In Deutschland wurden 2026 Qualitätsindikatoren des Instituts für Qualitätssicherung und Transparenz im Gesundheitswesen (IQTIG) zu Diagnostik und Therapie der Sepsis in Krankenhäusern verpflichtend eingeführt. Bisher existieren kaum Daten, inwiefern Qualitätsindikatoren in Form von Maßnahmen zu Sepsiserkennung und -therapie bereits etabliert sind. Sekundäranalyse des European Sepsis Care Survey, einer internationalen Querschnittstudie zu Strukturen der Sepsisversorgung in Akutkrankenhäusern. In Deutschland wurden leitende Ärzte aus Krankenhäusern aller Bundesländer und aller Versorgungsstufen systematisch zur Teilnahme eingeladen. Die Analyse erfolgte in Bezug auf 7 Qualitätsindikatoren des IQTIG zu Diagnostik und Therapie der Sepsis. In Deutschland wurden 253 Krankenhäuser (20

Background SARS-CoV-2 vaccines serve to protect and maintain health and are mostly well tolerated. However, there are only limited data on the extent to which vaccine side effects cause lost workdays, particularly among the critical group of health care workers. Methods Quantity of workdays lost and characteristics of side effects were assessed in previously unvaccinated health care workers without a history of SARS-CoV-2 infection at a tertiary German medical centre. Participants received either prime and boost with BNT162b2 or prime with ChAdOx1 and boost with BNT162b2. Results BNT162b2 for prime and boost were generally and to a large extent well tolerated. After the second dose of BNT162b2 more side effects were reported than after the prime (p < 0.001). Prime with ChAdOx1 was tolerated worse compared to prime and boost with BNT162b2 (p < 0.001). In total, 32.2 workdays lost per 100 vaccinations occurred in the homologous vaccinated group and 93.8 days per 100 vaccinations in the heterologous vaccinated group. Conclusions In this study, SARS-CoV-2 vaccination caused significant workdays lost among health care workers at a tertiary medical centre. Potential workdays lost after SARS-CoV-2 vaccination should be considered and anticipated when scheduling simultaneous or annually repeated vaccinations, especially among essential groups of employees.

ABSTRACT Invasive Candida infection (ICI) is the most common fungal infection in critically ill patients. This study analyzed the performance of various biomarkers in sera from the CandiSep trial, a randomized, multicenter trial including 342 sepsis patients at high risk for ICI across 18 German intensive care units. ICI and candidemia were diagnosed in 48 (14.0%) and 14 (4.1%) patients, respectively. Sera collected on 2 consecutive days at sepsis onset were analyzed for β-(1→3)-D-glucan (BDG; Fungitell), mannan (Platelia-Candida-Ag-Plus [Platelia-Mn] and Serion-ELISA-antigen-Candida [Serion-Mn]), and anti-Candida antibodies (Platelia-Candida-Ab-Plus, Serion-ELISA-Candida albicans-IgA/IgM/IgG, and Virclia-Candida albicans-germ-tube-antibody-IgG-Monotest). Only antigen levels (BDG, Platelia-Mn, Serion-Mn), but not anti-Candida antibody levels, were significantly elevated in ICI patients. Antigen levels were unaffected by Candida colonization, while antibody levels were significantly increased. Sensitivity and specificity at the manufacturer’s cutoffs were unsatisfactory. Performance improved by adjusting cutoffs: BDG required a 3-fold increase, while all others required lowering. At 80% specificity, sensitivities (95% confidence intervals) for the diagnosis of ICI and candidemia were as follows: BDG (cutoff >280 pg/mL), 46% (31.4–60.8) and 64% (35.1–87.2); Platelia-Mn (cutoff >50 pg/mL), 38% (24.0–52.6) and 64% (35.1–87.2); Serion-Mn (cutoff >0.7 U/mL), 38% (24.0–52.6) and 50% (23.0–77.0), and below 28% and 43% for all antibody assays. Area under the receiver operating characteristic curve comparisons showed no significant differences between antigen assays. Combining biomarkers, either simultaneously or sequentially, offered no diagnostic advantage over single-biomarker use. In conclusion, anti-Candida antibody assays are likely influenced by colonization and have limited diagnostic utility. Antigen assays offer similar diagnostic value but require cutoff optimization. Combining biomarkers did not enhance diagnostic yield in our cohort.IMPORTANCEOur main findings based on our specific ICU cohort were as follows: (i) only Candida antigen levels, not anti-Candida antibody levels, were significantly elevated in ICI and candidemia. (ii) In patients without ICI, Candida colonization was not associated with altered antigen levels, but with elevated antibody levels. (iii) Sensitivity and specificity at the manufacturer’s cutoffs were unsatisfactory, and cutoffs should be significantly adjusted. Potential optimal cutoff values are proposed by us. (iv) The evaluated antigen assays demonstrated overall comparable diagnostic performance in this study. (v) Anti-Candida antibody assays did not provide a meaningful diagnostic contribution. (vi) The combination of biomarkers offered no diagnostic advantage over the use of individual biomarkers, neither simultaneously nor sequentially. Our results suggest that the use of a single Candida antigen test with a cohort-adapted cutoff value may be sufficient. Furthermore, avoiding biomarker combinations could potentially reduce healthcare costs. The clinical implications of these findings should be interpreted with caution, given the limited data with associated large confidence intervals for candidemia and the cohort-specific nature of the study. Our results should therefore be confirmed in larger studies and additionally with other patient groups.

