Prevention Of Late-onset Sepsis Research Articles

Probiotic Use in a Randomized Controlled Trial to Prevent Sepsis and/or Necrotizing Enterocolitis in Low-Birth-Weight Infants

Neonatal sepsis is a major problem throughout the world. Early detection of neonatal sepsis is difficult because the first signs of this disease may be minimal, especially in preterm infants. The clinical signs are similar to those of non-infectious processes. Definitive blood culture results not being immediately available may prove detrimental. As a result, many babies are evaluated and treated for presumed sepsis with parenteral antibiotics while awaiting microbial isolation. This study was undertaken to evaluate the efficacy of probiotics in prevention of Late onset sepsis and or NEC in low-birth-weight babies.

Probiotics (Bacillus clausii) for Prevention of Late-onset Sepsis in Preterm Infants (<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 (<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, <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>0.05)) and duration of hospital stay (10.86±3.19 vs 11.23±2.98 days; (p>0.05)). However, incidence of feed intolerance in the probiotic group (11.11%) was significantly less than that the other (26%) (p<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.

Oral Application of Mother's Own Milk for Prevention of Late Onset Sepsis in Preterm Very Low Birth Weight Neonates: A Randomized Controlled Trial.

Background: Oral application of mother's own milk (MOM) in very low birth weight (VLBW) neonates may provide an effective method of cleaning the oral cavity and influencing the immunocompetent cells there. Methods: A double-blind randomized controlled trial was conducted in a tertiary level neonatal unit on VLBW neonates; that is, neonates with birth weight <1,500 g, hospitalized within 72 hours of birth. The intervention was oral care with MOM. The primary objective was to observe the effect of oral care with MOM on late onset sepsis (LOS) and also on mortality, days to attain full enteral feed, necrotizing enterocolitis (NEC), exclusive breastfeeding rates at discharge, and total hospital stay (THS). Results: One hundred ten neonates were randomized to intervention and no-intervention group; 55 in each group. Neonates in the intervention group developed LOS in 9.1% versus 27.3% in no-intervention group (p = 0.013). Mortality was 9.1% versus 16.4% (p = 0.252); days to attain full enteral feeds were 6.94 ± 2.34 versus7.4 ± 2.31 days (p = 0.306); exclusive BF rates at discharge were 83% versus 75% (p = 0.449); THS was 30.72 ± 8.72 versus 33.5 ± 8.7 days (p = 0.267) in the two groups, respectively. There was no effect on NEC. Conclusion: Oral care of VLBW neonates with MOM reduces LOS and mortality.

Bovine Lactoferrin to Prevent Neonatal Infections in Low-Birth-Weight Newborns in Pakistan: Protocol for a Three-Arm Double-Blind Randomized Controlled Trial.

BackgroundSepsis is a common and severe complication in premature neonates, particularly those born with low birth weights (<2500 g). Neonatal sepsis is steadily emerging as a leading cause of neonatal mortality in Pakistan. Lactoferrin is a natural product with broad-spectrum antimicrobial properties and glycoprotein that is actively involved in innate immune host responses. Clinical trials have revealed its protective effect on sepsis, but lactoferrin dosage, duration, and role in the prevention of sepsis are still uncertain.ObjectiveWe aimed to establish the efficacy of bovine lactoferrin in the prevention of late-onset sepsis and to determine the optimal dose and method of administering bovine lactoferrin that may contribute to improvement in overall survival of low birth weight infants.MethodsWe will implement the study in 2 phases at the Aga Khan University Hospital. The first phase, which we have completed, was formative research. This phase mainly focused on a qualitative exploration of perceptions about feeding and caring practices of low birth weight newborns and a trial of improved practices for the preparation and administration of bovine lactoferrin to newborns. The second phase is a 3-arm double-blind randomized controlled trial. In this phase, we randomly allocated 2 different daily oral prophylactic doses of bovine lactoferrin (150 mg or 300 mg) and placebo to 300 low–birth weight neonates starting within the first 72 hours of birth and continuing for the first 28 days of life.ResultsThe study protocol was approved by the Ethics Review Committee of Aga Khan University on August 16, 2017. Data collection began in April 2018 and was completed in September 2020. Data analyses are yet to be completed. We expect the results to be published in peer-reviewed journals by autumn of 2021.ConclusionsThis intervention, if effective, has the potential to be translated into a safe, affordable, and widely utilized treatment to prevent sepsis and, subsequently, may improve the survival outcomes of low birth weight neonates in Pakistan and other low- and middle-income countries.Trial RegistrationClinicalTrials.gov NCT03431558; https://clinicaltrials.gov/ct2/show/NCT03431558International Registered Report Identifier (IRRID)PRR1-10.2196/23994

Effect of lactoferrin in the prevention of late-onset sepsis in preterm neonates

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.

