Incidence Of Late-onset Sepsis Research Articles

Prenatal and Postnatal Disparities in Very-Preterm Infants in a Study of Infections between 2018-2023 in Southeastern US.

The birthrate of Black preterm (BPT) infants is 65% higher than White preterm (WPT) infants with a BPT mortality that is 2.3 times higher. The incidence of culture-positive late-onset sepsis is as high as 41% in very-preterm infants. The main purpose of this study was to examine thermal gradients and the heart rate in relation to the onset of infection. This report presents disparities in very-preterm infection incidence, bacteria, and mortality data amongst BPT and WPT infants. 367 preterms born at <32 weeks gestational age (GA) between 2019-2023 in five neonatal intensive care units (NICUs) were enrolled to study the onset of infections and dispositions; REDCap data were analyzed for descriptive statistics. The 362 infants for analyses included 227 BPTs (63.7%) and 107 WPTs (29.6%), with 28 infants of other races/ethnicities (Hispanic, Asian, and other), 50.6% female, mean GA of 27.66 weeks, and 985.24 g birthweight. BPT infants averaged 968.56 g at birth (SD 257.50), and 27.68 (SD 2.07) weeks GA, compared to WPT infants with a mean birthweight of 1006.25 g (SD 257.77, p = 0.2313) and 27.67 (SD 2.00, p = 0.982) weeks GA. Of the 426 episodes of suspected infections evaluated across all the enrolled infants, the incidence of early-onset sepsis (EOS) was 1.9%, with BPT infants having 2.50 times higher odds of EOS than WPT infants (p = 0.4130, OR (odds ratio) = 2.50, p_or = 0.408). The overall incidence of late-onset sepsis (LOS) was 10.8%, with LOS in 11.9% of BPT infants versus 9.3% (p = 0.489, OR = 1.21, p_or = 0.637) of WPT infants. BPT infants made up 69.2% of the 39 infants with Gram-positive infections vs. 25.6% for WPT infants; 16 infants had Gram-negative culture-positive infections, with 81.2% being BPT infants versus 18.8% being WPT infants. Of the 27 urinary tract infections, 78% were in BPTs. The necrotizing enterocolitis incidence was 6.9%; the incidence in BPT infants was 7.5% vs. 6.5% in WPT infants. The overall mortality was 8.3%, with BPTs at 8.4% vs. WPT infants at 9.3%, (p = 0.6715). BPTs had a higher rate of positive cultures, double the Gram-negative infections, a much higher rate of urinary tract infections, and a higher rate of mortality than their WPT counterparts. This study emphasizes the higher risk of morbidity and mortality for BPTs.

Daptomycin Use for Persistent Coagulase-Negative Staphylococcal Bacteremia in a Neonatal Intensive Care Unit.

During the last two decades, the incidence of late-onset sepsis (LOS) has increased due to improved survival of premature neonates. Persistent bacteremia (PB) in LOS is defined as more than two positive blood cultures obtained on different calendar days during the same infectious episode. Although rare, PB should be treated aggressively to prevent adverse outcomes. Daptomycin, a lipopeptide antibiotic, has been used in neonates with persistent coagulase-negative staphylococci (CoNS) bacteremia with promising results, but studies reporting on the efficacy and safety of the agent are scarce. The purpose of this study was to evaluate the efficacy and safety of daptomycin use for persistent CoNS bacteremia in a neonatal cohort. This is a retrospective, observational, single-center study of neonates treated with daptomycin during 2011-2022 in the Tertiary Neonatal Intensive Care Unit (NICU) of the University General Hospital of Patras, Greece. For the years 2011-2022, there were 3.413 admissions to the NICU. During the last 3 years (2020-2022)-the active epidemiological surveillance period-123 infants (out of 851 admissions, 14.4%) developed CoNS bacteremia (LOS). During the study period, twelve infants with PB were treated with daptomycin. They had a median gestational age of 32 weeks (IQR 31-34) and mean (SD) birth weight of 1.840 (867) grams. CoNS bacteremia isolates were s. epidermidis (50%), s. haemolyticus (20%), s. hominis (20%) and s. warneri (10%). The decision to start daptomycin (6 mg/kg/dose twice daily) was taken on median day 10 (ΙQR 7-15) of infection. None of the infants had focal complications or meningitis. Daptomycin therapy caused no renal, hepatic, muscular or gastrointestinal adverse events. One neonate developed seizures, and one death occurred due to multiple complications of prematurity. Most infants (11/12) were successfully treated and eventually had negative blood culture. Daptomycin monotherapy showed an adequate cure rate in premature neonates with persistent CoNS bacteremia in a tertiary NICU. In our study, daptomycin was effective and well tolerated; the safety profile, however, needs to be confirmed in larger studies and randomized controlled trials.

