Prevalence, aetiology, antimicrobial susceptibility testing, and predictors of urinary tract infection among neonates with clinical sepsis: a cross-sectional study

Background Urinary tract infection (UTI) is the most common and life-threatening bacterial infection among neonates. This study aimed to determine the prevalence, aetiology, and susceptible antimicrobial agents among neonates with UTI. Methods This was a cross-sectional analytical hospital-based study that included 152 neonates with clinical sepsis who were admitted at Dodoma regional referral hospital from January to June 2020. Bacterial growth of 1 × 103 colony forming units/mL of a single uropathogen was used to define the presence of UTI. Statistical analysis was performed using SPSS version 23.0 and multivariate analysis was used to determine the predicting factors of UTI. P <0.05 was regarded statistically significant. Results The prevalence of UTI was 18.4% (28/152). Klebsiella pneumoniae 64.3% (18/28) and Enterobacter spp. 35.7% (10/28) were the bacterial agents isolated. The bacterial isolates were 90%, and 60% sensitive to ciprofloxacin and amikacin, respectively. Low Apgar score (AOR = 12.76, 95% CI = 4.17–39.06, p<0.001), prolonged labour (AOR = 5.36, 95% CI = 1.28–22.52, p = 0.022), positive urine nitrite test (AOR = 26.67, 95% CI = 7.75–91.70, p<0.001), and positive leucocyte esterase test (AOR = 6.64, 95% CI = 1.47–29.97, p = 0.014) were potential predictors of UTI. Conclusion The prevalence of UTI confirmed by urine culture among neonates that were included in the present study indicates that this problem is common in the population where the study was conducted. Klebsiella pneumoniae and Enterobacter spp. were the uropathogens which were isolated. Ciprofloxacin, nitrofurantoin, and amikacin were sensitive to the isolated uropathogens.

Bacteriological profile, antibiotic susceptibility pattern and other factors related to neonatal meningitis: A cross-sectional hospital-based study from West Bengal

Background: Neonatal sepsis and meningitis is an important cause of neonatal mortality and morbidity especially in the developing countries. Bacteriological profile of meningitis and antibiotic sensitivity pattern may vary from one region to another. Aims and Objectives: We have planned this study to know the etiological agent of neonatal meningitis with its antibiotic sensitivity profile and to evaluate some other associated risk factors of meningitis. Materials and Methods: This observational, cross-sectional study was done for a period of 1 year in the SNCU and NICU of a district Medical College of West Bengal in neonates presented with clinical sepsis and meningitis. Sepsis screen, blood culture, cerebrospinal fluid (CSF) study, and culture sensitivity was done and recorded along with demographic data, clinical presentation, outcome, and other associated factors. Results: We found meningitis in 55 neonates out of 250 clinical sepsis. CSF culture was positive in 42 cases with Escherichia coli (30.9%), Klebsiella (26.1%), Staphylococcus aureus (16.6%), Acinetobacter (14.2%) and Coagulase negative Staphylococcus (CoNS 11.9%) as prevalent organism. E. coli and Klebsiella were mostly sensitive to Amikacin, Levofloxacin, and Colistin whereas less sensitive to Cefotaxime, Pipercilin-tazobactam or Meropenem and Acinetobacter showed good sensitivity only to Levofloxacin. Among the gram-positive organism, S. aureus and CoNS were only sensitive to Linezolid, Vancomycin, and Teicoplanin. Conclusion: This type of study should help to make a proper antibiotic policy for an institution so that the empirical first-line antibiotic can be started with good effect in cases of neonatal sepsis and meningitis before the arrival of culture sensitivity report.

Eliminating Contamination in Umbilical Cord Blood Culture Sampling for Early-Onset Neonatal Sepsis

Introduction: Despite the advantages of umbilical cord blood culture (UCBC) use for diagnosis of early onset sepsis (EOS), contamination rates have deterred neonatologists from its widespread use. We aimed to implement UCBC collection in a level III neonatal intensive care unit (NICU) and apply quality improvement (QI) methods to reduce contamination in the diagnosis of early onset sepsis.Methods: Single-center implementation study utilizing quality improvement methodology to achieve 0% contamination rate in UCBC samples using the Plan-Do-Study-Act (PDSA) model for improvement. UCBC was obtained in conjunction with peripheral blood cultures (PBC) in neonates admitted to the NICU due to maternal chorioamnionitis. Maternal and neonatal characteristics between clinical sepsis and asymptomatic groups were compared. Process, outcome, and balancing measures were monitored.Results: Eighty-two UCBC samples were collected in addition to peripheral blood culture from neonates admitted due to maternal chorioamnionitis. Ten (12%) neonates had a diagnosis of clinical sepsis. All PBCs were negative and 5 UCBCs were positive in the study period. After 2 PDSA cycles, there was special cause variation with improvement in the percent of contaminated samples from 7.3 to 0%. There was no change in antibiotic duration among asymptomatic neonates.Conclusions: Implementation of UCBC for the diagnosis of EOS in term infants is feasible and contamination can be minimized with the implementation of a core team of trained providers and a proper sterile technique without increasing antibiotic duration.

