Effect of &lt;i&gt;Bifidobacterium lactis&lt;/i&gt; on the Incidence of Nosocomial Infections in Very-Low-Birth-Weight Infants: A Randomized Controlled Trial

Mihatsch, Walter A.; Vossbeck, S; Eikmanns, Bernhard J.; Hoegel, Josef; Pohlandt, Frank

doi:10.1159/000280291

Cited by 116 publications

(95 citation statements)

References 93 publications

(63 reference statements)

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“…Our finding of a lack of effect of the probiotic combination on definite lateonset sepsis is consistent with most, 14,[19][20][21][22][23][24][25][26][27][28][29] but not all, 13,28,[30][31][32] RCTs, as well as published systematic reviews and meta-analyses. [8][9][10] Interestingly, our study suggests a differential benefit of this probiotic combination on late-onset sepsis and possibly NEC of Bell stage 2 or more in infants born at 28 to 31 6 weeks' gestation.…”

Section: Discussionsupporting

confidence: 87%

Probiotic Effects on Late-onset Sepsis in Very Preterm Infants: A Randomized Controlled Trial

Tobin²,

et al. 2013

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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 aimed to determine the effect of administering a specific combination of probiotics to very preterm infants on culture-proven late-onset sepsis. METHODS: A prospective multicenter, double-blinded, placebo-controlled, randomized 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 Zealand were randomized. 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.

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Section: Discussionsupporting

confidence: 87%

Probiotic Effects on Late-onset Sepsis in Very Preterm Infants: A Randomized Controlled Trial

Tobin²,

et al. 2013

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“…We did not find any influence on culture-proven sepsis in our study using Infloran (Laboratorio Farmaceutico), which is in line with other investigations (19,32). As in other studies (33), sepsis with probiotic germs did not occur-neither in the study population nor in infants excluded from the study (data not shown)-which is reassuring.…”

Section: Probiotics For Necsupporting

confidence: 92%

Probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum) prevent NEC in VLBW infants fed breast milk but not formula

et al. 2014

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Background: Specific probiotics prevent necrotizing enterocolitis (NEC). A mixture of lactobacilli and bifidobacteria (Infloran) was highly effective in Asian very-low-birth-weight (VLBW) infants. We analyzed the effect of Infloran on NEC, NEC severity, and the influence of enteral feedings (breast milk vs. formula) on NEC prevention in a cohort of European VLBW infants. Methods: Infloran was implemented for routine use at our department. VLBW infants receiving probiotics were prospectively followed (2010)(2011)(2012) and compared with historic controls (2008)(2009). Data on NEC, neonatal morbidity, feeding tolerance, and descriptive parameters on NEC cases were analyzed. results: Infloran had no statistically significant impact on NEC (controls: 24/233 (10.3%); probiotics: 16/230 (7%); P = 0.2). However, NEC was significantly reduced in infants of the probiotics group who were fed any breast milk (20/179 (11.2%) vs. 10/183 (5.5%); P = 0.027), whereas it was ineffective in infants exclusively fed formula (4/54 (7.4%) vs. 6/44 (13.6%); P = 0.345). Occurrence of severe NEC (IIIb), time until full feeds, and gastric residuals were similar. conclusion: Infloran was of lower efficacy in a European VLBW cohort and showed a reduction of NEC only in infants fed breast milk. Future studies should investigate the influence of feeding formula or breast milk on the effect of probiotics.n ecrotizing enterocolitis (NEC) is an important cause of mortality and morbidity in premature infants (1). Although its pathogenesis is incompletely understood, a relation to an immature intestinal barrier, aberrant bacterial colonization, and enteral feedings is well established (2). Due to the seriousness of the disease, preventive strategies like the use of human milk and standardized feeding protocols (3-5) are of highest interest.Probiotics are microorganisms that confer a health benefit after ingestion (6). They are generally regarded as safe, and only single cases of sepsis were described in patients with major comorbidities (7). In preterm infants, probiotics may act beneficially by improving the intestinal barrier (8) and promoting a healthy gut microflora (9). Furthermore, they exert antiinflammatory effects on the gut epithelium (10) and improve local and systemic immune responses (11) that may strengthen a preterm infant's still immature immune defense. In the recent past, a preventive effect against NEC was assumed (12), and a variety of probiotic preparations were studied in randomized trials. Meta-analyses of these trials reported on a reduction of NEC in very-low-birth-weight (VLBW) infants by 65% (13,14), and the use of probiotics in clinical routine was recommended. Based on these suggestions, we decided to introduce probiotics for NEC prophylaxis as standard of care at our department. The probiotic preparation Infloran (Laboratorio Farmaceutico, Mede, Italia) consists of a mixture of Lactobacillus acidophilus and Bifidobacterium infantis and was chosen as its use was suggested by European experts (14) and it was available ...