The Incidence of Necrotizing Enterocolitis and Late-Onset Sepsis during the COVID-19 Pandemic in Sweden: A Population-Based Cohort Study

Introduction: The effect of the pandemic restrictions in the NICUs is not well studied. Necrotizing enterocolitis (NEC) is characterized by intestinal inflammation and bacterial invasion. This study aimed to investigate whether the incidence of NEC has changed during the COVID-19 pandemic in Sweden and whether it was associated with a change in the frequency of extremely preterm births. Methods: Data were retrieved from the Swedish Neonatal Quality Register (SNQ) for infants registered between January 2017 and December 2021 born below a gestational age of 35 weeks. The registry completeness is 98–99%. The diagnosis of NEC was the primary outcome. Generalized linear model analysis was used to calculate the risk ratio for NEC. Results: Totally 13,239 infants were included. 235 (1.8%) infants developed NEC, out of which 91 required surgical treatment. 8,967 infants were born before COVID-19 pandemic and 4,272 during. Median gestational age at birth was 32.8 weeks in both periods. The incidence of NEC was significantly lower during COVID-19 pandemic compared to the prior period (1.43 vs. 1.94%, p 0.037), but not the incidence of surgical NEC. The crude risk ratio of developing NEC during COVID-19 pandemic was 0.74 (95% CI: 0.55–0.98). The incidence of late-onset sepsis with positive culture was also declined during COVID-19 (3.21 vs. 4.15%, p value 0.008). Conclusion: While we found significant reduction in the incidence of NEC and culture-positive late-onset sepsis during the COVID-19 pandemic, the number of extremely preterm births was unchanged.

Quality Improvement Project for Reducing Hypothermia on Admission in Neonates Admitted in A Tertiary Care (Level 3A) NICU in Ahmedabad, Western India

Title: Quality Improvement project for reducing hypothermia on admission in newborns admitted to a neonatal care unit in a large academic tertiary (Level 3A) NICU in Ahmedabad, Western India. Background: Neonatal hypothermia is a common and dangerous condition around the world. Moderate and severe hypothermia increase mortality and morbidity and predispose the fragile neonate to an increased risk of late-onset neonatal sepsis (LONS), intraventricular hemorrhage, and worsening of respiratory distress. Around 60% of neonates who are admitted to level 3 tertiary NICU in Ahmedabad, Gujarat, India, had a temperature below 36.5°C on admission. Method: We conducted plan-do-study-act (PDSA) cycles to test and adapt solutions for decreasing hypothermia in neonates admitted to NICU. Identifying the root cause of hypothermia in terms of Manpower, Material, and Methods and enlisting them as fishbone diagrams. We adopted the strategy of using a transport incubator in the Ambulance and turning on the incubator before thirty minutes of delivery for preventing neonatal hypothermia. Results: Within 8 months of starting our quality improvement project, the proportion of neonates who were hypothermic on admission decreased from 57% to 8%, Normothermic on admission increased from 23% to 53%, with an increase in mean admission temperature from 35.4°C during the pre-intervention phase to 36.6°C during post-intervention. There was also a reduction in the incidence of late-onset sepsis from 23% (pre-intervention phase) to 13% and subsequently 5% in the post-intervention period. Conclusion: This study is a cost-effective approach to reducing admission hypothermia in NICU in a resource-limited setting with all outborn babies. Our study also emphasizes the importance of maintaining euthermia, not only in delivery rooms but also during transportation.

23 Assessing the effects of introducing prophylactic hydrocortisone in extremely low gestational age infants in a tertiary Canadian NICU