BACKGROUND:In Germany quality indicators from the Institute for Quality Assurance and Transparency in the Healthcare System (IQTIG) on the diagnostics and treatment of sepsis in hospitals will be compulsorily introduced in 2026. Currently, there are few data on the extent to which quality indicators in the form of measures to recognize and treat sepsis are already established. METHODS:This was a secondary analysis of the European Sepsis Care Survey, an international, cross-sectional study of the organization of sepsis care in acute care hospitals. Head physicians from hospitals in all federal states and at all levels of care in Germany were systematically invited to participate. The analysis investigated seven quality indicators of the IQTIG on the diagnostics and treatment of sepsis. RESULTS:In Germany 253 hospitals (20% of all acute care hospitals in Germany) were analyzed. Standardized screening for early detection of sepsis existed in 34.8% (95% confidence interval, CI 27.9-42.3%) of hospitals and standardized measures for sepsis management in 36.6% (95% CI 29.2-44.5%) of hospitals. There were differences between emergency departments, general wards and intensive care units (p < 0.05) but no significant differences between university and non-university hospitals. Regular training of medical and nursing staff in all departments existed in 4.7% (95% CI 2.3-8.5%) of hospitals. CONCLUSION:In Germany only a few hospitals had hospital-wide standardized measures for the early detection and treatment of sepsis. Regular training of medical and nursing staff to improve quality was rarely implemented. Against this background, the establishment of quality improvement programs is urgently needed but at the same time requires clear structures and sufficient resources.

PURPOSE:Sepsis is a leading cause of morbidity and mortality, yet its documentation and coding in administrative health data remain unreliable. Accurate coding is essential for epidemiological surveillance, quality assurance, and reimbursement. This study aims to identify patient characteristics associated with under-diagnosis and under-coding of sepsis in German inpatient administrative health data (IAHD). METHODS:This secondary analysis of the multicenter OPTIMISE study included 10,334 hospital cases from ten German hospitals (2015-2017). Sepsis cases were identified via structured chart review and compared to ICD-coded diagnoses. Logistic regression and classification tree analyses were used to determine predictors of under-diagnosis and under-coding, including ICU admission, organ dysfunction, and infection source. RESULTS:Among 1,310 cases fulfilling severe sepsis-1 criteria, only 30.7% were correctly coded. The strongest predictor for coding accuracy was explicit mention of sepsis in the medical chart (OR 19.58). ICU treatment, organ dysfunction severity, and mechanical ventilation were also associated with higher coding rates, while pneumonia as the infection source was linked to a lower probability of sepsis being named and coded. CONCLUSION:Sepsis coding in administrative data is frequently inaccurate. Explicit naming of sepsis and severity markers strongly influence correct coding. As Germany introduces mandatory sepsis quality assurance in 2026, targeted interventions - including enhanced clinician documentation and electronic coding support - are essential to improve coding reliability and patient care.

Rationale: Early detection, standardized therapy, adequate infrastructure, and strategies for quality improvement should constitute essential components of every hospital's sepsis plan. Objectives: To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of patients with sepsis in acute-care hospitals. Methods: A multidisciplinary cross-sectional questionnaire was used to investigate sepsis care in hospitals. This included the use of sepsis definitions, the implementation of sepsis guideline recommendations, diagnostic and therapeutic infrastructure, antibiotic stewardship, and quality improvement initiatives (QIIs) in hospitals. Measurements and Main Results: A total of 1,023 hospitals in 69 countries were included. Most of them, 835 (81.6%), were in Europe. Sepsis screening was used in 54.2% of emergency departments (EDs), 47.9% of wards, and 61.7% of ICUs. Sepsis management was standardized in 57.3% of EDs, 45.2% of wards, and 70.7% of ICUs. The implementation of comprehensive QIIs was associated with increased screening (EDs, +33.3%; wards, +44.4%; ICUs, +23.8% absolute difference) and increased standardized sepsis management (EDs, +33.6%; wards, +40.0%; ICUs, +17.7% absolute difference) compared with hospitals without QIIs. A total of 9.8% of hospitals had implemented ongoing QIIs, and 4.6% had invested in sepsis programs. Conclusions: The findings indicate that there is considerable room for improvement in a large number of mainly European hospitals, particularly with regard to early identification and standardized management of sepsis, the availability of guidelines, diagnostic and therapeutic infrastructure, and the implementation of QIIs. Further efforts are required to implement a more comprehensive and appropriate quality of care.

