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  • 1.
    Brink, Magnus
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Infect Dis, Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Infect Dis, Gothenburg, Region Vastra G, Sweden.
    Glimåker, Martin
    Karolinska Inst, Dept Med, Div Infect Dis, Solna, Sweden;Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Naucler, Pontus
    Karolinska Inst, Dept Med, Div Infect Dis, Solna, Sweden;Karolinska Univ Hosp, Dept Infect Dis, Stockholm, Sweden.
    Meropenem versus Cefotaxime and Ampicillin as Empirical Antibiotic Treatment in Adult Bacterial Meningitis: a Quality Registry Study, 2008 to 20162019Ingår i: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 63, nr 11, artikel-id e00883-19Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cefotaxime, alone or with ampicillin, is frequently used in empirical treatment of acute bacterial meningitis (ABM). Meropenem is a less extensively investigated alternative. The aim of the study was to investigate the effects of empirical treatment with meropenem compared to cefotaxime plus ampicillin on outcome in ABM. The study was based on data from the Swedish quality register for ABM collected between January 2008 and December 2016. Propensity score matching was performed to adjust for baseline differences between the groups. Mortality within 30 days was the primary outcome. The treatment regimens of interest were administered to 623 patients; 328 were given cefotaxime plus ampicillin whereas 295 received meropenem. Using propensity score matching, the 30-day mortality rates were 3.2% in the cefotaxime plus ampicillin group and 3.6% in the meropenem group. For matched cases, the odds ratio (OR) for 30-day mortality for meropenem versus cefotaxime plus ampicillin was 1.15 (confidence interval [CI], 0.41 to 3.22; P = 0.79). The OR for 90-day mortality was 1.47 (CI, 0.62 to 3.52; P = 0.38) and for unfavorable outcome was 1.10 (CI, 0.75 to 1.63; P = 0.62). The findings of our study indicate that meropenem is an effective empirical treatment option for adults with community-acquired ABM. However, to spare carbapenems, guidelines should continue to recommend third-generation cephalosporins as an empirical treatment for the majority of patients with ABM.

  • 2.
    Carlsson, Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Tano, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk bakteriologi.
    Rubertsson, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Inflammatory and circulatory effects of the reduction of endotoxin concentration in established porcine endotoxemic shock: a model of endotoxin elimination2009Ingår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 37, nr 3, s. 1031-e4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective:

    To study whether a reduction of the endotoxin load, once a generalized inflammatory state has been established, reduces the inflammatory response and endotoxin-induced effects on circulation, hypoperfusion, and organ dysfunction.

    Design:

    Prospective parallel-grouped placebo-controlled randomized interventional experimental study.

    Setting:

    University research unit.

    Subjects:

    Healthy pigs.

    Interventions:

    The animals were subjected to a continuous endotoxin infusion rate of either 4.0 or 0.063 µg endotoxin × kg-1 × h-1 for 1, 2, or 6 hours. The 1- and 2-hour infusion groups represented the applied therapy by a reduction of the endotoxin load of 5/6 and 2/3, respectively.

    Measurements and Main Results:

    During a 6-hour experiment, laboratory and physiologic parameters were recorded hourly in 26 anesthetized and mechanically ventilated pigs. Primary end point was to detect differences in tumor necrosis factor-[alpha] (TNF-[alpha]) concentration during the last 3 hours of the experiment. Despite the early reduction of the endotoxin load, no effect on TNF-[alpha] concentration was observed. Similarly, in circulatory parameters, such as mean arterial pressure and oxygen delivery, and in platelet count and renal function, no effects were noted. However, there was some improvement in pulmonary compliance and function as determined by Pao2, Paco2, and pH. These changes were associated with slight improvements in leukocyte response and capillary leakage.

    Conclusions:

    Termination of the endotoxin infusion represents an incontestable model of endotoxin concentration reduction. Endotoxin elimination strategies applied at the TNF-[alpha] peak or later will have very little or no effect on TNF-[alpha]–mediated toxicity. Nevertheless, there was an effect on the leukocyte response that was associated with an improvement in respiratory function and microcirculation, making it impossible to rule out fully the beneficial effect of this strategy. However, the effects were limited in relation to the magnitude of the endotoxin concentration reduction and the very early application of the antiendotoxin measure.

  • 3.
    Castegren, Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Jonasson, Mikaela
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Castegren, Sara
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Initial levels of organ failure, microbial findings and mortality in intensive care-treated primary, secondary and tertiary sepsis2015Ingår i: CRITICAL CARE AND RESUSCITATION, ISSN 1441-2772, Vol. 17, nr 3, s. 174-181Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Analysis of whether patients with primary, secondary and tertiary sepsis, defined by the presence or absence of recent systemic inflammation-inducing events before the onset of sepsis, differ in clinical presentation, microbiological test results, treatment received and outcome. Design, setting and participants: A retrospective observational study in a single, general intensive care unit, of all patients treated for severe sepsis or septic shock from 2006 to 2011. Patients with haematological malignancies, with immunosuppressive diseases or being treated with immunosuppressive drugs were excluded. Interventions: None. Main outcome measures: Sequential Organ Failure Assessment score, incidence of organ failure, microbiological results of blood cultures and mortality. Results: We included 213 patients, who were classified as having primary (n = 121), secondary (n = 65) or tertiary sepsis (n = 27). The groups differed significantly in SOFA score, the incidence of kidney failure and coagulation failure at onset of sepsis in the ICU, as well as in blood culture findings. No differences in 7-day or 28-day mortality were seen, but the time of death occurred earlier among non-survivors in the primary sepsis group. Conclusions: Inflammatory insults before the onset of sepsis affect the clinical picture, blood microbial findings, and in non-survivors, the time of death. These results could, if validated in a prospective study, form a basis for a novel and simple strategy for stratifying patients in clinical studies for immunomodulation therapies in sepsis.

  • 4.
    Castegren, Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i D län (CKFD).
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Söderberg, Ewa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Skorup, Paul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Eriksson, Mats
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Biokemisk struktur och funktion.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Differences in Organ Dysfunction in Endotoxin Tolerant Pigs Under Intensive Care Exposed to a Second Hit of Endotoxin2012Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 37, nr 5, s. 501-510Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Endotoxin tolerance is a well-studied phenomenon associated with a reduced inflammatory response. In the switch from an inflammatory to an anti-inflammatory response in clinical sepsis the concept of endotoxin tolerance is of obvious interest. However, only limited data exist regarding the effect of endotoxin tolerance on organ dysfunction and, therefore, this was investigated in a porcine intensive care sepsis model. Twenty-seven healthy pigs, including nine control animals, were included in the study. Twelve pigs pre-exposed to 24 h of intravenous endotoxin infusion and intensive care and six unexposed pigs were given either a high- or low-dose endotoxin challenge for 6 h. Inflammatory, circulatory, hypoperfusion and organ dysfunction parameters were followed. The inflammatory responses as well as parameters representing circulation, hypoperfusion, cardiac and renal function were all markedly attenuated in animals pre-exposed to endotoxin and intensive care as compared with animals not pre-exposed. In animals pre-exposed to endotoxin and given the high-dose of endotoxin challenge, deterioration in pulmonary function was equal to or even worse than in animals not pre-exposed.In contrast to the overall protective effect of endotoxin tolerance observed in other organ systems, the lungs of endotoxin tolerant animals demonstrated an increased responsiveness to high-dose endotoxin challenge.