Abstract Background Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. A large trial and a meta-analysis support the early use of physiologic doses of hydrocortisone to reduce the incidence of death or moderate/severe BPD. In 2019, this practice was introduced for all preterm infants &amp;lt;28 weeks gestational age (GA) at our university-affiliated tertiary care NICU. Objectives To determine the effect of prophylactic hydrocortisone on the incidence of survival with mild or no BPD in neonates born &amp;lt;28 weeks GA. Secondary objectives were to compare safety outcomes related to prophylactic hydrocortisone use: late onset sepsis, gastrointestinal perforation, severe intraventricular hemorrhage (IVH) and use of postnatal dexamethasone. Design/Methods We performed a retrospective cohort study of infants born &amp;lt;28 weeks GA admitted to our NICU during 2 epochs, before and after the implementation of prophylactic hydrocortisone. The primary objective was evaluated using logistic regression adjusted for GA. Safety outcomes were compared using chi-square or Fisher’s exact test. Results Epoch 1 included 76 infants and epoch 2 included 71 infants, of whom 63 (88.7%) received prophylactic hydrocortisone. Infants in the two epochs were similar in terms of median (IQR) GA 26.5 (25.0, 27.2) vs 26.7 (25.1, 27.1) weeks GA, mean (SD) weight at admission (882g +/- 212 vs 841g +/- 176), APGAR at 5 minutes, use of antenatal steroids and/or surfactant, and need for intubation at delivery (all p&amp;gt;0.5). Three infants were transferred to another hospital and their BPD status could not be determined. Adjusting for GA, there was a statistically non-significant signal for increased survival with mild or no BPD in epoch 2 (adjusted odds ratio 1.68, 95% CI 0.80, 3.59, p= 0.17) compared to epoch 1. The two epochs had similar incidence of late onset sepsis, gastrointestinal perforation and need for postnatal dexamethasone, however, in epoch 2, fewer infants developed grade 3/4 IVH on head ultrasound within the first two weeks of life (7/71, 9.9%) compared to epoch 1 (21/76, 27.6%, p= 0.01). Conclusion Prophylactic hydrocortisone may be associated with increased survival with mild or no BPD. Safety outcomes in both epochs were similar, but with a significantly decreased incidence of grade 3/4 IVH in the prophylactic hydrocortisone group. Larger cohort studies are required before a clear recommendation for prophylactic hydrocortisone can be made.

Effects of early administration of buccal colostrum on reducing late onset sepsis among preterm in neonatal intensive care: Quasi-experimental, cohort study

IntroductionPreterm infants are at a particularly high risk of late onset sepsis (LOS), that can lead to death, increased morbidities, prolonged hospital stay, increased cost of care, and worse long-term outcomes among survivors. Administration of buccal colostrum in the first few days of life is safe, feasible, prophylactic measure against sepsis, Necrotizing Enterocolitis (NEC) and ventilator associated pneumonia. PurposeThe purpose of this study was to evaluate the effects of Early Administration of Buccal Colostrum on preterm infants’ outcomes, including the incidence of late onset sepsis in the Neonatal Intensive Care (NICU). MethodologyThis is a quasi-experimental, retrospective-prospective, clinical trial study, that took place in the NICU of Dubai Hospital, Dubai Health Authority (DHA), in the United Arab Emirates between January 2018–April 2020. The sample consisted of preterm-neonates who were selected and assigned into two groups; experimental and control. A purposive sample that met the inclusion criteria of babies born at 34 weeks and below, and whose parents were willing to participate in this study were included. AnalysisThe sample consisted of 175 preterm neonates. Neonates in Group 1 (n = 134) received buccal colostrum within 48 h, while neonates in Group 2 (n = 41) did not. Of the neonates in (Group 1) who received colostrum within 48 h, 5 (3.7%) had late onset sepsis and 129 (96.3%) did not. On the other hand, neonates in Group 2 who did not receive colostrum within 48 h, almost half 19 (46.3%) also developed late onset sepsis and 22 (53.7%) did not (p = .001). In terms of mortality, Group 1 neonates who received colostrum within 48 h in had a survival rate of 98.5% (132). While in Group 2, 3 (7.3%) neonatal deaths occurred, and 38 (92.7%) neonates were alive 28 days after birth. Despite the death rate in Group 2 being higher compared to Group 1, the results are not statistically significant (p = . 0.085). Fisher's exact test showed that the ratio of deaths in neonates who received colostrum within 48 h in Group 1 and also developed sepsis was 1 neonatal death: 4 alive. While 3 neonates in Group 2 who did not receive Colostrum within 48 h and developed sepsis and died. These results were statistically significant with (p = .001). Neonatal deaths were higher in neonates who did not receive colostrum within 48 h and who also developed sepsis. ConclusionThis study reported strong evidence to support the proposed clinical benefits of early administration of buccal colostrum. The results also demonstrated differences in the incidence of developing LOS and proven sepsis in preterm infants who did not received buccal colostrum, compared to the infants who received buccal colostrum soon after birth. While no differences were seen in infants’ clinical outcomes in terms of direct mortality, the results did show that early administration of buccal colostrum was associated with better outcomes in neonates who also developed sepsis.

