Importance: Efforts to quantify the burden of SARS-CoV-2-associated sepsis have been limited by inconsistent definitions and underrecognition of viral sepsis. Objective: To describe the incidence and outcomes of SARS-CoV-2-associated sepsis vs presumed bacterial sepsis using objective electronic clinical criteria. Design, setting, and participants: This retrospective cohort study included adults hospitalized at 5 Massachusetts hospitals between March 2020 and November 2022. Exposures: SARS-CoV-2-associated sepsis was defined as a positive SARS-CoV-2 polymerase chain reaction test and concurrent organ dysfunction (ie, oxygen support above simple nasal cannula, vasopressors, elevated lactate level, rise in creatine or bilirubin level, and/or decline in platelets). Presumed bacterial sepsis was defined by modified US Centers for Disease Control and Prevention adult sepsis event criteria (ie, blood culture order, sustained treatment with antibiotics, and organ dysfunction using identical thresholds as for SARS-CoV-2-associated sepsis). Main outcomes and measures: Trends in the quarterly incidence (ie, proportion of hospitalizations) and in-hospital mortality for SARS-CoV-2-associated and presumed bacterial sepsis were assessed using negative binomial and logistic regression models. Results: This study included 431 017 hospital encounters from 261 595 individuals (mean [SD] age 57.9 [19.8] years, 241 131 (55.9%) females, 286 397 [66.5%] from academic hospital site). Of these encounters, 23 276 (5.4%) were from SARS-CoV-2, 6558 (1.5%) had SARS-CoV-2-associated sepsis, and 30 604 patients (7.1%) had presumed bacterial sepsis without SARS-CoV-2 infection. Crude in-hospital mortality for SARS-CoV-2-associated sepsis declined from 490 of 1469 (33.4%) in the first quarter to 67 of 450 (14.9%) in the last (adjusted odds ratio [aOR], 0.88 [95% CI, 0.85-0.90] per quarter). Crude mortality for presumed bacterial sepsis was 4451 of 30 604 patients (14.5%) and stable across quarters (aOR, 1.00 [95% CI, 0.99-1.01]). Medical record reviews of 200 SARS-CoV-2-positive hospitalizations confirmed electronic health record (EHR)-based SARS-CoV-2-associated sepsis criteria performed well relative to sepsis-3 criteria (90.6% [95% CI, 80.7%-96.5%] sensitivity; 91.2% [95% CI, 85.1%-95.4%] specificity). Conclusions and relevance: In this retrospective cohort study of hospitalized adults, SARS-CoV-2 accounted for approximately 1 in 6 cases of sepsis during the first 33 months of the COVID-19 pandemic. In-hospital mortality rates for SARS-CoV-2-associated sepsis were high but declined over time and ultimately were similar to presumed bacterial sepsis. These findings highlight the high burden of SARS-CoV-2-associated sepsis and demonstrate the utility of EHR-based algorithms to conduct surveillance for viral and bacterial sepsis. Weniger anzeigen

Background: Septic shock is the development of sepsis to refractory circulatory collapse and metabolic derangements, characterized by persistent hypotension and increased lactate levels. Anisodamine hydrobromide (Ani HBr) is a Chinese medicine used to improve blood flow in circulatory disorders. The purpose of this study was to determine the therapeutic efficacy of Ani HBr in the treatment of patients with septic shock. Methods: This was a prospective, multicenter, randomized controlled trial focusing on patients with septic shock in 16 hospitals in China. Patients were randomly assigned in a 1:1 ratio to either the treatment group or the control group. The primary endpoint was 28-day mortality. The secondary outcomes included 7-day mortality, hospital mortality, hospital length of stay, vasopressor-free days within 7 days, etc. These indicators were measured and collected at 0, 6h, 24h, 48h, 72h and 7d after the diagnosis. Results: Between September 2017 and March 2021, 404 subjects were enrolled. 203 subjects received Ani HBr and 201 subjects were assigned to the control group. The treated group showed lower 28-day mortality than the control group. Stratified analysis further showed significant differences in 28-day mortality between the two groups for patients with a high level of illness severity. We also observed significant differences in 7-day mortality, hospital mortality and some other clinical indicators between the two groups. Conclusion: Ani HBr might be an important adjuvant to conventional treatment to reduce 28-day mortality in patients with septic shock. A large-scale prospective randomized multicenter trial is warranted to confirm our results. Weniger anzeigen