  • 5.
    Castegren, Markus
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i D län (CKFD).
    Skorup, Paul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Endotoxin tolerance variation over 24 h during porcine endotoxemia: association to changes in circulation and organ dysfunction2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 1, s. e53221-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Endotoxin tolerance (ET), defined as reduced inflammatory responsiveness to endotoxin challenge following a first encounter with endotoxin, is an extensively studied phenomenon. Although reduced mortality and morbidity in the presence of ET has been demonstrated in animal studies, little is known about the temporal development of ET. Further, in acute respiratory distress syndrome ET correlates to the severity of the disease, suggesting a complicated relation between ET and organ dysfunction. Eighteen pigs were subjected to intensive care and a continuous endotoxin infusion for 24 h with the aim to study the time course of early ET and to relate ET to outcome in organ dysfunction. Three animals served as non-endotoxemic controls. Blood samples for cytokine analyses were taken and physiological variables registered every third hour. Production of TNF-α, IL-6, and IL-10 before and after endotoxin stimulation ex vivo was measured. The difference between cytokine values after and before ex vivo LPS stimulation (Δ-values) was calculated for all time points. ΔTNF-α was employed as the principal marker of ET and lower ΔTNF-α values were interpreted as higher levels of ET. During endotoxin infusion, there was suppression of ex vivo productions of TNF-α and IL-6 but not of IL-10 in comparison with that at 0 h. The ex vivo TNF-α values followed another time concentration curve than those in vivo. ΔTNF-α was at the lowest already at 6 h, followed by an increase during the ensuing hours. ΔTNF-α at 6 h correlated positively to blood pressure and systemic vascular resistance and negatively to cardiac index at 24 h. In this study a temporal variation of ET was demonstrated that did not follow changes in plasma TNF-α concentrations. Maximal ET occurred early in the course and the higher the ET, the more hyperdynamic the circulation 18 h later.

  • 6.
    Edberg, M
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Furebring, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Neurointensive care of patients with severe community-acquired meningitis2011Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 55, nr 6, s. 732-739Artikel i tidskrift (Refereegranskat)
    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.

  • 7. Ericsson, J.
    et al.
    Chryssanthou, E.
    Klingspor, L.
    Johansson, A. G.
    Ljungman, P.
    Svensson, E.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Candidaemia in Sweden: a nationwide prospective observational survey2013Ingår i: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 19, nr 4, s. E218-E221Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A prospective observational nationwide investigation was performed from September 2005 to August 2006 to study the epidemiology of candidaemia in Sweden. From 385 patients, 403 isolates were recovered, yielding an incidence of 4.2 cases per 100000 inhabitants. Candida albicans was the most common species (61%), followed by Candida glabrata (20%) and Candida parapsilosis (9%). The rates of resistance to fluconazole were 1% in C.albicans and 629% in non-albicans species other than C.glabrata and Candida krusei. Resistance to voriconazole was rare, except for C.glabrata and C.krusei. Only three isolates had reduced susceptibility to amphotericinB, and one had reduced susceptibility to caspofungin.

  • 8.
    Eriksson, Britt-Marie
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Melhus, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi och infektionsmedicin.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Nya rekommendationer för akut faryngotonsillit kan leda felRisk att patienter inte får nödvändig antibiotikabehandling: [New recommendations for acute pharyngotonsillitis can cause errors. There is a risk that patients will not receive proper antibiotic treatment].2014Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, nr 3-4, s. 86-88Artikel i tidskrift (Refereegranskat)
    Abstract [sv]

    Akut faryngotonsillit är en av de vanligaste anledningarna till besök i öppen vård. 

    Cirka en tredjedel av fallen orsakas av bakterier, vanligen betahemolytiska streptokocker grupp A, men även grupp C och G förekommer. På senare år har Fusobacterium necrophorum uppmärksammats som en vanlig orsak, framför allt i åldersgruppen 16–30 år. 

    Akut faryngotonsillit kan ibland leda till allvarliga lokala eller generella komplikationer.

    Nuvarande svenska rekommendationer riskerar medföra att vissa patienter inte får erforderlig antibiotikabehandling.

  • 9.
    Floros, Lefteris
    et al.
    Covance Market Access, London, England.
    Kuessner, Daniel
    Basilea Pharmaceut Int Ltd, Basel, Switzerland.
    Posthumus, Jan
    Basilea Pharmaceut Int Ltd, Basel, Switzerland.
    Bagshaw, Emma
    Covance Market Access, London, England.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Cost-effectiveness analysis of isavuconazole versus voriconazole for the treatment of patients with possible invasive aspergillosis in Sweden2019Ingår i: BMC Infectious Diseases, ISSN 1471-2334, E-ISSN 1471-2334, Vol. 19, artikel-id 134Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Voriconazole is well established as standard treatment for invasive aspergillosis (IA). In 2017, isavuconazole, a new antifungal from the azole class, with a broader pathogen spectrum, was introduced in Sweden. A model has therefore been developed to compare the cost-effectiveness of isavuconazole and voriconazole in the treatment of possible IA in adults in Sweden.

    Methods: The cost-effectiveness of isavuconazole versus voriconazole was evaluated using a decision-tree model. Patients with possible IA entered the model, with 6% assumed to actually have mucormycosis. It was also assumed that pathogen information would become available during the course of treatment for only 50% of patients, with differential diagnosis unavailable for the remainder. Patients who were considered unresponsive to first-line treatment were switched to second-line treatment with liposomal amphotericin-B. Data and clinical definitions included in the model were taken from the published randomised clinical trial comparing isavuconazole with voriconazole for the treatment of IA and other filamentous fungi (SECURE) and the single-arm, open-label trial and case-control analysis of isavuconazole for the treatment of mucormycosis (VITAL). A probabilistic sensitivity analysis was used to estimate the combined parameter uncertainty, and a deterministic sensitivity analysis and a scenario analysis were performed to test the robustness of the model assumptions. The model followed a Swedish healthcare payer perspective, therefore only considering direct medical costs.

    Results: The base case analysis showed that isavuconazole resulted in an incremental cost-effectiveness ratio (ICER) of 174,890 Swedish krona (SEK) per additional quality adjusted life-year (QALY) gained. This was mainly due to the efficacy of isavuconazole against IA and mucormycosis, as opposed to voriconazole, which is only effective against IA. Sensitivity and scenario analyses of the data showed that the average ICER consistently fell below the willingness to pay (WTP) threshold of 1,000,000 SEK. The probability of isavuconazole being cost-effective at a WTP of 170,000 SEK per QALY gained was 50% and at a WTP of 500,000 SEK per QALY gained was 100%.

    Conclusions: This model suggests that the treatment of possible IA with isavuconazole is cost-effective compared with treatment with voriconazole from a Swedish healthcare payer perspective.

  • 10.
    Furebring, M
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Infektion.
    Håkansson, L
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Venge, P
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Klinisk kemi.
    Sjölin, J
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. 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.2006Ingår i: Scand J Immunol, ISSN 0300-9475, Vol. 63, nr 3, s. 208-16Artikel i tidskrift (Refereegranskat)
  • 11.
    Furebring, Mia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Håkansson, Lena Douhan
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Nilsson, Bo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Expression of the C5a receptor (CD88) on granulocytes and monocytes in patients with severe sepsis2002Ingår i: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 6, nr 4, s. 363-370Artikel i tidskrift (Refereegranskat)
    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.