A study of clinico-bacteriological profile and to determine incidence of meningitis in late onset sepsis in newborn unit of tertiary care teaching hospital in Northern India

Background: The daily risk of mortality in first 4 weeks of life is almost 30-fold higher than post-neonatal period. Late onset sepsis (LONS) and meningitis still continue to be major causes of mortality and morbidity in newborn period. Our study was done to study clinical profile of enrolled newborns with LONS along with incidence of meningitis in them. The objective of this study was to study clinico-bacteriological profile and to determine associated incidence of meningitis in neonates with late onset sepsis (LONS) in a hospital setting in Northern India.Methods: It was a hospital based prospective observational study conducted over a period of 12 months enrolling 122 newborn with &gt;72 hours of age fulfilling inclusion criterias.Results: Out of total 122 enrolled newborn, 37 (30.3%) neonates had meningitis. 71 (58.20%) were of term gestation with majority 61 (50.0%) in age group of 4-7days of life. Incidence of LONS in low birth weight and very low birth weight were 54% and 13.5%. Most commonly seen symptoms in at admission were lethargy, refusal to feed and fever. Blood culture was positive in 45 (36.88%) in neonates with Acinetobacter baumanii, klebsiella pneumonia and Escherichiae coli being most commonly seen organisms. Cerebrospinalfluid (CSF) culture was positive in 4 (10.81%) newborns. Mean duration of hospital stay was 24.75±13.96 days. Mortality in neonatal meningitis was 3 (3.2%).Conclusions: Our study proved that about one third of newborn admitted with LONS also had coexistent meningitis. Thus CSF analysis is a must and it should not be missed as untreated meningitis can be devastating for newborn. Antibiotics must be added as per antibiogram of specified institute. 

Decreasing Trend in Incidence of Late Onset Culture Positive Bloodstream Infections but Not Late Onset Meningitis in Preterm Infants

Introduction: Recent studies reported decreased incidence of late onset sepsis in the neonatal intensive care unit (NICU), but it is unclear whether this is also true for late onset meningitis. Recent reports that both meningitis and intraventricular hemorrhage (IVH) are associated with systemic inflammation also raise questions about an association between the 2. Methods: All preterm infants <33 weeks gestational age admitted to CNN NICUs from 2010 to 2018 were included. We compared incidence trends of late onset culture positive bloodstream infection (CPBSI) and late onset meningitis, and examined the association of meningitis and IVH (exposure), after adjustment for potential confounders. Results: Of 36,573 infants included, 32,198 had no infection, 3,977 had only late onset CPBSI and 398 had late onset meningitis. There was significant decrease in incidence of late onset CPBSI (14%–10%; adjusted odds ratio (AOR) = 0.93; 95% confidence interval [CI] 0.92, 0.95) but not late onset meningitis (1.6%–1.2%; AOR = 0.98; 95% CI 0.94, 1.01). Compared to infants with no IVH grade 3 or above, infants with IVH grade 3, or above had higher odds of late onset meningitis versus no infection (AOR 4.16; 95% CI 3.17, 5.44), and higher odds of late onset meningitis versus late onset CPBSI (AOR 4.11; 95% CI 3.08, 5.50). Conclusions: There was a decreasing trend of late onset CPBSI but not late onset meningitis. An association between late onset meningitis and IVH grade 3 or above was observed. Late onset CPBSI and meningitis may have different risk factors and require different prevention strategies.

Incidence and microbiological characteristics of neonatal late onset sepsis in a neonatal intensive care unit in Peru

ObjectivesOur study aimed to determine the incidence of late onset sepsis and the most frequent microorganisms causing it in the neonatal unit at Hospital Cayetano Heredia in Lima, Peru. MethodsDescriptive and retrospective study. We reviewed all positive blood cultures and cultures of cerebrospinal fluid drawn from inborn patients beyond 72 h of life, admitted to the neonatal unit from January 2015 to December 2019. ResultsThe incidence of late onset sepsis was 7.4% of admitted patients and 10.04 per 1000 live births. During our study period, 234 episodes of late onset sepsis occurred in 204 patients. The incidence was higher in very low birth weight infants, reaching 36.2% and even higher in extremely low birth weight infants (40.7%). Coagulase-negative Staphylococcus and then Klebsiella spp. were the most frequent causative microorganisms. The most frequent cause of late onset sepsis in very low birth weight infants was gram-negative bacteria (Klebsiella spp., was the most frequent causative microorganism). ConclusionsLate onset neonatal sepsis is prevalent in our neonatal unit. It is important to know which are the most prevalent causative microorganisms to be able to choose adequate antibiotic coverage and to design strategies to prevent infection.

Exposure to intrauterine inflammation and late-onset sepsis in very preterm infants.

