Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome.
Ontology highlight
ABSTRACT:
SUBMITTER: Romeo MG
PROVIDER: S-EPMC3016918 | biostudies-other | 2011 Jan
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Host immune responses during late-onset sepsis (LOS) in very preterm infants are poorly characterised due to a complex and dynamic pathophysiology and challenges in working with small available blood volumes. We present here an unbiased transcriptomic analysis of whole peripheral blood from very preterm infants at the time of LOS. RNA-Seq was performed on peripheral blood samples (6 – 29 days postnatal age) taken at the time of suspected LOS from very preterm infants <30 weeks gestational age. Infants were classified based on blood culture positivity and elevated C-reactive protein concentrations as having confirmed LOS (n=5), possible LOS (n=4) or no LOS (n=9). Bioinformatics and statistical analyses performed included pathway over-representation and protein-protein interaction network analyses. Plasma cytokine immunoassays were performed to validate differentially expressed cytokine pathways.The blood leukocyte transcriptional responses of infants with confirmed LOS differed significantly from infants without LOS (1,317 differentially expressed genes). However, infants with possible LOS could not be distinguished from infants with no LOS or confirmed LOS. Transcriptional alterations associated with LOS included genes involved in pathogen recognition (mainly TLR pathways), cytokine signalling (both pro-inflammatory and inhibitory responses), immune and haematological regulation (including cell death pathways), and metabolism (altered cholesterol biosynthesis). At the transcriptional-level cytokine responses during LOS were characterised by over-representation of IFN-α/β, IFN-γ, IL-1 and IL-6 signalling pathways and up-regulation of genes for inflammatory responses. Infants with confirmed LOS had significantly higher levels of IL-1α and IL-6 in their plasma. Blood responses in very preterm infants with LOS are characterised by altered host immune responses that appear to reflect unbalanced immuno-metabolic homeostasis.
2020-06-03 | GSE138712 | GEO
Project description:BACKGROUND:Host immune responses during late-onset sepsis (LOS) in very preterm infants are poorly characterised due to a complex and dynamic pathophysiology and challenges in working with small available blood volumes. We present here an unbiased transcriptomic analysis of whole peripheral blood from very preterm infants at the time of LOS. METHODS:RNA-Seq was performed on peripheral blood samples (6-29 days postnatal age) taken at the time of suspected LOS from very preterm infants <30 weeks gestational age. Infants were classified based on blood culture positivity and elevated C-reactive protein concentrations as having confirmed LOS (n = 5), possible LOS (n = 4) or no LOS (n = 9). Bioinformatics and statistical analyses performed included pathway over-representation and protein-protein interaction network analyses. Plasma cytokine immunoassays were performed to validate differentially expressed cytokine pathways. RESULTS:The blood leukocyte transcriptional responses of infants with confirmed LOS differed significantly from infants without LOS (1,317 differentially expressed genes). However, infants with possible LOS could not be distinguished from infants with no LOS or confirmed LOS. Transcriptional alterations associated with LOS included genes involved in pathogen recognition (mainly TLR pathways), cytokine signalling (both pro-inflammatory and inhibitory responses), immune and haematological regulation (including cell death pathways), and metabolism (altered cholesterol biosynthesis). At the transcriptional-level cytokine responses during LOS were characterised by over-representation of IFN-?/?, IFN-?, IL-1 and IL-6 signalling pathways and up-regulation of genes for inflammatory responses. Infants with confirmed LOS had significantly higher levels of IL-1? and IL-6 in their plasma. CONCLUSIONS:Blood responses in very preterm infants with LOS are characterised by altered host immune responses that appear to reflect unbalanced immuno-metabolic homeostasis.
| S-EPMC7263612 | biostudies-literature
Project description:ObjectiveLate onset sepsis (LOS) contributes to mortality and morbidity in preterm infants. We tested the hypotheses that microbes causing LOS originate from the gut, and that distortions in the gut microbial community increases subsequent risk of LOS.Study designWe examined the gut microbial community in prospectively collected stool samples from preterm infants with LOS and an equal number of age-matched controls at two sites (Cincinnati, OH and Birmingham, AL), by sequencing the bacterial 16S rDNA. We confirmed our findings in a subset of infants by whole genome shotgun sequencing, and analyzed the data using R and LEfSe.ResultsInfants with LOS in Cincinnati, as compared to controls, had less abundant Actinobacteria in the first samples after birth (median 18 days before sepsis onset), and less abundant Pseudomonadales in the last samples collected prior to LOS (median 8 days before sepsis onset). Infants with LOS in Birmingham, as compared to controls, had no differences identified in the first sample microbial communities, but Lactobacillales was less abundant in the last samples prior to LOS (median 4 days before sepsis onset). Sequencing identified detectable levels of the sepsis-causative organism in stool samples prior to disease onset for 82% of LOS cases.ConclusionsTranslocation of gut microbes may account for the majority of LOS cases. Distortions in the fecal microbiota occur prior to LOS, but the form of distortion depends on timing and site. The microbial composition of fecal samples does not predict LOS onset in a generalizable fashion.
