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The purpose of this study was to prospectively investigate the incidence of influenza-associated pulmonary aspergillosis (IAPA) in influenza patients admitted to intensive care units in Sweden. The study included consecutive adult patients with PCR-verified influenza A or B in 12 Swedish intensive care units (ICUs) over four influenza seasons (2019-2023). Patients were screened using serum galactomannan and β-d-glucan tests and fungal culture of a respiratory sample at inclusion and weekly during the ICU stay. Bronchoalveolar lavage was performed if clinically feasible. IAPA was classified according to recently proposed case definitions. The cohort included 55 patients; 42% were female, and the median age was 59 (IQR 48-71) years. All patients had at least one galactomannan test, β-d-glucan test and respiratory culture performed. Bronchoalveolar lavage was performed in 24 (44%) of the patients. Five (9%, 95% CI 3.8% − 20.4%) patients were classified as probable IAPA, of which four lacked classical risk factors. The overall ICU mortality was significantly higher among IAPA patients than non-IAPA patients (60% vs 8%, p = 0.01). The study represents the first prospective investigation of IAPA incidence. The 9% incidence of IAPA confirms the increased risk of invasive pulmonary aspergillosis among influenza patients admitted to the ICU. Therefore, it appears reasonable to implement a screening protocol for the early diagnosis and treatment of IAPA in influenza patients receiving intensive care. ClinicalTrials.gov NCT04172610, registered November 21, 2019 [ABSTRACT FROM AUTHOR]

Background Studies on the antiviral effects of remdesivir have shown conflicting results. SARS-CoV-2 viraemia could identify patients in whom antiviral treatment may be particularly beneficial. Objectives To investigate antiviral effects and clinical outcomes of remdesivir treatment in viraemic patients. Methods Viraemic patients hospitalized for COVID-19 with ratio of arterial oxygen partial pressure to fractional inspired oxygen of ≤300, symptom duration ≤10 days, and estimated glomerular filtration rate ≥30 mL/min were included in a cohort. The rate of serum viral clearance and serum viral load decline, 60 day mortality and in-hospital outcomes were estimated. A subgroup analysis including patients with symptom duration ≤7 days was performed. Results A total of 318 viraemic patients were included. Thirty-three percent (105/318) received remdesivir. The rate of serum viral clearance [subhazard risk ratio (SHR) 1.4 (95% CI 0.9–2.0), P  = 0.11] and serum viral load decline (P  = 0.11) were not significantly different between remdesivir-treated patients and controls. However, the rate of serum viral clearance was non-significantly higher [SHR 1.6 (95% CI 1.0–2.7), P  = 0.051] and the viral load decline was faster (P  = 0.03) in remdesivir-treated patients with symptom duration ≤7 days at admission. The 60 day mortality [HR 1.0 (95% CI 0.6–1.8), P  = 0.97] and adverse in-hospital outcomes [OR 1.4 (95% CI 0.8–2.4), P  = 0.31] were not significantly different between remdesivir-treated patients and controls. Conclusions Remdesivir treatment did not significantly change the duration of SARS-CoV-2 viraemia, decline of serum viral load, 60 day mortality or in-hospital adverse outcomes in patients with ≤10 days of symptoms at admission. Remdesivir appeared to reduce the duration of viraemia in a subgroup of patients with ≤7 days of symptoms at admission. [ABSTRACT FROM AUTHOR]

