Late-onset Sepsis In Preterm Neonates Research Articles

Inflammation, sepsis severity and neurodevelopmental outcomes of late-onset sepsis in preterm neonates.

The aim of this study was to investigate the association between inflammatory biomarkers (C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6)) and sepsis severity (neonatal-Sequential-Organ-Failure-Assessment (nSOFA)) and neurodevelopmental outcomes at 2 years, among very preterm neonates. Data on preterm neonates (gestational age <30 weeks) from 2016 until 2020 were reviewed. Outcomes of interest were NDI (no, mild, severe) and the motor and cognitive score on the Dutch-Bayley-Scales-of-Infant-and-Toddler-Development (Bayley-III-NL) assessed at the corrected age of 2 years. Logistic and linear regression analysis were used for categorical and continuous outcomes, respectively. All analyses were adjusted for gestational age, sex and birthweight-for-gestational-age SD-score. In total 410 patients were eligible for analysis. Maximum CRP concentrations were associated with lower motor and cognitive scores (effect estimate -0.03 points,(95% CI -0.07; -0.00) and -0.03 points,(95% CI -0.06; -0.004), respectively) and increased risk of severe NDI (odds ratio (OR) 1.01, (95% CI 1.00; 1.01)). High nSOFA scores (≥4) during sepsis episodes were associated with an increased risk of mild NDI (OR 2.01, (95% CI 1.34; 3.03)). There were no consistent associations between IL-6, PCT and the outcomes of interest. High CRP concentrations and sepsis severity in preterm neonates seem to be associated with neurodevelopmental outcomes in survivors at the age of 2 years. The level of inflammation and sepsis severity are associated with neurodevelopmental outcome in preterm neonates at 2 years of corrected age. Sepsis is a major health issue in preterm neonates and can lead to brain damage and impaired neurodevelopment. Biomarkers can be determined to assess the level of inflammation. However, the relation of inflammatory biomarkers with neurodevelopmental outcome is not known. The level of inflammation and sepsis severity are related to neurodevelopmental outcome in preterm neonates. Maximum CRP concentration and high nSOFA scores are associated with an increased risk of neurodevelopmental impairment in survivors at the corrected age of 2 years.

Carboxyhemoglobin Levels in Preterm Neonatal Late-Onset Sepsis: to Predict or not to Predict.

In this study, we aimed to evaluate carboxyhemoglobin (COHb) levels in diagnosing late-onset sepsis (LOS) in preterm neonates. The records of culture-positive LOS in preterm neonates hospitalized in NICU from January 2017 to July 2022 were reviewed. COHb levels, C-reactive protein, procalcitonin, and neutrophil to lymphocyte ratio of septic preterm infants were compared to controls. In addition, serial COHb levels measured within six hours before or 24h after blood culture sampling, three to seven days prior, and three to five days after starting antimicrobial therapy were retrieved from patient records. The study included 77 blood-culture-positive preterm infants and 77 non-septic controls. During the LOS episode, the COHb values were found to be significantly increased (median: 1.8, IQR: 1.4-2.5) when compared to the control group (median: 1.2, IQR: 0.8-1.6) (p < 0.001). ROC analysis yielded an AUC of 0.714 for COHb (95% CI: 0.631-0.796, p<0.001). At an optimal cut-off of >1.5%, the test's sensitivity was 64.94%, the specificity was 72.73%, the positive predictive value was 70.42%, and the negative predictive value was 67.47%. LOS led to a dramatic rise followed by a decrease after the initiation of the antimicrobial therapy [1.8 (1.4-2.5)] vs. [1.45 (0.2-4)] p<0.001. COHb levels increased at the beginning of LOS, decreasing in response to antibiotics. When used in conjunction with other sepsis biomarkers, the variation of COHb can be important in evaluating late-onset sepsis episodes in preterm infants.

Late-onset Sepsis in Preterm Neonates is Associated with Higher Risks of Cerebellar Hemorrhage and Lower Motor Scores at Three Years of Age.

