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  • 51.
    Ramezani, Amir
    et al.
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Nägga, Katarina
    Department of Clinical Sciences Malmö, Lunds University, Malmö.
    Hansson, Oskar
    Department of Clinical Sciences Malmö, Lunds University, Malmö.
    Lönn, Johanna
    , School of Health and Medical Sciences, Örebro University.
    Sjöwall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Katoozian, Fateme
    PEAS Institut, Linköping .
    Mansouri, Sepahdar
    PEAS Institut, Linköping .
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. PEAS Institut, Linköping .
    Hepatocyte growth factor in cerebrospinal fluid differentiates community-acquired or nosocomial septic meningitis from other causes of pleocytosis2015In: Fluids and Barriers of the CNS, ISSN 2045-8118, E-ISSN 2045-8118, Vol. 12, no 1Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Due to anatomical restrictions, the inflammatory response to intracerebral bacterial infections exposes swollen brain tissues to pressure and ischemia, resulting in life-threatening damage. Rapid diagnosis and immediate empirical antibiotic therapy is highly important. However, diagnosing meningitis in patients after neurosurgery is complicated, due to brain tissue damage and changes in cerebrospinal fluid (CSF) caused by surgery. Hepatocyte growth factor (HGF) is a local, acute-phase protein with healing properties. Previous studies on community-acquired septic meningitis reported high levels of intrathecally produced HGF. The present study focused on nosocomial meningitis in assessing the levels of HGF in the CSF.

    METHODS: HGF concentrations (ELISA) and HGF binding to receptors; c-Met receptor and heparan sulfate proteoglycan were determined in CSF samples (surface plasmon resonance). CSF samples from patients with community-acquired or nosocomial meningitis (217 samples from 135 patients) were compared to those from controls without signs of cerebral nervous system involvement (N = 36) and patients with Alzheimer's disease (N = 20).

    RESULTS: Compared to samples from patients that had undergone neurosurgery and had other infectious diseases, CSF samples from patients with nosocomial meningitis had significantly higher HGF concentrations (p < 0.001) and binding affinity to c-Met (p < 0.001) and HSPG (p = 0.043) receptors. The sensitivity and specificity to identify nosocomial septic meningitis were 69.7 and 93.4 %, respectively. The HGF concentration and binding affinity to HGF receptors were significantly higher in CSF from patients with community-acquired septic meningitis compared to patients with aseptic (viral and subacute) meningitis as well as controls (p < 0.001). The sensitivity and specificity to identify community-acquired septic meningitis were 95.4 and 95.7 %, respectively.

    DISCUSSION: In febrile nosocomial infections that occurred post neurosurgery, HGF assessment could substantially improve the differentiation of meningitis from other infections and therefore might be a tool for rapid diagnosis, limiting injuries and guiding antibiotic therapy.

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  • 52.
    Ridberg, Sara
    et al.
    Örebro University, Sweden.
    Hellmark, Bengt
    Örebro University, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Söderquist, Bo
    Örebro University, Sweden.
    Cutibacterium acnes (formerly Propionibacterium acnes) isolated from prosthetic joint infections is less susceptible to oxacillin than to benzylpenicillin2019In: Journal of bone and joint infection, ISSN 2206-3552, Vol. 4, no 3, p. 106-110Article in journal (Refereed)
    Abstract [en]

    Introduction: The frequency of prosthetic joint infections (PJIs) due to Cutibacterium acnes (formerly Propionibacterium acnes) is increasing, especially shoulder PJIs. The recommended antibiotic prophylaxis for hip and knee arthroplasties is beta-lactam antibiotics, predominantly cephalosporins. However, for example in Sweden, isoxazolyl-penicillin cloxacillin is used. No specific recommendations for shoulder arthroplasties are available. The aim of the present study was to determine the minimum inhibitory concentration (MIC) values for different antibiotics for C. acnes; and, more specifically, to compare the MIC values for benzylpenicillin and oxacillin.

    Materials and methods: Minimum inhibitory concentration (MIC) values for nine different antibiotic agents were obtained by gradient test (Etest) using strains of C. acnes (n= 57) isolated from PJIs from shoulders (n=31), hips (n=21), and knees (n=5).

    Results: All isolates had low MIC values for most of the tested antibiotic agents, and showed a wild type MIC distribution. The exception was clindamycin with 9% of the isolates displaying decreased susceptibility. The MIC values obtained for benzylpenicillin were significantly lower than the MIC values for isoxazolyl-penicillin (oxacillin).

    Conclusion: These in vitro results indicate that benzylpenicillin might be a more effective prophylactic treatment to prevent shoulder PJIs caused by C. acnes. However, further studies on the subject are needed, and the effectiveness of the prophylactic treatment should be evaluated using randomized controlled studies and/or register-based studies.

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  • 53.
    Salih, Lavin
    et al.
    Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Tevell, Staffan
    Faculty of Medicine and Health, Örebro University, Örebro, Sweden, Karlstad Hospital, Sweden.
    Månsson, Emeli
    Örebro University, Örebro, Sweden, Centre for Clinical Research, Hospital of Västmanland, Västerås, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Hellmark, Bengt
    Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Söderquist, Bo
    Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Staphylococcus epidermidis isolates from nares and prosthetic joint infections are mupirocin susceptible.2018In: Journal of bone and joint infection, ISSN 2206-3552, Vol. 3, no 1, p. 1-4Article in journal (Refereed)
    Abstract [en]

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

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  • 54.
    Schulman, H.
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Niward, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Abate, E.
    Univ Gondar, Ethiopia; Ethiopian Publ Hlth Inst, Ethiopia.
    Idh, Jonna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Axenram, P.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Bornefall, Anna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Forsgren, S.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Jakobsson, J.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Öhrling, C.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Kron, M.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Diro, E.
    Univ Gondar, Ethiopia.
    Kebede, A. Getachew
    Addis Ababa Univ, Ethiopia.
    Paues, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Bruchfeld, J.
    Karolinska Inst, Sweden.
    Wejse, C.
    Indepth Network, Guinea Bissau; Aarhus Univ Hosp, Denmark; Aarhus Univ, Denmark.
    Stendahl, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Sedimentation rate and suPAR in relation to disease activity and mortality in patients with tuberculosis2019In: The International Journal of Tuberculosis and Lung Disease, ISSN 1027-3719, E-ISSN 1815-7920, Vol. 23, no 11, p. 1155-1161Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE : To investigate how levels of the soluble urokinase plasminogen activator receptor (suPAR) and erythrocyte sedimentation rate (ESR) correlate with disease activity and prognosis in pulmonary tuberculosis (PTB). DESIGN: This was a retrospective analysis of patients with active PTB (n = 500) in Gondar, Ethiopia, for whom the suPAR (n = 301) and ESR (n = 330) were analysed at the start of treatment. Both biomarkers were available for 176 patients. Human immunodeficiency virus (HIV) status, chest X-ray (CXR) findings, classification according to the clinical TBscore and treatment outcome were all recorded. RESULTS : In a multivariable logistic regression analysis adjusted for age, sex and HIV status, surrogate markers of disease activity such as advanced CXR patterns correlated with increased levels of suPAR (adjusted OR [aOR] 8.24, Pamp;lt; 0.001) and of ESR (aOR 1.63, P = 0.030), whereas ESR only correlated significantly with a TBscore amp;gt;6 points. Increased levels of both suPAR and ESR were associated with unsuccessful treatment outcomes (aOR 2.93, P = 0.013; aOR 2.52, P = 0.025). The highest quartile of suPAR (aOR 13.3, P = 0.029) but not ESR levels correlated independently with increased mortality. CONCLUSION: SuPAR and ESR levels correlate with disease activity in PTB; however, the clinical role of these potentially prognostic biomarkers needs to be verified in prospective studies.

