Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations. Limitations of probiotic therapy in acute, severe dehydrating diarrhea. Probiotics have clinical, microbiologic, and immunologic efficacy in acute infectious diarrhea. Efficacy of Lactobacillus GG in aboriginal children with acute diarrhoeal disease: a randomised clinical trial. The probiotic Escherichia coli strain Nissle 1917 (EcN) stops acute diarrhoea in infants and toddlers. Efficacy of Lactobacillus rhamnosus GG in acute watery diarrhoea of Indian children: a randomised controlled trial. Role of a probiotic (Saccharomyces boulardii) in management and prevention of diarrhoea. Effect of probiotic Lactobacillus strains in young children hospitalized with acute diarrhea. Effect of probiotic Lactobacillus strains on acute diarrhea in a cohort of nonhospitalized children attending day-care centers.
To compare the efficacy of five probiotic preparations recommended to parents in the treatment of acute diarrhoea in children. Design Randomised controlled clinical trial in collaboration with family paediatricians over 12 months.
                Primary care.
                Children aged 3-36 months visiting a family paediatrician for acute diarrhoea.
                Children's parents were randomly assigned to receive written instructions to purchase a specific probiotic product: oral rehydration solution (control group); Lactobacillus rhamnosus strain GG; Saccharomyces boulardii; Bacillus clausii; mix of L delbrueckii var bulgaricus, Streptococcus thermophilus, L acidophilus, and Bifidobacterium bifidum; or Enterococcus faecium SF68.
                Primary outcomes were duration of diarrhoea and daily number and consistency of stools. Secondary outcomes were duration of vomiting and fever and rate of admission to hospital. Safety and tolerance were also recorded.
                571 children were allocated to intervention. Median duration of diarrhoea was significantly shorter (P<0.001) in children who received L rhamnosus strain GG (78.5 hours) and the mix of four bacterial strains (70.0 hours) than in children who received oral rehydration solution alone (115.0 hours). One day after the first probiotic administration, the daily number of stools was significantly lower (P<0.001) in children who received L rhamnosus strain GG and in those who received the probiotic mix than in the other groups. The remaining preparations did not affect primary outcomes. Secondary outcomes were similar in all groups.
                Not all commercially available probiotic preparations are effective in children with acute diarrhoea. Paediatricians should choose bacterial preparations based on effectiveness data.
                Current Controlled Trials ISRCTN56067537 [controlled-trials.com]. Recent studies have shown that probiotics, most commonly, may be useful in treating acute gastroenteritis. However, beneficial effects appear to be limited to a modest decrease in the duration of diarrhea. No studies have evaluated this therapy in moderate to severe dehydrating diarrhea in a metabolic facility.
                Male children less than 2 years of age were admitted to a metabolic unit of the Department of Pediatrics at the Federal University of Bahia, Brazil, with moderate dehydration and were randomized in a double-blind, placebo-controlled fashion. Oral rehydration solution (ORS) was administered per protocol and either placebo or was given in combination with the ORS. Output of urine, stool, and vomitus was recorded along with stool weight, nude body weight, and standard laboratory assessments for hydration.
                There was no significant reduction in diarrhea duration and stool output in the group. However, Kaplan-Meier survival analysis demonstrated that, even in moderate to severe diarrhea, resolution of the illness occurred so rapidly, that statistically significant benefits of probiotic therapy could not be demonstrated.
                Our data implies that colonization must occur before benefits of probiotics can be realized. Probiotics are, therefore, likely to be of limited benefit in treating diarrheal illnesses of short duration such as viral enteritis. The beneficial effects of probiotics may be limited to prophylactic usage in high-risk populations. Acute infectious diarrhea is a major cause of childhood morbidity and economic burden for families. We evaluate the clinical, microbiologic, and immunologic effects of probiotics in acute infectious diarrhea.
                Children (n = 304) aged 3 months to 6 years hospitalized for acute diarrhea were randomized to receive Bio-three (a mixture of Bacillus mesentericus, Enterococcus faecalis, and Clostridium butyricum) or placebo orally 3 times daily for 7 days. Fecal samples were homogenized for bacterial culture and blood cells were isolated for cell culture and cytokine analysis. This study is registered (NCT00463190).
                The mean duration of diarrhea after start of therapy was 60.1 hours in the probiotics group versus 86.3 hours in the placebo group (P = 0.003). Hospital stay was shorter in the probiotics group than in the placebo group (P = 0.009). Counts of Bifidobacteria and Lactobacillus species were elevated in stool culture of the probiotics (Bio-three) group. IL-10 was increased in the serum and supernatants of cell culture in the probiotics group, and tumor necrosis factor-alpha values were down-regulated. Interferon- gamma and IL-12 were mildly elevated in the probiotics group, compared with the placebo group.
