Sepsis is a high burden syndrome associated with increased morbidity and mortality in both the acute and longer-term phases of illness. Multiple treatment uncertainties remain that require resolution through high-quality research. This study aimed to identify the top 10 research priorities for sepsis research in the UK. We conducted a priority setting partnership study co-produced by sepsis survivors, carers and clinicians. This included five stages: initiation of steering group formation and confirmation of the scope of the priority setting partnership; identification of clinical uncertainties through an electronic survey; analysis and verification of uncertainties; interim prioritisation to the top 25 ranked questions; and final prioritisation to determine the top 10 research priorities, using the nominal group technique. Our initial survey respondents comprised 447/718 (62.3%) people who had survived sepsis, their friends and family members; 218/718 (30.4%) clinicians; and 53/718 (7.1%) multiple/other roles who identified 53 distinct research uncertainties. Our interim prioritisation survey comprised 429/941 (45.8%) people who had survived sepsis, their friends and family members; 431/941 (46.0%) clinicians; and 73/941 (8.2%) multiple/other roles, with the top 25 ranked summary questions taken forwards for final prioritisation. From these, final workshop participants (n = 27) agreed a top 10 list of research priorities. Improved sepsis diagnosis; characterisation and management of the post-sepsis syndrome; and non-antibiotic treatment of sepsis were the top three priorities. We establised priorities for sepsis research through a rigorous process of consensus involving sepsis survivors, carers and clinicians. These priorities will support future delivery of meaningful research to improve outcomes from sepsis. Weniger anzeigen

We examined the effect of a high-target mean arterial pressure (MAP) on septic shock in a previously underrepresented region. A multicentre, pragmatic, open-label, randomised controlled trial was conducted in 29 hospitals in Japan, where the prevalence of chronic hypertension among older individuals is 66.9%. Patients who were diagnosed with septic shock, aged ≥ 65 years, and admitted to an intensive care unit were randomised 1:1 to the high (target MAP = 80-85 mmHg) or control (target MAP = 65-70 mmHg) groups from 1 July 2021 to 12 December 2023. The target MAP was maintained for 72 h or until vasopressors were no longer required. The primary outcome was the 90-day all-cause mortality. Secondary outcomes included organ support-free days and adverse events. The trial was terminated early on the basis of the interim analysis results, suggesting the harm of the high-target strategy. Of the 518 patients, 258 were in the high-target group, and 260 were in the control group. By 90 days after randomisation, 101 patients (39.3%) in the high-target group and 74 (28.6%) in the control group had died from any cause (risk difference = 10.7; 95% confidence interval, 2.6-18.9). Renal replacement therapy-free days at 28 days were shorter in the high-target group. No clinical benefits for any outcome were observed in any subpopulation, including those with known chronic hypertension. Among older patients with septic shock, high-target MAP significantly increased mortality compared with standard care. UMIN Clinical Trials Registry; UMIN000041775; 13 September 2020. Weniger anzeigen

Platelets play a critical role in the inflammatory response and coagulation. We aimed to evaluate whether the use of acetylsalicylic acid (ASA) would reduce the intensity of organ dysfunction in septic patients. Randomized, blinded, parallel-group, placebo-controlled trial. Five general ICUs in Brazil. Adults with sepsis for no longer than 48 hours who had at least one severe organ dysfunction (lactate > 4 mmol/L, platelets < 100,000/mm3, Pao2/Fio2 ratio < 200, or septic shock). Patients were randomized to receive 200 mg of ASA or placebo for 7 days. The primary outcome was the change in the Sequential Organ Failure Assessment (SOFA) score between day 0 and day 7 or date of discharge/death. Safety outcomes were major bleeding and the number of blood transfusions within 14 days. The planned sample size was 218 with interim safety analyses after enrolling 109 and 163 patients. The study was discontinued due to higher frequency of major bleeding in the ASA group. We included 166 patients (ASA: 82 patients, placebo: 84). In the adjusted analysis, there was no difference in the SOFA change between the groups (mean placebo to ASA group difference, 0.60; 95% CI, -0.55 to 1.75; p = 0.30). There were no differences in any of the secondary outcomes. In the intervention group, there were a higher number of serious adverse events (9 [11%] vs. 1 [1.2%]; p = 0.009) and major bleeding (8 [8.5%] vs. 1 [1.2%]; p = 0.02). In this population of septic patients, ASA did not reduce the intensity of organ dysfunction. ASA increased the risk of severe bleeding compared with placebo. Weniger anzeigen

