Bacillus clausii for Prevention of Late-onset Sepsis in Preterm Infants: A Randomized Controlled Trial. Probiotic Effects on Late-onset Sepsis in Very Preterm Infants: A Randomized Controlled Trial Comparison of two empiric antibiotic regimen in late onset neonatal sepsis--a randomized controlled trial. Detection of Sepsis in Preterm Infants by Fecal Volatile Organic Compounds Analysis: A Proof of Principle Study A high burden of late-onset sepsis among newborns admitted to the largest neonatal unit in central Vietnam Reduction in necrotizing enterocolitis and improved outcomes in preterm infants following routine supplementation with Lactobacillus GG in combination with bovine lactoferrin. Procalcitonin-guided decision making for duration of antibiotic therapy in neonates with suspected early-onset sepsis: a multicentre, randomised controlled trial (NeoPIns) Use of Procalcitonin-Guided Decision-Making to Shorten Antibiotic Therapy in Suspected Neonatal Early-Onset Sepsis: Prospective Randomized Intervention Trial 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 Neonatal Procalcitonin Intervention Study (NeoPInS): Effect of Procalcitonin-guided decision making on Duration of antibiotic Therapy in suspected neonatal early-onset Sepsis: A multi-centre randomized superiority and non-inferiority Intervention Study Early-onset Sepsis and Antibiotic Exposure in Term Infants: A Nationwide Population-based Study in Norway Is Lactoferrin More Effective in Reducing Late-Onset Sepsis in Preterm Neonates Fed Formula Than in Those Receiving Mother's Own Milk? Secondary Analyses of Two Multicenter Randomized Controlled Trials. Randomized Trial of Donor Human Milk Versus Preterm Formula as Substitutes for Mothers' Own Milk in the Feeding of Extremely Premature Infants Influence of a combination of probiotics on bacterial infections in very low birthweight newborns Gut microbial colonisation in premature neonates predicts neonatal sepsis Hand hygiene with alcohol hand rub and gloves reduces the incidence of late onset sepsis in preterm neonates Role of probiotics VSL#3 in prevention of suspected sepsis in low birthweight infants in India: a randomised controlled trial
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 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 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 Objectives : Several studies associated altered gut microbiota composition in preterm infants with late-onset sepsis ( LOS ) , up to days before clinical onset of sepsis . Microbiota analysis as early diagnostic biomarker is , however , in clinical practice currently not feasible because of logistic aspects and high costs . Therefore , we hypothesized that analysis of  fecal volatile organic compounds ( VOCs ) may serve as noninvasive biomarker to predict LOS at a pre clinical stage , because VOC reflect the composition and activity of intestinal microbial communities . Methods : In a prospect i ve multicenter study , fecal sample s were collected daily from infants with a gestational age of < 30 weeks .  VOC signatures of fecal sample s from infants with LOS , collected up to 5 days before diagnosis , were analyzed by means of an electronic nose technology ( Cyranose 320 ) and compared to matched controls . Results : Fecal VOC profiles of infants with LOS ( n = 36 ) could be discriminated from controls ( n = 40 ) at 3 days ( area under the curve [ ±95 % confidence interval ] , P value , sensitivity , specificity ; 70.2 [ 52.2–88.3 ] , 0.033 , 57.1 % , 61.5 % ) , 2 days ( 77.7 [ 62.7–92.7 ] , 0.050 , 75.0 % , 70.8 % ) , and 1 day ( 70.4 [ 49.6–91.3 ] , 0.037 , 64.3 % , 64.3 % ) before the onset of LOS . Conclusions : Fecal VOC profiles of preterm infants with LOS could be discriminated from matched controls , up to 3 days before clinical onset of the disease , underlining the hypothesis that intestinal microbiota may play an etiological role in LOS . Notably , VOC profiling is clinical ly feasible and the potential of this technique in the early detection of LOS needs to be confirmed in future studies 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 Preterm infants remain at high risk of adverse outcomes following necrotizing