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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.

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

Background Recent studies have shown low caspofungin concentrations in critically ill patients. In some patients, the therapeutic target, area under the total plasma concentration curve in relation to the minimal inhibition concentration (AUCtot/MIC), seems not to be achieved and therapeutic drug monitoring (TDM) has been proposed. Caspofungin is highly protein-bound and the effect of reduced plasma protein levels on pharmacodynamics has not been investigated. Objectives Fungal killing activity of caspofungin in vitro was investigated under varying levels of human plasma protein. Methods Time-kill studies were performed with clinically relevant caspofungin concentrations of 1-9 mg/L on four blood isolates of C. glabrata, three susceptible and one strain with reduced susceptibility, in human plasma and plasma diluted to 50% and 25% using Ringer's acetate. Results Enhanced fungal killing of the three susceptible strains was observed in plasma with lower protein content (p < .001). AUCtot/MIC required for a 1 log10 CFU/ml kill at 24 h in 50% and 25% plasma was reduced with 36 + 12 and 80 + 9%, respectively. The maximum effect was seen at total caspofungin concentrations of 4–9 × MIC. For the strain with reduced susceptibility, growth was significantly decreased at lower protein levels. Conclusions Reduced human plasma protein levels increase the antifungal activity of caspofungin in vitro, most likely by increasing the free concentration. Low plasma protein levels in critically ill patients with candidemia might explain a better response to caspofungin than expected from generally accepted target attainment and should be taken into consideration when assessing TDM based on total plasma concentrations.

The T2Candida magnetic resonance assay is a direct-from-blood pathogen detection assay that delivers a result within 3-5 h, targeting the most clinically relevant Candida species. Between February 2019 and March 2021, the study included consecutive patients aged >18 years admitted to an intensive care unit or surgical high-dependency unit due to gastrointestinal surgery or necrotizing pancreatitis and from whom diagnostic blood cultures were obtained. Blood samples were tested in parallel with T2Candida and 1,3-beta-D-glucan. Of 134 evaluable patients, 13 (10%) were classified as having proven intraabdominal candidiasis (IAC) according to the EORTC/MSG criteria. Two of the thirteen patients (15%) had concurrent candidemia. The sensitivity, specificity, positive predictive value, and negative predictive value, respectively, were 46%, 97%, 61%, and 94% for T2Candida and 85%, 83%, 36%, and 98% for 1,3-beta-D-glucan. All positive T2Candida results were consistent with the culture results at the species level, except for one case of dual infection. The performance of T2Candida was comparable with that of 1,3-beta-D-glucan for candidemic IAC but had a lower sensitivity for non-candidemic IAC (36% vs. 82%). In conclusion, T2Candida may be a valuable complement to 1,3-beta-D-glucan in the clinical management of high-risk surgical patients because of its rapid results and ease of use.

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. Furtherm, Funding agencies:Laerdal, Falck FoundationEmergency Department of Södersjukhuset, Stockholm, Örebro UniversityNyckelfonden

Objectives: The aim was to analyze differences in clinical presentation, etiology, management, and outcome between immunocompromised and immunocompetent patients with acute bacterial meningitis (ABM). Methods: Data were extracted from 1056 adult ABM patients prospectively registered in the national Swedish quality register for ABM during 2008-2017. Primary endpoint was 30-day mortality and secondary endpoints 90-day mortality and unfavorable outcome. Results: An immunocompromised state was observed in 352 (33%) of the 1056 patients. Streptococcus pneumoniae dominated in both immunocompromised and immunocompetent patients (53% in both groups), whereas L monocytogenes occurred in 11% and 2%, respectively. The unadjusted odds ratio (OR) for 30-day mortality in immunocompromised compared to immunocompetent patients was 1.68 (95% confidence interval (CI): 1.07-2.63). Adjusted for age, sex, and mental status on admission the OR was 1.34 (CI: 0.82-2.21). Adjusted also for time to antibiotic treatment and corticosteroids the OR was 1.10 (CI: 0.59-2.05), and in patients without Listeria meningitis 0.98 (CI: 0.50-1.90). Although, the ORs were higher for 90-day mortality and unfavorable outcome the effects of adjustments were similar. Conclusion: Mortality in immunocompromised patients with ABM is only moderately increased unless caused by Listeria. This difference is further reduced in patients given early antibiotic treatment and adjunctive corticosteroids. Funding: This work was supported by Stockholm County Council.