  • 55.
    Sjöwall, Christopher
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Martinsson, Klara
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Cardell, Kristina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Gastroentorology.
    Soluble urokinase plasminogen activator receptor levels are associated with severity of fibrosis in nonalcoholic fatty liver disease2015In: Translational research : the journal of laboratory and clinical medicine, ISSN 1878-1810, Vol. 165, no 6, p. 658-666Article in journal (Refereed)
    Abstract [en]

    The identification of individuals with severe liver fibrosis among patients with chronic liver disease is of major importance when evaluating prognosis, potential risk for complications, and when deciding treatment strategies. Although percutaneous liver biopsy is still considered a "gold standard" for staging of liver fibrosis, attempts to find reliable noninvasive markers of liver fibrosis are frequent. Inflammation is essential for the progression of fibrosis. The urokinase plasminogen activator and its receptor have been associated with hepatic inflammation and fibrosis in mice. High serum concentrations of soluble urokinase plasminogen activator receptor (suPAR) are suggested to be involved in inflammation, tissue remodeling, and cancer metastasis. Here, we evaluated serum suPAR as a noninvasive test to detect liver fibrosis in 82 well-characterized patients with nonalcoholic fatty liver disease (NAFLD), and in 38 untreated patients with chronic hepatitis C virus (HCV) infection at the time of their first liver biopsy. suPAR levels were increased in chronic liver disease compared with blood donors (P < 0.001). Patients with HCV had higher suPAR concentrations than patients with NAFLD (P < 0.002). suPAR levels were associated with the severity of fibrosis, particularly in NAFLD, but did not correlate with inflammation. Regarding the performance in predicting severity of fibrosis, suPAR was essentially as good as other commonly used noninvasive fibrosis scoring systems. The results in HCV confirm previous observations. However, this is the first study to investigate suPAR as a biomarker in NAFLD, and the results indicate that suPAR may constitute a severity marker related to fibrosis and prognosis rather than reflecting inflammation.

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  • 56.
    Skogman, Barbro H.
    et al.
    Falun Gen Hospital, Sweden; Uppsala University, Sweden.
    Sjöwall, Johanna
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Faculty of Medicine and Health Sciences.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    The NeBoP score - a clinical prediction test for evaluation of children with Lyme Neuroborreliosis in Europe2015In: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 15, no 214Article in journal (Refereed)
    Abstract [en]

    Background: The diagnosis of Lyme neuroborreliosis (LNB) in Europe is based on clinical symptoms and laboratory data, such as pleocytosis and anti-Borrelia antibodies in serum and CSF according to guidelines. However, the decision to start antibiotic treatment on admission cannot be based on Borrelia serology since results are not available at the time of lumbar puncture. Therefore, an early prediction test would be useful in clinical practice. The aim of the study was to develop and evaluate a clinical prediction test for children with LNB in a relevant European setting. Method: Clinical and laboratory data were collected retrospectively from a cohort of children being evaluated for LNB in Southeast Sweden. A clinical neuroborreliosis prediction test, the NeBoP score, was designed to differentiate between a high and a low risk of having LNB. The NeBoP score was then prospectively validated in a cohort of children being evaluated for LNB in Central and Southeast Sweden (n = 190) and controls with other specific diagnoses (n = 49). Results: The sensitivity of the NeBoP score was 90 % (CI 95 %; 82-99 %) and the specificity was 90 % (CI 95 %; 85-96 %). Thus, the diagnostic accuracy (i.e. how the test correctly discriminates patients from controls) was 90 % and the area under the curve in a ROC analysis was 0.95. The positive predictive value (PPV) was 0.83 (CI 95 %; 0.75-0.93) and the negative predictive value (NPV) was 0.95 (CI 95 %; 0.90-0.99). Conclusion: The overall diagnostic performance of the NeBoP score is high (90 %) and the test is suggested to be useful for decision-making about early antibiotic treatment in children being evaluated for LNB in European Lyme endemic areas.

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  • 57.
    Skoog, G.
    et al.
    Public Health Agency Sweden, Sweden; Karolinska Institute, Sweden.
    Struwe, J.
    Public Health Agency Sweden, Sweden.
    Cars, O.
    Public Health Agency Sweden, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Odenholt, I.
    Lund University, Sweden.
    Prag, M.
    University Hospital Örebro, Sweden.
    Skarlund, K.
    Public Health Agency Sweden, Sweden.
    Ulleryd, P.
    Regional Vastra Gotaland, Sweden; University of Gothenburg, Sweden.
    Erntell, M.
    County Council, Sweden.
    Repeated nationwide point-prevalence surveys of antimicrobial use in Swedish hospitals: data for actions 2003-20102016In: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 21, no 25, p. 13-21Article in journal (Refereed)
    Abstract [en]

    This study sought to analyse antimicrobial pressure, indications for treatment, and compliance with treatment recommendations and to identify possible problem areas where inappropriate use could be improved through interventions by the network of the local Swedish Strategic Programme Against Antibiotic Resistance (Strama) groups. Five point-prevalence surveys were performed in between 49 and 72 participating hospitals from 2003 to 2010. Treatments were recorded for 19 predefined diagnosis groups and whether they were for community-acquired infection, hospital-acquired infection, or prophylaxis. Approximately one-third of inpatients were treated with antimicrobials. Compliance with guidelines for treatment of community-acquired pneumonia with narrow-spectrum penicillin was 17.0% during baseline 2003-2004, and significantly improved to 24.2% in 2010. Corresponding figures for quinolone use in uncomplicated cystitis in women were 28.5% in 2003-2004, and significantly improved, decreasing to 15.3% in 2010. The length of surgical prophylaxis improved significantly when data for a single dose and 1 day were combined, from 56.3% in 2003-2004 to 66.6% in 2010. Improved compliance was possibly the effect of active local feedback, repeated surveys, and increasing awareness of antimicrobial resistance. Strama groups are important for successful local implementation of antimicrobial stewardship programs in Sweden.

