Sepsis In Preterm Infants Research Articles

Sepsis in preterm infants causes alterations in mucosal gene expression and microbiota profiles compared to non-septic twins

Sepsis is a life-threatening condition in preterm infants. Neonatal microbiota plays a pivotal role in the immune system maturation. Changes in gut microbiota have been associated to inflammatory disorders; however, a link with sepsis in the neonatal period has not yet been established. We aimed to analyze gut microbiota and mucosal gene expression using non-invasively obtained samples to provide with an integrative perspective of host-microbe interactions in neonatal sepsis. For this purpose, a prospective observational case-control study was conducted in septic preterm dizygotic twins and their non-septic twin controls. Fecal samples were used for both microbiota analysis and host genome-wide expression using exfoliated intestinal cells. Gene expression of exfoliated intestinal cells in septic preterm showed an induction of inflammatory and oxidative stress pathways in the gut and pro-oxidant profile that caused dysbiosis in the gut microbiota with predominance of Enterobacteria and reduction of Bacteroides and Bifidobacterium spp.in fecal samples, leading to a global reduction of beneficial anaerobic bacteria. Sepsis in preterm infants induced low-grade inflammation and oxidative stress in the gut mucosa, and also changes in the gut microbiota. This study highlights the role of inflammation and oxidative stress in neonatal sepsis on gut microbial profiles.

Probiotic Supplementation and Late-Onset Sepsis in Preterm Infants: A Meta-analysis.

Late-onset sepsis (LOS) is a major cause of mortality and morbidity in preterm infants. Despite various preventive measures, its incidence continues to remain high, hence the urgent need for additional approaches. One such potential strategy is supplementation with probiotics. The updated Cochrane Review (2014) did not find benefits of probiotics in reducing the risk of LOS in preterm infants (19 studies, N = 5338). Currently there are >30 randomized controlled trials (RCTs) of probiotics in preterm infants that have reported on LOS. To conduct a systematic review including all relevant RCTs. PubMed, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature, and E-abstracts from the Pediatric Academic Society meetings and other pediatric and neonatal conference proceedings were searched in June and August 2015. RCTs comparing probiotics versus placebo/no probiotic were included. Relevant data were extracted independently by 3 reviewers. Pooled results from 37 RCTs (N = 9416) using fixed effects model meta analysis showed that probiotics significantly decreased the risk of LOS (675/4852 [13.9%] vs 744/4564 [16.3%]; relative risk, 0.86; 95% confidence interval, 0.78-0.94; P = .0007; I(2) = 35%; number needed to treat, 44). The results were significant even after excluding studies with high risk of bias. Probiotic supplementation reduces the risk of LOS in preterm infants.

Late-onset neonatal sepsis in preterm infants with birth weight under 1.500 g

The research objective was to characterize preterm infants with birth weight under 1500 g, and to identify the incidence of late-onset neonatal sepsis among this population. A prospective cohort study with a sample of 30 preterm newborns that weighed under 1500 g and were hospitalized in the NICU of the university hospital. Data were collected from January to December 2013 using a structured instrument. Of the 30 neonates included in the study, 14 developed late-onset neonatal sepsis with a prevalence of coagulase-negative staphylococci. The incidence of late-onset neonatal sepsis indicates a vulnerability in preterm infants due to immunological immaturity. These results reveal that knowledge of the profile of newborn infants admitted to the NICU and the risk factors to which they are exposed are central to the planning of nursing care for these patients. Future studies should address strategies for preventing nosocomial infection.

The role of elevated central-peripheral temperature difference in early detection of late-onset sepsis in preterm infants

