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  • 1. Arnelöv, Conny
    et al.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Aortagraftinfektion – ett komplicerat kärlkirurgiskt tillstånd2013In: Svensk Kirurgi, ISSN 0346-847X, Vol. 71, no 2, p. 84-88Article in journal (Refereed)
    Abstract [sv]

    Infektion runt ett aortagraft är en fruktad komplikation och utgör både en kirurgisk och antibakteriell utmaning där erfarenhet och multidisciplinär kompetens krävs. Åtgärder kan behövas akut vid graftenterisk blödning, men i andra fall med enbart infektion finns det tid för en noggrann utredning och diskussion angående kirurgisk strategi. 

  • 2.
    Edberg, M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Enblad, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Neurointensive care of patients with severe community-acquired meningitis2011In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, no 6, p. 732-739Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Reports about neurointensive care of severe community-acquired meningitis are few. The aims of this retrospective study were to review the acute clinical course, management and outcome in a series of bacterial meningitis patients receiving neurointensive care.

    METHODS:

    Thirty patients (median age 51, range 1-81) admitted from a population of 2 million people during 7 years were studied. The neurointensive care protocol included escalated stepwise treatment with mild hyperventilation, cerebrospinal fluid (CSF) drainage, continuous thiopentotal infusion and decompressive craniectomy. Clinical outcome was assessed using the Glasgow outcome scale.

    RESULTS:

    Twenty-eight patients did not respond to commands on arrival, five were non-reacting and five had dilated pupils. Twenty-two patients had positive CSF cultures: Streptococcus pneumoniae (n=18), Neisseria meningitidis (n=2), β-streptococcus group A (n=1) and Staphylococcus aureus (n=1). Thirty-five patients were mechanically ventilated. Intracranial pressure (ICP) was monitored in 28 patients (intraventricular catheter=26, intracerebral transducers=2). CSF was drained in 15 patients. Three patients received thiopentothal. Increased ICP (>20 mmHg) was observed in 7/26 patients with available ICP data. Six patients died during neurointensive care: total brain infarction (n=4), cardiac arrest (n=1) and treatment withdrawal (n=1). Seven patients died after discharge, three due to meningitis complications. At follow-up, 14 patients showed good recovery, six moderate disability, two severe disability and 13 were dead.

    CONCLUSION:

    Patients judged to have severe meningitis should be admitted to neurointensive care units without delay for ICP monitoring and management according to modern neurointensive care principles.

  • 3.
    Furebring, M
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Infektion.
    Håkansson, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Venge, P
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Klinisk kemi.
    Sjölin, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Infektion.
    C5a, interleukin-8 and tumour necrosis factor-alpha-induced changes in granulocyte and monocyte expression of complement receptors in whole blood and on isolated leukocytes.2006In: Scand J Immunol, ISSN 0300-9475, Vol. 63, no 3, p. 208-16Article in journal (Refereed)
  • 4.
    Furebring, Mia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Håkansson, Lena Douhan
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Expression of the C5a receptor (CD88) on granulocytes and monocytes in patients with severe sepsis2002In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 6, no 4, p. 363-370Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Treatment of patients with severe sepsis with agents antagonising the effects of C5a has been proposed based on beneficial effects in animal experiments and in vitro studies demonstrating upregulation of the C5a receptor (CD88) on granulocytes by endotoxin.

    MATERIALS AND METHODS: CD88 expression on leukocytes from 12 patients with severe sepsis or septic shock was analysed by flow cytometer, and serum complement factors C3a and C5b-9 were measured by enzyme immunoassay techniques.

    RESULTS: The granulocyte CD88 expression on day 1 was lowered (36; range, 2-59) in comparison with controls (63; range, 25-88) (P < 0.001), despite complement activation, while the monocyte CD88 expression was unchanged. The receptor reduction correlated significantly to the APACHE II score (r2 = 0.35, P < 0.05). The recovery of CD88 expression was slow.

    DISCUSSION: In contrast to the findings in animals, it is concluded that granulocyte CD88 expression is reduced at the time when the diagnosis of severe sepsis or septic shock can clinically be made. The reason for this needs further investigation but it may be due to a previous complement activation or to cytokine effects.

  • 5.
    Furebring, Mia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Håkansson, Lena
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Differential expression of the C5a receptor and complement receptors 1 and 3 after LPS stimulation of neutrophils and monocytes2004In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 60, no 5, p. 494-499Article in journal (Refereed)
    Abstract [en]

    Animal experiments recently suggested that administration of anti-C5a, anti-C5a receptor or soluble complement receptor type-1 may be of value in the treatment of septic shock. Because results regarding C5a receptor expression (C5a-R, CD-88) have been found to differ between septic animals and patients, the aim of this study was to investigate the neutrophil and monocyte receptor expression of CD-88 and complement receptor-1 (CR-1, CD-35) after stimulation with lipopolysaccharide (LPS) ex vivo. Whole blood or isolated neutrophils and monocytes from healthy people were incubated with LPS in a dose range of 0.1-1000 ng/ml. The expressions of CD-88 and CD-35 were analysed by means of flow cytometry. For comparison, the expressions of complement receptor-3 (CR-3, CD-11b/CD-18), Fc-gamma receptor type-I (CD-64) and CEACAM-8 (CD-66b) were also investigated. In whole blood, CD-88 expression on neutrophils was reduced (P < 0.05). The expressions of CD-35 and CD-11b were increased both on neutrophils (P < 0.001; P < 0.05) and on monocytes (P < 0.001; P < 0.001). No effect was observed on isolated cells. In agreement with the findings in septic patients, LPS reduced the neutrophil C5a-R expression, whereas the expressions of CR-1 and CR-3 were increased. The effects of LPS were indirect and were mediated via factors in the blood. The clinical significance of this is not known, but may be associated with decreased chemotaxis.

  • 6.
    Gavali, Hamid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Mogensen, John
    William Cook Europe, Bjaeverskov, Denmark.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Branched Endovascular Aortic Plug in Patients With Infrarenal Aortic Graft Infection and Hostile Anatomy2020In: Journal of Endovascular Therapy, ISSN 1526-6028, E-ISSN 1545-1550, Vol. 27, no 2, p. 328-333Article in journal (Refereed)
    Abstract [en]

    Purpose: To present a novel 4-branched endovascular aortic plug (BEVAP) for treatment of patients with infrarenal aortic graft infection.

