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1.
  • Björck, Viveka, et al. (author)
  • Morbidity and mortality in critically ill patients with invasive group A streptococcus infection : an observational study
  • 2020
  • In: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535. ; 24:1
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Group A streptococci (GAS) are known to cause serious invasive infections, but little is known about outcomes when patients with these infections are admitted to intensive care. We wanted to describe critically ill patients with severe sepsis or septic shock due to invasive GAS (iGAS) and compare them with other patients with severe sepsis or septic shock. METHODS: Adult patients admitted to a general intensive care unit (ICU) in Sweden (2007-2019) were screened for severe sepsis or septic shock according to Sepsis 2 definition. Individuals with iGAS infection were identified. The outcome variables were mortality, days alive and free of vasopressors and invasive mechanical ventilation, maximum acute kidney injury score for creatinine, use of continuous renal replacement therapy and maximum Sequential Organ Failure Assessment score during the ICU stay. Age, Simplified Acute Physiology Score (SAPS 3) and iGAS were used as independent, explanatory variables in regression analysis. Cox regression was used for survival analyses. RESULTS: iGAS was identified in 53 of 1021 (5.2%) patients. Patients with iGAS presented a lower median SAPS 3 score (62 [56-72]) vs 71 [61-81]), p < 0.001), had a higher frequency of cardiovascular cause of admission to the ICU (38 [72%] vs 145 [15%], p < 0.001) and had a higher median creatinine score (173 [100-311] vs 133 [86-208] μmol/L, p < 0.019). Of the GAS isolates, 50% were serotyped emm1/T1 and this group showed signs of more pronounced circulatory and renal failure than patients with non-emm1/T1 (p = 0.036 and p = 0.007, respectively). After correction for severity of illness (SAPS 3) and age, iGAS infection was associated with lower mortality risk (95% confidence interval (CI) of hazard ratio (HR) 0.204-0.746, p < 0.001). Morbidity analyses demonstrated that iGAS patients were more likely to develop renal failure. CONCLUSION: Critically ill patients with iGAS infection had a lower mortality risk but a higher degree of renal failure compared to similarly ill sepsis patients. emm1/T1 was found to be the most dominant serotype, and patients with emm1/T1 demonstrated more circulatory and renal failure than patients with other serotypes of iGAS.
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2.
  • Björkdahl, Ann, 1959, et al. (author)
  • Effect of very early supported discharge versus usual care on activi-ties of daily living ability after mild stroke: a randomized controlled trial.
  • 2023
  • In: Journal of rehabilitation medicine. - 1651-2081. ; 55
  • Journal article (peer-reviewed)abstract
    • To examine the ability to perform basic and instrumental activities of daily life after very early supported discharge vs usual discharge and referral routine during the first year after mild stroke.A secondary analysis of data from the Gothenburg Very Early Supported Discharge randomized controlled trial. Patients: A total of 104 patients (56% men; mean (standard deviation) age 75 (11) years) who had experienced a first stroke classified as mild.The primary outcome was the Activities of Daily Living Taxonomy score. Stroke Impact Scale (activities of daily living, and mobility) scores was a secondary measure. Patients were randomized to either very early supported discharge with 4 weeks of home rehabilitation provided by a multidisciplinary stroke team, or a control group discharged according to usual routine (referral to primary care when needed). Assessments were performed at discharge, 4 weeks post-discharge, and 3 and 12 months post-stroke.Instrumental activities of the Activities of Daily Living Taxonomy scores (the lower the better) in the very early supported discharge and control groups were median 4 and 6 (p=0.039) at 4 weeks post-discharge and 3 and 4.5 (p=0.013 at 3 months post-stroke, respectively. Stroke Impact Scale (Mobility) median scores (the higher the better) in the very early supported discharge and control groups at 3 months were 97 and 86 (p=0.040), respectively. There were no group differences in the 2 outcomes at 12 months post-stroke.Compared with usual discharge routine, team-based rehabilitation during the first month at home is beneficial for instrumental activity in the subacute phase, in patients with mild stroke. One year post-stroke both groups show equal results.