Late-onset sepsis is an important cause of mortality and morbidity in preterm infants. As these infants rely mostly on their innate immune system to fight off infection, enhancing this immune system by appropriate stimuli may prevent late-onset sepsis. However, it remains unclear which stimuli can enhance the neonatal immune system. This study aims to investigate the influence of intrauterine inflammation on late-onset sepsis. This is a retrospective cohort study in a Neonatal Intensive Care Unit in the Netherlands. Between 2005 and 2016, 1014 infants with ≤32 weeks gestational age and/or with a birth weight ≤1500 g were included. Intrauterine inflammation was subdivided into histological chorioamnionitis, fetal inflammatory response, and funisitis. Logistic and Cox regression analyses were performed to investigate the influence of intrauterine inflammation on late-onset sepsis. Thirty-six percent of the included infants developed late-onset sepsis; 24% of placentas showed intrauterine inflammation. Late-onset sepsis incidence did not differ between infants with or without exposure to intrauterine inflammation after adjustment for gestational age (histological chorioamnionitis aHR 0.928 [CI: 0.727-1.185], p = 0.551; fetal inflammatory response aHR 1.011 [CI: 0.793-1.288], p = 0.930); funisitis aHR 0.965 [CI: 0.738-1.263], p = 0.797). Late-onset sepsis in very preterm infants seems not to be associated with intrauterine inflammation. Intrauterine inflammation is not protective of developing late-onset sepsis in premature infants. A large cohort study on the effect of intrauterine inflammation on neonatal outcome. This study adds to existing knowledge on finding appropriate stimuli to enhance the immune system of premature infants to improve neonatal outcome.

Meningitis Trends and Association With Intraventricular Hemorrhage in Very Preterm Infants

Background: Meningitis is often considered to be a subset of neonatal infections that should respond to infection control strategies; however, a preliminary report from the Canadian Neonatal Network (CNN) indicated that an infection control program decreased late onset sepsis but not meningitis. There was also no significant decrease in the incidence of severe neurological injury. We aimed to compare trends in the incidence of late onset sepsis and meningitis among very preterm infants in Canada, and to determine whether there is an association between late onset meningitis and intraventricular hemorrhage (IVH). Methods: All very preterm infants <33 weeks gestational age admitted to tertiary level neonatal intensive care units (NICUs) in the CNN from 2010-2018 were included. Statistical analyses were performed to compare the trends for incidence rates of late onset culture positive bloodstream infection (CPBSI) and late onset meningitis, and to examine the association of meningitis and IVH (exposure), after adjustment for patient risks. Findings: Of 36,573 infants in this study, 32,198 had no infections, 3977 had only late onset CPBSI and 398 had late onset meningitis. Between 2010 and 2018, there was a significant decrease in the incidence of late onset CPBSI (rates decreased from 14% to 11%; (AOR)=0.93; 95%CI 0.92, 0.95) but not for late onset meningitis (rates were not significantly changed from 1.5% to 1.2%; (AOR)=0.98; 95%CI 0.94, 1.01). Infants with IVH grade 3 or above had higher odds of late onset meningitis compared with infants with no infection (AOR 4.16; 95%CI 3.17, 5.44), and infants with late onset CPBSI (AOR 4.11; 95%CI 3.08, 5.50). Interpretation: There was a decreasing trend of late onset CPBSI but not meningitis. An association between late onset meningitis and IVH was observed. Late onset CPBSI and meningitis may have different risk factors and require different prevention strategies. Funding Statement: Canadian Institutes of Health Research (CTP 87518), (APR-126340 to PSS). Declaration of Interests: The authors have no actual or potential financial or personal conflicts of interest to disclose. Ethics Approval Statement: Data collection at each site was approved by either a research ethics board or quality improvement committee. The current study was approved by the Executive Committee of the CNN and by the Mount Sinai Hospital Research Ethics Board in Toronto, Ontario.

Invasive devices as risk factors for neonatal sepsis in neonatal intensive care units

This study aimed to evaluate the impact of invasive devices as risk factors for the development of neonatal sepsis in Neonatal Intensive Care Units. Hospital-based retrospective cohort study performed in two Neonatal Intensive Care Units in Ponta Grossa, Paraná, Brazil. Documentary data were collected through consultation of electronic medical charts of all patients admitted to two hospitals and of the patients with diagnosis of sepsis in another hospital. Health conditions at admission and outcomes were evaluated. Frequencies of the reasons for admission and the outcomes were calculated. In the association analysis, exposure variables were calculated with odds ratio and confidence intervals (95%). The frequency of sepsis was 39%, and 45.7% of the cases were of early-onset sepsis and 54.3% of late-onset sepsis. The mortality rate associated with sepsis was 9.9%. The use of invasive devices was observed to increase by 6 times the risk of neonatal sepsis. Peripherally inserted central catheter and phlebotomy were the devices causing higher risk. The high incidence of late-onset sepsis, its association with the use of invasive devices and the higher mortality rate among newborns with sepsis suggest the presence of fragilities in neonatal care and the need to seek alternatives of neonatal approach to avoid new cases of neonatal sepsis and consequent death.

