Daily Sepsis Research Analysis

BACKGROUND: Timely antibiotics are key determinants of sepsis survival and are presumed to be especially critical in immunocompromised patients. However, evidence supporting this assumption is limited. METHODS: We identified all adults treated for suspected sepsis in the emergency departments of nine U.S. hospitals, 2015-2024. We identified immunocompromised patients using diagnosis codes, supplemented with clinical data to define a severely immunocompromised subgroup. We used multivariable logistic regression to assess associations between time-to-antibiotics (primary analysis: 1-3 vs 0-1h; secondary analysis: 3-6 vs 0-3h) and in-hospital mortality, stratified by immune status and sepsis severity. RESULTS: Among 39,842 hospitalizations with suspected sepsis, 20,721 occurred in non-immunocompromised patients and 19,121 in immunocompromised (2,283 severe). Overall, antibiotic administration at 1-3 vs 0-1h was associated with increased mortality in non-immunocompromised (OR 1.33, 95% CI 1.12-1.59) but not immunocompromised patients (OR 1.08, 95% CI 0.94-1.25). Increased risk was limited to septic shock, where delayed antibiotics were associated with higher mortality in both non-immunocompromised (OR 1.41, 95% CI 1.12-1.76) and immunocompromised patients (OR 1.21, 95% CI 1.002-1.47). In contrast, no association was observed in sepsis without shock regardless of immune status, including for antibiotic administrations at 3-6 vs 0-3h. Effect estimates were similar for mild-moderate and severe immunocompromise. CONCLUSIONS: Short delays in antibiotic administration were associated with increased mortality in septic shock but not in sepsis without shock, with no evidence of greater vulnerability among immunocompromised patients. These findings suggest antibiotic urgency should be guided primarily by clinical severity rather than immune competence.

IMPORTANCE: While skin cleansing with octenidine has shown promise in preventing health care infections, its effectiveness for preventing late-onset sepsis in neonates is unproven. OBJECTIVE: To compare the incidence rates of late-onset sepsis (LOS) in neonates admitted to the neonatal intensive care unit (NICU) who were cleansed daily with octenidine wipes vs those cleansed with sterile water. DESIGN, SETTING, AND PARTICIPANTS: This single-center, open-label, parallel-group randomized clinical trial was conducted in the level II and level III NICUs of a tertiary care hospital in India between September 1, 2023, and August 31, 2025. All neonates admitted to the NICU within 48 hours of birth without early-onset sepsis or preexisting skin lesions and not discharged from the NICU before 72 hours were included. INTERVENTION: Neonates were assessed and randomly assigned to receive once-daily full-body cleansing with either 0.1% octenidine dihydrochloride antimicrobial wipes or sterile water applied with sterile gauze until discharge, transfer to another facility, or death. Separate wipes or gauze were used for the upper and lower body, with genital cleansing performed last. No rinsing was performed after application to allow residual antimicrobial activity. Skin condition was assessed daily using the Neonatal Skin Condition Score. MAIN OUTCOMES AND MEASURES: The primary outcome was LOS rates (occurring >72 hours after birth through 28 days of life) among neonates cleansed with octenidine wipes vs with sterile water until discharge or transfer to the maternal bedside, assessed using relative risk (RR). Time to LOS was compared using the hazard ratio (HR). All cases were independently adjudicated by 2 blinded neonatologists. Secondary outcomes included LOS at 7 and 14 days, all-cause mortality, length of NICU stay, and adverse skin reactions. RESULTS: Of 530 neonates eligible for intention-to-treat analysis (299 males [56.4%]; median gestational age, 35.0 weeks [IQR, 32.0-37.0 weeks]), LOS occurred in 39 of 266 (14.7%) in the octenidine group and 34 of 264 (12.9%) in the sterile water group (RR, 1.10; 95% CI, 0.75-1.70; P = .60). Time to LOS was similar between groups (HR, 1.11; 95% CI, 0.71-1.78; P = .63). Secondary outcomes for the octenidine vs sterile water interventions were similar, including LOS by 7 days (24 neonates [9.0%] vs 23 [8.7%]) and 14 days (15 [5.6%] vs 11 [4.2%]), all-cause mortality (12 [4.5%] vs 5 [1.9%]), and length of NICU stay in days (median, 11.0 [IQR, 6.0-21.0] vs 10.0 [IQR, 6.0-19.0]). Adverse skin reactions occurred in 15 neonates (5.6%) in the octenidine group and 16 (6.1%) in the sterile water group (RR, 1.10; 95% CI, 0.55-2.10). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, daily skin cleansing with octenidine wipes showed no evidence of reducing the incidence of LOS in NICU neonates compared with sterile water, suggesting that infection prevention strategies should focus on multimodal interventions rather than relying solely on skin cleansing. TRIAL REGISTRATION: CTRI Identifier: CTRI/2023/08/056562.

BACKGROUND: In sepsis-induced immune dysregulation, monocytes contribute critically through their dual pro-inflammatory and immunosuppressive functions. Leading to multi-organ injury, the lungs are the most vulnerable initial target, dictating clinical outcomes. Thus, studying monocyte dynamics is essential to understand sepsis-induced acute lung injury (ALI) pathophysiology. METHODS: We analyzed publicly available mouse-derived single-cell RNA sequencing (scRNA-seq) and spatial transcriptomic (ST) datasets for sepsis-induced ALI from the GEO database. Computational characterization of monocyte heterogeneity included cell-cell communication, single-cell trajectory analysis, and functional enrichment analyses to identify subtype-specific signaling and injury-related signatures. Spatial mapping further confirmed monocyte subtype localization. Experimental validation was performed in a mouse model of sepsis-induced ALI established by intraperitoneal LPS injection. Histological evaluation, immunohistochemistry, immunofluorescence, Quantitative real-time PCR, and Western blot were integrated to verify the spatial distribution of the Mono-S100A4 subset and its associated pathway molecules. RESULTS: Clustering analysis revealed a restructured immune landscape in septic ALI, characterized by both cellular heterogeneity and prominent monocyte accumulation. Spatial transcriptomics revealed that inflammatory infiltration mediated by monocytes and other immune cells predominantly localized to bronchial and bronchiole regions. Monocyte heterogeneity analysis identified a distinct Mono-S100A4 subset, which exhibited enhanced intercellular communication capacity, influencing other subclusters through the (MIF)-(CD74+CD44) axis. KEGG and GSEA analyses of Mono-S100A4 revealed significant enrichment in the IL-17 signaling pathway and Th17 cell differentiation, suggesting a potential role in exacerbating inflammatory responses. In vivo experiments revealed a significant upregulation in both the mRNA and protein expression levels of S100A4, IL-17A, MIF, and CD74 in the lung tissue of ALI mice. CONCLUSION: The Mono-S100A4 subset is strongly associated with the activation of the Th17 signaling pathway via the MIF-(CD74+CD44) axis, and this correlative relationship supports a potential pathogenic role of Mono-S100A4 in sepsis-induced ALI, which forms a key hypothesis to be validated by subsequent functional experiments.