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3.
  • Cabak, Andrea, et al. (author)
  • Activity of airway antimicrobial peptides against cystic fibrosis pathogens
  • 2020
  • In: Pathogens and Disease. - : Oxford University Press. - 2049-632X. ; 78:7
  • Journal article (peer-reviewed)abstract
    • Antimicrobial peptides are important players of the innate host defence against invading microorganisms. The aim of this study was to evaluate the activity of airway antimicrobial peptides against the common cystic fibrosis (CF) pathogen Pseudomonas aeruginosa, and to compare it to the emerging multi-drug resistant CF pathogens Achromobacter xylosoxidans and Stenotrophomonas maltophilia. Clinical bacterial isolates from CF patients were used, and the antimicrobial activity of human beta-defensin 2 and 3, LL37 and lysozyme was evaluated using radial diffusion assay and viable counts. The cell surface zeta potential was analysed to estimate the net charge at the bacterial surface. Of the bacterial species included in the study, A. xylosoxidans was the most resistant to antimicrobial peptides, whereas P. aeruginosa was the most susceptible. The net charge of the bacterial surface was significantly more negative for P. aeruginosa compared to A. xylosoxidans, which may in part explain the differences in susceptibility.
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4.
  • Carlsson, Malin, et al. (author)
  • Pseudomonas aeruginosa in cystic fibrosis: Pyocyanin negative strains are associated with BPI-ANCA and progressive lung disease
  • 2011
  • In: Journal of Cystic Fibrosis. - : Elsevier Science B.V., Amsterdam.. - 1569-1993 .- 1873-5010. ; 10:4, s. 265-271
  • Journal article (peer-reviewed)abstract
    • The clinical consequence of chronic Pseudomonas aeruginosa colonization in cystic fibrosis (CF) varies between individuals for unknown reasons. Auto-antibodies against bactericidal/permeability increasing protein (BPI-ANCA) are associated with poor prognosis in CF. We hypothesize that there is a correlation between the presence of BPI-ANCA, the properties of the colonizing bacteria and the clinical conditions of the host. We compared isolates of P. aeruginosa from BPI-ANCA positive CF patients who have deteriorating lung disease with BPI-ANCA negative CF patients who are in stable clinical conditions. Epithelial cells (A549) and isolated polymorphonuclear granulocytes (PMNs) were stimulated with the isolates and cell death was analyzed with flow cytometry. We found that the ANCA associated strains in most cases showed pyocyanin negative phenotypes. These strains also induced less inflammatory response than the non-ANCA associated strains as shown by apoptosis and necrosis of epithelial cells and neutrophils. Our results suggest that colonization with strains of P. aeruginosa that induce a weak inflammatory response is associated with unfavorable outcome in CF. We speculate that inadequate control of pathogen proliferation through an insufficient inflammatory response results in a slowly increasing number of bacteria and accumulation of dying PMNs in the airways, contributing to progression in CF lung disease.
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5.
  • Jörgensen, Jimmy, et al. (author)
  • The majority of MRSA colonized children not given eradication treatment are still colonized one year later. Systemic antibiotics improve the eradication rate
  • 2018
  • In: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 50:9, s. 687-696
  • Journal article (peer-reviewed)abstract
    • Background: Colonization with methicillin-resistant Staphylococcus aureus (MRSA) can cause endogenously derived infections and be a source of transmission to other people. Neither colonization time of asymptomatic MRSA colonization nor the effect of treatment aiming at MRSA eradication in children has been thoroughly investigated. Methods: Two hundred ninety-three children <18 years in the mandatory follow-up program for MRSA-carriers in Malmö, Sweden were evaluated. Samples from the throat, nares, perineum and skin lesions from each child were screened for MRSA with a PCR-based broth enrichment method. PVL presence and spa-type were evaluated in a majority of cases. The sampling was repeated approximately every 6 month after initial detection. When three consecutive sets of negative samples during at least a 6-month period were obtained, the MRSA was considered permanently eradicated. MRSA eradication treatment given, on clinical grounds during follow-up, was noted. Results: One year after detection 62% of the untreated children were still MRSA positive and after 2 years 28%. MRSA throat colonization and having MRSA positive household contacts significantly prolonged the observed colonization time. Topical MRSA eradication treatment was successful in 36% of cases and in 65% if systemic antibiotics were added. Presence of PVL correlated with shorter observed colonization time in the older age group and with increased eradication success among throat carriers. Conclusion: MRSA throat colonization and having MRSA positive household contacts prolongs the time of MRSA colonization in children. Systemic antibiotics enhance the effect of MRSA eradication treatment.