Growth of Head Circumference and Body Length in Preterm Infants Receiving a Multicomponent vs a Soybean-Based Lipid Emulsion: A Randomized Controlled Trial.

The growth of very low-birth-weight (VLBW) infants relies, to a large extent, on parenteral nutrition (PN) during the early weeks of life. Despite the parenteral nutrients supply, extrauterine growth restriction remains the main concern for these infants. A parenteral multicomponent lipid emulsion (MLE) might improve growth and neurological outcomes, delivering fats for brain growth that the traditional soybean-based lipid emulsion (SLE) fails to provide. We hypothesize that the use of an MLE in PN may reduce the loss of head circumference (HC) z-score from birth to 36 weeks' postmenstrual age (PMA) or at discharge compared with the use of an SLE in VLBW infants. Infants with BW ≤1250 g, without malformations or chromosomal abnormalities, were randomly assigned to receive an MLE or an SLE. The primary outcome was the change in HC z-score (HC Δ z-score) from birth to 36 weeks' PMA or at discharge. Secondary outcomes included the change in weight and length z-score (W Δ z-score and L Δ z-score) as well as incidence of late-onset sepsis and PN-associated cholestasis (PNAC). Of the 128 infants randomized, 51 infants in the MLE group and 50 infants in the SLE group were analyzed. The MLE was significantly associated with a decreased loss in HC and length z-scores from birth to 36 weeks' PMA or at discharge. This is the first randomized controlled trial providing the evidence that an MLE is associated with improved HC growth in comparison with a pure SLE.

Prolonged minimal enteral nutrition versus early feeding advancements in preterm infants with birth weight ≤1250 g: a prospective randomized trial

Objective To determine the effect of two different feeding strategies on time to achieve full enteral feeding and the incidence of feeding intolerance in preterm infants with birth weight ≤1250 g. Methods A prospective randomized trial (NCT02913677) conducted at a tertiary level neonatal intensive care unit. Preterm infants with birth weight ≤1250 g were randomly allocated to either prolonged minimal enteral nutrition (MEN) in which feed volumes were not increased for five days or early feeding advancement groups in which feed volumes were advanced by 20–25 ml/kg/d until 150 ml/kg/d feed volume was achieved. The primary outcomes were time to reach full enteral feeding sustained for 72 h and incidence of feeding intolerance. Results A total of 199 infants (99 in prolonged MEN and 100 in early feeding advancement groups) were involved in the study. No statistically significant differences were observed in time to achieve full enteral feeding and feeding intolerance. Daily weight gain (19 versus 16 g; p < .001) was significantly higher in prolonged MEN group. There were no significant differences in weight percentiles and z-scores at discharge. Duration of hospitalization was comparable between the groups. The overall incidence of late onset sepsis and culture proven sepsis was similar in both groups (p = .92 and p = .22, respectively). Incidence of necrotizing enterocolitis (NEC) was 5% in early feeding advancement group, whereas no case of NEC was observed in prolonged MEN group (p = .06). Conclusions Prolonged MEN is not associated with a delay in time to achieve full enteral feedings. It may even provide an advantage for development of NEC in extremely low birth weight infants. Trial registration Clinical Trials.gov: NCT02913677.

Decretion of Late Onset Sepsis with Enteral Low Dose Lactulose in Very Premature Infants: A Double-Blind Randomized, Placebo-Controlled Pilot Study

Background Neonatal sepsis contributes substantially to neonatal morbidity and mortality, and is an ongoing major global public health challenge. We aimed to evaluate the effects of enteral feeding supplementation of low dose lactulose on the incidence of late onset sepsis in very premature infants. Materials and Methods In this randomized placebo-controlled trial preterm neonates with very low birth weight (VLBW) randomly received enteral supplementation of 1% lactulose (1 g per 100 mL feeds) (n=27) or distilled water (placebo, n=25) simultaneous with increasing volumes of milk. Incidence of late onset sepsis was considered as primary outcome. Feeding intolerance, time to reach full enteral feeding and duration of hospitalization in the course of the study were considered as secondary outcomes. Results Differences in baseline characteristics were not statistically important. The incidence of late onset sepsis was significantly lower in lactulose group compared to placebo (14.8% vs. 40%, p=0.04). The mean time to reach full enteral feeding was 12.85±3.33 and 15.20±5.24 in the lactulose vs. placebo group (p=0.03). Duration of hospitalization, occurrence of necrotizing enterocolitis and body weight on the 30th day of life were not significantly different between the two groups. Conclusion Enteral feeding supplementation with low dose lactulose in very premature infants for prebiotic purposes was deemed to be safe and reduced the incidence of late onset sepsis in our study.