BACKGROUND:Sepsis is an acute, life-threatening multiple organ dysfunction triggered by an infection. METHODS:This guideline is an update of the S3 guideline "Sepsis-prevention, diagnosis, therapy, and follow-up care" (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaft [AMWF] Registry No. 079-001) of the German Sepsis Society (DSG) dated 31 December 2018. The update of the "Surviving sepsis campaign (SSC): international guidelines for management of sepsis and septic shock 2021" dated 4 October 2021, was used as the reference guideline. The DSG Guideline Commission compared each recommendation on the underlying PICO questions of the DSG Guideline 2018 (literature search until December 2018) with those of the SSC Guideline 2021 (literature search until July 2019) and evaluated the newly available published data (literature search until December 2024) by means of systematic update searches and literature reviews in compliance with the rules of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system and the AWMF. RESULTS:A total of 88 PICO questions were addressed, including those related to the diagnosis and treatment of infection and organ failure. Of these, two were agreed upon as statements, 29 as expert consensus, and 57 as evidence-based recommendations (26 with a strong and 31 with a weak recommendation grade). Compared to the previous 2018 guideline, 43 recommendations were reviewed but retained, 16 recommendations were modified, and 29 recommendations were newly issued. CONCLUSION:Given the lack of evidence for numerous measures for the inpatient care of patients with sepsis or septic shock, old and new knowledge gaps were revealed. Among the evidence-based recommendations, the underlying GRADE quality of evidence was high for only 5 recommendations, moderate for 18 recommendations, low for 17 recommendations, and very low for 16. These evidence gaps can only be closed through future multicenter, noncommercial clinical trials. The update to the S3 guideline on sepsis includes some updates to the recommendations of the previous guideline. These updates will need to be incorporated into some of the case- and facility-specific quality assurance indicators of quality assurance (QA) procedure 2025. Impairments in health-related quality of life for survivors must be given greater focus in outpatient care.

Background:Blood cultures (BCs) are key diagnostic elements for sepsis patients. Accurate preanalytical procedures are substantial, and results should be available as soon as possible to guide adequate antimicrobial treatment. This study aimed to evaluate BC collection practices and diagnostic capacity across European hospitals. Methods:This cross-sectional survey investigated BC diagnostics in acute care hospitals across 37 European countries in the years 2021 and 2022. Analyses included BC guidelines, collection sites, number of BC sets in emergency departments (EDs), wards, and intensive care units (ICUs). We also examined transfer after collection, the use of on-site vs. external laboratories, opening hours, rapid testing capacity, and turn-around times of BCs processed in microbiology laboratories with different infrastructures. Findings:Responses were collected from 907 hospitals in Europe. BC guidelines were available in 84·4% (741/878) of the hospitals. BCs were preferably collected by multiple-site sampling in EDs (62·7%, 461/735), in wards (64·0%, 513/802) and ICUs (68·5%, 518/756). One BC set was preferred in EDs in 38·4% (270/704), in wards in 40·5% (314/775), and ICUs in 34·9% (261/748). Two BC sets were preferred in EDs in 31·0% (218/704), in wards in 28·1% (218/775), and ICUs in 39·2% (293/748). 48·0% (402/838) of hospitals used on-site and 52·0% (436/838) external microbiology laboratories. Around-the-clock microbiological services were available in 10⋅0% (91/907), and rapid pathogen identification in 43·7% (396/907) of hospitals. Infrastructure with around-the-clock microbiological service and rapid testing was available in 7·4% (62/840) of hospitals, and probability of a final microbiological result within two days was highest in these hospitals compared to hospitals with limited microbiology service (for BC collected on wards: 19·6% vs. 52·7%, Odds Ratio 4·59 [95% CI 2·50-7·79], p < 0·0001). Interpretation:Despite the availability of BC guidelines in many hospitals, current recommendations for BC collection were often neglected. Rapid testing capacity was limited in most microbiological laboratories, and around-the-clock service for BCs was very rare. As delay in results may have a detrimental impact on patient outcomes, strategies to improve these processes are urgently needed. Funding:The European Sepsis Alliance and a grant by Becton and Dickinson.

