Prevention of antibiotic-associated diarrhea in infants by probiotics. Prophylactic Lactobacillus GG reduces antibiotic-associated diarrhea in children with respiratory infections: a randomized study. [Prevention of antibiotic-associated diarrhea with Lactobacillus sporogens and fructo-oligosaccharides in children. A multicentric double-blind vs placebo study]. [Oral bacterial therapy in prevention of antibiotic-induced diarrhea in childhood]. A randomized formula controlled trial of Bifidobacterium lactis and Streptococcus thermophilus for prevention of antibiotic-associated diarrhea in infants. Does eating yogurt prevent antibiotic-associated diarrhoea? A placebo-controlled randomised controlled trial in general practice. A double-blind, placebo-controlled study of the efficacy of Lactinex in the prophylaxis of amoxicillin-induced diarrhea. Lactobacillus GG in the prevention of antibiotic-associated diarrhea in children. The probiotic effect of Saccharomyces boulardii in a pediatric age group. A randomized clinical trial measuring the influence of kefir on antibiotic-associated diarrhea: the measuring the influence of Kefir (MILK) Study. Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea in children. Bifidobacterium longum PL03, Lactobacillus rhamnosus KL53A, and Lactobacillus plantarum PL02 in the prevention of antibiotic-associated diarrhea in children: a randomized controlled pilot trial. Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea in children: a randomized double-blind placebo-controlled trial. Randomized, double-blind, placebo-controlled trial: effect of lactobacillus GG supplementation on Helicobacter pylori eradication rates and side effects during treatment in children.
Probiotics administration has been claimed to prevent antibiotic-associated diarrhea. The investigators thus conducted a double blind, placebo controlled study of providing probiotics to infants and children with severe bacterial infections and receiving broad spechum antibiotics. The results of the study showed that the group receiving probiotics had fewer diarrheal episodes (37.5%) than the control group (80%), although the numbers were too small for statistical analysis. In conclusion, probiotics administration to patients receiving high doses of broad spectrum antibiotics may prevent the occurrence of antibiotic-associated diarrhea. A further study with a larger number is required. Antimicrobial treatment may disturb the colonization resistance of gastrointestinal microflora, which may induce clinical symptoms, most commonly diarrhea. The severity of antibiotic-associated diarrhea may range from a brief, self-limiting disease to devastating diarrhea with electrolyte disturbances, dehydration, crampy abdominal pain, pseudomembranous colitis, toxic megacolon, or even death. The incidence of diarrhea in children receiving a single antimicrobial treatment is unclear. In addition to more critical use of antimicrobials, adjunctive preventive measures to antibiotic-associated diarrhea are needed. The objective of this study was to evaluate the incidence of diarrhea after antimicrobial treatment in children with no history of antimicrobial use during the previous 3 months. Another aim of this study was to assess the preventive potential of Lactobacillus rhamnosus GG (Lactobacillus GG; American Type Culture Collection 53103), a probiotic strain with a documented safety record and a therapeutic effect in viral gastroenteritis on antibiotic-associated diarrhea.
                Oral antimicrobial agents were prescribed for the treatment of acute respiratory infections at the clinics of the Health Care Center of the City of Tampere or Tampere University Hospital, Finland, to 167 patients who were invited to participate in the study. Of the patients, 48 were lost to follow-up; therefore, the final study population consisted of 119 children from 2 weeks to 12. 8 years of age (mean: 4.5 years). All study subjects met the inclusion criteria: they had not received any antimicrobial medication during the previous 3 months, they did not suffer from gastrointestinal disorders, and they did not need intravenous antimicrobial treatment. The patients were randomized to receive placebo or 2 x 10(10) colony-forming units of Lactobacillus GG in capsules given twice daily during the antimicrobial treatment. Lactobacillus GG and placebo capsules were indistinguishable in appearance and taste. The parents kept a daily symptom diary and recorded stool frequency and consistency at home for 3 months. Diarrhea was defined as at least three watery or loose stools per day for a minimum of 2 consecutive days. In the case of diarrhea, viral (adenovirus, rotavirus, calicivirus and astrovirus) and bacterial (Salmonella, Shigella, Yersinia, Campylobacter, Clostridium difficile, Staphylococcus aureus, and yeasts) analyses were studied in fecal samples. The metabolic activity of the gut microflora was assessed by analysis of fecal urease, beta-glucosidase, and beta-glucuronidase activities. The primary outcome measure was diarrhea during the first 2 weeks after the beginning of the antimicrobial treatment, because this period most likely reflects the effects of antimicrobial use. Secondary outcome measures were the activities of fecal urease, beta-glucuronidase, and beta-glucosidase.
