Daily Sepsis Research Analysis
Analyzed 33 papers and selected 3 impactful papers.
Summary
Across three high-impact studies, earlier antibiotics in neutropenic sepsis were linked to lower in-hospital mortality, sodium-glucose cotransporter 2 inhibitors in peritoneal dialysis were associated with fewer infections (including sepsis) and deaths, and prenatal/childhood acid-suppressive medications correlated with increased serious infections and sepsis in children. Together, these findings emphasize timely therapy, medication stewardship across the life course, and potential repurposing of cardiometabolic drugs to reduce infectious risk.
Research Themes
- Timeliness of antimicrobial therapy in high-risk sepsis phenotypes
- Medication stewardship and infection risk across prenatal to childhood periods
- Repurposing cardiometabolic therapies to reduce infectious complications in dialysis
Selected Articles
1. Impact of Time to Antibiotics on In-hospital Mortality in Neutropenic Sepsis: A Prospective Multicenter Cohort Study.
In a prospective multicenter cohort of 942 neutropenic sepsis patients, time to antibiotics under 1 hour was associated with lower in-hospital mortality than 1–3 hours or ≥3 hours after IPTW adjustment. Effects were stronger in septic shock and hematologic malignancy; elevated lactate emerged as a potential effect modifier in causal forest analyses.
Impact: Provides high-quality prospective evidence quantifying the mortality penalty for antibiotic delays specifically in neutropenic sepsis and identifies subgroups most sensitive to timing.
Clinical Implications: Implement processes to deliver first-dose antibiotics within 1 hour for neutropenic sepsis, prioritize rapid administration in septic shock and hematologic malignancy, and consider lactate to triage urgency.
Key Findings
- Delays in antibiotics (≥3 h) increased in-hospital mortality vs <1 h (OR 1.50; 95% CI 1.22–1.85).
- Intermediate delays (1–3 h) also raised mortality (OR 1.26; 95% CI 1.04–1.53).
- Stronger associations were observed in septic shock and hematologic malignancy subgroups.
- Causal forest suggested elevated lactate as a possible effect modifier for timing benefit.
Methodological Strengths
- Prospective multicenter design with predefined TTA categories.
- Causal inference techniques (IPTW) and causal forest to explore heterogeneity.
Limitations
- Observational design leaves potential residual confounding.
- Timing measurements and workflow factors may introduce misclassification; no long-term outcomes reported.
Future Directions: Test implementation strategies to consistently achieve <1-hour antibiotics in neutropenic sepsis and validate phenotypic modifiers (e.g., lactate) in pragmatic trials.
OBJECTIVE: Neutropenic sepsis is a high-risk form of sepsis associated with rapid deterioration and high mortality. Although early antibiotic administration is recommended, the benefit of shorter time to antibiotics (TTA) remains uncertain. This study aimed to determine the relationship between TTA and in-hospital mortality for patients with neutropenic sepsis and to identify specific phenotypes most vulnerable to TTA delays. DESIGN: Prospective, multicenter observational cohort study. SETTING: Twenty tertiary or university-affiliated hospitals in South Korea. PATIENTS: In this prospective multicenter cohort study, we analyzed 942 patients with sepsis and neutropenia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: TTA was categorized into three groups: less than 1 hour (early), 1-3 hours (intermediate), and greater than or equal to 3 hours (delayed). We used inverse probability of treatment weighting (IPTW) with logistic regression to evaluate the association between TTA and in-hospital mortality and a causal forest model to identify characteristics associated with the effect of longer TTA. Overall, 211, 531, and 200 patients belonged to the early, intermediate, and delayed groups, respectively. In IPTW-weighted logistic regression, odds ratio (OR) for in-hospital mortality was significantly higher in the delayed (OR: 1.50; 95% CI, 1.22-1.85; p < 0.001) and intermediate groups (OR: 1.26; 95% CI, 1.04-1.53; p = 0.021) than in the early group. The association between longer TTA and mortality was stronger among patients with septic shock and among those with hematologic malignancy in both models. The causal forest further identified elevated lactate as a potential effect modifier, indicating greater estimated benefit from earlier TTA; however, interaction tests in the weighted logistic model were not significant. CONCLUSIONS: Delayed antibiotic administration was associated with increased in-hospital mortality among patients with neutropenic sepsis. The impact on in-hospital mortality is heterogeneous, varying by patient characteristics, particularly septic shock and hematologic malignancy.
