L. reuteri DSM 17938 for the prevention of nosocomial diarrhea in children, high dose study

A randomised, double blind, placebo-controlled, multi-centre study to evaluate the efficacy of L. reuteri DSM 17938 (Protectis) in prevention of nosocomial diarrhoea in children admitted to hospital for reasons other than diarrhoea, aged 1-48 months. 91 children were given L. reuteri and 93 the equivalent placebo for the length of the hospital stay.

L. reuteri did not affect the incidence of hospital-acquired diarrhoeal disease. In addition, there was no difference between the L. reuteri and placebo groups for any of the secondary outcomes, including adverse effects. Rotavirus vaccination status had no impact on the results.

Conclusion: The trial did not find any preventive effect of L. reuteri in the dosage of 10^9 CFU/day compared to placebo.

Comment: This was a repeat of the Wanke trial of 2012, but with a 10 times higher dose = 10^9 CFU/day. The baseline incidence of nosocomial diarrhoea in this high dose trial became however much lower than estimated, 7% instead of 33%, and consequently the number of included and analysed subjects in the trial became too low to be able to detect any statistically significant differences between the two groups. Therefore it is still an open question whether this dosage may work for this indication.

Effects of the regular intake of the probiotic Lactobacillus reuteri (DSM 17938) on respiratory and gastrointestinal infections in a workplace setting

A randomised, double blind, placebo-controlled study evaluating the effect of L. reuteri DSM 17938 on the number of days of sick leave related to respiratory and/or gastrointestinal diseases among male steelworkers.

242 subjects were randomised to ingest L. reuteri (10^8 CFU/day) or the matching placebo for 90 days, whereof 79 and 80 completed the study, respectively.

L. reuteri significantly reduced the incidence of diarrhoea, which was reported on 0.60 days for subjects of the L. reuteri group vs. 1.33 days in the placebo group. There was no difference in primary outcome of  number of sick days due to respiratory or gastrointestinal symptoms. The drop-out rate of randomized subjects was 34%.  

Conclusion: The incidence of diarrhoea was significantly reduced by the daily intake of L. reuteri DSM 17938, but there was no effect on the number of days of sick leave related to respiratory and/or gastrointestinal disease.

Reduction of diarrhoea in day care children with L. reuteri

This randomised, double-blind, placebo-controlled study was performed to evaluate whether daily administration of Lactobacillus reuteri DSM 17938 (L. reuteri Protectis) could reduce the frequency and duration of diarrhoeal episodes and other health outcomes in day school children. 336 healthy children, 6-36 months, attending day care centres in Mexico City were randomised to either supplementation with five drops (10^8 CFU) of Lactobacillus reuteri Protectis (n=168) per day or placebo (n=168) for three months followed by three months without supplementation.

Data from all children were included in the final analysis. Lactobacillus reuteri Protectis significantly reduced frequency and duration of diarrhoeal episodes both during intervention and follow-up period (P<0.05). Additionally, the number of doctor visits, antibiotic use, absenteeism from day school and parental absenteeism from work were significantly reduced in the Lactobacillus reuteri group (P<0.05). A cost-benefit analysis revealed that supplementation with Lactobacillus reuteri Protectis is cost-effective for both family and community. No adverse events related to the study product were reported.

Lactobacillus reuteri DSM 17938 (L. reuteri Protectis) had a significant effect in reducing episodes and duration of diarrhea and respiratory tract (RTI) infection, with consequent cost savings for the community.

Conclusions
In healthy children attending day care centers, daily administration of Lactobacillus reuteri DSM 17938 (L. reuteri Protectis) had a significant effect in reducing episodes and duration of diarrhea and respiratory tract (RTI) infection, with consequent cost savings for the community. This study also adds independent support to previously published evidence (Weizman 2005, Agustina 2012) supporting the use of Lactobacillus reuteri Protectis in the prevention of infectious diseases in day care children.

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Lack of an effect of Lactobacillus reuteri in preventing nosocomial diarrhoea in children

To evaluate the efficacy of Lactobacillus reuteri DSM 17938 for the prevention of nosocomial (hospital-acquired) diarrhoea, 106 children (aged 1-48 months) admitted to the hospital for reasons other than diarrhoea were enrolled in a randomized, double-blind, placebocontrolled trial. The children received either Lactobacillus reuteri DSM 17938 at a dose of 10^8 CFU (n=54) or a placebo (n=52) orally, once daily for the duration of their hospital stay.