AimsThe study investigated the association between clinical symptoms and late-onset sepsis (LOS) in preterm infants with the aim of identifying a non-invasive tool for the early detection of LOS. MethodsThis was a prospective study of 83 episodes of suspected LOS in 67 preterm infants. At the time LOS was suspected, we recorded a standardized set of clinical symptoms. A diagnosis of “clinical LOS” (Clin-LOS), “culture-proven LOS” (Prov-LOS) or “LOS not present” (No-LOS) was made on the basis of C-reactive protein (CrP) and blood culture results where Clin-LOS was defined as CrP>10mg/l, Prov-LOS was defined as CrP>10mg/l AND positive blood cultures, or it was established that there was no sepsis present (No-LOS). We examined univariable associations between clinical signs and LOS using odds ratio (OR) analysis and then adjusted the odds ratio (adOR) through binary regression analysis. ResultsClin-LOS was diagnosed in 20/83 episodes, 19 cases were found to have Prov-LOS. Clinical signs which had a significant association with Clin-LOS were capillary refill time >2s (OR 2.9) and decreased responsiveness (OR 5.2), whereas there was a negative association between gastric residuals and LOS (OR 0.35). However, the most marked association was found for a greater central-peripheral temperature difference (cpTD) >2°C (OR 9). In Prov-LOS an increased heart rate (OR 3.1), prolonged capillary refill time (OR 3.3) and again an increased cpTD (OR 16) had a significant association with LOS, whereas gastric residuals were negatively associated (OR 0.29). Regression analysis showed that cpTD was the most striking clinical sign associated with both Clin- (adOR 6.3) and Prov-LOS (adOR 10.5). ConclusionsProlonged capillary refill time and – more impressive – elevated cpTD were the most useful clinical symptoms for detection of LOS in preterm infants. We especially suggest using cpTD as a predictor of LOS. It is a cheap, non-invasive and readily available tool for daily routines.

Does Haptoglobin Phenotype Influence Postnatal Morbidity in Preterm Neonates?

Haptoglobin (Hp) is an acute phase protein with antioxidant, bacteriostatic, and anti-inflammatory activities. Hp proteins associated with the three major phenotypes differ in their proinflammatory and anti-inflammatory action. Inflammation and oxidative stress are both involved in most pathophysiological processes in premature infants. The objective of this study was to determine whether Hp phenotype influences clinical manifestations and sepsis incidence in the premature infants. Infants born before 35 weeks gestational age were prospectively evaluated for Hp phenotype and clinical events, including sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, intraventricular hemorrhage, and retinopathy of prematurity. The participants were observed until discharge. A total of 122 preterm infants were enrolled in the study. Clinical events were not affected by the Hp phenotype. The expression of Hp protein was extremely low in the study population. More septic episodes were found in infants with a birth weight greater than 1,500 g, although, the difference was not statistically significant. Extremely low expression of Hp may explain the lack of a correlation between Hp phenotype and sepsis in preterm infants. Further research involving a larger neonatal population is required to better understand the role of the Hp phenotype in morbidity of premature infants.

Role of presepsin in the diagnosis of late-onset neonatal sepsis in preterm infants

Objective: One of the most challenging aspects in the management of neonates with late-onset neonatal sepsis (LOS) is to make the diagnosis. Presepsin is a novel and promising marker of sepsis. The aim of this study was to assess the role of presepsin in the diagnosis of LOS in preterm infants.Methods: Forty-two premature newborns ≤32 weeks gestational age with a diagnosis of LOS were prospectively involved in the study. Forty gestational and postnatal age-matched infants without sepsis served as controls. Levels of presepsin, C-reactive protein, and procalcitonin were measured at enrollment and on the third and seventh days of sepsis.Results: Initial presepsin levels in the LOS group were significantly higher than in the control group (1024 pg/mL, min–max: 295–8202; versus 530 pg/mL, min–max: 190–782; p < 0.0001). The area under the receiver-operating curve for presepsin was 0.864. A presepsin value of 800.5 pg/mL was established as a cut-off value, with 67% sensitivity and 100% specificity. Presepsin levels gradually decreased during treatment.Conclusion: Presepsin can be used as a reliable biomarker for LOS and treatment response in preterm infants. However, we could not demonstrate the efficacy of presepsin for the detection of disease severity or prognosis.

Center Variation in Intestinal Microbiota Prior to Late-Onset Sepsis in Preterm Infants.

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.

Pentoxifylline therapy for late-onset sepsis in preterm infants: a randomized controlled trial.