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  • 58.
    Soderquist, Bo
    et al.
    Örebro University Hospital.
    Andersson, Mira
    Örebro University Hospital.
    Nilsson, Martin
    Affibody AB.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Persson, Lennart
    Örebro University Hospital.
    Friberg, Orjan
    Örebro University Hospital.
    Jacobsson, Susanne
    Örebro University Hospital.
    Staphylococcus epidermidis surface protein I (SesI): a marker of the invasive capacity of S. epidermidis?2009In: JOURNAL OF MEDICAL MICROBIOLOGY, ISSN 0022-2615, Vol. 58, no 10, p. 1395-1397Article in journal (Refereed)
    Abstract [en]

    n/a

  • 59.
    Sundbom, Per
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Hübbert, Laila
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Serrander, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Progressive multifocal leukoencephalopathy after heart transplantation: 4 years of clinically stable infection on low-dose immunosuppressive therapy2017In: Oxford Medical Case Reports, E-ISSN 2053-8855, Vol. 2017, no 2, p. 15-17Article in journal (Refereed)
    Abstract [en]

    Progressive multifocal leukoencephalopathy (PML), caused by reactivation of JC-virus is a relatively rare complication seen in patients with compromised immune system. There are no evidence-based treatment available and prognosis is poor. Withdrawal of immunosuppressant can result in further neurological deterioration and for patients with solid organ transplantations, fatal graft rejection. We report a 52-year-old women that presented with seizures within 1 month after heart transplantation. Initial diagnosis was vascular disease. After clinical deterioration 10 months after transplantation, further examinations led to the diagnosis. Minimizing tacrolimus, to a concentration of 2 ng/ml, and extensive physical therapy has improved the physical capacity of the patient. The patient has now been clinically stable for 4 years and extended survival for 5 years. This case adds to the limited adult cases of PML within the population of heart transplant recipients and the need for increased awareness to minimize diagnosis delay.

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  • 60.
    Sune, Dan
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Rydberg, Helene
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Serrander, Lena
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Microbiology.
    Bergman Jungestrom, Malin
    Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Optimization of 16S rRNA gene analysis for use in the diagnostic clinical microbiology service2020In: Journal of Microbiological Methods, ISSN 0167-7012, E-ISSN 1872-8359, Vol. 170, article id 105854Article in journal (Refereed)
    Abstract [en]

    Broad-range amplification and sequencing of the 16S rRNA gene, directly from clinical samples, is a method that potentially allows detection of any cultivable or non-cultivable bacteria. However, the method is prone to false positive results due to PCR contamination. Another concern is the human DNA abundance compared to bacterial DNA in samples from sterile sites. Those factors may decrease the sensitivity and specificity of the assay and can complicate the analysis and interpretation of the results. The objective of this prospective study was to try to avoid the most common pitfalls, mentioned above, and develop a molecular 16S assay with a high clinical sensitivity and specificity. Fifty-six consecutive tissue samples from patients with suspected deep infections were extracted by 3 different DNA-extraction methods; two based on a principle of bacterial DNA enrichment, and one conventional DNA extraction method. We compared three primer pairs, including both conventional and DPO principle, targeting different variable regions of the 16S rRNA gene. Results from routine tissue culture were used as reference. Clinical data was recorded from patient charts and analyzed in parallel. Of a total of 56 samples, collected from 39 patients, 70% (39 samples) were assessed as true infections by analysis of clinical data. Bacterial enrichment extraction increased sensitivity from 54% to 72%. The 2 sets of primer pairs defining region V1-V3 and V3-V4, showed similar sensitivity, but DPO-primers resulted in better specificity, i.e. less contaminations. The primer pairs covering V1-V8 show significantly lower sensitivity (p amp;lt; .001) than V1-V3 and V3-V4. Optimizing extraction protocols and choice of primers can increase the sensitivity and specificity of a molecular 16S-analysis, rendering a valuable complement to tissue culture.

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  • 61.
    Svensson, Robin J.
    et al.
    Uppsala Univ, Sweden.
    Niward, Katarina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Forsman, Lina Davies
    Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden.
    Bruchfeld, Judith
    Karolinska Inst, Sweden; Karolinska Univ Hosp Solna, Sweden.
    Paues, Jakob
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Eliasson, Erik
    Karolinska Univ Hosp Huddinge, Sweden.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Hosp, Sweden.
    Simonsson, Uirika S. H.
    Uppsala Univ, Sweden.
    Individualised dosing algorithm and personalised treatment of high-dose rifampicin for tuberculosis2019In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 85, no 10, p. 2341-2350Article in journal (Refereed)
    Abstract [en]

    Aims To propose new exposure targets for Bayesian dose optimisation suited for high-dose rifampicin and to apply them using measured plasma concentrations coupled with a Bayesian forecasting algorithm allowing predictions of future doses, considering rifampicins auto-induction, saturable pharmacokinetics and high interoccasion variability. Methods Rifampicin exposure targets for Bayesian dose optimisation were defined based on literature data on safety and anti-mycobacterial activity in relation to rifampicins pharmacokinetics i.e. highest plasma concentration up to 24 hours and area under the plasma concentration-time curve up to 24 hours (AUC(0-24h)). Targets were suggested with and without considering minimum inhibitory concentration (MIC) information. Individual optimal doses were predicted for patients treated with rifampicin (10 mg/kg) using the targets with Bayesian forecasting together with sparse measurements of rifampicin plasma concentrations and baseline rifampicin MIC. Results The suggested exposure target for Bayesian dose optimisation was a steady state AUC(0-24h) of 181-214 h x mg/L. The observed MICs ranged from 0.016-0.125 mg/L (mode: 0.064 mg/L). The predicted optimal dose in patients using the suggested target ranged from 1200-3000 mg (20-50 mg/kg) with a mode of 1800 mg (30 mg/kg, n = 24). The predicted optimal doses when taking MIC into account were highly dependent on the known technical variability of measured individual MIC and the dose was substantially lower compared to when using the AUC(0-24h)-only target. Conclusions A new up-to-date exposure target for Bayesian dose optimisation suited for high-dose rifampicin was derived. Using measured plasma concentrations coupled with Bayesian forecasting allowed prediction of the future dose whilst accounting for the auto-induction, saturable pharmacokinetics and high between-occasion variability of rifampicin.