  • 12.
    Furebring, Mia
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Håkansson, Lena
    Venge, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Differential expression of the C5a receptor and complement receptors 1 and 3 after LPS stimulation of neutrophils and monocytes2004Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 60, nr 5, s. 494-499Artikel i tidskrift (Refereegranskat)
    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.

  • 13. Glimaker, Martin
    et al.
    Johansson, Bibi
    Bell, Max
    Ericsson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Blackberg, Jonas
    Brink, Magnus
    Lindquist, Lars
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Early lumbar puncture in adult bacterial meningitis-rationale for revised guidelines2013Ingår i: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 45, nr 9, s. 657-663Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Current international guidelines recommend cerebral computerized tomography (CT) before lumbar puncture (LP) in many adults with suspected acute bacterial meningitis (ABM), due to concern about LP-induced cerebral herniation. Despite guideline emphasis on early treatment based on symptoms, performing CT prior to LP implies a risk of delayed ABM treatment, which may be associated with a fatal outcome. Firm evidence for LP-induced herniation in adult ABM is absent and brain CT cannot discard herniation. Thus, the recommendation to perform CT before LP may contribute to an avoidable delay of LP and ABM treatment. The inappropriate use of the diagnostic treatment sequence of brain CT scan, followed by LP, followed by antibiotics and corticosteroids should be avoided in adults with suspected ABM by omitting needless contraindications for LP, thus eliminating an unnecessary fear of immediate LP. Revised Swedish guidelines regarding early LP are presented, and the background documentation and reasons for omitting impaired consciousness, new onset seizures, and immunocompromised state as contraindications to LP are discussed.

  • 14. Glimaker, Martin
    et al.
    Johansson, Bibi
    Grindborg, Orjan
    Bottai, Matteo
    Lindquist, Lars
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Adult Bacterial Meningitis: Earlier Treatment and Improved Outcome Following Guideline Revision Promoting Prompt Lumbar Puncture2015Ingår i: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 60, nr 8, s. 1162-1169Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. In suspected acute bacterial meningitis (ABM), cerebral computerized tomography (CT) is recommended before lumbar puncture (LP) if mental impairment. Despite guideline emphasis on early treatment, performing CT prior to LP implies a risk of delayed treatment and unfavorable outcome. Therefore, Swedish guidelines were revised in 2009, deleting impaired mental status as a contraindication for LP without prior CT scan. The aim of the present study was to evaluate the guideline revision. Methods. The Swedish quality registry for community-acquired ABM was analyzed retrospectively. Door-to-antibiotic time and outcome were compared among patients treated 2005-2009 (n = 394) and 2010-2012 (n = 318). The effect of different LP-CT sequences was analyzed during 2008-2012. Results. Adequate treatment was started 1.2 hours earlier, and significantly more patients were treated <2 hours from admission 2010-2012 than 2005-2009. Compared with CT before LP, immediate LP resulted in 1.6 hours earlier treatment, significant increase in door-to-antibiotic times of <1 and <2 hours, and a favorable outcome. In 2010-2012, mortality was lower (6.9% vs 11.7%) and the risk of sequelae at follow-up decreased (38% vs 49%) in comparison with 2005-2009. Treatment delay resulted in a significantly increased risk for fatal outcome, with a relative increase in mortality of 12.6% per hour of delay. Conclusions. The deletion of impaired mental status as contraindication for prompt LP and LP without prior CT scan are associated with significantly earlier treatment and a favorable outcome. A revision of current international guidelines should be considered.

  • 15. Glimaker, Martin
    et al.
    Johansson, Bibi
    Grindborg, Orjan
    Bottai, Matteo
    Lindquist, Lars
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Reply to Brouwer and van de Beek: Earlier Treatment and Improved Outcome in Adult Bacterial Meningitis Following Guideline Revision Promoting Prompt Lumbar Puncture Reply2015Ingår i: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 61, nr 4, s. 665-666Artikel i tidskrift (Refereegranskat)
  • 16. Glimåker, Martin
    et al.
    Lindquist, Lars
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Lumbar puncture in adult bacterial meningitis: time to reconsider guidelines?2013Ingår i: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 346, artikel-id f361Artikel i tidskrift (Refereegranskat)
  • 17.
    Glimåker, Martin
    et al.
    Karolinska Inst, Dept Med, Infect Dis Unit, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Lumbar Puncture Is Safe in Bacterial Meningitis: Impaired Mental Status Alone Does Not Motivate Cranial Computed Tomography Before Lumbar Puncture2019Ingår i: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 68, nr 1, s. 168-168Artikel i tidskrift (Övrigt vetenskapligt)
  • 18.
    Goscinski, Gunilla
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Mats B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Tano, Eva
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Anti-inflammatory effects of the antibiotics ceftazidime and tobramycin in porcine endotoxin shock: are they really anti-inflammatory? Authors' response.2004Ingår i: Crit Care, ISSN 1466-609X, Vol. 8, nr 2, s. 141-Artikel i tidskrift (Övrigt vetenskapligt)
  • 19.
    Goscinski, Gunilla
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Infektion.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Mats B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Tano, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Infektion.
    Endotoxin neutralisation and anti-inflammatory effects by tobramycin and ceftazidime in porcine endotoxic shock2003Ingår i: Cricical Care, Vol. Suppl2, s. 125-Artikel i tidskrift (Refereegranskat)
  • 20. Goscinski, Gunilla
    et al.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Mats B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Tano, Eva
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Endotoxin neutralization and anti-inflammatory effects of tobramycin and ceftazidime in porcine endotoxin shock2004Ingår i: Critical care, ISSN 1364-8535, Vol. 8, nr 1, s. 35-41Artikel i tidskrift (Refereegranskat)
  • 21.
    Goscinski, Gunilla
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Tano, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Löwdin, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Propensity to release endotoxin after two repeated doses of cefuroxime in an in vitro kinetic model: Higher release after the second dose2007Ingår i: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 60, nr 2, s. 328-333Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: To study endotoxin release from two strains of Escherichia coli after exposure to two repeated doses of cefuroxime in an in vitro kinetic model.

    Methods: Cefuroxime in concentrations simulating human pharmacokinetics was added to the bacterial solution with a repeated dose after 12 h. In another experiment, tobramycin was given concomitantly with the second dose of cefuroxime. Samples for viable counts and endotoxin analyses were drawn before the addition of antibiotics and at 2 and 4 h after each dose.

    Results: The propensity to release endotoxin, expressed as log10 endotoxin release (EU)/log10 killed bacteria, was higher after the second than after the first dose, 0.80 ± 0.04 and 0.65 ± 0.01, respectively, in the ATCC strain and 0.80 ± 0.04 and 0.65 ± 0.02, respectively, in the clinical strain (P < 0.001). Endotoxin was released earlier after the second dose (P < 0.001). Addition of tobramycin at the second dose reduced the endotoxin release in comparison with that of cefuroxime alone (P < 0.001).