Sepsis ist eine akut lebensbedrohliche multiple Organdysfunktion, ausgelöst durch eine Infektion. Bei der vorliegenden Leitlinie handelt es sich um ein Update der S3-Leitlinie „Sepsis – Prävention, Diagnose, Therapie und Nachsorge“ (AMWF-Register-Nr.: 079–001) der Deutschen Sepsis-Gesellschaft (DSG) vom 31.12.2018. Dabei wurde das Update der „Surviving sepsis campaign (SSC): international guidelines for management of sepsis and septic shock 2021“ vom 04.10.2021 als Referenzleitlinie zugrunde gelegt. Die DSG-Leitlinienkommission verglich jede Empfehlung zu den zugrunde liegenden PICO-Fragen der DSG-Leitlinie 2018 (Literaturrecherche bis 12/2018) mit denen der SSC-Leitlinie 2021 (Literaturrecherche bis 07/2019) und bewertete die in der Zwischenzeit neu verfügbare publizierte Datenlage (Literaturrecherche bis 12/2024) mittels systematischer Aktualisierungsrecherchen und Literaturbewertungen unter Befolgung des Regelwerkes des GRADE-Systems und der AWMF. Insgesamt wurden 88 PICO-Fragen u. a. zur Diagnose und Therapie der Infektion und des Organversagens adressiert. Davon wurden 2 als Statements, 29 als Expertenkonsens und 57 als evidenzbasierte Empfehlungen (26 mit starkem und 31 mit schwachem Empfehlungsgrad) konsentiert. Im Vergleich zur Vorgänger-Leitlinie 2018 wurden 43 Empfehlungen überprüft, aber beibehalten. 16 Empfehlungen wurden geändert, und 29 Empfehlungen wurden neu ausgesprochen. Angesichts fehlender Evidenz für zahlreiche Maßnahmen zur stationären Versorgung von Patienten mit Sepsis oder septischem Schock wurden alte und neue Wissenslücken offenbart. Bei den evidenzbasierten Empfehlungen war die zugrunde liegende Evidenzqualität nach GRADE nur bei 5 Empfehlungen hoch, bei 18 Empfehlungen moderat, bei 17 Empfehlungen niedrig und bei 16 sehr niedrig. Diese Evidenzlücken können nur durch zukünftige multizentrische, nichtkommerzielle klinische Prüfungen geschlossen werden. Das Update der S3-Leitlinie Sepsis beinhaltet einige Aktualisierungen zu Empfehlungen der Vorgängerleitlinie. Diese Aktualisierungen werden in einige der fall- und einrichtungsbezogenen QS-Indikatoren des QS-Verfahrens 2025 einfließen müssen. Beeinträchtigungen in der gesundheitsbezogenen Lebensqualität müssen bei Überlebenden mehr in den Fokus der ambulanten Versorgung gerückt werden.

Objective:To evaluate the feasibility of early computer-based assessment, quantify cognitive impairments and identify factors influencing cognition. Design:Prospective, cross-sectional study. Setting:Data were collected on a surgical intensive care unit. All patients underwent cognitive assessment once they reached a Richmond Agitation-Sedation Scale (RASS) score of -1 or higher. Participants:During data collection, 60 patients (N=60) met the inclusion criteria: sepsis and 24 hours of ventilation. Patients with prior cognitive impairment, or neurologic or psychiatric diagnoses, were excluded. Therefore, a total of 28 patients were included in the study. Interventions:Not applicable. Main Outcome Measures:Primary outcome variables were tonic alertness, the general level of attention and phasic alertness, the temporarily increased attentiveness after a stimulus. They were normalized for age and sex. The hypothesis proposed was that testing would be feasible starting from a RASS score of -1. Results:Testing was only possible when patients had a RASS of 0 and had regained orientation. On average, a successful test could be performed 6.6 (mean) days from RASS≥-1 or 4.7 (mean) days after the end of ventilation. On average, the results of tonic alertness were 3 standard deviations (95% CI, -3.8 to -2.2) worse. For phasic alertness, the mean score was -2.3 standard deviations (95% CI, -3.1 to -1.5).There are significant typical markers for sepsis severity with moderate correlations between an increasing number of ventilation days [r=-0.38, 95% CI: -0.66 to -0.01], number of days required between the cessation of ventilation and testing [r=-0.40, 95% CI: -0.68 to -0.04], days with noradrenaline [r=-0.48, 95% CI: -0.73 to -0.13], and days from awakening to the day of testing [r=-0.5, 95% CI: -0.74 to -0.15] and worsened tonic cognition. Conclusions:Early cognitive impairments are common in sepsis patients. Although early rehabilitation might be beneficial within this early stage, the utilization of computer-based assessments, appear to be limited. Detailed analysis of cognition should be considered later in recovery process. Further approaches could use demonstrated times at which assessment is likely to be successful.