  • 62.
    Taba, P.
    et al.
    University of Tartu, Estonia.
    Schmutzhard, E.
    Medical University of Innsbruck, Austria.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Lutsar, I.
    University of Tartu, Estonia.
    Ljostad, U.
    Sorlandet Hospital, Norway; University of Bergen, Norway.
    Mygland, A.
    Sorlandet Hospital, Norway; University of Bergen, Norway.
    Levchenko, I.
    National Academic Medical Science Ukraine, Ukraine.
    Strle, F.
    University of Medical Centre Ljubljana, Slovenia.
    Steiner, I.
    Rabin Medical Centre, Israel.
    EAN consensus review on prevention, diagnosis and management of tick-borne encephalitis2017In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, no 10, p. 1214-+Article, review/survey (Refereed)
    Abstract [en]

    Background and purpose: Tick-borne encephalitis (TBE) is an infection of the central nervous system (CNS) caused by tick-borne encephalitis virus (TBEV) and transmitted by ticks, with a variety of clinical manifestations. The incidence of TBE in Europe is increasing due to an extended season of the infection and the enlargement of endemic areas. Our objectives are to provide recommendations on the prevention, diagnosis and management of TBE, based on evidence or consensus decisions. Methods: For systematic evaluation, the literature was searched from 1970 to 2015 (including early online publications of 2016), and recommendations were based on evidence or consensus decisions of the Task Force when evidence-based data were not available. Recommendations: Vaccination against TBE is recommended for all age groups above 1 year in highly endemic areas (amp;gt;= 5 cases/100 000/year), but also for individuals at risk in areas with a lower incidence. Travellers to endemic areas should be vaccinated if their visits will include extensive outdoor activities. Post-exposure prophylaxis after a tick bite is not recommended. A case of TBE is defined by the presence of clinical signs of meningitis, meningoencephalitis or meningoencephalomyelitis with cerebrospinal fluid (CSF) pleocytosis (amp;gt;5 x 10(6) cells/l) and the presence of specific TBEV serum immunoglobulin M (IgM) and IgG antibodies, CSF IgM antibodies or TBEV IgG seroconversion. TBEV-specific polymerase chain reaction in blood is diagnostic in the first viremic phase but it is not sensitive in the second phase of TBE with clinical manifestations of CNS inflammation. Lumbar puncture should be performed in all patients with suspected CNS infection unless there are contraindications. Imaging of the brain and spinal cord has a low sensitivity and a low specificity, but it is useful for differential diagnosis. No effective antiviral or immunomodulating therapy is available for TBE; therefore the treatment is symptomatic. Patients with a potentially life threatening meningoencephalitis or meningoencephalomyelitis should be admitted to an intensive care unit. In the case of brain oedema, analgosedation should be deepened; osmotherapy and corticosteroids are not routinely recommended. If intracranial pressure is increased, therapeutic hypothermia or decompressive craniectomy might be considered. Seizures should be treated as any other symptomatic epileptic seizures. Conclusions: Tick-borne encephalitis is a viral CNS infection that may result in long-term neurological sequelae. Since its incidence in Europe is increasing due to broadening of endemic areas and prolongation of the tick activity season, the health burden of TBE is enlarging. There is no effective antiviral treatment for TBE, but the disease may be effectively prevented by vaccination.

  • 63.
    Taxbro, Knut
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Hammarskjöld, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Thelin, Bo
    Ryhov Cty Hosp, Sweden.
    Lewin, Freddi
    Ryhov Cty Hosp, Sweden.
    Hagman, Helga
    Skane Univ Hosp, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Berg, Sören
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Clinical impact of peripherally inserted central catheters vs implanted port catheters in patients with cancer: an open-label, randomised, two-centre trial2019In: British Journal of Anaesthesia, ISSN 0007-0912, E-ISSN 1471-6771, Vol. 122, no 6, p. 734-741Article in journal (Refereed)
    Abstract [en]

    Background

    Centrally inserted totally implanted vascular access ports (PORTs) and peripherally inserted central catheters (PICCs) are widely used for the administration of chemotherapy. Our aim was to study the incidence of catheter-related deep venous thrombosis in patients with cancer receiving chemotherapy through either a PICC or a PORT.

    Methods

    Adults with non-haematological cancer (mainly breast and colorectal) from two Swedish oncology centres were included and followed for up to 1 yr. Patients were randomly assigned to receive a single-lumen PICC or PORT. The primary end point was the occurrence of a clinically significant catheter-related deep venous thrombosis, and the secondary end point was a composite of adverse events related to the catheter: insertion complication, thrombosis, occlusion, infection, and mechanical problems.

    Results

    The trial recruited 399 participants (PICC, n=201; PORT, n=198) between March 2013 and February 2017. The PICCs were associated with 16 (8%) deep venous thromboses compared with two (1%) in the PORT group (HR=10.2; 95% confidence interval, 2.3–44.6; P=0.002). The overall incidence of composite adverse events was higher for patients with a PICC compared with those with a PORT (HR=2.7; 95% confidence interval, 1.6–4.6; P<0.001).

    Conclusions

    PICCs are associated with higher risk for catheter-related deep venous thrombosis and other adverse events when compared with PORTs. This increased risk should be considered when choosing a vascular access device for chemotherapy, especially in patients with solid malignancy.

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  • 64.
    Ternhag, Anders
    et al.
    Karolinska universitetssjukhuset, Solna, Sweden.
    Giske, Christian G
    Karolinska universitetssjukhuset, Solna, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Aminoglykosider är effektiva – men oto- och njurtoxiska2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 7, p. 268-269, article id CMLDArticle in journal (Refereed)
    Abstract [sv]

    Aminoglykosider har en snabb bakterie­avdödande effekt, men oto- och njurtoxicitet begränsar deras användning.

    Vid septisk chock bedöms nyttan med aminoglykosidbehandling överväga risken, men på grund av ökad distributionsvolym bör högre doser ges.

    Vid känd och/eller genetisk disposition för hörselnedsättning och gravt nedsatt njurfunktion ska aminoglykosider undvikas.

  • 65.
    Tevell, Staffan
    et al.
    Department of Infectious Diseases, Karlstad, and Centre for Clinical Research, County Council of Värmland, Sweden // School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Baig, Sharmin
    Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation.
    Stegger, Marc
    Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark.
    Söderquist, Bo
    School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Same Organism, Different Phenotype: Are Phenotypic Criteria Adequate In Coagulase-Negative Staphylococcal Orthopaedic Implant-Associated Infections?2019In: Journal of bone and joint infection, ISSN 2206-3552, Vol. 4, no 1, p. 16-19Article in journal (Refereed)
    Abstract [en]

    In current diagnostic criteria for implant-associated bone- and joint infections, phenotypically identical low-virulence bacteria in two intraoperative cultures are usually required. Using whole-genome sequencing, we have further characterized three phenotypically different Staphylococcus capitis isolated from one prosthetic joint infection, highlighting the challenges in defining microbiological criteria for low-virulence prosthetic joint infections.

