Time to Positivity of Blood Culture as a Predictor of Causative Pathogens and Survival in Neonatal Sepsis: A Retrospective Cohort Study from Indonesia.

Objectives: In the blood culture procedure for neonatal sepsis, time to positivity (TTP) reflects the pathogenic bacterial load and the time required for empirical antibiotic regimen administration prior to definitive treatment. This study aims to identify the differences in TTP among causative pathogens and its predictive value for the overall survival of neonates with sepsis at a tertiary healthcare center in Indonesia. Methods: A retrospective cohort study was conducted from January 2020 to August 2022 at Dr. Soetomo General Hospital, Surabaya, Indonesia. Neonates with blood culture-proven neonatal sepsis were included in the analysis. TTP was defined as the time between the acceptance of a blood culture specimen from the neonatal intensive care unit and reports of positive culture growth by the laboratory. Results: Across 125 cases, the median TTP was 58.1 hours (IQR = 24.48). Blood cultures were positive within 48 hours for 41.6% of cases, 72 hours for 86.4%, and 96 hours for 98.4%. A significantly shorter TTP was exhibited by the three major gram-negative organisms (Klebsiella pneumoniae,Acinetobacter baumannii,Enterobacter cloacae) compared to coagulase-negative Staphylococci. The neonatal sepsis mortality rate was 49.6% during the study period. In the Cox multivariate regression model, a shorter TTP was an independently predicted mortality in the entire cohort (hazard ratio (HR) = 0.985, 95% CI: 0.973-0.998) and the gram-negative sepsis cohort group (HR = 0.983, 95% CI: 0.968-0.999). Conclusions: TTP predicts different causative pathogens and the overall survival of neonatal sepsis cases at a tertiary healthcare facility in Indonesia.

Factors Associated With Culture-proven Neonatal Sepsis and Resistance to First-line Antibiotics in Indonesia.

BACKGROUND: Neonatal sepsis is one of the leading causes of neonatal morbidity and mortality in low- and middle-income countries. Blood culture positivity rates and antibiotic resistance pattern of neonatal sepsis differs across various regions. This study aims to identify clinical cofactors associated with blood culture-proven neonatal sepsis and in vitro resistance to first-line antibiotics (ampicillin and gentamicin) from cases originating in a tertiary healthcare center in Surabaya, Indonesia. METHODS: A retrospective cohort study was conducted from January 2020 to August 2022 by utilizing secondary data collected from standardized electronic medical records. Microbiologic characteristics and associated factors were statistically analyzed using multivariable logistic regression. RESULTS: Across 266 neonatal sepsis cases, 46.9% were culture-proven and 79.2% of confirmed sepsis were resistant to first-line antibiotics. The most common isolated pathogen is Klebsiella pneumoniae , followed by coagulase-negative Staphylococci , Acinetobacter baumannii and Enterobacter cloacae . Extremely preterm delivery [adjusted odds ratio (aOR): 5.813; 95% confidence interval (CI): 1.70-19.91] and late-onset sepsis (aOR: 9.165; 95% CI: 5.12-16.40) were associated with culture-proven neonatal sepsis. Increased odds of resistance to first-line antibiotics were identified in extremely preterm (<28 weeks) or very-preterm delivery (28 to <32 weeks) (aOR: 50.80; 95% CI: 1.66-1554.21 and aOR: 45.679; 95% CI: 3.22-647.46, respectively), cesarean section (aOR: 4.149; 95% CI: 1.04-16.53) and an absence of antenatal corticosteroid use (aOR: 0.233; 95% CI: 0.07-0.76). CONCLUSIONS: The association between clinical cofactors with culture-proven sepsis and antibiotic resistance emphasizes the importance for clinicians to adjust empirical antibiotic regimens based on the local antibiogram and resource availability.

Vitamin D, cell death pathways, and tuberculosis.

BACKGROUND: Mycobacterium tuberculosis induces cellular necrosis that could promote spread of infection. The aim of this study is to analyze the effects of Vitamin D3 supplementation to improve the effectiveness of 2nd-line anti-tuberculosis (TB) drug therapy, especially in relation with cell death pathways. METHODS: Mus musculus C3HeB/FeJ was randomly divided into four groups containing eight animals each. The 1st group (G1), consisting of mice that were intratracheally infected with multidrug-resistant strain of M. tuberculosis and sacrificed on 2-week postinfection to confirm successful infection. (G2) was a group of TB mice without therapy. Then, (G3) was a group of mice with the 2nd-line anti-TB therapy. The last group (G4) was a group of mice receiving not only the 2nd-line anti-TB therapy but also daily oral Vitamin D3 supplementation. Immunohistochemistry was used to measure expression of nuclear Vitamin D receptor, apoptosis marker cleaved caspase-3, cathelin-related antimicrobial peptide (CRAMP) and LC3B autophagy markers, necrosis marker RIPK3, and collagenase matrix metalloproteinase-1 (MMP1). The number of bacteria in the lung was calculated by colony forming units. The partial least square structural equation modeling with SmartPLS 3.2.6 software was used to analyze structural models among the variables. RESULTS: Supplementation of Vitamin D3 on the 2nd-line anti-TB therapy increases Vitamin D3 receptor, CRAMP, LC3B, caspase-3 (P = 0.026, P = 0.000, P= 0.001), presses MMP1, and the number of bacteria (P = 0.010 and P= 0.000, respectively). The structural equation modeling analysis shows that increasing autophagy pathways reduces necrosis by lowering MMP1, whereas apoptosis reduces necrosis by decreasing the number of bacteria (each with indirect effects - 0.543 and - 0.544). CONCLUSION: A comprehensive analysis with the partial least square structural equation modeling shows decreasing necrosis requires increasing autophagy and apoptosis.