To perform: 1) external validation of the Phoenix Sepsis Score and Phoenix sepsis criteria in a multicenter cohort of critically ill children with infection and a comparison with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria; 2) a study of Phoenix sepsis criteria performance in patient subgroups based on age and comorbidities; 3) an assessment of microbiological profile of children with Phoenix sepsis; and 4) a study of the performance of the Phoenix-8 score. Secondary, retrospective analysis of a multicenter cohort study from 2012 to 2018. Nine PICUs in the United States. PICU admissions with suspected infection. None. Among 25,680 encounters of children with suspected or confirmed infection on PICU admission (4.6% in-hospital mortality), 11,168 (43%) met Phoenix criteria for sepsis or septic shock (9% in-hospital mortality). The Phoenix criteria generally outperformed the IPSCC criteria at discriminating mortality in all critically ill children with infections and across all subgroup analyses, including age group, malignancy, or technology dependence. Of 11,168 patients who met Phoenix criteria, 28% were negative for IPSCC criteria for sepsis and these had higher in-hospital mortality than those who met IPSCC sepsis criteria but not Phoenix criteria (4.7% vs.1.7%; p < 0.001), which was similar to the mortality of patients without sepsis (1.3%). Sepsis was associated with respiratory or bloodstream infection, most commonly Pseudomonas aeruginosa or Staphylococcus aureus. The Phoenix-8 score had good discrimination of mortality in children with infections, comparable to or better than validated and widely used severity of illness and organ dysfunction scores. In 2012-2018, among U.S. patients with suspected or confirmed infection admitted to nine PICUs, those with the highest risk of mortality can be identified using the Phoenix sepsis criteria, including in children of different age groups and those with major comorbidities. Weniger anzeigen

In observational studies that use administrative data, it is essential to report technical details such as the number of International Classification of Disease (ICD) coding fields extracted. This information is crucial for ensuring comparability between studies and for avoiding truncation bias in estimates, particularly for complex conditions like sepsis. Specific sepsis codes (explicit sepsis) are suggested to be identified by extracting 15 diagnosis fields, while for implicit sepsis, which comprises an infection code combined with acute organ failure, the number of diagnosis field remains unknown. The objective was to explore the necessary number of diagnosis fields to capture explicit and implicit sepsis. We conducted a study utilizing The Norwegian Patient Register (NPR), which encompasses all medical ICD-10 codes from specialized health services in Norway. Data were extracted for all adult patients with hospital discharges registered with explicit and implicit sepsis codes from all Norwegian hospitals between 2008 through 2021. Out of 317,705 sepsis admissions, we identified 105,499 ICD-10 codes for explicit sepsis, while implicit sepsis was identified through 270,346 codes for infection in combination with 240,789 codes for acute organ failure. Through our analysis, we found that 55%, 37%, and 10% of the explicit, infection, and acute organ failure codes, respectively, were documented as the main diagnosis. The proportion of explicit and infection codes peaked in the primary diagnosis field, while for acute organ failure codes, this was true in the third secondary diagnosis field. Notably, the cumulative proportion reached 99% in diagnosis field 10 for explicit codes and in diagnosis field 13 for implicit codes. Expanding the utilization of multiple diagnosis fields can enhance the comparability of data in epidemiological studies, both internationally and within countries. To make truncation bias visible, reporting guidelines should specify the number of diagnosis fields when extracting ICD-10 codes. Weniger anzeigen

Maternal mortality is not on track to meet Sustainable Development Goal (SDG) target 3.1 of a global maternal mortality ratio below 70 per 100 000 livebirths by 2030. Updated evidence on causes of death is needed to accelerate progress. We conducted a multi-strategy systematic review to identify causes of maternal deaths occurring in 2009-20. Data sources included civil registration and vital statistics systems data from the WHO Mortality Database, reports published by Member States, and national and subnational journal articles identified via bibliographic databases. We used a Bayesian hierarchical model to estimate the maternal cause of death distribution by SDG regions and worldwide. Given the paucity of data on maternal suicide and late maternal deaths occurring beyond 42 days postpartum, additional analyses were conducted to estimate the proportion of maternal deaths from suicide and the ratio of maternal to late maternal deaths (all cause). Globally, the most common cause of maternal death was haemorrhage (27%; 80% uncertainty interval 22-32), followed by indirect obstetric deaths (23%, 18-30), and hypertensive disorders (16%, 14-19). The proportion of haemorrhage deaths varied substantially by region and was highest in sub-Saharan Africa and Western Asia and Northern Africa. The proportion of maternal deaths from hypertensive disorders was highest in Latin America and the Caribbean. Most maternal deaths from haemorrhage and sepsis occurred during the postpartum period. Only 12 countries recorded one or more maternal suicides; of those countries, the proportion of deaths from suicide ranged from below 1% to 26% of maternal deaths. For countries reporting at least one late maternal death (ie, deaths that occur more than 42 days but less than 1 year after the termination of pregnancy), the ratio of late maternal deaths to maternal deaths up to 42 days ranged from <0·01 to 0·07. Haemorrhage remains the leading cause of death, despite the existence of effective clinical interventions, emphasising the need for improved access to quality health care. The timing of most deaths in the postpartum period demands renewed commitment to improving the provision of postpartum care in addition to intrapartum care. Indirect causes of death require health system approaches to integrate obstetric and non-obstetric care. USAID; US Fund for UNICEF via the Bill & Melinda Gates Foundation; and UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development, and Research Training in Human Reproduction (HRP). Weniger anzeigen