Multiple vital signs analysis algorithm detects systemic inflammatory response in premature infants with late-onset sepsis and necrotising enterocolitis.

Commentary on: Mithal LB, Yogev R, Palac HL, Kaminsky D, Gur I, Mestan KK. Vital signs analysis algorithm detects inflammatory response in premature infants with late onset sepsis and necrotizing enterocolitis. Early Hum Dev. 2018 Feb; 117:83-89. https://doi.org/10.1016/j.earlhumdev.2018.01.008. Epub 2018 Jan 23. Neonatal sepsis substantially contributes to neonatal mortality and morbidity and presents a major public health challenge worldwide 1. Despite the decline in the incidence of late-onset sepsis (LOS) due to infection control measurements, it still disproportionately affects very low-birthweight (VLBW) infants causing significant morbidity, lifelong neurological impairments and prolonged hospitalisation 2, 3. The diagnosis of sepsis remains difficult due to its nonspecific clinical presentation which could be attributed to many other noninfectious aetiologies, as well as the lack of reliable laboratory biomarkers. Because of the potential dire consequences, clinicians have a low threshold for LOS treatment leading to antibiotic overuse in a large proportion of VLBW infants and its adverse effects such as increased antibiotic resistance, fungal infections, microbiota modification, necrotising enterocolitis (NEC) and death 4. NEC, defined as bowel infection, bacterial penetration and tissue destruction, presents with nonspecific signs at early stage, very often overlapping with sepsis 5. Both neonatal sepsis and NEC are associated with systemic inflammatory responses. The development of a reliable and specific method to detect an impending infection or systemic inflammatory response prior to the clinical deterioration has been of particular research interest in recent years 6, 7. Previous studies have shown that RALIS software with multiple vital signs monitoring was an effective tool in detecting sepsis 2.5 days earlier than the onset of the clinical suspicion of infection 8. The current study aimed to evaluate the performance of the revised RALIS algorithm in the detection of a systemic inflammatory response in LOS and NEC in preterm infants (23–32 GA). Vital sign data incorporated into the revised RALIS algorithm included heart rate, respiratory rate, temperature, desaturation events and bradycardia events. A score was generated (range: 0–10) and the clinical team was alerted if ≥5 for six consecutive hours. Premature infants with complete electronic vital sign data were included and classified according to the primary outcome into LOS, expanded LOS, NEC, culture-negative LOS or controls. This study consistently proved the effectiveness of the RALIS algorithm in detecting LOS and NEC with a mean alert of 33 hours before clinical suspicion, particularly emphasising its utility in excluding LOS with a high negative predictive value of 93%. Although sensitive, the positive diagnostic value in identifying LOS and NEC remained limited, showing a moderate PPV (67%) similar to that in previous reports 8. The authors note the study's limitations, mainly regarding the sample size and its retrospective nature. Thus, this study indicates the particular usefulness of the RALIS algorithm in identifying clinician concern ahead of clinical concern without consequence, which may more confidently aid the physician's decision-making with regard to withholding or discontinuing antibiotic treatment. This study adds additional data regarding the benefit of multiple sign monitoring algorithms in the prediction of neonatal infections; however, future prospective studies are warranted to investigate its association with existing or novel laboratory biomarkers, as well as its utility beyond the first month of life. https://ebneo.org/2019/05/late-onset-sepsis-necrotizing-enterocolitis/. The authors declare no financial or other conflict of interest.

Effect of a surveillance system for decreasing neonatal nosocomial infections.

Nosocomial infection in very low birthweight (VLBW) infants is a common complication with high morbimortality. New strategies to reduce its occurrence have recently led to the development of neonatal surveillance programs. To determine whether the NeoKissEs surveillance system implementation in our neonatal unit has been associated with a decrease in nosocomial infection in VLBW infants, as well as a reduction in the use of antibiotics and central venous catheters (CVC). Retrospective and descriptive study of infants <1500 g admitted between January 2011 and December 2017. Rates of use of antibiotics and CVC were calculated, as well as late-onset sepsis incidence. Data were compared before and after the surveillance system implementation. 299 patients were recruited. We excluded seven patients, who died <72 h. Of the remainder (n = 292), 149 were in the pre-intervention period and 143 in the post-intervention period. We found a significant decrease in the incidence density of sepsis comparing these two periods (5.98 vs. 4.08) (p = 0.03). Although no differences in antibiotic and CVC rates of use between both groups were found, a significant decrease in antibiotic use was observed comparing the first and last year of the intervention (38% vs. 24%) (p = 0.03). A higher percentage of breastfed infants was observed (39% vs. 59%) (p = 0.001) in the post-intervention group. Surveillance systems are useful to reduce nosocomial infection in VLBW infants. Reduction in antibiotic and CVC use requires longer intervention time. Promotion of breastfeeding seems to be a very effective associated strategy.