                On the entire follow-up, 80% of any gastrointestinal symptoms were reported during the first 2 weeks after the beginning of the antimicrobial treatment. The incidence of diarrhea was 5% in the Lactobacillus GG group and 16% in the placebo group within 2 weeks of antimicrobial therapy (chi(2) = 3.82). The treatment effect (95% confidence interval) of Lactobacillus GG was -11% (-21%-0%). In diarrheal episodes, the viral and bacterial analyses were positive for Clostridium difficile in 2 cases and for Norwalk-like calicivirus in 3 cases. The age of the patients with diarrhea was between 3 months and 5 years in 75% of cases in both groups. The severity of diarrhea was comparable in the study groups, as evidenced by similar stool frequency (mean: 5 per day; range: 3-6) and the duration of diarrhea (mean: 4 days; range: 2-8). The activities of fecal urease and beta-glucuronidase, but not beta-glucosidase, changed significantly after the beginning of the antimicrobial treatment in the Lactobacillus GG group and in the placebo group alike. (ABSTRACT TRUNCATED) The aim of this paper is to determine the efficacy of a fructo-oligosaccharides (FOS)-Lactobacillus sporogenes preparation in the prevention of diarrhea due to antibiotics in childhood.
                A multicentre, randomised, double-blind versus placebo study was carried out. A total of 120 children, with active infections requiring antibiotics, were enrolled in the study and treated for 10 days either in the experimental group (F) or in the placebo one (P). The results of the study were recorded from the patients' diary and from follow-up clinical examinations.
                Out of 98 evaluable patients, 71% in group F had no diarrhea versus 38% in group P. The duration of diarrhea in F and P groups was 0.7 vs 1.6 days (p=0.002), respectively.
                Prophylaxis with Lactobacillus sporogens, associated to FOS, significantly reduced the number of days and duration of events in children with antibiotic-induced diarrhea. Amoxycillin is currently the most widely used antibiotic in pediatrics. It is known that this antibiotic, as well as other kinds of antimicrobial treatments, may produce variations in the bowel ecosystem. A controlled randomised clinical trial was performed using commercially available fermented milk products in infants who had received an oral treatment with amoxycillin for an average of ten days. 40 children have been examined, randomly divided into two groups of twenty. Group 1 received treatment with antibiotic plus lactobacilli. Group 2 received only amoxycillin. At the end of the trial infants of group 1 showed a lower frequency of stool passages and more fully-formed feces, while patients of group 2 presented an increased frequency of gastrointestinal disorders. On the basis of the results obtained it is possible to conclude that oral bacterial therapy with lactobacilli is efficacious in preventing diarrhea from amoxycillin in infancy. This clinical trial was carried out to determine whether oral treatment with a commercial probiotic formula containing Bifidobacterium lactis and Streptococcus thermophilus would reduce the frequency of antibiotic-associated diarrhea (AAD) in infants.
                In this double-bind formula controlled study, 80 infants, 6 to 36 months of age, were randomly assigned to receive a commercial formula containing 10 viable cells of B. lactis and 10 viable cells of S. thermophilus at the initiation of antibiotics for a duration of 15 days. The infants were assessed daily for formula intake, stool frequency, and stool consistency for a total duration of 30 days. Seventy-seven infants received nonsupplemented formula for the entire duration.