This study investigates the global incidence of maternal sepsis, a life-threatening condition and major cause of maternal mortality. Through a systematic review and meta-analysis, we aim to provide a more precise estimation of its incidence, identify regional variations, and examine associated risk factors to inform improved prevention and management strategies. This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search of PubMed/MEDLINE, Scopus, Google Scholar, EMBASE, and the Web of Science was performed for studies published from inception to January 10, 2025. The methodological quality of the included studies was rigorously assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. The pooled incidence rate per 10,000 pregnancies was estimated using a random-effects meta-analysis model to account for study heterogeneity. Furthermore, the analysis also explored the risk factors that contribute to the development of maternal sepsis. A total of 44 studies, encompassing 141,200,302 pregnant women from 24 countries, were included in the analysis. The global cumulative incidence of maternal sepsis was found to be 13.16 per 10,000 pregnant women (95% CI: 9.91 – 17.47). Regional variations were significant, with the highest crude incidence observed in the African region (129.17 per 10,000; 95% CI: 67.05 – 248.85), while the lowest was recorded in the Region of the Americas (6.31 per 10,000; 95% CI: 4.36 – 9.12). These findings were based on six studies from the African region and 17 from the Americas. Additionally, the study identified several factors, such as age ≥ 35, multiple pregnancies, gestational diabetes, preeclampsia/eclampsia, hypertension, diabetes mellitus, obesity, and cesarean delivery, that were linked to an increased risk of maternal sepsis. This study provides global and regional estimates of maternal sepsis, with a cumulative incidence of 13.16 per 10,000 pregnancies, highlighting regional disparities. Key risk factors include multiple pregnancies, preeclampsia, hypertension, obesity, and cesarean delivery. The findings emphasize the need for improved healthcare access, better data collection, and early intervention to reduce maternal sepsis worldwide. Weniger anzeigen

Neonatal sepsis is a significant cause of newborn mortality in low- and middle-income countries (LMICs). Together, infections, complications of preterm birth, and intrapartum-related conditions contribute to nearly 90% of all neonatal deaths. Africa experiences high rates of neonatal deaths due to sepsis, with insufficient prevention efforts. Understanding the burden of neonatal sepsis is essential to reducing these deaths in the region. This study aims to estimate the pooled magnitude of neonatal sepsis and identify its associated risk factors in Africa. For this study, we gathered data by searching various databases until August 20, 2024, including PubMed/MEDLINE, PubMed Central, Hinari, Google, Cochrane Library, African Journals Online, Web of Science, and Google Scholar. Full-text articles in English, both published and unpublished, from 2000 to 2024 were included. However, sources like citations without abstracts or full texts, unidentified reports, editorials, summaries of research, meta-analyses, and qualitative studies were not included in the study. We evaluated the quality of the selected papers using the Joanna Briggs Institute (JBI) critical appraisal checklist for observational studies. Data extraction was completed in Microsoft Excel, and analysis was conducted using STATA V.17 Statistical Software. We assessed study heterogeneity with the I statistic and the Cochrane Q test. Publication bias was evaluated both visually through a funnel plot and statistically through Egger’s regression and Begg’s tests. Subgroup analyses were performed to identify sources of heterogeneity, and a sensitivity analysis was conducted to find any outlier studies. This review includes 49 studies with 87,548 neonates. The overall magnitude of neonatal sepsis in Africa was found to be 40.98% (95% confidence interval (CI): 30.50% to 51.46%) P: 0.00. The study found that factors such as prolonged rupture of membranes (Odds ratio (OR) 4.11, 95% CI: 2.81-5.41) P: 0.00, a history of the urinary tract or sexually transmitted infections (OR 3.28, 95% CI: 1.97-4.58) P: 0.00, low birth weight (< 2500 g) (OR 6.95, 95% CI: 3-10.89) P: 0.00, an Appearance, Pulse, Grimace, Activity, Respiration (APGAR) score below 7 at the first minute (OR 7.56, 95% CI: 3.39-11.73) P: 0.00, preterm birth (OR 5.38, 95% CI: 3.23-7.5) P: 0.00, and neonates who were resuscitated at birth (OR 3.26, 95% CI: 1.96-4.56) P: 0.00. The magnitude of neonatal sepsis in Africa remains high. This study identified several contributing factors, including prolonged rupture of membranes, a history of urinary tract or sexually transmitted infections, low birth weight (< 2500 g), an APGAR score below 7 at one minute, preterm birth, and resuscitation at birth. These findings underscore the importance of routinely screening for risk factors such as prolonged membrane rupture and maternal infections. Enhancing antenatal care, training providers in early neonatal sepsis management, and enforcing infection control measures. Weniger anzeigen