BACKGROUND:The decision to maintain or halt antiplatelet medication in septic patients admitted to intensive care units presents a clinical dilemma. This is due to the necessity to balance the benefits of preventing thromboembolic incidents and leveraging anti-inflammatory properties against the increased risk of bleeding. METHODS:This study involves a secondary analysis of data from a prospective cohort study focusing on patients diagnosed with severe sepsis or septic shock. We evaluated the outcomes of 203 patients, examining mortality rates and the requirement for transfusion. The cohort was divided into two groups: those whose antiplatelet therapy was sustained (n = 114) and those in whom it was discontinued (n = 89). To account for potential biases such as indication for antiplatelet therapy, propensity score matching was employed. RESULTS:Therapy continuation did not significantly alter transfusion requirements (discontinued vs. continued in matched samples: red blood cell concentrates 51.7% vs. 68.3%, p = 0.09; platelet concentrates 21.7% vs. 18.3%, p = 0.82; fresh frozen plasma concentrates 38.3% vs. 33.3%, p = 0.7). 90-day survival was higher within the continued group (30.0% vs. 70.0%; p < 0.001) and the Log-rank test (7-day survivors; p = 0.001) as well as Cox regression (both matched samples) suggested an association between continuation of antiplatelet therapy < 7 days and survival (HR: 0.24, 95%-CI 0.10 to 0.63, p = 0.004). Sepsis severity expressed by the SOFA score did not differ significantly in matched and unmatched patients (both p > 0.05). CONCLUSIONS:The findings suggest that continuing antiplatelet therapy in septic patients admitted to intensive care units could be associated with a significant survival benefit without substantially increasing the need for transfusion. These results highlight the importance of a nuanced approach to managing antiplatelet medication in the context of severe sepsis and septic shock.

The aim of this study was to characterize the systemic cytokine signature of critically ill COVID-19 patients in a high mortality setting aiming to identify biomarkers of severity, and to explore their associations with viral loads and clinical characteristics. We studied two COVID-19 critically ill patient cohorts from a referral centre located in Central Europe. The cohorts were recruited during the pre-alpha/alpha (November 2020 to April 2021) and delta (end of 2021) period respectively. We determined both the serum and bronchoalveolar SARS-CoV-2 viral load and identified the variant of concern (VoC) involved. Using a cytokine multiplex assay, we quantified systemic cytokine concentrations and analyzed their relationship with clinical findings, routine laboratory workup and pulmonary function data obtained during the ICU stay. Patients who did not survive had a significantly higher systemic and pulmonary viral load. Patients infected with the pre-alpha VoC showed a significantly lower viral load in comparison to those infected with the alpha- and delta-variants. Levels of systemic CTACK, M-CSF and IL-18 were significantly higher in non-survivors in comparison to survivors. CTACK correlated directly with APACHE II scores. We observed differences in lung compliance and the association between cytokine levels and pulmonary function, dependent on the VoC identified. An intra-cytokine analysis revealed a loss of correlation in the non-survival group in comparison to survivors in both cohorts. Critically ill COVID-19 patients exhibited a distinct systemic cytokine profile based on their survival outcomes. CTACK, M-CSF and IL-18 were identified as mortality-associated analytes independently of the VoC involved. The Intra-cytokine correlation analysis suggested the potential role of a dysregulated systemic network of inflammatory mediators in severe COVID-19 mortality.

BACKGROUND:Timely diagnosis is crucial for sepsis treatment. Current machine learning (ML) models suffer from high complexity and limited applicability. We therefore created an ML model using only complete blood count (CBC) diagnostics.METHODS:We collected non-intensive care unit (non-ICU) data from a German tertiary care centre (January 2014 to December 2021). Using patient age, sex, and CBC parameters (haemoglobin, platelets, mean corpuscular volume, white and red blood cells), we trained a boosted random forest, which predicts sepsis with ICU admission. Two external validations were conducted using data from another German tertiary care centre and the Medical Information Mart for Intensive Care IV database (MIMIC-IV). Using the subset of laboratory orders also including procalcitonin (PCT), an analogous model was trained with PCT as an additional feature.RESULTS:After exclusion, 1 381 358 laboratory requests (2016 from sepsis cases) were available. The CBC model shows an area under the receiver operating characteristic (AUROC) of 0.872 (95% CI, 0.857-0.887). External validations show AUROCs of 0.805 (95% CI, 0.787-0.824) for University Medicine Greifswald and 0.845 (95% CI, 0.837-0.852) for MIMIC-IV. The model including PCT revealed a significantly higher AUROC (0.857; 95% CI, 0.836-0.877) than PCT alone (0.790; 95% CI, 0.759-0.821; P < 0.001).CONCLUSIONS:Our results demonstrate that routine CBC results could significantly improve diagnosis of sepsis when combined with ML. The CBC model can facilitate early sepsis prediction in non-ICU patients with high robustness in external validations. Its implementation in clinical decision support systems has strong potential to provide an essential time advantage and increase patient safety.