    Case Reports: Two polymorbid male patients with aortic graft infections and an unsuturable diseased paravisceral aorta were treated under compassionate use with a custom-made stent-graft. The BEVAP is a factory-modified Zenith t-Branch thoracoabdominal endovascular graft with the distal tubular main graft portion removed, creating an aortic plug that excludes the abdominal aorta while maintaining perfusion to the visceral organs. The BEVAP device is deployed using a femoral approach, and the branches are accessed through an axillary approach. A standard axillobifemoral bypass is created to perfuse the lower body. One to 2 days later, the infected infrarenal graft is resected without the need of aortic clamping or closure of the aortic stump. The BEVAP device in these 2 cases resulted in thrombosis of the abdominal aorta and the infected graft prior to explantation.

    Conclusion: Using the BEVAP enables radical treatment of selected patients with hostile anatomy and infrarenal aortic graft infections who have an aneurysmal paravisceral aortic segment that prevents traditional radical surgical treatment with in situ reconstruction or extra-anatomical bypass.

  • 7.
    Gavali, Hamid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Olsson, Karl Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Lindström, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Department of Vascular Surgery, Karolinska University Hospital, Stockholm, Sweden.
    Sörelius, Karl
    Department of Vascular Surgery, Rigshospitalet, Copenhagen, Denmark;Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
    Sigvant, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Department of Medical Sciences, Örebro University, Örebro, Sweden.
    Gidlund, Khatereh D.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Department of Surgery, Gävle County Hospital, Gävle, Sweden.
    Torstensson, Gustav
    Department of Vascular Surgery, Helsingborg Regional Hospital, Helsingborg, Sweden.
    Andersson, Manne
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden;County Hospital Ryhov, Jönköping County, Department of Surgery, Ryhov, Sweden.
    Forssell, Claes
    Department of Cardiovascular Surgery, Division of Vascular Surgery, Linköping University Hospital, Linköping, Sweden.
    Åstrand, Håkan
    Department of Surgery, County Hospital Ryhov, Jönköping County, Jönköping, Sweden.
    Lundström, Tobias
    Department of Surgery and urology, Eskilstuna Hospital, Eskilstuna, Sweden.
    Khan, Shahzad
    Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
    Sonesson, Björn
    Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
    Stackelberg, Otto
    Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden;Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Gillgren, Peter
    Department of Clinical Science and Education, Karolinska Institutet, Stockholm, Sweden;Department of Surgery, Södersjukhuset, Stockholm, Sweden.
    Isaksson, Jon
    Department of Surgical and Peri-operative Sciences, Umeå University, Umeå, Sweden.
    Kragsterman, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Department of Surgery, Västerås Central Hospital, Västerås, Sweden.
    Horer, Tal
    Department of Cardiothoracic and Vascular Surgery and Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Sadeghi, Mitra
    Department of Cardiothoracic and Vascular Surgery and Department of Surgery, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Outcome of Radical Surgical Treatment of Abdominal Aortic Graft and Endograft Infections Comparing Extra-anatomic Bypass with In Situ Reconstruction: A Nationwide Multicentre Study2021In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 62, no 6, p. 918-926Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Abdominal aortic graft and endograft infection (AGI) is primarily treated by resection of the infected graft and restoration of distal perfusion through extra-anatomic bypass (EAB) or in situ reconstruction/repair (ISR). The aim of this study was to compare these surgical strategies in a nationwide multicentre retrospective cohort study.

    METHODS: The Swedish Vascular Registry (Swedvasc) was used to identify surgically treated abdominal AGIs in Sweden between January 1995 and May 2017. The primary aim was to compare short and long term survival, as well as complications for EAB and ISR.

    RESULTS: Some 126 radically surgically treated AGI patients were identified - 102 graft infections and 24 endograft infections - treated by EAB: 71 and ISR: 55 (23 neo-aorto-iliac systems, NAISs). No differences in early 30 day (EAB 81.7% vs. ISR 76.4%, p = .46), or long term five year survival (48.2% vs. 49.9%, p = .87) were identified. There was no survival difference comparing NAIS to other ISR strategies. The frequency of recurrent graft infection during follow up was similar: EAB 20.3% vs. ISR 17.0% (p = .56). Survival and re-infection rates of the new conduit did not differ between NAIS and other ISR strategies. Age ≥ 75 years (odds ratio [OR] 4.0, confidence interval [CI] 1.1 - 14.8), coronary artery disease (OR 4.2, CI 1.2 - 15.1) and post-operative circulatory complications (OR 5.2, CI 1.2 - 22.5) were associated with early death. Prolonged antimicrobial therapy (> 3 months) was associated with reduced long term mortality (HR 0.3, CI 0.1 - 0.9).

    CONCLUSION: In this nationwide multicentre study comparing outcomes of radically treated AGI, no differences in survival or re-infection rate could be identified comparing EAB and ISR.

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  • 8.
    Gavali, Hamid
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Olsson, Karl Wilhelm
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Lindström, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Sörelius, Karl
    Rigshospitalet, Dept Vasc Surg, Copenhagen, Denmark..
    Sigvant, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Karlstad Cent Hosp, Dept Vasc Surg, Karlstad, Sweden..
    Torstensson, Gustav
    Helsingborg Hosp, Dept Surg, Helsingborg, Sweden..
    Andersson, Manne
    Linköping Univ, Dept Clin & Expt Med, Norrköping, Sweden.;Cty Hosp Ryhov, Dept Surg, Jönköping, Sweden..
    Forssell, Claes
    Linköping Univ Hosp, Dept Cardiovasc Surg, Div Vasc Surg, Linköping, Sweden..
    Åstrand, Håkan
    Cty Hosp Ryhov, Dept Surg, Jönköping, Sweden..
    Lundström, Tobias
    Eskilstuna Hosp, Dept Surg & Urol, Eskilstuna, Sweden..
    Khan, Shahzad
    Lund Univ, Malmö Univ Hosp, Dept Surg, Malmö, Sweden..
    Sonesson, Björn
    Lund Univ, Malmö Univ Hosp, Dept Surg, Malmö, Sweden..
    Stackelberg, Otto
    Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden.;Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Stockholm, Sweden..
    Gillgren, Peter
    Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden.;Soder Sjukhuset, Dept Vasc Surg, Stockholm, Sweden..
    Isaksson, Jon
    Umeå Univ, Dept Surg & Perioperat Sci, Umeå, Sweden..
    Kragsterman, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Västerås Hosp, Dept Surg, Västerås, Sweden..
    Gidlund, Khatereh Djavani
    Örebro Univ, Dept Cardiothorac & Vasc Surg, Örebro, Sweden.;Örebro Univ, Fac Med & Hlth, Dept Surg, Örebro, Sweden..
    Horer, Tal
    Örebro Univ, Dept Cardiothorac & Vasc Surg, Örebro, Sweden.;Örebro Univ, Fac Med & Hlth, Dept Surg, Örebro, Sweden..
    Sadeghi, Mitra
    Örebro Univ, Dept Cardiothorac & Vasc Surg, Örebro, Sweden.;Örebro Univ, Fac Med & Hlth, Dept Surg, Örebro, Sweden..
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Umeå Univ, Dept Surg & Perioperat Sci, Umeå, Sweden..
    Semi-Conservative Treatment Versus Radical Surgery in Abdominal Aortic Graft and Endograft Infections2023In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 66, no 3, p. 397-406Article in journal (Refereed)
    Abstract [en]

