Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations. Treatment of acute infectious diarrhoea in infants and children with a mixture of three Lactobacillus rhamnosus strains--a randomized, double-blind, placebo-controlled trial. Efficacy of Lactobacillus GG in aboriginal children with acute diarrhoeal disease: a randomised clinical trial. Limitations of probiotic therapy in acute, severe dehydrating diarrhea. Saccharomyces boulardii in acute childhood diarrhoea: a randomized, placebo-controlled study. Lactobacillus paracasei strain ST11 has no effect on rotavirus but ameliorates the outcome of nonrotavirus diarrhea in children from Bangladesh. Probiotics have clinical, microbiologic, and immunologic efficacy in acute infectious diarrhea. Nitazoxanide vs. probiotics for the treatment of acute rotavirus diarrhea in children: a randomized, single-blind, controlled trial in Bolivian children. 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. Effect of a lactose-free milk formula supplemented with bifidobacteria and streptococci on the recovery from acute diarrhoea.
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]. Multiple studies document that probiotics are effective in treating infectious diarrhoea in children. Lactobacillus rhamnosus GG is the most extensively studied but effectiveness of other strains has been poorly examined.
                To determine whether L. rhamnosus strains (573L/1; 573L/2; 573L/3) (Lakcid L, Biomed, Lublin, Poland) would be effective in shortening infectious diarrhoea.
                In a randomized, double-blind, placebo-controlled trial, 87 children (age range: 2 months to 6 years) with infectious diarrhoea were administered Lakcid L at a dose 1.2 x 10(10) CFU or placebo, twice daily, for 5 days. Primary outcome measure was the duration of diarrhoea. Secondary measures were duration of parenteral rehydration, adverse events, and gastrointestinal tract colonization by administered strains.
                In an intention to treat analysis of 87 children, the mean duration of diarrhoea in the treated group: 84 +/- 56 h; placebo: 96 +/- 72 h (P = 0.36). In rotavirus infection: 76 +/- 35 h vs. 115 +/- 67 h (P = 0.03), respectively. Duration of parenteral rehydration: 15 +/- 14 h vs. 38 +/- 33 h (P = 0.006). Gut colonization by administered strains was 80% and 41% at five and 14 days, respectively. No adverse events were noted.
                Administration of L. rhamnosus strains shortens the duration of rotaviral diarrhoea in children but not of diarrhoea of any aetiology. Intervention shortens the time of intravenous rehydration. 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. 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. To evaluate the efficacy of the probiotic yeast Saccharomyces boulardii (S. boulardii) as an adjuvant to oral rehydration solution (ORS) in shortening the duration of acute infectious gastroenteritis in children less than 2 years old in ambulatory care.
                In a period of 1 year, 100 outpatients between 3 and 24 months old presenting with acute mild to moderate diarrhoea of less than 7 days duration, were included in a double-blind, randomized, placebo-controlled trial evaluating the efficacy of S. boulardii administered for 6 days. Twelve children were lost in follow-up; the data of 88 children could be analysed (44 in the placebo and 44 in the S. boulardii group). Seventy-two patients were followed for one month (37 in the placebo and 35 in the S. boulardii group) allowing the calculation of the duration of diarrhoea.
                The mean duration of diarrhoea was 6.16 days (range 2-13 days) in the placebo group and 4.70 days (range 2-10 days) in the S. boulardii group (p<0.05). On the 4th day, the patients in the S. boulardii group passed 2.5+/-1.4 stools/day versus 3.5+/-1.8 in the placebo group (p<0.001). The risk of having diarrhoea lasting more than 7 days was lower in the S. boulardii group (3/44 versus 12/44; RR 0.25; 95% CI 0.1-0.8). In no patient diarrhoea persisted longer than 14 days. A statistically significant difference was observed in the number of stools on the 4th and 7th day favouring the subgroup that received early treatment (within the first 48 h of the onset of diarrhoea). The administration of antibiotics before inclusion did not make any difference.