Lactobacillus reuteri DSM 17938 did not significantly affect the risk of developing nosocomial diarrhoea, defined as 3 loose or watery stools per day in a 24 hour period that occurred >72 hours after admission (risk ratio 1.06, 95% CI 0.7–1.5) or rotavirus infection (1.04, 0.6-1.6). There was also no difference between the probiotic and placebo groups for any of the other secondary outcomes (incidence of rotavirus infection, incidence of diarrhoea, duration of diarrhoea, incidence of recurrent diarrhoea, incidence of chronic diarrhoea, length of hospital stay and frequency of need for rehydration). No adverse events were reported.

Conclusion:
In hospitalized children, the administration of Lactobacillus reuteri DSM 17938 compared with placebo had no effect on the overall incidence of nosocomial diarrhoea, including rotavirus infection.

Randomized trial of probiotics and calcium on diarrhea and respiratory tract infections

This trial investigated the effects of probiotics on the incidence and duration of diarrhoea and respiratory infections in low-socioeconomic communities of East Jakarta, Indonesia.

Reduction of diarrhea with Lactobacillus reuteri Protectis

In a 6-month double-blind, placebocontrolled study, 494 apparently healthy children aged 1-6 years were randomly assigned to 4 groups: to receive low-lactose milk with low calcium content of ≈50 mg/day, (LC, n=124); low lactose milk with high calcium ≈440 mg Ca/day (RC, n=126); RC with 5×10^8 CFU/day Lactobacillus casei 431 (n=120); or RC with 5×10^8 CFU/day Lactobacillus reuteri DSM 17938 (n=124).

Primary outcomes were the number and duration of acute diarrhoeal episodes. Number and duration of acute respiratory infections were secondary outcomes. The incidence of WHO-defined diarrhoea (≥ 3 loose/liquid stools in 24 h) did not differ between Lactobacillus casei and RC (RR: 1.21 [95% CI: 0.76–1.95]) or between Lactobacillus reuteri and RC (RR: 0.76 [95% CI: 0.46–1.25]). There was also no difference between the LC and RC groups. The incidence of all diarrhoea episodes (≥ 2 loose/liquid stools in 24 h) was significantly lower for Lactobacillus reuteri compared to RC (RR: 0.68 [95% CI: 0.46–0.99]). Further, the incidence of both WHO-defined and all episodes of diarrhoea were significantly reduced in the Lactobacillus reuteri group among children with lower nutritional status (below-median height- and weight-for-age Z-score). None of the interventions affected the incidence or duration of respiratory infections.

The incidence of all diarrhoea episodes (≥ 2 loose/liquid stools in 24 h) was significantly lower for Lactobacillus reuteri

Conclusions
Regular calcium milk alone or with Lactobacillus casei did not reduce diarrhoea or acute respiratory infections in Indonesian children. Lactobacillus reuteri DSM 17938 prevented diarrhoea and exerted effects especially in children with lower nutritional status.

Role of probiotics in the prevention of the enteric colonization by Candida in preterm newborns

This open, prospective and randomised study investigated whether two different probiotics could decrease the risk of gastrointestinal colonisation of Candida species, of late-onset sepsis and neurological outcome in preterm neonates in an intensive care unit.

249 infants, of which 56 had a birth weight <1500 g, were consecutively assigned to either supplementation with Lactobacillus reuteri ATCC 55730 (10^8 CFU/day, group I), supplementation with Lactobacillus rhamnosus ATCC 53103 (=LGG, 6×10^9 CFU/day, group II) or no supplementation (group III). The supplementation started within 72 hours of admittance and continued for six weeks or until discharge.

Compared to the control group, both probiotics significantly reduced the incidence of high Candida faecal counts (>10^4 CFU/g of faeces), p<0.01, and there were also fewer fungal and bacterial infections, although the differences were not statistically significant. The number of infants with gastrointestinal symptoms was significantly reduced in the Lactobacillus reuteri group (3/83) vs. group II (29/83) and III (36/83), p<0.05. Consequently, the infants given Lactobacillus reuteri were weaned from parental nutrition more quickly and the time to reach full energy intake was also significantly shorter. Days on antibiotic treatment were reduced by Lactobacillus reuteri: 3.4 days vs. 5.8 days and 6.9 days in group II and III, respectively (p<0.05). Hospital stays were also significantly shorter in the Lactobacillus reuteri group: 18 days vs. 27 and 31 in group II and III, respectively (p<0.0001). At the follow-up of neurological outcomes at 12 months there were significantly fewer children with suboptimal scores in both probiotic groups compared to the control group, p<0.05.

Conclusion
Both probiotics reduced the incidence of high faecal counts of Candida in these preterm infants and demonstrated no safety problems. Fewer infants given Lactobacillus reuteri needed antibiotic treatment, fewer of them had any gastrointestinal problems and the hospital stay was reduced; these outcomes were significantly different to the results for the infants in the LGG and the control group. Infants supplemented with probiotics had a significantly reduced incidence of suboptimal neurological outcome at one year of age compared to the control group.