ObjectivesTo evaluate the impact of late-onset sepsis (LOS) in preterm infants on brain injury and neurodevelopmental outcomes at 36 months corrected age (CA).MethodsWe retrospectively analyzed the medical records of 203 preterm neonates of 24–32 weeks gestational age who were admitted between January and December 2017 at the neonatal intensive care unit (NICU) of a maternity hospital in Kuwait. The cases were stratified into no sepsis, early-onset sepsis (first onset of sepsis ≤ 72 hours postnatally), and LOS (> 72 hours postnatally). Brain injury was assessed from MRI records. Neurodevelopmental outcomes were evaluated at 36 months CA using Bayley-III scales of infant development.ResultsOut of 203 neonates, 16 had early-onset sepsis with Klebsiella pneumonia and group B streptococcus, and 93 developed LOS with K. pneumonia and gram-positive cocci in clusters. There were no group-wise differences in the prevalence of intraventricular hemorrhage (n = 68) or white matter injury (n = 42). However, higher cerebellar hemorrhage risk (adjusted odds ratio = 4.6 (1.3–18.6; p = 0.030) was observed in LOS group. At 36 months CA, infants in the LOS group were more likely to have lower motor, cognitive, and language composite scores. After adjusting for gestational age, birth weight, cerebellar hemorrhage, and white matter injury, the relationship between LOS and lower motor scores remained significant (adjusted β = –9.5, 95% CI: –16.4 to –2.7; p = 0.007), whereas the association with cognitive and language scores were no longer significant.ConclusionsLOS in preterm neonates significantly raises the risk of cerebellar hemorrhage and lower motor scores by three years of age.

Oral Application of Colostrum and Mother's Own Milk in Preterm Infants-A Randomized, Controlled Trial.

To evaluate the effects of oral application of mother's own milk (OMOM) on clinical outcomes in preterm infants of 260/7-306/7 wk gestation. In this placebo-controlled randomized trial, subjects received either OMOM or sterile water, beginning at 24-72h of life, until the infant reached 32 wk postmenstrual age or spoon-feeds were initiated, whichever was earlier. The primary outcome was a composite adverse health outcome, defined as the occurrence of either mortality, late-onset sepsis (LOS), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), or retinopathy of prematurity (ROP). Antibiotic usage and time to full enteral feed were secondary outcomes. Salivary IgA (sIgA) levels at baseline and after 7 d of application in a subset of infants were also compared. A total of 133 neonates (66 colostrum and 67 placebo) were analyzed for the primary outcome. OMOM group had lower incidence of composite adverse health outcome (43.9% vs. 61.2%, RR: 0.70; 95% CI: 0.50-0.99, p = 0.046) and LOS (22.7% vs. 43.3%, RR: 0.73; 95% CI: 0.57-0.93; p = 0.012). There were no significant differences in mortality, NEC, IVH, BPD, ROP, and time to full feeds. The effects were more pronounced in the 290/7-306/7 wk subgroup, in whom the colostrum group also achieved full feeds earlier. There were no differences in the change of sIgA levels from baseline to the seventh day of the application. No adverse effects related to the OMOM application were found. OMOM decreases the incidence of late-onset sepsis in preterm neonates (260/7-306/7 wk) and is safe. Clinical Trials Registry-IndiaCTRI/2017/03/008031.

Probiotics (Bacillus clausii) for Prevention of Late-onset Sepsis in Preterm Infants (&lt;34 weeks): A Randomised Controlled Trial

Introduction: Late-onset Sepsis (LOS) causes significant morbidity and mortality in preterm infants. Probiotics have been suggested to improve the integrity of mucosal barrier by modifying the enteric microflora and suppress the overgrowth and translocation of pathogens in the gut, thus preventing life- threatening infections. Although probiotics have a definite role in prevention of Necrotising Enterocolitis (NEC) in preterm neonates, their effect on prevention of LOS in preterm neonates is still uncertain. Aim: To evaluate the role of probiotics in reducing incidence of LOS in preterm neonates (&lt;34 weeks). Materials and Methods: A double blinded randomised control trial was conducted in a tertiary care Neonatal Intensive Care Unit (NICU) in Karnataka, India between 1st January 2019 to 31st December 2019. Seventy haemodynamically stable preterm neonates, &lt;34 weeks of Gestational Age (GA), were randomised into ‘Probiotic’ and ‘Placebo’ groups. The probiotic group (n=36) was prophylactically administered Bacillus clausii suspension at a dose of 2.5 mL per-oral (0.4×109 spores in 1 mL) BD with breast milk, from initiation of enteral feeds till seven days, discharge/ death/LOS, whichever was earlier. The placebo group (n=34) received breast milk with sterile water 2.5 mL per- oral BD. All the neonates were investigated and managed as per standard hospital protocol. Primary outcome of the study was to find the incidence of LOS. Student’s t-test, Mann-Whitney U test, Chi-square test and Fisher’s exact test were used for statistical analysis. Results: There was no significant difference between the probiotic vs placebo group, with respect to incidence of LOS (11.11% vs 17.64%; (p&gt;0.05)) and duration of hospital stay (10.86±3.19 vs 11.23±2.98 days; (p&gt;0.05)). However, incidence of feed intolerance in the probiotic group (11.11%) was significantly less than that the other (26%) (p&lt;0.05). Conclusion: Probiotics, prophylactically fed enterally, did not reduce the incidence of LOS but provide a promising strategy to prevent feed intolerance in premature neonates.