                This probiotics mixture reduced the severity of diarrhea and length of hospital stay in children with acute diarrhea. In addition to restoring beneficial intestinal flora, probiotics may enhance host protective immunity such as down-regulation of pro-inflammatory cytokines and up-regulation of anti-inflammatory cytokines. The effectiveness of probiotic therapy for acute rotavirus infectious diarrhoea in an indigenous setting with bacterial/parasitic diarrhoea is unclear. In the present study, we assessed the efficacy of probiotics in Australian Aboriginal children in the Northern Territory admitted to hospital with diarrhoeal disease.
                A randomised double-blind placebo-controlled study was conducted in Aboriginal children (ages 4 months-2 years), admitted to hospital with acute diarrhoeal disease (>3 loose stools per day). Children received either oral Lactobacillus GG (5 x 10(9) colony-forming units 3 times per day for 3 days; n = 33) or placebo (n = 31). Small intestinal functional capacity was assessed by the noninvasive 13C-sucrose breath test on days 1 and 4.
                Both groups showed mean improvement in the sucrose breath test after 4 days; however, there was no difference (mean, 95% confidence interval) between probiotic (2.9 [cumulative percentage of dose recovered at 90 minutes]; 1.7-4.2) and placebo (3.7; 2.3-5.2) groups. Probiotics did not change the duration of diarrhoea, total diarrhoea stools, or diarrhoea score compared with placebo. There was a significant (P < 0.05) difference in diarrhoea frequency on day 2 between probiotics (3.3 [loose stools]; 2.5-4.3) and placebo (4.7; 3.8-5.7) groups.
                Lactobacillus GG did not appear to enhance short-term recovery following acute diarrhoeal illness in this setting. In most cases, acute diarrhoea will become self-limiting during the first few days after onset. For young children, however, health risks may develop when the disease lasts longer than 3 days. The purpose of the present trial was to determine whether the stool frequency of infants and toddlers suffering from acute diarrhoea could be normalised more quickly by administering the probiotic Escherichia coli Nissle 1917 (EcN) solution than by administering a placebo. The safety of EcN were also assessed. A total of 113 children (aged 2-47 months) with acute diarrhoea (> three watery or loose stools in 24 h) were randomised to either a group receiving the probiotic EcN suspension (n = 55) or a group receiving the placebo suspension (n = 58) in a confirmative, double-blind clinical trial. Depending on the age of patients, 1-3 ml per day of verum suspension (10(8) viable EcN cells per millilitre) or placebo were administered orally. The causes of the diarrhoea were viral rather than bacterial, but they were mainly unspecific infections. The median onset of treatment response (reduction of daily stool frequency to </= three watery or loose stools over at least 2 consecutive days) occurred more rapidly in the children receiving the EcN solution (2.5 days) than in those receiving the placebo (4.8 days), a significant difference (2.3 days; p = 0.0007). The number of patients showing a response was clearly higher (p < 0.0001) in the EcN group (52/55; 94.5%) than in the placebo group (39/58; 67.2%). EcN was found to be safe and well-tolerated, and it showed a significant superiority compared to the placebo in the treatment of acute diarrhoea in infants and toddlers. To evaluate the role of Lactobacillus rhamnosus GG (LGG) as probiotic in acute watery diarrhoea (AWD).
                Hospital-based study.
                Randomised, controlled, blinded trial.
                All patients of AWD (n = 684) admitted over 1-year period were invited to participate in the study as per predefined inclusion and exclusion criteria and were randomised to intervention and control groups. After adequate rehydration the intervention group (n = 330) received ORS with probiotic powder containing 60 million cells of LGG, while the control group (n = 332) received ORS alone twice daily for a minimum period of 7 days or till diarrhoea ceased. During the study period all patients received ORS and/or IV fluids for ongoing losses, and nutritional supplementation. None of them received any antibiotic or antidiarrhoeal medication. After exclusion of 16 patients, 646 (323 in each arm) patients completed the study. The daily frequency and total duration of diarrhoea and vomiting and the length of hospital stay were studied. Data were analysed by SPSS-10 software. Statistical significance was calculated by Student's t-test and chi2-test.
                Rotavirus was isolated in 75.85%. There was no significant difference between treatment groups in the daily frequency or duration of diarrhoea or vomiting or in the length of hospital stay. No complication was observed from the use of LGG.
