INTRODUCTION

Neonatal sepsis is a significant cause of morbidity and mortality, particularly among preterm infants, and remains a pressing global health concern. Early-onset neonatal sepsis is particularly challenging to diagnose due to its nonspecific clinical presentation, necessitating effective and timely diagnostic tools to reduce adverse outcomes. Traditional methods, such as microbial cultures, are slow and often unavailable in resource-limited settings. This study aimed to develop a robust multivariable risk prediction model tailored to improve early detection of Early Onset Sepsis (EOS) among preterm infants in the Philippines.

We conducted a retrospective analysis at a tertiary hospital in the Philippines using data from 1,354 preterm infants admitted between January 2019 and June 2024. Logistic regression models were employed, and predictors were selected through reverse stepwise elimination. Two scoring methods were developed: one based on beta coefficients divided by standard errors and another standardized to a total score of 100. The models were validated using Receiver Operator Characteristic curve analysis.

Version 1 of the scoring model demonstrated an Area Under the Curve (AUC) of 0.991, with a sensitivity of 90.91% and a specificity of 98.10%. Version 2 achieved an AUC of 0.999, with a sensitivity of 96.4% and a specificity of 92.44%.

The developed models provide a reliable, region specific tool for early detection of neonatal sepsis. Further validation across diverse populations and the integration of emerging diagnostic technologies, such as biomarkers and artificial intelligence, are warranted to enhance their applicability and accuracy.

BACKGROUND

Sepsis is a life-threatening organ dysfunction in response to an infection, and immediate administration of the first antibiotic dose, along with other resuscitative efforts, improves patient outcomes. This paved the way for the development of evidence-based sepsis pathways in different health institutions.

This study aims to assess the process of initial antibiotic therapy, from the time the loading dose of antibiotic was ordered to the time it was administered, for adult patients with sepsis admitted at the Emergency Department (ED) of the University of the Philippines – Philippine General Hospital (UP-PGH).

In phase 1 of the study, a review of medical records was done to identify all adult patients diagnosed with sepsis in the ED from February 1 to August 31, 2022. A variant of time-motion analysis was used wherein three points in the sepsis pathway were identified: the t ime of diagnosis of sepsis/first chart order of antibiotics (point A), the time the chart order was noted by the nurse-in-charge (point B), and the documented time of f irst dose administration (point C). The mean and median duration (in hours) were then computed between these points. As an additional aim, we briefly presented the outcome of the population used. In phase 2, individual interviews and focused group discussions were done, involving key medical personnel in the sepsis pathway: physicians, nurses, pharmacists, and utility personnel. The data transcribed from these interviews was analyzed through a thematic examination.

A total of 508 adult patients were diagnosed with sepsis on record review, 442 of whom met the inclusion criteria. The median time it took for the nursein-charge to acknowledge the antibiotic order (points A to B) is 0.73 hours (IQR 0.27-1.7). Meanwhile, the median time between acknowledgment of the order to administration of antibiotics is 1.94 hours (IQR 0.83-6.63). More importantly, the median time from diagnosis-to-first dose (points A to C) is 3.53 hours (IQR 1.59–7.96), while the corresponding mean duration is 5.72 hours. In all cases, 44.6% and 12.4% of loading doses were given within three hours and within one hour after diagnosis, respectively. The all-cause mortality of all qualified cases was 64.7%. A total of 28 key medical personnel were recruited for phase 2. Issues regarding governance, information systems, finances, service delivery, and human resources were identified. In particular, the electronic chart system, a more stable supply of antibiotics, and the new pharmacy at the ER helped facilitate antibiotic delivery. Lack of personnel, gaps in information, and repetitive paperwork were cited as areas for improvement in the existing system.

In more than half of the study population, the target time from diagnosis to loading dose of at least 1 hour was not reached. The significant delays in sepsis treatment call for system-wide improvements to hasten the process of antibiotic delivery and reduce the poor outcomes associated with sepsis.

Early secreted antigenic target of 6 kDa protein (ESAT-6) is the major virulence factor of Mycobacterium tuberculosis (MTB), which can resist the clearance of MTB in bodies by inhibiting macrophage phagocytosis and autophagy reaction, thus impeding the immune defense function of the body against MTB infection. In addition, ESAT-6-induced apoptosis of macrophage and massive necrosis of innate immune cells can foster MTB proliferation and colonization, leading to systemic MTB infection. Moreover, ESAT-6 hampers the protective immune response of Th1 cells, reducing the secretion of pro-inflammatory cytokines and contributing to immune dysfunction, thus accelerating the course of MTB infection. During the process, the high immunogenicity of ESAT-6 can be leveraged as a dominant antigen in the development of new TB vaccines, making it a promising candidate with broad prospects for further development.
Humans ; Mycobacterium tuberculosis ; Vaccines ; Cytokines ; Apoptosis ; Autophagy ; Sepsis

