Maya-Barrios A, 2021
Mexico
To evaluate the safety and ef f icacy of L. reuteri ATCC PTA 5289 combined with L. reuteri DSM 17938, as an adjuvant to non-steroidal anti-inflammatory drug (NSAID) in children with upper respira tory tract infections (URTIs) aged 6 months to 5 years.
R, DB, PC, 10 days
L. reuteri : 35 (4×108 CFU) Placebo: 35
Compared to placebo the supplement containing L. reuteri significantly reduced:
• Days with fever
• Duration of symptoms
• Severity of sore throat
• Rhinorrhea
• Average cost per child
• Nasal congestion
• TNF-α
Gutiérrez Castrellón P, 2014
Mexico
Evaluate if daily administration of L. reuteri DSM 17938 reduces the frequency and duration of diarrhoea episodes and respiratory tract infections (RTI) in Mexican day school children aged 6-36 months. A cost-effectiveness analysis was also made.
R, DB, PC 3 months of intervention, follow-up at 6 months
L. reuteri: 168 (1×108 CFU) Placebo: 168
Compared to placebo:
• L. reuteri significantly reduced the frequency and duration of episodes of diarrhoea and respiratory tract infection at both 3 and 6 months
• The number of doctor visits, antibiotic use, absenteeism from day school and parental absenteeism from work were signifi cantly reduced
• The use of L. reuteri was associated with a reduction of costs by 36 US dollars (USD) for each case of diarrhoea, and by 37 USD for each case of RTI
Agustina R, 2012a
Indonesia
To investigate milk with low and re gular calcium content, respectively, and the addition of probiotics (L. reuteri DSM 17938 or L. casei CRL431) to milk with regular calcium con tent, on the incidence and duration of diarrhoea and acute respiratory infections in healthy Indonesian children, 1-6y old.
R, DB, PC 6 months
L. reuteri: 124 (5×108 CFU) L. casei: 120 (5×108 CFU) Low calcium milk: 124 Regular calcium milk: 126
Only L. reuteri significantly reduced:
• Incidence of diarrhoea in children with lower nutritional sta tus, irrespective of definition of diarrhoea
• Incidence of diarrhoea in all children when diarrhoea was defined as ≥ 2 loose/liquid stools/24h instead of ≥ 3 loose/ liquid stools/24h
The interventions had no effect on incidence or duration of acute respiratory infection
Agustina R, 2013
(substudy of the Agustina 2012 trial) Indonesia
To investigate the hypotheses that cow’s milk with added probiotics L. reuteri DSM 17938 or L. casei CRL431 would improve growth and iron and zinc status of Indonesian children, whereas milk calcium alone would improve growth but reduce iron and zinc status. A 6-mo. randomized trial was conducted in low-socio economic urban communities, in healthy children, 1-6y old.
R, DB, PC 6 months
L. reuteri: 124 (5×108 CFU) L. casei: 120 (5×108 CFU) Low calcium milk: 124 Regular calcium milk: 126
• Changes in underweight, stunting, anaemia prevalence, and iron and zinc status were similar between groups.
• Regular milk calcium in itself did not affect growth or iron and zinc status. Compared with Regular calcium group:
• L. casei CRL 431 modestly improved monthly weight velocity.
• L. reuteri DSM 17938 modestly improved growth by increasing weight gain, changes in weight-for-age Z-score over 6 mo., and monthly weight and height velocity.
Weizman Z, 2005
Israel
Prevention of common infections in day-care children 4–10 months old.
R, DB, PC 12 weeks
L. reuteri: 68 (1.2×109 CFU) Bb-12: 73 (1.2×109 CFU) Control: 60
L. reuteri significantly reduced (compared to Bb-12 and con trol):
• Days with fever
• Need to consult doctor and need of antibiotics
• Absence from day-care
Both probiotics significantly reduced:
• Episodes with fever • Episodes and days with diarrhoea
Di Nardo G, 2014
Italy
The aim of this study was to evalua te the effect of L. reuteri DSM 17938 in patients with cystic fibrosis, with mild-to-moderate lung disease and aged 6-29y (median age 18y), on the rate of respiratory exacerbations and of infections of the upper respi ratory and the GI tracts. NOTE: The right designation of the probiotic strain of this trial is L. reuteri DSM 17938, not ATCC 55730 as sta ted in the paper.
R, DB, PC 6 months
L. reuteri: 30 (1×108 CFU) Placebo: 30
Compared to placebo, L. reuteri significantly:
• Reduced the frequency of pulmonary exacerbations
• Reduced the number of upper respiratory tract infections = otitis The groups did not differ statistically in the mean number and duration of hospitalizations for pulmonary exacerbations and gastrointestinal infections.