enterocolitis  ( NEC ) and late onset sepsis ( LOS ) . Meta- analysis of r and omized trials has indicated a reduction in severe NEC following use of probiotics and bovine lactoferrin ( LF ) . Overall , however , uncertainty remains over which probiotic , or combination to use . The aim of this study was to compare the incidence of severe NEC and LOS before and after routine supplementation with Lactobacillus GG ( LGG ) and LF . METHODS In this retrospective cohort study , infants < 32 weeks or < 1500 g routinely received LGG and 100 mg lactoferrin daily from 2011 -2015 were compared with similar infants born from 2004 - 2008 . Cases of NEC were Bell stage 2 or greater and LOS was blood or spinal fluid culture positive after 48 hrs of age . RESULTS We noted a marked decline in the incidence of NEC from 3 % to 1 % with a RR of 0.29 ( CI 0.1 - 0.9 ) and a number needed to benefit of 50 . The cost of preventing one case of NEC was estimated to be NZ $ 2800 , considerably lower than the cost of treatment . LOS rates were not significantly different . There was a decrease in retinopathy treatment rates . During the period there was one case of LGG sepsis in a 23 week gestation infant with abdominal pathology and one infant developed NEC after stopping prophylaxis . CONCLUSION The rates of severe NEC was markedly reduced following prophylaxis . The case of LGG sepsis indicates caution is required in extremely preterm infants BACKGROUND Up to 7 % of term and late-preterm neonates in high-income countries receive antibiotics during the first 3 days of life because of suspected early-onset sepsis . The prevalence of culture-proven early-onset sepsis is 0·1 % or less in high-income countries , suggesting substantial overtreatment . We assess whether procalcitonin-guided decision making for suspected early-onset sepsis can safely reduce the duration of  antibiotic treatment . METHODS We did this r and omised controlled intervention trial in Dutch ( n=11 ) , Swiss ( n=4 ) , Canadian ( n=2 ) , and Czech ( n=1 ) hospitals . Neonates of gestational age 34 weeks or older , with suspected early-onset sepsis requiring antibiotic treatment  were stratified into four risk categories by their treating physicians and r and omly assigned [ 1:1 ] using a computer-generated list stratified per centre to procalcitonin-guided decision making or st and ard care-based antibiotic treatment . Neonates who underwent surgery within the first week of life or had major congenital malformations that would have required hospital admission were excluded . Only principal investigators were masked for group assignment . Co- primary outcomes were non-inferiority for re-infection or death in the first month of life ( margin 2·0 % ) and superiority for duration of antibiotic therapy . Intention-to-treat and per- protocol analyses were done . This trial was registered with Clinical Trials.gov , number NCT00854932 . FINDINGS Between May 21 , 2009 , and Feb 14 , 2015 , we screened 2440 neonates with suspected early-onset sepsis . 622 infants were excluded due to lack of parental consent , 93 were ineligible for reasons unknown ( 68 ) , congenital malformation ( 22 ) , or surgery in the first week of life ( 3 ) . 14 neonates were excluded as 100 % data monitoring or retrieval was not feasible , and one neonate was excluded because their procalcitonin measurements could not be taken . 1710 neonates were enrolled and r and omly assigned to either procalcitonin-guided therapy ( n=866 ) or st and ard therapy ( n=844 ) . 1408 neonates underwent per- protocol analysis ( 745 in the procalcitonin group and 663 st and ard group ) . For the procalcitonin group , the duration of antibiotic therapy  was reduced ( intention to treat : 55·1 vs 65·0 h , p<0·0001 ; per protocol : 51·8 vs 64·0 h ; p<0·0001 ) . No sepsis-related deaths occurred , and 9 ( < 1 % ) of 1710 neonates had possible re-infection . The risk difference for non-inferiority was 0·1 % ( 95 % CI -4·6 to 4·8 ) in the intention-to-treat analysis ( 5 [ 0·6 % ] of 866 neonates in the procalcitonin group vs 4 [ 0·5 % ] of 844 neonates in the st and ard group ) and 0·1 % ( -5·2 to 5·3 ) in the per- protocol analysis ( 5 [ 0·7 % ] of 