title: Comparison between killed and living probiotic usage versus placebo for the prevention of necrotizing enterocolitis and sepsis in neonates. Role of Enteric Supplementation of Probiotics on Late-onset Sepsis by Candida species in Preterm Low Birth Weight Neonates: A Randomized, Double Blind, Placebo-controlled Trial Probiotics and growth in preterm infants: A randomized controlled trial, PREMAPRO study. Efficacy of Saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: a randomised controlled trial. Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns: incidence of late-onset sepsis and neurological outcome Prophylactic Probiotics to Prevent Death and Nosocomial Infection in Preterm Infants Effect of Bifidobacterium lactis on the Incidence of Nosocomial Infections in Very-Low-Birth-Weight Infants: A Randomized Controlled Trial Probiotic Effects on Late-onset Sepsis in Very Preterm Infants: A Randomized Controlled Trial Cohort study of probiotics in a North American neonatal intensive care unit. Double-blind, randomised clinical assay to evaluate the efficacy of probiotics in preterm newborns weighing less than 1500 g in the prevention of necrotising enterocolitis Enteral feeding of premature infants with Saccharomyces boulardii. Lactobacillus Reuteri for the prevention of necrotising enterocolitis in very low birthweight infants: a randomised controlled trial Effect of Bifidobacterium breve M-16V Supplementation on Fecal Bifidobacteria in Preterm Neonates - A Randomised Double Blind Placebo Controlled Trial Bifidobacterium and enteral feeding in preterm infants: Cluster-randomized trial Enteral feeding of premature infants with Lactobacillus GG. Bacillus clausii for Prevention of Late-onset Sepsis in Preterm Infants: A Randomized Controlled Trial. [Effects of probiotics on feeding intolerance in low birth weight premature infants]. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. The effect of a bifidobacter supplemented bovine milk on intestinal permeability of preterm infants. [Effects of probiotics on intestinal bacterial colonization in premature infants]. [Effect of oral administration of probiotics on intestinal colonization with drug-resistant bacteria in preterm infants]. Effects of early prebiotic and probiotic supplementation on development of gut microbiota and fussing and crying in preterm infants: a randomized, double-blind, placebo-controlled trial. Probiotics Feeding in Prevention of Urinary Tract Infection, Bacterial Sepsis and Necrotizing Enterocolitis in Preterm Infants Probiotics-supplemented feeding in extremely low-birth-weight infants Oral supplementation with Lactobacillus casei subspecies rhamnosus prevents enteric colonization by Candida species in preterm neonates: a randomized study. Neonatal sepsis 2004-2013: the rise and fall of coagulase-negative staphylococci. Oral probiotics: Lactobacillus sporogenes for prevention of necrotizing enterocolitis in very low-birth weight infants: a randomized, controlled trial The propre-save study: effects of probiotics and prebiotics alone or combined on necrotizing enterocolitis in very low birth weight infants. Functional impairments at school age of preterm born children with late-onset sepsis. Oral supplementation with probiotics in very-low-birth-weight preterm infants: a randomized, double-blind, placebo-controlled trial. Early administration of Bifidobacterium breve to preterm infants: randomised controlled trial Comparison of two empiric antibiotic regimen in late onset neonatal sepsis--a randomized controlled trial. A high burden of late-onset sepsis among newborns admitted to the largest neonatal unit in central Vietnam Effect of oral probiotics supplementation in the prevention of necrotizing enterocolitis among very low birth weight preterm infants. Comparison of stool colonization in premature infants by three dose regimes of a probiotic combination: a randomized controlled trial. Neonatal infections in China, Malaysia, Hong Kong and Thailand Hand hygiene with alcohol hand rub and gloves reduces the incidence of late onset sepsis in preterm neonates
abstract: UNLABELLED The aim of the study is to compare the role of killed ( KP ) Lactobacillus acidophilus with living ( LP ) in reducing incidence of sepsis ( NS ) and necrotizing enterocolitis ( NEC ) in neonates . R and omized double blind placebo study , included 150 neonates admitted to NICU at day 1 , sixty received oral ( LP ) and 60 received ( KP ) and 30 received placebo .  One gram of stools was collected on admission , at day 7 , at end of the study , as well as on suspected NEC or NS and was sent for culture . RESULTS LP and KP were preventive factors for NEC with absolute risk reduction ( AAR ) 16 , 15 % , respectively and 18 % for NS compared to placebo .  Incidence of NEC and NS did not differ significantly between neonates supplemented with LP and those with KP . Preterm neonates supplemented with KP showed significantly lower incidence of NEC compared to placebo , while incidence of NS showed no significant difference between both groups . There is significant reduction in NS and NEC among neonates with positive Lactobacillus colonization of gut compared to those none colonized at day 7 ( 27.9 vs. 85.9 % , 0 vs. 7.8 % ) and at day 14 ( 48.7 vs. 91.7 % for NS and 0 vs. 20.8 % for NEC ) . Overall comparison between the three groups showed statistical significant reduction in the incidence of NEC . Present conclusions are that early gut colonization with beneficial bacteria lowers the incidence of NEC and NS . KP retained similar benefits to live bacteria Background : The increase in invasive fungal infections ( IFIs ) in neonatal intensive care unit ( NICU ) is jeopardizing the survival of preterm neonates . Probiotics modulating the intestinal microflora of preterm neonates may minimize enteral fungal colonization . Aims : This study was to examine whether probiotic supplementation in neonates reduced fungal septicemia . Material s and Methods : This prospect i ve , r and omized , double blind trial investigating the  supplementation of preterm infants with a probiotic  was done from May 2012 to April 2013 , with 112 subjects r and omized into two groups . Primary outcome : Decreased fungal colonization in gastrointestinal tract . Others : Incidence of late onset septicemia ; duration of the primary hospital admission ; number of days until full enteral feeds established . Results : Full feed establishment was earlier in probiotics group compared to placebo group ( P = 0.016 ) . The duration of hospitalization was less in the probiotic group ( P = 0.002 ) . Stool fungal colonization , an important outcome parameter was 3.03 ± 2.33 × 105 colony formation units ( CFU ) in the probiotics group compared to 3 ± 1.5 × 105 CFU in the placebo group ( P = 0.03 ) . Fungal infection is less in the study group ( P = 0.001 ) . Conclusion : The key features of our study were reduced enteral fungal colonization , reduce invasive fungal sepsis , earlier establishment of full enteral feeds , and reduced duration of hospital stay in the probiotics group BACKGROUND & AIMS Recent studies have suggested that the gut microflora has metabolic effects . We aim ed to evaluate postnatal growth in preterm infants who received different probiotic supplements  , and to assess the safety of probiotic administration . METHODS This prospect i ve , r and omized , double-blind , controlled trial was performed at three tertiary care neonatal units . Preterm infants were r and omly assigned to receive daily supplementation over 4 - 6 weeks with placebo ( group C ) or probiotics ( group P ) . Group P comprised three subgroups : P1 received Bifidobacterium lactis , P2 received Bifidobacterium longum , and P3 received B. lactis and B. longum . We assessed postnatal growth during the supplementation period and up to a corrected gestational age ( GA ) of 41 weeks when body composition was assessed using whole-body dual-energy X-ray absorptiometry . Aerobic and anaerobic blood cultures were performed on suspicion of late-onset sepsis . RESULTS The study comprised 199 preterm infants with a mean GA of 29.1 ± 1.4 weeks and a mean birth weight of 