Invasive group A Streptococcus (GAS) infections are associated with substantial morbidity, mortality, and economic burden. To update trends in invasive GAS disease incidence rates in 10 US states between 2013 and 2022. Clinical, demographic, and laboratory data for invasive GAS cases were collected as part of population-based surveillance in the Active Bacterial Core surveillance network covering 34.9 million persons across 10 US states. A case was defined as isolation of GAS from a normally sterile site or from a wound in a patient with necrotizing fasciitis or streptococcal toxic shock syndrome between January 1, 2013, and December 31, 2022. Demographic and clinical data were collected from medical record review. From 2013 to 2014, available isolates were emm typed and antimicrobial susceptibilities determined using conventional methods; from 2015 onward, whole-genome sequencing was used. Incidence rates by sex, age, race, and selected risk factors; clinical syndromes, outcomes, and underlying patient conditions; and isolate characteristics, including antimicrobial susceptibility. Surveillance in 10 US states identified 21 312 cases of invasive GAS from 2013 through 2022, including 1981 deaths. The majority of cases (57.5%) were in males. Among case-patients, 1272 (6.0%) were aged 0 to 17 years, 13 565 (63.7%) were aged 18 to 64 years, and 6474 (30.4%) were 65 years or older; 5.5% were American Indian or Alaska Native, 14.3% were Black, and 67.1% were White. Incidence rose from 3.6 per 100 000 persons in 2013 to 8.2 per 100 000 persons in 2022 (P < .001 for trend). Incidence was highest among persons 65 years or older; however, the relative increase over time was greatest among adults aged 18 to 64 years (3.2 to 8.7 per 100 000 persons). Incidence was higher among American Indian or Alaska Native persons than in other racial and ethnic groups. People experiencing homelessness, people who inject drugs, and residents of long-term care facilities had substantially elevated GAS incidence rates. Among tested isolates, those nonsusceptible to macrolides and clindamycin increased from 12.7% in 2013 to 33.1% in 2022. Invasive GAS infections increased substantially in 10 US states during a surveillance period from 2013 to 2022. Accelerated efforts to prevent and control GAS are needed, especially among groups at highest risk of infection. Weniger anzeigen

Emerging evidence links sepsis-related inflammation to dementia risk, but the dose-dependent effects of recurrent sepsis episodes remain unclear. This study assessed whether sepsis increases dementia risk and explored a potential dose-response relationship between sepsis frequency and dementia. We conducted a retrospective cohort study using Taiwan’s National Health Insurance Research Database (2005-2022), enrolling patients aged ≥18 years hospitalized with sepsis. An index period (2008-2013) was used to identify patients without prior dementia. A fixed 12-month landmark period (calendar year 2014) was applied to assess the number of sepsis episodes. Patients who died during the landmark period were excluded. Propensity score matching was performed to generate well-balanced sepsis and non-sepsis groups. Follow-up for dementia and mortality began after the landmark period and continued for up to 64 months. Cox and Fine-Gray models were used to account for competing risks of death. Sepsis was associated with a significantly increased risk of all-cause dementia (HR 1.59; 95 % CI, 1.47-1.72; P < 0.0001). A dose-response relationship was observed: patients with multiple sepsis episodes had the highest dementia risk (sHR 1.63; 95 % CI, 1.39-1.91). Vascular dementia showed the strongest association, with a higher incidence in the sepsis group (1.2 % vs. 0.6 %, P = 0.0003). Our findings provide robust evidence of a dose-dependent association between sepsis and increased dementia risk, particularly vascular dementia, even after adjusting for competing mortality risks. This study addresses the limitations of previous research by not only employing propensity score matching (PSM) to balance confounding factors between the sepsis and non-sepsis groups but also using an index period and landmark period design to better explore potential causal relationships. These periods ensure that dementia onset occurred after sepsis and allow for the examination of dose-response relationship between sepsis episode frequency and dementia. Furthermore, this is the largest study to date involving sepsis patients, providing more robust evidence than prior studies, which were often smaller and lacked adjustments for competing risks of death. Weniger anzeigen