Background Both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viremia and nasopharyngeal viral load have been suggested to be predictors of unfavorable outcome in coronavirus disease 2019 (COVID-19). This study aimed to investigate whether nasopharyngeal viral load is correlated with viremia and unfavorable outcome. Methods The presence of SARS-CoV-2 RNA was determined in paired nasopharyngeal and serum samples collected at admission from patients hospitalized for COVID-19. Standardized cycle threshold values (CT values) were used as an indicator of viral load. An adjusted logistic regression was used to estimate the risk of viremia at different nasopharyngeal CT values. A Cox regression was used to estimate the risk of 60-day mortality. Results A total of 688 patients were included. Viremia at admission was detected in 63% (146/230), 46% (105/226), and 31% (73/232) of patients with low, intermediate, and high nasopharyngeal CT values. The adjusted odds ratios of being viremic were 4.4 (95% CI, 2.9–6.8) and 2.0 (95% CI, 1.4–3.0) for patients with low and intermediate CT values, compared with high CT values. The 60-day mortality rate was 37% (84/230), 15% (36/226), and 10% (23/232) for patients with low, intermediate, and high nasopharyngeal CT values at admission, respectively. Adjusted hazard ratios were 2.6 (95% CI, 1.6–4.2) and 1.4 (95% CI, 0.8–2.4) for patients with low and intermediate CT values compared with high CT values. Conclusions There was a dose-dependent correlation between nasopharyngeal CT values and viremia at admission for COVID-19. Moreover, there was an increased risk of 60-day mortality for patients with low, compared with high, nasopharyngeal CT values. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). This study aimed to determine if SARS-CoV-2 RNA in serum at admission correlated with clinical outcome in COVID-19. Methods COVID-19 patients admitted to the infectious diseases department of a tertiary level Swedish hospital and sampled for SARS-CoV-2 RNA in serum at admission during 10 April to 30 June 2020 were included. Primary outcomes were day 28 all-cause mortality and progress to critical disease. Results The cohort (N = 167) consisted of 106 SARS-CoV-2 RNA serum-negative and 61 serum-positive patients. Median sampling time for initial SARS-CoV-2 in serum was 1 day (interquartile range [IQR], 1–2 days) after admission, corresponding to day 10 (IQR, 8–12) after symptom onset. Median age was 53 years (IQR, 44–67 years) and 63 years (IQR, 52–74 years) for the serum–negative and -positive patients, respectively. In the serum-negative and -positive groups, 3 of 106 and 15 of 61 patients died, respectively. The hazard ratios for critical disease and all-cause mortality were 7.2 (95% confidence interval [CI], 3.0–17) and 8.6 (95% CI, 2.4–30), respectively, for patients with serum–positive compared to serum–negative results. Conclusions SARS-CoV-2 RNA in serum at hospital admission indicates a high risk of progression to critical disease and death. [ABSTRACT FROM AUTHOR]

Sepsis is a severe medical condition characterized by a systemic inflammatory response of the body caused by pathogenic microorganisms in the bloodstream. Blood or plasma is typically used for diagnosis, both containing large amount of human DNA, greatly exceeding the DNA of microbial origin. In order to enrich bacterial DNA, we applied the C0t effect to reduce human DNA background: a model system was set up with human and Escherichia coli (E. coli) DNA to mimic the conditions of bloodstream infections; and this system was adapted to plasma and blood samples from septic patients. As a consequence of the C0t effect, abundant DNA hybridizes faster than rare DNA. Following denaturation and re-hybridization, the amount of abundant DNA can be decreased with the application of double strand specific nucleases, leaving the non-hybridized rare DNA intact. Our experiments show that human DNA concentration can be reduced approximately 100,000-fold without affecting the E. coli DNA concentration in a model system with similarly sized amplicons. With clinical samples, the human DNA background was decreased 100-fold, as bacterial genomes are approximately 1,000-fold smaller compared to the human genome. According to our results, background suppression can be a valuable tool to enrich rare DNA in clinical samples where a high amount of background DNA can be found. [ABSTRACT FROM AUTHOR]