Introduction Sepsis remains the major cause of death among hospitalised patients in intensive care. While targeting sepsis-causing pathogens with source control or antimicrobials has had a dramatic impact on morbidity and mortality of sepsis patients, this strategy remains insufficient for about one-third of the affected individuals who succumb. Pharmacological targeting of mechanisms that reduce sepsis-defining organ dysfunction may be beneficial. When given at low doses, the anthracycline epirubicin promotes tissue damage control and lessens the severity of sepsis independently of the host–pathogen load by conferring disease tolerance to infection. Since epirubicin at higher doses can be myelotoxic, a first dose–response trial is necessary to assess the potential harm of this drug in this new indication.Methods and analysis Epirubicin for the Treatment of Sepsis and Septic Shock-1 is a randomised, double-blind, placebo-controlled phase 2 dose-escalation phase IIa clinical trial to assess the safety of epirubicin as an adjunctive in patients with sepsis. The primary endpoint is the 14-day myelotoxicity. Secondary and explorative outcomes include 30-day and 90-day mortality, organ dysfunction, pharmacokinetic/pharmacodynamic (PK/PD) and cytokine release. Patients will be randomised in three consecutive phases. For each study phase, patients are randomised to one of the two study arms (epirubicin or placebo) in a 4:1 ratio. Approximately 45 patients will be recruited. Patients in the epirubicin group will receive a single dose of epirubicin (3.75, 7.5 or 15 mg/m2 depending on the study phase. After each study phase, a data and safety monitoring board will recommend continuation or premature stopping of the trial. The primary analyses for each dose level will report the proportion of myelotoxicity together with a 95% CI. A potential dose-toxicity association will be analysed using a logistic regression model with dose as a covariate. All further analyses will be descriptive.Ethics and dissemination The protocol is approved by the German Federal Institute for Drugs and Medical Devices. The results will be submitted for publication in peer-reviewed journals.Trial registration number NCT05033808.

Timely and accurate data on the epidemiology of sepsis are essential to inform policy decisions and research priorities. We aimed to investigate the validity of inpatient administrative health data (IAHD) for surveillance and quality assurance of sepsis care. We conducted a retrospective validation study in a disproportional stratified random sample of 10,334 inpatient cases of age ≥ 15 years treated in 2015–2017 in ten German hospitals. The accuracy of coding of sepsis and risk factors for mortality in IAHD was assessed compared to reference standard diagnoses obtained by a chart review. Hospital-level risk-adjusted mortality of sepsis as calculated from IAHD information was compared to mortality calculated from chart review information. ICD-coding of sepsis in IAHD showed high positive predictive value (76.9–85.7