    Objective: Abdominal aortic graft and endograft infections (AGIs) are rare complications following aortic surgery. Radical surgery (RS) with resection of the infected graft and reconstruction with extra-anatomical bypass or in situ reconstruction is the preferred therapy. For patients unfit for RS, a semi-conservative (SC), graft preserving strategy is possible. This paper aimed to compare survival and infection outcomes between RS and SC treatment for AGI in a nationwide cohort.

    Methods: Patients with abdominal AGI related surgery in Sweden between January 1995 and May 2017 were identified. The Management of Aortic Graft Infection Collaboration (MAGIC) criteria were used for the definition of AGI. Multivariable regression was performed to identify factors associated with mortality.

    Results: One hundred and sixty-nine patients with surgically treated abdominal AGI were identified, comprising 43 SC (14 endografts; 53% with a graft enteric fistula [GEF] in total) and 126 RS (26 endografts; 50% with a GEF in total). The SC cohort was older and had a higher frequency of cardiac comorbidities. There was a non-significant trend towards lower Kaplan -Meier estimated five year survival for SC vs. RS (30.2% vs. 48.4%; p = .066). A non-significant trend was identified towards worse Kaplan -Meier estimated five year survival for SC patients with a GEF vs. without a GEF (21.7% vs. 40.1%; p = .097). There were significantly more recurrent graft infections comparing SC with RS (45.4% vs. 19.3%; p < .001). In a Cox regression model adjusting for confounders, there was no difference in five year survival comparing SC vs. RS (HR 1.0, 95% CI 0.6 -1.5).

    Conclusion: In this national AGI cohort, there was no mortality difference comparing SC and RS for AGI when adjusting for comorbidities. Presence of GEF probably negatively impacts survival outcomes of SC patients. Rates of recurrent infection remain high for SC treated patients.

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  • 9.
    Gedeborg, Rolf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Diagnosis-dependent misclassification of infections using administrative data variably affected incidence and mortality estimates in ICU patients2007In: Journal of Clinical Epidemiology, ISSN 0895-4356, E-ISSN 1878-5921, Vol. 60, no 2, p. 155-162Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To determine the accuracy of hospital discharge diagnoses in identifying severe infections among intensive care unit (ICU) patients, and estimate the impact of misclassification on incidence and 1-year mortality. STUDY DESIGN AND SETTING: Sepsis, pneumonia, and central nervous system (CNS) infections among 7,615 ICU admissions were identified using ICD-9 and ICD-10 diagnoses from the Swedish hospital discharge register (HDR). Sensitivity, specificity, and likelihood ratios were calculated using ICU database diagnoses as reference standard, with inclusion in sepsis trials (IST) as secondary reference for sepsis. RESULTS: CNS infections were accurately captured (sensitivity 95.4% [confidence interval (CI)=86.8-100] and specificity 99.6% [CI=99.4-99.8]). Community-acquired sepsis (sensitivity 51.1% [CI=41.0-61.2] and specificity 99.4% [CI=99.2-99.6]) and primary pneumonia (sensitivity 38.2% [CI=31.2-45.2] and specificity 98.6% [CI=98.2-99.0]) were more accurately detected than sepsis and pneumonia in general. One-year mortality was accurately estimated for primary pneumonia but underestimated for community-acquired sepsis. However, there were only small differences in sensitivity and specificity between HDR and ICU data in the ability to identify IST. ICD-9 appeared more accurate for sepsis, whereas ICD-10 was more accurate for pneumonia. CONCLUSION: Accuracy of hospital discharge diagnoses varied depending on diagnosis and case definition. The pattern of misclassification makes estimates of relative risk more accurate than estimates of absolute risk.

  • 10. Gårdlund, Bengt
    et al.
    Cronqvist, Jonas
    Follin, Per
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Gille-Johnson, Patrik
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Svår sepsis och septisk chock kräver omedelbart omhändertagande: [Severe sepsis and septic shock require immediate care]2011In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 6, p. 271-275Article in journal (Refereed)
    Abstract [en]

    Severe sepsis and septic shock are life threatening conditions that require immediate medical attention. Such patients must be given highest priority in the health care system in a similar way that multitrauma and myocardial infarction are given today. During the first 24 h, the condition may deteriorate and after the initial resuscitation, the patient must be observed and monitored for vital functions and matched against the treatment goals. Severe sepsis and septic shock may occur within all medical and surgical specialities. Increased awareness of how elusive this condition may appear and of the necessity for prompt care is needed among all healthcare professionals.

