| 1. |
- von Seth, Magnus, et al.
(author)
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Rapid Bolus Administration Does Not Increase the Extravasation Rate of Albumin : A Randomized Controlled Trial in the Endotoxemic Pig
- 2017
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In: Shock. - 1073-2322 .- 1540-0514. ; 47:4, s. 514-519
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Journal article (peer-reviewed)abstract
- Some experimental data suggest that rapid bolus administration of albumin causes less plasma-expanding effects than slow, continuous infusion. To determine whether rapid bolus administration, in comparison with slow infusion, results in greater extravasation of albumin in experimental septic shock we performed a randomized controlled trial with 32 endotoxemic pigs. The animals were monitored and ventilated with standard intensive care equipment and given 10 mL x kg 5% albumin labeled with Technetium-99m, either as a rapid 15-minute bolus (Bolus group, n = 16) or as a 2-hour (h) infusion (Infusion group, n = 16). Radioactivity was monitored in plasma, extracellular microdialysate and urine for 6 h. Physiological parameters were monitored hourly. Radioactivity in the liver, spleen, kidney and lung was analyzed post-mortem.The plasma area under the curve (AUC) activity0-6h was 4.4 ± 0.9 x 10 in the Bolus group and 4.4 ± 1.1 x 10 counts x min x mL x h in the Infusion group. Blood hemoglobin levels increased in both groups, suggesting severe capillary leakage. Yet, there were no group differences in albumin radioactivity in plasma, muscle tissue, urine or in the post-mortem analysis of the organs. Following albumin administration, circulatory and respiratory parameters were similar in the two groups.In conclusion, the present results suggest that albumin might be given as a bolus without leading to increased extravasation of albumin, in contrast to previous animal experiments in rodents.
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| 2. |
- Glimaker, M., et al.
(author)
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Early lumbar puncture in adult bacterial meningitis-rationale for revised guidelines
- 2013
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In: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 45:9, s. 657-663
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Journal article (peer-reviewed)abstract
- 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.
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| 3. |
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| 4. |
- Skorup, Paul
(author)
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Antibacterial Effect and Inflammatory Response in Relation to Antibiotic Treatment of Sepsis
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Sepsis defines as life-threatening organ dysfunction caused by a dysregulated host response to infection. The importance of early administration of antibiotics in septic shock is undisputed, but the optimal antibiotic choice remains uncertain. Some national guidelines advocate single β-lactam antibiotic treatment while others recommend a combination of β-lactam and aminoglycoside. This thesis aimed to investigate the anti-bacterial properties and antibiotic-induced inflammatory responses of ß-lactam antibiotic compared with effects of the addition of an aminoglycoside in clinically relevant E. coli porcine intensive care sepsis/septic shock models. We also studied the host's antibacterial capacities in primary and secondary sepsis.In Paper I the addition of an aminoglycoside, in comparison with single β-lactam antibiotic treatment, caused decreased bacterial growth in the liver and greater antibiotic-induced blood killing activity ex vivo. The results thereby constitute possible mechanisms to the previously reported improved survival in the most critically ill sepsis patients receiving the β-lactam/aminoglycoside combination. Also observed in this paper was that individual blood bactericidal capacity may have significant effects on antimicrobial outcome. In Paper II we investigated endotoxin release in vivo after antibiotic treatment in comparison with no treatment. There were no differences, however, antibiotics did increase an inflammatory IL-6 response that was associated with leukocyte activation and pulmonary organ dysfunction. A secondary finding was that the addition of an aminoglycoside to a β-lactam induced trends towards less inflammation compared with β-lactam alone.Paper III compared how challenge with different pre-killed E. coli activates the inflammatory response, resulting in higher cytokine responses, more leucocyte activation and inflammatory capillary leakage after single β-lactam compared with live or heat-killed bacteria. The addition of an aminoglycoside lowered the β-lactam-induced responses.Paper IV demonstrated that animals with secondary sepsis exhibited an attenuated inflammatory response as expected; however, contrary to our hypothesis, the animals’ antibacterial capacities were intact and partly enhanced.We conclude that there are likely several beneficial effects of the addition of an aminoglycoside to a β-lactam therapy regimen in septic shock. Because host antibacterial capacities in secondary sepsis are enhanced, the need for bactericidal antibiotic combinations is not greater in secondary than in primary sepsis.