Bovine Colostrum For Prevention Of Late Onset Sepsis In Preterm Neonates: A Randomized Control Trial

Abstract Objective to determine whether gut priming with bovine colostrum reduces nosocomial sepsis episodes and to determine its effect on sepsis severity and weight increment. Study Design In this prospective, placebo-controlled, double-blinded, randomized trial, infants born before 34 weeks were assigned to receive either placebo (n 33) or bovine colostrum (n 32) as gut priming. Episodes of nosocomial sepsis (diagnosed by using Rodwell and Töllner sepsis scores) were recorded. A third comparison was made with standard care group of preterm neonates (n 17). Results Fewer sepsis episodes were observed in bovine colostrum-treated infants (3 vs. 6, p-value 0.482) with none developed severe sepsis. There was no significant difference in the weight increment (p-value 0.355) Conclusion Gut priming with oral Bovine Colostrum decreases severe sepsis in preterm neonates.

Is Mother’s Own Milk Lactoferrin Intake Associated with Reduced Neonatal Sepsis, Necrotizing Enterocolitis, and Death?

Introduction: Lactoferrin (LF) is a protective protein present in milk with anti-infective and immune-modulating properties. Objectives: The aim of this study was to determine the association of maternal LF intake and mother’s own milk intake in the first 10 days of life on the prevention of late-onset sepsis (LOS), necrotizing enterocolitis (NEC), or death in the first 8 weeks of life in newborns with a birth weight <2,000 g. Methods: A retrospective cohort study was conducted, with the exposure being the consumption of mother’s own LF and mother’s own milk in the first 10 days of life, and the outcome being LOS, NEC, or death during days 11 and 56 of life, analyzed by Cox regression. Results: Two hundred and ninety-nine infants were enrolled, including 240 with human LF intake information. The average daily human LF intake over days 4–10 of life was 283 mg/kg/day (IQR 114–606 mg/kg/day). The hazard ratio (HR) of mother’s own milk LF intake ≥100 mg/kg/day in days 4–10 for LOS, NEC, or death was 0.297 (95% CI 0.156–0.568, p < 0.001); the adjusted HR was 0.752 (95% CI 0.301–1.877, p = 0.541). The adjusted HR of mother’s own milk cumulative intake (days 4–10) of 54–344 mL/kg (25–75 quartiles) for LOS, NEC, or death was 0.414 (95% CI 0.196–0.873, p = 0.02). Infants who developed an event (LOS, NEC, or death) had significantly less median daily human LF intake than those that did not (89 vs. 334 mg/kg/day, respectively, p < 0.0001). Conclusion: Consumption of higher amounts of mother’s own milk in the first days of life is associated with less infection, NEC, and death. Early human milk intake should be strongly encouraged in all newborns.

Randomized Controlled Trial of Bovine Lactoferrin for Prevention of Sepsis and Neurodevelopment Impairment in Infants Weighing Less Than 2000 Grams