Chorioamnionitis and Risk for Maternal and Neonatal Sepsis: A Systematic Review and Meta-analysis.

To estimate the risk of maternal and neonatal sepsis associated with chorioamnionitis. PubMed, BIOSIS, and ClinicalTrials.gov databases were systematically searched for full-text articles in English from inception until May 11, 2020. We screened 1,251 studies. Randomized controlled trials, case-control, or cohort studies quantifying a relationship between chorioamnionitis and sepsis in mothers (postpartum) or neonates born at greater than 22 weeks of gestation were eligible. Studies were grouped for meta-analyses according to exposures of histologic or clinical chorioamnionitis and outcomes of maternal or neonatal sepsis. One hundred three studies were included, and 55 met criteria for meta-analysis (39 studies of preterm neonates, 10 studies of general populations of preterm and term neonates, and six studies of late preterm and term neonates). Study details and quantitative data were abstracted. Random-effects models were used to generate pooled odds ratios (ORs); most studies only reported unadjusted results. Histologic chorioamnionitis was associated with confirmed and any early-onset neonatal sepsis (unadjusted pooled ORs 4.42 [95% CI 2.68-7.29] and 5.88 [95% CI 3.68-9.41], respectively). Clinical chorioamnionitis was also associated with confirmed and any early-onset neonatal sepsis (unadjusted pooled ORs 6.82 [95% CI 4.93-9.45] and 3.90 [95% CI 2.74-5.55], respectively). Additionally, histologic and clinical chorioamnionitis were each associated with higher odds of late-onset sepsis in preterm neonates. Confirmed sepsis incidence was 7% (early-onset) and 22% (late-onset) for histologic and 6% (early-onset) and 26% (late-onset) for clinical chorioamnionitis-exposed neonates. Three studies evaluated chorioamnionitis and maternal sepsis and were inconclusive. Both histologic and clinical chorioamnionitis were associated with early- and late-onset sepsis in neonates. Overall, our findings support current guidelines for preventative neonatal care. There was insufficient evidence to determine the association between chorioamnionitis and maternal sepsis. PROSPERO, CRD42020156812.

Gut priming with bovine colostrum and T regulatory cells in preterm neonates: a randomized controlled trial.

Necrotizing enterocolitis (NEC) and neonatal sepsis are still considered major problems, especially in formula-fed preterm neonates. This study aimed to investigate the effect of bovine colostrum on T regulatory cells, NEC, and late-onset sepsis in preterm neonates ≤34 weeks. This prospective double-blind randomized controlled trial was conducted on 80 preterm infants who were randomly assigned to either the bovine colostrum group (n = 32) or control group (n = 48). T lymphocytes and their subsets, necrotizing enterocolitis, late-onset sepsis (LOS) and its severity, feeding tolerance, growth, length of hospital stay, and mortality were documented. The bovine colostrum group showed higher follow-up levels of CD4+CD25+ FOXP3+ T lymphocyte % (FOXP3 Tregs). FOXP3 Tregs and its difference in change levels between baseline and follow-up were considered as the most related factors to the bovine colostrum. Bovine colostrum group showed positive trends for reduction of sepsis severity and mortality with no significant difference in the incidence of NEC, LOS, and length of hospital stay. Preterm neonates who received bovine colostrum showed a higher FOXP3 Treg level. Bovine colostrum has no significant effect on the incidence of necrotizing enterocolitis. FOXP3 T regulatory cells and their increased level between baseline and follow-up is considered as the most influencing factors related to the bovine colostrum. Positive trends were noted for reduction of sepsis severity and concomitant mortality, but the study lacked the power to assess these outcomes.