                There was a significant difference in the incidence of AAD in the children receiving probiotic-supplemented formula (16%) than nonsupplemented formula (31%).
                The present study shows that prevention against AAD in infants was obtained by oral treatment with daily dose of B. lactis and S. thermophilus. Probiotic capsules have been shown to reduce the incidence of antibiotic-associated diarrhoea in a number of settings. If probiotic yogurt were equally efficacious then it would provide a simple and cost-effective means of preventing antibiotic-associated diarrhoea.
                To investigate whether eating live bio yogurt at the time of taking oral antibiotics can prevent antibiotic-associated diarrhoea.
                This study was a three-arm (bio yogurt, commercial yogurt, no yogurt) randomised controlled trial with double blinding between the two yogurt arms.
                A single primary care general practice surgery in Hingham, Norfolk. The study population included all ages except babies.
                Patients aged over 1 year who required a 1-week course of antibiotics were included in the study. There was complete follow up for 369 patients. The intervention was the consumption of 150 ml of live strawberry-flavoured yogurt for 12 days, starting on the first day of taking the antibiotic. Diarrhoea was defined as 'three or more loose stools per day over at least 2 consecutive days' within 12 days of starting the antibiotics.
                Of the 120 patients in the no-yogurt group, 17 (14%, 95% confidence interval [CI] = 9.0 to 21.5) developed diarrhoea. Of the 118 given commercial yogurt, 13 (11%, 95% CI = 6.6 to 17.9) developed diarrhoea; nine of the 131 patients (7%; 95% CI = 3.7 to 12.5) given bio yogurt developed diarrhoea (P = 0.17).
                Overall, this study failed to demonstrate that yogurt has any effect on antibiotic-associated diarrhoea. The disruption of the natural flora of the gastrointestinal tract (especially Lactobacillus acidophilus) may occur during antibiotic therapy. This may lead to diarrhea, dehydration, and electrolyte imbalances. It has been suggested that replacement of the lactobacilli with a commercially available product may prevent the diarrhea. The efficacy and safety of prophylactically administered Lactinex (culture of L. acidophilus and L. bulgaricus) was compared with placebo for the prevention of amoxicillin-induced diarrhea in pediatric patients. Lactinex or placebo was administered four times a day for ten days to coincide with the antibiotic therapy. The Lactobacillus preparation did not appear to consistently prevent diarrhea in this patient population. Patients' age, diet, and parental definition of diarrhea were factors that may have influenced the results. The objective of this study was to determine the efficacy of Lactobacillus casei sps. rhamnosus (Lactobacillus GG) (LGG) in reducing the incidence of antibiotic-associated diarrhea when coadministered with an oral antibiotic in children with acute infectious disorders.
                Two hundred two children between 6 months and 10 years of age were enrolled; 188 completed all phases of the protocol. LGG, 1 x 10(10) - 2 x 10(10) colony forming units per day, or comparable placebo was administered in a double-blind randomized trial to children receiving oral antibiotic therapy in an outpatient setting. The primary caregiver was questioned every 3 days regarding the incidence of gastrointestinal symptoms, predominantly stool frequency and consistency, through telephone contact by blinded investigators.
                Twenty-five placebo-treated but only 7 LGG-treated patients had diarrhea as defined by liquid stools numbering 2 or greater per day. Lactobacillus GG overall significantly reduced stool frequency and increased stool consistency during antibiotic therapy by the tenth day compared with the placebo group.