  • 66.
    Tevell, Staffan
    et al.
    Karlstad Hospital, Karlstad, Sweden; Örebro University, Örebro, Sweden.
    Hellmark, B
    Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Nilsdotter-Augustinsson, Åsa
    Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Söderquist, B
    Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Staphylococcus capitis isolated from prosthetic joint infections2017In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 36, no 1, p. 115-122Article in journal (Refereed)
    Abstract [en]

    Further knowledge about the clinical and microbiological characteristics of prosthetic joint infections (PJIs) caused by different coagulase-negative staphylococci (CoNS) may facilitate interpretation of microbiological findings and improve treatment algorithms. Staphylococcus capitis is a CoNS with documented potential for both human disease and nosocomial spread. As data on orthopaedic infections are scarce, our aim was to describe the clinical and microbiological characteristics of PJIs caused by S. capitis. This retrospective cohort study included three centres and 21 patients with significant growth of S. capitis during revision surgery for PJI between 2005 and 2014. Clinical data were extracted and further microbiological characterisation of the S. capitis isolates was performed. Multidrug-resistant (≥3 antibiotic groups) S. capitis was detected in 28.6 % of isolates, methicillin resistance in 38.1 % and fluoroquinolone resistance in 14.3 %; no isolates were rifampin-resistant. Heterogeneous glycopeptide-intermediate resistance was detected in 38.1 %. Biofilm-forming ability was common. All episodes were either early post-interventional or chronic, and there were no haematogenous infections. Ten patients experienced monomicrobial infections. Among patients available for evaluation, 86 % of chronic infections and 70 % of early post-interventional infections achieved clinical cure; 90 % of monomicrobial infections remained infection-free. Genetic fingerprinting with repetitive sequence-based polymerase chain reaction (rep-PCR; DiversiLab®) displayed clustering of isolates, suggesting that nosocomial spread might be present. Staphylococcus capitis has the potential to cause PJIs, with infection most likely being contracted during surgery or in the early postoperative period. As S. capitis might be an emerging nosocomial pathogen, surveillance of the prevalence of PJIs caused by S. capitis could be recommended.

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  • 67.
    Tien Viet Dung, Vu
    et al.
    Univ Oxford, Vietnam.
    Thi Thuy Nga, Do
    Univ Oxford, Vietnam.
    Rydell, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart E
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Olson, Linus
    Karolinska Inst, Sweden; Training and Res Acad Collaborat Sweden Viet Nam, Vietnam.
    Larsson, Mattias
    Univ Oxford, Vietnam; Karolinska Inst, Sweden; Training and Res Acad Collaborat Sweden Viet Nam, Vietnam.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Training and Res Acad Collaborat Sweden Viet Nam, Vietnam.
    Choisy, Marc
    Univ Oxford, Vietnam; French Natl Res Inst Sustainable Dev, France; French Natl Ctr Sci Res, France; Univ Montpellier, France.
    Tuyet Trinh, Dao
    Natl Hosp Trop Dis, Vietnam.
    van Doorn, H. Rogier
    Univ Oxford, Vietnam.
    Van Kinh, Nguyen
    Natl Hosp Trop Dis, Vietnam.
    Vu Trung, Nguyen
    Natl Hosp Trop Dis, Vietnam.
    Wertheim, Heiman F. L.
    Univ Oxford, Vietnam; Radboudumc, Netherlands; Radboudumc, Netherlands.
    Antimicrobial susceptibility testing and antibiotic consumption results from 16 hospitals in Viet Nam: The VINARES project 2012-20132019In: Journal of Global Antimicrobial Resistance, ISSN 2213-7165, E-ISSN 2213-7173, Vol. 18, p. 269-278Article in journal (Refereed)
    Abstract [en]

    Objective: To establish a hospital-based surveillance network with national coverage for antimicrobial resistance (AMR) and antibiotic consumption in Viet Nam. Methods: A 16-hospital network (Viet Nam Resistance: VINARES) was established and consisted of national and provincial-level hospitals across the country. Antimicrobial susceptibility testing results from routine clinical diagnostic specimens and antibiotic consumption data in Defined Daily Dose per 1000 bed days (DDD/1000 patient-days) were prospectively collected and analysed between October 2012 and September 2013. Results: Data from a total of 24 732 de-duplicated clinical isolates were reported. The most common bacteria were: Escherichia coli (4437 isolates, 18%), Klebsiella spp. (3290 isolates, 13%) and Acinetobacter spp. (2895 isolates, 12%). The hospital average antibiotic consumption was 918 DDD/1000 patient-days. Third-generation cephalosporins were the most frequently used antibiotic class (223 DDD/1000 patient-days, 24%), followed by fluoroquinolones (151 DDD/1000 patient-days, 16%) and second-generation cephalosporins (112 DDD/1000 patient-days, 12%). Proportions of antibiotic resistance were high: 1098/1580 (69%) Staphylococcus aureus isolates were methicillin-resistant (MRSA); 115/344 isolates (33%) and 90/358 (25%) Streptococcus pneumoniae had reduced susceptibility to penicillin and ceftriaxone, respectively. A total of 180/2977 (6%) E. coli and 242/1526 (16%) Klebsiella pneumoniae were resistant to imipenem, respectively; 602/1826 (33%) Pseudomonas aeruginosa were resistant to ceftazidime and 578/1765 (33%) to imipenem. Of Acinetobacter spp. 1495/2138 (70%) were resistant to carbapenems and 2/333 (1%) to colistin. Conclusions: These data are valuable in providing a baseline for AMR among common bacterial pathogens in Vietnamese hospitals and to assess the impact of interventions. (C) 2019 The Authors. Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.

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  • 68.
    Torres, Antoni
    et al.
    Dept of Pulmonology, Hospital Clínic de Barcelona, Universitat de Barcelona, IDIBAPS, CIBERES Barcelona, Barcelona, Spain.
    Niederman, Michael S.
    Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, NY, USA.
    Chastre, Jean
    Réanimation Médicale, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
    Ewig, Santiago
    Fernandez-Vandellos, Patricia
    IDIBAPS, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Kollef, Marin
    Pulmonary and Critical Care Division, Washington University School of Medicine, St Louis, MO, USA.
    Li Bassi, Gianluigi
    Dept of Pulmonology, Hospital Clínic de Barcelona, Universitat de Barcelona, IDIBAPS, CIBERES Barcelona, Barcelona, Spain.
    Luna, Carlos
    Hospital de Clínicas ’José de San Martin’, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.
    Martin-Loeches, Ignacio
    Dept of Clinical Medicine, Wellcome Trust – HRB Clinical Research Facility, St. James’s Hospital, Trinity College, Dublin, Ireland.
    Paiva10,1, J. Artur
    Emergency and Intensive Care Dept, Centro Hospitalar São João EPE, Porto, Portugal // Dept of Medicine, University of Porto Medical School, Porto, Portugal.
    Read, Robert C.
    Dept of Infectious Diseases, Southampton General Hospital, Southampton, UK.
    Rigau, David
    Iberoamerican Cochrane Center, Barcelona, Spain.
    Timsit, Jean François
    IAME, INSERM UMR 1137, Paris Diderot University, Paris, France // Medical and Infectious Diseases Intensive Care Unit, Paris Diderot University and Bichat Hospital, Paris, France.
    Welte, Tobias
    CAPNETZ STIFTUNG, Hannover, Germany // Thorax Centre in the Ruhr Area, Dept of Respiratory Medicine and Infectious Diseases, Evangelic Hospital in Herne and Augusta Hospital in Bochum, Bochum, Germany // Dept of Respiratory Medicine, Medizinische Hoschschule Hannover, Germany and German Center of Lung Research (DZL).
    Wunderink, Richard
    Northwestern University Feinberg School of Medicine, Division of Pulmonary and Critical Care Medicine, Chicago, IL, USA.
    Summary of the international clinical guidelines for the management of hospital-acquired and ventilator-acquired pneumonia2018In: ERJ Open Res, E-ISSN 2312-0541, Vol. 4, article id 00028-2018Article in journal (Refereed)
    Abstract [en]