To determine the effect of bovine lactoferrin on prevention of late-onset sepsis (LOS) and neurodevelopment delay. Randomized, double-blind, controlled trial in neonates with a birth weight of 500-2000 g in 3 neonatal units in Lima, Peru, comparing bovine lactoferrin 200mg/kg/day with placebo administered for 8weeks. The primary outcome was the first episode of culture-proven LOS or sepsis-associated death. Neurodevelopment delay was assessed by the Mullen Scales at 24months corrected age. Of the 414 infants enrolled, 209 received bovine lactoferrin and 205 received placebo. LOS or sepsis-associated death occurred in 22 infants (10.5%) in the bovine lactoferrin group vs 30 (14.6%) in the placebo group; there was no difference after adjusting for hospital and birth weight; hazard ratio 0.73 (95% CI, 0.42-1.26). For infants with birth weights of <1500g the hazard ratio was 0.69 (95% CI, 0.39-1.25). The mean age-adjusted normalized Mullen composite score at 24months was 83.3±13.6 in the bovine lactoferrin group vs 82.6±13.1 in the placebo group. Growth outcomes and rehospitalization rates during the 2-year follow-up were similar in both groups, except for significantly less bronchiolitis in the bovine lactoferrin group (rate ratio, 0.34; 95% CI, 0.14-0.86). Supplementation with bovine lactoferrin did not decrease the incidence of sepsis in infants with birth weights of <2000 g. Growth and neurodevelopment outcomes at 24months of age were similar. Neonatal bovine lactoferrin supplementation had no adverse effects. ClinicalTrials.gov: NCT01525316.

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.

Exposure to Gastric Acid Inhibitors Increases the Risk of Infection in Preterm Very Low Birth Weight Infants but Concomitant Administration of Lactoferrin Counteracts This Effect

To investigate whether exposure to inhibitors of gastric acidity, such as H2 blockers or proton pump inhibitors, can independently increase the risk of infections in very low birth weight (VLBW) preterm infants in the neonatal intensive care unit. This is a secondary analysis of prospectively collected data from a multicenter, randomized controlled trial of bovine lactoferrin (BLF) supplementation (with or without the probiotic Lactobacillus rhamnosus GG) vs placebo in prevention of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants. Inhibitors of gastric acidity were used at the recommended dosages/schedules based on the clinical judgment of attending physicians. The distribution of days of inhibitors of gastric acidity exposure between infants with and without LOS/NEC was assessed. The mutually adjusted effects of birth weight, gestational age, duration of inhibitors of gastric acidity treatment, and exposure to BLF were controlled through multivariable logistic regression. Interaction between inhibitors of gastric acidity and BLF was tested; the effects of any day of inhibitors of gastric acidity exposure were then computed for BLF-treated vs -untreated infants. Two hundred thirty-five of 743 infants underwent treatment with inhibitors of gastric acidity, and 86 LOS episodes occurred. After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS (OR, 1.03; 95% CI, 1.008-1.067; P = .01); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS. Risk was significant for Gram-negative (P < .001) and fungal (P = .001) pathogens, but not for Gram-positive pathogens (P = .97). On the test for interaction, 1 additional day of exposure to inhibitors of gastric acidity conferred an additional 7.7% risk for LOS (P = .003) in BLF-untreated infants, compared with 1.2% (P = .58) in BLF-treated infants. Exposure to inhibitors of gastric acidity is significantly associated with the occurrence of LOS in preterm VLBW infants. Concomitant administration of BLF counteracts this selective disadvantage. isrctn.org: ISRCTN53107700.

Prevention of Late Onset Sepsis and Central-line Associated Blood Stream Infection in Preterm Infants.

Late onset sepsis (LOS) and central-line associated blood stream infection (CLA-BSI) contribute toward the mortality and morbidity in prematurely born infants. The aim of this study is to investigate the effects of hospital-wide and unit-based interventions on LOS and CLA-BSI in infants born at <32 weeks gestation. Intensive care, high dependency days and catheter days were obtained from the unit database and blood culture results from a microbiology laboratory database. Poisson regression was used to evaluate the effects of interventions on LOS and CLA-BSI. Quarterly rates of LOS reduced from 26.1 to 2.9 per 1000 intensive care, high dependency days and CLA-BSI from 31.6 to 4.3 per 1000 catheter days between 2007 and 2012. Appointment of a hospital specialist vascular device nurse, a change in the mode of administration of vancomycin, standardization of the hospital skin and hub disinfection policy and the introduction of a venous infusion phlebitis scoring system were associated with a reduction of LOS to 55% (95% confidence interval: 40-74%) and CLA-BSI 45% (95% confidence interval: 33-61%) of pre-intervention levels. The standardization of the neonatal unit policy for skin disinfection and a move to a new building were associated with reductions of LOS to 64% (47-87%) and 54% (34-88%), respectively, and aseptic no touch technique for infusion access with CLA-BSI to 53% (37-75%) of pre-intervention levels. A multifaceted approach involving changes in antimicrobial and skin disinfection policy, training for aseptic no touch technique and surveillance resulted in sustained reduction in LOS and CLA-BSI rates.