    Conclusions: The propensity to liberate endotoxin is higher after the second dose of cefuroxime than after the first, resulting in a higher release of endotoxin than expected from bacterial count. The release after the second dose can be reduced by the addition of tobramycin.

  • 22.
    Goscinski, Gunilla
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Tano, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Thulin, Pontus
    Norrby-Teglund, Anna
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Release of SpeA from Streptococcus pyogenes after exposure to penicillin: dependency on dose and inhibition by clindamycin2006Ingår i: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 38, nr 11-12, s. 983-987Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The amount and time course of SpeA release from group A streptococci (GAS) was studied at different starting inoculae after exposure to different doses of penicillin, clindamycin or a combination of the 2. The release was related to the bacterial concentration and killing rate. A clinical GAS strain was exposed to benzylpenicillin, 2 and 1000 × MIC, clindamycin, 2 and 32 × MIC, or combinations of the 2. Samples for viable counts and SpeA analyses were drawn before and after the addition of antibiotics and at 3, 6 and 24 h. The SpeA release was higher at low than at high concentrations of penicillin and the combination (both, p < 0.05). The addition of clindamycin to penicillin reduced SpeA production at both concentrations (p < 0.01). Most SpeA was released before 3 h, and for penicillin and the combination, the amount correlated to the number of killed bacteria during this period (r = 0.50; p < 0.05). A positive correlation was found between the inoculum size and the SpeA concentration at time zero (r = 0.54; p < 0.05). The SpeA concentration was dependent on the initial number of bacteria, the class of antibiotic, the dose of penicillin and the killing rate.

  • 23. Grindborg, O.
    et al.
    Naucler, P.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Glimaker, M.
    Adult bacterial meningitis-a quality registry study: earlier treatment and favourable outcome if initial management by infectious diseases physicians2015Ingår i: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 21, nr 6, s. 560-566Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Acute bacterial meningitis (ABM) is challenging for the admitting physician because it is a rare but fulminant disease, usually presenting without typical symptoms, and rapid treatment is pivotal. The purpose of this study was to evaluate the effect of initial management by infectious diseases (ID) physicians vs. non-ID physicians. A total of 520 consecutive adults (>17 years old), 110 with initial ID management and 410 with non-ID management, registered in the Swedish quality registry for community-acquired ABM January 2008 to December 2013, were analysed retrospectively. Primary outcome was appropriate treatment with antibiotics and corticosteroids <1 hour from admission. Secondary analyses were mortality during hospital stay and persisting neurological and hearing deficits at follow-up after 2 to 6 months. Differences in diagnostic treatment sequences also were analysed. Appropriate treatment <1 hour from admission was achieved, significantly more often (41%) by ID physicians vs. non-ID physicians (24%) with an odds ratio (OR) of 2.4 (95% confidence interval [CI]: 1.40 to 4.14; p < 0.01) adjusted for confounders. The door-to-antibiotic time was significantly shorter, and significantly more patients were administered corticosteroids together with the first doses of antibiotics in the ID group. A trend of decreased mortality (4.5% vs. 8.0%) and sequelae at follow-up (24% vs. 44%; adjusted OR 0.55: 95% CI 0.31 to 1.00; p 0.05) were observed in the ID group vs. the non-ID group. Antibiotics were started without prior neuroimaging more often in the ID group (86% vs. 57%; p < 0.001). Initial management at the emergency department by ID physicians is associated with earlier appropriate treatment, more appropriate diagnostic treatment sequences and favourable outcome.

  • 24. Hanberger, Håkan
    et al.
    Edlund, Charlotta
    Furebring, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    G Giske, Christian
    Melhus, Asa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi och infektionsmedicin, Klinisk bakteriologi.
    Nilsson, Lennart E
    Petersson, Johan
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Ternhag, Anders
    Werner, Maria
    Eliasson, Erik
    Rational use of aminoglycosides-Review and recommendations by the Swedish Reference Group for Antibiotics (SRGA)2013Ingår i: Scandinavian journal of infectious diseases, ISSN 1651-1980, Vol. 45, nr 3, s. 161-175Artikel, forskningsöversikt (Refereegranskat)
    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.

  • 25.
    Hanslin, Katja
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Skorup, Paul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Wilske, Frida
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Castegren, Marcus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Lipcsey, Miklos
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Pre-existing systemic inflammation attenuates bacterial clearance by the liver in porcine abdominal sepsis2016Ingår i: Intensive Care Medicine Experimental, ISSN 1646-2335, E-ISSN 2197-425X, Vol. 3, nr suppl. 1, s. A620-Artikel i tidskrift (Refereegranskat)
  • 26.
    Hanslin, Katja
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Skorup, Paul
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Wilske, Frida
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Castegren, Markus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin. Perioperative Medicine and Intensive Care, Karolinska University Hospital and CLINTEC, Karolinska Institute, Stockholm, Sweden.
    Tano, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk mikrobiologi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    The impact of the systemic inflammatory response on hepatic bacterial elimination in experimental abdominal sepsis2019Ingår i: Intensive Care Medicine Experimental, ISSN 2197-425X, Vol. 7, nr 1, artikel-id 52Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Bacterial translocation from the gut has been suggested to induce a systemic inflammatory response syndrome (SIRS) and organ dysfunction. The liver has a pivotal role in eliminating circulating bacteria entering from the gut. We investigated whether pre-existing inflammation affects hepatic bacterial elimination.

    METHODS: Fifteen anaesthetised piglets were infused with E. coli in the portal vein for 3 h. The naive group (n = 6) received the bacterial infusion without endotoxin exposure. SIRS (SIRS group, n = 6) was induced by endotoxin infusion 24 h before the bacterial infusion. For effects of anaesthesia, controls (n = 3) received saline instead of endotoxin for 24 h. Bacterial counts and endotoxin levels in the portal and hepatic veins were analysed during bacterial infusion.

    RESULTS: The bacterial killing rate was higher in the naive group compared with the SIRS group (p = 0.001). The ratio of hepatic to portal venous bacterial counts, i.e. the median bacterial influx from the splanchnic circulation, was 0.06 (IQR 0.01-0.11) in the naive group and 0.71 (0.03-1.77) in the SIRS group at 3 h, and a magnitude lower in the naive group during bacteraemia (p = 0.03). Similar results were seen for hepatic endotoxin elimination. Peak log tumour necrosis factor alpha was higher in the naive 4.84 (4.77-4.89) vs. the SIRS group 3.27 (3.26-3.32) mg/L (p < 0.001).

    CONCLUSIONS: Our results suggest that hepatic bacterial and endotoxin elimination is impaired in pigs with pre-existing SIRS while the inflammatory response to bacterial infusion is diminished. If similar mechanisms operate in human critical illness, the hepatic elimination of bacteria from the gut could be impaired by SIRS.

  • 27.
    Hedberg, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Hårdemark, Hans-Göran
    Olsson-Liljequist, B.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Penetration of fusidic acid and rifampicin into cerebrospinal fluid in low-grade inflammatory meningitis caused by Staphylococcus epidermidis2004Ingår i: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 10, nr 8, s. 765-768Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Cerebrospinal fluid (CSF) concentration-time curves of rifampicin and fusidic acid were studied in a patient with post-operative meningitis caused by Staphylococcus epidermidis. The patient was treated with this combination of antimicrobial agents because of a severe hypersensitivity reaction to vancomycin. Peak CSF concentrations of rifampicin exceeded the MIC by > 60-fold, while those of fusidic acid just reached the MIC. CSF concentrations of fusidic acid were relatively stable within the range reported for patients with uninflamed meninges, but serum levels were surprisingly low. An increase in the metabolism of fusidic acid induced by rifampicin cannot be excluded.