    The most recent European guidelines and task force reports on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) were published almost 10 years ago. Since then, further randomised clinical trials of HAP and VAP have been conducted and new information has become available. Studies of epidemiology, diagnosis, empirical treatment, response to treatment, new antibiotics or new forms of antibiotic administration, and disease prevention have changed old paradigms. In addition, important differences between approaches in Europe and the USA have become apparent. The European Respiratory Society (ERS) launched a project to develop new international guidelines for HAP and VAP. Other European societies, including the European Society of Intensive Care Medicine (ESICM) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), were invited to participate and appointed their representatives. The Latin American Society of Thoracic Diseases (ALAT) was also invited to participate. This manuscript summarises the evidence and recommendations of these international guidelines on HAP and VAP.

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  • 69.
    Torres, Antoni
    et al.
    University of Barcelona, Spain; CIBERES, Spain.
    Niederman, Michael S.
    Weill Cornell Med, NY USA.
    Chastre, Jean
    Grp Hospital Pitie Salpetriere, France.
    Ewig, Santiago
    Evangel Hospital Herne, Germany; Augusta Hospital Bochum, Germany.
    Fernandez-Vandellos, Patricia
    CIBERES, Spain.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Kollef, Marin
    Washington University, MO USA.
    Li Bassi, Gianluigi
    University of Barcelona, Spain; CIBERES, Spain.
    Luna, Carlos M.
    University of Buenos Aires, Argentina.
    Martin-Loeches, Ignacio
    Trinity Coll Dublin, Ireland; CIBERES, Spain.
    Artur Paiva, J.
    University of Porto, Portugal; University of Porto, Portugal.
    Read, Robert C.
    University of Southampton, England; University of Southampton, England; University of Southampton, England.
    Rigau, David
    Iberoamer Cochrane Centre, Spain.
    Francois Timsit, Jean
    Paris Diderot University, France; Hop Xavier Bichat, France.
    Welte, Tobias
    Hannover Medical Sch, Germany; German Centre Lung Research DZL, Germany.
    Wunderink, Richard
    Northwestern University, IL 60611 USA.
    International ERS/ESICM/ESCMID/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia2017In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 50, no 3, article id 1700582Article in journal (Refereed)
    Abstract [en]

    The most recent European guidelines and task force reports on hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) were published almost 10 years ago. Since then, further randomised clinical trials of HAP and VAP have been conducted and new information has become available. Studies of epidemiology, diagnosis, empiric treatment, response to treatment, new antibiotics or new forms of antibiotic administration and disease prevention have changed old paradigms. In addition, important differences between approaches in Europe and the USA have become apparent. The European Respiratory Society launched a project to develop new international guidelines for HAP and VAP. Other European societies, including the European Society of Intensive Care Medicine and the European Society of Clinical Microbiology and Infectious Diseases, were invited to participate and appointed their representatives. The Latin American Thoracic Association was also invited. A total of 15 experts and two methodologists made up the panel. Three experts from the USA were also invited (Michael S. Niederman, Marin Kollef and Richard Wunderink). Applying the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology, the panel selected seven PICO (population-intervention-comparison-outcome) questions that generated a series of recommendations for HAP/VAP diagnosis, treatment and prevention.

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  • 70.
    Tran, Dien M.
    et al.
    Vietnam National Children’s Hospital, Hanoi, Vietnam,.
    Larsson, Mattias
    Training and Research Academic Collaboration Sweden-Vietnam / Department of Public Health Sciences, Karolinska Institutet, Sweden.
    Olson, Linus
    Training and Research Academic Collaboration Sweden-Vietnam / Department of Public Health Sciences, Karolinska Institutet, Sweden.
    Hoang, Ngoc T.B.
    Vietnam National Children’s Hospital, Hanoi, Vietnam.
    Le, Ngai K.
    Vietnam National Children’s Hospital, Hanoi, Vietnam / Training and Research Academic Collaboration Sweden-Vietnam.
    Khu, Dung T.K.
    Vietnam National Children’s Hospital, Hanoi, Vietnam / Training and Research Academic Collaboration Sweden-Vietnam.
    Nguyen, Hung D.
    St Paul Hospital, Hanoi, Vietnam.
    Vu, Tam V.
    Uong Bi Hospital, Quang Ninh, Vietnam.
    Trinh, Tinh H.
    Binh Dinh General Hospital, Vietnam.
    Le, Thinh Q.
    Children’s Hospital 1, Ho Chi Minh City (HCMC), Vietnam.
    Phan, Phuong T.T.
    Phu San Hanoi, Vietnam.
    Nguyen, Binh G.
    Bach Mai Hospital, Hanoi, Vietnam.
    Pham, Nhung H.
    Bach Mai Hospital, Hanoi, Vietnam.
    Mai, Bang H.
    108 Military Central Hospital, Hanoi, Vietnam.
    Nguyen, Tuan V.
    108 Military Central Hospital, Hanoi, Vietnam.
    Nguyen, Phuong T.K.
    108 Military Central Hospital, Hanoi, Vietnam.
    Le, Nhan D.
    Da Nang General Hospital, Vietnam.
    Huynh, Tuan M.
    University Medical Clinic, HCMC, Vietnam.
    Thu, Le T.H.
    Cho Ray Hospital, HCMC, Vietnam.
    Thanh, Tran Chi
    Training and Research Academic Collaboration Sweden-Vietnam.
    Berglund, Björn
    Vietnam National Children’s Hospital, Hanoi, Vietnam / St Paul Hospital, Hanoi, Vietnam.
    Nilsson, Lennart E.
    Vietnam National Children’s Hospital, Hanoi, Vietnam / St Paul Hospital, Hanoi, Vietnam.
    Bornefall, Elin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences.
    Song, Le H.
    108 Military Central Hospital, Hanoi, Vietnam.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology, Infection and Inflammation. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Training and Research Academic Collaboration Sweden-Vietnam.
    High prevalence of colonisation with carbapenem-resistant Enterobacteriaceae among patients admitted to Vietnamese hospitals: Risk factors and burden of disease2019In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 79, no 2, p. 115-122Article in journal (Refereed)
    Abstract [en]

    Background

    Carbapenem-resistant Enterobacteriaceae (CRE) is an increasing problem worldwide, but particularly problematic in low- and middle-income countries (LMIC) due to limitations of resources for surveillance of CRE and infection prevention and control (IPC).