1173 ± 210 g , who received a placebo  ( group C , n = 52 )  or probiotics  ( group P , n = 147 ) from the first week of life . At the end of the supplementation period , no statistically significant differences were seen between the groups in relation to the mean body weight ( group C = 1906 ± 23 g , group P = 1875 ± 14 g , p = 0.25 ) , length , or head circumference . The incidence rates of necrotizing enterocolitis and late-onset sepsis were similar in the two groups . At the corrected GA of 41 weeks , there were no differences between the groups with respect to anthropometric measurements or body composition analysis . CONCLUSIONS Preterm infants receiving  Bifidobacterium supplements did not exhibit better postnatal growth compared with those who received placebo treatment . No adverse effects were associated with probiotic administration . Registered under Clinical Trials.gov Identifier no. NCT01379417 BACKGROUND Probiotics have strain specific effects and the effects of fungi in preventing diseases in preterm infants have been investigated poorly . Saccharomyces boulardii is a yeast which acts both as a probiotic and a polyamine producer . AIM The objective of this study was to investigate the efficacy of S. boulardii in preventing necrotizing enterocolitis ( NEC ) or sepsis in very low birth weight infants . STUDY DESIGN AND SUBJECTS A prospect i ve , double blind , placebo controlled trial was conducted in preterm infants ( ≤ 32 GWs , ≤ 1500 g birth weight ) . They were r and omized either to receive feeding supplementation with S. boulardii 50 mg/kg every 12 h or placebo , starting with the first feed until discharged . OUTCOME MEASURES Necrotizing enterocolitis ( NEC ) or sepsis and NEC or death . RESULTS Birth weight and gestational age of the study ( n = 104 ) and the control ( n = 104 ) groups were 1126 ± 232 vs 1162 ± 216 g and 28.8 ± 2.2 vs 28.7 ± 2.1 weeks , respectively . Neither the incidence of stage ≥ 2 NEC or death nor stage ≥ 2 NEC or late onset culture proven sepsis was significantly lower in the study group when compared with the control group ( 9.6 % vs 7.7 % , p = 0.62 ; 28.8 % vs 23 % , p = 0.34 ) . Time to reach 100 mL/kg/day of enteral feeding ( 11.9 ± 7 vs 12.6 ± 7 days , p = 0.37 ) was not different between the groups . CONCLUSIONS Saccharomyces boulardii did not decrease the incidence of NEC or sepsis Objective : To evaluate the efficacy of probiotics in the prevention of gastrointestinal colonization by C and ida species , of late-onset sepsis and neurological outcome in preterm newborns . Study Design : A prospect i ve study was conducted in 249 preterms who were subdivided into three groups :  one group ( n=83 ) was supplemented with Lactobacillus ( L. ) reuteri , one group with L. rhamnosus ( n=83 ) and the other with no supplementation ( n=83 ) . The fungal colonization in the gastrointestinal tract , the late onset of sepsis and clinical parameters were recorded . A neurological structured assessment was further performed at 1 year of age . Result : C and ida stool colonization was significantly higher ( P<0.01 ) in the control group than in the groups treated with probiotics . The L. reuteri group presented a significantly higher reduction in gastrointestinal symptoms than did the L. rhamnosus and control groups . Infants treated with probiotics showed a statistically significant lower incidence of abnormal neurological outcome than did the control group . Conclusion : The use of both probiotics seems to be effective in the prevention of gastrointestinal colonization by C and ida , in the protection from late-onset sepis and in reducing abnormal neurological outcomes in preterms BACKGROUND AND OBJECTIVE : It has been suggested that probiotics may decrease  infant mortality and nosocomial infections because of their ability to suppress colonization and translocation of bacterial pathogens in the gastrointestinal tract . We design ed a large double-blinded placebo-controlled trial using Lactobacillus reuteri to test this hypothesis in preterm infants . METHODS : Eligible infants were r and omly assigned during the first 48 hours of life to either daily probiotic administration or placebo .  Infants in the intervention group were administered enterally 5 drops of a probiotic preparation containing 108 colony-forming units of L reuteri DSM 17938 until death or discharge from the NICU . RESULTS : A total of 750 infants ≤2000 g were enrolled . The frequency of the primary outcome , death , or nosocomial infection , was similar in the probiotic and placebo groups ( relative risk 0.87 ; 95 % confidence interval : 0.63–1.19 ; P = .376 ) . There was a trend toward a lower rate of nosocomial pneumonia in the probiotic group ( 2.4 % vs 5.0 % ; P = .06 ) and a nonsignificant 40 % decrease in necrotizing enterocolitis ( 2.4 % vs 4.0 % ; P = .23 ) . Episodes of feeding intolerance and duration of hospitalization were lower in infants ≤ 1500 g ( 9.6 % vs 16.8 % [ P = .04 ] ; 32.5 days vs 37 days [ P = .03 ] ) . CONCLUSIONS : Although L reuteri did not appear to decrease the rate of the composite outcome , the trends suggest a protective role consistent with what has been observed in the literature . Feeding intolerance and duration of hospitalization were decreased in premature infants ≤1500 Background : Nosocomial infections endanger preterm infants . Objective : The aim of the present controlled r and omized trial was to investigate whether Bifidobacterium lactis reduces the incidence of nosocomial infections in infants with very low birth weight ( VLBW ; < 1,500 g ) < 30 weeks of gestation . Patients and Methods : In a r and omized controlled trial , 183 VLBW infants < 30 weeks of gestation were stratified according to gestational age ( 23–26 and 27–29 weeks ) and early antibiotic therapy ( days 1–3 , yes or no ) and r and omly assigned to have their milk feedings supplemented with B. lactis ( 6 × 2.0 × 109 CFU/kg/day , 12 billion CFU/kg/day ) or placebo for the first 6 weeks of life . Primary outcome was the ‘ incidence density ’ of nosocomial infections defined as periods of elevated C-reactive protein ( > 10 mg/l ) from day 7 after initiation of milk feedings until the 42nd day of life ( number of nosocomial infections/total number of patient days ) . The main secondary outcome was necrotizing enterocolitis ( NEC ; ≧stage 2 ) . Results : There were 93 infants in the B. lactis group and 90 in the placebo group . There was no significant difference between the two groups with regard to the incidence density of nosocomial infections ( 0.021 vs. 0.016 ; p = 0.9 , χ2 test ) . There were 2 cases of NEC in the B. lactis group and 4 in the placebo group . None of the blood cultures grew B. lactis . Conclusion : In the present setting , B. lactis at a dosage of 6 × 2.0 × 109 CFU/kg/day ( 12 billion CFU/kg/day ) did not reduce the incidence density of nosocomial infections in VLBW infants . No adverse effect of B. lactis was observed BACKGROUND AND OBJECTIVE : Late-onset sepsis frequently complicates prematurity , contributing to morbidity and mortality . Probiotics may reduce mortality and necrotizing enterocolitis ( NEC ) in preterm infants , with unclear effect on late-onset sepsis . This study aim ed to determine the effect of administering a specific combination of probiotics to very preterm infants on culture-proven late-onset  sepsis . METHODS : A prospect i ve multicenter , double-blinded , placebo-controlled , r and omized trial compared daily administration of a probiotic combination ( Bifidobacterium infantis , Streptococcus thermophilus , and Bifidobacterium lactis , containing 1 × 109 total organisms ) with placebo ( maltodextrin ) in infants born before 32 completed weeks ’ gestation weighing < 1500 g. The primary outcome was at least 1 episode of definite late-onset sepsis . RESULTS : Between October 2007 and November 2011 , 1099 very preterm infants from Australia and New Zeal and were r and omized . Rates of definite late-onset sepsis ( 16.2 % ) , NEC of Bell stage 2 or more ( 4.4 % ) , and mortality ( 5.1 % ) were low in controls , with high breast milk feeding rates ( 96.9 % ) . No significant difference in definite