2. Prenatal and/or childhood acid-suppressive medication use and risk of serious infections in children: A retrospective analysis of Taiwanese medical claims data.
In a nationwide active-comparator cohort, prenatal and childhood exposure to PPIs/H2RAs was associated with increased risks of serious infections, including sepsis. Joint exposure during both periods conferred the highest risk (e.g., sepsis AHR 1.62), and findings were consistent across PPI and H2RA subgroups.
Impact: Establishes life-course associations between acid-suppressive therapy and serious pediatric infections, including sepsis, at national scale with an active-comparator design.
Clinical Implications: Reassess indications and duration of PPI/H2RA use in pregnancy and early childhood; favor non-pharmacologic measures and step-down strategies; incorporate infection risk counseling into shared decision-making.
Key Findings
- Prenatal PPI/H2RA exposure increased overall serious infection risk vs antacids (AHR 1.09; 95% CI 1.06–1.12).
- Prenatal exposure raised specific infection risks, including sepsis (AHR 1.21), pneumonia (AHR 1.10), and gastroenteritis (AHR 1.12).
- Childhood exposure also increased risks; combined prenatal+childhood exposure produced the highest risks (e.g., sepsis AHR 1.62).
- Results were consistent when analyzing PPIs and H2RAs separately.
Methodological Strengths
- Nationwide active-comparator cohort using complete claims coverage with very large sample size.
- Adjusted Cox models with multiple specific infection outcomes including sepsis; subgroup consistency across PPI/H2RA.
Limitations
- Observational design with potential residual confounding and indication bias.
- Exposure and outcome misclassification possible in claims; timing/dose details limited in abstract.
Future Directions: Mechanistic studies on gastric acid suppression, microbiome, and immune development; pragmatic de-implementation and dose-minimization trials in pregnancy/infancy.
BACKGROUND: Recent studies suggest an increased risk of serious infections associated with proton pump inhibitor (PPI) use in young children, but no study simultaneously examined the impact of acid-suppressive medication (ASM) use during pregnancy and childhood on infection risk in children. This study aimed to investigate the associations between prenatal and/or childhood exposure to ASMs and serious infections in children. METHODS: A national cohort study was conducted based on the entire medical claims data in Taiwan, comparing prenatal and/or childhood exposure to PPIs or histamine-2 receptor antagonists (H2RAs) with antacid exposure in an active-comparator design. We quantified the risks of hospitalization for overall serious infection and specific infections, including sepsis, acute bronchiolitis or bronchitis, pneumonia, acute gastroenteritis, pyelonephritis, cellulitis or soft-tissue infection, meningitis or encephalitis, and septic arthritis or osteoarthritis, among children with prenatal and/or childhood exposure to PPIs or H2RAs. Adjusted hazard ratios (AHRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazard models. RESULTS: Among 195,377 mother-child pairs prenatally exposed to PPIs or H2RAs (13.39% of the prenatal cohort) and 1,263,741 pairs exposed to antacids, prenatal exposure to PPIs or H2RAs was associated with an increased risk of overall serious infection compared with antacid exposure (AHR: 1.09; 95% CI: 1.06-1.12), as well as specific infections, including sepsis (AHR: 1.21; 95% CI: 1.03-1.12), acute bronchiolitis or bronchitis (AHR: 1.07; 95% CI: 1.03-1.11), pneumonia (AHR: 1.10; 95% CI: 1.04-1.15), acute gastroenteritis (AHR: 1.12; 95% CI: 1.06-1.18), and pyelonephritis (AHR: 1.10; 95% CI: 1.02-1.19). Subgroup analyses demonstrated consistent results for PPI and H2RA exposure when analyzed separately. Childhood exposure to PPIs or H2RAs was also associated with increased risks of serious infections, with the highest risks generally observed among children exposed during both prenatal and childhood periods (AHR 1.12 for overall serious infection; AHR 1.62 for sepsis; AHR 1.29 for acute bronchiolitis or bronchitis; AHR 1.06 for pneumonia; AHR 1.30 for acute gastroenteritis; and AHR 1.24 for pyelonephritis). CONCLUSIONS: This nationwide cohort study provides real-world evidence of an association between prenatal and childhood exposure to PPIs or H2RAs and an increased risk of serious infections in children.