Sepsis remains one of the leading causes of morbidity and mortality in critically ill children worldwide. Identifying reliable prognostic markers is essential for improving risk stratification and guiding targeted therapies. While some studies in adults suggest that procalcitonin (PCT) clearance may better predict sepsis outcomes, there is limited information regarding pediatric sepsis. This study aimed to evaluate whether PCT clearance is associated with mortality among children with severe sepsis and septic shock. We retrospectively reviewed medical records of children aged 1 month to 18 years admitted to the PICU who were diagnosed with severe sepsis and septic shock at Srinagarind Hospital, Thailand, between January 2016 and October 2021. Serum PCT was measured at 0, 24, and 48 hours after the initial diagnosis. PCT clearance was calculated using the relative change from baseline. The primary outcome was in-hospital mortality. A total of 242 children were included, with a median age of 8 years (interquartile range [IQR]: 3-14). Most participants (62.8%) had no underlying conditions. The overall mortality rate was 26.5%. An initial PCT level > 2 ng/mL was not significantly associated with mortality (adjusted odds ratio [aOR] = 1.17; 95% confidence interval [CI]: 0.44-3.16, p = 0.8). However, decreased PCT clearance at 24 hours was strongly associated with mortality (aOR = 2.79; 95% CI: 1.11-7.01, p = 0.029). The area under the receiver operating characteristic curve for 24-hour PCT clearance to predict mortality was 0.71 (95% CI: 0.63-0.80). Lower PCT clearance in the first 24 hours was significantly associated with higher mortality in pediatric patients with sepsis. Serial PCT measurements and PCT clearance monitoring may offer valuable prognostic information and could be considered as part of routine clinical evaluations in pediatric sepsis management. Weniger anzeigen

The efficacy of the SEP-1 Bundle has been questioned in the treatment of patients with hospital-acquired sepsis. We aimed to investigate bundle compliance and its association with survival in a subset of patients with HA sepsis: those with ICU-acquired sepsis. A single-center retrospective cohort study was conducted in a tertiary care referral hospital. Adult patients diagnosed with ICU-acquired sepsis between 1 January 2019 and 31 December 2022 were identified. Survival to hospital discharge adjusted for disease severity based on 3-hour, 6-hour, and total bundle compliance was calculated. Secondary outcomes included the need for mechanical ventilation, vasopressors, initiation of acute hemodialysis, and discharge location. Of 191 patients with ICU-acquired sepsis, 61 patients (31.9%) demonstrated total bundle compliance. There was no difference in survival based on the unadjusted analysis of 3-hour bundle compliance, compliant versus non-compliant (78.9% vs. 67.0%; P = 0.100). However, there was a survival benefit in 6-hour and total bundle, compliance versus non-compliance (82.2% vs. 60.0%, P < 0.001; 86.9% vs. 64.6%, P = 0.002). When adjusted for SOFA and CCI, logistic regression demonstrated similar results: 3-hour compliance (OR: 0.60; 95% CI: 0.29-1.18, P = 0.150), 6-hour compliance (OR: 0.35; 95% CI: 0.17-0.68, P = 0.002) and total compliance (OR: 0.31; 95% CI: 0.13-0.69, P = 0.006). Components of the SEP-1 Bundle that showed a mortality benefit included the collection of "blood cultures prior to antibiotic administration" (OR: 0.46; 95% CI 0.22-0.96, P = 0.037) and "tissue perfusion assessment" (OR: 0.41; 95% CI 0.18-0.90, P = 0.028). Six-hour and total SEP-1 bundle compliance was associated with increased hospital survival in patients with ICU-acquired sepsis. These findings suggest the importance of sepsis bundle compliance in the ICU environment. Not Applicable. Weniger anzeigen

Sepsis is a life-threatening, dysregulated host response to infection. Immunosuppression is a risk factor for infections and sepsis. However, the specific immune derangements elevating the risk for infections and sepsis remain unclear in the individual patient, raising the question of whether a general state of immunosuppression exists. In this Review, we explore the relationship between immunosuppression and sepsis, detailing the definitions, causes, and clinical implications. We address the effect of primary immunodeficiencies, acquired conditions, and drugs on the risk of infection and the development of sepsis. Patients with sepsis who are immunocompromised often present with atypical symptoms and diagnostic test results can differ, making early recognition difficult. Future perspectives entail novel biomarkers to improve early sepsis detection and tailored treatments to modulate immune function. Including patients who are immunocompromised in clinical trials is crucial to enhance the relevance of research findings and improve treatment strategies for this vulnerable population. Weniger anzeigen