late-onset sepsis or all-cause mortality was found , but this probiotic combination reduced NEC of Bell stage 2 or more ( 2.0 % versus 4.4 % ; relative risk 0.46 , 95 % confidence interval 0.23 to 0.93 , P = .03 ; number needed to treat 43 , 95 % confidence interval 23 to 333 ) . CONCLUSIONS : The probiotics B infantis , S thermophilus , and B lactis significantly reduced NEC of Bell stage 2 or more in very preterm infants , but not definite late-onset sepsis or mortality . Treatment with this combination of probiotics appears to be safe OBJECTIVE To determine whether routine probiotic administration to very preterm infants would reduce the incidence of necrotizing enterocolitis ( NEC ) without adverse consequences . STUDY DESIGN Since the end of July 2011 , we have administered a probiotic mixture to all admitted infants of < 32 weeks ' gestation . We give 0.5 g of a mixture of 4 bifidobacteria ( Bifidobacterium breve , bifidum , infantis , and longum ) and Lactobacillus rhamnosus HA-111 [ corrected ] ( 2 × 10(9 ) colony-forming units ) per day , starting with the first feed , until the infant reaches 34 weeks . We compared complications among infants admitted during the first 17 months of routine use with those admitted during the previous 17 months . RESULTS Two hundred ninety-four infants received probiotics , and 317 infants formed the comparison group . Introduction of probiotics was associated with a reduction in NEC ( from 9.8 % to 5.4 % , P < .02 ) , a nonsignificant decrease in death ( 9.8 % to 6.8 % ) , and a significant reduction in the combined outcome of death or NEC ( from 17 % to 10.5 % , P < .05 ) . After adjustment for gestational age , intrauterine growth restriction , and sex , the improvements remained significant ( OR for NEC , 0.51 ; 95 % CI , 0.26 - 0.98 ; OR for death or NEC , 0.56 ; 95 % CI , 0.33 - 0.93 ) . There was no effect of probiotics on health care-associated infection . DISCUSSION A product that is readily available in North America , that has excellent quality control , and that contains strains similar to those that have been shown effective in r and omized controlled trials substantially reduced the frequency of NEC in our neonatal intensive care unit Background A r and omised , double-blind clinical trial was undertaken in order to assess the effectiveness of probiotics in the prevention of  necrotising enterocolitis ( NEC ) in newborns weighing < 1500 g. Methods We studied a group of 150 patients who were r and omised in two groups after parental consent was obtained , to receive either a daily feeding supplementation with a multispecies probiotic ( Lactobacillus acidophilus , Lactobacillus rhamnosus , Lactobacillus casei , Lactobacillus plantarum , Bifidobacteruim infantis , Streptococcus thermophillus ) 1 g per day plus their regular feedings or to receive their regular feedings with nothing added ( control group ) , over the period of January 2007 through June 2010 . Clinicians in care of the infants were blinded to the group assignment . Results The primary outcome was the development of NEC . Both groups were comparable , with no differences during hospitalisation , including the type of nutrition received . Blood cultures obtained from cases that developed sepsis did not reveal lactobacillus or Bifidobacteria growth . No differences were detected in terms of NEC risk reduction ( RR : 0.54 , 95 % CI 0.21 to 1.39 ) although we did observe a clear trend in the reduction of NEC frequency in the studied cases : 6 ( 8 % ) versus 12 ( 16 % ) in the control group . When the combined risk of NEC or death was calculated as a post hoc analysis , we found a significantly lower risk ( RR : 0.39 , 95 % CI 0.17 to 0.87 ) for the study group . Conclusions Probiotics may offer potential benefits for premature infants and are a promising strategy in the reduction of the risk of NEC in preterm newborns BACKGROUND Saccharomyces boulardii ( SB ) is a yeast that acts both as a probiotic and as a polyamine producer . Probiotics prevent the overgrowth of pathogens in the gut while polyamines enhance intestinal maturation . The aim of this r and omized study was to investigate the ability of SB to modify the gut microbial ecology and its function . METHODS A total of 87 healthy babies with gestational age 28 - 32 weeks were studied . They were r and omly assigned to receive a preterm formula to which SB or maltodextrins was added for 30 days . Evaluations were made on the following : SB tolerance and weight gain , faecal flora analysis , intestinal D-xylose absorption and faecal lipid excretion . RESULTS SB was well tolerated by the infants . There was no difference in weight gain between the two groups . Median log of colony forming units per gram of faeces for Escherichia coli and enterococci was significantly lower in the SB group [ E. coli : 2.67 ( 0.045 ) vs. 2.75 ( 0.058 ) , P<0.001 ; enterococci : 2.14 ( 0.359 ) vs. 2.19 ( 0.138 ) , P<0.05 ] . On the other h and , the number of bifidobacteria and staphylococci in the stools was significantly higher in the SB group [ bifidobacteria : 2.65 ( 0.083 ) vs. 2.27 ( 0.075 ) , P<0.001 ; staphylococci : 1.23 ( 0.869 ) vs. 0.6 ( 0.281 ) , P<0.001 ] . D-Xylose and lipid absorption was not improved by SB [ median blood D-xylose : 1.5 ( 0.4 ) mmol/l vs. 1.35 ( 0.3 ) mmol/l , P>0.1 ; median stool steatocrit : 64 % ( 3.05 % ) vs. 65 % ( 2.72 % ) P>0.5 ] . CONCLUSIONS An SB-supplemented formula is well tolerated by preterm infants , it has a beneficial effect on stool flora bringing it closer to that of breast fed babies but it does not improve D-xylose or lipid gut absorption Objective To evaluate the effect of oral Lactobacillus reuteri ( L reuteri ) first on the incidence and severity of Necrotising enterocolitis ( NEC ) and second on sepsis . Design Prospect i ve r and omised controlled study . Setting Tertiary neonatal intensive care unit . Patients and interventions Preterm infants with a gestational age of ≤32 weeks and a birth weight of ≤1500 g were included ( n=400 ) . Infants in the first group were given 100 million CFU/day ( 5 drops ) of lyophilised L reuteri ( DSM 17938 ) mixed in breast milk or formula , starting from first feeding until discharge . Participants in the control group were given a placebo . Main outcome measures To determine and compare the frequency of NEC and /or death after 7 days , frequency of proven sepsis , rates of feeding intolerance and duration of hospital stay . Results There was no statistically significant difference between groups in terms of frequency of NEC stage ≥2 ( 4 % vs 5 % ; p=0.63 ) or overall NEC or mortality rates ( 10 % vs 13.5 % ; p=0.27 ) . Frequency of proven sepsis was significantly lower in the probiotic group compared to the control group ( 6.5 % vs 12.5 % ; p=0.041 ) . A significant difference was also observed with regard to rates of feeding intolerance ( 28 % vs 39.5 % ; p=0.015 ) and duration of hospital stay ( 38 ( 10–131 ) vs 46 ( 10–180 ) days ; p=0.022 ) . Conclusions Our results show that oral L reuteri does not seem to affect the overall rates of NEC and /or death in preterm infants followed up in the neonatal intensive care unit , and significant reductions were observed in the frequency of proven sepsis , rates of feeding intolerance and duration of hospital stay . Trial registration number NCT01531179 Background Probiotic supplementation significantly reduces the risk of necrotising enterocolitis ( NEC ) and all cause mortality  in preterm neonates . Independent quality assessment is important before introducing routine probiotic supplementation in this cohort . Aim To assess product quality , and confirm that Bifidobacterium breve ( B. breve ) M-16V supplementation will increase fecal B. breve counts without adverse effects . Methods and Participants Strain identity ( 16S rRNA gene sequencing ) , viability over 2 year shelf-life were confirmed , and microbial contamination of the product was ruled out . In a controlled trial preterm neonates ( Gestation <33 weeks ) ready to commence or on feeds for < 12 hours were r and omly allocated to either B. breve M-16V ( 3 × 109 cfu/day ) or placebo ( dextrin ) supplementation  until