| S-EPMC4482142 | biostudies-literature
Project description:BackgroundThe pathogenesis of late-onset sepsis (LOS) in preterm infants is poorly understood and knowledge about risk factors, especially prenatal risk factors, is limited. This study aimed to assess the association between the cause of preterm birth and LOS in very preterm infants.Methods2052 very preterm singletons from a national population-based cohort study alive at 72 h of life were included. Survival without LOS was compared by cause of preterm birth using survival analysis and Cox regression models.Results437 (20.1%) had at least one episode of LOS. The frequency of LOS varied by cause of preterm birth: 17.1% for infants born after preterm labor, 17.9% after preterm premature rupture of membranes, 20.3% after a placental abruption, 20.3% after isolated hypertensive disorders, 27.5% after hypertensive disorders with fetal growth restriction (FGR), and 29.4% after isolated FGR. In multivariate analysis, when compared to infants born after preterm labor, the risk remained higher for infants born after hypertensive disorders (hazard ratio HR = 1.7, 95% CI = 1.2-2.5), hypertensive disorders with FGR (HR = 2.6, 95% CI = 1.9-3.6) and isolated FGR (HR = 2.9, 95% CI = 1.9-4.4).ConclusionVery preterm infants born after hypertensive disorders or born after FGR had an increased risk of LOS compared to those born after preterm labor.ImpactLate-onset sepsis risk differs according to the cause of preterm birth. Compared with those born after preterm labor, infants born very preterm because of hypertensive disorders of pregnancy and/or fetal growth restriction display an increased risk for late-onset sepsis. Antenatal factors, in particular the full spectrum of causes leading to preterm birth, should be taken into consideration to better prevent and manage neonatal infectious morbidity and inform the parents.
| S-EPMC7903216 | biostudies-literature
Project description:Late-onset sepsis is a major problem in neonatology, but the habitat of the pathogens before bloodstream invasion occurs is not well established.We examined prospectively collected stools from premature infants with sepsis to find pathogens that subsequently invaded their bloodstreams, and sought the same organisms in stools of infants without sepsis. Culture-based techniques were used to isolate stool bacteria that provisionally matched the bloodstream organisms, which were then genome sequenced to confirm or refute commonality.Of 11 children with late-onset neonatal bloodstream infections, 7 produced at least 1 stool that contained group B Streptococcus (GBS), Serratia marcescens, or Escherichia coli before their sepsis episode with provisionally matching organisms. Of 96 overlap comparison subjects without sepsis temporally associated with these cases, 4 were colonized with provisionally matching GBS or S. marcescens. Of 175 comparisons of stools from randomly selected infants without sepsis, 1 contained a GBS (this infant had also served as an overlap comparison subject and both specimens contained provisionally matching GBS). Genome sequencing confirmed common origin of provisionally matching fecal and blood isolates. The invasive E. coli were present in all presepticemic stools since birth, but gut colonization with GBS and S. marcescens occurred closer to time of bloodstream infection.The neonatal gut harbors sepsis-causing pathogens, but such organisms are not inevitable members of the normal microbiota. Surveillance microbiology, decolonization, and augmented hygiene might prevent dissemination of invasive bacteria between and within premature infants.
| S-EPMC3982840 | biostudies-other
Project description:ObjectivesPrediction of late-onset sepsis (onset beyond day 3 of life) in preterm infants, based on multiple patient monitoring signals 24 hours before onset.DesignContinuous high-resolution electrocardiogram and respiration (chest impedance) data from the monitoring signals were extracted and used to create time-interval features representing heart rate variability, respiration, and body motion. For each infant with a blood culture-proven late-onset sepsis, a Cultures, Resuscitation, and Antibiotics Started Here moment was defined. The Cultures, Resuscitation, and Antibiotics Started Here moment served as an anchor point for the prediction analysis. In the group with controls (C), an "equivalent crash moment" was calculated as anchor point, based on comparable gestational and postnatal age. Three common machine learning approaches (logistic regressor, naive Bayes, and nearest mean classifier) were used to binary classify samples of late-onset sepsis from C. For training and evaluation of the three classifiers, a leave-k-subjects-out cross-validation was used.SettingLevel III neonatal ICU.PatientsThe patient population consisted of 32 premature infants with sepsis and 32 age-matched control patients.InterventionsNo interventions were performed.Measurements and main resultsFor the interval features representing heart rate variability, respiration, and body motion, differences between late-onset sepsis and C were visible up to 5 hours preceding the Cultures, Resuscitation, and Antibiotics Started Here moment. Using a combination of all features, classification of late-onset sepsis and C showed a mean accuracy of 0.79 ± 0.12 and mean precision rate of 0.82 ± 0.18 3 hours before the onset of sepsis.ConclusionsInformation from routine patient monitoring can be used to predict sepsis. Specifically, this study shows that a combination of electrocardiogram-based, respiration-based, and motion-based features enables the prediction of late-onset sepsis hours before the clinical crash moment.