  • 11. Hanberger, Håkan
    et al.
    Edlund, Charlotta
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    G Giske, Christian
    Melhus, Asa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine, Clinical Bacteriology.
    Nilsson, Lennart E
    Petersson, Johan
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Ternhag, Anders
    Werner, Maria
    Eliasson, Erik
    Rational use of aminoglycosides-Review and recommendations by the Swedish Reference Group for Antibiotics (SRGA)2013In: Scandinavian journal of infectious diseases, ISSN 1651-1980, Vol. 45, no 3, p. 161-175Article, review/survey (Refereed)
    Abstract [en]

    The Swedish Reference Group for Antibiotics (SRGA) has carried out a risk-benefit analysis of aminoglycoside treatment based on clinical efficacy, antibacterial spectrum, and synergistic effect with beta-lactam antibiotics, endotoxin release, toxicity, and side effects. In addition, SRGA has considered optimal dosage schedules and advice on serum concentration monitoring, with respect to variability in volume of drug distribution and renal clearance. SRGA recommends that aminoglycoside therapy should be considered in the following situations: (1) progressive severe sepsis and septic shock, in combination with broad-spectrum beta-lactam antibiotics, (2) sepsis without shock, in combination with broad-spectrum beta-lactam antibiotics if the infection is suspected to be caused by multi-resistant Gram-negative pathogens, (3) pyelonephritis, in combination with a beta-lactam or quinolone until culture and susceptibility results are obtained, or as monotherapy if a serious allergy to beta-lactam or quinolone antibiotics exists, (4) serious infections caused by multi-resistant Gram-negative bacteria when other alternatives are lacking, and (5) endocarditis caused by difficult-to-treat pathogens when monotherapy with beta-lactam antibiotics is not sufficient. Amikacin is generally more active against extended-spectrum beta-lactamase (ESBL)-producing and quinolone-resistant Escherichia coli than other aminoglycosides, making it a better option in cases of suspected infection caused by multidrug-resistant Enterobacteriaceae. Based on their resistance data, local drug committees should decide on the choice of first-line aminoglycoside. Unfortunately, aminoglycoside use is rarely followed up with audiometry, and in Sweden we currently have no systematic surveillance of adverse events after aminoglycoside treatment. We recommend routine assessment of adverse effects, including hearing loss and impairment of renal function, if possible at the start and after treatment with aminoglycosides, and that these data should be included in hospital patient safety surveillance and national quality registries.

  • 12.
    Kinch, Amelie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Chryssanthou, Erja
    Karolinska Univ Hosp, Dept Clin Microbiol, Stockholm, Sweden.
    Hallböök, Helene
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Haematology.
    Invasive fungal infection by Peziza ostracoderma in an immunocompromised patient2023In: Medical Mycology Case Reports, ISSN 2211-7539, Vol. 39, p. 26-30Article in journal (Refereed)
    Abstract [en]

    We report for the first time a case of disseminated infection caused by Peziza ostracoderma, a mold not previously associated with invasive infections in humans. P. ostracoderma occurs in natural and sterilized soil and may cause hypersensitivity pneumonitis in greenhouse workers. The immunocompromised patient presented with neutropenic fever that did not respond to broad-spectrum antibiotics and developed multiple skin and lung lesions. A skin biopsy demonstrated an angioinvasive mold, identified as Peziza ostracoderma by culture and DNA sequencing. Minimum inhibitory concentration (MIC) for amphotericin B was 0.125 mg/L, for isavuconazole 0.125 mg/L, for voriconazole 0.06 mg/L, and for posaconazole 0.03 mg/L. The skin lesions have resolved completely, and the lung lesions have decreased significantly in size after 14 months of mold-active antifungal therapy, mostly isavuconazole. In conclusion, Peziza species can be opportunistic pathogens causing considerable morbidity in immunocompromised hosts. The infection may be successfully treated with mold-active antifungal drugs.

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  • 13.
    Kurland, Siri
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Löwdin, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Eliasson, E.
    Karolinska Inst, Karolinska Univ Hosp, Dept Lab Med, Clin Pharmacol, Stockholm, Sweden.
    Nielsen, Elisabet I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Pharmacokinetics of Caspofungin in Critically Ill Patients in Relation to Liver Dysfunction: Differential Impact of Plasma Albumin and Bilirubin Levels2019In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 63, no 6, article id e02466-18Article in journal (Refereed)
    Abstract [en]

    Caspofungin has a liver-dependent metabolism. Reduction of the dose is recommended based on Child-Pugh (C-P) score. In critically ill patients, drug pharmacokinetics (PK) may be altered. The aim of this study was to investigate the prevalence of abnormal liver function tests, increased C-P scores, their effects on caspofungin PK, and whether pharmacokinetic-pharmacodynamic (PK/PD) targets were attained in patients with suspected candidiasis. Intensive care unit patients receiving caspofungin were prospectively included. PK parameters were determined on days 2, 5, and 10, and their correlations to the individual liver function tests and the C-P score were analyzed. Forty-six patients were included with C-P class A (n = 5), B (n = 40), and C (n = 1). On day 5 (steady state), the median and interquartile range for area under the curve from 0 to 24 h (AUC(0-24)), clearance (CL), and central volume of distribution (V-1) were 57.8 (51.6 to 69.8) mg.h/liter, 0.88 (0.78 to 1.04) liters/h, and 11.9 (9.6 to 13.1) liters, respectively. The C-P score did not correlate with AUC(0-24) (r = 0.03; P = 0.84), CL (r = -0.07; P = 0.68), or V-1 (r = 0.19; P = 0.26), but there was a bilirubin-driven negative correlation with the elimination rate constant (r = -0.46; P = 0.004). Hypoalbuminemia correlated with low AUC(0-24) (r = 0.45; P = 0.005) and was associated with higher clearance (r = -0.31; P = 0.062) and somewhat higher V-1 (r = -0.15; P = 0.37), resulting in a negative correlation with the elimination rate constant (r = -0.34; P = 0.042). For Candida strains with minimal inhibitory concentrations of >= 0.064 mu g/ml, PK/PD targets were not attained in all patients. The caspofungin dose should not be reduced in critically ill patients in the absence of cirrhosis, and we advise against the use of the C-P score in patients with trauma- or sepsis-induced liver injury.