    Methods

    A point prevalence survey (PPS) with screening for colonisation with CRE was conducted on 2233 patients admitted to neonatal, paediatric and adult care at 12 Vietnamese hospitals located in northern, central and southern Vietnam during 2017 and 2018. CRE colonisation was determined by culturing of faecal specimens on selective agar for CRE. Risk factors for CRE colonisation were evaluated. A CRE admission and discharge screening sub-study was conducted among one of the most vulnerable patient groups; infants treated at an 80-bed Neonatal ICU from March throughout June 2017 to assess CRE acquisition, hospital-acquired infection (HAI) and treatment outcome.

    Results

    A total of 1165 (52%) patients were colonised with CRE, most commonly Klebsiella pneumoniae (n=805), Escherichia coli (n=682) and Enterobacter spp. (n=61). Duration of hospital stay, HAI and treatment with a carbapenem were independent risk factors for CRE colonisation. The PPS showed that the prevalence of CRE colonisation increased on average 4.2 % per day and mean CRE colonisation rates increased from 13% on the day of admission to 89% at day 15 of hospital stay. At the NICU CRE colonisation increased from 32% at admission to 87% at discharge, mortality was significantly associated (OR 5•5, P < 0•01) with CRE colonisation and HAI on admission.

    Conclusion

    These data indicate that there is an epidemic spread of CRE in Vietnamese hospitals with rapid transmission to hospitalised patients.

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  • 71.
    Wilhelmsson, Peter
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Fryland, Linda
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Lindblom, Pontus
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Sjöwall, Johanna
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine.
    Ahlm, Clas
    Division of Infectious Diseases, Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
    Berglund, Johan
    School of Health Science, Blekinge Institute of Technology, Karlskrona, Sweden.
    Haglund, Mats
    Department of Infectious Diseases, Kalmar County Hospital, Kalmar, Sweden.
    Henningsson, Anna
    Department of Clinical Microbiology, Division of Medical Services, Ryhov County Hospital, Jönkoping, Sweden.
    Nolskog, Peter
    Department of Communicable Disease Control and Prevention, Region Västra Götaland, Skaraborg Hospital, Skövde, Sweden.
    Nordberg, Marika
    The Åland Group for Borrelia Research, Mariehamn, Åland, Finland.
    Nyberg, Clara
    The Åland Group for Borrelia Research, Mariehamn, Åland, Finland.
    Ornstein, Katharina
    Department of Internal Medicine, Hässleholm Hospital, Hässleholm, Sweden/Department of Clinical Sciences, Lund University, Lund, Sweden.
    Nyman, Dag
    The Åland Group for Borrelia Research, Mariehamn, Åland, Finland.
    Ekerfelt, Christina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Forsberg, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    A prospective study on the incidence of Borrelia infection after a tick bite in Sweden and on the Åland Islands, Finland (2008-2009)2016In: Ticks and Tick-borne Diseases, ISSN 1877-959X, E-ISSN 1877-9603, Vol. 7, no 1, p. 71-79Article in journal (Refereed)
    Abstract [en]

    Lyme borreliosis (LB) is a common and increasing tick-borne disease in Europe. The risk of acquiring a Borrelia infection after a tick bite is not fully known. Therefore, we investigated the incidence of Borrelia infection after a tick bite and if the Borrelia load and/or the duration of tick-feeding influenced the risk of infection. During 2008-2009, ticks and blood samples were collected from 1546 tick-bitten persons from Sweden and the Åland Islands, Finland. Follow-up blood samples were taken three months after the tick bite. The duration of tick feeding was microscopically estimated and Borrelia was detected and quantified in ticks by real-time PCR. Anti-Borrelia antibodies were detected in sera using ELISA assays and immunoblot.

    Even though 28 % of the participants were bitten by a Borrelia-positive tick, only 7.5% (32/428) of them developed a Borrelia infection, half of them LB. All who seroconverted removed “their” ticks significantly later than those who did not. The Borrelia load in the ticks did not explain the risk of seroconversion. Regional as well as gender differences in the Borrelia seroprevalence were found. The risk of developing a Borrelia infection after a bite by a Borrelia-infected tick is small but increases with the duration of tick feeding.

  • 72.
    Williams, George Sie
    et al.
    World Health Organization, Liberia Mission, Liberia .
    Naiene, Jeremias
    World Health Organization, Liberia Mission, Liberia .
    Gayflor, Joseph
    Ministry of Health & Social Welfare, Liberia .
    Malibiche, Theophil
    African Union-ASEOWA Liberia, Liberia .
    Zoogley, Bentoe
    World Health Organization, Liberia Mission, Liberia .
    Frank, Wimot G
    Ministry of Health & Social Welfare, Liberia .
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Twenty-one days of isolation: A prospective observational cohort study of an Ebola-exposed hot zone community in Liberia2015In: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 71, no 2, p. 150-7Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: As West Africa continues to suffer from a deadly Ebola epidemic, the national health sectors struggle to minimize the damages and stop the spread of disease.

    METHODS: A cohort of inhabitants of a small village and an Ebola hot zone in Sinoe County of Liberia was followed on a day-by-day basis to search for new cases and to minimize the spread of Ebola to the other community members or to other regions. Technical, clinical, and humanistic aspects of the response are discussed in this report.

    RESULTS: Of the 22 confirmed Ebola cases in Sinoe County since the beginning of outbreak (June 16, 2014), 7 cases were inhabitants of Polay Town, a small village 5.5 miles east of Greenville, the Sinoe County capital. After the last wave of outbreak at the beginning of December, enhanced response activity provided essential coordination and mobilized the resources to stop the epidemic. Despite unprotected contacts in crowded houses, no new cases were detected among the contact families, or in the surrounding houses or communities.

    CONCLUSIONS: Strong national mobilization in a decentralized but harmonized system at the community level has been of great value in controlling the epidemic in Liberia. The major interventions include epidemiological surveillance, public information dissemination, effective communication, case management, and infection control.