The role of pentoxifylline (PTX) in reducing mortality associated with neonatal sepsis is not well established. We aimed to assess the efficacy and safety of PTX as an adjunct to antibiotics on mortality and morbidity in preterm infants with late-onset sepsis (LOS). Double blind, randomized controlled trial was conducted on 120 preterm infants with LOS. They were randomly assigned to receive either intravenous PTX 5 mg/kg/hr for 6 hours on 6 successive days or placebo. Death before hospital discharge was our primary outcome and secondary outcomes were length of hospital stay, duration of respiratory support, duration of antibiotics use, short-term morbidity of preterm infants, tumor necrosis factor-alpha concentrations, C-reactive protein concentrations, and adverse effects of PTX. A total of 120 infants were enrolled, 60 in each group, 78 (65%) infants had confirmed and 42 (35%) had suspected LOS. There were no significant differences between groups regarding mortality [6 (10%) in PTX vs. 10 (16.5%) in placebo, P = 0.44], short-term morbidity and combined mortality and/or short-term morbidity [18 (30%) vs. 24 (40%), P = 0.23]. PTX therapy was associated with significant reduction of serum tumor necrosis factor-alpha and C-reactive protein concentrations. The length of hospital stay, durations of respiratory support and antibiotic therapy were significantly shorter in the PTX group. Patients in PTX group had less need for vasopressors, lower incidence of metabolic acidosis, disseminated intravascular coagulopathy and thrombocytopenia. No adverse effects to PTX were reported. PTX has a beneficial adjuvant effect to antibiotic therapy in preterm infants with LOS without significant impact on neonatal mortality and morbidity.

Antibiotics Before Removal of Percutaneously Inserted Central Venous Catheters Reduces Clinical Sepsis in Premature Infants.

Evaluate the incidence of postcatheter removal clinical sepsis when antibiotics were infused prior to the removal of percutaneously inserted central venous catheters (PICCs). A retrospective chart review of premature neonates (n = 196) weighing ≤1250 g at birth with 218 PICC line removals in the presence or absence of antibiotics at a tertiary level neonatal intensive care unit (NICU) between January 1, 2010, and May 31, 2012. Charts were reviewed looking for the presence of clinical sepsis defined as a sepsis workup including white blood cell count, differential, C-reactive protein, blood and/or cerebral spinal fluid (CSF), and urine cultures along with at least 48 hours of antibiotic therapy given within 72 hours after removal of a PICC line. Antibiotics were considered present at line removal if given within 12 hours before catheter removal either electively or at completion of a planned course. When antibiotics were given within 12 hours before PICC line removal, only 2% of the line removal episodes (1/48) resulted in a neonate developing clinical sepsis versus 13% (21/165) when no antibiotics were given prior to removal (p = 0.03, Fisher's exact test). Despite the increased use of elective antibiotics with line removal, there was no increase in total antibiotic usage due to the overall decrease in episodes of clinical sepsis or changes in antibiogram susceptibility patterns. There was an 11% absolute decrease and a 6-fold relative decrease in postcatheter removal clinical sepsis events in premature neonates who received antibiotics prior to PICC line removal.

Staphylococcus epidermidis Bacteremia Induces Brain Injury in Neonatal Mice via Toll-like Receptor 2-Dependent and -Independent Pathways.

Staphylococcus epidermidis causes late-onset sepsis in preterm infants. Staphylococcus epidermidis activates host responses in part via Toll-like receptor 2 (TLR2). Epidemiologic studies link bacteremia and neonatal brain injury, but direct evidence is lacking. Wild-type and TLR2-deficient (TLR2-/-) mice were injected intravenously with S. epidermidis at postnatal day 1 prior to measuring plasma and brain cytokine and chemokine levels, bacterial clearance, brain caspase-3 activation, white/gray matter volume, and innate transcriptome. Staphylococcus epidermidis bacteremia spontaneously resolved over 24 hours without detectable bacteria in the cerebrospinal fluid (CSF). TLR2-/- mice demonstrated delayed S. epidermidis clearance from blood, spleen, and liver. Staphylococcus epidermidis increased the white blood cell count in the CSF, increased interleukin 6, interleukin 12p40, CCL2, and CXCL1 concentrations in plasma; increased the CCL2 concentration in the brain; and caused rapid (within 6 hours) TLR2-dependent brain activation of caspase-3 and TLR2-independent white matter injury. Staphylococcus epidermidis bacteremia, in the absence of bacterial entry into the CSF, impairs neonatal brain development. Staphylococcus epidermidis bacteremia induced both TLR2-dependent and -independent brain injury, with the latter occurring in the absence of TLR2, a condition associated with an increased bacterial burden. Our study indicates that the consequences of transient bacteremia in early life may be more severe than commonly appreciated, and our findings may inform novel approaches to reduce bacteremia-associated brain injury.

Pharmacokinetics of linezolid treatment using intravenous and oral administrations in extremely premature infants.