  • 14.
    Kurland, Siri
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Löwdin, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Nielsen, Elisabet I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Elimination ability of caspofungin in critically ill patients in relation to liver dysfunction in an ICU setting2017In: Mycoses, ISSN 0933-7407, E-ISSN 1439-0507, Vol. 60, p. 225-225Article in journal (Other academic)
  • 15.
    Kurland, Siri
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Löwdin, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Shams, Ayda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Chryssanthou, Erja
    Karolinska Univ Hosp, Dept Clin Microbiol, Stockholm, Sweden..
    Lagerbäck, Pernilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Tängdén, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Breuer, Olof
    Karolinska Univ Hosp, Karolinska Inst, Dept Lab Med, Clin Pharmacol, Stockholm, Sweden..
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Human plasma protein levels alter the in vitro antifungal activity of caspofungin: An explanation to the effect in critically ill?2022In: Mycoses, ISSN 0933-7407, E-ISSN 1439-0507, Vol. 65, no 1, p. 79-87Article in journal (Refereed)
    Abstract [en]

    Background

    Recent studies have shown low caspofungin concentrations in critically ill patients. In some patients, the therapeutic target, area under the total plasma concentration curve in relation to the minimal inhibition concentration (AUCtot/MIC), seems not to be achieved and therapeutic drug monitoring (TDM) has been proposed. Caspofungin is highly protein-bound and the effect of reduced plasma protein levels on pharmacodynamics has not been investigated.

    Objectives

    Fungal killing activity of caspofungin in vitro was investigated under varying levels of human plasma protein.

    Methods

    Time-kill studies were performed with clinically relevant caspofungin concentrations of 1-9 mg/L on four blood isolates of Cglabrata, three susceptible and one strain with reduced susceptibility, in human plasma and plasma diluted to 50% and 25% using Ringer's acetate.

    Results

    Enhanced fungal killing of the three susceptible strains was observed in plasma with lower protein content (p < .001). AUCtot/MIC required for a 1 log10 CFU/ml kill at 24 h in 50% and 25% plasma was reduced with 36 + 12 and 80 + 9%, respectively. The maximum effect was seen at total caspofungin concentrations of 4–9 × MIC. For the strain with reduced susceptibility, growth was significantly decreased at lower protein levels.

    Conclusions

    Reduced human plasma protein levels increase the antifungal activity of caspofungin in vitro, most likely by increasing the free concentration. Low plasma protein levels in critically ill patients with candidemia might explain a better response to caspofungin than expected from generally accepted target attainment and should be taken into consideration when assessing TDM based on total plasma concentrations.

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  • 16.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Bergquist, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Sirén, Rebecca
    Department of Medicine, Danderyd Hospital, 18288 Stockholm, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Huss, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery. Burn Center, Department of Plastic and Maxillofacial Surgery, Uppsala University Hospital, 75185 Uppsala, Sweden..
    Pravda, Jay
    Inflammatory Disease Research Centre, Therashock LLC, Palm Beach Gardens, FL 33410, USA.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Janols, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Urine Hydrogen Peroxide Levels and Their Relation to Outcome in Patients with Sepsis, Septic Shock, and Major Burn Injury2022In: Biomedicines, E-ISSN 2227-9059, Vol. 10, no 4, article id 848Article in journal (Refereed)
    Abstract [en]

    Hydrogen peroxide (H2O2) and oxidative stress have been suggested as possible instigators of both the systemic inflammatory response and the increased vascular permeability associated with sepsis and septic shock. We measured H2O2 concentrations in the urine of 82 patients with severe infections, such as sepsis, septic shock, and infections not fulfilling sepsis-3 criteria, in patients with major burn injury with associated systemic inflammation, and healthy subjects. The mean concentrations of H2O2 were found to be lower in patients with severe infections compared to burn injury patients and healthy subjects. Patients with acute kidney injury (AKI), vs. those without AKI, in all diagnostic groups displayed higher concentrations of urine H2O2 (p &lt; 0.001). Likewise, urine concentrations of H2O2 were higher in non-survivors as compared to survivors (p &lt; 0.001) at day 28 in all diagnostic groups, as well as in patients with severe infections and burn injury (p &lt; 0.001 for both). In this cohort, increased H2O2 in urine is thus associated with mortality in patients with sepsis and septic shock as well as in patients with burn injury.

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  • 17.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Castegren, Markus
    Karolinska Univ Hosp, Dept Anaesthesia, Intens Care Serv, Solna, Sweden; Karolinska Univ Hosp, Dept Anaesthesia, Surg Serv, Solna, Sweden.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Should the Aminoglycoside β-Lactam Combination Be Abandoned in All Severely Ill Patients With Presumed Gram-Negative Infection?2018In: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 66, no 3, p. 480-482Article in journal (Other academic)
  • 18.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Significant differences when using creatinine, modification of diet in renal disease, or cystatin C for estimating glomerular filtration rate in ICU patients2011In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 116, no 1, p. 39-46Article in journal (Refereed)
    Abstract [en]

    Background. Renal dysfunction is associated with increased morbidity and mortality in intensive care patients. In most cases the glomerular filtration rate (GFR) is estimated based on serum creatinine and the Modification of Diet in Renal Disease (MDRD) formula, but cystatin C-estimated GFR is being used increasingly. The aim of this study was to compare creatinine and MDRD and cystatin C-estimated GFR in intensive care patients. Methods. Retrospective observational study was performed, on patients treated within the general intensive care unit (ICU) during 2004-2006, in a Swedish university hospital. Results. GFR markers are frequently ordered in the ICU; 92% of the patient test results had cystatin C-estimated GFR (eGFR(cystatinC)) ≤ 80 mL/min/1.73 m(2), 75% had eGFR ≤ 50 mL/min/1.73 m(2), and 30% had eGFR ≤ 20 mL/min/1.73 m(2). In contrast, only 46% of the patients had reduced renal function assessed by plasma creatinine alone, and only 47% had eGFR(MDRD) ≤ 80 mL/min/1.73 m(2). The mean difference between eGFR(MDRD) and eGFR(cystatinC) was 39 mL/min/1.73 m(2) for eGFR(cystatinC) values ≤ 60 mL/min/1.73 m(2). Conclusions. GFR is commonly assessed in the ICU. Cystatin C-estimated GFR yields markedly lower GFR results than plasma creatinine and eGFR(MDRD). Many pharmaceuticals are eliminated by the kidney, and their dosage is adjusted for kidney function. Thus, the differences in GFR estimates by the methods used indicate that the GFR method used in the intensive care unit may influence the treatment.

