Daily Sepsis Research Analysis

IMPORTANCE: Early and accurate identification of clinical warning signs in young infants may help avert sepsis morbidity and mortality in resource-limited settings. OBJECTIVE: To systematically review evidence on the association and accuracy of clinical signs to diagnose sepsis or predict mortality in young infants aged 0 to 59 days to inform management in settings with limited laboratory diagnostics. DATA SOURCES: MEDLINE, Embase, CINAHL, Global Index Medicus, and Cochrane CENTRAL Register were searched from inception through May 2023, with updated searches on September 5, 2024. An umbrella search of systematic reviews was conducted in January 2024. STUDY SELECTION: Included studies reported data on 24 infant clinical signs informed by current World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) and hospital-based algorithms for the care of sick young infants reporting odds ratios (OR), risk ratios, or sensitivity and specificity. DATA EXTRACTION AND SYNTHESIS: Data were extracted independently by 2 reviewers. Quality assessment used the Newcastle-Ottawa, Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), and Quality Assessment of Prognostic Accuracy Studies (QUAPAS) scales. OR data were pooled using random-effects models. Data analysis was performed from July to September 2025. MAIN OUTCOMES AND MEASURES: OR of all-cause mortality, culture-confirmed sepsis, or clinical sepsis (with access to laboratory investigations). RESULTS: Of 7641 studies, 52 studies with 140 885 participants were included. A total of 16 clinical signs were significantly associated with mortality, 11 with culture-confirmed sepsis, and 13 with clinical sepsis. For mortality, the 5 strongest associations were weak, abnormal, or absent cry (OR, 20.48; 95% CI, 6.59-63.67); not able to feed at all (OR, 18.32; 95% CI, 6.00-55.97); not feeding well (OR, 13.39; 95% CI, 6.97-25.72); drowsiness or unconsciousness (OR, 12.46; 95% CI, 6.06-25.62); and prolonged capillary refill (OR, 12.06; 95% CI, 2.77-52.53). The top 5 signs associated with culture-confirmed sepsis were not feeding well (OR, 4.52; 95% CI, 1.10-18.59); prolonged capillary refill (OR, 3.59; 95% CI, 2.05-6.28); lethargy (OR, 3.44; 95% CI, 1.89-6.26); drowsiness or unconsciousness (OR, 3.07; 95% CI, 2.01-4.68); and feeding intolerance (OR, 2.95; 95% CI, 1.67-5.21). CONCLUSIONS AND RELEVANCE: All current WHO IMCI clinical signs were significantly associated with mortality or culture-confirmed sepsis. Several signs not in IMCI were identified that may improve identification of life-threatening illness in young infants in resource-limited settings where clinical sign algorithms are the primary diagnostic tool.

BACKGROUND: Sepsis is a leading cause of hospitalisation and mortality, particularly among older adults with multiple chronic conditions. While comorbidities are known to influence outcomes, the role of chronic medication use before sepsis onset remains underexplored. This study aimed to evaluate the impact of baseline health status and chronic treatments on sepsis-related mortality. METHODS: A retrospective population-based cohort study was conducted using linked administrative data from the Catalan Health System. Adults hospitalised with sepsis across 65 public hospitals in Catalonia during 2018-2019 were included. Baseline morbidity was assessed using the Adjusted Morbidity Groups (GMA) tool. Chronic medication use was defined as having received six or more prescription fills of a drug class in the 8 months prior to admission. The primary outcome was in-hospital mortality. RESULTS: Among 59,578 sepsis patients (mean age 75.4 years), the in-hospital mortality rate was 18.5%. Most infections were community-acquired (88%) and associated with renal (58.3%) or cardiovascular (25.7%) dysfunction. The cohort had high comorbidity rates, with a GMA of 37.3, high level of dependency on health services; and high baseline health expenditure. Chronic use of statins, corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs), was observed in 28.5%, 5.6%, and 2.3% of patients respectively. Patients with high or very high GMA scores had the highest mortality rates. In multivariable analysis, chronic statin use was associated with lower odds of death (OR 0.782; 95% CI: 0.740-0.825), while corticosteroid (OR 1.191, 95% CI 1.085-1.306) and NSAID use (OR 1.415, 95% CI 1.226-1.632) were linked to increased mortality. Other risk factors included advanced age, active cancer, cirrhosis, and bloodstream infection. CONCLUSION: In this large population-based study, baseline comorbidities and chronic treatments significantly influenced sepsis outcomes. Statin use was associated with lower in-hospital mortality, whereas corticosteroids and NSAIDs were linked to worse prognosis. The GMA score proved useful in stratifying patient risk and may help to inform clinical decision-making and resource planning. ClinicalTrials.gov: NCT06354452.

IMPORTANCE: Extraintestinal invasive Escherichia coli infections are a leading cause of sepsis and hospitalization, further complicated by increasing rates of antimicrobial resistance. OBJECTIVE: To describe the US epidemiology of invasive E coli infections and their clinical and molecular features. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used active laboratory- and population-based surveillance data from 9 US sites with a total population of more than 7.2 million people for invasive E coli in normally sterile body sites, collected from June to August 2023 from medical records and isolate characterization. Data were analyzed from November 2023 to February 2024. EXPOSURES: Laboratory-confirmed identification of any E coli organism isolated from a normally sterile body site obtained from a resident of the surveillance area. MAIN OUTCOMES AND MEASURES: Outcomes of interest were population-based and site-specific incidence rate estimates of E coli infections, demographic and clinical characteristics, antimicrobial susceptibility profiles, and predicted O serotypes by in silico serotyping. RESULTS: Among 1345 cases of E coli infection in 1334 unique case-patients, the median (IQR) age was 68 (55-79) years, and 762 case-patients (57.1%) were female; 1223 infections (90.9%) were from blood and 122 infections (9.1%) were from other sterile sites. The overall estimated annual incidence rate was 74.7 per 100 000 population (surveillance site range, 51.4-96.0 per 100 000 population). Estimated incidence rates were higher among cases in patients aged 60 years or older compared with younger patients (225.0 vs 30.6 per 100 000 population), although rates were similar for females and males aged 60 years or older (224.5 vs 224.0 per 100 000 population). The most common underlying medical condition reported was diabetes (457 patients [34.0%]). Pyelonephritis (267 infections [19.9%]) and lower urinary tract infections (495 infections [36.8%]) were the most frequently associated infection types. In total, 1279 cases (95.1%) were hospitalized for less than 30 days after isolate collection; 106 case-patients (7.9%) died. Overall, 185 infections (13.8%) were due to extended-spectrum β-lactamase-producing E coli; 275 of 1061 isolates (25.9%) were resistant to ciprofloxacin and 370 of 1286 (28.8%) were resistant to trimethoprim-sulfamethoxazole. Of 846 sequenced isolates, the most prevalent O serotypes were O25B (137 isolates [16.2%]), O2 (93 isolates [11.0%]), and O6 (84 isolates [9.9%]). CONCLUSIONS AND RELEVANCE: This cohort study using population-based public health surveillance data identified a substantial burden of invasive E coli disease, especially in older people, with high rates of antimicrobial resistance. These results can help inform national public health prevention efforts.