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| 5. |
- Skorup, Paul, et al.
(author)
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Dynamics of Endotoxin, Inflammatory Variables, and Organ Dysfunction After Treatment With Antibiotics in an Escherichia coli Porcine Intensive Care Sepsis Model
- 2018
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In: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 46:7, s. e634-e641
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Journal article (peer-reviewed)abstract
- Objectives: To investigate the dynamics of antibiotic-induced endotoxin liberation and inflammatory response in vivo in a clinically relevant large animal intensive care sepsis model and whether the addition of an aminoglycoside to beta-lactam antibiotic affects these responses.Design: Prospective, placebo-controlled interventional experimental study.Setting: University research unit.Subjects: Thirty-six healthy pigs administered Escherichia coli as a 3-hour infusion.Interventions: After 2 hours, during E. coli infusion, the animals were exposed to cefuroxime alone, the combination of cefuroxime and tobramycin, or saline.Measurements and Main Results: Plasma endotoxin, interleukin-6, tumor necrosis factor-alpha, leucocytes, and organ dysfunction were recorded for 4 hours after antibiotic treatment, and differences to the values before treatment were calculated. In vitro experiments were performed to ascertain whether endotoxin is released during antibiotic-induced bacterial killing of this E. coli strain. Despite differences between the treatment arms in vitro, no differences in plasma endotoxin were observed in vivo. Antibiotic-treated animals demonstrated a higher interleukin-6 response (p < 0.001), greater leucocyte activation (p < 0.001), and more pronounced deterioration in pulmonary static compliance (p < 0.01) over time than controls. Animals treated with the combination showed a trend toward less inflammation.Conclusions: Treatment with antibiotics may elicit an increased inflammatory interleukin-6 response that is associated with leucocyte activation and pulmonary organ dysfunction. No observable differences were detected in plasma endotoxin concentrations. The reduction in cefuroxime-induced endotoxin release after the addition of an aminoglycoside in vitro could not be reproduced in this model.
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| 6. |
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| 7. |
- Wallgren, Ulrika M., 1971-, et al.
(author)
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Association between variables measured in the ambulance and in-hospital mortality among adult patients with and without infection : a prospective cohort study
- 2022
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In: BMC Emergency Medicine. - : BioMed Central (BMC). - 1471-227X. ; 22:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Patients presenting with infection to the ambulance are common, but risk factors for poor outcome are not known. The primary aim of the current study was to study the association between variables measured in the ambulance and mortality among adult patients with and without infection. The secondary aim was to study the association between these variables and mortality in a subgroup of patients who developed sepsis within 36 h.METHODS: Prospective cohort study of 553 ambulance patients with, and 318 patients without infection, performed in Stockholm during 2017-2018. The association between 21 variables (8 keywords related to medical history, 6 vital signs, 4 blood tests, and age, gender, comorbidity) and in-hospital mortality was analysed using logistic regression.RESULTS: Among patients with infection, inability of the patient to answer questions relating to certain symptoms such as pain and gastrointestinal symptoms was significantly associated with mortality in univariable analysis, in addition to oxygen saturation < 94%, heart rate > 110 /min, Glasgow Coma Scale (GCS) < 15, soluble urokinase Plasminogen Activator Receptor (suPAR) 4.0-7.9 ng/mL, suPAR ≥ 8.0 ng/mL and a Charlson comorbidity score ≥ 5. suPAR ≥ 8.0 ng/mL remained significant in multivariable analysis (OR 25.4; 95% CI, 3.2-199.8). Among patients without infection, suPAR ≥ 8.0 ng/mL and a Charlson comorbidity score ≥ 5 were significantly associated with mortality in univariable analysis, while suPAR ≥ 8.0 ng/mL remained significant in multivariable analysis (OR 56.1; 95% CI, 4.5-700.0). Among patients who developed sepsis, inability to answer questions relating to pain remained significant in multivariable analysis (OR 13.2; 95% CI, 2.2-78.9), in addition to suPAR ≥ 8.0 ng/mL (OR 16.1; 95% CI, 2.0-128.6).CONCLUSIONS: suPAR ≥ 8.0 ng/mL was associated with mortality in patients presenting to the ambulance both with and without infection and in those who developed sepsis. Furthermore, the inability of the ambulance patient with an infection to answer questions relating to specific symptoms was associated with a surprisingly high mortality. These results suggest that suPAR and medical history are valuable tools with which to identify patients at risk of poor outcome in the ambulance and could potentially signal the need of enhanced attention.TRIAL REGISTRATION: ClinicalTrials.gov, NCT03249597. Registered 15 August 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03249597 .