OBJECTIVE: To examine the therapeutic effect of Fangji Fuling Decoction (FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo experiments. METHODS: A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide (LPS). RAW264.7 cells were stimulated by 250 ng/mL LPS to establish an in vitro cell model. Network pharmacology analysis identified the key molecular pathway associated with FFD in sepsis. Through ectopic expression and depletion experiments, the effect of FFD on multiple organ damage in septic mice, as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A (MAPK14/FOXO3A) signaling pathway, was analyzed. RESULTS: FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro (P<0.05). Network pharmacology analysis showed that FFD could regulate the MAPK14/FOXO signaling pathway during sepsis. As confirmed by in vitro cell experiments, FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation (P<0.05). Furthermore, FFD inhibited the MAPK14/FOXO3A signaling pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice (P<0.05). CONCLUSION FFD could ameliorate the LPS-induced inflammatory response in septic mice by inhibiting the MAPK14/FOXO3A signaling pathway.
Mice ; Animals ; Mitogen-Activated Protein Kinase 14/metabolism* ; Wolfiporia ; Lipopolysaccharides/pharmacology* ; Sepsis/complications* ; Signal Transduction ; Inflammation/drug therapy* ; Oxygen Radioisotopes

Objective: This study aims to assess the correlation of ferritin serum level and PELOD-2 score, and determine the effectiveness of ferritin serum level as early indicator of organ dysfunction. Methods: This was a cross-sectional study carried out to pediatric patients with sepsis in the Pediatric Intensive Care Unit Haji Adam Malik and Universitas Sumatera Utara hospital from June 2021 – January 2022. Complete blood work was done, and ferritin serum level and PELOD-2 score were measured on the first and third day of hospital stay of all the sixty participants aged 1-18 years old with sepsis. The correlation was measured using Spearman test, with p<0.05 indicating a significant correlation. Results: The median level of serum ferritin level was 480 (24.7 – 22652) ng/mL. There were 20% patients with ferritin level <200 ng/mL, 26.7% with ferritin level 200-500 ng/mL, and 53.3% patients with ferritin >500 ng/mL. The median score of PELOD-2 was 4. There was a significant correlation of serum ferritin and PELOD-2 score on day 1 of hospital stay. Conclusion The ferritin serum level is effective as an early indicator of organ dysfunction until PELOD-2 score is established. There is a positive correlation between serum ferritin and PELOD-2 score. There is a link between elevated ferritin and worse disease prognosis.
Ferritins ; Sepsis ; Infections

BACKGROUND

Many neonates are started on antibiotics even if they are well-appearing due to presence of risk factors. The Early Onset Sepsis (EOS) calculator is a web-based tool that calculates for composite risk scores for sepsis and limits empiric antibiotic therapy only as necessary.

This study aims to determine if there is a significant difference between the proportion of neonates recommended for antibiotics using the EOS calculator and AAP guidelines for neonatal sepsis.

This is a retrospective hospital-based cohort study where review of charts of neonates ≥34 weeks age of gestation (AOG) who were started on intravenous antibiotics within 72 hours of life for the period of 2019 to 2023 was done. Peripartum risk factors were used to calculate for EOS risk score and categorize those to be recommended for treatment using the score as well as the AAP guidelines. Newborns with growth on blood culture were identified. McNemar’s test was used to determine if there is a significant difference between the two proportions. Sensitivity and specificity of both tools were calculated.

Out of 916 neonates, 345 (38%) and 469 newborns (51%) were advised empiric antibiotic therapy by the EOS calculator and AAP 2018 guidelines respectively. A McNemar Test revealed a significantly lower proportion of neonates recommended for antibiotic treatment using the EOS calculator (p < 0.001). Blood culture was taken from 208 newborns and six had positive isolates. Both the EOS calculator and AAP guidelines had 100% sensitivity and recommended antibiotics for these culture-proven sepsis cases. EOS calculator had a higher specificity (45% vs 32%).

The EOS calculator as a risk assessment tool could significantly reduce use of antibiotics. The proportion of those who were recommended for antibiotics using the EOS calculator was significantly lower by 13% (p value =
Sepsis ; Infant, Newborn