Clinical profile of sepsis and choice of antimicrobials in babies admitted to special newborn care unit Kalaburagi

Background: Sepsis is one of the common clinical conditions seen in neonates. Sepsis being major cause of neonatal morbidity and mortality in neonates, early recognition and treatment with antibiotics remains a mainstay of NICU protocols for neonatologists.Methods: It is a hospital based retrospective study conducted from July 2019 to February 2020 in GIMS, Kalaburagi. Neonates with suspicion of clinical sepsis were investigated for complete blood count (CBC), C-reactive protein (CRP) and blood culture (BC). Antibiotics were started based on CBC and CRP reports, or on high index of clinical suspicion. Based on common organisms isolated in previous 3 months statistics, antibiotics were decided. On confirmation by blood culture, antibiotics were changed as per blood culture report.Results: Out of 100 neonates, CRP was positive in 80 (70%) neonates, BC showed growth among 24 (24%) neonates. Although neonates had clinical sepsis, CRP was negative in 20 (10%), 76 (76%) did not show any kind of growth on BC. Mortality was seen in 04 (5%) neonates with only CRP positive, 02 (08%) neonates with only BC growth, 02 (10%) neonates with both CRP positive and BC growth, 02 (03%) neonates with CRP positive but no growth on BC. Clinical features were from subtle to severe.Conclusions: Although CRP and blood culture confirmation remains one of the main diagnostic parameter in sepsis, as mortality is seen among neonates with negative blood parameters, high index of clinical suspicion is essential to treat sepsis at an early stage.

The Use of Artificial Neural Networks to Forecast the Behavior of Agent-Based Models of Pathophysiology: An Example Utilizing an Agent-Based Model of Sepsis

Introduction: Disease states are being characterized at finer and finer levels of resolution via biomarker or gene expression profiles, while at the same time. Machine learning (ML) is increasingly used to analyze and potentially classify or predict the behavior of biological systems based on such characterization. As ML applications are extremely data-intensive, given the relative sparsity of biomedical data sets ML training of artificial neural networks (ANNs) often require the use of synthetic training data. Agent-based models (ABMs) that incorporate known biological mechanisms and their associated stochastic properties are a potential means of generating synthetic data. Herein we present an example of ML used to train an artificial neural network (ANN) as a surrogate system used to predict the time evolution of an ABM focusing on the clinical condition of sepsis.Methods: The disease trajectories for clinical sepsis, in terms of temporal cytokine and phenotypic dynamics, can be interpreted as a random dynamical system. The Innate Immune Response Agent-based Model (IIRABM) is a well-established model that utilizes known cellular and molecular rules to simulate disease trajectories corresponding to clinical sepsis. We have utilized two distinct neural network architectures, Long Short-Term Memory and Multi-Layer Perceptron, to take a time sequence of five measurements of eleven IIRABM simulated serum cytokine concentrations as input and to return both the future cytokine trajectories as well as an aggregate metric representing the patient’s state of health.Results: The ANNs predicted model trajectories with the expected amount of error, due to stochasticity in the simulation, and recognizing that the mapping from a specific cytokine profile to a state-of-health is not unique. The Multi-Layer Perceptron neural network, generated predictions with a more accurate forecasted trajectory cone.Discussion: This work serves as a proof-of-concept for the use of ANNs to predict disease progression in sepsis as represented by an ABM. The findings demonstrate that multicellular systems with intrinsic stochasticity can be approximated with an ANN, but that forecasting a specific trajectory of the system requires sequential updating of the system state to provide a rolling forecast horizon.