Effect of Prophylaxis for Early Adrenal Insufficiency Using Low-Dose Hydrocortisone in Very Preterm Infants: An Individual Patient Data Meta-Analysis

To assess the effect of prophylaxis for early adrenal insufficiency using low-dose hydrocortisone on survival without bronchopulmonary dysplasia (BPD) in very preterm infants using an individual patient data meta-analysis. All existing randomized controlled trials testing the efficacy of the prophylaxis of early adrenal insufficiency using low-dose hydrocortisone on survival without BPD were considered for inclusion when data were available. The primary outcome was the binary variable survival without BPD at 36 weeks of postmenstrual age. Among 5 eligible studies, 4 randomized controlled trials had individual patient data available (96% of participants identified; n = 982). Early low-dose hydrocortisone treatment for 10-15 days was associated with a significant increase in survival without BPD (OR, 1.45; 95% CI, 1.11-1.90; P = .007; I2 = 0%), as well as with decreases in medical treatment for patent ductus arteriosus (OR, 0.72; 95% CI, 0.56-0.93; P = .01; I2 = 0%) and death before discharge (OR, 0.70; 95% CI, 0.51-0.97; P = .03; I2 = 0%). The therapy was associated with an increased risk of spontaneous gastrointestinal perforation (OR, 2.50; 95% CI, 1.33-4.69; P = .004; I2 = 31.9%) when hydrocortisone was given in association with indomethacin exposure. The incidence of late-onset sepsis was increased in infants exposed to hydrocortisone (OR, 1.34; 95% CI, 1.02-1.75; P = .04; I2 = 0%), but no adverse effects were reported for either death or 2-year neurodevelopmental outcomes as assessed in an aggregate meta-analysis. This individual patient data meta-analysis showed that early low-dose hydrocortisone therapy is beneficial for survival without BPD in very preterm infants.

The Effect of Probiotics on Late-Onset Sepsis in Very Preterm Infants: A Randomized Clinical Trial

Background Late onset sepsis is a frequent complication of prematurity, associated with increased mortality and morbidity. Probiotics may prevent late onset sepsis in premature infants. The aim of this study was to determine prophylactic effect of oral probiotics in prevention of late onset sepsis of very preterm infants. Materials and Methods This study was a randomized, double blinded, placebo controlled trial. Eighty preterm infants born at 0.05). Conclusion According to the results, usage of prophylactic probiotics can reduce the incidence of late onset sepsis and its mortality. By consuming probiotics preterm infants could reach the full enteral feeding in a shorter period of time, but the duration of hospitalization not reduced.

[Prolonged initial empirical antibiotic treatment and the risk of morbidity and mortality in very low birthweight infants].

The objective of this study is to evaluate the association between the duration of ini tial empirical antibiotic treatment and the subsequent development of late-onset sepsis, necrotizing enterocolitis (NEC) and death in very low birth weight (VLBW) infants. Quantitative, cross-sectional, analytical study of VLBW infants admitted to the neonatal ICU were included over a period of five years. Initial empirical antibiotic therapy was that which started immediately after birth, without knowing the results of blood cultures. It was considered prolonged antibiotic therapy when the treatment duration was > 5 days. Perinatal variables, as well as the inci dence of late-onset sepsis, confirmed NEC and mortality were analyzed. 266 VLBW infants were studied, with an average gestational age and birth weight of 28.8 ± 2.5 weeks and 1.127 ± 264 g respectively. 213 infants received initial empiric antibiotic therapy (80.0%), which was prolonged in 67.6% of cases. All infants received two different antibiotics. 136 episodes of late-onset sepsis were described. The most common pathogens were coagulase-negative Staphylococcus and Staphylococcus aureus. Among the newborns with prolonged antibiotic therapy, there were 20 cases of confirmed NEC and 15 of the studied infants died (10.4%). When comparing the use of antibiotic therapy during > 5 days versus treatment less than 5 days duration, a statistically significant association was observed between prolonged antibiotic therapy and late-onset sepsis (p = 0.03) and confirmed NEC (p = 0.03), but not of mortality (p = 0.12). The use of empirical antibiotic therapy for five days or more was associated with an increased risk of late-onset sepsis and NEC, but not of mortality in VLBW infants.