3. Safety and clinical impact of SGLT2 inhibitor in patients undergoing peritoneal dialysis: a target-trial emulation study.
In a large target-trial emulation with propensity-matched PD patients, SGLT2 inhibitor use was associated with reduced all-cause mortality and lower risks of sepsis, severe sepsis, pneumonia, and PD-associated peritonitis over a median 0.79-year follow-up, without excess safety signals.
Impact: Suggests a potentially practice-changing infection and survival benefit of SGLT2 inhibitors in PD, an infection-prone population lacking trial data.
Clinical Implications: Consider SGLT2 inhibitors in PD patients with type 2 diabetes while awaiting RCTs, integrate infection risk reduction into shared decision-making, and monitor standard safety parameters.
Key Findings
- After matching (n=2,749 per group), SGLT2i use lowered all-cause mortality (aHR 0.818).
- Sepsis risks decreased with SGLT2i: severe sepsis (aHR 0.802), sepsis (aHR 0.661), pneumonia (aHR 0.664).
- PD-associated peritonitis risk was markedly reduced (aHR 0.340).
- No significant increase in diabetic ketoacidosis, hypoglycemia, genital infection, volume depletion, or amputation.
Methodological Strengths
- Target-trial emulation with propensity score matching in a large, federated EHR dataset.
- Multiple clinically relevant infectious outcomes with adjusted hazard ratios and safety assessment.
Limitations
- Observational emulation susceptible to residual confounding and selection biases.
- Short median follow-up (0.79 years) and potential misclassification of exposure/adherence in EHR data.
Future Directions: Randomized trials in PD to confirm infection and survival benefits and mechanistic studies on glycemic-independent immunomodulatory effects.
OBJECTIVE: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in chronic kidney disease, but their effects in peritoneal dialysis (PD) patients who are infection prone, remain unclear. STUDY DESIGN: The study design of this research is target-trial emulation using the global federated electronic health record database. Adults (18-90 years) with type 2 diabetes on PD for ≥3 months between February 2015 and June 2025 were included. Propensity score matching balanced SGLT2i and nonuser. Primary outcomes were all-cause mortality, severe sepsis, sepsis, and pneumonia; secondary outcomes included major adverse cardiovascular events (MACE) and PD-associated peritonitis. RESULTS: Among 29 529 eligible patients, 2815 (9.5%) received SGLT2i. After matching, 2749 patients were retained in each group with well-balanced baseline characteristics. Over a median follow-up of 0.79 years, SGLT2i users were associated with lower risks of all-cause mortality [adjusted hazard ratio (aHR) 0.818], severe sepsis (aHR 0.802), sepsis (aHR 0.661), pneumonia (aHR 0.664), and PD-associated peritonitis (aHR 0.340). MACE was not significantly different (aHR 0.798). SGLT2i was not associated with increased diabetic ketoacidosis, hypoglycemia, genital infection, volume depletion, or amputation. CONCLUSIONS: In this large real-world PD cohort with type 2 diabetes, SGLT2i use was associated with lower risks of death and major infections without safety concerns, supporting potential benefit pending randomized trial confirmation.