quantitative real-time PCR (qPCR). Resistance-associated mutations were determined by sequencing. Strains of MG and other mycoplasma species in different concentrations were also tested.

    Results: In total 5269 patients were included. The prevalence of MG was 7.2% (382/5269; 4.9-9.8% in the countries). The sensitivity of the CE/IVD AMG, MG Alt TMA-1 and mgpB qPCR ranged 99.13-100%, 99.13 -100% and 73.24-81.60%, respectively, in the countries. The specificity ranged 99.57-99.96%, 100% and 99.69-100%, respectively. The prevalence of resistance-associated mutations for azithromycin and moxifloxacin was 41.4% (120/290; 17.7-56.6%) and 6.6% (18/274; 4.1-10.2%), respectively. Multidrug resistance was found in all countries (2.7%; 1.1-4.2%).

    Conclusions: Both transcription-mediated amplification (TMA)-based MG assays had a highly superior sensitivity compared to the mgpB qPCR. The prevalence of MG and azithromycin resistance was high. Validated and quality-assured molecular tests for MG, routine resistance testing of MG-positive samples and antimicrobial resistance surveillance are crucial.

  • 200.
    Unnerstad, Helle
    et al.
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swed. Univ. of Agricultural Sciences, Uppsala, Sweden .
    Ericsson, Henrik
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swed. Univ. of Agricultural Sciences, Uppsala, Sweden .
    Alderborn, Allan
    Prosequencing AB, Uppsala, Sweden .
    Tham, Wilhelm
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swed. Univ. of Agricultural Sciences, Uppsala, Sweden .
    Danielsson-Tham, Marie-Louise
    Department of Food Hygiene, Faculty of Veterinary Medicine, Swed. Univ. of Agricultural Sciences, Uppsala, Sweden .
    Mattsson, Jens G.
    Department of Parasitology (SWEPAR), National Veterinary Institute, Uppsala, Sweden.
    Pyrosequencing as a method for grouping of Listeria monocytogenes strains on the basis of single-nucleotide polymorphisms in the inlB gene2001In: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 67, no 11, p. 5339-5342Article in journal (Refereed)
    Abstract [en]

    By using pyrosequencing (i.e., sequencing by synthesis) 106 strains of different serovars of Listeria monocytogenes were rapidly grouped into four categories based on nucleotide variations at positions 1575 and 1578 of the inlB gene. Strains of serovars 1/2a and 1/2c constituted one group, and strains of serovars 1/2b and 3b constituted another group, whereas serovar 4b strains were separated into two groups.

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