the corrected age 37 weeks . Stool sample s were collected before ( S1 ) and after 3 weeks of supplementation ( S2 ) for study ing fecal B. breve levels using quantitative PCR ( Primary outcome ) . Secondary outcomes included total fecal bifidobacteria and NEC≥Stage II . Categorical and continuous outcomes were analysed using Chi-square and Mann-Whitney tests , and McNemar and Wilcoxon signed-rank tests for paired comparisons . Results A total of 159 neonates ( Probiotic : 79 , Placebo : 80 ) were enrolled . Maternal and neonatal demographic characteristics were comparable between the groups . The proportion of neonates with detectable B. breve increased significantly post intervention : Placebo : [ S1:2/66 ( 3 % ) , S2 : 25/66 ( 38 % ) , p<0.001 ] Probiotic : [ S1 : 29/74 ( 40 % ) , S2 : 67/74 ( 91 % ) , p<0.001 ] . Median S1 B. breve counts in both groups were below detection ( < 4.7 log cells.g−1 ) , increasing significantly in S2 for the probiotic group ( log 8.6 ) while remaining < 4.7 log in the control group ( p<0.001 ) . There were no adverse effects including probiotic sepsis and no deaths . NEC≥Stage II occurred in only 1 neonate ( placebo group ) . Conclusion B. breve M-16V is a suitable probiotic strain for routine use in preterm neonates . Trial Registration Australia New Zeal and Clinical Trial Registry ACTRN Background This study evaluated the benefit of Bifidobacterium bifidum OLB6378 ( B. bifidum ) in very low-birthweight ( VLBW ) infants ( birthweight < 1500 g ) for the acceleration of enteral feeding . Methods A cluster-r and omized , double-blind , placebo-controlled trial was conducted in 19 hospitals , divided into two groups : the B group ( n = 10 hospitals ; B. bifidum given to infants within 48 h of birth ) and the P group ( n = 9 hospitals ; infants received a placebo ) . The primary outcome was establishment of enteral feeding after birth , defined as the postnatal day at which enteral feeding exceeded 100 mL/(kg/day ) . Secondary outcomes were defined as incidence of morbidity and somatic growth before discharge . Results Overall , 283 VLBW infants were enrolled in the study : B group , n = 153 ; and P group , n = 130 . Enteral feeding was established within 21 days after birth in 233 infants , of whom 119 received B. bifidum and 114 received placebo until their bodyweight reached 2000 g. Enteral feeding was established significantly earlier in the B group , at 11.0 ± 3.6 days versus 12.1 ± 3.8days in P group ( P < 0.05 ) . Infant growth during the stay in the neonatal intensive care unit was not different between groups , but the incidence of late-onset sepsis among all enrolled infants was significantly lower in the B group ( 3.9 % , 6/153 ) than in the P group ( 10.0 % , 13/130 ; P < 0.05 ) . No differences were observed in the incidence of other adverse outcomes including mortality . Conclusions B. bifidum in VLBW infants accelerated the establishment of enteral feeding after birth without increasing the incidence of adverse effects The objectives of this study were to determine whether or not the probiotic Lactobacillus GG can colonise the immature bowel of premature infants and if so , does colonisation result in a reduction of the size of the bowel reservoir of nosocomial pathogens such as enterobacteriaceae , enterococci , yeasts or staphylococci , and does colonisation with Lactobacillus GG have any effect on the clinical progress and outcome . Twenty preterm infants with a gestational age of 33 weeks or less who were resident on a neonatal unit were studied from the initiation of milk feeds until discharge . The infants were r and omised to receive either milk feeds or milk feeds supplemented with Lactobacillus GG 10(8 ) colony forming units twice a day for two weeks . The clinical features of the two groups of infants were similar . Orally administered Lactobacillus GG was well tolerated and did colonise the bowel of premature infants . However , colonisation with Lactobacillus GG did not reduce the faecal reservoir of potential pathogens and there was no evidence that colonisation had any positive clinical benefit for this particular group of infants BACKGROUND OF THE STUDY Preterm infants are managed with antibiotics for sepsis , including suspected or probable sepsis . This leads to a delayed and abnormal colonization of the gut with potentially pathogenic organisms and a microbiome , which lacks biodiversity and increases the risk for late-onset sepsis ( LOS ) . Probiotics have been proven to reduce the risk for necrotizing enterocolitis , but evidence for prevention of LOS is inconclusive . Probiotic effect depends also on the strain used , dose and indication for use . This study evaluated Bacillus clausii probiotic administered prophylactically to preterm neonates for prevention of LOS . OBJECTIVES To study B.clausii given prophylactically to preterm neonates for prevention of LOS . DESIGN Double-blinded , placebo-controlled , r and omized trial . SETTING S Tertiary care neonatal unit in India . PARTICIPANTS Consecutive preterm neonates < 34 weeks , admitted from 1 March 2012 to 28 February 2014 were stratified as extreme preterm and very preterm . INTERVENTION R and omized to receive either probiotic or placebo for 6 weeks , discharge from hospital , death or occurrence of sepsis , whichever was earlier . PRIMARY OUTCOME Incidence of definite and probable LOS in probiotic group compared with placebo . RESULTS Of 326 eligible preterm infants , 244 were enrolled and 82 were excluded . Of these , 120 were stratified as extreme preterm and r and omized to receive placebo ( n = 59 ) and probiotic ( n = 61 ) . Of 124 babies stratified as very preterm , an equal number was r and omized to receive placebo ( n = 62 ) and probiotic ( n = 62 ) . There was no significant difference in the incidence of LOS between the two arms in the extreme preterm group [ 29 % vs. 23 % ; relative risk ( RR ) 1.27 ; 95 % confidence interval ( CI ) 0.88 - 1.66 ; p = 0.36 ] and the very preterm group ( 13 % vs. 10 % ; RR 1.33 ; 95 % CI 0.96 - 1.70 ; p = 0.32 ) . Full feeds were achieved significantly faster in the probiotic group in both the extreme preterm ( RR 0.82 ; 95 % CI 0.74 - 0.88 ) and the very preterm ( RR 0.67 ; 95 % 0.32 - 0.77 ) . CONCLUSIONS Prophylactic administration of B.clausii to preterm neonates did not result in a significant difference in the incidence of LOS as compared with placebo OBJECTIVE To study the efficacy and safety of probiotics for the prevention of feeding intolerance in low birth weight ( LBW ) premature infants . METHODS Sixty eligible LBW premature infants were r and omly divided into probiotics and conventional treatment groups ( n=30 each ) . Both groups received treatment of the primary disease . Additionally , the probiotics treatment group was administered with probiotics ( 0.25 g , twice daily ) . The incidence of feeding intolerance , the time to regain birth weight and to reach full enteral nutrition and the length of hospitalization were compared between the two groups . The occurrence of adverse reactions was recorded . RESULTS The incidence of feeding intolerance in the probiotics treatment group was lower than that in the conventional treatment group ( 4 % vs 14 % ; P<0.01 ) . The time to regain birth weight ( 6.8±1.2 days vs 7.7±1.6 days ; P<0.05 ) and the time to reach full enteral nutrition ( 8.0±1.4 days vs 9.0±2.0 days ; P<0.05 ) in the probiotics treatment group were shorter than those in the conventional treatment group . No adverse reactions were observed in the probiotics treatment group . CONCLUSIONS Probiotics can reduce the incidence of feeding intolerance in LBW premature infants , can promote weight gain and shorten the time to reach full enteral nutrition . The application of probiotics appears to be safe in LBW premature infants OBJECTIVE Late-onset sepsis ( occurring after 3 days of age ) is an important problem in very low birth weight ( VLBW ) infants . To determine the current incidence of late-onset sepsis , risk factors for disease , and the impact of late-onset sepsis on subsequent hospital course , we evaluated a cohort of 6956 VLBW ( 401 - 1500 g ) neonates admitted