  • 19.
    Smekal, Anna-Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Karolinska Univ Hosp, Clin Microbiol, Solna, Sweden.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Eliasson, Erik
    Karolinska Inst, Clin Pharmacol Lab Med & Med Diagnost MDK KUL, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden..
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Low attainment to PK/PD-targets for β-lactams in a multi-center study on the first 72 h of treatment in ICU patients2022In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 21891Article in journal (Refereed)
    Abstract [en]

    Severe infections are life-threatening conditions commonly seen in the intensive care units (ICUs). Antibiotic treatment with adequate concentrations is of great importance during the first days when the bacterial load is the highest. Therapeutic drug monitoring (TDM) of β-lactam antibiotics has been suggested to monitor target attainment and to improve the outcome. This prospective multi-center study in seven ICUs in Sweden investigated pharmacokinetic/pharmacodynamic-target (PK/PD-target) attainment for cefotaxime, piperacillin-tazobactam and meropenem, commonly used β-lactams in Sweden. A mid-dose and trough antibiotic concentration blood sample were taken from patients with severe infection daily during the first 72 h of treatment. Antibiotic plasma concentrations were analysed by liquid chromatography-mass spectrometry (LC–MS). Antibiotic concentrations 100% time above MIC (minimal inhibitory concentration), (100% T > MIC) and four times above MIC 50% of the time (50% T > 4xMIC) were used as PK/PD-targets. We included 138 patients with the median age of 67 years and the median Simplified Acute Physiology Score 3 (SAPS3) of 59. Forty-five percent of the study-population failed to reach 100% T > MIC during the first day of treatment. The results were similar the following two days. There was a three-fold risk of not meeting the PK/PD target if the patient was treated with cefotaxime. For the cefotaxime treated patients 8 out of 55 (15%) had at least one end-dose concentrations below the level of detection during the study. Low age, low illness severity, low plasma creatinine, lower respiratory tract infection and cefotaxime treatment were risk factors for not reaching 100% T > MIC. In Swedish ICU-patients treated with β-lactam antibiotics, a high proportion of patients did not reach the PK/PD target. TDM could identify patients that need individual higher dosing regimens already on the first day of treatment. Further studies on optimal empirical start dosing of β-lactams, especially for cefotaxime, in the ICU are needed.

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  • 20.
    Smekal, Anna-Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala , Sweden;Clinical Microbiology, Karolinska University Hospital , Solna, Stockholm , Sweden.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala , Sweden.
    Lipcsey, Miklos
    Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala , Sweden;Department of Surgical Sciences, Hedenstierna Laboratory, Uppsala University, Uppsala , Sweden.
    Giske, Christian G
    Clinical Microbiology, Karolinska University Hospital , Solna, Stockholm , Sweden;Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet , Stockholm , Sweden.
    Swedish multicentre study of target attainments with β-lactams in the ICU: which MIC parameter should be used?2023In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091Article in journal (Refereed)
  • 21.
    Sorelius, Karl
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Rigshosp, Dept Vasc Surg, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark..
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Resch, T.
    Rigshosp, Dept Vasc Surg, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark..
    Hultgren, R.
    Karolinska Hosp, Dept Vasc Surg, Stockholm, Sweden..
    Wahlgren, C. M.
    Karolinska Hosp, Dept Vasc Surg, Stockholm, Sweden..
    Roos, H.
    Sahlgrens Univ Hosp, Dept Hybrid & Intervent Surg, Unit Vasc Surg, Gothenburg, Sweden..
    Ojersjo, A.
    Kalmar Hosp, Dept Surg, Kalmar, Sweden..
    Lindström, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Vaccarino, R.
    Skane Univ Hosp, Vasc Ctr, Malmö, Sweden..
    Arvidsson, B.
    Linköping Univ, Dept Thorac & Vasc Surg, Linköping, Sweden.;Linköping Univ, Dept Med & Hlth Sci, Linköping, Sweden..
    Bilos, L.
    Örebro Univ Hosp, Fac Med & Vasc Surg, Dept Cardiothorac & Vasc Surg, Örebro, Sweden..
    Pirouzram, A.
    Örebro Univ Hosp, Fac Med & Vasc Surg, Dept Cardiothorac & Vasc Surg, Örebro, Sweden..
    Arnerlov, C.
    Umeå Univ Hosp, Dept Surg & Perioperat Sci, Surg, Umeå, Sweden..
    Simo, G.
    Cent Hosp Karlstad, Dept Surg, Karlstad, Sweden..
    Svensson, M.
    Falun Cent Hosp, Dept Surg, Falun, Sweden..
    Magnusson, J.
    Helsingborg Hosp, Dept Surg, Helsingborg, Sweden..
    Astrand, H.
    Jönköping Hosp, Dept Surg, Jönköping, Sweden..
    Palm, M.
    Sunderby Hosp, Dept Surg, Sunderbyn, Sweden..
    Holsti, M.
    Umeå Univ Hosp, Dept Surg & Perioperat Sci, Surg, Umeå, Sweden..
    Mellander, S.
    NU Hospitalgrp, Dept Surg, Trollhättan Uddevalla, Sweden..
    Korman, D.
    Östersunds Hosp, Dept Surg, Östersund, Sweden..
    Djavani-Gidlund, K.
    Gävle Cent Hosp, Dept Surg, Gävle, Sweden..
    Huss, M.
    Karolinska Hosp, Dept Vasc Surg, Stockholm, Sweden..
    Bertszel, A.
    Västerås Hosp, Dept Vasc Surg, Västerås, Sweden..
    Docter, M.
    Hudiksvall Hosp, Dept Surg, Hudiksvall, Sweden..
    Drott, C.
    Borås Hosp, Dept Surg, Borås, Sweden..
    Nelzen, O.
    Skaraborg Hosp, Dept Vasc Surg, Skoevde, Sweden..
    Wetterling, T.
    Kristianstad Hosp, Dept Surg, Kristianstad, Sweden..
    Chu, M.
    Reg Hosp Sundsvall, Dept Surg, Sundsvall, Sweden..
    Gilgen, N-P
    Malar Hosp, Dept Surg, Eskilstuna, Sweden..
    Gillgren, P.
    Soder Sjukhuset, Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden.;Soder Sjukhuset, Unit Vasc Surg, Dept Surg, Stockholm, Sweden..
    The Microbiology of Infective Native Aortic Aneurysms in a Population-Based Setting2022In: Annals of Vascular Surgery, ISSN 0890-5096, E-ISSN 1615-5947, Vol. 78, p. 112-122Article in journal (Refereed)
    Abstract [en]