Objective: To compare mortality and length of hospital stay between patients with ESBL-producing E. coli bloodstream infections (BSIs) and patients with non-ESBL E. coli BSIs. We also aimed at describing risk factors for ESBL-producing E. coli BSIs and time to effective antibiotic treatment for the two groups. Methods: A retrospective case-control study among adults admitted between 2014 and 2021 to a Norwegian University Hospital. Results: A total of 468 E. coli BSI episodes from 441 patients were included (234 BSIs each in the ESBL- and non-ESBL group). Among the ESBL-producing E. coli BSIs, 10.9% (25/230) deaths occurred within 30 days compared to 9.0% (21/234) in the non-ESBL group. The adjusted 30-day mortality OR was 1.6 (95% CI 0.7-3.7, p = 0.248). Effective antibiotic treatment was administered within 24 hours to 55.2% (129/234) in the ESBL-group compared to 86.8% (203/234) in the non-ESBL group. Among BSIs of urinary tract origin (n = 317), the median length of hospital stay increased by two days in the ESBL group (six versus four days, p < 0.001). No significant difference in the length of hospital stay was found for other sources of infection (n = 151), with a median of seven versus six days (p = 0.550) in the ESBL- and non-ESBL groups, respectively. Conclusion: There was no statistically significant difference in 30-day mortality in ESBL-producing E. coli compared to non-ESBL E. coli BSI, despite a delay in the administration of an effective antibiotic in the former group. ESBL-production was associated with an increased length of stay in BSIs of urinary tract origin. Weniger anzeigen

Importance: Early warning scores (EWSs) are designed for in-hospital use but are widely used in the prehospital field, especially in select groups of patients potentially at high risk. To be useful for paramedics in daily prehospital clinical practice, evaluations are needed of the predictive value of EWSs based on first measured vital signs on scene in large cohorts covering unselected patients using ambulance services. Objective: To validate EWSs‘ ability to predict mortality and intensive care unit (ICU) stay in an unselected cohort of adult patients who used ambulances. Design, setting, and participants: This prognostic study conducted a validation based on a cohort of adult patients (aged ≥18 years) who used ambulances in the North Denmark Region from July 1, 2016, to December 31, 2020. EWSs (National Early Warning Score 2 [NEWS2], modified NEWS score without temperature [mNEWS], Quick Sepsis Related Organ Failure Assessment [qSOFA], Rapid Emergency Triage and Treatment System [RETTS], and Danish Emergency Process Triage [DEPT]) were calculated using first vital signs measured by ambulance personnel. Data were analyzed from September 2022 through May 2023. Main outcomes and measures: The primary outcome was 30-day-mortality. Secondary outcomes were 1-day-mortality and ICU admission. Discrimination was assessed using area under the receiver operating characteristic curve (AUROC) and area under the precision recall curve (AUPRC). Results: There were 107 569 unique patients (52 650 females [48.9%]; median [IQR] age, 65 [45-77] years) from the entire cohort of 219 323 patients who used ambulance services, among whom 119 992 patients (54.7%) had called the Danish national emergency number. NEWS2, mNEWS, RETTS, and DEPT performed similarly concerning 30-day mortality (AUROC range, 0.67 [95% CI, 0.66-0.68] for DEPT to 0.68 [95% CI, 0.68-0.69] for mNEWS), while qSOFA had lower performance (AUROC, 0.59 [95% CI, 0.59-0.60]; P vs other scores < .001). All EWSs had low AUPRCs, ranging from 0.09 (95% CI, 0.09-0.09) for qSOFA to 0.14 (95% CI, 0.13-0.14) for mNEWS.. Concerning 1-day mortality and ICU admission NEWS2, mNEWS, RETTS, and DEPT performed similarly, with AUROCs ranging from 0.72 (95% CI, 0.71-0.73) for RETTS to 0.75 (95% CI, 0.74-0.76) for DEPT in 1-day mortality and 0.66 (95% CI, 0.65-0.67) for RETTS to 0.68 (95% CI, 0.67-0.69) for mNEWS in ICU admission, and all EWSs had low AUPRCs. These ranged from 0.02 (95% CI, 0.02-0.03) for qSOFA to 0.04 (95% CI, 0.04-0.04) for DEPT in 1-day mortality and 0.03 (95% CI, 0.03-0.03) for qSOFA to 0.05 (95% CI, 0.04-0.05) for DEPT in ICU admission. Conclusions and relevance: This study found that EWSs in daily clinical use in emergency medical settings performed moderately in the prehospital field among unselected patients who used ambulances when assessed based on initial measurements of vital signs. These findings suggest the need of appropriate triage and early identification of patients at low and high risk with new and better EWSs also suitable for prehospital use. Weniger anzeigen

