Daily Sepsis Research Analysis
Three studies advance sepsis care across prevention, treatment optimization, and diagnostics. A meta-analysis of 14 RCTs shows colostrum oral immune therapy reduces late-onset sepsis, necrotizing enterocolitis, mortality, and time to full feeds in very low birth weight infants. Prospective PK data reveal subtherapeutic meropenem exposure is common in pediatric septic shock, supporting early therapeutic drug monitoring; a diagnostic study finds heparin-binding protein outperforms PCT and other bi
Summary
Three studies advance sepsis care across prevention, treatment optimization, and diagnostics. A meta-analysis of 14 RCTs shows colostrum oral immune therapy reduces late-onset sepsis, necrotizing enterocolitis, mortality, and time to full feeds in very low birth weight infants. Prospective PK data reveal subtherapeutic meropenem exposure is common in pediatric septic shock, supporting early therapeutic drug monitoring; a diagnostic study finds heparin-binding protein outperforms PCT and other biomarkers for bacteremia.
Research Themes
- Neonatal sepsis prevention via colostrum oral immune therapy
- Antibiotic PK/PD and therapeutic drug monitoring in pediatric septic shock
- Biomarker-based rapid identification of bacteremia in sepsis
Selected Articles
1. [Effect of colostrum oral immune therapy on the the clinical outcomes in very low birth weight infants: a Meta analysis].
This meta-analysis of 14 RCTs (n=1,386) shows that colostrum oral immune therapy in very low birth weight infants significantly reduces late-onset sepsis, necrotizing enterocolitis, feeding intolerance, and mortality, and shortens time to full enteral feeds. Findings support COIT as a low-cost, biologically plausible preventive strategy in NICUs.
Impact: Highest-level evidence indicates a scalable intervention can prevent neonatal sepsis and improve survival. It may shift standard care practices for VLBW infants.
Clinical Implications: NICUs should consider implementing standardized COIT protocols for VLBW infants to reduce late-onset sepsis and mortality, with attention to dosing, timing, and hygiene to ensure safety.
Key Findings
- Meta-analysis included 14 RCTs with 1,386 VLBW infants (690 COIT vs 696 control).
- COIT significantly reduced clinical late-onset sepsis incidence.
- COIT decreased necrotizing enterocolitis and feeding intolerance and reduced mortality.
- Time to achieve full enteral nutrition was shortened with COIT.
Methodological Strengths
- Synthesis of randomized controlled trials across multiple databases
- Consistent direction of effect across several clinically important outcomes
Limitations
- Heterogeneity in COIT protocols (timing/dose) and study settings
- Potential publication and language bias; PRISMA adherence not explicitly stated
Future Directions: Conduct pragmatic multicenter trials to standardize COIT regimen and assess safety; perform individual participant data meta-analysis and evaluate long-term neurodevelopment.
OBJECTIVES: To evaluate the effect of colostrum oral immune therapy (COIT) on clinical outcomes in very low birth weight (VLBW) infants. METHODS: A computer-based search was conducted in databases including China National Knowledge Infrastructure, Wanfang Data, Weipu Database, Chinese Biomedical Literature Service System, PubMed, Embase, Web of Science, the Cochrane Library, and CINAHL for randomized controlled trials regarding the application of COIT in VLBW infants published from the establishment of the database to February 2024. Meta analysis was performed using RevMan 5.3 software. RESULTS: A total of 14 randomized controlled trials were included, involving 1 386 VLBW infants, with 690 in the COIT group and 696 in the control group. The results showed that COIT significantly reduced the incidence of clinical late-onset sepsis (LOS) ( CONCLUSIONS: COIT can reduce the incidence rates of LOS, necrotizing enterocolitis, and feeding intolerance, as well as the mortality rate, while also shortening the time to achieve full enteral nutrition in VLBW infants.
2. Subtherapeutic Meropenem Antibiotic Exposure in Children With Septic Shock Assessed by Noncompartmental Pharmacokinetic Analysis in a Prospective Dataset.
In 19 children with septic shock receiving standard meropenem dosing, 53% and 47% failed to meet 70% and 100% fT>MIC targets on day 1, respectively, with augmented renal clearance in 42%. Findings support early therapeutic drug monitoring and ARC surveillance to tailor dosing during the first 72 hours.
Impact: Demonstrates frequent pharmacodynamic target failure under standard dosing in pediatric septic shock, highlighting an actionable need for TDM and dosing individualization.
Clinical Implications: Consider early meropenem TDM and monitoring for augmented renal clearance; reassess dosing daily in the first 72 hours and consider strategies like higher doses or extended/continuous infusion to achieve PD targets.
Key Findings
- Augmented renal clearance was present in 8/19 and acute kidney injury in 3/19 children.
- On PICU day 1, 10/19 and 9/19 failed to meet 70% and 100% fT>MIC targets, respectively.
- Therapeutic exposures associated with positive fluid balance on day 1 and negative by day 3, amid high variability.
- Noncompartmental PK with simulations at 40 and 60 mg/kg/dose informed exposure projections.
Methodological Strengths
- Prospective serial PK sampling over the first 3 PICU days
- Clear pharmacodynamic targets and inclusion of ARC/AKI characterization
Limitations
- Small, single-center cohort without outcome-adjusted dosing interventions
- Limited generalizability; clinical outcomes not powered and MIC assumptions may vary
Future Directions: Randomized or adaptive studies of TDM-guided dosing and extended/continuous infusion; integrate ARC screening algorithms and link PK/PD attainment to clinical outcomes.