Probiotics in critically ill children.

Gut microflora contribute greatly to immune and nutritive functions and act as a physical barrier against pathogenic organisms across the gut mucosa. Critical illness disrupts the balance between host and gut microflora, facilitating colonization, overgrowth, and translocation of pathogens and microbial products across intestinal mucosal barrier and causing systemic inflammatory response syndrome and sepsis. Commonly used probiotics, which have been developed from organisms that form gut microbiota, singly or in combination, can restore gut microflora and offer the benefits similar to those offered by normal gut flora, namely immune enhancement, improved barrier function of the gastrointestinal tract (GIT), and prevention of bacterial translocation. Enteral supplementation of probiotic strains containing either Lactobacillus alone or in combination with Bifidobacterium reduced the incidence and severity of necrotizing enterocolitis and all-cause mortality in preterm infants. Orally administered Lactobacillus casei subspecies rhamnosus, Lactobacillus reuteri, and Lactobacillus rhamnosus were effective in the prevention of late-onset sepsis and GIT colonization by Candida in preterm very low birth weight infants. In critically ill children, probiotics are effective in the prevention and treatment of antibiotic-associated diarrhea. Oral administration of a mix of probiotics for 1 week to children on broad-spectrum antibiotics in a pediatric intensive care unit decreased GIT colonization by Candida, led to a 50% reduction in candiduria, and showed a trend toward decreased incidence of candidemia. However, routine use of probiotics cannot be supported on the basis of current scientific evidence. Safety of probiotics is also a concern; rarely, probiotics may cause bacteremia, fungemia, and sepsis in immunocompromised critically ill children. More studies are needed to answer questions on the effectiveness of a mix versus single-strain probiotics, optimum dosage regimens and duration of treatment, cost effectiveness, and risk-benefit potential for the prevention and treatment of various critical illnesses.

Gut colonization by aerobic microorganisms is associated with route and type of nutrition in premature neonates

We hypothesized that the beneficial effects of early enteral compared with parenteral feeding are related to the increased variety of aerobic microorganisms that colonize the gut. Our aim was to describe the relationship, first, between the type of feeding and mucosal colonization and, second, between the type of feeding and the development of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm neonates. In total, 159 neonates aged 72 hours or less with risk factors for early-onset sepsis were recruited to a prospective 2-center study. Rectal swabs were collected on admission and twice per week thereafter. The feeding regimen was recorded for the first 7 days and categorized into total parenteral nutrition (TPN) and 2 regimens of enteral nutrition, that is, breast milk containing regimen (BMCR), for which breast milk constituted at least 11% of the enteral diet, or formula. Herein, 70 neonates received formula, 48 received BMCR, and 41 received TPN; 69 cases of LOS and 15 cases of NEC were observed in 50 neonates. A multiple logistic regression analysis indicated that formula and BMCR were associated with 4- to 5-fold increases in colonization by Gram-negative bacteria (odds ratio [OR], 4.52; 1.87-10.95, and OR, 4.95; 1.90-12.87, respectively) and 5 to 9 times higher odds of colonization by Gram-positive microorganisms (OR, 5.75; 1.89-16.72, and OR, 8.61; 2.52-29.36, respectively) compared with TPN. The only difference between BMCR and the other feeding groups was the higher colonization with Staphylococcus haemolyticus in the latter (formula—OR, 6.24; 1.73-22.50; TPN—OR, 2.75; 1.08-6.97). Compared with BMCR, TPN was associated with an increased odds of LOS (OR, 3.04; 1.02-9.07) and an increased odds of death (19.75; 3.64-107.12) compared with formula. Although early enteral feeding is associated with a higher odds of colonization with opportunistic microorganisms, it should be preferred over TPN whenever feasible, due to the favorable effect on the prevention of LOS.

G534(P) Prevention of late onset sepsis and central line associated blood stream infection in preterm infants

Late onset sepsis (LOS) and Central line associated blood stream infection (CLA-BSI) remains a major cause of mortality and morbidity in preterm infants. Numerous interventions were introduced between 2007 and...