  • 28.
    Jansson, Anna-Karin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Efficacy and safety of cefotaxime in combination with metronidazole for empirical treatment of brain abscess in clinical practice: a retrospective study of 66 consecutive cases2004Ingår i: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 23, nr 1, s. 7-14Artikel i tidskrift (Refereegranskat)
  • 29.
    Jansson-Nettelbladt, Evelyn
    et al.
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Infektion.
    Meurling, Staffan
    Petrini, Björn
    Sjölin, Jan
    Uppsala universitet, Medicinska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Infektion.
    Endogenous ethanol fermentation in a child with short bowel syndrome.2006Ingår i: Acta Paediatr, ISSN 0803-5253, Vol. 95, nr 4, s. 502-4Artikel i tidskrift (Övrigt vetenskapligt)
  • 30.
    Kurland, Siri
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Furebring, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionsmedicin.
    Löwdin, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Eliasson, E.
    Karolinska Inst, Karolinska Univ Hosp, Dept Lab Med, Clin Pharmacol, Stockholm, Sweden.
    Nielsen, Elisabet I.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Pharmacokinetics of Caspofungin in Critically Ill Patients in Relation to Liver Dysfunction: Differential Impact of Plasma Albumin and Bilirubin Levels2019Ingår i: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 63, nr 6, artikel-id e02466-18Artikel i tidskrift (Refereegranskat)
    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.

  • 31.
    Kurland, Siri
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Furebring, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Löwdin, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Nielsen, Elisabet I.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Elimination ability of caspofungin in critically ill patients in relation to liver dysfunction in an ICU setting2017Ingår i: Mycoses (Berlin), ISSN 0933-7407, E-ISSN 1439-0507, Vol. 60, s. 225-225Artikel i tidskrift (Övrigt vetenskapligt)
  • 32.
    Larsson, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Klinisk kemi.
    Lipcsey, Miklós
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Infektion.
    Hansson, Lars-Olof
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper. Klinisk kemi.
    Eriksson, Mats B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Slight Increase of Serum S-100B During Porcine Endotoxemic Shock May Indicate Blood-Brain Barrier Damage.2005Ingår i: Anesth Analg, ISSN 0003-2999, Vol. 101, nr 5, s. 1465-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Septic shock is a condition that affects many organs, but little is known about the effects on the central nervous system. S-100B, an acidic low molecular weight protein, has attracted considerable interest as a marker for brain damage and disintegration of the blood-brain barrier. It is released into the cerebrospinal fluid and blood from brain tissue after brain damage. We studied S-100B in a porcine model of endotoxemic shock that resembles human Gram-negative septic shock. Ten piglets received IV endotoxin, and plasma samples were collected before the endotoxin infusion and each hour (1-6 h) during the endotoxin infusion. S-100B was measured by sandwich enzyme-linked immunosorbent assay. Low levels of plasma S-100B were detected, but there was a significant increase in S-100B during Hours 1-5 in comparison with the 0 values. We determined that endotoxemia causes a very small but significant increase in the levels of the widely used brain damage marker serum S-100B. However, it cannot be excluded that the increase in S-100B could be caused by release from organs other than the brain.

  • 33.
    Lignell, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Johansson, A.
    Löwdin, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Cars, Otto
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    A new in-vitro kinetic model to study the pharmacodynamics of antifungal agents: inhibition of the fungicidal activity of amphotericin B against Candida albicans by voriconazole2007Ingår i: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 13, nr 6, s. 613-619Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to develop and validate a new in-vitro kinetic model for the combination of two drugs with different half-lives, and to use this model for the study of the pharmacodynamic effects of amphotericin B and voriconazole, alone or in combination, against a strain of Candida albicans. Bolus doses of voriconazole and amphotericin B were administered to a starting inoculum of C. albicans. Antifungal-containing medium was eliminated and replaced by fresh medium using a peristaltic pump, with the flow-rate adjusted to obtain the desired half-life of the drug with the shorter half-life. A computer-controlled dosing pump compensated for the agent with the longer half-life. Voriconazole and amphotericin B half-lives were set to 6 and 24 h, respectively. Pharmacokinetic parameters were close to target values when both single doses and sequential doses were simulated. Voriconazole and amphotericin B administered alone demonstrated fungistatic and fungicidal activity, respectively. Simultaneous administration resulted in fungicidal activity, whereas pre-exposure of C. albicans to voriconazole, followed by amphotericin at 8 and 32 h, resulted in fungistatic activity similar to that observed with voriconazole alone. Using this model, which allowed a combination of antifungal agents with different half-lives, it was possible to demonstrate an antagonistic effect of voriconazole on the fungicidal activity of amphotericin B. The characteristics and clinical relevance of this interaction require further investigation.

  • 34.
    Lignell, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Löwdin, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Cars, Otto
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Chryssanthou, Erja
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Posaconazole in human serum: A greater pharmacodynamic effect than predicted by the non-protein-bound serum concentration2011Ingår i: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 55, nr 7, s. 3099-3104Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is generally accepted that only the unbound fraction of a drug is pharmacologically active. Posaconazole is an antifungal agent with a protein binding of 98 to 99%. Taking into account the degree of protein binding, plasma levels in patients, and MIC levels of susceptible strains, it can be assumed that the free concentration of posaconazole sometimes will be too low to exert the expected antifungal effect. The aim was therefore to test the activity of posaconazole in serum in comparison with that of the calculated unbound concentrations in protein-free media. Significant differences (P < 0.05) from the serum control were found at serum concentrations of posaconazole of 1.0 and 0.10 mg/liter, with calculated free concentrations corresponding to 1× MIC and 0.1× MIC, respectively, against one Candida lusitaniae strain selected for proof of principle. In RPMI 1640, the corresponding calculated unbound concentration of 0.015 mg/liter resulted in a significant effect, whereas that of 0.0015 mg/liter did not. Also, against seven additional Candida strains tested, there was an effect of the low posaconazole concentration in serum, in contrast to the results in RPMI 1640. Fluconazole, a low-grade-protein-bound antifungal, was used for comparison at corresponding concentrations in serum and RPMI 1640. No effect was observed at the serum concentration, resulting in a calculated unbound concentration of 0.1× MIC. In summary, there was a substantially greater pharmacodynamic effect of posaconazole in human serum than could be predicted by the non-protein-bound serum concentration. A flux from serum protein-bound to fungal lanosterol 14α-demethylase-bound posaconazole is suggested.

  • 35.
    Lignell, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Siegbahn, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Stridsberg, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Pauksen, Karlis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Gedeborg, Rolf
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Low utilisation of unactivated protein C in a patient with meningococcal septic shock and disseminated intravascular coagulation2003Ingår i: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 47, nr 7, s. 897-900Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Activated protein C has recently been shown in a multicentre trial to significantly reduce mortality in patients with septic shock. There are also some case reports and minor studies demonstrating promising results with the unactivated form of protein C. However, in children with severe meningococcal infection, skin biopsies have demonstrated low expression of endothelial thrombomodulin and protein C receptors, suggesting low protein C activation capacity in severe meningococcal sepsis.