                S. boulardii as an adjuvant to ORS in ambulatory care in children less than 2 years old with mild or moderate acute diarrhoea decreased the duration of diarrhoea, accelerated recovery and reduced the risk of prolonged diarrhoea. The data also indicate increased efficacy if S. boulardii is administered within the first 48 h of the onset of diarrhoea. Previous studies have shown that selected strains of lactobacilli that are administered orally result in a modest reduction of diarrhea duration. However, duration alone is not considered optimal for therapeutic evaluation of any agent in diarrhea.
                To examine the effect of a new probiotic, Lactobacillus paracasei strain ST11 (ST11), in acute childhood diarrhea by using evaluation criteria recommended by the World Health Organization.
                In a randomized, double-blind, placebo-controlled clinical trial, 230 male infants and young children, 4 to 24 months of age, presenting with diarrhea of <2 days' duration were admitted to the metabolic research ward of the International Centre for Diarrheal Disease Research, Bangladesh, and fed 10(10) colony-forming units of lyophilized ST11 or placebo daily for 5 days. Stool output and frequency, oral rehydration solution intake, and excretion of rotavirus were monitored daily.
                No effect of ST11 treatment on severe rotavirus diarrhea was observed. However, the probiotic treatment did significantly reduce cumulative stool output (225 +/- 218 vs 381 +/- 240 mL/kg), stool frequency (27.9 +/- 17 vs 42.5 +/- 26), and oral rehydration solution intake (180 +/- 207 vs 331 +/- 236 mL/kg) in children with less-severe nonrotavirus diarrhea compared with those receiving placebo treatment. A significantly higher proportion of nonrotavirus children receiving ST11 had their diarrhea resolve within 6 days of therapy (ST11 versus placebo: 76% vs 49%).
                ST11 has a clinically significant benefit in the management of children with nonrotavirus-induced diarrhea, but it is ineffective in those with rotavirus diarrhea. 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. In previous studies, nitazoxanide has demonstrated a cytoprotective effect against rotavirus, reducing the duration of diarrhea in comparison to placebo. We designed a randomized, single-blind, controlled trial in order to assess the effectiveness of nitazoxanide and probiotics in comparison with a control group.
                Seventy-five children aged from 28 days to 24 months, with rotavirus diarrhea, were randomly assigned to receive either oral nitazoxanide (15 mg/kg/day) twice a day for three days, a combination of oral probiotics, 1 g twice a day for five days, or only oral or systemic rehydration solutions. The duration of diarrhea and of hospitalization were the primary outcome measures, and daily stool frequency, vomiting, and fever were some of the secondary outcome measures analyzed.
                The median duration of hospitalization was significantly shorter (p = 0.017) in patients who received nitazoxanide (81 h) and probiotics (72 h) compared to patients who received oral rehydration solution alone (108 h). Similarly, the median duration of diarrhea was significantly reduced (p = 0.009) in children who received nitazoxanide (54 h) and probiotics (48 h) compared to the control group (79 h).
                Treatment with nitazoxanide and probiotics is effective in the management of children with acute rotavirus diarrhea. Small differences in favor of nitazoxanide were found in comparison with probiotics. Nitazoxanide is an important treatment option for rotavirus diarrhea. 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. Probiotics have been proposed for the management and prevention of acute diarrhoea in infants. A double-blind, randomised, placebo controlled study was carried out in 224 Chinese infants 6 to 36 months of age with severe acute diarrhoea and free from moderate or severe malnutrition. After oral or parenteral rehydration, they were allocated to one of three groups: a lactose-free formula (Control); the same formula but with viable 10(8)CFU B. lactis Bb12 and 5x10(7)CFU St. thermophilus TH4 per gram of powder and, the same formula with the same microorganisms, but with 10(9)CFU/g and 5x10(8)CFU, respectively. Anthropometric parameters, duration of the diarrhoea and rotavirus shedding were evaluated. Eighty seven percent of the episodes were associated with rotavirus infection. The duration of the diarrhoea was not influenced by the intake of probiotics. However, a decrease of rotavirus shedding was observed in infants fed the formula with 10(9) Bb12/g, a finding of probable epidemiological importance in the transmission of this agent.
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.