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“…The B. lactis used by Mihatsch et al 36 was checked monthly to ensure the viability and purity of the product together with the 24-hour stability of the prepared suspension. The six-strain product used by Fernández-Carrocera et al 40 (four strains of Lactobacillus, one of B. infantis and one of S. thermophilus) was checked twice against the manufacturer's quality control register and the ABC Dophilus used for the ProPrems trial 41 was imported under licence into Australia.…”

Section: Qualitymentioning

confidence: 99%

A randomised controlled trial of the probiotic Bifidobacterium breve BBG-001 in preterm babies to prevent sepsis, necrotising enterocolitis and death: the Probiotics in Preterm infantS (PiPS) trial

Costeloe

Bowler

Brocklehurst

et al. 2016

Health Technol Assess

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BackgroundNecrotising enterocolitis (NEC) and late-onset sepsis remain important causes of death and morbidity in preterm babies. Probiotic administration might strengthen intestinal barrier function and provide protection; this is supported by published meta-analyses, but there is a lack of large well-designed trials.ObjectiveTo test the use of the probioticBifidobacterium brevestrain BBG-001 to prevent NEC, late-onset sepsis and death in preterm babies while monitoring probiotic colonisation of participants.DesignDouble-blind, randomised, placebo-controlled trial.SettingRecruitment was carried out in 24 hospitals, and the randomisation programme used a minimisation algorithm. Parents, clinicians and outcome assessors were blinded to the allocation.ParticipantsBabies born between 23 and 30 weeks’ gestation and randomised within 48 hours of birth. Exclusions included life-threatening or any gastrointestinal malformation detected within 48 hours of birth and no realistic chance of survival.InterventionsActive intervention: 1 ml ofB. breveBBG-001 in one-eighth-strength infant formula Neocate®(Nutricia Ltd, Trowbridge, UK), (6.7 × 107to 6.7 × 109colony-forming units) per dose administered enterally. Placebo: 1 ml of one-eighth-strength infant formula Neocate. Started as soon as practicable and continued daily until 36 weeks’ postmenstrual age.Main outcome measuresPrimary outcomes were an episode of bloodstream infection, with any organism other than a skin commensal, in any baby between 72 hours and 46 weeks’ postmenstrual age; an episode of NEC Bell stage ≥ 2 in any baby; and death before discharge from hospital. Secondary outcomes included stool colonisation withB. breve.ResultsIn total, 654 babies were allocated to receive probiotic and 661 to receive placebo over 37 months from July 2010. Five babies were withdrawn; 650 babies from the probiotic group and 660 from the placebo group were included in the primary analysis. Baseline characteristics were well balanced. There was no evidence of benefit for the primary outcomes {sepsis: 11.2% vs. 11.7% [adjusted relative risk (RR) 0.97, 95% confidence interval (CI) 0.73 to 1.29]; NEC Bell stage ≥ 2: 9.4% vs. 10.0% [adjusted RR 0.93, 95% CI 0.68 to 1.27]; and death: 8.3% vs. 8.5% [adjusted RR 0.93, 95% CI 0.67 to 1.30]}.B. brevecolonisation status was available for 1186 (94%) survivors at 2 weeks’ postnatal age, of whom 724 (61%) were positive: 85% of the probiotic group and 37% of the placebo group. There were no differences for subgroup analyses by minimisation criteria and by stool colonisation withB. breveat 2 weeks. No harms associated with the interventions were reported.LimitationsCross-colonisation of the placebo arm could have reduced statistical power and confounded results; analyses suggest that this did not happen.ConclusionsThis is the largest trial to date of a probiotic intervention. It shows no evidence of benefit and does not support routine use of probiotics for preterm infants.Future work recommendationsThe increasing understanding of the pathogenesis of NEC and sepsis will inform the choice of probiotics for testing and better define the target population. Future Phase III trials should incorporate monitoring of the quality and viability of the intervention and colonisation rates of participants; cluster design should be considered.Trial registrationCurrent Controlled Trials ISRCTN05511098 and EudraCT 2006-003445-17.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 20, No. 66. See the NIHR Journals Library website for further project information.

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Effect of <i>Bifidobacterium lactis</i> on the Incidence of Nosocomial Infections in Very-Low-Birth-Weight Infants: A Randomized Controlled Trial

Cited by 116 publications

References 93 publications

Probiotic Effects on Late-onset Sepsis in Very Preterm Infants: A Randomized Controlled Trial

Probiotic Effects on Late-onset Sepsis in Very Preterm Infants: A Randomized Controlled Trial

Probiotics (Lactobacillus acidophilus and Bifidobacterium bifidum) prevent NEC in VLBW infants fed breast milk but not formula

A randomised controlled trial of the probiotic Bifidobacterium breve BBG-001 in preterm babies to prevent sepsis, necrotising enterocolitis and death: the Probiotics in Preterm infantS (PiPS) trial

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