                Lactobacillus GG reduces the incidence of antibiotic-associated diarrhea in children treated with oral antibiotics for common childhood infections. The aim of this study was to determine the efficacy of S. boulardii in diarrhea associated with commonly used antibiotics such as sulbactam-ampicillin (SAM) and azithromycin (AZT). Four hundred and sixty-six patients were assigned to four different groups as follows: group 1:117 patients receiving SAM alone; group 2:117 patients receiving SAM and S. boulardii, group 3:105 patients receiving AZT alone; group 4:127 patients receiving AZT and S. boulardii. Antibiotic-associated diarrhea was seen in 42 of the 222 patients (18.9 per cent) receiving an antibiotic without the probiotic, and in 14 of the 244 patients (5.7 per cent) who received both the probiotic and the antibiotic (p < 0.05). In the group receiving SAM where S. boulardii use was found to be significant, the use of S. boulardii decreased the diarrhea rate from 32.3 to 11.4 per cent in the 1-5 years age group (p < 0.05). This is a pioneering study investigating combined antibiotic and probiotic use in pediatric diarrhea patients. To examine the role of commercially available kefir, a fermented milk similar to yogurt but containing different fermentation microbes, in preventing antibiotic-associated diarrhea (AAD). Probiotics have shown some promise in preventing AAD.
                A double-blinded randomized placebo-controlled allocation concealment clinical trial.
                Primary care patients in the Washington, DC, metropolitan area.
                A total of 125 children aged 1 to 5 years presenting to primary care physicians. Intervention Kefir drink or heat-killed matching placebo. Main Outcome Measure The primary outcome was the incidence of diarrhea during the 14-day follow-up period in children receiving antibiotics.
                There were no differences in the rates of diarrhea per group, with 18% in the active group and 21.9% in the placebo group (relative risk, 0.82; 95% confidence interval, 0.54-1.43). Additionally, there were no differences in any secondary outcomes among the groups. However, there were some interesting interactions among initial health at enrollment, age of participants, and sex that require further study.
                In our trial, kefir did not prevent AAD. Further independent research on the potential of kefir needs to be conducted. Convincing evidence that probiotic administration can lower the risk of antibiotic-associated diarrhoea is limited to certain micro-organisms.
                To determine the efficacy of administration of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) for the prevention of antibiotic-associated diarrhoea in children.
                Children (aged 3 months to 14 years) with common infections were enrolled in a double-blind, randomized, placebo-controlled trial in which they received standard antibiotic treatment plus 2 x 10(10) colony forming units of a probiotic (n = 120) or a placebo (n = 120), administered orally twice daily throughout antibiotic treatment. Analyses were by intention to treat.
                Any diarrhoea (>or=3 loose or watery stools/day for >or=48 h occurring during or up to 2 weeks after the antibiotic therapy) occurred in nine (7.5%) patients in the probiotic group and in 20 (17%) patients in the placebo group (relative risk, RR 0.45, 95% confidence interval, CI 0.2-0.9). Three (2.5%) children in the probiotic group developed AAD (diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea) compared to nine (7.5%) in the placebo group (RR 0.33, 95% CI 0.1-1.06). No adverse events were observed.
                Administration of L. rhamnosus (strains E/N, Oxy and Pen) to children receiving antibiotics reduced the risk of any diarrhoea, as defined in this study. To determine the efficacy of a combination of Bifidobacterium longum PL03, Lactobacillus rhamnosus KL53A and Lactobacillus plantarum PL02 for the prevention of antibiotic-associated diarrhea in children.
                Seventy-eight children (age: 5 months to 16 years) with otitis media, and/or respiratory tract infections, and/or urinary tract infections were enrolled in a double-blind randomized control trial in which they received standard antibiotic treatment plus a food supplement containing 10(8) colony-forming units of B. longum, L. rhamnosus and L. plantarum (n = 40) or a placebo (n = 38) orally twice daily for the duration of antibiotic treatment.
                Patients receiving probiotics had a similar rate of diarrhea (> or =3 loose or watery stools/day for > or =48 h occurring during or up to 2 weeks after the antibiotic therapy) as those receiving placebo (relative risk 0.5, 95% CI 0.06-3.5). The mean number of stools per day was significantly lower in the experimental group (mean difference -0.3 stool/day, 95% CI -0.5 to -0.07). No adverse events were reported.