                LGG supplementation does not decrease the frequency and duration of diarrhoea and vomiting in children with AWD, and does not reduce hospital stay in these patients. To assess the efficacy and safety of Saccharomyces boulardii (S. boulardii) in acute watery diarrhoea and its role in reducing the frequency of episodes of diarrhoea in subsequent two months.
                Children from 2 mo to 12 years of age, with acute diarrhoea were selected according to inclusion criteria and randomised in S. boulardii group (treated with ORS, nutritional support and S. boulardii, 250 mg bid) and in control group (treated with ORS and nutritional support only). Active treatment phase was 5 d and each child was followed for two months afterwards. Frequency and consistency of stools as well as safety of drug was assessed on every visit. A comparison of two groups was done in terms of number of diarrhoeal episode in subsequent two months.
                There were fifty patients in each group. Baseline characteristics such as mean age and the average frequency of stools were comparable in S. boulardii and control group at the time of inclusion in the trial. By d 3 it reduced to 2.7 and 4.2 stools per d respectively and by d 6 it reduced to 1.6 (S. boulardii Group) and 3.3 (control group). The duration of diarrhoea was 3.6 d in S. boulardii group whereas it was 4.8 d in control group (P = 0.001). In the following two months, S. boulardii group had a significantly lower frequency of 0.54 episodes as compared to 1.08 episodes in control group. The drug was well accepted and tolerated. There were no reports of the side effects during treatment period.
                S. boulardii significantly reduces the frequency and duration of acute diarrhoea. The consistency of stool also improves. The drug is well-tolerated. Oral bacteriotherapy promotes recovery from acute childhood diarrhea, but few strains have been shown to have therapeutic potentials. We examined the effect of two newly identified probiotic Lactobacillus strains in acute childhood diarrhea.
                Sixty-nine children were randomized during hospitalization for acute diarrhea to receive a mixture of Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 12246, 10(10) colony-forming units of each strain or placebo twice daily for 5 days. Before selection of these stains their potential probiotic characteristics were demonstrated in vitro and in healthy volunteers.
                In patients receiving probiotics, the diarrheal phase was reduced by 20%. The duration of diarrhea was 82 h in the treatment group vs. 101 h in the control group (not significant, P = 0.07). However, 3 of 30 patients from the treatment group vs. 13 of 39 from the control group still had loose stools at the end of the study period (P = 0.03). In patients with diarrhea for <60 h before start of treatment (early intervention), a clear effect of the probiotics was demonstrated (80 h in the treatment group vs. 130 h in the control group, P = 0.003). After early intervention, the length of hospitalization was reduced by 48% (3.5 vs. 1.7 days, P = 0.03). At the end of the intervention, rotavirus antigen was found in 12% of patients from the treatment group vs. 46% from the control group (P = 0.02).
                The two probiotics, L. rhamnosus 19070-2 and L. reuteri DSM 12246, ameliorated acute diarrhea in hospitalized children and reduced the period of rotavirus excretion. Oral bacteriotherapy was associated with a reduced length of hospital stay. The beneficial effects were most prominent in children treated early in the diarrheal phase. Certain strains of lactobacilli have been shown to promote recovery from rotavirus enteritis in hospitalized children. Few studies have examined the effect of probiotics in nonhospitalized children with mild diarrhea.
                We studied in a randomized placebo-controlled trial the effect of lyophilized Lactobacillus rhamnosus 19070-2 and Lactobacillus reuteri DSM 12246, 10(10) colony-forming units of each strain twice daily for 5 days, on acute diarrhea in children in a cohort of children recruited from local day-care centers. The duration of diarrhea and assessment of stool consistency were recorded by the parents.
                In patients treated with the selected Lactobacillus strains, the mean duration of diarrhea after intervention was reduced (76 h in patients treated with probiotics vs. 116 h in the placebo group; P = 0.05). In patients with diarrhea for <60 h before start of treatment (early intervention), a more pronounced effect of probiotics was found. The time to recovery after early treatment was 79 h vs. 139 h in the placebo group (P = 0.02); 1 of 17 patients treated early vs. 6 of 13 in the control group still had loose stools 120 h after start of treatment (P = 0.03).
                In children from day-care centers with mild gastroenteritis, the combination of L. rhamnosus 19070-2 and L. reuteri DSM 12246 was effective in reducing the duration of diarrhea.
Used alongside rehydration therapy, probiotics appear to be safe and have clear beneficial effects in shortening the duration and reducing stool frequency in acute infectious diarrhoea. However, more research is needed to guide the use of particular probiotic regimens in specific patient groups.