Background: Few studies have reported on mortality beyond one year after sepsis. We aim to describe trends in short- and long-term mortality among patients admitted with sepsis, and to describe the association between clinical characteristics and mortality for improved monitoring, treatment and prognosis. Methods: Patients ≥ 18 years admitted to all Norwegian hospitals (2008-2021) with a first sepsis episode were identified using Norwegian Patient Registry and International Classification of Diseases 10th Revision codes. Sepsis was classified as implicit (known infection site plus organ dysfunction), explicit (unknown infection site), or COVID-19-related sepsis. The outcome was all-cause mortality. We describe age-standardized 30-day, 90-day, 1-, 5- and 10-year mortality for each admission year and estimated the annual percentage change with 95% confidence interval (CI). The association between clinical characteristics and all-cause mortality is reported as hazard ratios (HRs) adjusted for age, sex and calendar year in Cox regression. Results: The study included 222,832 patients, of whom 127,059 (57.1%) had implicit, 92,928 (41.7%) had explicit, and 2,845 (1.3%) had COVID-19-related sepsis (data from 2020 and 2021). Trends in overall age-standardized 30-day, 90-day, 1- and 5-year mortality decreased by 0.29 (95% CI – 0.39 to – 0.19), 0.43 (95% CI – 0.56 to – 0.29), 0.61 (95% CI – 0.73 to – 0.49) and 0.66 (95% CI – 0.84 to – 0.48) percent per year, respectively. The decrease was observed for all infections sites but was largest among patients with respiratory tract infections. Implicit, explicit and COVID-19-related sepsis had largely similar overall mortality, with explicit sepsis having an adjusted HR of 0.980 (95% CI 0.969 to 0.991) and COVID-19-related sepsis an adjusted HR of 0.916 (95% CI 0.836 to 1.003) compared to implicit sepsis. Patients with respiratory tract infections have somewhat higher mortality than those with other infection sites. Number of comorbidities was positively associated with mortality, but mortality varied considerably between different comorbidities. Similarly, number of acute organ dysfunctions was strongly associated with mortality, whereas the risk varied for each type of organ dysfunction. Conclusion: Overall mortality has declined over the past 14 years among patients with a first sepsis admission. Comorbidity, site of infection, and acute organ dysfunction are patient characteristics that are associated with mortality. This could inform health care workers and raise the awareness toward subgroups of patients that needs particular attention to improve long-term mortality. Weniger anzeigen

Objective: To determine if the introduction of an emergency department (ED) sepsis screening tool and management bundle affects antibiotic prescribing and use. Design: Multicentre, cohort, before-and-after study design. Setting: Three tertiary hospitals in Queensland, Australia (median bed size 543, range 520-742). Participants: Adult patients, presenting to the ED with symptoms and signs suggestive of sepsis who had blood cultures collected. These participants were further assessed and stratified as having septic shock, sepsis or infection alone, using Sepsis-3 definitions. The study dates were 1 July 2017-31 March 2020. Intervention: The breakthrough series collaborative ‚Could this be Sepsis?‘ Programme, aimed at embedding a sepsis screening tool and treatment bundle with weighted-incidence syndromic combined antibiogram-derived antibiotic guidelines in EDs. Main outcome measures: The primary outcome was the rate of empirical prescriptions adherent to antibiotic guidelines during the ED encounter. Secondary outcomes included the empirical prescriptions considered appropriate, effective antibiotics administered within 3 hours and assessment of harm measures. Results: Of 2591 eligible patients, 721 were randomly selected: 241 in the baseline phase and 480 in the post-intervention phase. The rates of guideline adherence were 54.0% and 59.5%, respectively (adjusted OR (aOR) 1.41 (95% CI 1.00, 1.98)). As compared with baseline, there was an increase in the rates of appropriate antibiotic prescription after bundle implementation (69.9% vs 57.1%, aOR 1.92 (95% CI 1.37, 2.68)). There were no differences between the baseline and post-intervention groups with respect to time to effective antibiotics, adverse effects or ED rates of broad-spectrum antibiotic use. Conclusion and relevance: The use of an ED sepsis screening tool and management bundle was associated with an improvement in the rates of appropriate antibiotic prescription without evidence of adverse effects. Weniger anzeigen

Early treatment is the mainstay of sepsis therapy. We suspected that early recognition of sepsis by prehospital healthcare providers may shorten the time for antibiotic administration in the emergency department. We retrospectively evaluated all patients above 18 years of age who were diagnosed with sepsis or severe infection in our emergency department between 2018 and 2020. We recorded the suspected diagnosis at the time of presentation, the type of referring healthcare provider, and the time until initiation of antibiotic treatment. Differences between groups were calculated using the Kruskal-Wallis rank sum test. Of the 277 patients who were diagnosed with severe infection or sepsis in the emergency department, an infection was suspected in 124 (44.8%) patients, and sepsis was suspected in 31 (11.2%) patients by referring healthcare providers. Time to initiation of antibiotic treatment was shorter in patients where sepsis or infection had been suspected prior to arrival for both patients with severe infections (p = 0.022) and sepsis (p = 0.004). Given the well-described outcome benefits of early sepsis therapy, recognition of sepsis needs to be improved. Appropriate scores should be used as part of routine patient assessment to reduce the time to antibiotic administration and improve patient outcomes. Weniger anzeigen