to the clinical centers of the National Institute of Child Health and Human Development Neonatal Research Network over a 2-year period ( 1998 - 2000 ) . METHODS The National Institute of Child Health and Human Development Neonatal Research Network maintains a prospect i ve registry of all VLBW neonates admitted to participating centers within 14 days of birth . Exp and ed infection surveillance was added in 1998 . RESULTS Of 6215 infants who survived beyond 3 days , 1313 ( 21 % ) had 1 or more episodes of blood culture-proven late-onset sepsis . The vast majority of infections ( 70 % ) were caused by Gram-positive organisms , with coagulase-negative staphylococci accounting for 48 % of infections . Rate of infection was inversely related to birth weight and gestational age . Complications of prematurity associated with an increased rate of late-onset sepsis included patent ductus arteriosus , prolonged ventilation , prolonged intravascular access , bronchopulmonary dysplasia , and necrotizing enterocolitis . Infants who developed late-onset sepsis had a significantly prolonged hospital stay ( mean length of stay : 79 vs 60 days ) . They were significantly more likely to die than those who were uninfected ( 18 % vs 7 % ) , especially if they were infected with Gram-negative organisms ( 36 % ) or fungi ( 32 % ) . CONCLUSIONS Late-onset sepsis remains an important risk factor for death among VLBW preterm infants and for prolonged hospital stay among VLBW survivors . Strategies to reduce late-onset sepsis and its medical , social , and economic toll need to be addressed urgently BACKGROUND Preterm infants have increased intestinal permeability which can render them susceptible to infections from enterobacteriae . OBJECTIVES The primary objective was to investigate whether probiotic administration to preterm infants decreases intestinal permeability . Secondary outcomes studied were : somatic growth , tolerance , rates of sepsis and necrotizing enterocolitis . METHODS In a prospect i ve r and omized case-control study 41 stable preterm infants of 27 to 36 weeks gestation and 34 matched comparison infants consecutively admitted to the neonatal unit were studied . The study group received a preterm formula supplemented with Bifidobacter lactis ( 2 x 10(7 ) cfu/g of dry milk ) while the control group received the same formula but without supplementation .  Intestinal permeability was measured within two days of birth and then seven and thirty days later using the sugar absorption test . Additionally anthropometric parameters were recorded throughout the study as well as acceptance and tolerance of the formula . RESULTS All infants tolerated the study formula well . Median counts of stool bifidobacteria and lactulose/mannitol ratios at baseline were comparable . After 7 days of supplementation median bifidobacteria counts were significantly higher in the study group than in the control group ( p=0.0356 ) and they remained higher to the end of the study ( p at day 30=0.075 ) . The L/M ratio in the study group was significantly lower at day 30 of the study as compared to the control group ( p=0.003 ) . Head growth was significantly higher in the study group ( p=0.001 ) . CONCLUSIONS The administration of a bifidobacter supplemented infant formula decreases intestinal permeability of preterm infants and leads to increased head growth OBJECTIVE To study the possible roles of probiotics in decreasing intestinal bacterial colonization rate and the incidence of enterogenic infections in premature infants . METHODS Seventy premature infants were r and omly assigned to two groups : probiotics and conventional treatment groups ( control ) ( n=35 each ) . The probiotics treatment group was administered with oral Clostridium butyricum powder ( 250 mg , twice daily up to discharge ) 24 hrs after birth except conventional treatment .  Rectal swab cultures were done at admission , 5 and 12 days after admission , and before discharge . Clinical and laboratory findings were compared between the two groups . RESULTS The intestinal bacterial colonization rate in the probiotics treatment group was lower than that in the control group 12 days after admission ( 60 % vs 83 % ; p<0.05 ) and before discharge ( 51 % vs 80 % ; p<0.05 ) . Klebsiella pneumoniae , Escherichia coli and Enterococcus faecium were common colonization bacteria in the two groups . Diarrhea occurred in 7 cases ( 20 % ) in the probiotics treatment group compared with 16 cases ( 46 % ) in the control group ( p<0.05 ) . Two infants ( 6 % ) developed sepsis in the probiotics treatment group compared with 9 cases ( 26 % ) in the control group ( p<0.05 ) . CONCLUSIONS Probiotics can decrease intestinal bacterial colonization rate and the incidence of diarrhea and sepsis in premature infants OBJECTIVE To evaluate the effect of oral administration of probiotics on intestinal colonization with drug-resistant bacteria among preterm infants in the neonatal intensive care unit ( NICU ) . METHODS A double-blind , r and omized , placebo-controlled trial was carried out in the preterm infants who were transferred to the NICU immediately after birth . These infants were stratified by whether they were breastfed and then r and omized into test group and control group . The test group was given probiotics from the day when enteral feeding began , while the control group was treated conventionally without probiotics . The two groups were compared in terms of the colonization with extended-spectrum beta-lactamase-producing bacteria , as assessed by rectal swabs on days 1 , 3 , 7 , and 14 after birth , and the incidence of diseases . RESULTS Rectal colonization with drug-resistant bacteria was found in the test group ( n=119 ) and control group ( n=138 ) on days 1 , 3 , 7 , and 14 after birth . There were no significant differences in the incidence of late-onset sepsis and necrotizing enterocolitis between the two groups ( P>0.05 ) . Among non-breastfed infants , the test group had significantly decreased rectal colonization with drug-resistant bacteria compared with the control group on day 14 after birth ( 71.1 % vs 88.9 % ; P=0.04 ) . No probiotic-related adverse events were observed in the study . CONCLUSIONS Oral administration of probiotics may reduce rectal colonization with drug-resistant bacteria in preterm infants under certain conditions and shows good safety OBJECTIVE To evaluate the impact of early prebiotic and probiotic intervention on  preterm infants ' well-being , crying , growth , and microbiological programming . STUDY DESIGN Ninety-four preterm infants ( gestational age 32 - 36 weeks and birth weight > 1500 g ) r and omized to receive prebiotics ( mixture of galacto-oligosaccharide and polydextrose 1:1 ) , probiotics ( Lactobacillus rhamnosus GG ) , or placebo during the first 2 months of life were followed up for 1 year . Infants were categorized based on the extent of crying and irritability during the first 2 months of life , and their gut microbiota was investigated by fluorescence in situ hybridization ( n = 66 ) and quantitative polymerase chain reaction ( n = 63 ) . RESULTS A total of 27 of 94 infants ( 29 % ) infants were classified as excessive criers , significantly less frequently in the prebiotic and the probiotic groups than in the placebo group ( 19 % vs 19 % vs 47 % , respectively ; P = .02 ) . The placebo group had a higher percentage of Clostridium histolyticum group bacteria in their stools than did the probiotic group ( 13.9 % vs 8.9 % , respectively ; P = .05 ) . There were no adverse events related to either supplementation . CONCLUSIONS Early prebiotic and probiotic supplementation may alleviate symptoms associated with crying and fussing in preterm infants . This original finding may offer new therapeutic and preventive measures for this common disturbance in early life Background : It has been suggested that probiotics can reduce the overgrowth of pathogens in the bowels of preterm infants and contribute to the reduction of the incidence of nosocomial infections in neonatal intensive care units ( NICUs ) . The purpose of this study was to evaluate the effectiveness of Lactobacillus GG supplementation