Effect of lactoferrin in the prevention of late-onset sepsis in preterm neonates: a randomized-controlled trial

Background Lactoferrin (LTF) is a promising drug in the prevention of late-onset sepsis (LOS) in preterm infants as it causes priming of the immune system before the occurrence of insult.Aim The aim of this study is to evaluate the effect of LTF in the prevention of LOS.Participants and methods Preterm infants of gestational age less than or equal to 34 weeks showing no signs of sepsis in the first 72 h and admitted to NICU of Alexandria University Children Hospital from August 2019 to April 2020 were included in this study. Fifty six patients were randomly allocated into two groups: LTF group (n=28 patients) and control group (n=28 patients). Patients in the LTF group received LTF for 28 days postnatally or till 36 weeks postmenstrual age, whichever is reached first. All patients were monitored for development of LOS.Results Compared with the control group, LTF treatment was associated with a significantly lower incidence of culture-proven LOS (8/28 vs. 2/28, respectively) with a P value of 0.036. The administration of LTF decreased the serum C-reactive protein level at the end of the study in comparison with the level at the beginning of the study in the LTF group, with a mean value of 5.44±16.18 versus 3.71±2.57, respectively (P=0.021), and in comparison with the control group, with a mean value of 5.44±16.18 versus 27.45±55.20, respectively (P=0.021).Conclusion LTF reduces the incidence of culture-proven LOS in preterm neonates aged less than or equal to 34 weeks. LTF has been proven to have anti-inflammatory properties through its ability to decrease the C-reactive protein level.

Staphylococcus epidermidis in feedings and feces of preterm neonates.

Staphylococcus epidermidis has emerged as the leading agent causing neonatal late-onset sepsis in preterm neonates; although the severity of the episodes caused by this species is often underestimated, it might exert relevant short- and long-term detrimental effects on neonatal outcomes. In this context, the objective of this study was to characterize a collection of S. epidermidis strains obtained from meconium and feces of preterm infants, and to assess the potential role of the enteral feeding tubes as potential reservoirs for this microorganism. A total of 26 preterm infants were enrolled in the study. Meconium and fecal samples were collected weekly during their first month of life (n = 92). Feeding samples were collected after their pass through the enteral feeding tubes (n = 84). S. epidermidis was present in the fecal samples of all the infants in, at least, one sampling time at concentrations ranging from 6.5 to 7.8 log10 CFU/g. Initially, 344 isolates were obtained and pulsed-field gel electrophoresis (PFGE) profiling allowed the reduction of the collection to 101 strains. Among them, multilocus sequence typing (MLST) profiling showed the presence of 32 different sequence types (ST). Globally, most of the STs to hospital-adapted high-risk clones and belonged to clonal complexes (CC) associated to the hospital environment, such as CC2. The virulence gene most commonly detected among the strains was altE. High resistance rates to macrolides and aminoglycosides were detected and 64% of the strains harboured the mecA gene, which was codified in SCCmec types. Our results indicates the existence of a complex and genetically diverse S. epidermidis population in the NICU environment. A better knowledge of S. epidermidis strains may help to devise strategies to avoid their conversion from symbiont to pathobiont microorganisms in the NICUs.

Toward Early Diagnosis of Late-Onset Sepsis in Preterm Neonates: Dual Magnetoimmunosensor for Simultaneous Procalcitonin and C-Reactive Protein Determination in Diagnosed Clinical Samples.

Early diagnosis of sepsis, combining blood cultures and inflammation biomarkers, continues to be a challenge, especially in very low birth weight (VLBW) infants because of limited availability of blood samples. Traditional diagnostic procedures are cumbersome, not fast enough, and require relatively large volumes of sample. Empiric use of antibiotics, before diagnostic confirmation, is required to decrease mortality, leading to potential antibiotic resistance and side effects in VLBW infants. To solve such a serious problem, a dual magnetoimmunosensor is proposed for simultaneous assessment of two of the most important sepsis biomarkers: procalcitonin (PCT for early phase) and C-reactive protein (CRP for late phase). This "sample-to-result" approach exhibited excellent sensitivity, selectivity, precision, and stability using low sample volumes (<30 μL) and under 20 min of total assay. The analytical usefulness of the approach was demonstrated by analyzing clinically relevant samples of preterm neonates with suspicion of sepsis.