                The administration of the 3 probiotics did not significantly alter the rate of diarrhea, although it reduced the frequency of stools per day. As the overall frequency of diarrhea was surprisingly low, these results should be interpreted with caution.
                2008 S. Karger AG, Basel. Co-treatment with Saccharomyces boulardii appears to lower the risk of antibiotic-associated diarrhoea in adults receiving broad-spectrum antibiotics.
                To determine whether S. boulardii prevents antibiotic-associated diarrhoea in children.
                A total of 269 children (aged 6 months to 14 years) with otitis media and/or respiratory tract infections were enrolled in a double-blind, randomized placebo-controlled trial in which they received standard antibiotic treatment plus 250 mg of S. boulardii (experimental group, n = 132) or a placebo (control group, n = 137) orally twice daily for the duration of antibiotic treatment. Analyses were based on allocated treatment and included data from 246 children.
                Patients receiving S. boulardii had a lower prevalence of diarrhoea (> or =3 loose or watery stools/day for > or =48 h occurring during or up to 2 weeks after the antibiotic therapy) than those receiving placebo [nine of 119 (8%) vs. 29 of 127 (23%), relative risk: 0.3, 95% confidence interval: 0.2-0.7]. S. boulardii also reduced the risk of antibiotic-associated diarrhoea (diarrhoea caused by Clostridium difficile or otherwise unexplained diarrhoea) compared with placebo [four of 119 (3.4%) vs. 22 of 127 (17.3%), relative risk: 0.2; 95% confidence interval: 0.07-0.5]. No adverse events were observed.
                This is the first randomized-controlled trial evidence that S. boulardii effectively reduces the risk of antibiotic-associated diarrhoea in children. To determine the effectiveness of Lactobacillus GG (LGG) in children with Helicobacter pylori infection undergoing eradication therapy.
                We conducted a double-blind, placebo-controlled, randomized trial comparing a 7-day, triple eradication regimen consisting of 2 antibiotics (amoxicillin tablets, 25 mg/kg twice per day, and clarithromycin tablets, 10 mg/kg twice per day) plus a proton pump inhibitor (omeprazole capsules, 0.5 mg/kg twice per day) supplemented with LGG (109 colony-forming units) or placebo in 83 children with H pylori infection confirmed by 2 of 3 tests (13C-urea breath test, histopathology, rapid urease test). The primary outcome measure was the H pylori eradication rate. The secondary outcome measure was the proportion of patients who experienced therapy-related adverse effects during anti-H pylori treatment.
                The groups did not differ with respect to H pylori eradication rates. Of the 34 children in the LGG group, 23 (69%) experienced eradication, compared with 22 of 32 children (68%) in the placebo group (RR 0.98, 95% CI 0.7-1.4). The groups did not differ with respect to adverse effects.
                In children with H pylori infection, supplementation of standard triple therapy with LGG did not significantly alter the eradication rate or side effects.
Despite heterogeneity in probiotic strain, dose, and duration, as well as in study quality, the overall evidence suggests a protective effect of probiotics in preventing AAD. Using 11 criteria to evaluate the credibility of the subgroup analysis on probiotic dose, the results indicate that the subgroup effect based on dose (≥5 billion CFU/day) was credible. Based on high-dose probiotics, the number needed to treat (NNT) to prevent one case of diarrhea is seven (NNT 7; 95% CI 6 to 10). However, a GRADE analysis indicated that the overall quality of the evidence for the primary endpoint (incidence of diarrhea) was low due to issues with risk of bias (due to high loss to follow-up) and imprecision (sparse data, 225 events). The benefit for high dose probiotics (Lactobacillus rhamnosus or Saccharomyces boulardii) needs to be confirmed by a large well-designed randomized trial. More refined trials are also needed that test strain specific probiotics and evaluate the efficacy (e.g. incidence and duration of diarrhea) and safety of probiotics with limited losses to follow-up. It is premature to draw conclusions about the efficacy and safety of other probiotic agents for pediatric AAD. Future trials would benefit from a standard and valid outcomes to measure AAD.