Background: In the Resolution 70.7 in 2017, the World Health Assembly urged member states to integrate sepsis in their national health systems. In May 2022, the G7 Health Ministers reiterated the necessity to implement such resolution focusing on early detection, diagnosis, and therapy. Defining and implementing standards and established guidelines, infrastructure, laboratory capacity, and strategies should be fundamental elements of any sepsis plan. Up to now, no data exist describing the current state of care, the availability of diagnostics or the provision of training in sepsis within hospitals.Methods: A harmonised multidisciplinary cross-sectional questionnaire was used to explore sepsis care in acute care hospitals in Europe and worldwide. Eleven main indicators representing sepsis care in emergency departments, general wards, intensive care units (ICUs) and hospitals in general were assessed.Findings: Participants from 1087 hospitals in 73 countries took part. Measures for early recognition of sepsis were available in 61·9% (530/856) of the ICUs, 54·5% (429/787) of emergency departments and 47·8% (420/878) of the wards. Sepsis protocols or sepsis bundles were applied in 70·7% (597/845) of ICUs, 57·6% (452/785) of emergency departments and 45·5% (391/860) of the wards. 24-hour microbiological service providing 24/7 blood culture incubation, pathogen identification and communication of results, was available in 10·1% (106/1046), antibiotic stewardship programs existed in 68·3% (678/992) and quality improvement programs or sepsis training were provided in 31·3·% (272/868) of the hospitals.Interpretation: This study reports structures and measures of sepsis care in hospitals in Europe and worldwide for the first time. Although the results are not generalisable, this exploratory sample represents 609,650 curative care beds and, including almost a quarter of the total curative care bed capacity of the European Union and revealed significant room for improvement of sepsis care, availability of diagnostics and implementation of quality improvement programs.Trial Registration: Registered at ClinicalTrials.gov (Identifier: NCT05059808).Funding: The European Sepsis Care Survey was funded by the European Sepsis Alliance and an educational grant by Becton Dickinson S.A. (BD).Declaration of Interest: Christian S. Scheer discloses funding from European Sepsis Alliance for conducting the European Sepsis Care Survey and funding from Becton and Dickinson for technical realisation of the project. Evangelos J. Giamarellos-Bourboulis discloses grants, contracts and payment to the Hellenic Institute for the Study of Sepsis and National and Kapodistrian University of Athens from Abbott Products Operations, bioMérieux Inc, Johnson & Johnson, MSD, Sobi AB, AbbVie, InflaRx GmbH, Johnson & Johnson, Novartis, UCB Horizon 2020 grant ImmunoSep, Horizon Health Grant EPIC- CROWN-2 and RISKinCOVID; consulting fees with payment done to the National and Kapodistrian University of Athens from GSK, InflaRx GmbH, UCB, Sobi AB; Payment for lectures and presentation done to the National and Kapodistrian University of Athens from Abbott Products Operations AG, bioMérieux, Sobi AB. He is chairman of the European Sepsis Alliance (ESA). Ricard Ferrer has nothing to disclose. Evgeny A. Idelevich discloses a Institutional grant “Accelerated detection of antibiotic-resistant pathogens with epidemic potential (LAB-in-MOTION) - Determination, optimisation, and validation of test conditions for rapid tests to detect antibiotic-resistant pathogens from the German Federal Ministry of Education and Research (BMBF); An institutional grant “Rapid and sensitive detection of bacteria and fungi by direct microscopy.” from MetaSystems Hard & Software GmbH; An institutional grant “MALDI Biotyper Sirius IVD System – Project: Innovative Matrix-Assisted Laser Desorption Ionization - Time of Flight (MALDI-TOF) Mass Spectrometry Application Extensions” from the Federal state Mecklenburg-Western Pomerania through the European Regional Development Fund (ERDF); An institutional grant “MASTeR-test - Development of universal rapid tests for phenotypic antimicrobial resistance determination in microorganisms based on Matrix- Assisted Laser Desorption Ionization - Time of Flight Mass Spectrometry (MALDI-TOF MS) - Determination, optimization, and validation of test components and parameters from the German Federal Ministry of Education and Research (BMBF); Inventor remuneration for patent licenses - 3 patent applications licensed from the University of Münster to Bruker.; Consulting fees for Expert role in the quality assurance procedure for the diagnosis, treatment, and follow-up care of sepsis from Institute for Quality Assurance and Transparency in Health Care (IQTIG); Honorarium for the educational lecture “Acceleration of microbiological diagnostics of sepsis” at the 8th paediatric workshop from MSD; Chair of the symposiums at ECCMID 2022 organised by Bruker (support for congress travel). Djillali Annane has nothing to disclose. Antonio Artigas discloses a BIOVAP-2 PSP study grant from Abionic; a Septibell study grant from Loop-Dx; Consulting fees from Grifols for Evaluation Albus awards, Fabentech for Scientific advisor of EPIC-CROWN-2 project, Lilly Foundation for Scientific Advisor committee, Aerogen for Spanish Advisory meeting; Board participation ImmuneSep (DSMB Committee), Apeptico (DSMB Committee), Exvastat (Scientific Advisor Board). Abdullah Tarik