    METHODS: A patient with meningococcal septic shock was treated with two doses of the unactivated form of protein C, the first during intense activation of the coagulation system and the second during a phase of low grade or no activation. Repeated plasma samples were analysed for protein C concentration, which made it possible to compare pharmacokinetics and half-lives of the two administrations. A shorter half-life during intense coagulation was expected if there was an activation and consumption of the protein C administered.

    RESULTS: The calculated half-lives of protein C during intense and low grade activation were 32 h and 19 h, respectively, a magnitude similar to that reported in protein C-deficient patients without infection.

    CONCLUSION: The result indicates that whole body utilisation of the unactivated protein C was low. Endothelial impairment of protein C activation does not seem to be restricted to the skin vessels only.

  • 36. Linner, Anna
    et al.
    Darenberg, Jessica
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Henriques-Normark, Birgitta
    Norrby-Teglund, Anna
    Clinical Efficacy of Polyspecific Intravenous Immunoglobulin Therapy in Patients With Streptococcal Toxic Shock Syndrome: A Comparative Observational Study2014Ingår i: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 59, nr 6, s. 851-857Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis are the 2 most severe invasive manifestations caused by group A Streptococcus (GAS). Intravenous immunoglobulin (IVIG) therapy has been suggested as adjunctive treatment with a beneficial effect on mortality. However the clinical evidence is limited. Here we aim to further document the clinical efficacy of administered IVIG therapy in a comparative observational study of well-defined patients with STSS. Methods. The effect of IVIG was evaluated in patients with STSS prospectively identified in a nationwide Swedish surveillance study conducted between April 2002 and December 2004. Detailed data on symptoms, severity of disease, treatment, and outcome were obtained from 67 patients. Crude and adjusted analyses with logistic regression were performed. Results. Twenty-three patients received IVIG therapy compared with 44 who did not. No significant difference in comorbidities, severity of disease, organ failures, or sex was seen, but the IVIG group was slightly younger and had a higher degree of necrotizing fasciitis (56% vs 14%). The primary endpoint was 28-day survival. Adjusted analysis revealed that factors influencing survival in STSS were Simplified Acute Physiology Score II (odds ratio [OR], 1.1; P = .007), clindamycin (OR, 8.6; P = .007), and IVIG (OR, 5.6; P = .030). Conclusions. This comparative observational study of prospectively identified STSS patients demonstrates that both IVIG and clindamycin therapy contribute to a significantly improved survival in STSS.

  • 37. Linner, Anna
    et al.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Darenberg, Jessica
    Henriques-Normark, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Norrby-Teglund, Anna
    Efficacy of Polyspecific Intravenous Immunoglobulin Therapy in Streptococcal Toxic Shock Syndrome Reply2015Ingår i: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 60, nr 2Artikel i tidskrift (Refereegranskat)
  • 38.
    Lipcsey, Miklos
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Larsson, Erik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Einarsson, Roland
    Abdul Qadhr, Goran
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för radiologi.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    The brain is a source of S100B increase during endotoxemia in the pig2010Ingår i: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 110, nr 1, s. 174-180Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND:

    Cerebral dysfunction frequently complicates septic shock. A marker of cerebral dysfunction could be of significant value in managing sedated septic patients. Plasma S100 (S100B) proteins increase in sepsis. S100B is present not only in the brain but also in other tissues. The source of this protein has not been investigated in sepsis. Our aim in this study was to determine whether the brain is an important source of S100B in an experimental sepsis model.

    METHODS:

    Twenty-seven pigs were anesthetized and randomized to either infusion of endotoxin at the rate of 1 µg · kg-1 · h-1 (n = 19) or saline (n = 8). Catheters were inserted into a cervical artery and the superior sagittal sinus. Blood samples were collected from both sites and physiologic data were registered before the start of the endotoxin infusion and hourly during the experiment. After 6 h, the animals were killed and brain tissue samples were taken from the left hemisphere. S100B in plasma was measured by enzyme-linked immunosorbent assay. Brain tissue samples were stained with biotinylated S100B antibodies.

    RESULTS:

    In the endotoxemic animals, the arterial S100B concentration increased to 442 ± 33 and 421 ± 24 ng/L at 1 and 2 h, respectively, vs 306 ± 28 and 261 ± 25 ng/L in controls (P = 0.018 and 0.00053, respectively). Mean superior sagittal sinus S100B concentrations were higher than mean arterial concentrations at all time points in the endotoxemic animals; however, significance was only reached at 2 h (P = 0.033). The focal glial S100B expression was more intense in the endotoxemic pigs than in controls (P = 0.0047).

    CONCLUSIONS:

    Our results support the hypothesis that the brain is an important source of S100B in endotoxemia even though there may be other sources. These findings make S100B a candidate as a marker of cerebral dysfunction in septic shock.

  • 39.
    Lipcsey, Miklós
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Carlsson, Markus
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Algotsson, Lars
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Lukinius, Agneta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Effect of a single dose of tobramycin on systemic inflammatory response-induced acute kidney injury in a 6-hour porcine model2009Ingår i: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 37, nr 10, s. 2782-2790Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:

    To evaluate whether the addition of tobramycin further compromises renal function in inflammatory response-induced acute kidney injury. Effective antibiotic treatment in septic shock is crucial for the outcome. The combination of aminoglycosides with different beta-lactam antibiotics offers a broad antimicrobial coverage, rapid bacterial killing, synergistic effects, and low antibiotic-induced endotoxin release. However, aminoglycosides have nephrotoxic effects that may aggravate sepsis-induced acute kidney injury.

    DESIGN:

    Prospective, randomized, placebo-controlled experimental study.

    SETTING:

    University research unit.

    SUBJECTS:

    Twenty-four healthy pigs.

    INTERVENTIONS:

    The animals were anesthetized and randomized to four groups. Groups I (n = 8) and II (n = 8) received endotoxin infusion for 6 hrs, whereas groups III (n = 4) and IV (n = 4) received saline. Groups I and III received 7 mg/kg of tobramycin 20 mins after the initiation of the protocol, whereas groups II and IV received saline.

    MEASUREMENTS AND MAIN RESULTS:

    The renal elimination rate of a bolus dose of cefuroxime was chosen as the primary end point. Renal function was also evaluated by urine output, creatinine clearance, plasma cystatin C, plasma urea, and urine NAG (N-acetyl-beta-D-glucoaminidase). After 3 hrs, there were significantly lower cefuroxime elimination rates in the two endotoxin groups than in the nonendotoxin groups. No difference in cefuroxime elimination rates between groups I and II could be detected at any time point. Similarly, there were changes indicating acute kidney injury in urine output, creatinine clearance, and plasma cystatin C in the endotoxin groups with no differences between groups I and II. Plasma urea and urine NAG did not differ between any of the groups.

    CONCLUSIONS:

    The result of this study does not lend any support to the hypothesis that a single dose of tobramycin enhances the risk of acute renal failure in cases with systemic inflammatory response-induced acute kidney injury.