Probiotics in the prevention of bacterial and Candida infections in newborns

An open, prospective and randomised study that investigated the effects of daily oral probiotic supplementation on the incidence of bacterial and fungal infections, the incidence of gastrointestinal symptoms, and time to tolerate enteral nutrition in surgical newborns attending a Neonatal Intensive Care Unit (NICU).

24 newborns with a gestational age of 36.4 ± 2.7 weeks, a birth weight of 2568.3 ± 644 g, and admitted in the NICU due to greater surgical interventions were included.

Group 1 (n=8) was supplemented with Lactobacillus reuteri ATCC 55730, group 2 (n=8) was supplemented with Lactobacillus GG and group 3 (n=8) was not given probiotics. Both probiotics were administered from the time of admittance to the NICU.

The clinical parameters evaluated were: No. of bacterial and Candida infections, No. of days with antimycotic treatment, duration of parenteral nutrition, time to tolerance of enteral/oral food intake, weight increase, gastrointestinal symptoms, and duration of hospital stay.

Results: Significantly fewer infective episodes were observed in groups 1 and 2 compared with controls: 0%, 12%, and 37.5%, respectively, for bacterial infections and 12.5%, 25%, 37.5% for Candida infections. Group 3 needed antimycotic treatment for a significantly longer period of time: the medium duration of antimycotic treatment was 19 days in group 1, 29 days in group 2, and 41 days in group 3. The medium duration of parenteral nutrition was 18 days in group 1, 34 days in group 2, and 42 in group 3 (p<0.05).

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Conclusion: Probiotic supplementation to this high-risk group of newborns can reduce the risk of bacterial and Candida sepsis, shorten the period of time with parenteral nutrition, reduce gastrointestinal symptoms and increase oral food tolerance, with significant reduction in hospital stay.

Increasing work-place healthiness with Lactobacillus reuteri

Short term illnesses, usually caused by respiratory or gastrointestinal diseases are disruptive to productivity and there is relatively little focus on preventative measures. This study examined the effect of the probiotic Lactobacillus reuteri protectis (ATCC55730) on its ability to improve work-place healthiness by reducing short term sick-leave caused by respiratory or gastrointestinal infections.

262 employees at TetraPak in Sweden (day-workers and three-shift-workers) that were healthy at study start were randomised in a double-blind fashion to receive either a daily dose of 10^8 Colony Forming Units of Lactobacillus reuteri or placebo for 80 days. The study products were administered with a drinking straw. 181 subjects complied with the study protocol, 94 were randomised to receive Lactobacillus reuteri and 87 received placebo.

In the placebo group 26.4% reported sick-leave for the defined causes during the study as compared with 10.6% in the Lactobacillus reuteri group (p < 0.01). The frequency of sick-days was 0.9% in the placebo group and 0.4% in the Lactobacillus reuteri group (p < 0.01). Among the 53 shift-workers, 33% in the placebo group reported sick during the study period as compared with none in the Lactobacillus reuteri group(p < 0.005).

Conclusions
The present study demonstrates that Lactobacillus reuteri is effective to promote work-place healthiness. In the studied population sick-days caused by respiratory or gastrointestinal diseases could be reduced by 55% by the use of Lactobacillus reuteri group as compared with the placebo group. Translated to the total Swedish work-force, this translates to a total of 4.3 million working days of improved productivity per year (3.9 million employed, 220 working days per year and 0,5% “saved” days). Our results indicate that the effect on shift-work productivity could probably be even more profound but this issue should be addressed in further studies.

Effect of a probiotic infant formula on infections in child care centres

This was a prospective, randomised, double blind, placebo-controlled study, investigating whether probiotics affect the occurrence of infections in infants in day care.

201 healthy children, aged 4–10 months, were studied for 12 weeks in three different groups: They were given formula with Lactobacillus reuteri ATCC 55730 or Bifidobacterium lactis Bb-12, or formula without probiotics (control).

Probiotics resulted in significantly fewer infections compared to the placebo, measured by the number of febrile episodes and episodes of gastrointestinal infection. Lactobacillus reuteri, however, had a significantly superior effect compared to B. lactis and the control group: there were significantly fewer doctors’ visits, less use of antibiotics, and fewer absent days from day care in the Lactobacillus reuteri group. 

Conclusion: The addition of probiotics to infant formula had a significantly positive effect on the incidence of common infections in children in day care, with superior effect shown for Lactobacillus reuteri. There were no safety issues during the three months of the study.