Clinical Early-Onset Sepsis Is Equally Valid to Culture-Proven Sepsis in Predicting Outcome in Infants after Preterm Rupture of Membranes

Background: Culture-proven sepsis is the gold standard in early-onset neonatal sepsis diagnosis. Infants born ≤29 weeks gestation after preterm rupture of membranes in the years 2009–2015 were included in a retrospective cohort study performed at a level III fetal-maternal unit. The study aimed to compare culture-proven sepsis, clinical sepsis and positive laboratory biomarkers ≤72 h as predictors of mortality before discharge and the combined outcome of mortality or severe short-term morbidity (severe cerebral morbidity, bronchopulmonary dysplasia and retinopathy). Results: Of the 354 patients included, culture-proven sepsis, clinical sepsis and laboratory biomarkers were positive in 2.3%, 8.5% and 9.6%, respectively. The mortality rate was 37.5% for patients with culture-proven sepsis (3/8), 33.3% for patients with clinical sepsis (10/30) and 8.8% for patients with positive laboratory biomarkers (3/34), respectively. Mortality or severe morbidity occurred in 75.0% of patients with culture-proven sepsis (6/8), 80.0% of patients with clinical sepsis (24/30) and 44.1% of patients with positive laboratory biomarkers (15/34), respectively. Conclusion: In preterm infants after preterm rupture of membranes, clinical sepsis was almost four times more common and at least equally valuable in predicting mortality and mortality or severe morbidity compared to culture-proven sepsis.

Evaluating the Incidence of Sepsis Post–Central Catheter Removal When Using Prophylactic Vancomycin in the Neonatal Intensive Care Unit

OBJECTIVE With no consensus, the practice of using prophylactic antibiotics prior to central venous catheter (CVC) removal in NICU patients remains controversial. The objective of this study was to compare the incidence of sepsis post–CVC removal in those who received a dose of vancomycin prophylactically with those who did not. METHODS This single-center, retrospective chart review included NICU patients who had CVCs removed. Patients were excluded if they had a confirmed or suspected infection at the time of CVC removal or if the indwelling CVC was removed prior to 30 days from insertion. Primary outcome was the occurrence of a sepsis evaluation within 72 hours from CVC removal. Secondary outcomes included the development of acute kidney injury, source and identification of positive cultures, time to onset of suspected or confirmed sepsis, and the appropriate administration of intravenous vancomycin. RESULTS Eighty-two CVC removals received prophylactic vancomycin (P-VAN), and 22 CVCs did not receive prophylactic vancomycin (NP-VAN) prior to CVC removal. There were no significant differences in patient demographics between groups and median duration of indwelling CVC. Two clinical sepsis evaluations occurred in the P-VAN group compared with none in the NP-VAN group. Of all the P-VAN CVC removals, 45 (55%) received vancomycin appropriately. There were no statistical differences in all evaluated secondary outcomes. CONCLUSIONS Vancomycin administered prophylactically prior to CVC removal did not reduce the number of subsequent clinical sepsis evaluations or infections in NICU patients.

Citrullinated Histone H3 Level as a Novel Biomarker in Pediatric Clinical Sepsis

BACKGROUND: Sepsis is still leading cause of death in critically ill children. Early recognition of sepsis and treatments are needed to reduce its mortality. The use of citrullinated Histone H3 (Cit-H3) as an early sepsis marker and outcome predictor has been validated in previous studies among adults. However, only one study in pediatric meningococcal sepsis was reported with contradictory results. This study aims to determine Cit-H3 levels in pediatric clinical sepsis and analyze its association with sepsis severity and survival rate.METHODS: A prospective observational cohort study involving 67 pediatric subjects clinically diagnosed with sepsis was conducted. Cit-H3 levels, Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score, and Pediatric Sequential Organ Failure Assessment (pSOFA) score were assessed at the time of diagnosis (0-hour) and 48 hours later. Pearson Correlation test was used to determine the correlation between Cit-H3 levels with PELOD-2 and pSOFA scores and receiver operating curve to find the cut-off of Cit-H3 levels on clinical sepsis patients.RESULTS: Among clinically sepsis patients, the median Cit-H3 level was 1,210 (800-32,160) ng/mL, with optimal cut-off point ≥1200 ng/mL (sensitivity 83.3% and specificity 75.7%) to discriminate sepsis. The median Cit-H3 levels at 0-hour were lower in survivor compared to non-survivor group (p=0.016). Cit-H3 level was able to predict mortality with optimal cut-off point ≥1,200 ng/mL, sensitivity 72.2% and specificity 57.1% (AUC of 69.2%; p=0.017). Using survival analysis, Cit-H3 was significantly associated with the mortality rate (p=0.023; hazard ratio of 3.45).CONCLUSION: Cit-H3 level could be potential to predict pediatric sepsis events and its outcome.KEYWORDS: citrullinated histone H3, neutrophil extracellular traps, pediatric sepsis, PELOD-2 score, pSOFA score, survival