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  • 73.
    Wu, Chongcong
    et al.
    PEAS Institute, Institute Prot Environm Affin Surveys, Linkoping, Sweden; Maternal and Children Health Care Hospital Zhuhai City, Peoples R China.
    Nakka, Sravya
    PEAS Institute, Institute Prot Environm Affin Surveys, Linkoping, Sweden; University of Örebro, Sweden.
    Mansouri, Sepahdar
    PEAS Institute, Institute Prot Environm Affin Surveys, Linkoping, Sweden.
    Bengtsson, Torbjörn
    University of Örebro, Sweden.
    Nayeri, Tayeb
    PEAS Institute, Institute Prot Environm Affin Surveys, Linkoping, Sweden.
    Nayeri, Fariba
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases. PEAS Institute, Institute Prot Environm Affin Surveys, Linkoping, Sweden.
    In vitro model of production of antibodies; a new approach to reveal the presence of key bacteria in polymicrobial environments2016In: BMC Microbiology, ISSN 1471-2180, E-ISSN 1471-2180, Vol. 16, article id 209Article in journal (Refereed)
    Abstract [en]

    Background: There is a rapid emergence of multiple resistant gram-negative bacteria due to overuse of antibiotics in the treatment of infections. Biofilms consist of polymicrobial communities that survive the hosts defense system. The key bacteria in biofilms are slow growing and support an attachment and rapid growth of other microorganisms. Current antimicrobial strategies often fail due to poor diagnosis of key pathogens in biofilms. The study aims to develop anti-bacterial human antibodies in vitro from patients who had recently undergone a systemic infection by pathogenic bacteria and to use these antibodies as a tool for detecting bacteria in biofilms. Methods: Lymphocytes were separated from whole blood of patients (n = 10) and stimulated with heat-killed bacteria to produce antibodies in vitro. The specificity of antibodies in recognizing the bacteria against which they were directed was evaluated by surface plasmon resonance system (SPR) and electron microscopy. The ulcer secretions from patients with chronic and acute leg ulcers and healthy controls were analyzed by the SPR system and the results were compared with culture studies. Results: The produced antibodies recognized bacteria with high sensitivity (SPR). The antibodies against Enterococcus fecalis bound specifically to the microorganism in a bacterial co-culture that was visualized by electron microscopy. Conclusion: In the present work, a method for producing specific antibodies against bacteria is introduced to recognize bacterial components in body fluids of patients suffering from pathogenic biofilms. This diagnostic technique may be most useful in clinical microbiology and in the choice of antibiotics in the treatment of serious infections.

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  • 74.
    Wågström, Per
    et al.
    Ryhov County Hospital, Jönköping, Sweden.
    Bengnér, Malin
    Ryhov County Hospital, Jönköping, Sweden.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Neumark, Thomas
    Primary Health in Lindsdal, Kalmar, Sweden.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Sweden.
    Björkander, Janne
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Ryhov County Hospital, Jönköping, Sweden.
    Does the frequency of respiratory tract infections help to identify humoral immunodeficiencies in a primary health-care cohort?2015In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 47, no 1, p. 13-19Article in journal (Refereed)
    Abstract [en]

    Background: Primary immune deficiency (PID) due to humoral defects is associated with recurrent respiratory tract infections (RTIs). Reliable clinical warning signs of PID would facilitate early diagnosis and thereby reduce long-term complications. The aim of the present study was to evaluate the accuracy of the warning sign, 'four or more antibiotic-treated RTIs annually for 3 or more consecutive years,' for detecting PID among adults in a primary health-care setting. Methods: Fifty-three cases with 'four or more antibiotic-treated RTIs annually for 3 or more consecutive years' were selected from a Swedish primary health-care registry of RTIs. In addition, 66 age- and sex-matched controls were selected having a maximum of one antibiotic-treated RTI during the period covered by the study. Levels of immunoglobulin (Ig) IgG, IgA, IgM, IgG subclasses, and IgG antibodies against Haemophilus influenzae and Streptococcus pneumoniae as well as the inflammatory markers, C-reactive protein, interleukin (IL)-6 and IL-8 were determined. Results: IgG subclass deficiencies (IgGsd) were found in 5/53 (9.4%) of the cases and in 7/66 (10.6%) controls. The most frequent deficiency was IgG3sd and this was found in three participants in the case group and seven in the control group. The mean level of IgG3 was lower in the control group (p = 0.02). The mean level of IL-8 was lower in the case group (p = 0.02). Conclusion: The results show that physicians working in primary health care cannot solely rely on the frequency of antibiotic-treated RTIs as a warning sign for the detection of common humoral immune deficiencies.

  • 75.
    Wågström, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Yamada, Naomi
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Dahle, Charlotte
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Nilsdotter-Augustinsson, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Bengner, Malin
    Ryhov Cty Hosp, Sweden.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical genetics.
    Björkander, Jan Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Fc gamma-receptor polymorphisms associated with clinical symptoms in patients with immunoglobulin G subclass deficiency2018In: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 50, no 11-12, p. 853-858Article in journal (Refereed)
    Abstract [en]

    Background: Immunoglobulin G subclass deficiencies (IgGsd) are associated with recurrent respiratory tract infections. Immunoglobulin substitution therapy may be needed to prevent chronic lung tissue damage but tools for identifying the patients that will benefit from this treatment are still insufficient. Some Fc gamma R polymorphisms seem to predispose for an increased risk for infections. In this study we wanted to evaluate if the Fc gamma R-profile differs between individuals with IgGsd and a control population. Methods: Single nucleotide polymorphisms (SNPs) of Fc gamma RIIa, Fc gamma RIIIa and Fc gamma RIIc in 36 IgGsd patients and 192 controls with similar sex and geographical distribution were analyzed by TaqMan allelic discrimination assay or Sanger sequencing. Results: In the IgGsd-group, homozygous frequency for Fc gamma RIIa-R/R131 (low-binding capacity isoform) was higher (p = .03) as well as for non-classical Fc gamma RIIc-ORF (p = .03) and classical Fc gamma RIIc-ORF tended (p = .07) to be more common compared to the controls. There was no difference between the groups regarding Fc gamma RIIIa. Conclusion: The gene for classical Fc gamma RIIc-ORF tended to be more frequent in individuals with immunoglobulin G subclass deficiency and the genes for non-classical Fc gamma RIIc-ORF as well as low-binding capacity receptor Fc gamma RIIa-R/R131 were more frequent. Further studies on the Fc gamma R polymorphisms may pave way for identifying individuals that will benefit from immunoglobulin substitution.

  • 76.
    Åkerlund, Anna
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sundqvist, Martin
    Universitetssjukhuset, Örebro, Sweden.
    Hanberger, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Infectious Diseases.
    Åhrén, Christina
    regionala Strama, Västra Götalandsregionen, Göteborg, Sweden.
    Serrander, Lena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Giske, Christian G
    Karolinska universitetssjukhuset, Solna, Sweden.
    Svarstiderna kan kortas vid mikrobiologisk diagnostik av sepsis: Bättre öppettider på laboratorier och aktiv rådgivning ger snabbare terapi2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 7, article id C73SArticle in journal (Refereed)
    Abstract [sv]

    Snabbt insatt adekvat antibiotikabehandling är livräddande vid allvarliga bakteriella infektioner. 

    Snabb mikrobiologisk diagnostik krävs i och med ökande antibiotikaresistens och kommer att ge medicinska vinster.

    En enkät till landets mikrobiologiska laboratorier visar på stora skillnader avseende tillgänglighet, snabbhet och kommunikation med svarsmottagande enhet vad gäller positiva blododlingar.

    För snabbare svar krävs att mikrobiologiska laboratorier erbjuder mer generösa öppettider, effektivare transportsystem och patientnära blododlingsinkubatorer samt tidig och aktiv rådgivning till behandlande läkare.

    n/a

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