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6.
  • Kahn, Fredrik, et al. (author)
  • Axillary abscess complicated by venous thrombosis, identification of Streptococcus pyogenes by 16S PCR.
  • 2010
  • In: Journal of Clinical Microbiology. - 1098-660X. ; 48:9, s. 3435-3437
  • Journal article (peer-reviewed)abstract
    • We report a case of an axillary abscess with Streptococcus pyogenes complicated by venous thrombosis. Bacterial etiology and typing was obtained by PCR and sequencing of the 16S rRNA and the M-protein genes from abscess material. The bacterium was of M41 serotype and serology indicated that it had expressed pro-coagulant factors.
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7.
  • Lager, Malin, et al. (author)
  • Molecular detection of Borrelia burgdorferi sensu lato - An analytical comparison of real-time PCR protocols from five different Scandinavian laboratories
  • 2017
  • In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 12:9
  • Journal article (peer-reviewed)abstract
    • Introduction Lyme borreliosis (LB) is the most common tick transmitted disease in Europe. The diagnosis of LB today is based on the patient A s medical history, clinical presentation and laboratory findings. The laboratory diagnostics are mainly based on antibody detection, but in certain conditions molecular detection by polymerase chain reaction (PCR) may serve as a complement. Aim The purpose of this study was to evaluate the analytical sensitivity, analytical specificity and concordance of eight different real-time PCR methods at five laboratories in Sweden, Norway and Denmark. Method Each participating laboratory was asked to analyse three different sets of samples (reference panels; all blinded) i) cDNA extracted and transcribed from water spiked with cultured Borrelia strains, ii) cerebrospinal fluid spiked with cultured Borrelia strains, and iii) DNA dilution series extracted from cultured Borrelia and relapsing fever strains. The results and the method descriptions of each laboratory were systematically evaluated. Results and conclusions The analytical sensitivities and the concordance between the eight protocols were in general high. The concordance was especially high between the protocols using 16S rRNA as the target gene, however, this concordance was mainly related to cDNA as the type of template. When comparing cDNA and DNA as the type of template the analytical sensitivity was in general higher for the protocols using DNA as template regardless of the use of target gene. The analytical specificity for all eight protocols was high. However, some protocols were not able to detect Borrelia spielmanii, Borrelia lusitaniae or Borrelia japonica.
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8.
  • Linge, Helena, et al. (author)
  • Midkine is expressed and differentially processed during COPD exacerbations and ventilator-associated pneumonia associated with Staphylococcus aureus infection.