| S-EPMC7846455 | biostudies-literature
Project description:BackgroundLate-onset sepsis (LOS) in preterm infants is a leading cause of mortality and morbidity. Timely recognition and initiation of antibiotics are important factors for improved outcomes. Identification of risk factors could allow selection of infants at an increased risk for LOS.ObjectivesThe aim was to identify risk factors for LOS.MethodsIn this multicenter case-control study, preterm infants born at ≤30 weeks of gestation were included at 9 neonatal intensive care units. Detailed demographical and clinical data were collected daily up to day 28 postnatally. Clinical and demographic risk factors were identified using univariate and multivariate regression analyses in a 1: 1 matched case-control cohort.ResultsIn total, 755 infants were included, including 194 LOS cases (41 gram-negative cases, 152 gram-positive cases, and 1 fungus). In the case-control cohort, every additional day of parenteral feeding increased the risk for LOS (adjusted OR = 1.29; 95% CI 1.07-1.55; p = 0.006), whereas antibiotics administration decreased this risk (OR = 0.08; 95% CI 0.01-0.88; p = 0.039). These findings could largely be attributed to specific LOS-causative pathogens, since these predictive factors could be identified for gram-positive, but not for gram-negative, LOS cases. Specifically cephalosporins administration prior to clinical onset was inversely related to coagulase-negative staphylococcus LOS (CoNS-LOS) development. Formula feeding was an independent risk factor for development of CoNS-LOS (OR = 3.779; 95% CI 1.257-11.363; p = 0.018).ConclusionThe length of parenteral feeding was associated with LOS, whereas breastmilk administration was protective against CoNS-LOS. A rapid advancement of enteral feeding, preferably with breastmilk, may proportionally reduce the number of parenteral feeding days and consequently the risk for LOS.
| S-EPMC6690411 | biostudies-literature
Project description:Background:Serum levels of markers of endothelial cell activation are associated with bacteremia and mortality in sepsis in adults, children, and newborns with early onset sepsis. We hypothesize that levels of these markers are associated with these outcomes in hospitalized newborns with suspected late onset neonatal sepsis (LONS). Methods:In this prospective cohort study, newborns admitted to the tertiary neonatal care facility of Suriname were included upon clinical suspicion of LONS and before start of antibiotic treatment, between April 1, 2015 and May 31, 2016. Serum concentrations of angiopoietin-1, angiopoietin-2, and soluble isoforms of P-selectin, E-selectin, vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), platelet and endothelial cell adhesion molecule-1 (sPECAM-1), matrix metalloproteinase-9 (MMP-9), neutrophil elastase, and tissue-inhibitor of metalloproteinases-1 (TIMP-1) were measured. Results:Twenty-thee newborns were included. Baseline characteristics were similar between newborns with and without bacteremia and between non-survivors and survivors. Only soluble E-selectin (sE-selectin) was higher in newborns with bacteremia versus non-bacteremia (P=0.04) and lower in non-survivors (P=0.04). No conclusions could be made for sVCAM-1 due to high serum concentrations. Conclusions:In conclusion, the data from this pilot study indicate that serum levels of markers of endothelial cell activation are poorly associated with bacteremia and mortality.
| S-EPMC6970123 | biostudies-literature
Project description:This study investigates the impact of antenatal and postnatal infection or inflammation on the onset and progression of Retinopathy of Prematurity (ROP). We retrospectively collected clinical and demographic data of preterm infants with birth weight ≤ 1500 g or gestational age < 30 weeks admitted to the neonatal intensive care unit of Verona from 2015 to 2019. Uni- and multivariable analysis was performed to evaluate the potential effect of selected variables on the occurrence of any stage ROP and its progression to severe ROP, defined as ROP requiring treatment. Two hundred and eighty neonates were enrolled and 60 of them developed ROP (21.4%). Oxygen need for 28 days and late-onset sepsis (LOS) increased the risk of any grade ROP after adjusting for birth weight and gestational age (OR 6.35, 95% CI 2.14-18.85 and OR 2.49, 95% CI 1.04-5.94, respectively). Days of mechanical ventilation and of non-invasive ventilation increased the risk of progression to severe ROP after adjusting for birth weight and gestational age (OR 1.08, CI 1.02-1.14 and OR 1.06, CI 1.01-1.11, respectively). Exposure to infection with production of inflammatory mediators may contribute to increase the risk of ROP occurrence in very preterm neonates.
| S-EPMC9270376 | biostudies-literature
Project description:Nosocomial sepsis is associated with increased mortality and morbidity including neurodevelopmental impairment and prolonged hospital stay. Prevention of sepsis especially in the preterm infants in the neonatal intensive care unit remains a major challenge. The gastrointestinal tract is an important source of potential pathogens causing nosocomial sepsis as the immature intestinal epithelium can permit translocation of bacteria and yeast. The intestinal tract and its microflora play an important role in the immunity. Altering the gut microflora has been extensively studied for immunomodulation in preterm infants. Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. Probiotics have been used for prevention and treatment of various medical conditions in children and adults. Studies on probiotics in premature infants have focused on normalizing intestinal flora, improvement in feeding intolerance, prevention of necrotizing enterocolitis and sepsis. In this paper, we discuss the intestinal bacterial colonization pattern; the rational for probiotics and prebiotic therapy with special focus on the prevention of nosocomial sepsis in preterm infants.
| S-EPMC3557621 | biostudies-other