745 neonates in the procalcitonin group vs 4 [ 0·6 % ] of 663 neonates in the st and ard group ) . INTERPRETATION Procalcitonin-guided decision making was superior to st and ard care in reducing antibiotic therapy in neonates with suspected early-onset sepsis . Non-inferiority for re-infection or death could not be shown due to the low occurrence of re-infections and absence of study -related death . FUNDING The Thrasher Foundation , the NutsOhra Foundation , the Sophia Foundation for Scientific research Background : Diagnosis of neonatal early-onset sepsis is difficult because clinical signs and laboratory tests are non-specific . Early antibiotic therapy is crucial for treatment success . Objective : To evaluate the effect of procalcitonin (PCT)-guided decision-making on duration of antibiotic therapy in suspected neonatal early-onset sepsis . Methods : This single-center , prospect i ve , r and omized intervention study was conducted in a tertiary neonatal and pediatric intensive care unit in the Children ’s Hospital of Lucerne , Switzerl and , between June 1 , 2005 and December 31 , 2006 . All term and near-term infants ( gestational age ≧34 weeks ) with suspected early-onset sepsis were r and omly assigned either to st and ard treatment based on conventional laboratory parameters ( st and ard group ) or to PCT-guided treatment ( PCT group ) . Minimum duration of antibiotic  therapy was 48–72 h in the st and ard group , whereas in the PCT group antibiotic therapy was discontinued when two consecutive PCT values were below predefined age-adjusted cut-off values . Results : 121 newborns were r and omly assigned either to the st and ard group ( n = 61 ) or the PCT group ( n = 60 ) . The two groups were similar for baseline demographics , risk factors for early-onset sepsis , likelihood of infection as assessed by the attending physician and early conventional laboratory findings . There was a significant difference in the proportion of newborns treated with antibiotics ≧72 h between the st and ard group ( 82 % ) and the PCT group ( 55 % ) ( absolute risk reduction 27 % ; odds ratio 0.27 ( 95 % CI 0.12–0.62 ) , p = 0.002 ) . On average , PCT-guided decision-making result ed in a shortening of 22.4 h of antibiotic therapy . Clinical outcome was similar and favorable in both groups but sample size was insufficient to exclude rare adverse events . Conclusion : Serial PCT determinations allow to shorten the duration of antibiotic therapy in term and near-term infants with suspected early-onset sepsis . Before this PCT-guided strategy can be recommended , its safety has to be confirmed in a larger cohort of neonates 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 Early diagnosis and treatment of the newborn infant with suspected sepsis are essential to prevent severe and life threatening complications . Diagnosis of neonatal sepsis is difficult because of the variable and nonspecific clinical presentation . Therefore , many newborns with nonspecific symptoms are started on antibiotic treatment before the presence of sepsis has been proven . With our recently published single-centre intervention study we were able to show that Procalcitonin determinations allowed to shorten the duration of antibiotic therapy in newborns with suspected early-onset sepsis . Methods / Design The study is design ed as r and omized controlled international multicenter intervention trial on the efficacy and safety of Procalcitonin guided treatment .  Term and near-term infants ( gestational age ≥ 34 0/7 weeks ) with suspected sepsis in the first 3 days of life requiring empiric antibiotic therapy will be included . The duration of antibiotic therapy in the st and ard group is based on the attending physician 's assessment of the likelihood of infection ( infection unlikely , possible , probable or proven ) . In the Procalcitonin group , if infection is considered to be unlikely or possible , antibiotic therapy is discontinued when two consecutive Procalcitonin values are within the normal range . Co- primary outcome measures are the duration of antibiotic therapy ( superiority aspect of the trial ) and the proportion of infants with a recurrence of infection