    Objective: The aim was to describe the microbiology of surgically treated infective native (mycotic) aortic aneurysms (INAAs), and associated survival and development of infection-related complications (IRCs). Methods: Data were pooled from 2 nationwide studies on surgically treated patients with INAAs in Sweden, between 1994 - 2016. Patients were grouped and analyzed according to culture results: 1) Staphylococcus aureus, 2) Streptococcus species (sp.), 3) Salmonella sp., 4) Enterococcus sp., 5) Gram-negative intestinal bacteria, 6) Other sp. (all other species found in culture), and 7) Negative cultures. Results: A sum of 182 patients were included, mean age 71 years (standard deviation; SD: 8.9). The median follow-up was 50.3 months (range 0 - 360). 128 (70.3%) patients had positive blood and/or tissue culture; Staphylococcus aureus n = 38 (20.9%), Streptococcus sp. n = 37 (20.3%), Salmonella sp. n = 19 (10.4%), Enterococcus sp. n = 16 (8.8%), Gram-negative intestinal bacteria n = 6, (3.3%), Other sp. n = 12 (6.6%) and Negative cultures n = 54 (29.7%). The estimated survival for the largest groups at 2-years after surgery was: Staphylococcus aureus 62% (95% Confidence interval 53.9 - 70.1), Streptococcus sp. 74.7% (67.4 - 82.0), Salmonella sp. 73.7% (63.6 - 83.8), Enterococcus sp. 61.9% (49.6 - 74.2), and Negative cultures 89.8% (85.5 - 94.1), P =.051. There were 37 IRCs (20.3%), and 19 (51.4%) were fatal, the frequency was insignificant between the groups. The majority of IRCs, 30/37 (81%), developed during the first postoperative year. Conclusion: In this assessment of microbiological findings of INAAs in Sweden, 50% of the pathogens were Staphylococcus aureus, Streptococcus sp., or Salmonella sp.. The overall 20%-frequency of IRCs, and its association with high mortality, motivates long-term antibiotic treatment regardless of microbial findings.

  • 22. Svefors, Jesper
    et al.
    Vikerfors, Tomas
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Lanbeck, Peter
    Otto, Gisela
    Gårdlund, Bengt
    Nationellt kvalitetsregister kan ge bättre vård vid livshotande sepsis: [National quality registry can improve care in life-threatening sepsis]2011In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 6, p. 279-281Article in journal (Refereed)
    Abstract [en]

    A number of evidence based treatment goals have been identified for the initial care of patients with severe sepsis and septic shock. To assess the compliance with these goals in Sweden, the Swedish Society of Infectious Diseases has created a web based registry for patients with community acquired severe sepsis or septic shock that are treated at the Intensive Care Unit within 24 h of arrival to the hospital. Data from the registry are returned regularly to the participating departments allowing comparison of their own performance with aggregate data from all Sweden which may constitute a basis for improvements in the respective emergency departments. Data from the registry suggest that there is considerable room for improvement in the initial care of patients with severe community acquired infections.

  • 23.
    Swartling, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Smekal, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Jönsson, Siv
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Nielsen, Elisabet I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Population pharmacokinetics of cefotaxime in intensive care patients2022In: European Journal of Clinical Pharmacology, ISSN 0031-6970, E-ISSN 1432-1041, Vol. 78, no 2, p. 251-258Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To characterise the pharmacokinetics and associated variability of cefotaxime in adult intensive care unit (ICU) patients and to assess the impact of patient covariates.

    METHODS: This work was based on data from cefotaxime-treated patients included in the ACCIS (Antibiotic Concentrations in Critical Ill ICU Patients in Sweden) study. Clinical data from 51 patients at seven different ICUs in Sweden, given cefotaxime (1000-3000 mg given 2-6 times daily), were collected from the first day of treatment for up to three consecutive days. In total, 263 cefotaxime samples were included in the population pharmacokinetic analysis.

    RESULTS: A two-compartment model with linear elimination, proportional residual error and inter-individual variability (IIV) on clearance and central volume of distribution best described the data. The typical individual was 64 years, with body weight at ICU admission of 92 kg and estimated creatinine clearance of 94 mL/min. The resulting typical value of clearance was 11.1 L/h, central volume of distribution 5.1 L, peripheral volume of distribution 18.2 L and inter-compartmental clearance 14.5 L/h. The estimated creatinine clearance proved to be a significant covariate on clearance (p < 0.001), reducing IIV from 68 to 49%.

    CONCLUSION: A population pharmacokinetic model was developed to describe cefotaxime pharmacokinetics and associated variability in adult ICU patients. The estimated creatinine clearance partly explained the IIV in cefotaxime clearance. However, the remaining unexplained IIV is high and suggests a need for dose individualisation using therapeutic drug monitoring where the developed model, after evaluation of predictive performance, may provide support.

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  • 24.
    Sörelius, Karl
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Gillgren, Peter
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Nationwide Study of the Treatment of Mycotic Abdominal Aortic Aneurysms Comparing Open and Endovascular Repair2016In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 134, no 23, p. 1822-1832Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: -No reliable comparative data exist between open repair (OR) and endovascular repair (EVAR) for mycotic abdominal aortic aneurysms (MAAAs). This nationwide study assessed outcomes after OR and EVAR for MAAA in a population-based cohort.

    METHODS: -All patients treated for MAAAs in Sweden between1994-2014 were identified in the Swedish vascular registry. The primary aim was to assess survival after MAAA with OR and EVAR. Secondary aims were analyses of the rate of recurrent infections and reoperations, and time-trends in surgical treatment. Survival was analyzed using Kaplan-Meier and log-rank test. A propensity score weighted correction for risk factor differences in the two groups was performed, including the operation year to account for differences in treatment and outcomes over time.