Background: Sepsis is a life-threatening organ dysfunction in response to an infection, and immediate administration of the first antibiotic dose, along with other resuscitative efforts, improves patient outcomes. This paved the way for the development of evidence-based sepsis pathways in different health institutions. Objectives: This study aims to assess the process of initial antibiotic therapy, from the time the loading dose of antibiotic was ordered to the time it was administered, for adult patients with sepsis admitted at the Emergency Department (ED) of the University of the Philippines – Philippine General Hospital (UP-PGH). Methods: In phase 1 of the study, a review of medical records was done to identify all adult patients diagnosed with sepsis in the ED from February 1 to August 31, 2022. A variant of time-motion analysis was used wherein three points in the sepsis pathway were identified: the t ime of diagnosis of sepsis/first chart order of antibiotics (point A), the time the chart order was noted by the nurse-in-charge (point B), and the documented time of f irst dose administration (point C). The mean and median duration (in hours) were then computed between these points. As an additional aim, we briefly presented the outcome of the population used. In phase 2, individual interviews and focused group discussions were done, involving key medical personnel in the sepsis pathway: physicians, nurses, pharmacists, and utility personnel. The data transcribed from these interviews was analyzed through a thematic examination. Results: A total of 508 adult patients were diagnosed with sepsis on record review, 442 of whom met the inclusion criteria. The median time it took for the nursein-charge to acknowledge the antibiotic order (points A to B) is 0.73 hours (IQR 0.27-1.7). Meanwhile, the median time between acknowledgment of the order to administration of antibiotics is 1.94 hours (IQR 0.83-6.63). More importantly, the median time from diagnosis-to-first dose (points A to C) is 3.53 hours (IQR 1.59–7.96), while the corresponding mean duration is 5.72 hours. In all cases, 44.6% and 12.4% of loading doses were given within three hours and within one hour after diagnosis, respectively. The all-cause mortality of all qualified cases was 64.7%. A total of 28 key medical personnel were recruited for phase 2. Issues regarding governance, information systems, finances, service delivery, and human resources were identified. In particular, the electronic chart system, a more stable supply of antibiotics, and the new pharmacy at the ER helped facilitate antibiotic delivery. Lack of personnel, gaps in information, and repetitive paperwork were cited as areas for improvement in the existing system. Conclusion In more than half of the study population, the target time from diagnosis to loading dose of at least 1 hour was not reached. The significant delays in sepsis treatment call for system-wide improvements to hasten the process of antibiotic delivery and reduce the poor outcomes associated with sepsis.
Human ; sepsis

OBJECTIVE: This paper aimed to describe the clinical profile and short-term clinical outcomes of children with Acute Kidney Injury (AKI) requiring hemodialysis in a tertiary pediatric hospital. MATERIALS AND METHODS: A retrospective cohort on in-patients who received hemodialysis treatments at our institution was performed. Medical charts of patients admitted between July 2018 and July 2023 were retrieved. Demographic data, clinical profiles and subsequent outcomes in terms of mortality and recovery or non-recovery from AKI were recorded. RESULTS: After meeting the inclusion and exclusion criteria, 129 patients were included in the study‘s statistical analysis. There was an even distribution between males and females. The average age of treated patients was 10 years old (SD ± 4.3). The average weight of patients was 35kg (SD ± 16.9). The most common diagnosis of patients was severe dengue (21.7%), followed by severe sepsis (14.7%). More than half of patients (51.9%) had an existing co-morbidity, of which Systemic Lupus Erythematosus (22.4%) and solid tumors (22.4%) were most common. The most common indication for hemodialysis was uremia (52.7%). In terms of short-term outcome, majority of patients died during the same admission (56.5%), while 31 patients (24.0%) recovered. CONCLUSION The clinical profile of patients who underwent hemodialysis treatments for AKI were comparable to international data. The study did not differentiate deaths from AKI or underlying illness, but demonstrated a higher mortality rate compared to other existing studies. This study is the first known local paper to describe the profile and outcomes of children who received hemodialysis for AKI.
Hemodialysis ; Renal Dialysis ; Severe Sepsis ; Sepsis ; Severe Dengue

Background: The quick Sequential Organ Failure Assessment (qSOFA) score was introduced by Sepsis-3 or the Third International Consensus Definitions for Sepsis and Septic Shock to help physicians in identifying patients outside the intensive care unit with suspected infection who are at high risk for in-hospital mortality. However, sepsis is not a homogenous entity and the outcomes vary based on several factors. This study aimed to determine the predictive accuracy of qSOFA in identifying those at high-risk of in-hospital mortality among adult patients with sepsis secondary to urinary tract infection. Methodology: A retrospective cohort study was done involving the use of qSOFA score to predict in-hospital mortality of adult patients with a diagnosis of sepsis secondary to urinary tract infection, admitted in the hospital from January 1, 2013 to December 31, 2020. qSOFA is computed based on the following independent variables: systolic blood pressure (SBP), respiratory rate (RR), and Glasgow Coma Scale (GCS). Results: Of the 128 charts retrieved, 121 patients were included in the study. Fifteen (12.40%) died while 106 (87.60%) survived. Mean age was 60.76 years old, with more females (71.90%) than males (28.10%). Hypertension and Diabetes Mellitus Type 2 were the most frequent comorbidities. Complicated UTI was the most frequent source of infection. Mean length of stay was 8.29 days. Forty (33.06%) patients had qSOFA ≥ 2 wherein 11 (27.5%) died. Diagnostic performance results revealed: sensitivity (73.33%), specificity (72.64%), positive (27.5%) and negative (95.06%) predictive values, and positive (2.68) and negative (0.37) likelihood ratios. qSOFA accuracy was 72.73% with an AUROC of 0.76. Conclusion Among the admitted adult patients with sepsis secondary to a UTI, qSOFA had a good prognostic accuracy for in-hospital mortality.
Sepsis ; Urinary Tract Infections ; Hospital Mortality

Humans ; Young Adult ; Fusobacterium necrophorum ; Pharyngitis/microbiology* ; Streptococcal Infections ; Sepsis/diagnosis*