in reducing the incidence of urinary tract infections ( UTIs ) , bacterial sepsis and necrotizing enterocolitis ( NEC ) in preterm infants . Methods : A double-blind study was conducted in 12 Italian NICUs . Newborn infants with a gestational age <33 weeks or birthweight < 1,500 g were r and omized to receive st and ard milk feed supplemented with Lactobacillus GG ( Dicoflor ® , Dicofarm , Rome , Italy ) in a dose of 6 × 109 colony-forming units ( cfu ) once a day until discharge , starting with the first feed or placebo . Results : Five hundred eighty-five patients were studied . The probiotics group ( n = 295 ) and the placebo group ( n = 290 ) exhibited similar clinical characteristics . The duration  of Lactobacillus GG and placebo supplementation was 47.3 ± 26.0 and 48.2 ± 24.3 days , respectively . Although UTIs ( 3.4 vs. 5.8 % ) and NEC ( 1.4 vs. 2.7 % ) were found less frequently in the probiotic group compared to the control group , these differences were not significant . Bacterial sepsis was more frequent in the probiotics group ( 4.4 % , n = 11 ) than in the placebo group ( 3.8 % , n = 9 ) , but the difference was not significant . Conclusion : Seven days of Lactobacillus GG supplementation starting with the first feed is not effective in reducing the incidence of UTIs , NEC and sepsis in preterm infants . Further studies are required to confirm our results in lower birthweight population Objective : The objective of this trial was to test whether probiotic-supplemented feeding to extremely low-birth-weight ( ELBW ) infants will improve growth as determined by decreasing the percentage of infants with weight below the 10th percentile at 34 weeks postmenstrual age ( PMA ) . Other important outcome measures , such as improving feeding tolerance determined by tolerating larger volume of feeding per day and reducing antimicrobial treatment days during the first 28 days from the initiation of feeding supplementation were also evaluated . Study Design : We conducted a multicenter r and omized controlled double-blinded clinical study . The probiotics-supplementation ( PS ) group received Lactobacillus rhamnosus GG and Bifidobacterium infantis added to the first enteral feeding and continued once daily with feedings thereafter until discharge or until 34 weeks ( PMA ) . The control ( C ) group received unsupplemented feedings .  Infant weight and feeding volumes were recorded daily during the first 28 days of study period . Weights were also recorded at 34 weeks PMA . Result : A total of 101 infants were enrolled ( PS 50 versus C 51 ) . There was no difference between the two groups in the percentage of infants with weight below the 10th percentile at 34 weeks PMA ( PS group 58 % versus C group 60 % , ( P value 0.83 ) ) or in the average volume of feeding during 28 days after study entry ( PS group 59 ml kg−1 versus C group 71 ml kg−1 , ( P value 0.11 ) ) . Calculated growth velocity was higher in the PS group compared with the C group ( 14.9 versus 12.6 g per day , ( P value 0.05 ) ) . Incidences of necrotizing enterocolitis ( NEC ) , as well as mortality were similar between the two groups . Conclusion : Although probiotic-supplemented feedings improve growth velocity in ELBW infants , there was no improvement in the percentage of infants with growth delay at 34 weeks PMA . There were no probiotic-related adverse events reported BACKGROUND Colonization by C and ida species is the most important predictor of the development of invasive fungal disease in preterm neonates , and the enteric reservoir is a major site of colonization . We evaluated the effectiveness of an orally supplemented probiotic ( Lactobacillus casei subspecies rhamnosus ; Dicoflor [ Dicofarm spa ] ; 6 x 10(9 ) cfu/day ) in the prevention of gastrointestinal colonization by C and ida species in preterm , very low birth weight ( i.e. , < 1500-g ) neonates during their stay in a neonatal intensive care unit . METHODS Over a 12-month period , a prospect i ve , r and omized , blind , clinical trial that involved 80 preterm neonates with a very low birth weight was conducted in a large tertiary neonatal intensive care unit . During the first 3 days of life , the neonates were r and omly assigned to receive either an oral probiotic added to human ( maternal or pooled donors ' ) milk ( group A ) or human milk alone ( group B ) for 6 weeks or until discharge from the NICU , if the neonate was discharged before 6 weeks . On a weekly basis , specimens obtained from various sites ( i.e. , oropharyngeal , stool , gastric aspirate , and rectal specimens ) were collected from all patients for surveillance culture , to assess the occurrence and intensity of fungal colonization in the gastrointestinal tract . RESULTS The incidence of fungal enteric colonization ( with colonization defined as at least 1 positive culture result for specimens obtained from at least 1 site ) was significantly lower in group A than in group B ( 23.1 % vs. 48.8 % ; relative risk , 0.315 [ 95 % confidence interval , 0.120 - 0.826 ] ; P = .01 ) . The numbers of fungal isolates obtained from each neonate ( P = .005 ) and from each colonized patient ( P = .005 ) were also lower in group A than in group B. L. casei subspecies rhamnosus was more effective in the subgroup of neonates with a birth weight of 1001 - 1500 g. There were no changes in the relative proportions of the different C and ida strains . No adverse effects potentially associated with the probiotic were recorded . CONCLUSIONS Orally administered L. casei subspecies rhamnosus significantly reduces the incidence and the intensity of enteric colonization by C and ida species among very low birth weight neonates OBJECTIVES To evaluate data for the period 2004 - 2013 to identify changes in demographics , pathogens , and outcomes in a single , level IV neonatal intensive care unit . STUDY DESIGN Sepsis episodes were identified prospect ively and additional information obtained retrospectively from infants with sepsis while in the neonatal intensive care unit from 2004 to 2013 .  Demographics , hospital course , and outcome data were collected and analyzed . Sepsis was categorized as early ( ≤3 days of life ) or late-onset ( > 3 days of life ) . RESULTS Four hundred fifty-two organisms were identified from 410 episodes of sepsis in 340 infants . Ninety percent of cases were late-onset . Rates of early-onset sepsis remained relatively static throughout the study period ( 0.9 per 1000 live births ) . For the first time in decades , most ( 60 % ) infants with early-onset sepsis were very low birth weight and Escherichia coli ( 45 % ) replaced group B streptococcus ( 36 % ) as the most common organism associated with early-onset sepsis . Rates of late-onset sepsis , particularly due to coagulase-negative staphylococci , decreased significantly after implementation of several infection-prevention initiatives . Coagulase-negative staphylococci were responsible for 31 % of all cases from 2004 to 2009 but accounted for no cases of late-onset sepsis after 2011 . CONCLUSIONS The epidemiology and microbiology of early- and late-onset sepsis continue to change , impacted by targeted infection prevention efforts . We believe the decrease in sepsis indicates that these interventions have been successful , but additional surveillance and strategies based on evolving trends are necessary Background / Objective : The identification of probiotic species involved in gut homeostasis and their potential therapeutic benefits have led to an interest in their use for preventing necrotizing enterocolitis ( NEC ) . Although bifidobacterium and lactobacilli sp. have been used to reduce the incidence of NEC in clinical trials . Lactobacillus sporogenes has not been used in the prevention of NEC in very low-birth weight infants yet . The objective of this study was to evaluate the efficacy of orally administered L sporogenes in reducing the incidence and severity of NEC in very low-birth weight ( VLBW ) infants . Subjects/ Methods : A prospect i ve , blinded , r and omized controlled trial was conducted in preterm infants with a gestational age of <33 weeks or birth weight of < 1500 g. VLBW