Vancomycin is the usual antibiotic treatment in coagulase-negative staphylococcus sepsis in premature infants but causes renal toxicity. As linezolid is effective in Gram-positive cocci infection, and devoid of renal side-effects, it has been used in Nantes neonatal intensive care units and linezolid plasma concentrations were monitored. The aims of this study are to report data on linezolid concentrations in premature infants, describe clinical and bacteriological evolution during treatment, and determine potential side effects. A retrospective observational study of premature infants treated with linezolid in Nantes Hospital from January 2008 through November 2011 was conducted. Linezolid plasma concentrations, possible side effects due to linezolid, and clinical response to linezolid treatment were collected from folder review. Twenty-four linezolid plasma concentrations were monitored in 16 premature patients, at steady state for continuous intravenous administration or 7 ± 1.5 h after last oral administration. Except for one case, linezolid plasma concentrations were ≥minimal inhibition concentration (MIC) for linezolid for both parenteral and oral administrations. We observed three cases of thrombocytopenia, two of leukopenia, three of neutropenia, and one of severe hyperlactacidemia, resolving after discontinuation of treatment. Clinical signs of infection resolved in 13/16 cases. Bacteria were coagulase-negative Staphylococci in 12/16 cases and were eradicated in 9/12 evaluable cases. This study reports an adequate linezolid plasma concentration with regard to the linezolid MIC in extremely premature infants. However, considering adverse events reported, its use should be cautious and may concern only oral administration during the late phase of infection, to limit paradoxical catheter use to treat nosocomial infections. Moreover, safe and efficient anti-Staphylococcus therapies should be identified to treat this vulnerable population.

Challenges in the diagnosis and management of neonatal sepsis.

Neonatal sepsis is the third leading cause of neonatal mortality and a major public health problem, especially in developing countries. Although recent medical advances have improved neonatal care, many challenges remain in the diagnosis and management of neonatal infections. The diagnosis of neonatal sepsis is complicated by the frequent presence of noninfectious conditions that resemble sepsis, especially in preterm infants, and by the absence of optimal diagnostic tests. Since neonatal sepsis is a high-risk disease, especially in preterm infants, clinicians are compelled to empirically administer antibiotics to infants with risk factors and/or signs of suspected sepsis. Unfortunately, both broad-spectrum antibiotics and prolonged treatment with empirical antibiotics are associated with adverse outcomes and increase antimicrobial resistance rates. Given the high incidence and mortality of sepsis in preterm infants and its long-term consequences on growth and development, efforts to reduce the rates of infection in this vulnerable population are one of the most important interventions in neonatal care. In this review, we discuss the most common questions and challenges in the diagnosis and management of neonatal sepsis, with a focus on developing countries.

Risk factors of sepsis in premature infants

Introduction: Neonatal sepsis is one of the most important causes of morbidity and mortality in preterm infants. Neonatal sepsis is defined as invasive bacterial infection that occurs in newborn children from the first to the ninetieth day of life. Hemoculture still represents the gold standard for the detection of sepsis. Blood culture may be falsely positive due to contamination of the samples. Contaminated blood cultures increase treatment costs and extend the length of stay of premature babies in hospitals. The aim of the study was to determine the incidence and risk factors of sepsis in premature infants who are being treated in the intensive care. Also to determine whether preventive medical-technical procedures will reduce the incidence of neonatal sepsis, as well as a reduction in contamination hemocultures. Materials and Methods: 239 premature infants have been analysed in whom the observed risk factors can lead to the onset neonatal sepsis. The preventive actions that could lead to a reduction of contamination in hemocultures have also been analysed. Results: The most common risk factors for sepsis is a small gestational age and body weight below 2000g. By using aseptic techniques for taking hemocultures there was a significant reduction in contamination of the same. Conclusion. Statistical analysis of the data identified the most common factors that lead to the occurrence of neonatal sepsis and proved the significance of the reduction of hemoculture contamination after the introduction of aseptic procedures and check lists.