Is Lactoferrin More Effective in Reducing Late-Onset Sepsis in Preterm Neonates Fed Formula Than in Those Receiving Mother's Own Milk? Secondary Analyses of Two Multicenter Randomized Controlled Trials.

Lactoferrin is the major antimicrobial protein in human milk. In our randomized controlled trial (RCT) of bovine lactoferrin (BLF) supplementation in preterm neonates, BLF reduced late-onset sepsis (LOS). Mother's own milk (MM) contains higher concentrations of lactoferrin than donor milk or formula, but whether BLF is more effective in infants who receive formula or donor milk is uncertain. To evaluate the incidence of LOS in preterm infants fed MM and in those fed formula and/or donor milk. This is a (A) post hoc subgroup analysis, in our RCT of BLF, of its effects in preterm infants fed MM, with or without formula, versus those fed formula and/or donor milk (no-MM) and (B) post hoc meta-analysis, in our RCT of BLF and in the ELFIN (Enteral Lactoferrin in Neonates) RCT, of the effect of BLF in subgroups not exclusively fed MM. (A) Of 472 infants in our RCT, 168 were randomized to placebo and 304 were randomized to BLF. Among MM infants, LOS occurred in 22/133 (16.5%) infants randomized to placebo and in 14/250 (5.6%) randomized to BLF (relative risk or risk ratio (RR): 0.34; relative risk reduction (RRR): 0.66; 95% confidence interval (95% CI) for RR: 0.18-0.64; p < 0.0008). Among no-MM infants, LOS occurred in 7/35 (20.0%) randomized to placebo and in 2/54 (3.7%) randomized to BLF (RR: 0.19; RRR: 0.81; 95% CI for RR: 0.16-0.96; p = 0.026). In multivariable logistic regression analysis, there was no interaction between BLF treatment effect and type of feeding (p = 0.628). (B) In 1,891 infants not exclusively fed MM in our RCT of BLF and in the ELFIN RCT, BLF reduced the RR of LOS by 18% (RR: 0.82; 95% CI: 0.71-0.96; p = 0.01). Adequately powered studies should address the hypothesis that BLF is more effective in infants fed formula or donor milk than those fed MM. Such studies should evaluate whether a specific threshold of total lactoferrin intake can be identified to protect such patients from LOS.

Genetic Relatedness of Staphylococcus haemolyticus in Gut and Skin of Preterm Neonates and Breast Milk of Their Mothers.

Staphylococcus haemolyticus is a common colonizer and cause of late-onset sepsis (LOS) in preterm neonates. By describing genetic relatedness, we aimed to determine whether mother's breast milk (BM) is a source of S. haemolyticus colonizing neonatal gut and skin and/or causing LOS. S. haemolyticus was isolated from stool and skin swabs of 49 BM-fed preterm neonates admitted to neonatal intensive care unit, 20 healthy BM-fed term neonates and BM of mothers once a week and typed by multilocus variable number tandem repeat analysis and multilocus sequence typing. Virulence-related genes were determined by polymerase chain reaction. Compared with term neonates, S. haemolyticus colonized more commonly gut (35% vs. 89.9%; P < 0.001) and skin (50% vs. 91.8%; P < 0.001) of preterm neonates and mothers' BM (15% vs. 38.8%). Isolates from preterm compared with term neonates and their mothers carried more commonly the mecA gene (83.5% vs. 5.4%; P < 0.001) and IS256 (52.4% vs. 2.7%; P < 0.001) and belonged to clonal complex 29 (89.1% vs. 63%; P = 0.014). Only 7 (14.3%) preterm and 3 (15%) term neonates were colonized in gut or on skin with multilocus variable number tandem repeat analysis types indistinguishable from those in BM. Most frequent multilocus variable number tandem repeat analysis types belonged to sequence type 3 or 42, comprised 71.1%-78.4% of isolates from preterm neonates/mothers and caused all 7 LOS episodes. LOS-causing strain colonized the gut of 4/7 and the skin of 5/7 neonates, but not BM, before onset of LOS. S. haemolyticus colonizing gut and skin or causing LOS in preterm neonates rarely originate from BM but are mecA-positive strains adapted to hospital environment.

Association between birth route and late-onset sepsis in very preterm neonates.