Background: Severe sepsis is a common condition with a reported high mortality, but most studies have been confined to intensive care unit (ICU) populations. The systemic inflammatory response syndrome (SIRS) has been used to define sepsis, however its usefulness has been questioned. Our aim was to describe the prevalence and clinical impact of severe sepsis and SIRS in patients admitted from the emergency department (ED) with a suspected serious infection. Methods: Four hundred and four adult patients were enrolled prospectively from the ED. Variables defining severe sepsis and SIRS were measured and the relationship between severe sepsis, SIRS, and the clinical course was analyzed. Results: Infections were diagnosed in 344 patients (85%). The overall mortality rate at 28 days was 2.7%, and 4.5% of patients were treated in the ICU. Patients with severe sepsis within 24 h of admission (42%) were more likely to suffer a critical course (ICU admission 9.0%, death 5.1%; p < 0.001). While SIRS was observed in 72% of the subjects at presentation, it was not associated with severe sepsis within 24 h or a subsequent critical course. Furthermore, 23% of patients with severe sepsis within 24 h did not present with SIRS. Conclusions: Severe sepsis was a common condition among ED patients with a clinically suspected serious infection. Mortality was low compared with results from the ICU setting, suggesting that severe sepsis is a more benign disease than earlier reported. As a tool for the definition of sepsis and for the selection of patients for clinical sepsis trials, SIRS lacks acceptable discriminative ability in an ED population with a high prevalence of serious infections. [ABSTRACT FROM AUTHOR]

Background: While early antimicrobial treatment is of critical importance to patients with severe infections, excessive use of antibiotics has caused escalating bacterial resistance. Better diagnostic tools are needed to secure antibiotic stewardship. Methods: The diagnostic value of clinical and laboratory variables in predicting infections that require antibiotic treatment was evaluated in a prospective observational study of 404 adult patients admitted from the emergency department (ED) with suspected severe infections. We also investigated the association of these variables with bacteraemia and severe sepsis. Results: In a univariate analysis, increased levels of C-reactive protein (CRP), procalcitonin (PCT), interleukin 6 (IL-6), lipopolysaccharide binding protein (LBP), white blood cell count (WBC), neutrophils, respiratory rate (RR) ( p ≤ 0.001), and a decreased haemoglobin (Hb) level ( p = 0.005) were associated with an indicated demand for antibiotics ( n = 286). In a multivariate analysis, only WBC, Hb, RR, and CRP remained independent predictors. When compared to the clinician's ability to make accurate antibiotic decisions, all variables tested had inferior diagnostic accuracy except CRP. Increased levels of PCT, IL-6, LBP, CRP, bilirubin, and RR were significantly associated with bacteraemia ( n = 68) ( p ≤ 0.001). Of these, PCT and IL-6 were also associated with severe sepsis ( n = 156) ( p < 0.001). In a multivariate analysis, CRP, RR, PCT, and bilirubin remained associated with bacteraemia. Conclusions: Special attention should be directed to CRP, WBC, RR, and Hb when selecting patients for antibiotic treatment in the emergency department. PCT, IL-6, and LBP did not provide additional guidance on antibiotic decisions and better tests are required in order to improve antibiotic stewardship. [ABSTRACT FROM AUTHOR]

We report here a case of meningitis caused by Salmonella virchow in a woman without signs or history of immunosuppression. Salmonella meningitis is a rare complication of human salmonellosis. The patient was successfully treated with ciprofloxacin. To our knowledge, this is the first reported case of confirmed meningitis in an adult caused by this serotype. [ABSTRACT FROM AUTHOR]

• A longitudinal cohort of 121 viremic adults hospitalized with COVID-19 was studied. • Viremia/RNAemia was cleared from serum a median of 7 days after admission. • The odds for mortality increased with 40% for each additional day of viremia. • Serum viral clearance coincided with defervescence and decreasing CRP. • Repeated testing for SARS-CoV-2 RNA in blood enables a continuous risk assessment. SARS-CoV-2 viremia at admission is associated with high risk for mortality. However, longitudinal data on viremia duration are limited. Viremic patients hospitalized for COVID-19 were included in a cohort. Time to serum viral clearance and the effect of viremia duration on the odds of mortality were calculated. One hundred and twenty-one viremic patients were included. Median age was 62 (IQR 52−71) years and 68% were males. The total in-hospital mortality of the cohort was 33%. Median time from admission to serum viral clearance was 7 (95% CI 6−8) days. Duration of viremia showed a relative risk ratio of 1.40 (95% CI 1.02−1.92) for the odds of mortality in an adjusted multinomial logistic regression. Serum viral clearance coincided with defervescence and decreasing C-reactive protein. Median time to serum viral clearance was 7 days after admission. The odds of mortality increased with 40% for each additional day of viremia. [ABSTRACT FROM AUTHOR]