infants who survived to start enteral feeding were r and omized into two groups The infants in the study group were given L. sporogenes with a dose of 350 000 000 c.f.u . added to breast milk or formula , once a day , starting with the first feed until discharged . The infants in the control group were fed without L. sporogenes supplementation . The primary outcome measurement was death or NEC ( Bell 's stage ⩾2 ) . Results : A total of 221 infants were studied : 110 in the study group and 111 in the control group . There was no significant difference in the incidence of death or NEC between the groups . Feeding intolerance was significantly lower in the probiotics group than in the control group ( 44.5 % ( n : 49 ) vs 63.1 % ( n : 70 ) , respectively ; P=0.006 ) . Conclusions : L. sporogenes supplementation at the dose of 350 000 000 c.f.u/day is not effective in reducing the incidence of death or NEC in VLBW infants , however , it could improve the feeding tolerance OBJECTIVE To test the efficacy of probiotic and prebiotic , alone or combined ( synbiotic ) , on the prevention of necrotizing enterocolitis ( NEC ) in very low birth weight ( VLBW ) infants . STUDY DESIGN A prospect i ve , r and omized , controlled trial was conducted at 5 neonatal intensive care units in Turkey . VLBW infants ( n = 400 ) were assigned to a control group and 3 study groups that were given probiotic ( Bifidobacterium lactis ) , prebiotic ( inulin ) , or synbiotic ( Bifidobacterium lactis plus inulin ) added to breastmilk or formula for a maximum of 8 weeks before discharge or death . The primary outcome was NEC ( Bell stage ≥2 ) . RESULTS The rate of NEC was lower in probiotic ( 2.0 % ) and synbiotic ( 4.0 % ) groups compared with prebiotic ( 12.0 % ) and placebo ( 18.0 % ) groups ( P < .001 ) . The times to reach full enteral feeding were faster ( P < .001 ) , the rates of clinical nosocomial sepsis were lower ( P = .004 ) , stays in the neonatal intensive care unit were shorter , ( P = .002 ) , and mortality rates were lower ( P = .003 ) for infants receiving probiotics , prebiotics , or synbiotic than controls . The use of antenatal steroid ( OR 0.5 , 95 % CI 0.3 - 0.9 ) and postnatal probiotic ( alone or in synbiotic ) ( OR 0.5 , 95 % CI 0.2 - 0.8 ) decreased the risk of NEC , and maternal antibiotic exposure increased this risk ( OR 1.9 , 95 % CI 1.1 - 3.6 ) . CONCLUSIONS In VLBW infants  , probiotic ( Bifidobacterium lactis ) and synbiotic ( Bifidobacterium lactis plus inulin ) but not prebiotic ( inulin ) alone decrease NEC BACKGROUND Late-onset sepsis is a relatively common complication particularly of preterm birth that affects approximately a quarter of very low birth weight infants . AIM We aim ed to determine the motor , cognitive , and behavioural outcome at school age of preterm children with late-onset sepsis compared to matched controls . STUDY DESIGN AND SUBJECTS A prospect i ve case-control study that included preterm infants ( gestational age<32weeks and /or birth weight<1500 g ) admitted to our Neonatal Intensive Care Unit in 2000 - 2001 with a culture-proven late-onset sepsis , and controls matched for gestational age . OUTCOME MEASURES At school age we assessed motor skills , intelligence , visual perception , visuomotor integration , verbal memory , attention , executive functioning , and behaviour . RESULTS At 6 - 9years , 21 of 32 children with late-onset sepsis ( 68 % ) had borderline or abnormal motor outcome with most problems in fine motor skills . Their total IQ was 89 compared to 98 in controls . In addition , verbal memory and attention were affected compared to controls ( 0.61 st and ard deviations ( SD ) , 95 % confidence interval ( CI ) 0.04 - 1.17 , p=0.033 and 0.94 SD , 95 % CI 0.32 - 1.62 , p=0.011 , respectively ) . Multiple episodes of sepsis and gram-negative sepsis were risk factors for worse cognitive outcome . CONCLUSIONS At school age , a majority of preterm children with late-onset sepsis had motor problems . Their IQ was considerably lower than matched controls , and memory and attention were specifically impaired . Outcome at school age of preterm children with late-onset sepsis was worse than previously thought BACKGROUND Although recent reports suggest that supplementation with probiotics may enhance intestinal function in premature infants , the mechanisms are unclear , and questions remain regarding the safety and efficacy of probiotics in extremely low-birth-weight infants . OBJECTIVE The objective was to evaluate the efficacy of probiotics on the digestive tolerance to enteral feeding in preterm infants born with a very low or extremely low birth weight . DESIGN In a bicentric , double-blind , r and omized controlled clinical trial that was stratified for center and birth weight , 45 infants received enteral probiotics ( Bifidobacterium longum BB536 and Lactobacillus rhamnosus GG ; BB536-LGG )  and 49 received placebo .  The primary endpoint was the percentage of infants receiving > 50 % of their nutritional needs via enteral feeding on the 14th day of life . A triangular test was used to perform sequential analysis . RESULTS The trial was discontinued after the fourth sequential analysis concluded a lack of effect . The primary endpoint was not significantly different between the probiotic ( 57.8 % ) and placebo ( 57.1 % ) groups ( P = 0.95 ) . However , in infants who weighed > 1000 g , probiotic supplementation was associated with a shortening in the time to reach full enteral feeding ( P = 0.04 ) . Other than colonization by the probiotic strains , no alteration in the composition of intestinal microbiota or changes in the fecal excretion of calprotectin was observed . No colonization by probiotic strains was detected in infants who weighed < or = 1000 g , presumably because of more frequent suspensions of enteral feeding , more courses of antibiotic treatment , or both . CONCLUSIONS Supplementation with BB536-LGG may not improve the gastrointestinal tolerance to enteral feeding in very-low-birth-weight infants but may improve gastrointestinal tolerance in infants weighing > 1000 g. This trial was registered at clinical trials.gov as NCT 00290576 AIM To investigate the colonisation withBifidobacterium breve of the bowels of very low birthweight ( VLBW ) infants . METHODS The adverse effects of B breve were examined in 66 VLBW infants ( preliminary study ) . A prospect i ve r and omised clinical study of 91 VLBW infants was also completed and these infants were followed up for three years . Precise viable bacterial counts of serial stool specimens were examined for the first eight weeks after birth in 10 infants . The colonisation rates of administered bacteria were examined using immunohistochemical staining of stool specimens with a B breve specific monoclonal antibody . RESULTS In the preliminary study there were no side effects attributable to the bacteria . Immunohistochemical staining of stool specimens showed that the colonisation rates of the administered bacteria were 73 % at 2 weeks of age , but only 12 % in the control group . Early administration of B brevesignificantly decreased aspirated air volume from the stomach and improved weight gain . CONCLUSIONS B breve can colonise the immature bowel very effectively and is associated with fewer abnormal abdominal signs and better weight gain in VLBW infants , probably as a result of stabilisation of their intestinal flora and accelerated feeding schedules OBJECTIVE To compare the effectiveness of two antibiotic regimens among neonates with late onset sepsis ( LOS ) . METHODS This r and omized controlled trial conducted in a tertiary care teaching hospital , South India , included 90 babies with LOS . Detailed history , examination and appropriate investigations were done for all the babies . Cloxacillin + Amikacin were administered to 40 and Cefotaxime + Gentamicin to 50 babies . Outcomes including mortality , complications and treatment failure were evaluated . Chi-square test was used for categorical variables and Student 's unpaired t-test for continuous variables . RESULTS LOS had a male preponderance , and median time of onset was 13 days . Mortality was more