requiring additional courses of antibiotic therapy and /or death in the first month of life ( safety of study intervention , non-inferiority aspect of the trial ) . The number of infants to be included equals 800 per arm . With these numbers the power of the study to demonstrate superiority for duration of antibiotic therapy as well as non-inferiority regarding safety , i.e. excluding a disadvantage difference larger than 2 % for the experimental arm , will both be greater than 80 % . Discussion Benefit of the study is a possible limitation of unnecessary use of antibiotics . The results of our first study suggest that there is a low risk on discontinuing antibiotic treatment too early , result ing in the development of a neonatal infection with its morbidity and mortality . Trial registration This trial is registered in the U.S. National Institutes of Health 's register , located at http://www . clinical trials.gov . ( NCT00854932 ) Background : Sepsis is a leading cause of neonatal morbidity and mortality . Clinical suspicion may lead to overuse of antibiotics . The objective of this study was to assess the epidemiology of early-onset sepsis ( EOS ) and antibiotic exposure during the first week of life in Norwegian term infants . Methods : This is a nationwide population -based study from the Norwegian Neonatal Network . During the 3-year study period ( 2009–2011 ) , 20 of Norway ’s 21 neonatal units prospect ively collected data . Among 168,877 live-born ( LB ) term infants born during the study period , 10,175 ( 6.0 % ) infants were hospitalized in the first week of life and included in the study . Results : There were 91 cases of culture-confirmed EOS ( 0.54 per 1000 LB ) and 1447 cases classified as culture-negative EOS ( 8.57 per 1000 LB ) . The majority of culture-confirmed EOS cases were caused by Gram-positives ( 83/91 ; 91 % ) , most commonly group B streptococci ( 0.31 per 1000 LB ) . Intravenous antibiotics were administered to 3964 infants ; 39 % of all admissions and 2.3 % of all LB term infants . Empiric therapy consisted of an aminoglycoside and either benzylpenicillin or ampicillin in 95 % of the cases . The median ( interquartile range ) treatment duration was 8 ( 7–10 ) days for culture-confirmed EOS and 6 ( 5–7 ) days for culture-negative EOS . There was 1 EOS-attributable death ( group B streptococcal EOS ) during the study period . Conclusions : In this registry-based study , the incidence of culture-confirmed EOS was in line with previous international reports and the mortality was very low . A large proportion of infants without infection were treated with antibiotics . Measures should be taken to spare neonates unnecessary antibiotic treatment BACKGROUND Lactoferrin is the major antimicrobial protein in human milk . In our r and omized controlled trial ( RCT ) of bovine lactoferrin ( BLF ) supplementation in preterm neonates , BLF reduced  late-onset sepsis ( LOS ) .  Mother 's own milk ( MM ) contains higher concentrations of lactoferrin than donor milk or formula , but whether BLF is more effective in infants who receive formula or donor milk is uncertain . AIM To evaluate the incidence of LOS in preterm infants fed MM and in those fed formula and /or donor milk . STUDY DESIGN This is a ( A ) post hoc subgroup analysis , in our RCT of BLF , of its effects in preterm infants fed MM , with or without formula , versus those fed formula and /or donor milk ( no-MM ) and ( B ) post hoc meta- analysis , in our RCT of BLF and in the ELFIN ( Enteral Lactoferrin in Neonates ) RCT , of the effect of BLF in subgroups not exclusively fed MM . RESULTS ( A ) Of 472 infants in our RCT , 168 were r and omized to placebo and 304 were r and omized to BLF . Among MM infants , LOS occurred in 22/133 ( 16.5 % ) infants r and omized to placebo and in 14/250 ( 5.6 % ) r and omized to BLF ( relative risk or risk ratio ( RR ) : 0.34 ; relative risk reduction ( RRR ) : 0.66 ; 95 % confidence interval ( 95 % CI ) for RR : 0.18 - 0.64 ; p < 0.0008 ) . Among no-MM infants , LOS occurred in 7/35 ( 20.0 % ) r and omized to placebo and in 2/54 ( 3.7 % ) r and omized to BLF ( RR : 0.19 ; RRR : 0.81 ; 95 % CI for RR : 0.16 - 0.96 ; p = 0.026 ) . In multivariable logistic regression analysis , there was no interaction between BLF treatment effect and type of feeding ( p = 0.628 ) . ( B ) In 1,891 infants not exclusively fed MM in our RCT of BLF and in the ELFIN RCT , BLF reduced the RR of LOS by 18 % ( RR : 0.82 ; 95 % CI : 0.71 - 0.96 ; p = 0.01 ) . CONCLUSION Adequately powered studies should address the hypothesis that BLF is more effective in infants fed formula or donor milk than those fed MM . Such studies should evaluate whether a specific threshold of total lactoferrin intake can be identified to protect such patients from LOS Objective . Compared with preterm formula ( PF ) , mother 's milk ( MM ) is associated with lower rates of late-onset sepsis ( LOS ) and necrotizing enterocolitis ( NEC ) among premature infants . Because not all mothers of premature infants produce sufficient milk to supply their infants throughout hospitalization , we reasoned that pasteurized donor human milk ( DM ) would be a suitable alternative . Methods . Extremely premature infants ( < 30 weeks of gestation ) whose mothers intended to breastfeed were assigned r and omly to receive either pasteurized DM or PF if the supply of their own MM became insufficient during the study ( birth to 90 days of age or hospital discharge ) . Infection-related events ( LOS , NEC , meningitis , presumed sepsis , or urinary tract infection ) that occurred after the attainment of a milk intake of 50 mL/kg , dietary intake , growth , skin-to-skin contact , and duration of hospital stay were compared . The primary analysis compared groups DM and PF on an intent-to-treat basis . If no differences were noted , then these groups were combined and compared with the reference group , group MM . If differences were noted , then the subsequent analyses compared each group with group MM . Results . Of 243 infants , 70 ( 29 % ) received only MM ; group DM included 81 infants and group PF included 92 infants . Because of poor weight gain , 17 infants ( 21 % ) , all in group DM , were switched to PF . There were no differences in birth weight , gestational age , multiple births , and age at attainment of feeding of 50 mL/kg among groups . There were no differences between group DM and group PF in LOS and /or NEC , other infection-related events , hospital stay , or number of deaths . Group DM received a greater intake of milk and more nutritional supplements but had a slower rate of weight gain , compared with group PF . Compared with groups DM and PF , group MM had fewer episodes of LOS and /or NEC and total infection-related events and a shorter duration of hospital stay . Group MM also had fewer Gram-negative organisms isolated from blood cultures than did the other groups . Conclusions . In this r and omized , blinded trial of feeding of extremely premature infants , we found that , as a substitute for MM , DM offered little observed short-term advantage over PF for feeding extremely premature infants . Advantages to an exclusive diet of MM were observed in terms of fewer infection-related events and shorter hospital stays Summary Background Late-onset infections are an important cause of morbidity and mortality in preterm infants . The purpose of our prospect i ve r and omised study was to establish whether a combination of probiotics ( Lactobacillus acidophilus , Enterococcus faecium and Bifidobacterium infantum ) affects the incidence of late-onset sepsis and other infections in very low birthweight infants ( birthweight under 1500 g , gestational age under 33 weeks ) . Methods From 80 included infants , one half received probiotics ( L. acidophilus , E. faecium and B. infantum ) in the ratio 1.5:1:1.5 , at a dose of 0.6 × 107 colony-forming units twice daily , given with the first portions of milk until discharge , whereas the other half did not . Results In the group receiving probiotics , 16 children had late-onset sepsis compared with 29 in the group without probiotics ; p = 0.006 . The number of late-onset septic events was lower ( 30 ) in the group receiving probiotics than in the group that did not receive probiotics ( 69 ) ; p = 0.003 . Furthermore , fewer children had at least one late-onset infection ( 20 