Aslan has nothing to disclose. Ruslan Baltaga has nothing to disclose. Gabriella Bottari discloses Coordination for spreading the survey to pediatric hospital and PICUs across Europe as deputy chair of the infection systemic inflammation and sepsis section of the European Society of Pediatric and Neonatal Intensive Care without any payment. Hjalmar R. Bouma discloses a Research grant to his institution from Becton Dickinson, Inflammatix, Levels Diagnostics; He is unpaid board member of Dutch SepsisNet society (non- profit organization). Vladimir Černý discloses honoraria for lectures from Octapharma and Astra Zeneca; He is unpaid president of the Czech Society of Anesthesiology and Intensive Care Renata Curić Radivojević has nothing to disclose. Ken Dewitte has nothing to disclose. Mohamed Elbahnasawy has nothing to disclose. Matthias Gründling discloses a grant from the German Federal Ministry of Health to the SepsisDialog / University of Greifswald for #DeutschlandErkenntSepsis; Payment, honoraria for lectures from Becton Dickinson and bioMerieux to SepsisDialog / University of Greifswald. He is board member of Deutschland Erkennt Sepsis. Mohan Gurjar discloses receiving royalties for the Edited Books (‘Manual of ICU Procedures’ and ‘Textbook of Ventilation Fluids, Electrolytes and Blood Gases’) from the publisher Jaypee Brothers Medical Publishers (Pvt.) Ltd., New Delhi; He received financial support from the institute to attend the Annual Conferences of Indian Society of Critical Care Medicine; He was unpaid Executive committee member of the Indian Society of Critical Care Medicine (ISCCM) for the duration 2020-2022. Johanna Hästbacka discloses consulting fees from Braun; Lecturer honoraria for a Sepsis- related webinar in May 2023 from Duodecim; She is Advisory board member Paion; She is founder an unpaid chairperson of the Finnish sepsis society; Stock options Orion Pharma. Said Laribi discloses consulting fees from BRAHMS. Annmarie Lassen discloses a grant from Novo Nordish Foundation to her institution, consulting fees and support for meetings and travel from Odense University Medicine. Konstantin Lebedinskii has nothing to disclose. Jan Máca has nothing to disclose. Manu L.N.G. Malbrain discloses consulting fees from BBraun, Becton Dickinson, ConvaTec, Spiegelberg; Speakers Fee from PeerVoice and Cytosorbents; Meeting and travel support from MedCaptain; A European Patent on CiMON probe and GEF/GEDVI Pulsion Medical systems; He is member of the medical advisory board Getinge group, Serenno, Medical, Potrero Medical, Sentinel Medical and Baxter, CMO Medaman, Senior advisor LynxCare; He is president of the International Fluid Academy and Treasurer Abdominal Compartment Society; Stock options Serenno Medical and Potrero Medical Gianpaola Monti discloses honoraria for lectures from MD, PFIZER and GETINGE; She is communication referent of SIAART (Italian Society of Anaesthesia and Intensive Care Medicine) Marlies Ostermann has nothing to disclose. Michael Osthoff discloses grants from Swiss National Science Foundation and Botnar Research Center for Child Health to his institution; Consulting fees from Pharming Biotechnologies B.V. paid to his institution and support to attend ECCMID 2023 from Tillots Pharma. José Artur Paiva discloses consulting fees from MSD, Pfizer, Gilead, AOP and honoraria for lectures from MSD, Pfizer, Gilead, Cepheid Michela Sabbatucci discloses National coordination for spreading the call for participation in 19 regions and 2 autonomous provinces in Italy in this study with any payment neither for myself nor for the participating centres/hospitals/patients. Jakub Śmiechowicz discloses consulting fees from Alteco Medical AB and honoraria for lectures from Radiometer and Alteco Medical AB. Mihai Gabriel Ştefan discloses honoraria for lectures from Vifor Pharma, Takeda Pharmaceuticals and AstraZeneca; He is Advisory board member Livanova and unpaid Board member of the Romanian Society of Anaesthesia and Intensive Care. Marcus Vollmer has nothing to disclose. Natalija Vukovic has nothing to disclose. Kyriakos Zaragkoulias discloses national coordination to disseminate the call for participation in this study. I ensure that neither I nor the participating centers/hospitals/patients have received any payment. Konrad Reinhart discloses holding shares from InflaRx NV, which is based in Jena, Germany and listed at NASDQ, this company recently received emergency use authorization by the FDA for an antibody against C5a. Gohibic (vilobelimab) – to treat critically ill COVID-19 patients, which fulfill the criteria for viral sepsis. He is the Founding President of the Global Sepsis Alliance. Adam Linder has nothing to disclose. Daniela Filipescu is Deputy chair of the European Sepsis Alliance (ESA) and representative of the European Society of Anaesthesiology and Intensive Care (ESAIC) to the ESA, both unpaid.Ethical Approval: The study received ethical approval (BB 124/21) from the ethics committee of the University Medicine Greifswald, Germany.

Wegen der oftmals sehr unspezifischen Sepsissymptome ist die Früherkennung des Notfalls Sepsis schwierig. Rechtzeitiges Erkennen ermöglicht es, Diagnostik und Therapie der Erkrankung zügig einzuleiten. Eine schnelle Behandlung der Sepsis führt zu einer geringeren Sterblichkeit und weniger schweren Langzeitfolgen. Die Früherkennung hat daher im diagnostischen und therapeutischen Prozess auch im ambulanten Bereich eine ganz zentrale Bedeutung.