To evaluate the association between birth route and late-onset sepsis (LOS), and coagulase-negative Staphylococcal (CONS)-related LOS in preterm neonates. In this observational study, data from 20,038 infants born between 22 and 32 weeks' gestation and admitted to Canadian neonatal intensive care units between 2010 and 2014 were analyzed retrospectively. The impact of birth route on LOS was assessed using univariate analysis and multiple logistic regression. A total of 8218 neonates were born via vaginal route and 11,820 via cesarean section. Incidence rates of LOS for infants born vaginally and via a cesarean section were 13.1 and 13.2%, respectively, and there was no significant difference in odds of LOS between the groups (adjusted odds ratio (AOR): 0.99; 95% CI 0.87 to 1.12); however, the odds of CONS sepsis were higher in the cesarean group (AOR: 1.15; 95% CI: 1.01 to 1.32). Birth route did not have an impact on LOS, but was associated with CONS-related LOS.

Probiotics for Preventing Late-Onset Sepsis in Preterm Neonates: A PRISMA-Compliant Systematic Review and Meta-Analysis of Randomized Controlled Trials.

The effect of probiotics on late-onset sepsis (LOS) in preterm neonates remains controversial. The authors systematically reviewed the literature to investigate whether enteral probiotic supplementation reduced the risk of LOS in preterm neonates in neonatal intensive care units.PubMed, Embase, and Cochrane Central Register of Controlled Trials were systematically searched for randomized controlled trials (RCTs) regarding the effect of probiotics in preterm neonates. The primary outcome was culture-proven bacterial and/or fungal sepsis. The Mantel–Haenszel method with random-effects model was used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs).Twenty-seven trials were included in our review, and 25 trials involving 6104 preterm neonates were statistically analyzed. Pooled analysis indicated that enteral probiotic supplementation significantly reduced the risk of any sepsis (25 RCTs; RR 0.83, 95% CI 0.73–0.94; I2 = 26%), bacterial sepsis (11 RCTs; RR 0.82, 95% CI 0.71–0.95; I2 = 0%), and fungal sepsis (6 RCTs; RR 0.57, 95% CI 0.41–0.78; I2 = 0%). This beneficial effect remains in very low birth weight infants (<1500 g) (19 RCTs; RR 0.86, 95% CI 0.75–0.97; I2 = 18%), but not in extremely low birth weight infants (<1000 g) (3 RCTs; RR 0.73, 95% CI 0.45–1.19; I2 = 53%). All the included trials reported no systemic infection caused by the supplemental probiotic organisms.Current evidence indicates that probiotic supplementation is safe, and effective in reducing the risk of LOS in preterm neonates in neonatal intensive care units. Further studies are needed to address the optimal probiotic organism, dosing, timing, and duration. High-quality and adequately powered RCTs regarding the efficacy and safety of the use of probiotics in extremely low birth weight infants are still warranted.

Risk Factors and Outcomes of Late-Onset Bacterial Sepsis in Preterm Neonates Born at < 32 Weeks' Gestation.

This study aims to identify the incidence, risk factors, and outcomes of late-onset sepsis in preterm neonates in Canadian neonatal intensive care units (NICUs). This retrospective analysis included preterm infants born at < 32 weeks' gestation and admitted to 29 NICUs in the Canadian Neonatal Network during the years 2010 and 2011. Infants were classified into three groups: no infection, gram-positive infection, and gram-negative infection. Late-onset sepsis was defined as positive blood and/or spinal fluid cultures after 3 days of birth. Risk factors and the primary outcome of mortality or bronchopulmonary dysplasia (BPD) were compared between the groups. Out of the 7,509 neonates, 6,405 (85%) had no infection, 909 (12%) had gram-positive, and 195 (3%) had gram-negative infections. Lower gestation, higher Score for Neonatal Acute Physiology, version II scores, the presence of central catheters for > 4 days, parenteral nutrition for > 7 days, and prolonged duration of nothing by mouth were associated with late-onset sepsis. After controlling for confounders, the odds ratio (OR) of mortality/BPD were higher in infants who had gram-negative (OR 2.79, 95% confidence interval [CI] 1.96-3.97) and gram-positive (OR 1.44, 95% CI 1.21-1.71) sepsis as compared with no infection. Bacterial late-onset sepsis in very preterm neonates was associated with mortality and BPD. Neonates with gram-negative sepsis had the highest risk of adverse outcomes as compared with gram-positive sepsis or no sepsis.