  • 40.
    Lipcsey, Miklós
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Castegren, Markus
    Karolinska Univ Hosp, Dept Anaesthesia, Intens Care Serv, Solna, Sweden; Karolinska Univ Hosp, Dept Anaesthesia, Surg Serv, Solna, Sweden.
    Furebring, Mia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Should the Aminoglycoside β-Lactam Combination Be Abandoned in All Severely Ill Patients With Presumed Gram-Negative Infection?2018Ingår i: Clinical Infectious Diseases, ISSN 1058-4838, E-ISSN 1537-6591, Vol. 66, nr 3, s. 480-482Artikel i tidskrift (Övrigt vetenskapligt)
  • 41.
    Lipcsey, Miklós
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Eriksson, Mats B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Inflammatory, coagulatory and circulatory responses to logarithmic increases in the endotoxin dose in the anaesthetised pig2006Ingår i: Journal of Endotoxin Research, ISSN 0968-0519, E-ISSN 1743-2839, Vol. 12, nr 2, s. 99-112Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Although porcine intravenous endotoxin shock models are widely employed in experimental sepsis, endotoxin dose-effect studies are scarce. Our primary aim was to establish the dose response to increasing endotoxin doses in inflammatory, coagulatory and haemodynamic effect variables, as well as to determine the optimal time point for assessment in a pig model. A secondary aim was to study pathophysiological covariations between the different responses. Twenty anaesthetised piglets received endotoxin intravenously in doses of 0.063 (n = 3), 0.25 (n = 3), 1.0 (n = 3), 4.0 (n = 3), 8 (n = 3) and 16 microg/kg/h (n = 2). In addition, non-endotoxin piglets constituted a control group (n = 3). Physiological variables were registered and blood samples analysed for TNF-alpha, IL-6, leukocyte, platelet and haemoglobin concentrations hourly for 6 h. Increases in the endotoxin dose induced significant log-log cytokine responses as well as log-linear leukocyte and platelet responses. Significant log-linear responses were observed for circulatory parameters, plasma leakage, hypoperfusion and pulmonary compliance. Significant covariations in the responses were noted. In conclusion, there were log-log or log-linear responses to endotoxin suggesting a greater effect of a given dose at lower pre-existing endotoxin concentrations and lower doses of < or = 1 microg/kg/h may be of advantage in experiments designed to study potential anti-endotoxin effects of experimental drugs or measures.

  • 42.
    Lipcsey, Miklós
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Eriksson, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Effect of the Administration Rate on the Biological Responses To A Fixed Dose of Endotoxin in the Anesthetized Pig2008Ingår i: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 29, nr 2, s. 173-180Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There have been difficulties to demonstrate a relationship between endotoxin concentration and clinical response. One hypothesis for this difficulty might be that a fast increase in endotoxin concentration elicits a stronger biological response than a more gradual one of the same dose. The aim of the present study was to investigate the existence of such a response. Eighteen randomized pigs were given the same amount of endotoxin either with an initial infusion rate of 4 μg kg-1 h-1, which after 1 h was tapered to 0.5 μg kg-1 h-1, and after 2 h to 0.063 μg kg-1 h-1 (group I), or with a reverse escalating order with the lowest infusion rate given first (group II). After 3 h, the endotoxin infusion was stopped, and the pigs were observed for another 3 h. The responses in TNF-α, core temperature, leukocytes, platelets, MAP, left ventricular stroke work index, mixed venous saturation, base excess, pH, and pulmonary compliance were greater in group I than in group II, whereas the IL-6 response did not differ between groups. The biological responses of inflammation, hypotension, hypoperfusion, and organ dysfunction are increased if the organism is exposed to a fixed amount of endotoxin more quickly.

    Abbreviations - BE-Base excess; CI-Cardiac index; DO2-Oxygen delivery; Fio2-fraction of oxygen; Hb-Hemoglobin; LVSWI-Left ventricular stroke work index; MPAP-Mean pulmonary arterial pressure; Paco2-Arterial partial pressure of carbon dioxide; Pao2-Arterial partial pressure of oxygen; pH-Potentia Hydrogenii; SEM-Standard error of the mean; Svo2-Venous oxygen saturation

  • 43.
    Lipcsey, Miklós
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Olovsson, Matts
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Obstetrik & gynekologi.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Eriksson, Mats B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Early endotoxin-mediated haemostatic and inflammatory responses in the clopidogrel-treated pig2005Ingår i: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 16, nr 7, s. 408-414Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have previously shown that the thrombin inhibiting agent melagatran markedly prolongs aPTT and counteracts creatinine increase in endotoxemic pigs. Against this background the effects of the platelet-inhibiting agent, clopidogrel on basic haemostatic, inflammatory and physiological variables were evaluated during porcine endotoxemia. Clopidogrel (10 mg/kg) or saline was randomly injected i.v. 30 min before start of a 6-h continuous infusion of endotoxin in 12 anaesthetised pigs. Another three pigs were given clopidogrel but not endotoxin. Clopidogrel did not affect physiological variables, formation of activated platelet microparticles, PK, aPTT, platelet count, plasma fibrinogen, TNF-alpha, or IL-6 during porcine endotoxemia. Although renal function, as evaluated by creatinine clearance (CLcr) deteriorated significantly (P = 0.01) in the saline-endotoxin, but not in the clopidogrel-endotoxin group, there was no significant difference between the saline-endotoxin and the clopidogrel-endotoxin groups. Renal biopsies were marked with a FITC-labelled chicken anti-fibrinogen antibody detecting fibrinogen and platelet bound fibrinogen, as a marker of porcine platelet activation, and examined by light microscopy. Evaluation of these immunohistochemical slides did not indicate that clopidogrel, significantly reduced the amount of intrarenal fibrin or fibrinogen depositions. Besides a trend to preserve renal function, clopidogrel did not affect haemodynamics or the coagulatory and inflammatory responses in porcine endotoxemia.