infants in the group receiving probiotics compared with 32 in the group without them ; p = 0.009 ) . There were less episodes of late-onset infections in the group receiving probiotics ( 35 ) than in the group without probiotics ( 79 ) ; p = 0.002 . Conclusions A combination of probiotics at a low dose ( 1.2 × 107 colony-forming units ) decreased the frequency of late-onset sepsis and other infections , as described in previous studies . In addition , children were discharged at a lower postmenstrual age . There were no side effects of probiotics reported Background Neonatal sepsis due to intestinal bacterial translocation is a major cause of morbidity and mortality . Underst and ing microbial colonisation of the gut in prematurity may predict risk of sepsis to guide future strategies to manipulate the microbiome . Methods Prospect i ve longitudinal study of premature infants . Stool sample s were obtained weekly . DNA was extracted and the V6 hypervariable region of 16S rRNA was amplified followed by high throughput pyrosequencing , comparing subjects with and without sepsis . Results Six neonates were 24–27 weeks gestation at birth and had 18 sample s analysed . Two subjects had no sepsis during the study period , two developed late-onset culture-positive sepsis and two had culture-negative systemic inflammation . 324 350 sequences were obtained . The meconium was not sterile and had predominance of Lactobacillus , Staphylococcus and Enterobacteriales . Overall , infants who developed sepsis began life with low microbial diversity , and acquired a predominance of Staphylococcus , while healthy infants had more diversity and predominance of Clostridium , Klebsiella and Veillonella . Conclusions In very low birth weight infants , the authors found that meconium is not sterile and is less diverse from birth in infants who will develop late-onset sepsis . Empiric , prolonged antibiotics profoundly decrease microbial diversity and promote a microbiota that is associated not only with neonatal sepsis , but the predominant pathogen previously identified in the microbiome . Our data suggest that there may be a ‘ healthy microbiome ’ present in extremely premature neonates that may ameliorate risk of sepsis . More research is needed to determine whether altered antibiotics , probiotics or other novel therapies can re-establish a healthy microbiome in neonates 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 ) Objectives To assess the effect of the probiotic VSL#3 in prevention of neonatal sepsis in low birthweight ( LBW ) infants . Design R and omised , double-blind , placebo-controlled trial . Setting Community setting in rural India . Participants LBW infants aged 3–7 days . Interventions Infants were r and omised to receive probiotic ( VSL#3 , 10 billion colony-forming units ( cfu ) ) or placebo for 30 days , and were followed up for 2 months . Main outcome measure Possible serious bacterial infection ( PSBI ) as per the Integrated Management of Neonatal Childhood Illnesses algorithm , as diagnosed by fieldworkers/physicians . Results 668 infants were r and omised to VSL#3 and 672 to placebo .  By intention-to-treat analysis , the risk of PSBI among infants in the overall population of LBW infants was not statistically significant ( RR 0.79 ( 95 % CI 0.56 to 1.03 ) ) . Probiotics  reduced median days of hospitalisation ( 6 days vs 3 days in probiotics ) ( p=0.018 ) but not the risk of hospitalisation ( RR 0.66 ( 95 % CI 0.42 to 1.04 ) . The onset of PSBI in 10 % of infants occurred on the 40th day in the probiotics arm versus the 25th day in the control arm ( p=0.063 ) . Conclusions Daily supplementation of LBW infants with probiotics VSL#3 ( 10 billion cfu ) for 30 days led to a non-significant 21 % reduction in risk of neonatal sepsis . A larger study with sufficient power and a more specific primary end point is warranted to confirm the preventive effect of VSL#3 on neonatal sepsis in LBW infants . Trial registration number The study is registered at the Clinical Trial Registry of India ( CTRI/2008/091/000049 )
: Probiotic supplementation reduces the risk of LOS in preterm infants
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 .