among low birth weight babies irrespective of the antibiotics . Predominant bacteria isolated were coagulase-negative staphylococci ( 26.67 % ) , Escherichia coli ( 13.33 % ) and Streptococcus pneumoniae ( 13.33 % ) . Complications , mortality and cost were similar in both regimens . CONCLUSION There was no significant difference between the two antibiotic regimens with regard to outcome of LOS Objective : The objective of this study is to determine the prevalence , causes and outcome of sepsis in hospitalized neonates in the largest neonatal unit in central Vietnam . Study Design : A 1-year prospect i ve cohort study of newborns admitted to the neonatal unit in Da Nang . A sepsis work-up including blood culture was undertaken before commencing antibiotics for neonates with suspected sepsis . Result : Of 2555 neonatal admissions , 616 neonates had 729 episodes of suspected invasive sepsis . A pathogen was isolated from blood in 115 ( 16 % ) episodes in 106 neonates . The prevalence of early-onset sepsis ( EOS ) was 8 ( 95 % confidence interval ( CI ) : 4 to 11 ) per 1000 admissions , and of late-onset sepsis ( LOS ) was 34 ( 95 % CI : 27 to 41 ) per 1000 admissions . Of 86 neonates with LOS , 69 ( 80 % ) also fulfilled the criteria for nosocomial sepsis . The commonest bacterial causes of EOS were coagulase-negative Staphylococcus ( CoNS ) and Staphylococcus aureus , and of LOS were Acinetobacter , CoNS and Klebsiella pneumoniae . Fungal sepsis occurred in 35 neonates of which most were nosocomial sepsis . In vitro resistance to multiple antibiotics was common among Gram-negative bacteria . Antibiotics were prescribed and given to 68 % of all admissions , and 14 % of all admissions received four or more different antibiotics . The case fatality rate for confirmed sepsis was 46 % . Conclusion : Late-onset , nosocomial sepsis was common and associated with a high mortality in hospitalized newborns in the largest neonatal unit in central Vietnam . These findings highlighted the need for improved infection control measures and antibiotic stewardship , which have since been implemented BACKGROUND Necrotizing enterocolitis ( NEC ) is the most serious gastrointestinal problem in very low birth weight preterm infants . Multiple risk factors activate the inflammatory cascade leading to high expressions of pro-inflammatory mediators causing bowel injury in NEC . The anti-inflammatory effect of probiotics is due to the inhibition and reduction of inflammatory signal in intestinal epithelium . OBJECTIVE To evaluate the efficacy of probiotics supplementation in the prevention of NEC among very low birth weight preterm infants . STUDY DESIGN A prospect i ve r and omized controlled trial . MATERIAL AND METHOD All preterm infants with gestational age less than or equal to 34 weeks and birth weight less than or equal to 1,500 grams admitted in neonatal care unit , Queen Sirikit National Institute of Child Health during June 1st , 2012 and January 31th , 2013 were enrolled in this study . They were r and omized into two groups , study and control group . Infants in the study group were fed Infloran ( Lactobacillus acidophilus 1 x 10(9 ) and Bifidobacterium bifidum 1 x 10(9 ) organisms ) dose 125 mg/kg/dose twice a day with breast milk or premature formula from the start of feeding until 6 weeks or discharge . Infants in the control group were fed with either breast milk or premature formula alone . The primary outcome was NEC stage ≥ 2 . RESULTS Sixty infants completed the study , 31 infants in the study group and 29 infants in the control group . The baseline characteristic data of infants were similar except for more males in the present study group . Incidence of NEC stage ≥ 2 were similar in both the groups , 3.2 vs. 3.4 % ( p = 0.74 ) . There were no deaths during the study period . Days to reach full feeding , 150 ml/kg/day , were no differences between the two groups , 12.03 ± 5.49 days vs. 13.76 ± 8.25 days ( p = 0.31 ) . No adverse effects such as sepsis , flatulence or diarrhea were noted . CONCLUSION In this study , there was no difference in incidence of NEC stage ≥ 2 between the two groups . No adverse effects of probiotics supplementation were observed OBJECTIVE To compare stool colonization among premature infants receiving high-dose probiotics versus st and ard dose . STUDY DESIGN This blinded , r and omized , placebo-controlled trial was conducted in a Level III neonatal unit . Eligibility criteria were gestational age 27 - 33 weeks , age < 96 hours , tolerating milk ≥ 15 mL/kg/day and availability for follow-up . Gastro-intestinal/life-threatening malformations and necrotizing enterocolitis/sepsis were exclusions . A total of 149 subjects were r and omly allocated to groups A through D ( received 12-hourly probiotic supplements of 10(10 ) cells for 21 days , 10(10 ) cells for 14 days , 10(9 ) cells for 21 days and placebo , respectively ) . Key outcome was stool colonization by a probiotic organism at 28 days . RESULTS Colonization with Lactobacillus and Bifidobacterium was significantly higher in groups A , B , and C versus placebo respectively , but groups A through C did not differ from each other . There were trends toward more colony forming unit ( cfu ) of Lactobacillus and Bifidobacterium per milliliter of stool in group A versus B and B versus C. Groups A and B and spontaneous preterm labor ( SPL ) independently predicted high Lactobacillus counts on day 28 ; groups A , B , and C and SPL predicted high Bifidobacterium counts . CONCLUSION Proportion of infants colonized with probiotic species was similar with high-dose and st and ard dose regimes Objective Neonatal sepsis is a major cause of neonatal deaths in Asia but data remain scarce . We aim ed to investigate the causative organisms and antibiotic resistance in neonatal care units in China , Malaysia , Hong Kong and Thail and . Methods Prospect i ve cohort study of neonatal sepsis defined as positive culture of a single potentially pathogenic organism from blood or cerebrospinal fluid differentiated into early-onset sepsis ( EOS ) occurring <3 days of birth and late-onset sepsis ( LOS ) ≥3 days after birth . Results During the study period , there were 963 episodes of neonatal sepsis . The incidence of EOS was 0.62 ( 95 % CI 0.45 to 0.82 ) per 1000 live births or 4.91 ( 95 % CI 4.22 to 5.68 ) per 1000 admissions while the incidence of LOS was 5.00 ( 95 % CI 4.51 to 5.53 ) per 1000 live births or 21.22 ( 95 % CI 19.79 to 22.77 ) per 1000 admissions . The incidence of Group B Streptococcus ( GBS ) sepsis was low but remained the most common single pathogen for EOS among inborn babies . Klebsiella spp . was the most common Gram-negative organism causing most deaths . The case-fatality was 7.0 % ( 95 % CI 3.9 % to 12.0 % ) for EOS and 16.0 % ( 95 % CI 13.7 % to 19.0 % ) for LOS , and was significantly different between participating units after adjusting for potential confounders . Of all Gram-negative organisms , 47 % , 37 % and 32 % were resistant to third-generation cephalosporins , gentamicin or both , respectively . Conclusions The pattern of EOS in Asian setting s is similar to that in industrialised countries with low incidence of GBS sepsis . The important features of neonatal sepsis in Asia are the burden of Klebsiella spp . and high level of antibiotic resistance . These should be addressed while developing measures to reduce neonatal mortality due to infection To assess the impact of a h and hygiene protocol , using h and washing , alcohol h and rub and gloves when caring for preterm infants born after 31 weeks of gestation , on the incidence of neonatal late onset sepsis ( LOS )
target: : Probiotic supplementation reduces the risk of LOS in preterm infants
background: CONTEXT : Late-onset sepsis ( LOS ) is a major cause of mortality and morbidity in preterm infants .
  Despite various preventive measures , its incidence continues to remain high , hence the urgent need for additional approaches .
  One such potential strategy is supplementation with probiotics .
  Currently there are > 30 r and omized controlled trials ( RCTs ) of probiotics in preterm infants that have reported on LOS .