Sepsis is one of the leading causes of neonatal mortality. There is heterogeneity in the outcomes measured and reported in studies of neonatal sepsis. To address this challenge, a core outcome set (COS) for research on neonatal sepsis was needed. The Neonatal Sepsis Core Outcome Set (NESCOS) project aims to develop a COS for research evaluating the effectiveness of neonatal sepsis treatments. For this consensus statement, the research team obtained ethics approval and used a 4-stage process: (1) a systematic review of qualitative studies, (2) a real-time Delphi (RTD) survey to identify important outcomes for consensus meetings, (3) consensus meetings to finalize the COS, and (4) dissemination of the findings. The study was conducted from May 2, 2022, to October 27, 2023. The steering group and project participants consisted of health care workers, researchers, academics, parents, and parent representatives from low-, middle-, and high-income countries. An RTD survey and consensus meetings were conducted, with measures including a 9-point Likert scale rating (where 1 indicated not at all important and 9 indicated critically important) for outcome importance and a minimum 80% agreement threshold among stakeholders for final COS inclusion. The systematic review identified 19 outcomes, which were combined with outcomes from previous systematic reviews of clinical trials. The RTD survey included 306 participants, leading to the identification of 55 outcomes for further discussion in consensus meetings. The finalized COS comprises 9 outcomes: all-cause mortality, need for mechanical ventilation, brain injury on imaging, neurologic status at discharge, escalation of antimicrobial therapy, central nervous system infections, multiorgan dysfunction, neurodevelopmental impairment, and quality of life of parents. This consensus-based COS for research on neonatal sepsis treatments will help standardize the outcomes measured and reported, enhancing the comparability of research findings. Future efforts should focus on establishing standardized and reliable methods for measuring these outcomes. Weniger anzeigen

Importance: Experimental and observational studies have suggested that empirical treatment for bacterial sepsis with antianaerobic antibiotics (eg, piperacillin-tazobactam) is associated with adverse outcomes compared with anaerobe-sparing antibiotics (eg, cefepime). However, a recent pragmatic clinical trial of piperacillin-tazobactam and cefepime showed no difference in short-term outcomes at 14 days. Further studies are needed to help clarify the empirical use of these agents. Objective: To examine the use of piperacillin-tazobactam compared with cefepime in 90-day mortality in patients treated empirically for sepsis, using instrumental variable analysis of a 15-month piperacillin-tazobactam shortage. Design, setting, and participants: In a retrospective cohort study, hospital admissions at the University of Michigan from July 1, 2014, to December 31, 2018, including a piperacillin-tazobactam shortage period from June 12, 2015, to September 18, 2016, were examined. Adult patients with suspected sepsis treated with vancomycin and either piperacillin-tazobactam or cefepime for conditions with presumed equipoise between piperacillin-tazobactam and cefepime were included in the study. Data analysis was conducted from December 17, 2022, to April 11, 2023. Main outcomes and measures: The primary outcome was 90-day mortality. Secondary outcomes included organ failure-free, ventilator-free, and vasopressor-free days. The 15-month piperacillin-tazobactam shortage period was used as an instrumental variable for unmeasured confounding in antibiotic selection. Results: Among 7569 patients (4174 men [55%]; median age, 63 [IQR 52-73] years) with sepsis meeting study eligibility, 4523 were treated with vancomycin and piperacillin-tazobactam and 3046 were treated with vancomycin and cefepime. Of patients who received piperacillin-tazobactam, only 152 (3%) received it during the shortage. Treatment groups did not differ significantly in age, Charlson Comorbidity Index score, Sequential Organ Failure Assessment score, or time to antibiotic administration. In an instrumental variable analysis, piperacillin-tazobactam was associated with an absolute mortality increase of 5.0% at 90 days (95% CI, 1.9%-8.1%) and 2.1 (95% CI, 1.4-2.7) fewer organ failure-free days, 1.1 (95% CI, 0.57-1.62) fewer ventilator-free days, and 1.5 (95% CI, 1.01-2.01) fewer vasopressor-free days. Conclusions and relevance: Among patients with suspected sepsis and no clear indication for antianaerobic coverage, administration of piperacillin-tazobactam was associated with higher mortality and increased duration of organ dysfunction compared with cefepime. These findings suggest that the widespread use of empirical antianaerobic antibiotics in sepsis may be harmful. Weniger anzeigen