Pre-inflammatory Mediators and Lymphocyte Subpopulations in Preterm Neonates with Sepsis

The aim of this study is to investigate prospectively specific immune system factors in preterm neonates with late-onset sepsis and infection-free controls. Matched preterm neonates (n = 82) were divided into three groups: suspected infection (n = 25), sepsis (n = 17), and infection-free controls (n = 40). Serial measurements were made of interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), lymphocyte subsets [CD3+, CD4+, CD8+, natural killer (NK) cells, and B cells], the immunoglobulins (IgG, IgM, and IgA), C-reactive protein (CRP), and the total blood count, before, 2days after initiation of treatment, and after stopping treatment. The percentages of NK and B cells were higher in the sepsis group, but those of CD3+, CD4+, and CD8+ showed no differences. IgG was lower in the sepsis group. IL-6 >30pg/ml and TNF-α >30pg/ml were sensitive sepsis predictors with sensitivity 1 (0.78-1) and 1 (0.79-1), respectively, but their specificity was poor. CRP was a specific [0.90 (0.80-0.96)] but not sensitive index [0.68 (0.48-0.85)], and its combination with IL-6 or TNF-α could enhance their diagnostic accuracy. It is concluded that NK and B cells may be elevated in late neonatal sepsis. IL-6 or TNF-α combined with CRP is a good diagnostic marker for late-onset sepsis in preterm neonates.

Cold Spots in Neonatal Incubators Are Hot Spots for Microbial Contamination

Thermal stability is essential for the survival and well-being of preterm neonates. This is achieved in neonatal incubators by raising the ambient temperature and humidity to sufficiently high levels. However, potentially pathogenic microorganisms also can thrive in such warm and humid environments. We therefore investigated whether the level of microbial contamination (i.e., the bacterial load) inside neonatal incubators can be predicted on the basis of their average temperature and relative humidity settings, paying special attention to local temperature differences. Swab samples were taken from the warmest and coldest spots found within Caleo incubators, and these were plated to determine the number of microbial CFU per location. In incubators with high average temperature (≥ 34°C) and relative humidity (≥ 60%) values, the level of microbial contamination was significantly higher at cold spots than at hot spots. This relates to the fact that the local equilibrium relative humidity at cold spots is sufficiently high to sustain microbial growth. The abundance of staphylococci, which are the main causative agents of late-onset sepsis in preterm neonates, was found to be elevated significantly in cold areas. These findings can be used to improve basic incubator hygiene.

519 Predictive Value of Clinical Signs in Late-Onset Sepsis (LOS) in Preterm Neonates

Background: Accurate diagnosis of LOS in preterm neonates is a major challenge because clinical signs are aspecific leading to unnecessary antibiotic treatment. Aims: To determine the predictive value of clinical signs for identifying LOS in preterm infants. Methods: In all patients 2 seconds, dys/tachypnea, increasing oxygen-need, tachycardia, thermal instability, hyper/hypothermia, feeding difficulties, increasing apnoeic spells, lethargy and irritability) and 4 risk factors (gestational age (GA), weight, sex, central venous catheter (CVC), mechanical ventilation, postnatal age) were prospectively assessed. LOS was defined as bloodculture-proven sepsis occurring after 3 days of age. Results: LOS was diagnosed in 28% of 180 episodes of suspected infection, occurring in 142 neonates (mean GA 30+3 ±2+2 weeks). Only 3 signs were significantly associated with LOS: deterioration of respiratory condition (OR 3,2;95%CI 1,6-6,3), capillary refill >2 seconds (OR 2,9;95%CI 1,5- 5,7) and lethargy (OR 4,4;95%CI 2,2-8,7). Multiple regression resulted in a model with these 3 signs and the presence of a CVC (AUC 0,828; 95%CI 0,764-0,892, p< 0,001). In the absence of these 4 factors, LOS was found in 2,3% (1/43). In case of one or more of the 4 factors sensitivity was 98%, specificity 32%, positive LR 1,45 and negative LR 0,06. Conclusion: Deterioration of respiratory condition, capillary refill, lethargy and the presence of a CVC are the most important clinical signs in predicting LOS in preterm infants. In the absence of all these signs probably antibiotics can be safely withheld.