    RESULTS: -132 patients were identified, (0.6% of all operated AAA in Sweden). Mean age was 70 years (SD 9.2), and 50 presented with rupture. Survival at 3-months was 86% (95% CI 80-92%), 1-year 79% (72-86%), and 5-years 59% (50-68%). The preferred operative technique shifted from OR to EVAR after 2001 (proportion EVAR 1994-2000 0%, 2001-2007 58%, 2008-2014 60%). Open repair was performed in 62 patients (47%); aortic resection and extra-anatomical bypass (n=7), in-situ reconstruction (n=50), patch plasty (n=3), and 2 patients died intraoperatively. EVAR was performed in 70 patients (53%); standard EVAR (n=55), fenestrated/branched EVAR (n=8), and visceral deviation with stent grafting (n=7); no deaths occurred intraoperatively. Survival at 3-months was lower for OR compared with EVAR (74% vs 96%, p<0.001), with a similar trend present at 1-year (73% vs 84%, p=0.054). A propensity score weighted risk-adjusted analysis confirmed the early better survival associated with EVAR. During median follow-up of 36 and 41 months for OR and EVAR, respectively, there was no difference in long-term survival (5-years 60 vs 58%, p=0.771), infection-related complications (18 vs 24%, p=0.439), or reoperation (21% vs 24%, p=0.650).

    CONCLUSIONS: -This study demonstrates a paradigm shift in treatment of MAAA in Sweden, with EVAR being the preferred treatment modality. EVAR was associated with improved short-term survival compared with OR, without higher associated incidence of serious infection-related complications or reoperations.

  • 25.
    Sörelius, Karl
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Mia, Furebring
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Martin, Björck
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Peter, Gillgren
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Nationwide study demonstrates paradigm shift in treatment of mycotic abdominal aortic aneurysmsManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Radical open surgery (OR) is considered gold standard for management of mycotic abdominal aortic aneurysms (MAAAs). Endovascular repair (EVAR) is a less invasive but controversial treatment option for MAAA because the stentgraft is implanted in an infected field, whilst recent reports indicate promising outcome. No reliable comparative data exists. This nationwide study assesses outcome after OR and EVAR for MAAA in a population-based cohort.

    Methods: All patients treated in Sweden for MAAAs 1994-2014 were identified in the Swedish vascular registry. Twenty-seven vascular units participated in data collection according to a predefined protocol. Survival was cross-matched with the population registry.

    Results: 132 patients with 144 MAAAs were identified, (0.6% of all operated AAA in Sweden). Median age was 70 years (SD 9.2), 51 were immunosuppressed, and 50 presented with rupture. Survival at 3-months was 86% (95% CI 80-92%), 1-year 79% (72-86%), and 5- years 59% (50-68%).

    The preferred operative technique shifted from OR to EVAR after 2001 (proportion EVAR 1994-2000 0%, 2001-2007 58%, 2008-2014 60%). Open repair was performed in 62 patients (47%); aortic resection and extra-anatomical bypass (n=7), in-situ reconstruction (n=50), patch plasty (n=3), and two died intraoperatively OR attempt. EVAR was performed in 70 patients (53%); standard EVAR (n=55), fenestrated/branched EVAR (n=8), and visceral deviation with stentgrafting (n=7).

    Survival at 3-months was inferior for OR compared to EVAR in Kaplan-Meier analysis (74% vs 96%, p<0.001), with a similar trend present at 1-year (73% vs 84%, p=0.054). A propensity score weighted risk-adjusted analysis confirmed the early survival benefit of EVAR. During follow-up (median OR 36, EVAR 41 months) there was no difference in long- term survival (5-years 60 vs 58%, p=0.771), infection-related complications (18 vs 24%, p=0.439), or reoperation (21% vs 24%, p=0.650). In a multivariable analysis OR was a significant risk factor for death at 3-months (odds ratio 6.96, p=0.004).

    Conclusion: This study demonstrates a paradigm shift in treatment of MAAA in Sweden, with EVAR being the preferred treatment modality. EVAR achieved improved short-term survival compared to OR, without increasing the risk of serious infection-related complications or reoperations.

  • 26.
    Tängdén, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Löwdin, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Werner, Sonja
    Korsallergi mellan penicilliner och övriga betalaktam­antibiotikaRisken är betydligt mindre än man tidigare trott: [Cross allergy between penicillins and other beta lactam antibiotics--the risk is much less than previously thought]2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, article id C9A4Article in journal (Refereed)
    Abstract [sv]

    Vid misstänkt IgE-medierad allergi mot antibiotika bör ansvarig läkare dokumentera substans, symtom och förlopp i journalen, informera patienten och skriva remiss för allergiutredning.Patienter med anafylaxi, angio-ödem eller annan livshotande reaktion mot penicillin bör inte ånyo behandlas med penicilliner eller andra betalaktamantibio-tika.Risken för korsallergi mot cefa-losporiner och karbapenemer hos patienter med misstänkt penicillinallergi är betydligt lägre än vad man tidigare har trott.Till patienter med lindriga symtom och låg misstanke om IgE-medierad penicillinallergi kan man särskilt vid allvarliga infektioner överväga att ge beta-laktamantibiotika direkt eller efter provdos.

  • 27.
    Zhao, Linshu
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Furebring, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Xu, Shengyuan
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Subcellular localization and mobolization of carcinoembryonic antigen-related cell adhesion molecule 8 in human neutrophils2004In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 125, no 5, p. 666-673Article in journal (Refereed)
    Abstract [en]

    The subcellular localization and mobilization of carcinoembryonic antigen-related cell adhesion molecule 8 (CEACAM8) was investigated quantitatively in human neutrophils. In resting neutrophils the majority of CEACAM8 was present in the secondary granules, and a small amount of CEACAM8 was present in a light membrane fraction. Stimulation of the neutrophils with phorbol 12-myristate 13-acetate caused a dramatic increase in the content of CEACAM8 in the light membrane fraction, suggesting a translocation of CEACAM8 to the plasma membrane from intracellular pools. The cellular content of CEACAM8 in the neutrophils was estimated to be 82.4 +/- 8.9 ng/10(6) cells (mean +/- SE, n = 10). Administration of granulocyte colony-stimulating factor (G-CSF) to healthy individuals resulted in an increased content of CEACAM8 in neutrophils on day 1, which decreased on day 4. However, the content of CEACAM8 in the light membrane fraction was increased on day 4, possibly due to the stimulation by induced secondary cytokines, such as tumour necrosis factor-alpha (TNF-alpha). This study establishes the secondary granules as the major intracellular pools of CEACAM8 in human neutrophils, from which it may translocate to the plasma membranes upon stimulation of the cells. The translocation of CEACAM8 seen in vivo after G-CSF administration is probably indirect and caused by cytokines such as TNF-alpha.

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