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| 8. |
- Wallgren, Ulrika M., 1971-, et al.
(author)
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Performance of NEWS2, RETTS, clinical judgment and the Predict Sepsis screening tools with respect to identification of sepsis among ambulance patients with suspected infection : a prospective cohort study
- 2021
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In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine. - : BioMed Central. - 1757-7241. ; 29:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: There is little evidence of which sepsis screening tool to use in the ambulance setting. The primary aim of the current study was to compare the performance of NEWS2 (National Early Warning score 2) and RETTS (Rapid Emergency Triage and Treatment System) with respect to identification of sepsis among ambulance patients with clinically suspected infection. The secondary aim was to compare the performance of the novel Predict Sepsis screening tools with that of NEWS2, RETTS and clinical judgment.METHODS: Prospective cohort study of 323 adult ambulance patients with clinically suspected infection, transported to hospitals in Stockholm, during 2017/2018. The sensitivity, specificity, and AUC (Area Under the receiver operating Curve) were calculated and compared by using McNemar´s test and DeLong's test.RESULTS: The prevalence of sepsis in the current study population was 44.6% (144 of 323 patients). No significant difference in AUC was demonstrated between NEWS2 ≥ 5 and RETTS ≥ orange. NEWS2 ≥ 7 demonstrated a significantly greater AUC than RETTS red. The Predict Sepsis screening tools ≥ 2 demonstrated the highest sensitivity (range 0.87-0.91), along with RETTS ≥ orange (0.83), but the lowest specificity (range 0.39-0.49). The AUC of NEWS2 (0.73) and the Predict Sepsis screening tools (range 0.75-0.77) was similar.CONCLUSIONS: The results indicate that NEWS2 could be the better alternative for sepsis identification in the ambulance, as compared to RETTS. The Predict Sepsis screening tools demonstrated a high sensitivity and AUCs similar to that of NEWS2. However, these results need to be interpreted with caution as the Predict Sepsis screening tools require external validation.TRIAL REGISTRATION: ClinicalTrials.gov, NCT03249597. Registered 15 August 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03249597 .
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| 9. |
- Angelin, Martin, et al.
(author)
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Qdenga® - A promising dengue fever vaccine; can it be recommended to non-immune travelers?
- 2023
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In: Travel Medicine and Infectious Disease. - : Elsevier. - 1477-8939 .- 1873-0442. ; 54
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Journal article (peer-reviewed)abstract
- Qdenga® has been approved by the European Medicines Agency (EMA) for individuals > 4 years of age and for use according to national recommendations. The vaccine shows high efficacy against virologically confirmed dengue and severe dengue in clinical studies on 4–16-year old's living in endemic areas. For individuals 16–60 years old only serological data exists and there is no data for individuals > 60 years. Its use as a travel vaccine is still unclear. We present the studies behind the approval and the recommendations for travelers as issued by the Swedish Society for Infectious Diseases Physicians.
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| 10. |
- Brink, Magnus, 1960, et al.
(author)
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Meropenem versus cefotaxime and ampicillin as empirical antibiotic treatment in adult bacterial meningitis: A quality registry study, 2008 to 2016
- 2019
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In: Antimicrobial Agents and Chemotherapy. - : AMER SOC MICROBIOLOGY. - 0066-4804 .- 1098-6596. ; 63:11
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Journal article (peer-reviewed)abstract
- © 2019 American Society for Microbiology. All Rights Reserved. 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.
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