Sepsis remains a major health concern with high associated mortality. Adequate treatment involves the use of antibiotic therapy although the timing of antibiotics is controversial. A decision analysis model of antibiotic initiation was created to determine optimal management of patients with suspected sepsis. Two decision trees were created using data from the published literature. A limited model used mortality as the primary outcome using the impact of antibiotic timing on rates of progression to shock and in-hospital mortality. The primary model included mortality and stewardship-related factors such as antibiotic avoidance and antibiotic-associated adverse events. Rapid initiation of antibiotics was defined as universal antibiotic administration within 3 h of presentation whereas deferred initiation included administration up to 6 h. Sensitivity analyses were performed to evaluate the effectiveness of each option. When considering only mortality, rapid initiation was the optimal strategy. When considering stewardship-related factors, rapid initiation of antibiotics maximized utility in only 40.6% of model iterations. One-way sensitivity analysis demonstrated rapid initiation of antibiotics was optimal when initiation times were above 1.33 h and the prevalence of infection was above 89.5%. Two-way sensitivity analysis demonstrated that as time to antibiotics increased, rate of true infection above which rapid antibiotics is optimal drops from just under 91% to approximately 88.5%. We constructed decision analysis models to characterize optimal conditions for antibiotic initiation in suspected sepsis. Our model suggests that the prevalence of infection needs to be approximately 90% for rapid initiation of antibiotics to be the optimal strategy. Weniger anzeigen

Sepsis is a leading cause of disease and affects approximately a third of ICU patients worldwide. Despite the rising number of sepsis survivors, the burden of cognitive and quality of life related post-sepsis morbidities remains understudied. This narrative review aimed to summarize and discuss current research investigating the quality of life and the burden of cognitive, mental, and functional health morbidities in sepsis survivors at different stages of life. Sepsis survivors of all ages were affected by cognitive dysfunction, with very preterm neonatal sepsis survivors reporting higher odds of neurodevelopmental disabilities, childhood sepsis survivors reporting delayed development, and adult sepsis survivors reporting cognitive decline, including a higher risk of dementia. Mental health concerns were reported in both survivors and family members, with limited mixed evidence for post-traumatic stress disorder, depression, suicide, and anxiety. Survivor functional status is frequently impacted in diverse ways, with both physical and mental changes often inhibiting daily life. Lastly, the impact of sepsis on survivor quality of life is mixed. While sepsis survivors frequently report poorer quality of life compared to the general population, studies have reported no difference in quality of life when comparing sepsis survivors with other critical illness survivors. Sepsis impacts the quality of life and cognitive, mental, and functional health in numerous diverse ways across the lifespan. Future research should focus on sepsis survivorship in children, and the mental health burden of sepsis across all age groups. Weniger anzeigen

To assess whether initial fluid resuscitation with lactated Ringer’s solution compared with 0.9% saline is associated with improved clinical outcomes in patients with sepsis-induced hypotension. Secondary analysis of the randomized controlled Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis (CLOVERS) trial. ICUs and emergency departments in 60 U.S. centers from March 2018 to January 2022. Participants from the CLOVERS trial. Adult patients with a suspected or confirmed infection and hypotension caused by sepsis. Participants received 1-3 L of crystalloid fluid for initial fluid resuscitation before randomization. In this analysis, participants were categorized into a lactated Ringer’s group and a 0.9% saline group based on the fluid type predominantly used for the initial fluid resuscitation (i.e., ≥ 95% of pre-randomization fluid). Of 1563 participants with sepsis-induced hypotension included in the CLOVERS trial, 622 (39.8%) received lactated Ringer’s solution and 690 (44.1%) received 0.9% saline as solution for the initial fluid bolus. Death before discharge home by day 90 occurred in 76 of 622 participants (12.2%) in the lactated Ringer’s group and in 110 of 690 participants (15.9%) in the 0.9% saline group, resulting in an adjusted hazard ratio of 0.71 (95% CI, 0.51-0.99; p = 0.043). Patients receiving lactated Ringer’s solution had more hospital-free days at 28 days than those receiving 0.9% saline (16.6 ± 10.8 vs. 15.4 ± 11.4, respectively; adjusted mean difference, 1.6 d [95% CI, 0.4-2.8 d; p = 0.009]). Treatment with 0.9% saline was associated with higher levels of serum chloride and decreased levels of serum bicarbonate. Initial fluid resuscitation with lactated Ringer’s solution, compared with 0.9% saline, might be associated with improved survival in patients with sepsis-induced hypotension. Weniger anzeigen