  • 2013
  • In: Molecular medicine (Cambridge, Mass.). - : Springer Science and Business Media LLC. - 1528-3658 .- 1076-1551. ; 19, s. 314-323
  • Journal article (peer-reviewed)abstract
    • Staphylococcus aureus is sometimes isolated from the airways during acute exacerbations of chronic obstructive pulmonary disease (COPD) but more commonly recognized as a cause of ventilator-associated pneumonia (VAP). Antimicrobial proteins, among them midkine (MK), are an important part of innate immunity in the airways. In this study, the levels and possible processing of MK in relation to S. aureus infection of the airways were investigated, comparing COPD and VAP, thus comparing a state of disease with preceding chronic inflammation and remodeling (COPD) with acute inflammation (i.e. VAP). MK was detected in the small airways and alveoli of COPD lung tissue but less so in normal lung tissue. MK at below micromolar concentrations killed S. aureus in vitro. Proteolytic processing of MK by the staphylococcal metalloprotease AL but not cysteine protease SA, resulted in impaired bactericidal activity. Degradation was foremost seen in the COOH-terminal portion of the molecule that harbors high bactericidal activity. In addition, MK was detected in sputum from patients suffering from VAP caused by S. aureus but less so in sputum from COPD-exacerbations associated with the same bacterium. Recombinant MK was degraded more rapidly in sputum from the COPD patients than from the VAP patients and a greater proteolytic activity in COPD sputum was confirmed by zymography. Taken together, proteases of both bacteria and the host contribute to degradation of the antibacterial protein MK, resulting in an impaired defense of the airways, in particular in COPD where the state of chronic inflammation could be of importance.
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9.
  • Malmström, Lars, et al. (author)
  • Quantitative proteogenomics of human pathogens using DIA-MS.
  • 2015
  • In: Journal of Proteomics. - : Elsevier BV. - 1874-3919 .- 1876-7737. ; 129, s. 98-107
  • Journal article (peer-reviewed)abstract
    • The increasing number of bacterial genomes in combination with reproducible quantitative proteome measurements provides new opportunities to explore how genetic differences modulate proteome composition and virulence. It is challenging to combine genome and proteome data as the underlying genome influences the proteome. We present a strategy to facilitate the integration of genome data from several genetically similar bacterial strains with data-independent analysis mass spectrometry (DIA-MS) for rapid interrogation of the combined data sets. The strategy relies on the construction of a composite genome combining all genetic data in a compact format, which can accommodate the fusion with quantitative peptide and protein information determined via DIA-MS. We demonstrate the method by combining data sets from whole genome sequencing, shotgun MS and DIA-MS from 34 clinical isolates of Streptococcus pyogenes. The data structure allows for fast exploration of the data showing that undetected proteins are on average more amenable to amino acid substitution than expressed proteins. We identified several significantly differentially expressed proteins between invasive and non-invasive strains. The work underlines how integration of whole genome sequencing with accurately quantified proteomes can further advance the interpretation of the relationship between genomes, proteomes and virulence.
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10.
  • Neumark, Thomas, 1954-, et al. (author)
  • Spontaneously draining acute otitis media in children : An observational study of clinical findings, microbiology and clinical course
  • 2011
  • In: Scandinavian Journal of Infectious Diseases. - : Informa Healthcare. - 0036-5548 .- 1651-1980. ; 43:11-12, s. 891-898
  • Journal article (peer-reviewed)abstract
    • Conclusion: The study indicates that an active ‘‘wait and see’’ policy during the first 3 days can be justified in most children with otorrhea but antibiotics should be considered in children who initially present with abundant purulent secretion and pulsating eardrum. Objectives: To study the clinical recovery of acute otitis media (AOM) with otorrhea in children managed initially without antibiotics. Methods: Children aged 2-16, presenting with AOM and spontaneous otorrhea, were followed. Specimens for bacterial investigations were obtained, and symptoms were registered on daily basis. The main outcome measures were the frequency of patients treated with antibiotics due to persisting AOM within 9 days in relation to clinical and bacteriologic findings and new AOM within 3 months. Results: Twelve of 71 children who completed the trial received antibiotics during the first nine days due to lack of improvement, one child after 16 days due to recurrent AOM and six had new AOM after 30 days. A.otitidis was found in 23 samples, S.pneumoniae in 12, S.pyogenes in 6, F.nucleatum in five. M.pneumoniae, C.pneumoniae and F.necrophorum could not be detected Antibiotics were prescribed more extensively to patients with pulsating eardrum and abundant purulent secretion. All patients with presence of S.pyogenes received antibiotics.
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