Risk factors for nosocomial sepsis in preterm infants

Objective To identify the risk factors for nosocomial sepsis in preterm infants.Methods A case-control study (1 ∶ 2) was conducted in 81 preterm infants with nosocomial sepsis and 162 preterm infants without nosocomial sepsis as age-matched controls (admission time was the most closely) hospitalized in Fujian Maternity and Children Hospital from January 1,2007 to December 31,2011.Data of preterm infants including maternal,delivery and neonatal records were collected.Risk factors for nosocomial sepsis were analyzed using t test,x2 test and multivariate Logistic regression.Results Nosocomial sepsis occurred in 81 preterm infants with an incidence rate of 1.50％ (81/5 392).Univariate analysis showed that the gestational age [(31.8 ±2.4)vs(33.8 ± 1.8)weeks,t=-7.260,P＜0.01] and birth weight [(1 545± 349) vs (2 174±465) g,t=-10.750,P＜0.01] of neonates with nosocomial sepsis were lower than those in the controls.Compared with the controls,the neonates with nosocomial sepsis had higher incidence of small for gestational age [27.2％ (22/81) vs 11.7％ (19/162)],multiple birth [35.8％ (29/81) vs 21.6％ (35/162)],neonatal asphyxia [19.8％(16/81)vs 8.6％(14/162)],admission to neonatal intensive care unit [81.5％(66/81) vs 49.4％ (80/162)],incubator usage [87.7％ (71/81) vs 29.0％ (47/162)],intracranial hemorrhage [27.2％ (22/81)vs 14.2％ (23/162)],noninvasive ventilation [35.8％ (29/81)vs 14.8％ (24/162)],feeding intolerance [64.2％ (52/81) vs 17.9％ (29/162)],using probiotics [65.4％ (53/81) vs 37.0％ (60/162)],duration of parenteral nutrition ＞7 days [77.8％ (63/81) vs 16.0％ (26/162)],combined administration of antibiotics [61.7％(50/81) vs 43.8％(71/162)],duration of antibiotics administration ＞7 days [65.4％(53/81) vs 9.3％ (15/162)],intravenous immunoglobulin [76.5％ (62/81) vs 46.9％ (76/162)] and central vena catheterization [16.0％ (13/81) vs 1.2％ (2/162)] (all P＜0.05).The Logistic regression analysis showed that low birth weight (OR=2.087,95％CI:1.074 4.057),duration of parenteral nutrition ＞7 days (OR=3.075,95％CI:1.158 8.164),feeding intolerance (OR-4.328,95％CI:1.776-10.544) and duration of antibiotic administration ＞7 days (OR=18.443,95％CI:5.084-66.913) were independent risk factors for nosocomial sepsis in preterm infants (all P＜0.05).Conclusions Preterm infants with low birth weight,long duration of parenteral nutrition,long-term antibiotic treatment and feeding intolerance have high risk for nosocomial sepsis. Key words: Infant, premature; Nosocomial infection; Sepsis; Risk factors

PC.99 PINC UK (Probiotics in Neonatal Collaboration in UK)

BackgroundProbiotics have been shown to reduce the risk for definite Necrotising enterocolitis (NEC) and all-cause mortality in very low birth weight babies without any significant adverse effects in > 5000...

Correlation between neopterin levels in premature infants with sepsis and the signs and symptoms of neonatal sepsis using the Töllner sepsis score

Abstract Neonatal sepsis in premature infants is difficult to diagnose, and available markers are still varied. Neopterin is a derivative of pyrazino-pyrimidine produced by macrophages when stimulated by interferon γ. This study aimed to measure and compare the concentration of serum neopterin between groups of neonates with and without sepsis, and its correlation with Töllner’s sepsis score (TSS). This analytic observational study with a cross-sectional design included 46 premature infants with (n=23) and without neonatal sepsis (n=23). Data analysis using the Mann-Whitney U-test was performed to compare the levels of neopterin in premature infants with and without neonatal sepsis, and the Spearman rank correlation test to determine the correlation between neopterin levels and TSS. Neopterin levels in the sepsis group were higher than in the non-sepsis group (116 vs. 41.1 nmol/L; p&lt;0.001). This study also showed a positive correlation between neopterin levels in premature infants with neonatal sepsis and TSS (r=0.776, p&lt;0.001). Neopterin levels were higher in premature infants with neonatal sepsis than in those without it and positively correlated with TSS.

Cord blood procalcitonin and Interleukin-6 are highly sensitive and specific in the prediction of early-onset sepsis in preterm infants

We studied the predictive value of cord blood procalcitonin (PCT) and interleukin-6 (IL-6) in the diagnosis of early-onset sepsis (EOS) in the preterm infant. Retrospectively, PCT and IL-6 were correlated with clinical and/or blood culture positive EOS and negative infectious status between February 2008 and March 2011. Receiver operating curves (ROC) were generated and the area under the curve (AUC) was calculated by use of Youden's Index to detect the best cut-off values for sensitivity and specificity. Thirty of 218 preterm infants (13.8%) were diagnosed as having EOS. The optimal cut-off value for PCT was 0.235 μg/L (sensitivity 78.6%, specificity 86.3%), and for IL-6 15.85 ng/L (sensitivity 73.7%, specificity 84.2%), the combination of PCT and IL-6 revealed sensitivity 77.1% and specificity 91.7%. The combined determination of PCT and IL-6 from cord blood was highly sensitive and specific in the prediction of EOS.