Sepsis requires stratification for host-directed therapies through the discovery of adequate biomarkers enabling prediction of outcomes and treatment responses. Adrenomedullin has previously demonstrated potential for prognostic enrichment. This study aimed to assess associations of bioactive adrenomedullin (bio-ADM) levels at ICU admission and sepsis outcomes and to evaluate the potential of bio-ADM as marker to identify subgroups of patients with moderate disease severity that might benefit from hydrocortisone treatment. We used data from the HYPRESS trial (NCT00670254) to investigate, if bio-ADM is useful to predict sepsis outcomes (septic shock, 90- and 180-day mortality) and benefit or harm by hydrocortisone treatment. Optimal cut-offs for outcome predictions were determined by Youden’s index. Logistic regression was used to assess bio-ADM subgroups and treatment interaction. Bio-ADM levels differed significantly in patients with or without septic shock within 14 days (p = 0.011). While the area under the ROC curve (AUC) was only 0.603 (CI 0.531-0.676), patient subgrouping using bio-ADM levels showed significantly higher cumulative incidence of septic shock within 14 days in the subgroup of patients with bio-ADM levels ≥ 37 pg/mL (p < 0.001). The odds ratio for the development of septic shock in this group was 4.67 (95% CI 1.53, 20.3, p = 0.016). A bio-ADM cut-off of ≥ 136 pg/mL was predictive for 90-day (OR 8.21, 95% CI 2.46-27.9, p < 0.001) and 180-day mortality (OR 4.87, 95% CI 1.49-16.0, p = 0.008). Hydrocortisone therapy did not reduce the incidence of septic shock (OR 1.59, 95% CI 0.37-8.15, p = 0.54), 90-day (OR 1.53, p = 0.23) or 180-day mortality (OR 1.41, p = 0.25), regardless of bio-ADM stratification (interaction term p = 0.58 for septic shock; p = 0.31 for 90-day mortality; p = 0.51 for 180-day mortality). Whereas bio-ADM levels are associated with sepsis outcomes, our data do not indicate usefulness of the marker to identify patients potentially benefitting from hydrocortisone therapy. Weniger anzeigen

Sepsis-associated acute kidney injury (SA-AKI) is a common and clinically important condition in patients who are critically ill. Dysregulated inflammation may contribute to it. Intravenous hydrocortisone may decrease the risk of SA-AKI progression. To describe the associations of hydrocortisone use with the incidence and outcomes of requirement for kidney replacement therapy (KRT), as well as source of sepsis, mean arterial pressure (MAP), and MAP indexed to required vasopressor (norepinephrine equivalent [NEE]). This cohort study was conducted as a post hoc analysis of the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock (ADRENAL) randomized clinical trial (RCT), a multicenter placebo-controlled RCT of hydrocortisone in patients with septic shock in 69 intensive care units in Australia, the United Kingdom, New Zealand, Saudi Arabia, and Denmark that recruited between 2013 and 2017. Participants were patients enrolled in the ADRENAL study with septic shock who did not require KRT in the 24 hours prior to randomization and who did not have a prior longstanding dialysis requirement. Data were analyzed between July and September 2024. Receipt of hydrocortisone (vs placebo), MAP at enrollment, vasopressor dose (NEE) and MAP:NEE ratio, source of sepsis, causative organism, bacteremia, and the use of nephrotoxic antimicrobials, vasopressin, or specific inotropes. Outcomes of interest were KRT requirement and liberation from KRT, measured as days alive and free of KRT. A cohort of 3161 patients (median [IQR] age, 65 [53-74] years, 1921 [61%] male) was identified, including 1589 patients randomized to receive hydrocortisone and 1572 patients who received the placebo. Allocation to treatment with hydrocortisone was associated with a significantly reduced incidence of KRT requirement compared with placebo (329 patients [21%] vs 372 patients [24%]; odds ratio [OR], 0.84 [95% CI, 0.70 to 0.99]; P = .04). When controlled for factors associated with KRT requirement, randomization to hydrocortisone remained significantly associated with a reduced odds of new KRT requirement (OR, 0.79 [95% CI, 0.66 to 0.95]; P = .01). Among patients who started KRT following randomization, hydrocortisone was not associated with reduced days alive and free of KRT (mean difference, 1.28 [95% CI, -4.31 to 6.87] days; P = .65). In this post hoc cohort study of patients with septic shock enrolled in a large RCT, intravenous hydrocortisone was associated with a reduced risk of new KRT requirement following randomization. Weniger anzeigen