There was no effect on lung function (mean delta value of FEV1), faecal calprotectin concentration, and tested cytokines (tumour necrosis factor-a and interleukin-8) between the two groups.
Wanke M, 2012
Poland
The efficacy of L. reuteri DSM 17938 in prevention of nosocomial diarr hoea in hospitalized children, 1-48 months old.
R, DB, PC During hospi tal stay
L. reuteri: 54 (1×108 CFU) Placebo: 52
L. reuteri did not affect the incidence of hospital-acquired diarrhoeal disease.
Urbanska M, 2016
Poland
The efficacy of L. reuteri DSM 17938 in prevention of nosocomial diarr hoea in hospitalized children, 1-48 months old. A repeat of Wanke’s trial with a 10 times higher dose.
R, DB, PC During hospi tal stay
L. reuteri: 91 (1×109 CFU) Placebo: 93
L. reuteri did not affect the incidence of hospital-acquired diarrhoeal disease.
There was also 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.
Georgieva M, 2015
Bulgaria
To evaluate the preventive effect of L. reuteri DSM 17938 on antibiotic associated diarrhoea and Clostri dium difficile-related infections in hospitalized children, 3-12 years old.
R, DB, PC Study product ing ested during the antibiotic course and 7 days there after.
Follow-up at 21 days post antibiotic treatment
L. reuteri: 49 (1×108 CFU) Placebo: 48
The incidence of diarrhoea was unexpectedly low with only one case in each group. Hence, the study was underpowered to be able to detect any statistical differences between groups. There were no Cl. difficile-related infections, and no diffe rences between groups on proportion of subjects who were positive for Cl. difficile toxin A and B at baseline and on day 21, respectively. There were no differences between groups on the incidence of other GI-related symptoms.
The study products were well tolerated and there was no report of any adverse events.
Savino F, 2015b
Italy
To evaluate the effects of early administration of L. reuteri DSM 17938 on microbial composition in faecal samples of newly hospitali zed, exclusively formula-fed infants below 6 mo. of age. Infants given L. reuteri during at least one month preceding hospitalization were compared to matched controls not given any probiotic.
A case–con trol observa tional study
L. reuteri: 30 (1×108 CFU) Control: 30
Compared to the control group:
• Infants with previous consumption of L. reuteri DSM 17938 (Lr) had significantly lower total counts of anaerobic Gram-neg. bacteria, enterobacteriaceae and enterococci. The Lr group had significantly higher total counts of anaerobic Gram-pos. bacteria. There was no difference in total counts of lactoba cilli and bifidobacteria.
• Infants of the Lr group were negative for atypical entero pathogenic E. coli, Salmonella spp., Cronobacter sakazakii and Serratia odorifera.
• The Lr group had significantly less of Hafnia alvei and Kleb siella oxytoca.
Weizman Z, 2009 (abstract, substudy of Weizman, 2005) Israel
To evaluate if day-care infants acquire a long- term protection against common infections, fol lowing a probiotic supplementation period.
R, DB, PC Follow-up af ter 12 weeks
L. reuteri: 66 (1.2×109 CFU) Bb-12: 69 (1.2×109 CFU) Control: 59
• Protection only observed during supplementation period
• No long-term protection against common infections for any of the probiotics compared to control
Oncel MY, 2015 Turkey
To compare the efficacy of orally administered L. reuteri DSM 17938 vs. the anti-fungal nystatin in pre vention of fungal colonisation and invasive candidiasis in very low birth weight infants ≤1,500 g
R, open
L. reuteri: 150 (1 x108 CFU) Nystatin: 150
Prophylactic L. reuteri was equal to nystatin in reduction of Candida colonisation and invasive candidiasis. Secondary outcomes, compared to nystatin L. reuteri signifi cantly reduced:
• frequency of proven sepsis
• rates of feeding intolerance
• duration of hospital stay
None of the positive blood cultures grew L. reuteri. No other adverse events related to L. reuteri were noted.
Romeo MG, 2011
Italy
To study effects of L. reuteri and another probiotic on Candida co lonisation and of late-onset sepsis in premature newborns in intensive care. Neurological outcome at 12 months of age.
R, open 6 weeks or un til discharged from intensive care
L. reuteri: 83 (1×108 CFU) LGG: 83 (6×109 CFU) Control: 83
• L. reuteri significantly reduced the incidence of GI problems, need of antibiotics and halved the hospital stay, compared to both LGG and control group
Both probiotics compared to control group:
• Significantly reduced incidence of high faecal levels of Candida