  • 44.
    Lipcsey, Miklós
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Olovsson, Matts
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Eriksson, Mats B
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Early endotoxin-mediated haemostatic and inflammatory responses in the clopidogrel-treated pig2005Ingår i: Platelets, ISSN 0953-7104, Vol. 16, nr 7, s. 408-14Artikel i tidskrift (Refereegranskat)
  • 45.
    Lipcsey, Miklós
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Hedenstiernalaboratoriet.
    Tenhunen, Jyrki
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Frithiof, Robert
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Bendel, Stepani
    Kuopio Univ Hosp, Dept Intens Care, Kuopio, Finland..
    Flaatten, Hans
    UiB, Haukeland Univ Hosp, Dept Clin Med, Bergen, Norway..
    Kawati, Rafael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Kuitunen, Anne
    Tampere Univ Hosp, Crit Care Med Res Grp, POB 200033521, Tampere, Finland..
    Tonnessen, Tor Inge
    Oslo Univ Hosp, Div Emergencies & Crit Care, N-0450 Oslo, Norway.;Inst Clin Med, N-0450 Oslo, Norway..
    Rubertsson, Sten
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Abdominal Septic Shock - Endotoxin Adsorption Treatment (ASSET) - endotoxin removal in abdominal and urogenital septic shock with the Alteco (R) LPS Adsorber: study protocol for a double-blinded, randomized placebo-controlled trial2016Ingår i: Trials, ISSN 1745-6215, E-ISSN 1745-6215, Vol. 17, artikel-id 587Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Severe sepsis and septic shock are common in intensive care and carry high mortality rates. In patients with Gram-negative infections, early and extensive removal of endotoxin may limit the inflammatory response that characterizes septic shock. The Alteco (R) LPS Adsorber (hereafter referred to cited as the lipopolysaccharide (LPS) Adsorber) can be used for endotoxin removal and attenuate the deleterious inflammatory and clinical responses seen in septic shock. Methods/design: The Abdominal Septic Shock - Endotoxin Adsorption Treatment (ASSET) trial is a pilot study investigating the feasibility and safety of LPS Adsorber therapy. This pilot, multicenter, stratified, parallel, double-blinded, randomized, phase IIa, feasibility clinical investigation will be performed in five Scandinavian intensive care units. Thirty-two subjects with early septic shock and organ failure, following adequate resuscitation, will be randomized to receive either: extracorporeal veno-venous hemoperfusion therapy with the LPS Adsorber or veno-venous hemoperfusion therapy with a placebo adsorber (without active LPS-binding peptide). Patients will be stratified by infection focus such that 20 subjects with an abdominal focus (stratum A) and 12 subjects with a urogenital focus (stratum B) will be included in a parallel design. Thereafter, an interim analysis will be performed and an additional 12 patients may be included in the study. The study is designed as adaptive a priori: the patients from this study can be included in a later phase IIb study. The aim of the study is to investigate the feasibility of LPS Adsorber therapy commenced early in the time-course of septic shock. The primary endpoint will be a characterization of all reported unanticipated serious adverse device effects and anticipated serious adverse device effects. Secondary outcomes are decrease in endotoxin plasma concentration, impact on clinical outcome measures and impact on inflammatory response by LPS Adsorber therapy, as well as detailed description of the relevant mediators bound to the LPS Adsorber. Recruitment of patients will start in September 2015. Discussion: The ASSET trial will give insight into the feasibility and safety of this LPS Adsorber therapy and preliminary data on its potential clinical effects in septic shock. Moreover, this pilot trial will provide with necessary data for designing future studies.

  • 46.
    Ljunghill Hedberg, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Berglund, Sofia
    Wilske, Frida
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lewén, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Winqvist, Ola
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
    Decreased T-lymphocyte response to T-cell-dependent vaccines after neurotrauma or neurosurgeryManuskript (preprint) (Övrigt vetenskapligt)
  • 47.
    Ljunghill Hedberg, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Pauksen, Karlis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Larsson, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk kemi.
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Relationship between T-cell-dependent and T-cell-independent vaccines after neurotrauma; Can the response be predicted?Manuskript (preprint) (Övrigt vetenskapligt)
  • 48.
    Ljunghill Hedberg, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Pauksen, Karlis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Ronne-Engström, Elisabeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Lundberg, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar. Uppsala Univ, Infect Dis Sect, Dept Med Sci, Uppsala, Sweden..
    Johansson, Bjorn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Rehabiliteringsmedicin. Uppsala Univ, Sect Rehabil Med, Dept Neurosci, Uppsala, Sweden..
    Kayhty, Helena
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Lower response to early T-cell-dependent vaccination after neurotrauma or neurosurgery in adults2015Ingår i: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 70, nr 6, s. 577-584Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Recent international guidelines recommend vaccination with a 13-valent pneumococcal conjugate vaccine to reduce the risk of meningitis after neurotrauma with cerebrospinal fluid leak. The antibody response and optimal time point for vaccination have not been established and because the risk of meningitis is at the highest shortly after trauma, early vaccination is preferable. This study aimed to investigate the antibody response and to ensure that central nervous system injury-induced immunodepression did not affect the response to a T-cell-dependent conjugate vaccine when administered shortly after the injury. Methods: So as not to interfere with routine pneumococcal vaccination, a conjugate vaccine against Haemophilus influenza type b (Hib) was chosen for the study. Thirty-three patients with basilar skull fracture and 23 patients undergoing transsphenoidal pituitary gland surgery were vaccinated within 10 days after trauma/surgery and 29 control patients at least three weeks after trauma/surgery. Sera were collected pre- and post-vaccination for analysis of anti-Hib concentration. Results: Four patients with post-vaccination target antibody concentration before vaccination were excluded from analysis. In the neurotrauma and neurosurgery groups 10/32 (31%) and 5/20 (25%) patients, respectively, were non-responders compared with 3/29 (10%) in the control group. Log(10) anti-Hib concentrations in the neurotrauma, neurosurgery and control groups were 1.52 +/- 0.15, 1.38 +/- 0.15 and 1.81 +/- 0.12 mu g/ml, respectively. Conclusions: The majority of the patients responded to vaccination. However, the number of responders was significantly decreased and antibody concentration significantly lower in patients vaccinated early after the trauma/surgery. Investigation of the pneumococcal conjugate vaccine response in neurotrauma patients is therefore urgent. (C) 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  • 49.
    Ljunghill Hedberg, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Pauksens, Karlis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Enblad, Per
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Neurokirurgi.
    Söderberg, Jessika
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Johansson, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Rehabiliteringsmedicin.
    Kayhty, Helena
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Pneumococcal polysaccharide vaccination administered early after neurotrauma or neurosurgery2017Ingår i: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 35, nr 6, s. 909-915Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: Pneumococcal vaccination is recommended to lower the risk of posttraumatic meningitis, and early vaccination may be of importance. After both trauma and central nervous system injury, immune suppression may occur, which could affect T-cell function and the response to T-cell dependent vaccines. We therefore aimed to investigate the response to early vaccination with a T-cell independent pneumococcal polysaccharide vaccine (PPSV). Methods: Thirty-three patients with basilar skull fracture and 23 patients undergoing transsphenoidal pituitary gland surgery were vaccinated with PPSV within 10 days after neurotrauma or neurosurgery. Twenty-nine neurosurgical patients vaccinated >= 3 weeks after neurotrauma or neurosurgery served as controls. Serotype-specific anti-polysaccharide binding IgG antibody levels to serotypes 4, 6B, 9V, 14, 18C, 19F and 23F were determined by enzyme immunoassay. Results: The vaccination was safe and a highly significant antibody response was found against all serotypes in all groups (p < 0.001 for each of the serotypes). There were no differences between groups or in the group by time interaction in any of the serotypes. After early and late vaccination, protective levels were found in >80% for serotypes 9V, 14, 18C, 19F and 23F and in 70% and 50% for serotypes 6B and 4, respectively. Conclusion: Patients vaccinated with PPSV within 10 days after neurotrauma or neurosurgery respond similarly to those vaccinated after >= 3 weeks, indicating that PPSV can be administered early after neurotrauma or neurosurgery.

  • 50.
    Ljunghill Hedberg, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Pauksens, Karlis
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Ronne-Engström, Elisabeth
    Lundberg, Maria
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Johansson, Björn
    Käyhty, Helena
    Sjölin, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Infektionssjukdomar.
    Lower response to early T-cell-dependent vaccination after neurotrauma or neurosurgery in adults.2015Ingår i: Journal of Infection, ISSN 0163-4453, E-ISSN 1532-2742, Vol. 70, s. 577-584Artikel i tidskrift (Refereegranskat)
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