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to postacute sequelae in multiple organ systems, but evidence is mostly limited to the first year postinfection. We built a cohort of 138,818 individuals with SARS-CoV-2 infection and 5,985,227 noninfected control group from the US Department of Veterans Affairs and followed them for 2 years to estimate the risks of death and 80 prespecified postacute sequelae of COVID-19 (PASC) according to care setting during the acute phase of infection. The increased risk of death was not significant beyond 6 months after infection among nonhospitalized but remained significantly elevated through the 2 years in hospitalized individuals. Within the 80 prespecified sequelae, 69% and 35% of them became not significant at 2 years after infection among nonhospitalized and hospitalized individuals, respectively. Cumulatively at 2 years, PASC contributed 80.4 (95% confidence interval (CI): 71.6-89.6) and 642.8 (95% CI: 596.9-689.3) disability-adjusted life years (DALYs) per 1,000 persons among nonhospitalized and hospitalized individuals; 25.3% (18.9-31.0%) and 21.3% (18.2-24.5%) of the cumulative 2-year DALYs in nonhospitalized and hospitalized were from the second year. In sum, while risks of many sequelae declined 2 years after infection, the substantial cumulative burden of health loss due to PASC calls for attention to the care needs of people with long-term health effects due to SARS-CoV-2 infection. Weniger anzeigen

Purpose: To determine whether a novel intervention improves the adherence to guideline-based preventive measures in asplenic patients at risk of post-splenectomy sepsis (PSS). Methods: We used a prospective controlled, two-armed historical control group design to compare a novel, health action process approach (HAPA)-based telephonic intervention involving both patients and their general practitioners to usual care. Eligible patients were identified in cooperation with the insurance provider AOK Baden-Wuerttemberg, Germany. Patients with anatomic asplenia (n = 106) were prospectively enrolled and compared to a historical control group (n = 113). Comparisons were done using a propensity-score-based overlap-weighting model. Adherence to preventive measures was quantified by the study-specific ‚Preventing PSS score‘ (PrePSS score) which includes pneumococcal and meningococcal vaccination status, the availability of a stand-by antibiotic and a medical alert card. Results: At six months after the intervention, we estimated an effect of 3.96 (95% CI 3.68-4.24) points on the PrePSS score scale (range 0-10) with mean PrePSS scores of 3.73 and 7.70 in control and intervention group, respectively. Substantial improvement was seen in all subcategories of the PrePSS score with the highest absolute gains in the availability of stand-by antibiotics. We graded the degree of participation by the general practitioner (no contact, short contact, full intervention) and noted that the observed effect was only marginally influenced by the degree of physician participation. Conclusions: Patients who had received the intervention exhibited a significantly higher adherence to guideline-based preventive measures compared to the control group. These data suggest that widespread adoption of this pragmatic intervention may improve management of asplenic patients. Health insurance provider-initiated identification of at-risk patients combined with a patient-focused intervention may serve as a blueprint for a wide range of other preventive efforts leading to patient empowerment and ultimately to better adherence to standards of care. Weniger anzeigen

Background: The scarcity of sepsis epidemiologic data from most low- and middle-income countries (LMICs) hampered estimation of regional and global burden of the disease, and provided limited guidance for policy makers. We aimed to characterize and analyze the temporal trends of sepsis-related mortality in China, by population groups, underlying causes of death, geographic regions, and sociodemographic index (SDI) levels. Methods: Sepsis-related deaths were identified from the National Mortality Surveillance System (NMSS) of China from 2006 to 2020. Trends of sepsis-related mortality and years of life lost (YLLs), stratified by age, sex, underlying diseases, and regions were analyzed using the Jointpoint regression analysis. We investigated the association of SDI with trends of sepsis-related mortality. Results: In 2020, sepsis was estimated to be responsible for 986,929 deaths and 17.1 million YLLs in China. Age-standardized sepsis-related mortality significantly declined from 130.2 (95%CI, 129.4-131) per 100,000 population in 2006 to 76.6 (76.3-76.9) in 2020. Age-standardized YLLs decreased from 2172.7 (2169.4-2176) per 100,000 population in 2006 to 1271 (1269.8-1272.2) in 2020. Substantial variations of sepsis-related mortality and YLLs were observed between population groups and regions, with higher burden in males, the elderly, and western China. An inverse relation was noted between SDI and sepsis-related mortality or YLLs. Conclusions: Despite declining trends of age-standardized mortality and YLLs of sepsis in China, significant disparities between population groups and regions highlight a need for targeted policies and measures to close the gaps and improve the outcome of sepsis. Weniger anzeigen