Genetics and late-onset septicemia in pre-term infants

Using a retrospective cohort of twins born from 1994 to 2009 in NICUs in New Haven and Farmington, Connecticut, sepsis concordance rates were compared between 170 monozygotic and 665 dizygotic twin pairs. With caveats of limitations outlined by the authors, the findings suggest that approximately one-half of the variation in incidence of late-onset sepsis in pre-term infants is due to genetic factors. These findings will influence future research and will need to be considered in analysis of causation and prevention of late-onset sepsis.

Strategies to Limit Infections in the Neonate and to Reduce Infection-related Mortality

Health-care associated infections remain a major problem in the neonatal intensive care unit (NICU), resulting in significant morbidity and mortality. Specifically, bloodstream infections have been associated with adverse neurodevelopmental outcomes among preterm infants with birth weight <1000 grams. In addition, these infections are associated with prolonged duration of hospitalization among survivors and increased cost of neonatal health care. It is clear that preventive strategies are urgently needed. Many bloodstream infections in the NICU are associated with the use of central venous catheters, and implementation of evidence-based measures as well as bundles has reduced their occurrence. Nevertheless, much work remains. Candidal infections have become more prevalent in the NICU, and fluconazole prophylaxis is being recommended and used to prevent candidiasis among infants with birth weight <1000 grams. Although fluconazole prophylaxis has reduced invasive candidal infections, the underlying risk factors that result in Candida becoming a more common pathogen remain, namely the overuse of antibiotics especially the third generation cephalosporins. In addition, the use of H2 blocker also has contributed to Candidal colonization and late onset sepsis. Recent results of randomized clinical trials have shown beneficial effects of probiotics for prevention of necrotizing enterocolitis and lactoferrin for prevention of late onset sepsis. Finally, the need to vaccinate not only our preemies but also staff and family members of babies in the NICU will further reduce the likelihood of introducing community-associated pathogens into the NICU. Abstracts for SupplementInternational Journal of Infectious DiseasesVol. 14Preview Full-Text PDF Open Archive

Lactoferrin and prevention of late-onset sepsis in the pre-term neonates

Late-onset sepsis (LOS) affects a large proportion of pre-term neonates in neonatal intensive care units (NICUs) worldwide, with high morbidity and related mortality, and frequent occurrence of severe late neurodevelopmental impairment. Due to the frequency, severity and difficulties in early diagnosis and prompt therapy, prevention is crucial for decreasing the burden of infection-related complications in NICUs. It is well known that feeding with fresh maternal milk, hygiene measures and the cautious use of H2-blockers are related with a decreased risk of developing sepsis. However, evidence from randomised clinical trials exists only for fluconazole in the prevention of fungal infections in the NICU. Lactoferrin is the main whey protein in mammalian milk, and is involved in innate immune host defences. Notably, human lactoferrin can be found at increased concentrations in colostrum and in milk from mothers of premature neonates. Human (hLF) and bovine lactoferrin (bLF) share a high (77%) amino-acid homology, and the same N-terminal peptide responsible for antimicrobial activity, called lactoferricin. In vitro, bLF shows potent direct antimicrobial activity against all types of pathogens, which occurs via anti-cell wall actions and leads to disintegration of the micro-organism's membranes. bLF is also synergistic with many antimicrobials and antifungals, and promotes growth and differentiation of the immature gut. Based on this background data, a randomised clinical trial was recently conducted in very low birth weight pre-term neonates given bLF alone or with the probiotic Lactobacillus GG. The aim of the trial was to assess the ability of bLF to prevent late-onset sepsis of any origin in the studied infants during their stay in the NICU. This article discusses the preliminary data from this study, along with the proposed mechanisms of action of bLF in pre-term infants.

Bovine Lactoferrin Supplementation for Prevention of Late-Onset Sepsis in Very Low-Birth-Weight Neonates: A Randomized Trial

Bovine Lactoferrin Supplementation for Prevention of Late-Onset Sepsis in Very Low-Birth-Weight Neonates: A Randomized Trial

A multicenter, randomized trial on prophylactic bovine lactoferrin in preterm neonates for prevention of late-onset sepsis

A multicenter, randomized trial on prophylactic bovine lactoferrin in preterm neonates for prevention of late-onset sepsis