The effect of topical ointment on neonatal sepsis in preterm infants

Objective: To investigate the effects of topical ointment therapy on neonatal sepsis in premature infants.Methods: A total of 197 premature infants ≤ 34 weeks gestation were randomized to receive topical ointment (Aquaphor Original Emollient) or routine skin care group. Skin cultures were obtained on 3th, 7th and 14th day and blood cultures were obtained if sepsis was suspected clinically. Data included the maternal and neonatal characteristics, factors affecting the risk of sepsis and neonatal outcomes of both groups were collected.Results: There were no significant differences in terms of gestational age, birth weight, gender, mode of delivery, multiple pregnancy and receiving antenatal corticosteroids between the study and control group. No statistically significant difference was found in the prevalence of sepsis, in the positive skin culture rates at any follow-up and in terms of the neonatal morbidities including patent ductus arteriosus and necrotizing enterocolitis between the groups. Although the rate of death was higher in the topical ointment group, no statistically significant difference was found between the groups.Conclusions: Our data suggests that applying topical ointment during the first 2 postnatal weeks did not affect the risk of neonatal sepsis in preterm infants, although it changed the bacterial flora on the skin compare to the routine care group.

Intestinal microbiome colonization patterns differ prior to late onset sepsis in premature infants (637.3)

Late onset sepsis (LOS), a major cause of illness and death in premature infants, may be caused by translocation of bacteria through the permeable gut of the preterm infant. To test this, we studied 28 LOS cases frequency matched on gestational age (GA) to 28 controls. Infants were &lt;33 weeks GA from Cincinnati. Cases and controls did not differ by race, gender, delivery mode or birthweight. Stool samples were collected prospectively prior to sepsis for the first 2 weeks of life. Using DNA from stool samples, we sequenced the 16s rRNA gene with universal primers by Illumina MiSeq. Operational taxonomic unit (OTU) tables were analyzed by linear discriminant analysis effect size algorithm with significance at p&lt;0.05. Week 1 of life case samples were significantly enriched in OTUs classified as Enterobacteriaceae. Analysis of week 2 samples found that infants who developed Gram positive LOS were significantly enriched in OTUs of Gram positive Staphylococcus, while infants who subsequently developed Gram negative LOS were significantly enriched in OTUs of Gram negative Enterobacteriaeae. The most common causative organisms in our study were Staphylococcus species in Gram positive LOS and Enterobacteriaceae species in Gram negative LOS. Our findings support the hypothesis that the gut microbiota contribute to increased risk of LOS. A larger study of LOS, infant genetics, and microbial colonization is ongoing.Grant Funding Source: Supported by NIAID contract no. HHSN272200900018C; NICHD R01 HD059140; and NIEHS T32 ES010957

NOD1 and NOD2 expression and function in very preterm infant mononuclear cells

To evaluate mononuclear cell expression and function of the cytosolic nucleotide-binding oligomerization domain-containing receptors, NOD1 and NOD2, in very preterm and full-term infants. NOD1 and NOD2 gene and protein expression in very preterm infants, term infants and healthy adult, cord and peripheral blood mononuclear cells (C/PBMC) were quantified using qPCR and flow cytometry. Cytokine responses of purified infant and adult monocytes to NOD1- and NOD2-specific agonists were assessed using a multiplex immunoassay (Bioplex). NOD1 and NOD2 were expressed by a range of infant and adult mononuclear cell types, including T- and B cells, with highest expression in classical (CD14(++) CD16(-) ) and intermediate (CD14(++) CD16(+) ) monocytes. NOD1 and NOD2 expression levels by monocytes from very preterm infant were similar to those in term infants or adults. Monocyte production of TNFα, IL-6 and IL-1β induced by activation of NOD1 and NOD2 was similar between very preterm infants, term infants and adults. Monocyte expression and function of NOD1 and NOD2 in very preterm infants are intact and comparable/equivalent to term infants and adults. Functional deficiencies in monocyte NOD signalling pathways are unlikely to contribute to the increased susceptibility to bacterial sepsis in preterm infants.