OBJECTIVES: To define meropenem plasma concentrations and pharmacodynamic exposure metrics in children with septic shock during the first 3 days of PICU hospitalization. DESIGN: Pharmacokinetic sampling was undertaken in 19 subjects receiving standard meropenem dosing (20 mg/kg/dose, 8 hr) recruited from March 2019 to March 2022. Sampling occurred once each day following meropenem given 24 hours apart, during the first 3 PICU days. Data analysis was completed in 2023 and noncompartmental analysis was performed to assess pharmacodynamic exposure targets for sepsis. Clearance and volume of distribution at 20 mg/kg/dose were used to simulate mean exposures at 40 and 60 mg/kg/dose. SETTING: PICU in a tertiary care center. SUBJECTS: Patients 4 weeks old or older with hypotension requiring fluid resuscitation and vasopressor therapy, receiving meropenem as empiric therapy for sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Augmented renal clearance (ARC) was documented in eight of 19 subjects, previously associated with subtherapeutic plasma concentrations, while three of 19 had acute kidney injury and decreased renal clearance. When assessed by pharmacodynamic exposure targets for sepsis (plasma meropenem concentrations above the minimum inhibitory concentration [MIC] of Pseudomonas aeruginosa for 70% or 100% of the dosing interval), ten of 19 and nine of 19 children, respectively, had subtherapeutic plasma meropenem exposures during PICU day 1, even for pathogens with an MIC considered "susceptible" by U.S. Food and Drug Administration criteria. Therapeutic meropenem pharmacodynamic exposures were associated with a positive 24-hour fluid balance on PICU day 1 and a negative 24-hour fluid balance by day 3, although profound variability was noted in fluid administered and renal output. CONCLUSIONS: Given the variability in meropenem systemic exposure in pediatric septic shock, therapeutic drug monitoring, or monitoring for ARC, is suggested during the first days of hospitalization to allow daily assessments of dosing needs to achieve pharmacodynamic exposure targets for sepsis.
3. Accuracy of blood heparin-binding protein (HBP) for diagnosis bacteremia in patients with sepsis.
In 146 sepsis patients, heparin-binding protein showed superior accuracy for bacteremia (AUC 0.88) compared with PCT (0.78), CRP (0.73), IL-6 (0.59), WBC (0.56), and neutrophils (0.64). A cutoff of 95.69 ng/mL yielded high sensitivity (88.6%) and negative predictive value (89.7%), supporting HBP for early bacteremia screening.
Impact: A readily measurable biomarker outperforms established markers for bacteremia, potentially improving early triage and antimicrobial decision-making in sepsis.
Clinical Implications: In ED/ICU sepsis evaluations, adding HBP to standard labs can improve bacteremia detection; use a rule-out approach given high sensitivity/NPV and combine with clinical assessment and cultures.
Key Findings
- HBP levels were significantly higher in bacteremia (204.13±87.30 ng/mL) versus non-bacteremia (81.43±61.53 ng/mL).
- HBP achieved the highest AUC (0.88) surpassing PCT (0.78), CRP (0.73), IL-6 (0.59), WBC (0.56), and neutrophils (0.64).
- Optimal cutoff 95.69 ng/mL: sensitivity 88.64%, specificity 68.06%, PPV 64.1%, NPV 89.71%.
- HBP correlated moderately with CRP (rho=0.528) while other inter-biomarker correlations were weaker.
Methodological Strengths
- Head-to-head diagnostic accuracy comparison across multiple biomarkers
- Consecutive patient enrollment and ROC-based performance metrics
Limitations
- Single-center observational design without external validation
- Potential spectrum/selection bias; timing of sampling and repeat measures not addressed
Future Directions: Multicenter validation and integration of HBP into sepsis diagnostic algorithms; assess combined scores with PCT/CRP and clinical variables and test impact on antibiotic stewardship and outcomes.
Blood heparin-binding protein (HBP) for diagnosing bacteremia in patients with sepsis has not been fully investigated. This study aims to explore the diagnostic value of blood HBP in predicting bacteremia in patients with sepsis compared with procalcitonin (PCT), Interleukin 6 (IL-6), C-reactive protein (CRP), white blood count (WBC), and neutrophil. In this observational study, we enrolled consecutive 146 patients, who were divided into two groups as the bacteremia group (n = 57) and the control group (n = 89). HBP, PCT, IL-6, CRP, WBC, and neutrophil were measured. The Chi-squared test and Student's t-test were used to compare the baseline characteristics. The area under the receiver operating characteristic curve (AUC) was calculated to describe the diagnostic accuracy of the biomarkers for predicting bacteremia in patients with sepsis. Spearman's correlation was used to analyze associations between the biomarkers. The concentration of HBP (204.13 ± 87.30 ng/mL ) in the bacteremia group was significantly higher than that in the control group (81.43 ± 61.53). HBP achieved the largest AUC for predicting bacteremia, with a value of 0.88 (95% confidence interval [CI], 0.82-0.94 ). This value was higher than those of the other biomarkers: 0.78 (95% CI 0.69-0.86) for PCT, 0.59 (95% CI 0.48-0.70) for IL-6, 0.56 (95% CI 0.45-0.67) for WBC, 0.73 (95% CI 0.64-0.83) for CRP, and 0.64 (95% CI 0.53-0.74) for neutrophil. The best cut-off value of blood HBP for identifying bacteremia was 95.69 ng/mL, with a sensitivity of 88.64%, a specificity of 68.06%, a positive predictive value of 64.1%, and a negative predictive value of 89.71%. A significant association was found between HBP and CRP (Spearman's rho = 0.528, p < 0.01). However, the correlations among PCT, IL-6, WBC, and neutrophil (Spearman's rho < 0.5, p < 0.01) were relatively weak. Blood HBP may be a useful auxiliary diagnostic marker that is preferable over PCT, IL-6, CRP, WBC, and neutrophil in identifying bacteremia in patients with sepsis.